Insight in human skin microcirculation using in vivo reflectance-mode confocal laser scanning microscopy.

Reflectance-mode confocal laser scanning microscopy allows in vivo imaging of the human skin. We hypothesized that this high-resolution technique enables observation of dynamic changes of the cutaneous microcirculation. Twenty-two volunteers were randomly divided in two groups. Group 1 was exposed to local heating and group 2 to local cold stress. Confocal microscopy was performed prior t (0) (control), directly t (1) and 5 min t (2) after local temperature changes to evaluate quantitative blood cell flow, capillary loop diameter, and density of dermal capillaries. In group 1, blood flow increased at t (1) (75.82 +/- 2.86/min) and further at t (2) (84.09 +/- 3.39/min) compared to the control (61.09 +/- 3.21/min). The control capillary size was 9.59 +/- 0.25 microm, increased to 11.16 +/- 0.21 microm (t (1)) and 11.57 +/- 0.24 microm (t (2)). The dermal capillary density increased in t (1) (7.26 +/- 0.76/mm(2)) and t (2) (8.16 +/- 0.52/mm(2)), compared to the control (7.04 +/- 0.62/mm(2)). In group 2, blood flow decreased at t (1) (41.73 +/- 2.61/min) and increased at t (2) (83.27 +/- 3.29/min) compared to the control (60.73 +/- 2.90/min). The control capillary size was 9.55 +/- 0.25 microm, decreased at t (1) (7.78 +/- 0.26 microm) and increased at t (2) (11.38 +/- 0.26 microm). Capillary density decreased at t (1) (5.01 +/- 0.49/mm(2)) and increased at t (2) (7.28 +/- 0.53/mm(2)) compared to the control (7.01 +/- 0.52/mm(2)). Confocal microscopy is a sensitive and noninvasive imaging tool for characterizing and quantifying dynamic changes of cutaneous microcirculation on a histomorphological level.

Interferon: production by chick erythrocytes activated by cell fusion.

In the presence of Sendai virus inactivated with ultraviolet light, nucleated chick erythrocytes can be fused with several types of human cells to form heterokaryons. Although chick erythrocytes alone cannot be stimulated by Sendai virus to produce interferon, fusion with a human cell (AH-1) which itself may produce human interferon results in heterokaryons in which the erythrocyte genome is activated and chick interferon is produced. When nucleated chick erythrocytes are fused with another type of human cell (HeLa clone S-3) which does not produce human interferon when stimulated, no chick interferon is detectable, despite morphologic changes suggestive of activation of the erythrocyte nuclei.

Is superficial burn caused by ultraviolet radiation (sunburn) comparable to superficial burn caused by heat--a histomorphological comparison by in vivo Reflectance-Mode-Confocal Microscopy.

BACKGROUND: Regardless of the underlying cause, both sunburn and superficial thermal injuries are classified as first-degree burns, since data on morphological differences are scarce. Reflectance-Mode-Confocal Microscopy (RMCM) enables high-resolution non-invasive investigation of the human skin. OBJECTIVE: We studied in vivo histomorphological alterations in both sunburn and superficial thermal injuries using RMCM. METHODS: Ten patients (6 female, 4 male; aged 28.4 +/- 10.6 years) with first-degree thermal-contact Injuries (TI group), and 9 sunburned patients (SB group; 7 female, 2 male; aged 30.2 +/- 16.4 years), to a maximum extent of 10% of the body surface were evaluated 24 h after burn injury using RMCM. The following parameters were obtained using RMCM: stratum corneum thickness, epidermal thickness, basal layer thickness, granular cell size. RESULTS: Compared to the controls (12.8 +/- 2.5 microm), stratum corneum thickness decreased significantly to 10.6 +/- 2.1 microm in the TI group, whereas it increased significantly to 16.4 +/- 3.1 microm in the SB group. The epidermal thickness did not differ significantly in the TI group (47.9 +/- 2.3 microm) and SB group (49.1 +/- 3.5 microm); however, both increased significantly compared to their respective controls (41.8 +/- 1.4 microm). The basal layer thickness increased more in the SB group compared to the TI group (17.9 +/- 1.4 microm vs. 15.6 +/- 1.1 microm). Both differed also significantly compared to their controls (13.8 +/- 0.9 microm). The granular cell size increased significantly in both groups compared to the controls (731 +/- 42 microm); however, a significantly higher increase was observed in the TI group (852 +/- 58 microm) compared to the SB group (784 +/- 61 microm). CONCLUSIONS: Ultraviolet radiation seems to influence predominantly deeper epidermal layers, whereas heat-induced burns affect more superficial epidermal layers. The term 'First-degree burn' should not be used synonymously for sunburn and superficial thermal burn injuries. Conflicts of interest None declared.

