Negative pressure wound therapy in burns: a prospective, randomized-controlled trial.

BACKGROUND: Negative-pressure-wound-therapy (NPWT) has become a widely used tool for the coverage and active treatment of complex wounds, including burns. This study aimed to evaluate the effectiveness of NPWT in acute burns of upper and lower extremities and to compare results to the standard-of-care (SOC) at our institution. METHODS: Patients that were admitted to our institution between May 2019 and November 2021 with burns on extremities between 0.5 % and 10 % of the total body surface area (%TBSA) were included and randomized to either NPWT or SOC (polyhexanide gel, fatty gauze, and cotton wool). Treatment was performed until complete wound healing. Patients that required skin grafts, received additional NPWT after grafting independent on the initial group allocation. RESULTS: Sixty-five patients suffering from burn injury between May 2019 and November 2021 were randomized into treatment with NPWT (n = 33) or SOC (n = 32); of these, 33 patients (NPWT) and 28 patients (SOC) had complete data sets and were included in the analysis. Both groups were similar regarding age (39.8 ± 13.7 vs. 44.8 ± 16.2 years,p = 0.192), total burn size (3.1 ± 2.3 vs. 3.4 ± 2.8 %TBSA,p = 0.721) and treated wound size (1.9 ± 1.2 vs. 1.5 ± 0.8 %TBSA,p = 0.138). We found no differences regarding healing time (11.0 ± 4.9 vs. 8.6 ± 3.8,p = 0.074, and significant differences in a number of dressing changes throughout the study (2.4 ± 1.5 vs 4.2 ± 1.9,p < 0.001). The Kaplan-Meier time-to-event analysis exhibited no statistically significant difference in the time to healing or skin grafting (p = 0.085) in NPWT group compared with SOC group. The median time to healing or skin grafting was 10(8-11) days for NPWT and 9(7-11) days for SOC. The hazard ratio for healing or skin graft was HR= 0.64(0.38-1.08). The results of the time-to-event analysis as well as the Kaplan-Meier curve on the PPS confirmed this result. We found no differences in secondary surgical operations 15.2 vs 21.4 % pain or functional outcomes. CONCLUSIONS: In this study, we found no significant difference between the two groups in terms of time to detect wound healing. We also found no difference regarding further operations for wound closure, pain and/or scarring. However, dressing changes were significantly less frequent for patients that were treated with NPWT, which may be a psychological and logistical advantage.

[Interdisciplinary defect reconstruction of upper aerodigestive fistulas-case series and treatment algorithm]. / Interdisziplinäre Defektrekonstruktion bei Fisteln des oberen Aerodigestivtrakts ­ Fallserie und Behandlungsalgorithmus.

BACKGROUND: Persistent complex defects and dysfunctions of the upper aerodigestive tract after tumor surgery represent a major challenge. The aim of this study was to evaluate the effectiveness of an interdisciplinary approach using the free anterolateral thigh flap (ALT) as a reconstruction option in the upper aerodigestive tract. MATERIALS AND METHODS: The retrospective study identified 5 patients with complex defects after laryngectomy/pharyngolaryngectomy (LE/PLE) and multiple revision surgeries between 2017 and 2023. The operations were performed by an interdisciplinary team from otolaryngology, plastic surgery, and visceral/thoracic surgery. The results of the microsurgical reconstruction were analyzed. RESULTS: There was an average of six previous operations. The defects included tracheoesophageal fistulas, pharyngocutaneous fistulas, neopharyngeal stenosis, and combinations thereof. Successful reconstruction was achieved in 100% of patients using the ALT flap. In 2 patients, ALT flow-through flaps were used with an additional free jejunal interposition (JI) and in 3 patients split-ALT flaps were used. The major complication rate was 40% and the minor complication rate was 20%. CONCLUSION: Complex defects of the upper aerodigestive tract with multiple previous operations can be successfully reconstructed. Because of its versatility, the ALT flap seems to be a very good option. Prerequisite for this is an interdisciplinary treatment approach with a critical assessment of patient- and disease-specific factors.

Enzymatic debridement in scalds is not as effective as in flame burns regarding additional eschar excision: A retrospective matched-control study.

