This study was supported by a fund from the University-Industry Collaborative Education Program of the Ministry of Education in 2021 (project number: 202101312014) and a fund from the University-Industry Collaborative Education Program of the Ministry of Education in 2022 (project number: 220905634190447).

This study was approved by the ethics committee of our institution and all patients provided informed consent before participating in the study.
1. Preoperative steps
<ol>
	<li>Exclude patients with cervical radiculitis, brachial plexus lesion, pronator syndrome, and nerve tear before the operation.</li>
	<li>Define carpal tunnel syndrome based on persistent numbness, tingling, pain, and muscle weakness in the median nerve distribution area, positive physical examination (Tinel sign, wrist compression test, thenar muscle weakness or atrophy), and electromyography.</li>
</ol>
2. Initial surgical procedures
NOTE: Pay attention to the abnormal anatomy of nerves and blood vessels during the operation.
<ol>
	<li>Preoperative preparation
	<ol>
		<li>Position the patient in the supine position on the operating table with the affected limb and a tourniquet is tied to the proximal end of the upper arm. Prepare the distal end of the affected limb and wrap it in a routine aseptic manner under brachial plexus anesthesia or general anesthesia. Place the patient&#39;s palms upward on the table and properly fix them on a small square piece of cloth. 
		NOTE: During the operation, avoid damaging the visible palmar cutaneous branch of the median nerve and prolonging the use of the tourniquet.</li>
	</ol>
	</li>
	<li>Skin incision
	<ol>
		<li>Cut the skin longitudinally along the surgically marked incision in the palm and make a longitudinal incision 3 cm in length. Carefully dissect the subcutaneous fat layer (Figure 2C), taking care to protect the small branches of the palmar cutaneous nerve, which may traverse proximally through the incision.</li>
	</ol>
	</li>
	<li>Subcutaneous separation
	<ol>
		<li>Retract the subcutaneous tissue and protect the median nerve. Then, sharply separate and incise the palmar fascia. Use a smooth, curved vascular clamp to sharply separate the tissue below the transverse carpal ligament, and use curved, blunt-headed scissors to cut the proximal transverse carpal ligament or forearm fascia.</li>
	</ol>
	</li>
	<li>Release of the carpal canal
	<ol>
		<li>Locate the distal end of the transverse carpal ligament, where the ligament is relatively weak. Make a sharp incision of the transverse carpal ligament between the superficial palmar arch and the distal end of the transverse carpal ligament, under the guidance of accurate identification of the median nerve position to avoid median nerve injury due to any deviation in position.
		<ol>
			<li>Identify the tissue before cutting off any tissue structure, and avoid damaging the ulnar nerve, the median nerve (including the motor branch), and the palmar arch.</li>
		</ol>
		</li>
		<li>Perform the dissection below the transverse carpal ligament using smooth, curved vascular forceps. When separating along the ulnar side of the median nerve during the operation, avoid damaging its motor branch, which can be located below or across the ligament. 
		NOTE: Operating on the ulnar side of the median nerve avoids damage to the ulnar nerve that runs within Guyon&#39;s canal while allowing greater identification of the dorsal structures of the carpal tunnel.</li>
	</ol>
	</li>
	<li>Release of the transverse carpal ligament
	<ol>
		<li>Sharply separate and incise the transverse carpal ligament. Take care to pull the retractor up the incised transverse carpal ligament at this time to protect the median nerve below it and avoid damage to the communication branch between the median nerve and the ulnar nerve.</li>
		<li>Cut the transverse carpal ligament with scissors along the ulnar side of the median nerve under direct vision through the incision (Figure 3A). Keep the incision on the ulnar side of the long palmar muscle and cut along the ulnar edge of the transverse carpal ligament and the ulnar edge of the long palmar tendon to avoid damage to the superficial palmar arch, palmar cutaneous nerve, and the recurrent branch of the median nerve.</li>
		<li>Fully stop the bleeding when the incision is exposed. Before releasing the transverse carpal ligament during the operation, take care to distinguish the superficial palmar arch, Guyon canal (wrist ulnar nerve canal), and carpal tunnel.</li>
		<li>Use a retractor to pull up the skin near the incision and release the transverse carpal ligament to the level of the far flexion carpal crease&#160;(Figure 3B). Under direct vision, use blunt-tip scissors to incise the proximal forearm fascia 2-3 cm to allow a finger to pass through the fascia (Figure 3C). Then, use a retractor to pull the skin distal to the incision, and loosen the transverse carpal ligament and palmar fascia to the level of the median nerve branch.</li>
		<li>During the operation, take care to check whether there is any lesion or injury at the bottom of the carpal canal so that the median nerve can be completely released and vital structures are not damaged (Figure 3D). If residual local compression is still present, consider additional release procedures to release the epineurium.</li>
	</ol>
	</li>
	<li>Closed incision
	<ol>
		<li>After the incision completely stops bleeding, loosen the tourniquet, rinse the surgical incision with normal saline, check the incision again for bleeding, and use bipolar electrocoagulation to stop bleeding if there is any bleeding. Be familiar with the course of the ulnar finger nerve in the middle finger and ring finger. Finally, fold the edge of the skin without tension.</li>
		<li>Anesthetize the skin margin of the incision with lidocaine and close it intermittently with 5-0 sutures. Cover the incision with loose, thick gauze so that the fingers can move freely (Figure 2D). Encourage finger movement and mild finger use immediately after the operation.</li>
	</ol>
	</li>
</ol>
3. Postoperative care
<ol>
	<li>Choose thick gauze to cover the wound; to ensure that the fingers can move freely, choose a palmar brace to fix for 3-4 weeks.</li>
	<li>After 3-4 weeks, remove the palmar brace and continue the treatment. 
	NOTE: In general, it takes 6-9 months for the patient for the symptoms to disappear completely.</li>
	<li>Ensure that the patient moves the fingers immediately after the operation and provide the patient with appropriate painkillers.</li>
	<li>Raise the affected limb and ice it for 48-72 h after the operation.</li>
	<li>Change the dressing 3-5 days after the operation. Guide postoperative wound care. Remove the stitches 10-14 days after the operation. Develop a reasonable plan for hand treatment and return to work.</li>
	<li>Encourage the patient to move the wrist freely at 2-3 months after the operation and at full intensity at 6-12 months after the operation. Evaluate the relief of postoperative numbness and tingling symptoms and changes in sensation, thenar atrophy, and muscle strength after the operation.</li>
</ol>

