The combination of hyaluronic acid and collagenase in the treatment of skin ulcers: an open, multicenter clinical study assessing safety and tolerability of Bionect Start®.

OBJECTIVE: Several clinical studies have shown that hyaluronic acid collagenase is well-tolerated and very effective in managing chronic venous ulcers. The aim of the present study is to confirm the safety and tolerability of daily application in patients suffering from cutaneous ulcers of different etiologies. The efficacy of the treatment and its impact on patients' quality of life are also assessed. PATIENTS AND METHODS: Patients with a clinical diagnosis of skin ulcer with devitalized/fibrinous/slough tissue that could delay the healing process were enrolled in the study. The hyaluronic acid/collagenase ointment was applied topically until wound closure or total debridement of non-viable tissue was achieved, however, with a limit of 30 days. Monitoring was performed weekly, either through outpatient visits or telephone surveys. Assessments included adverse events, local irritation reactions, pain at dressing changes, and wound bed status. Patients were also requested to complete a quality-of-life questionnaire. RESULTS: The study involved 96 patients with a mean age of 71 years. The patients suffered mainly from traumatic (21.9%), venous (15.6%), or pressure ulcers (12.5%); in 26% of cases, ulcers had mixed etiology. In approximately 32% of patients, the ulcer had been present for more than 6 months, and 18.1% of subjects had previously undergone surgical wound debridement. CONCLUSIONS: Daily application of hyaluronic acid-collagenase achieved the following results: i) absence of adverse events related to the use of the product; ii) significant reduction in the degree of localized irritation and pain at dressing changes; iii) significant support to wound bed preparation; iv) trend towards improvement in the quality of life and health status of the patients.

Remodeling of uterine innervation.

This minireview reports current hypotheses concerning the remodeling of sympathetic innervation in rodent and human uterus during the estrous cycle and gestation. Neural modulation in this organ is related to sexual hormone concentrations, and a reduction in nerve density is observed when estrogen levels are high during the estrous cycle. Estrogen receptor alpha is considered to be the major receptor mediating the action of estrogen. In the uterus, the expression of neurotrophins, such as nerve growth factor, which are involved in the survival and growth of nerve fibers, changes in response to steroid levels. Despite much research, further studies are necessary to clarify various aspects of nerve growth control under diverse physiological conditions. These studies could be of importance, since alterations of the biological mechanisms of uterus innervation may play significant roles in various pathologies, such as infertility and spontaneous abortion.

Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice.

Accumulation of visceral fat is a key phenomenon in the onset of obesity-associated metabolic disorders. Macrophage infiltration induces chronic mild inflammation widely considered as a causative factor for insulin resistance and eventually diabetes. We previously showed that >90% of macrophages infiltrating the adipose tissue of obese animals and humans are arranged around dead adipocytes, forming characteristic crown-like structures (CLS). In this study we quantified CLS in visceral and subcutaneous depots from two strains of genetically obese mice, db/db and ob/ob. In both strains, CLS were prevalent in visceral compared with subcutaneous fat. Adipocyte size and CLS density exhibited a positive correlation both in visceral and in subcutaneous depots; however, the finding that adipocyte size was smallest and CLS density highest in visceral fat suggests a different susceptibility of visceral and subcutaneous adipocytes to death. Visceral fat CLS density was 3.4-fold greater in db/db than in ob/ob animals, which at the age at which our experimental strain was used are more prone to glucose metabolic disorders.

Combined surgical approach for carotid and coronary stenosis. Sixty-four patients and review of literature.

BACKGROUND: The proper role of combined carotid endarterectomy (CEA) and coronary bypass (CABG) is still controversial. We contribute to the discussion through the critical evaluation of 64 consecutive patients, whose data have been collected in a prospective way. METHODS: Between 1990 and 1999, 64 patients presenting a critical coronary disease (unemendable by PTA) associated with severe carotid stenosis (= or >70% if symptomatic, = or >80% if asymptomatic), underwent combined CEA-CABG. Cardiological symptoms were evident in 90.6% of cases. Thirty-five patients (54.7%) had a three-vessel coronaropathy, 18 (28.1%) a two-vessel disease and 11 (17.2%) severe stenosis of the common trunk; furthermore 7 patients (10.9%) had a low ejection fraction (<50%). A positive neurologic history was present in 22 (44%) patients. Thirty-four patients (55%) had a carotid stenosis >90%; a significant disease of the contralateral carotid axis was observed in 53% of cases: stenosis >50% in 30 patients and thrombosis in 4. CEA was performed with somato-sensorial evoked potential monitoring. RESULTS: The hospital mortality rate was 6.2% (4 patients). The cause of death was cardiac in 2 cases (1 early bypass thrombosis and 1 irreversible coronary spasm) and related to a multiorgan failure in 2. The neurologic morbidity rate was 0%. CONCLUSIONS: Our data highlight that in these high-risk patients the combined approach dramatically reduces the stroke risk although the mortality rate is still higher than that observed after CEA or CABG.

Divided nevus of the eyelid: a case report.

Divided nevus of the eyelid as a rare pathologic entity and develops during fetal growth, when the two eyelids are still fused together. Its surgical treatment is mostly based on full thickness skin grafts. We report a case of a 22-year-old woman with a congenital divided nevus affecting the left upper and lower eyelid. The patient was treated in our Department because of the onset of a purple red nodule in the lower part of the nevus. We examined the case from embryological, histopathological, clinical, and diagnostic standpoints, and discuss surgical options in order to reach an optimal functional and aestetic result.

Combined radius and ulna reconstruction with a free fibula transfer.

A 20-year-old man sustained a high energy injury to his right forearm resulting in comminuted open fractures of the forearm with 6 cm bone loss of the radius and 7 cm bone loss of the ulna. A bone segment was removed from the middle of a free fibula transfer to produce a single flap with two vascularised bone segments to reconstruct both the radius and ulna defects. Step osteotomies were stabilised with a single lag screw for each fracture line and, with a rigid external fixation device on the ulna, two vein grafts were used to anastomose the flap pedicle to the recipient vessels in the forearm. The postoperative period was uneventful. X-rays and scintigrams confirmed good healing of the fractures and normal perfusion of the flap so that the external fixation device could be removed 3 months after surgery. One year after the injury, the patient underwent a functional evaluation showing excellent results with very good preservation of rotation of the forearm.

Modulation of keratinocyte growth factor and its receptor in reepithelializing human skin.

We investigated the expression and distribution of keratinocyte growth factor (KGF) (FGF-7) and its receptor (KGFR) during reepithelialization of human skin. KGF mRNA levels increased rapidly by 8-10-fold and remained elevated for several days. In contrast, KGFR transcript levels decreased early but were significantly elevated by 8-9 d. A KGF-immunoglobulin G fusion protein (KGF-HFc), which specifically and sensitively detects the KGFR, localized the receptor to differentiating keratinocytes of control epidermis, but revealed a striking decrease in receptor protein expression during the intermediate period of reepithelization. Suramin, which blocked KGF binding and stripped already bound KGF from its receptor, failed to unmask KGFRs in tissue sections from the intermediate phase of wound repair. The absence of KGFR protein despite increased KGFR transcript levels implies functional receptor downregulation in the presence of increased KGF. This temporal modulation of KGF and KGFRs provides strong evidence for the functional involvement of KGF in human skin reepithelialization.