OBJECTIVE: Enzymatic debridement of burn eschar became an accepted and widely used technique for burn wound treatment over the last years. However, this practice is not exempt from failure and recent experimental studies indicate that it may not be as efficient in scalds as in flame burns. METHODS: Patients that were admitted to the burn intensive care unit between June 2017 and February 2021 and received enzymatic debridement within the first 72 h after scald and flame burn were included. Patients with scald burns were matched regarding age, sex and per cent total body surface area (%TBSA) burned in a 1:2 ratio with patients presenting with flame burns. RESULTS: Eighteen patients with scald burns were matched with 36 with flame burns. After matching, both groups were similar in terms of age (flame burns 44.5 ± 21.1 years vs. scald 41.8 ± 22.6 years, p = 0.666), and %TBSA burned (11.0 ± 8.2% vs. 10.6 ± 9.6%, p = 0.851). Patients with scald burns significantly more often underwent further surgical eschar excision compared to controls (scald 16 (88.9%) vs. flame 19 (52.8%), p = 0.016). Length of stay per %TBSA was significantly longer in scald burns (scald 7.8 ± 9.2 days vs. flame 3.7 ± 3.8, p = 0.013). CONCLUSION: This study indicates that enzymatic debridement may not be as effective in scalds as in flame burns. It was shown that patients with scalds and subsequent enzymatic debridement more frequently underwent additional surgical intervention and that the size of the transplanted area was larger compared to control. Moreover, those patients had a longer length of stay at the hospital per %TBSA burned.

ICF-based multidisciplinary rehabilitation program for complex regional pain syndrome of the hand: efficacy, long-term outcomes, and impact of therapy duration.

BACKGROUND: Complex regional pain syndrome (CRPS) is a rare but feared complication in hand surgery. Although multimodal therapy concepts are recommended, there is only low evidence on efficacy of such approaches. Furthermore, recommendations regarding therapy duration are lacking. Aim of this study was to validate the efficacy of an International Classification of Functioning, Disability and Health (ICF)-based multidisciplinary rehabilitation concept for treatment of CRPS of the hand and to find correlations between therapy duration and outcome measures. METHODS: Patients with CRPS of the hand after occupational trauma that underwent an ICF-based rehabilitation program between 2010 and 2014 were included in this retrospective study. Besides demographic data, outcomes included pain (VAS), range of motion assessed by fingertip-to-palm-distance (PTPD) and fingernail-to-table-distance (FTTD) as well as strength in grip, 3-point pinch and lateral pinch. All measures were gathered at admission to and discharge from inpatient rehabilitation therapy as well as at follow-up. Statistical analysis included paired t-test, ANOVA and Pearson's correlation analysis. RESULTS: Eighty-nine patients with a mean age of 45 years were included in this study. Duration of rehabilitation therapy was 53 days on average. All outcomes improved significantly during rehabilitation therapy. Pain decreased from 6.4 to 2.2. PTPD of digit 2 to 5 improved from 2.5, 2.8, 2.6, and 2.3 cm to 1.3, 1.4, 1.2, and 1.1 cm, respectively. FTTD of digit 2 to 5 decreased from 1.5, 1.7, 1.5, and 1.6 cm to 0.6, 0.8, 0.7, and 0.7 cm, respectively. Strength ameliorated from 9.5, 3.7, 2.7 kg to 17.9, 5.6, 5.0 kg in grip, lateral pinch, and 3-point pinch, respectively. Improvement in range of motion significantly correlated with therapy duration. 54% of patients participated at follow-up after a mean of 7.5 months. Outcome measures at follow-up remained stable compared to discharge values without significant differences. CONCLUSION: The ICF-based rehabilitation concept is a reliable and durable treatment option for CRPS of the hand. Range of motion improved continuously with therapy duration and thus may serve as an indicator for optimum length of therapy.

Evidence of stage progression in a novel, validated fluorescence-navigated and microsurgical-assisted secondary lymphedema rodent model.