<ol>
	<li>Malakootian, M., Soveizi, M., Gholipour, A., Oveisee, M. Pathophysiology, diagnosis, treatment, and genetics of carpal tunnel syndrome: a review. Cellular and Molecular Neurobiology. 43 (5), 1817-1831 (2023).</li>
	<li>Sobeeh, M. G., Ghozy, S., Elshazli, R. M., Landry, M. Pain mechanisms in carpal tunnel syndrome: a systematic review and meta-analysis of quantitative sensory testing outcomes. Pain. 163 (10): E1054-E1094 (2022).</li>
	<li>Aydin, K., Cokluk, C., Cengiz, N., Bilgici, A. Microsurgical open mini uniskin incision technique in the surgical treatment of carpal tunnel syndrome. Neurology India. 54 (1), 64-67 (2006).</li>
	<li>Aydin, K., Cokluk, C., Piskin, A., Kocabicak, E. Ultrasonographically checking the sectioning of the transverse carpal ligament during carpal tunnel surgery with limited uniskin incisions. Turkish Neurosurgery. 17 (3), 219-223 (2007).</li>
	<li>Huisstede, B. M. et al. Carpal tunnel syndrome. Part 2. Effectiveness of surgical treatments. A systematic review. Archives of Physical Medicine and Rehabilitation. 91 (7), 1005-1024 (2010).</li>
	<li>Osiak, K., Elnazir, P., Walocha, J. A., Pasternak, A. Carpal tunnel syndrome: state-of-the-art review. Folia Morphologica. 81 (4), 851-862 (2022).</li>
	<li>Aroori, S., Spence, R. A. Carpal tunnel syndrome.The Ulster medical journal. 77(1),6-17 (2008).</li>
	<li>Lida, J., Hirabayashi, H., Nakase, H., Sakaki, T. Carpal tunnel syndrome: electrophysiological grading and surgical results by minimum incision open carpal tunnel release.&#160;Neurologia Medico-chirurgica.&#160;48&#160;(12), 554-559 (2008).</li>
	<li>Phalen, G. S. The carpal-tunnel syndrome: seventeen years&#39; experience in diagnosis and treatment of six hundred fifty-four hands. The Journal of Bone and Joint Surgery. American Volume.&#160;48&#160;(2), 211-228 (1966).</li>
	<li>Abdullah, A. F., Wolber, P. H., Ditto, E. W. Sequelae of carpal tunnel surgery: rationale for design of a surgical approach.&#160;Neurosurgery.&#160;37&#160;(5), 931-936 (1995).</li>
	<li>Dawson, D. M. Entrapment neuropathies of the upper extremities.&#160;The New England Journal of Medicine.&#160;329&#160;(27), 2013-2018 (1993).</li>
	<li>Hybbinette, C. H., Mannerfelt, L. The carpal tunnel syndrome: a retrospective study of 400 operated patients. Acta Orthopaedica Scandinavica. 46 (4), 610-620 (1975).</li>
	<li>Malla, M. A., Bhat, A. A., Samiullah, M., Farooq, M. Mini-open carpal tunnel release in carpal tunnel syndrome. Integrative Journal of Orthopaedics and Traumatology. 5 (2), 1-6 (2022).</li>
	<li>Harris, C. M., Tanner, E., Goldstein, M. N., Pettee, D. S. The surgical treatment of the carpal tunnel syndrome correlated with preoperative nerve conduction studies. The Journal of Bone and Joint Surgery. American Volume. 61 (1), 93-98 (1979).</li>
	<li>Hidayati, H. B., Subadi, I., Fidiana., Puspamaniar, V. A. Current diagnosis and management of carpal tunnel syndrome: A review. Anaesthesia Pain &#38; Intensive Care. 26 (3), 394-404 (2022).</li>
	<li>Carmo, J. D. &#39;INSIGHT-PRECISION&#39;: a new, mini-invasive technique for the surgical treatment of carpal tunnel syndrome. Journal of International Medical Research. 48 (1), 0300060519878082 (2020).</li>
	<li>Atthakomol, P. et al. Short incision versus minimally invasive surgery with tool-kit for carpal tunnel syndrome release: a prospective randomized control trial to evaluate the anterior wrist pain and time to return to work or activities. BMC Musculoskeletal Disorders. 23 (1), 708 (2022).</li>
	<li>Vetrano, I., Devigili, G., Nazzi, V. Minimally invasive carpal tunnel release: a technical note and a 20-year retrospective series. Cureus Journal of Medical Science. 14 (1), e21426 (2022).</li>