The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma--a retrospective analysis of 392 cases.

Twenty per cent of sentinel lymph node (SLN)-positive melanoma patients have positive non-SLN lymph nodes in completion lymph node dissection (CLND). We investigated SLN tumour load, non-sentinel positivity and disease-free survival (DFS) to assess whether certain patients could be spared CLND. Sentinel lymph node biopsy was performed on 392 patients between 1999 and 2005. Median observation period was 38.8 months. Sentinel lymph node tumour load did not predict non-SLN positivity: 30.8% of patients with SLN macrometastases (> or =2 mm) and 16.4% with micrometastases (< or =2 mm) had non-SLN positivity (P=0.09). Tumour recurrences after positive SLNs were more than twice as frequent for SLN macrometastases (51.3%) than for micrometastases (24.6%) (P=0.005). For patients with SLN micrometastases, the DFS analysis was worse (P=0.003) when comparing those with positive non-SLNs (60% recurrences) to those without (17.6% recurrences). This difference did not translate into significant differences in DFS: patients with SLN micrometastasis, either with (P=0.022) or without additional positive non-SLNs (P<0.0001), fared worse than patients with tumour-free SLNs. The 2-mm cutoff for SLN tumour load accurately predicts differences in DFS. Non-SLN positivity in CLND, however, cannot be predicted. Therefore, contrary to other studies, no recommendations concerning discontinuation of CLND based on SLN tumour load can be deduced.

[Surgical treatment of high-voltage electrical injuries]. / Die chirurgische Behandlung von Hochspannungsverletzungen.

PURPOSE/BACKGROUND: High-voltage burns represent a challenging surgical entity. Compared to conventional burns, these injuries are characterized by an increased morbidity and worse potential for rehabilitation. The aim of the present study was to analyse the management of high-voltage injuries during the early posttraumatic period with special emphasis on the surgical procedures. PATIENTS/MATERIAL AND METHOD: We retrospectively evaluated the medical records of patients with electrical injuries treated from 1995 - 2007. A total of 61 patients (57 men, 4 females, mean age: 34 +/- 13 years) with high-voltage burns was included for analysis. RESULTS: The majority of high-voltage burns was work-related (75 %). The mean total burn area was 35 % of the total body surface, with a mean of 29 % deep burns. An average of 4.8 +/- 4 operations were performed per patient (range: 1 - 23 operations). Surgical procedures included repeated debridement/necrectomy (100 % of all patients), early escharotomy/fasciotomy (47.5 %), and amputations (18 %). 14 patients (23 %) underwent reconstructive surgery using either local or free flaps. The mortality rate was 15 %. CONCLUSION: The surgical management of high-voltage burns is characterised by repetitive debridements and necrectomies. Despite an aggressive approach to remove necrotic tissue, the mortality in this type of injury is considerably high. Limb salvage may be achieved with the use of free microvascular flaps. However, an amputation of necrotic extremities must be considered in the copresence of septic complications.

["True neurologic thoracic outlet syndrome" -- anatomical features and electrophysiological long-term follow-up of lateral thenar atrophy]. / "True Neurologic Thoracic Outlet Syndrome" -- Anatomie und elektrophysiologischer Langzeitverlauf bei lateraler Thenaratrophie.