Secondary lymphedema (SL)is a frequent and devastating complication of modern oncological therapy and filarial infections. A lack of a reliable preclinical model to investigate the underlying mechanism of clinical stage progression has limited the development of new therapeutic strategies. Current first line treatment has shown to be merely symptomatic and relies on lifetime use of compression garments and decongestive physiotherapy. In this study, we present the development of a secondary lymphedema model in 35 rats using pre- and intraoperative fluorescence-guided mapping of the lymphatics and microsurgical induction. In contrast to the few models reported so far, we decided to avoid the use of radiation for lymphedema induction. It turned out, that the model is nearly free of complications and capable of generating a statistically significant limb volume increase by water displacement measurements, sustained for at least 48 days. A translational, accurate lymphatic dysfunction was visualized by a novel VIS-NIR X-ray ICG-Clearance-Capacity imaging technology. For the first-time SL stage progression was validated by characteristic histological alterations, such as subdermal mast cell infiltration, adipose tissue deposition, and fibrosis by increased skin collagen content. Immunofluorescence confocal microscopy analysis suggested that stage progression is related to the presence of a characteristic α SMA+/HSP-47+/vimentin+ fibroblast subpopulation phenotype. These findings demonstrate that the in-vivo model is a reliable and clinically relevant SL model for the development of further secondary lymphedema therapeutic strategies and the analysis of the veiled molecular mechanisms of lymphatic dysfunction.

Indocyanine green fluorescence-guided sentinel node biopsy: a meta-analysis on detection rate and diagnostic performance.

BACKGROUND: Indocyanine green (ICG) fluorescence-guided sentinel node biopsy (SLNB) has been successfully employed in various kinds of tumors. Clinical results of previous studies on this technique are at different levels of evidence. This Meta-analysis was conducted to provide a more precise estimation on its clinical performance. METHODS: Eligible studies were identified from systematical PubMed and EMBASE searches; data were extracted. A Meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operator characteristic curves. RESULTS: Fifteen published articles were included. Clinical data of 513 patients were obtained. The pooled detection rate, the pooled sensitivity, the pooled specificity, the pooled DOR and their 95% confidence intervals (95% CI) were 0.96 (0.91-0.99), 0.87 (0.79-0.92), 1.00 (0.99-1.00) and 150.13 (57.42-392.56), respectively. Significant heterogeneities existed among studies. Significant publication bias was found in detection rate. The concentration < 5 mg/ml subgroup and the injected volume ≥2 ml subgroup had higher DORs, sensitivities and detection rates than the concentration ≥ 5 mg/ml subgroup and the injected volume <2 ml subgroup, respectively. CONCLUSION: Based on this Meta-analysis, this technique could be valued promising for detecting the presence of LN metastases. ICG injection with reduced concentration and larger volume may provide improved performance.

Current techniques for lymphatic imaging: State of the art and future perspectives.

Techniques for lymphatic imaging are aiming at accurate, simple and minimal-invasive approaches with less side-effects and repetitive application. Limitations are emerging in conventional techniques, and new techniques have shown their advantages in high resolution and sensitivity as well as transcutaneous imaging. In the present review, these techniques and their applications are reviewed and elucidated, aiming at a better understanding of recent advancements and current trends of lymphatic imaging as well as promising techniques for future research.

[Aspects of microsurgical reconstruction for lower extremity defects]. / Aspekte der mikrochirurgischen Rekonstruktion an der unteren Extremität.

The interdisciplinary approach to lower extremity reconstruction between orthopaedic and plastic surgeons is the basis for an efficient soft-tissue coverage. The joint team and the transfer of local, regional and free flaps have been shown to reduce the rate of amputation. After the spread of microsurgical techniques and further innovations, e. g., bony reconstruction by vascularized bone grafts, microsurgery now plays an important role in lower extremity reconstruction. Main considerations for the microsurgical approach are the choice of flap type aiming at good functional results with a stable soft-tissue coverage. The use of innervated flaps and functioning muscle transfer have led to an increased patient satisfaction and quality of life. Timing of reconstruction has been shown to have an impact on the results of microsurgical reconstruction. The importance of "composite tissue allotransplantation - CTA" applied for lower extremity reconstruction has to be evaluated in further studies.