	<li>Lowry, W. E., Follender, A. B. Interfascicular neurolysis in the severe carpal tunnel syndrome. A prospective, randomized, double-blind, controlled study. Clinical Orthopaedics and Related Research. 227, 251-254 (1988).</li>
	<li>Franzini, A., Broggi, G., Servello, D., Dones, I., Pluchino, M. G. Transillumination in minimally invasive surgery for carpal tunnel release. Technical note. Journal of Neurosurgery. 85 (6), 1184-1186 (1996).</li>
	<li>Agee, J. M., McCarroll, H. R., North, E. R. Endoscopic carpal tunnel release using the single proximal incision technique. Hand Clinics. 10 (4), 647-659 (1994).</li>
	<li>Chow, J. C. Endoscopic release of the carpal ligament: a new technique for carpal tunnel syndrome. Arthroscopy: The Journal of Arthroscopic &#38; Related Surgery. 5 (1), 19-24 (1989).</li>
	<li>Okada, M., Tsubata, O., Yasumoto, S., Toda, N., Matsumoto, T. Clinical study of surgical treatment of carpal tunnel syndrome: open versus endoscopic technique. Journal of Orthopaedic Surgery. 8 (2), 19-25 (2000).</li>
	<li>Teh, K. K., Ng, E. S., Choon, D. S. K. Mini open carpal tunnel release using knifelight: evaluation of the safety and effectiveness of using a single wrist incision (cadaveric study). The Journal of Hand Surgery, European Volume. 34 (4), 506-510 (2009).</li>
	<li>Trumble, T. E., Diao, E., Abrams, R. A., Gilbert-Anderson, M. M. Single-portal endoscopic carpal tunnel release compared with open release: a prospective randomized trial. The Journal of Bone and Joint Surgery. American Volume. 84 (7), 1107-1115 (2002).</li>
	<li>Wongsiri, S., Suwanno, P., Tangtrakulwanich, B., Yuenyongviwat, V., Wongsiri, E. A new tool for mini open carpal tunnel release-the PSU retractor. BMC Musculoskeletal Disorders. 9, 126 (2008).</li>
	<li>Nazzi, V., Franzini, A., Messina, G., Broggi, G. Carpal tunnel syndrome: matching minimally invasive surgical techniques, technical note. Journal of Neurosurgery. 108 (5), 1033-1036 (2008).</li>
	<li>Martinez-Catasus, A. et al. Comparison between single portal endoscopic and 1-cm open carpal tunnel release. Hand Surgery and Rehabilitation. 38 (3), 202-206 (2019).</li>
	<li>Lam, K. H. S. et al. Ultrasound-guided interventions for carpal tunnel syndrome: a systematic review and meta-analyses. Diagnostics. 13 (6), 1138 (2023).</li>
	<li>Kamel, S. I., Freid, B., Pomeranz, C., Halpern, E. J., Nazarian, L. N. Minimally invasive ultrasound-guided carpal tunnel release improves long-term clinical outcomes in carpal tunnel syndrome. AJR American Journal of Roentgenology. 217 (2), 460-468 (2021).</li>
	<li>Chang, K. V. Ultrasound diagnosis and guided intervention of musculoskeletal/neuromuscular pathology 2022. Diagnostics. 13 (11), 1945 (2023).</li>
	<li>Peters, S., Page, M. J., Coppieters, M. W., Ross, M., Johnston, V. Rehabilitation following carpal tunnel release. The Cochrane Database of Systematic Reviews. 17 (2), CD004158 (2016).</li>
	<li>Bai, J. et al. Carpal tunnel release with a new mini-incision approach versus a conventional approach, a retrospective cohort study. International Journal of Surgery. 52, 105-109 (2018).</li>
	<li>Eberlin, K. R. et al. Multicenter randomized trial of carpal tunnel release with ultrasound guidance versus mini-open technique. Expert Review of Medical Devices. 20 (7), 597-605 (2023).</li>
	<li>Lee, Y. S., Youn, H., Shin, S. H., Chung, Y. G. Minimally invasive carpal tunnel release using a hook knife through a small transverse carpal incision: technique and outcome. Clinics In Orthopedic Surgery. 15 (2), 318-326 (2023).</li>
</ol>