Atrophies of the intrinsic muscles of the hand are considered to be a typical symptom of the "true neurologic" form of thoracic outlet syndrome (TOS). The classical form of this entity was described as early as 1970, consisting of a cervical rib or a prolonged transverse process of C7, complete with a fibrous band to the first thoracic rib, resulting in atrophy of the intrinsic muscles of the hand. All our TOS patients presenting with such atrophy displayed anatomical findings consistent with this definition. Based on this observation, the TOS classification currently in clinical use, which differentiates between "disputed" and "true neurologic" subgroups of the neurologic form, is reviewed. In all cases of "true neurologic TOS" with atrophy of the intrinsic muscles of the hand, the lateral thenar muscles are affected first. We present the electrophysiological long-term results of such thenar atrophies of seven patients with eight operated extremities after brachial plexus decompression. The amplitude of the neurographically measured potential over the opponens pollicis and the abductor pollicis brevis muscle, respectively, was defined as quantitative parameter for muscles atrophy. Neither distinct reinnervation nor progressive denervation was evident in any of the cases after a follow-up period, on average, of more than five years post surgery. These findings are in conflict with clinical observations reporting a major postoperative improvement of the motor deficits.

Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation.

Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritransplant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients.

Major burn injuries associated with Christmas celebrations: a 41-year experience from Switzerland.

In Switzerland it is customary to light candles on Christmas trees and advent wreaths. This tradition leads to an increased risk of home fires. We reviewed the records of patients who sustained burn injuries from a lit Christmas tree or advent wreath during the Christmas holidays between January 1971 and January 2012. We treated 28 patients and observed 4 fatalities (mortality rate: 14%). 61% of the patients were male, 39% were female. The mean abbreviated burn severity index (ABSI) was 6.5 points in the group of the survivors and 10.8 points in the group of the non-survivors. The mean total body surface area burned (TBSA) for survivors was 18.9%, with 14.1% having full thickness burns; for the non-survivors the mean TBSA was 45.2%, with 38% having full thickness burns. The Mann-Whitney U-test showed a significant difference between the survivors and the fatalities concerning the mean total and full thickness burned body surface area (p value 0.009 and 0.012). More than sixty percent of the fires occurred in January and the most severe accidents were seen after January 4th. Despite Christmas decoration-associated fires being relatively uncommon, they tend to cause more serious injuries than regular household fires. We recommend that in countries where it is customary to set up flammable Christmas decorations, state-issued information pamphlets with instructions on fire safety conduct should be distributed.

En Suisse il est de coutume de mettre des bougies allumées sur les arbres de Noël et sur les couronnes de l'Avent. Cette tradition aument le risque d'incendies de maison. Nous avons examiné les dossiers de patients ayant subi des brûlures causées par un arbre de Noël ou une couronne de l'Avent pendant les vacances de Noël entre Janvier 1971 et Janvier 2012. Nous avons traité 28 patients et observé 4 décès (taux de mortalité: 14%). 61% des patients étaient des hommes, 39% étaient des femmes. La moyenne "indice abrégée de gravité de la brûlure" était de 6,5 points dans le groupe des survivants et 10,8 points dans le groupe des décédés. La moyenne de la surface corporelle totale brûlée (SCT) pour les survivants était de 18,9% - avec 14,1% ayant des brûlures au troisième degré; pour les non-survivants la moyenne SCT était de 45,2% - avec 38% ayant des brûlures au troisième degré. Le test U de Mann-Whitney a montré une différence significative entre les survivants et les non-survivants qui concerne la totale moyenne et l'épaisseur total brûlé de la surface du corps (valeur p de 0,009 et 0,012). Plus de 60% des incendies a eu lieu en Janvier et les accidents les plus graves ont été observés après le 4 Janvier. Meme si les incendies associés aux décorations de Noël sont relativement rares, ils ont tendance à causer des blessures plus graves que les incendies domestiques réguliers. Nous recommandons que, dans les pays où il est d'usage de mettre en place des décorations de Noël inflammables, les brochures d'information soient distribués par l'état avec des instructions sur le comportement de sécurité.

Congenital retardation and central motor defect with later evolution of seizure disorder, orofacial dysplasia, and amyotrophy. A clinicopathologic report.

Retarded mental and motor development was observed during the first year of life of a full-term female who had been delivered with difficulty. Generalized psychomotor seizures and dysplastic "acromegalic" facial changes began to develop when she was 8 years old, and generalized amyotrophy developed over the next several years. The course was generally progressive, and she died at age 31. A variety of clinical laboratory studies were nondiagnostic. Autopsy findings showed normal brain weight and normal-appearing cerebral hemispheres, a peculiar atrophy of the inferior portion of the cerebellar hemispheres, a demyelinating process in the dorsal columns of the cervical and thoracic spinal cord, and lateral column and motor neuron degeneration. The pathogenesis of the syndrome is undetermined.