Optimizing Suprathel®-therapy by the use of Octenidine-Gel®.

OBJECTIVE: A prospective, randomized, non-blinded, clinical study was conducted to evaluate the feasibility and practicability as well as pain reduction and ease of handling of Flammazine® versus Octenidine-Gel® s a primary local antiseptic before synthetic skin substitute application in partial-thickness burns. METHODS: Thirty patients with a median age of 42 years suffering from second-degree burns were included in the study. Burns were randomly selected, one area was treated with Flammazine®/gauze, another area in the same patient was treated with Octenidine-Gel®/gauze as initial antiseptic treatment. Within 24 h the first gauze change was performed followed by wound inspection, disinfection and synthetic skin substitute application. The study focused on patient pain score, analysis of wound bed and ease of handling of the two local antiseptic agents. RESULTS: There was a significant difference between Flammazine® versus Octenidine-Gel® regarding patient pain score and ease of handling. Octenidine-Gel® was less painful (p < 0.05) and easier to handle (p < 0.05). There was no significant difference for wound bed evaluation between the two antiseptic agents. A tendency for better wound bed preparation was seen with the use of Octenidine-Gel®. CONCLUSION: Based on the findings of this study Octenidine-Gel® is recommended as a local antiseptic agent, because when compared to Flammazine®, Octenidine-Gel® proved to be better in terms of ease of care, simplicity application, with gentler and faster detachment of the gel from wound surfaces and consequently far less pain during dressing changes.

Dermal substitution with Matriderm(®) in burns on the dorsum of the hand.

BACKGROUND: Dermal substitutes are used increasingly in deep partial and full-thickness burn wounds in order to enhance elasticity and pliability. In particular, the dorsum of the hand is an area requiring extraordinary mobility for full range of motion. The aim of this comparative study was to evaluate intra-individual outcomes among patients with full-thickness burns of the dorsum of both hands. One hand was treated with split-thickness skin grafts (STSG) alone, and the other with the dermal substitute Matriderm(®) and split-thickness skin grafts. MATERIAL AND METHODS: In this study 36 burn wounds of the complete dorsum of both hands in 18 patients with severe burns (age 45.1±17.4 years, 43.8±11.8% TBSA) were treated with the simultaneous application of Matriderm(®), a bovine based collagen I, III, V and elastin-hydrolysate based dermal substitute, and split-thickness skin grafting (STSG) in the form of sheets on one hand, and STSG in the form of sheets alone on the other hand. The study was designed as a prospective comparative study. Using both objective and subjective assessments, data were collected at one week and 6 months after surgery. The following parameters were included: After one week all wounds were assessed for autograft survival. Skin quality was measured 6 months postoperatively using the Vancouver Burn Skin Score (VBSS). Range of motion was measured by Finger-Tip-Palmar-Crease-Distance (FPD) and Finger-Nail-Table-Distance (FNTD). RESULTS: Autograft survival was not altered by simultaneous application of the dermal matrix (p>0.05). The VBSS demonstrated a significant increase in skin quality in the group with dermal substitutes (p=0.02) compared to the control group with non-substituted wounds. Range of motion was significantly improved in the group treated with the dermal substitute (p=0.04). CONCLUSION: From our results it can be concluded that simultaneous use of Matriderm(®) and STSG is safe and feasible, leading to significantly better results in respect to skin quality of the dorsum of the hand and range of motion of the fingers. Skin elasticity was significantly improved by the collagen/elastin dermal substitute in combination with sheet-autografts.

Matriderm® in depth-adjusted reconstruction of necrotising fasciitis defects.

Necrotising fasciitis (NF) and Fournier's gangrene are still a source of high morbidity and mortality and a significant health-care resource consumption. These difficult cases are increasingly being referred to burn centres for specialised wound and critical care issues. Besides the total body surface area (TBSA) affected, location, co-morbidities, age and an immediate surgical treatment are important prognostic factors. The treatment of these patients is challenging and best performed by prompt diagnosis, immediate radical surgical debridement and aggressive critical care management. Referral to a major burn centre may help provide optimal surgical intervention, wound care and critical care management.As soon as the patient is stabilised, reconstruction of the injured areas becomes the main focus. As often seen, complete loss of dermal structures needs a depth adjusted--'multilayer'--reconstruction especially in critical areas. In modern reconstructive surgery, concepts of layer-specific reconstruction, including dermal substitution have to be considered. In this article, we present our recent experiences of five patients with NF who underwent dermal reconstruction with Matriderm® not only for better skin quality but also in some cases as an alternative to flap surgery when joint capsules or tendons were exposed.