The authors have no conflicts of interest to disclose.

Carpal tunnel surgical decompression combined with transection of the transverse carpal ligament has been a very successful operation for the treatment of CTS11,12,13,14,15,16. Over the years, the carpal tunnel decompression procedure has been developed to reduce complications and side effects associated with the operation. A...

Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder caused by the compression of the median nerve in the wrist region, especially in the carpal canal. The clinical manifestations of CTS are diverse and may include pain, numbness, weakness, and hand muscle atrophy1,2, which can significantly impact the quality of life of patients. The diagnosis of CTS is typically based on clinical manifestations and physical examination, supported by electrophysiological studies such as electrodiagnostic testing3,4. For patients with mild symptoms, conservative treatment may be sufficient, but for those with moderate to severe symptoms, surgical intervention is often necessary5.
Many surgical techniques6,7,8,9,10,11,12,13,14,15,16,17, 
18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35 have been developed for the treatment of CTS, each with its advantages and disadvantages6,7,8. Open carpal tunnel decompression with a standard long palmar curved incision is a commonly used technique; however, it is associated with various complications such as scar tenderness, cosmetic dissatisfaction, and loss of hand grip and pinch strength3,7,9,10. Therefore, there is a need for a surgical technique that is effective in treating CTS but is also minimally invasive and associated with fewer complications.
The purpose of this study is to introduce a metacarpal small incision for carpal tunnel release (MSICTR) technique in the treatment of CTS and summarize our experience. This technique utilizes a small incision made at the base of the palm, over the carpal tunnel, allowing direct visualization of the median nerve and carpal tunnel contents (Figure 1). The advantages of MSICTR include shorter operation time, less postoperative pain, faster recovery, and improved cosmetic results when compared to traditional open carpal tunnel decompression techniques3.
Previous studies have shown that MSICTR is an effective and safe surgical technique for the treatment of CTS13,16,17,18,20,24,26,27,28. MSICTR has been associated with low rates of postoperative complications such as scar tenderness, infection, and median nerve damage17. Additionally, MSICTR can provide direct visualization of the median nerve and carpal tunnel contents, ensuring the complete release of the carpal tunnel and reducing the risk of residual compression18. The MSICTR technique is suitable for patients with CTS who have failed conservative management and are suitable for surgery. It can be used in patients with mild to severe symptoms of CTS and is particularly suitable for those who are concerned about cosmetic results and postoperative recovery time. However, MSICTR should not be used in patients with coagulation disorders or those who are not suitable for general anesthesia.
In summary, MSICTR is a safe and effective surgical technique for the treatment of CTS that has advantages over traditional open carpal tunnel decompression techniques. It is associated with shorter operation time, less postoperative pain, faster recovery, and improved cosmetic results. However, further randomized controlled trials are needed to compare MSICTR with other surgical techniques for CTS to establish its true efficacy and safety.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Absorbable suture</td>
			<td>Shandong Boda Medical supplies Co., Ltd.</td>
			<td>01-1517-8817-2</td>
			<td>Absorbable suture in surgical suture, after implantation into human tissue, can be degraded and absorbed by the human body, and does not need to remove stitches, but to avoid the pain of suture removal of a new type of suture material.</td>
		</tr>
		<tr>
			<td>Disposable aseptic surgical blade</td>
			<td>Huaiyin Medical equipment Co., Ltd.</td>
			<td>yuxiezhuzhun20192150063</td>
			<td>It is used to cut soft tissue during surgery.</td>
		</tr>
		<tr>
			<td>Disposable aseptic surgical membrane</td>
			<td>Zhejiang Chun&#39;an Renhe Medical products Industry and Trade Co., Ltd.</td>
			<td>zhechunxiebei20180017hao</td>
			<td>It can be used to cover and protect the organs of surgical patients from bacterial infection in hospital operations. at the same time, it can be used for CT, nuclear magnetic resonance, organ B-ultrasound and other inspection imaging examination.</td>
		</tr>
		<tr>
			<td>Disposable infusion device</td>
			<td>Shandong Weigao Group Medical Polymer products Co., Ltd.</td>
			<td>1401275143736</td>
			<td>Clinical intravenous infusion</td>
		</tr>
		<tr>
			<td>Disposable sterilized rubber surgical gloves</td>
			<td>Shanghai Huaxin Medical Materials Co., Ltd.</td>
			<td>huxiezhuzhun20172660706</td>
			<td>It is used in surgical procedures to protect patients and users, to avoid cross-infection, and is not suitable for examination gloves or procedural gloves.</td>
		</tr>
		<tr>
			<td>Hemostatic forceps</td>
			<td>Hunan Kefu Medical Technology Development Co., Ltd.</td>
			<td>xiangxiezhuzhun20192150038</td>
			<td>Hemostatic forceps is a kind of surgical instrument which can block blood by clamping blood vessels.</td>
		</tr>
		<tr>
			<td>LM bipolar drop hydrocoagulation forceps (hemostatic ablation electrode during surgery)</td>
			<td>Jiangsu Yibo Leiming Medical Technology Co., Ltd.</td>
			<td>20222068536P</td>
			<td>LM bipolar drop hydrocoagulation forceps (hemostatic ablation electrode during surgery) for electrocoagulation of tissue</td>
		</tr>
		<tr>
			<td>Medical forceps</td>
			<td>Yangzhou Euro Science and Technology Development Co., Ltd.</td>
			<td>6803</td>
			<td>Medical forceps are used to hold human tissue.</td>
		</tr>
		<tr>
			<td>Medical gauze piece</td>
			<td>Steady medical supplies co., Ltd.</td>
			<td>59400869174</td>
			<td>Medical gauze is a disposable item used in surgery and wound care.</td>
		</tr>
		<tr>
			<td>Medical surgical towel</td>
			<td>Xuchang Zhende Medical dressing Co., Ltd.</td>
			<td>yushiyaojianxiezhunzi2006di2640197hao</td>
			<td>It is used for hemostasis and isolation in all kinds of operations. at the same time, it can be used to observe and protect the important parts of patients in bedside photography and fluoroscopic surgery.</td>
		</tr>
		<tr>
			<td>Needle holder</td>
			<td>Shanghai Youqun Medical equipment Co., Ltd.</td>
			<td>91310113758584951A</td>
			<td>The needle holder is mainly used to hold stitches and suture various tissues.</td>
		</tr>
		<tr>
			<td>Single-use suction connecting pipe</td>
			<td>Suzhou Jingle Polymer Medical equipment Co., Ltd.</td>
			<td>huxiezhuzhun20183100062</td>
			<td>It is used to attract, aspirate blood, lavage, and rinse during the operation and play an auxiliary role in the operation.</td>
		</tr>
		<tr>
			<td>Surgical hilt</td>
			<td>Zhejiang Suichang Shuangjian Medical equipment Co., Ltd.</td>
			<td>zhexiezhuzhun2020207162234</td>
			<td>The scalpel is divided into a blade and a handle. The blade is disposable, the handle is not. Other instruments are not disposable, but they are autoclaved each time they are used.</td>
		</tr>
		<tr>
			<td>Surgical scissors</td>
			<td>Maichuang Medical Technology (Suzhou) Co., Ltd.</td>
			<td>91320509MA1MMLGX80</td>
			<td>For cutting dressings, human epidermis or soft tissue. Tissue scissors: used for cutting tissue.</td>
		</tr>
	</tbody>
</table>