Ultrastructural and histochemical abnormalities of skeletal muscle in patients with chronic vitamin E deficiency.

We report muscle biopsy abnormalities in four patients with a chronic cholestatic syndrome, low serum vitamin E levels, absent reflexes, mild limb weakness, ataxia, and sensory loss in arms and legs. Skeletal muscle fibers contained multiple autofluorescent inclusions that show strong acid phosphatase and esterase reactivity. By electronmicroscopy, the inclusions lying between myofibrils were membrane-bound dense bodies having characteristics of both lysosomes and lipopigment material. The material was similar to that observed in vitamin E-deficient animals and probably formed in response to disordered intracellular lipid peroxidation.

Schizencephaly: a clinical and CT study.

Schizencephaly is a primary developmental defect of the brain, presumably caused by failure of formation of the cerebral mantle in the regions of the cerebral fissures. Identification has usually been at autopsy, in association with severe neurologic abnormalities. We identified the characteristic features of schizencephaly on CTs in 11 patients. Age at detection ranged from an infant at 8 months to a 30-year-old adult. Clinical abnormalities varied from mild to severe, including developmental delays and retardation, microcephaly, focal or generalized motor abnormalities, and seizures. CT findings included cerebral clefts, infolding of cortical gray matter along the clefts, an abnormal ventricular system, and other associated cerebral anomalies.

Neonatal hyperviscosity. II. Effect of partial plasma exchange transfusion.

To determine the effect of partial plasma exchange transfusion, 20 newborn infants with neonatal hyperviscosity were randomly assigned to observation or treatment with partial plasma exchange transfusion within the first eight hours after birth. They were studied for organ involvement by roentgenogram, blood count, coagulation studies, and neurologic behavior and were followed up using the Brazelton Neonatal Behavior Assessment scale at 8, 24, and 72 hours and 2 weeks of age; in addition, ten control infants without hyperviscosity of similar birth weights and gestational ages were also studied. Exchange transfusion improved blood viscosity but both hyperviscous groups showed a higher proportion of abnormal results than did the control subjects. Infants receiving exchange transfusions subsequently improved during the period from 8 hours to 2 to 3 weeks of age, until they were indistinguishable from the control subjects. Neurologic improvement in hyperviscous infants who had not received exchange transfusions were significantly slower during this period. At 8 months of age, abnormal neurologic and developmental findings were impressive in both groups; no significant differences in neurologic abnormalities were noted at that time. Developmental delays, tremors, spastic diplegia, and monoparesis were found in four of six untreated infants and five of ten infants who had received exchange transfusions. A fine tremor was present in one control child.

Role of coagulopathy in newborn intracranial hemorrhage.

Fifty newborn infants of less than 33 weeks' gestation were followed prospectively from birth with serial coagulation and real-time ultrasound studies. A significant association of hypocoagulability in the first four hours of life with subsequent onset or progression of intraventricular or other clinical hemorrhages was documented. Abnormalities included lower values for fibrinogen, platelet count, antithrombin III, and factor VIII with higher values for fibrin monomer and longer Laidlaw whole blood clotting times. These abnormalities tended to correct spontaneously in surviving infants. An association between gestational complications and incidence of hypocoagulability and intracranial hemorrhage (ICH) was noted. Babies of preeclamptic mothers had fewer abnormalities and babies born to mothers with premature rupture of membranes and suspected amnionitis manifested more hypocoagulability and more severe intracranial hemorrhages.

Timing and antecedents of intracranial hemorrhage in the newborn.

Fifty newborn infants of less than 33 weeks' gestation were followed prospectively from birth to evaluate the temporal relationships of various clinical factors to the onset and progression of intracranial hemorrhage (ICH) in an inborn population given maximal support. ICH was diagnosed and followed with bedside ultrasound every eight hours. The incidence of intraventricular hemorrhage was 30% and of any ICH was 40% with onset from less than 2 hours to 8 days of age. Grades 2, 3, and 4 ICH correlated with Apgar scores of less than 5 at five minutes, vaginal delivery, longer labors, and intrapartum hemorrhage. There was a significant correlation between ICH and both blood pressure fluctuations of greater than 100% and rapid colloid infusions. Slow transfusions of packed red cells did not appear to precipitate episodes of ICH. In a setting of optimal care, ICH appears to be more related to prenatal stresses than to specific postnatal complications.

Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: clinical and muscle biopsy findings and treatment with alpha-tocopherol.

We have studied four children (ages 6 to 17 years) with chronic cholestasis who developed a slowly progressive neuromuscular disease characterized by ataxia, dysmetria, areflexia, loss of vibratory sensation, and a variable ophthalmoplegia. Serum vitamin E concentrations were low in all patients prior to treatment (0.17-2.0 mg/g cholesterol, normal greater than 3 mg/g). Muscle histochemical studies showed prominent yellow autofluorescence, basophilic cytoplasmic inclusions which stain with esterase and acid phosphatase, and occasional necrotic fibers. Ultrastructural findings consisted of increased number and size of membrane-bound dense bodies (lysosomes), membranous whorls, and autophagic vacuoles. Intramuscular injections of all-rac-alpha-tocopherol (0.55-1.42 mg/kg per 24 hours based on individualized pharmacokinetic data) were required in three patients to achieve normal serum vitamin E values. High-dose (32 mg/kg per 24 hours) oral supplementation was effective in one patient. After normalization of serum vitamin E concentrations for 12 to 20 months, the neurologic disease has improved in all four patients.

Neonatal intracranial hemorrhage and maternal use of aspirin.

A prospective study of 108 infants born at 34 weeks' gestation or earlier or weighing 1500 g or less was carried out to determine the incidence of intracranial hemorrhage and the multiple risk factors that may cause or aggravate this hemorrhage in premature infants. On day 2 post partum, mothers were questioned regarding maternal risk factors, including the use of either aspirin or acetaminophen during the last week of pregnancy. Between days 3 and 7 post partum, computed tomographic scanning was performed on the 108 infants. Of the total, 53 (49%) developed intracranial hemorrhage. The incidence of hemorrhage in the infants whose mothers had ingested aspirin was significantly greater (P less than .05) than that seen in infants whose mothers did not take either aspirin or acetaminophen (control group). The incidence of intracranial hemorrhage among infants whose mothers ingested acetaminophen was not significantly different from that of the control group. This study indicates that aspirin is associated with an increased incidence of intracranial hemorrhage in the authors' population. The use of aspirin in the last 3 months of pregnancy is highly questionable and probably inappropriate.

Treatment of radiocarpal degenerative osteoarthritis by radioscapholunate arthrodesis: long-term follow-up.

Radioscapholunate arthrodesis is the treatment of choice for symptomatic, degenerative radioscapholunate osteoarthritis. We report on three patients after radioscapholunate arthrodesis with a follow-up of 22-28 years. There were no short-term postoperative complications; range of motion and strength were stable. All three patients showed radiological evidence of progressive, but clinically asymptomatic midcarpal osteoarthritis. The conversion rate for radioscapholunate to panarthrodesis of the wrist is reported at 31% with follow-ups of more than five years, invariably due to either non-union, or progressive, symptomatic midcarpal osteoarthritis. Primary excision of the distal pole of the scaphoid during radioscapholunate arthrodesis probably plays an important role in avoiding these conditions in the long-term. This measure allows a residual range of motion more than previously believed; considering that the dart thrower's motion is the physiological axis of wrist motion.

[The role of surgery in the treatment of cutaneous melanoma]. / Die Rolle der Chirurgie in der Behandlung des kutanen Melanoms.

Historically, melanoma patients were subject to wide local excisions and elective lymph node dissections. Both approaches were the focus of intense scrutiny in the past three decades, and many surgical dogmas were abolished. The role of surgery in providing local control over the primary tumor is largely undisputed. In addition, the surgical management strategies of the regional lymph nodes have undergone considerable change in the past; with lymphatic mapping and sentinel lymph node identification being the most relevant contribution, allowing selection of patients for adjuvant treatment (completion lymph node dissection, Interferon therapy). Surgery has also a place in palliative treatment of isolated systemic metastases for selected cases with good performance status in Stage IV melanoma.