Long-term results and the Disabilities of the Arm, Shoulder, and Hand score analysis after modified Brooks and D'Aubigne tendon transfer for radial nerve palsy.

PURPOSE: Radial nerve damage results in substantial functional limitations of the upper extremity. No detailed data exist regarding long-term results, patient satisfaction, and professional and social reintegration after tendon transfer for irreparable damage to the radial nerve. In this retrospective study, we investigated these data through the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. METHODS: Between 1995 and 2006, 77 patients underwent a modified Brooks and d'Aubigne surgical technique for radial nerve palsy in our department. In 19 cases, the flexor carpi radialis muscle was used as a donor instead of the flexor carpi ulnaris muscle. The mean follow-up period was 60 months (range, 24-150 months); motion of the wrist and finger joints and pinch-grip power were compared with the healthy side. We assessed the limitation in pursuing daily activities using the DASH score. RESULTS: Wrist extension averaged 73% of the contralateral side, whereas the value for movement of digital extension was 32% and for thumb abduction in the palmar direction it was 80%. The power grip was reduced to 49% and the pinch grip was reduced to 28%. The mean DASH score was 15 +/- 9, the symptom score mean was 15 +/- 7, and the working score mean was 12 +/- 10. The mean total DASH score was 16 +/- 10. The proportion of patients who remained employed after surgical treatment was 89%. CONCLUSIONS: Functional results, adequate patient satisfaction, and sufficient professional and social reintegration can be achieved after modified Brooks and d'Aubigne tendon transfer. Accordingly, the tendon transfer offers an important alternative-possibly the procedure of choice-to microsurgical nerve reconstruction, particularly when early professional and social reintegration is important.

The use of MatriDerm in early excision and simultaneous autologous skin grafting in burns--a pilot study.

The application of dermal substitutes in deep partial and full-thickness burn wounds in a two-stage procedure prior to skin grafting has become increasingly popular. Synchronous application of dermal substitutes and skin graft has not yet been established as a standard procedure. In a consecutive study 20 wounds in 10 patients with severe burns (age 49.5+/-16.2 years; TBSA 45.6+/-14.5%) were treated with either simultaneous transplantation of Matriderm, a bovine based collagen I, III, V and elastin hydrolysate based dermal substitute and split-thickness skin grafting (STSG), or STSG alone after appropriate excision of the burn wound. The study was designed as a prospective intra-individual comparative study. After 1 week all wounds were assessed for the percentage of autograft survival. Autograft survival was not altered by simultaneous application of a dermal matrix (p=0.015). Skin elasticity was measured after 3-4 months with the Vancouver Burn Skin Score (VBSS). The VBSS demonstrated a significant increase of elasticity in the group with dermal substitutes (p=0.04) as compared with non-substituted wounds for sheet autograft, but not for meshed autograft (p=0.24). From this pilot study it can be concluded that simultaneous application of a dermal matrix is safe and feasible, yielding significantly better results with respect to skin elasticity. Skin elasticity was considerably improved by the collagen/elastin dermal substitute Matriderm in combination with sheet autograft.

[Vacuum-assisted closure therapy. Current status and basic research]. / Vakuumtherapie. Aktueller Stand der Grundlagenforschung.