metacarpal small incision for carpal tunnel syndrome

Endoscopic carpal tunnel release (ECTR) techniques have been established as a successful treatment for carpal tunnel syndrome and have proven equally effective as traditional open carpal tunnel release (OCTR) techniques in relieving pain and numbness. However, patients who undergo OCTR are more likely to experience scar tenderness and pillar pain and take longer to return to work.
We present here a method of metacarpal small incision for carpal tunnel release (MSICTR) as a safe, reliable, cost-effective alternative surgical decompression of the median nerve of the wrist. This technique utilizes a metacarpal small incision and direct visualization of the median nerve and carpal tunnel contents, reducing the risk of permanent injury and neurasthenia when compared to traditional OCTR. MSICTR is also suitable for the examination of the median nerve, surrounding tendon sheath, or space-occupying lesions.
MSICTR is associated with shorter operation times, less postoperative pain, faster recovery, and improved cosmetic results when compared to traditional OCTR. Therefore, MSICTR is an effective surgical decompression of the median nerve for the treatment of carpal tunnel syndrome.

It is important to discuss the recovery time with the patient before the operation to make the patient&#39;s expectation of the outcome of the operation realistic. The surgical marker simplifies the identification of surgical incisions (Figure 2A).
When the surgical approach is performed in accordance with the above steps, all the diseased sites of the transverse carpal ligament and adjacent metacarpal fascia can be touched without any problem (<strong class="xfig...

Watch this Scientific Journal Video about Metacarpal Small Incision for Carpal Tunnel Syndrome at JoVE.com

Metacarpal Small Incision for Carpal Tunnel Syndrome

Carpal tunnel decompression with transverse carpal ligament transection is a very successful treatment of carpal tunnel syndrome. The standard long-curved incision technique has become the best treatment for median nerve entrapment decompression. Here we introduce the metacarpal small incision carpal tunnel release (MSICTR) in the treatment of carpal tunnel syndrome (CTS).

