Cytokines and growth factors in keratinocytes and sweat glands in chronic venous leg ulcers. An immunohistochemical study

The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing.     

Effectiveness of electroconvulsive therapy in community settings.

BACKGROUND: Clinical trials indicate that electroconvulsive therapy (ECT) is the most effective treatment for major depression, but its effectiveness in community settings has not been examined. METHODS: In a prospective, naturalistic study involving 347 patients at seven hospitals, clinical outcomes immediately after ECT and over a 24-week follow-up period were examined in relation to patient characteristics and treatment variables. RESULTS: The sites differed markedly in patient features and ECT administration but did not differ in clinical outcomes. In contrast to the 70%-90% remission rates expected with ECT, remission rates, depending on criteria, were 30.3%-46.7%. Longer episode duration, comorbid personality disorder, and schizoaffective disorder were associated with poorer outcome. Among remitters, the relapse rate during follow-up was 64.3%. Relapse was more frequent in patients with psychotic depression or comorbid Axis I or Axis II disorders. Only 23.4% of ECT nonremitters had sustained remission during follow-up. CONCLUSIONS: The remission rate with ECT in community settings is substantially less than that in clinical trials. Providers frequently end the ECT course with the view that patients have benefited fully, yet formal assessment shows significant residual symptoms. Patients who do not remit with ECT have a poor prognosis; this underscores the need to achieve maximal improvement with this modality.     

A new model for objective assessment of cervical ripening: the effect of prostaglandin E2 and prelabor contractility

A rabbit cervix preparation designed to evaluate the effects of locally administered substances and those of prelabor contractility on cervical ripening is described. In one experiment, one of the two cervices was exposed to prostaglandin E2 gel and the contralateral cervix was exposed to plain gel. In another experiment, one cervix was completely isolated from prelabor contractility, whereas the contralateral cervix remained intact. Cervical ripening was assessed by measurement of the stretch modulus and rate of creep 2 days later. Treatment with prostaglandin E2 gel and exposure to prelabor contractility resulted in significant unilateral cervical changes, suggesting that at least part of the prostaglandin E2 effect is locally mediated and that spontaneous prelabor contractility may play a role in cervical preparation for labor. Furthermore, because of its simplicity, this animal preparation can be useful in the investigation of the effects of other locally administered substances on cervical ripening.     

Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine

The cause and mechanism of post-carotid endarterectomy hypertension remains unknown. To determine the influence of the sympathetic and renin-angiotensin system, we measured cranial and peripheral plasma levels of catecholamine and renin in patients undergoing carotid endarterectomy. Baseline samples were drawn just before carotid clamping (sample I) and compared with study samples drawn immediately after clamp release (sample II), 2 to 6 hours after surgery (sample III), and then 18 to 24 hours after surgery (sample IV). The patients with post-carotid endarterectomy hypertension had an associated increase of cranial and peripheral norepinephrine levels in the postoperative hypertensive period whereas the patients without post-carotid endarterectomy hypertension did not. This association was most pronounced and statistically significant in cranial samples II (p = 0.032) and III (p = 0.005). Epinephrine and dopamine values did not correlate with post-carotid endarterectomy hypertension. Renin values were higher in cranial than in peripheral samples at time period 2 (p = 0.011), suggestive of a central nervous system Goldblatt phenomenon. However, the renin values did not correlate with post-carotid endarterectomy hypertension. We conclude that post-carotid endarterectomy hypertension is associated with elevated cranial norepinephrine levels, suggestive of a central nervous system sympathomimetic mechanism. Optimal prevention and treatment of this brief but frequently occurring hypertension should include a central-acting sympatholytic agent.     

Correspondence between theoretical models and dual energy X-ray absorptiometry measurements of femoral cross-sectional growth during adolescence

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9–26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.     

The membrane potential of vestibular dark cells is controlled by a large Cl- conductance.

The K+ secretory epithelium of the vestibular labyrinth (dark cells) was impaled with glass microelectrodes in order to test the hypothesis that it contains a large Cl- conductance. In the first series of experiments, the short-circuited epithelium was perfused on both sides by a solution containing 150 mmol/l Cl-. The membrane voltage (PD) was -18 +/- 1 mV (N = 101), showed a Gaussian distribution, and the estimated input resistance of the cell (R 'cell') was 17 +/- 3 M omega. The PD responded to 10(-4) mol/l ouabain with a depolarization, suggesting the presence of a (Na(+) + K+)-ATPase. The PD responses to Cl- steps yielded an apparent transference number tCl = 0.34 +/- 0.03 (N = 65) and those to K+ steps yielded a tK = 0.16 +/- 0.01 (N = 48). In the second series of experiments, cells presumed to be Cl(-)-depleted were impaled in Cl(-)-free solutions. The distribution of the PD was not Gaussian; PDs as negative as -90 mV were observed. Cells with a highly negative PD also had a high R 'cell'. With the addition of Cl- the PD collapsed to -19 +/- 1 mV and R collapsed to 16 +/- 3 M omega (N = 145) which are not significantly different from values obtained in the first series of experiments when cells were impaled in a solution containing 150 mmol/l Cl-. Alternating the bath perfusate between Cl(-)-free and Cl(-)-containing solutions led to large PD transients.(ABSTRACT TRUNCATED AT 250 WORDS)