The gap between the broad clinical use of vacuum-assisted closure therapy (VT) and knowledge of the physiological mechanisms leading to its effectiveness is great. The value of the technique and its future development are dependent on research into these mechanisms. A meta-analysis evaluating the results of basic research on the effectiveness of VT was carried out based on peer reviewed publications. This is considered in relation to other therapeutic approaches of basic research to wound healing (growth factors etc.). Our study includes a concise description of the scientific background to the mechanisms of cell stimulation using basic work on tissue expansion, bone, vessel and nerve distraction as well as in vitro cell stimulation. Evaluation of the scientific data on all known effects of VT was made based on the results from experimental animal studies, the results of randomized clinical studies, observations on clinical applications and case reports. Assessment of the studies was based on design and significance as well as the appraisal of our own clinical experience. Data involving cellular effects (proliferation, synthesis, wound healing), systemic effects (mediators, systemic inflammatory disease), extracellular effects (perfusion, edema, local wound environment, stabilization, barriers) and complex effects of VT (inflammation, matrix function, blood supply) were examined. Systematic analysis of the data allows scientifically interested surgeons rapid access to the theme, the first, to this extent, extensive overview of the current scientific situation as well as a comprehensive bibliography for all areas involving the theme of mechanical cell stimulation. The authors list major areas for future research and encourage the development of multicenter studies.

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery.

BACKGROUND: Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. METHODS/DESIGN: CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. DISCUSSION: As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice.

[Experiences with the distally based dorsal metacarpal artery (DMCA) flap and its variants in 41 cases]. / Erfahrungen mit der distal gestielten, dorsalen Metakarpalarterien (DMCA)-Lappenplastik und ihren Varianten in 41 Fällen.

Distally based DMCA flaps are an established procedure for soft tissue reconstruction in the hand. Since the introduction of the DMCA flaps, several variants have been developed to match specific defect requirements. The aim of this retrospective study is to give an overview of the experience with the DMCA flaps based on a single center's experience. 41 distally based DMCA flaps have been performed from 2000 to 2004. Twenty-nine times a distally based DMCA flap has been performed, nine times the extended distally based DMCA flap and three times a distally based DMCA fascial flap. In summary, 34 flaps showed no complications, five had a partial necrosis, but were successfully treated with split-thickness skin graft, and two flaps were lost due to infections. The distally based DMCA flaps II to IV have proven to be reliable flaps, but nevertheless require sufficient surgical experience. They are suitable for any kind of defects, including burn reconstruction. Defects of the entire finger can be covered by the various variants of the DMCA flaps.

[Burned palm reconstruction. Current concepts regarding grafting techniques, sensibility and hand function]. / Palmare Verbrennung der Hand. Aktuelles Therapiekonzept unter Berücksichtigung der Transplantatwahl, Sensibilität, Kraftentwicklung und Funktionalität.

BACKGROUND: The purpose of this study was to evaluate the results of conservative and operative treatment for burn injuries in the palmar region of the hand. METHODS AND CLINICAL MATERIAL: One hundred ten patients from the severe burn center in Ludwigshafen, Germany were evaluated a mean of 28 months postoperatively. Sixty-one had been treated with split-thickness skin grafts (43 sheet and 18 mesh grafts). In addition to subjective evaluation (including pain assessment and aesthetic outcome rating by visual analog scale), objective outcome analysis included clinical tests, measurement of active range of motion and grip strength, and sensibility testing with the two-point discrimination and Semmes-Weinstein monofilament tests. RESULTS: Of the patients, 90% were satisfied with the results, showing excellent pain relief with an average score under 13 on the visual analog scale. Aesthetic outcome was rated good with sheet grafts; in appearance, mesh grafts tended to be rated average or insufficient. Functional outcome tests demonstrated a significant correlation between depth of injury and range of motion. Grip strength analysis revealed superior results with sheet grafts. Sensibility in the injured areas was lower than on the contralateral hands. The Semmes-Weinstein test average was 3.4 degrees at the burned area vs 3.0 degrees in healthy hands, underscoring lower sensibility after burns. CONCLUSION: Surgical treatment of burned palms leads to good subjective and objective results, if specialized burn units are involved. Overall sheet transplantation seems to be the better choice for surgical reconstruction of the palmar burned hand.

Postnatal development of opioid receptors modulating acetylcholine release in hippocampus and septum of the rat.