Endoscopic carpal tunnel release (ECTR) techniques have been established as a successful treatment for carpal tunnel syndrome and have proven equally ...

metacarpal-small-incision-for-carpal-tunnel-syndrome

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315 Views.  Zhejiang University. Carpal tunnel decompression with transverse carpal ligament transection is a very successful treatment of carpal tunnel syndrome. The standard long-curved incision technique has become the best treatment for median nerve entrapment decompression. Here we introduce the metacarpal small incision carpal tunnel release (MSICTR) in the treatment of carpal tunnel syndrome (CTS).

Video: Metacarpal Small Incision for Carpal Tunnel Syndrome

Protocol for Long Duration Whole Body Hyperthermia in Mice

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body temperature that is observed during fever. The use of hyperthermia as an adjuvant has emerged as a promising procedure for tumor regression in the field of cancer biology. For this purpose, the most important requirement is to have reliable and uniform heating protocols. We have developed a protocol for hyperthermia (whole body) in mice. In this protocol, animals are exposed to cycles of hyperthermia for 90 min followed by a rest period of 15 min. During this period mice have easy access to food and water. High body temperature spikes in the mice during first few hyperthermia exposure cycles are prevented by immobilizing the animal. Additionally, normal saline is administered in first few cycles to minimize the effects of dehydration. This protocol can simulate fever like conditions in mice up to 12-24 hr. We have used 8-12 weeks old BALB/Cj female mice to demonstrate the protocol.

This paper describes a protocol for whole body hyperthermia in mice that can stimulate fever like conditions up to 12-24 hr.

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body ...

Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal model to investigate bladder remodeling in pBOO are female rodents undergoing partial obstruction at the proximal urethra. Variability in the degree of obstruction and animal mortality are major concerns with proximal obstruction. Furthermore, dissecting around the proximal urethra and bladder neck jeopardizes bladder innervation.
We developed a nerve-sparing mid-urethral obstruction (NeMO) model for pBOO avoiding the disadvantages of the traditional model. We approached the urethra just inferior to the pubic symphysis, which obviated the need for laparotomy as well as for dissection in this area; also, the striated urethral sphincter remained untouched. We performed NeMO in female Sprague-Dawley rats (12 obstructions, 6 sham animals) as well as in female C57/bl6 mice (20 obstructions, 18 sham animals). After two weeks, we evaluated bladder function, bladder mass, and body mass.
We had no mortalities among obstructed- or sham-operated female rats; as described for the traditional proximal pBOO-method, we tied the suture around the proximal urethra and a temporarily placed 0.9 mm metal rod. NeMO induced an 85% increase in bladder mass after two weeks, average residual urine volume was 0.4 mL in partially obstructed rats while only 0.03 mL in sham animals. In mice, we tested 3 sizes of cannulas that we placed along the urethra when tying the suture. We found that using a 27-gauge cannula resulted in over 50% animal mortality; placing the 25-gauge cannula did not yield the desired response in increasing bladder mass; utilizing a 26-gauge cannula yielded favorable results with minimal animal mortality (1/8) yet a significant 2-fold increase in bladder mass.

Nerve-sparing Mid-urethral Obstruction NeMO in Female Small Rodents

Traditional modeling of partial bladder outlet obstruction in rodents is fraught with animal mortality. A denervation injury from dissection around the proximal urethra and bladder neck is also of major concern. We developed and evaluated a safe and reliable mid-urethral obstruction model, avoiding the shortcomings of the traditional model.

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal ...

Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered. This precludes conducting early feasibility studies as insufficient drug is available at the research or early development stage to support the dose delivery requirements for conventional aerosol delivery systems. When designing an aerosol drug product, aerodynamic performance can relate directly to delivery efficiency and efficacy. Dispersion of powder into an aerosol requires energy input sufficient to overcome interparticulate forces, and particle engineering approaches can substantially improve aerosol performance. We have developed a dispersion system (dosator) which can aerosolize engineered dry powder aerosols efficiently for the purpose of direct pulmonary insufflation, dispersion into an exposure system or generation for analytical purposes.

During development of drugs for pulmonary delivery, it is necessary to evaluate pharmacokinetics and efficacy in an animal model. We present a method to build a disposable aerosol dispersion system from of-the-shelf components that can be used to administer intrapulmonary dry powder aerosol to rodents.

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver ...

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and &#181;CT imaging. However, both techniques are only able to distinguish between mineralized and non-mineralized tissue. Consequently, it is impossible to discriminate cartilage from fibrous tissue. In contrast, magnetic resonance imaging (MRI) visualizes anatomical structures based on their water content and might therefore be able to noninvasively identify soft tissue and cartilage in the fracture callus. Here, we report the use of an MRI-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice. The experiments demonstrated that the fixator and a custom-made mounting device allow repetitive MRI scans, thus enabling longitudinal analysis of fracture-callus tissue development.

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

The evaluation of tissue development in the fracture callus during endochondral bone healing is essential to monitor the healing process. Here, we report the use of a magnetic resonance imaging (MRI)-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice.

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The ...

Oleic Acid-Injection in Pigs As a Model for Acute Respiratory Distress Syndrome

The acute respiratory distress syndrome is a relevant intensive care disease with an incidence ranging between 2.2% and 19% of intensive care unit patients. Despite treatment advances over the last decades, ARDS patients still suffer mortality rates between 35 and 40%. There is still a need for further research to improve the outcome of patients suffering from ARDS. One problem is that no single animal model can mimic the complex pathomechanism of the acute respiratory distress syndrome, but several models exist to study different parts of it. Oleic acid injection (OAI)-induced lung injury is a well-established model for studying ventilation strategies, lung mechanics and ventilation/perfusion distribution in animals. OAI leads to severely impaired gas exchange, deterioration of lung mechanics and disruption of the alveolo-capillary barrier. The disadvantage of this model is the controversial mechanistic relevance of this model and the necessity for central venous access, which is challenging especially in smaller animal models. In summary, OAI-induced lung injury leads to reproducible results in small and large animals and hence represents a well-suited model for studying ARDS. Nevertheless, further research is necessary to find a model that mimics all parts of ARDS and lacks the problems associated with the different models existing today.

In this article, we present a protocol to induce acute lung injury in pigs by central-venous injection of oleic acid. This is an established animal model for studying the acute respiratory distress syndrome (ARDS).

The acute respiratory distress syndrome is a relevant intensive care disease with an incidence ranging between 2.2% and 19% of intensive care unit ...

An Efficient Sieving Method to Isolate Intact Glomeruli from Adult Rat Kidney

Preservation of glomerular structure and function is pivotal in the prevention of glomerulonephritis, a category of kidney disease characterized by proteinuria which can eventually lead to chronic and end-stage renal disease. The glomerulus is a complex apparatus responsible for the filtration of plasma from the body. In disease, structural integrity is lost and allows for the abnormal leakage of plasma contents into the urine. A method to isolate and examine glomeruli in culture is critical for the study of these diseases. In this protocol, an efficient method of retrieving intact glomeruli from adult rat kidneys while conserving structural and morphological characteristics is described. This process is capable of generating high yields of glomeruli per kidney with minimal contamination from other nephron segments. With these glomeruli, injury conditions can be mimicked by incubating them with a variety of chemical toxins, including protamine sulfate, which causes foot process effacement and proteinuria in animal models. Degree of injury can be assessed using transmission electron microscopy, immunofluorescence staining, and western blotting. Nephrin and Wilms Tumor 1 (WT1) levels can also be assessed from these cultures. Due to the ease and flexibility of this protocol, the isolated glomeruli can be utilized as described or in a way that best suits the needs of the researcher to help better study glomerular health and structure in diseased states.

The main focus of this protocol is to efficiently isolate viable primary glomeruli cultures with minimal contaminants for use in a variety of downstream applications. The isolated glomeruli retain structural relationships between component cell types and can be cultured ex vivo for a short time.

Preservation of glomerular structure and function is pivotal in the prevention of glomerulonephritis, a category of kidney disease characterized by ...

Transaxillary First Rib Resection for Treatment of the Thoracic Outlet Syndrome

Thoracic outlet syndrome (TOS) is a common disorder that causes a significant loss of productivity. The transaxillary first rib resection (TFRR) protocol has been used for the decompression of trapped neurovascular structures in the TOS. Among the other surgical procedures, the advantage of the TFRR is that it has the smallest rate of recurrence and better cosmetic outcomes. The disadvantage of TFRR is that it provides a narrow, and deep working corridor that makes obtaining vascular control challenging.

Here, we present a protocol of the transaxillary resection of the first rib for treatment of thoracic outlet syndrome caused by compression of the brachial plexus, subclavian vein and artery.

Thoracic outlet syndrome (TOS) is a common disorder that causes a significant loss of productivity. The transaxillary first rib resection (TFRR) protocol ...

Continuous Blood Sampling in Small Animal Positron Emission Tomography/Computed Tomography Enables the Measurement of the Arterial Input Function

For quantitative analysis and bio-kinetic modeling of positron emission tomography/computed tomography (PET/CT) data, the determination of the temporal blood time-activity concentration also known as arterial input function (AIF) is a key point, especially for the characterization of animal disease models and the introduction of newly developed radiotracers. The knowledge of radiotracer availability in the blood helps to interpret PET/CT-derived data of tissue activity. For this purpose, online blood sampling during the PET/CT imaging is advisable to measure the AIF. In contrast to manual blood sampling and image-derived approaches, continuous online blood sampling has several advantages. Besides the minimized blood loss, there is an improved resolution and a superior accuracy for the blood activity measurement. However, the major drawback of online blood sampling is the costly and time-consuming preparation to catheterize the femoral vessels of the animal. Here, we describe an easy and complete workflow for catheterization and continuous blood sampling during small animal PET/CT imaging and compared it to manual blood sampling and an image-derived approach. Using this highly-standardized workflow, the determination of the fluorodeoxyglucose ([18F]FDG) AIF is demonstrated. Further, this procedure can be applied to any radiotracer in combination with different animal models to create fundamental knowledge of tracer kinetic and model characteristics. This allows a more precise evaluation of the behavior of pharmaceuticals, both for diagnostic and therapeutic approaches in the preclinical research of oncological, neurodegenerative and myocardial diseases.