The postnatal development of presynaptic opioid receptors inhibiting the release of acetylcholine (ACh) was studied in rat brain hippocampus, medial septum (MS) and diagonal band of Broca (DB). To this end, the corresponding brain slices (350 microm thick) of rats of various postnatal ages (postnatal day 4 [P4] to P16, and adult) were preincubated with [(3)H]choline and stimulated twice for 2 min (S(1), S(2): at 3 Hz, 2 ms, 60 mA) during superfusion with physiological buffer containing hemicholinium-3. In parallel, the activity of choline acetyltransferase (ChAT) was determined in crude homogenates of the tissues as a marker for the development of cholinergic neurons. At any postnatal age, the electrically evoked overflow of tritium from slices preincubated with [(3)H]choline was highest in the DB, followed by the MS and the hippocampus. The evoked [(3)H]overflow increased with postnatal age, reached about 50% (MS, DB) or 30% (hippocampus) of the corresponding adult levels at P16 and correlated significantly with the corresponding ChAT activities. Presence of the preferential mu-opioid receptor agonist DAMGO during S(2) significantly inhibited the evoked overflow of tritium already at P4 in DB and MS, whereas in the hippocampus significant inhibitory effects were first observed at P8 only. Moreover, adult levels of inhibition due to DAMGO were reached at P16 in the DB and MS but not in the hippocampus. In septal areas, also the effect of the preferential delta-opioid receptor agonist DPDPE on the evoked [(3)H]overflow was studied: in contrast to DAMGO, however, significant inhibitory effects of DPDPE were first observed at P12 only. In conclusion, the postnatal development of presynaptic mu-opioid receptors on cholinergic neurons in the DB and MS starts earlier than in the hippocampus and precedes that of presynaptic delta-opioid receptors.

Characterization of opioid receptor types modulating acetylcholine release in septal regions of the rat brain.

Presynaptic opioid receptors of the delta- and mu-types have been shown to inhibit the release of acetylcholine (ACh) in the rat striatum and hippocampus, respectively, but it is unknown whether opioid receptors modulate the release of ACh also in the region of origin of the hippocampal cholinergic innervation, the septum. To answer this question, slices (350 microm) of the medial septal area and of the diagonal band of Broca, as well as (for comparison) of the hippocampus, were prepared from adult male Wistar rats. The slices were incubated with [3H]choline, superfused in the presence of hemicholinium-3 (10 microM) and stimulated twice (S1, S2) by electrical fields (360 pulses, 3 Hz, 2 ms, 60 mA); opioid receptor agonists were present during S2. The preferential mu-agonist [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) inhibited the evoked ACh release by maximally about 40% in hippocampal slices and acted even more strongly in the medial septal area, or the diagonal band of Broca (about 60% or 75% maximal inhibition, respectively). These effects were reduced or abolished by the preferential mu-antagonist naloxone, which showed no effects when given alone. Using naloxone in the presence of a cocktail of peptidase inhibitors, no evidence for an endogenous tone of opioid peptides was found in the medial septal area, diagonal band of Broca or the hippocampus. Using the preferential delta-agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) and the delta-antagonist naltrindole, a delta-opioid receptor inhibiting evoked ACh release was clearly detectable both in the medial septal area and the diagonal band of Broca, but not in the hippocampus, whereas the preferential kappa-agonist trans-3,4-dichloro-N-methyl-N-[2(1-pyrrolidinyl)cyclo-hexyl] benzeneacetamide (U50,488H) had only weak or no effects. In addition to the functional experiments, double in-situ hybridization studies were performed, in which cells containing mRNA for choline acetyltransferase (ChAT) were labeled by an antibody-linked enzymatic staining procedure, whereas mRNAs for mu- or delta-opioid receptors were detected with radioactive probes. These experiments revealed that in the septal region mainly mu-opioid receptors were expressed by neurons positive for ChAT mRNA, whereas in the rat striatum the expression of delta-opioid receptors prevailed in those neurons. We conclude that in the septal area of the rat brain, in contrast to the rat striatum and hippocampus, both presynaptic mu- and delta-opioid receptors modulate the evoked release of ACh. Whether presynaptic mu- and delta-opioid receptors occur on the same or on different septal cells or axon terminals remains to be clarified.