Here a protocol for continuous blood sampling during PET/CT imaging of rats to measure the arterial input function (AIF) is described. The catheterization, the calibration and setup of the system and the data analysis of the blood radioactivity are demonstrated. The generated data provide input parameters for subsequent bio-kinetic modeling.

For quantitative analysis and bio-kinetic modeling of positron emission tomography/computed tomography (PET/CT) data, the determination of the temporal ...

Laparoscopic Oocyte Retrieval and Cryopreservation during Vaginoplasty for Treatment of Mayer-Rokitansky-Kuster-Hauser Syndrome

In Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS) patients who are scheduled for laparoscopic vaginoplasty and have a desire for biological motherhood, we propose that a concomitant laparoscopic oocyte retrieval for cryopreservation is performed. Oocyte retrieval is pursued at the beginning of the laparoscopy. Right and left 5 mm trocars are positioned, through which a 17 G ovum aspiration needle is used for puncture of the right and left ovaries, respectively. To facilitate exposure of the follicles, the ovaries are mobilized and held with laparoscopic forceps.
When aspirating multiple follicles near each other, the needle tip is retained in the ovary to reduce the number of times that the ovarian cortex is transfixed and due to the inherent risk of bleeding. Subsequent steps are unchanged compared to the Davydov laparoscopic modified technique for vaginoplasty. Prior to surgery, controlled ovarian stimulation is performed with a gonadotropin hormone-releasing hormone (Gn-RH) antagonist protocol, and the concomitant procedure of oocyte retrieval and vaginoplasty is scheduled 36 h after the final follicular maturation trigger. Follicular fluid is collected in the same 10 mL sterile tubes used during transvaginal oocyte retrieval and transferred in a warming block (37 &#176;C) to the assisted reproduction laboratory, where mature (metaphase II) oocytes are vitrified.
In this case, a series of 23 women with MRKH, oocytes were successfully retrieved and cryopreserved in all patients; vaginoplasty was subsequently conducted without modifications, and the inpatient and outpatient postoperative care (day of urinary catheter removal, day of hospital discharge, dilator use, and comfort at follow-up) remained unaffected. One postoperative complication occurred in one patient (fever developing on day 5 post surgery and intraperitoneal fluid detection on transabdominal ultrasound) and resolved after conservative treatment. Rather than performing surgical vaginoplasty and delaying oocyte retrieval in MRKH patients, this approach combines both procedures in a single laparoscopy, thereby minimizing surgical invasiveness and anesthesiologic risks.

A dedicated team can offer Mayer-Rokitansky-Kuster-Hauser patients the option to perform controlled ovarian stimulation and oocyte cryopreservation at the time of laparoscopic vaginoplasty.

In Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS) patients who are scheduled for laparoscopic vaginoplasty and have a desire for biological motherhood, ...

High-Resolution Cardiac Positron Emission Tomography/Computed Tomography for Small Animals

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding cardiac function and metabolism. In preclinical research, dedicated scanners with high sensitivity and high spatio-temporal resolution are employed, designed to cope with the demanding technological requirements posed by the small heart size and very high heart rates of mice and rats. In this paper, a bimodal cardiac PET/CT imaging protocol for experimental mouse and/or rat models of cardiac diseases is described, from animal preparation and image acquisition and reconstruction to image processing and visualization.
In particular, the 18F-labeled fluorodeoxyglucose ([18F]FDG)-PET scan allows for the measurement and visualization of glucose metabolism in the different segments of the left ventricle (LV). Polar maps are convenient tools to display this information. The CT part consists of a time-resolved 3D reconstruction of the entire heart (4D-CT) using retrospective gating without electrocardiography (ECG) leads, allowing the morphofunctional evaluation of the LV and the subsequent quantification of the most important cardiac function parameters, such as ejection fraction (EF) and stroke volume (SV). Using an integrated PET/CT scanner, this protocol can be executed within the same anesthesia induction without the need to reposition the animal between different scanners. Hence, PET/CT can be seen as a comprehensive tool for the morphofunctional and metabolic evaluation of the heart in several small animal models of cardiac diseases.

Here, we present an experimental imaging protocol for the quantification of cardiac function and morphology using high-resolution positron emission tomography/computed tomography for small animals. Both mice and rats are considered, discussing the different requirements of computed tomography contrast agents for the two species.

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding ...