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.     

A comparison of betaxolol and timolol in open angle glaucoma and ocular hypertension

In a randomized, double-masked study, 41 patients with primary open-angle glaucoma or ocular hypertension were treated with betaxolol 0.5% or timolol 0.5% drops for 26 weeks. The average decrease in intraocular pressure (IOP) over the total study period was significant with both betaxolol (-6.3 mmHg) and timolol (-7.2 mmHg) in patients receiving no adjunctive therapy. There was no difference between betaxolol and timolol with respect to changes from baseline IOP. Significantly decreased mean brachial arterial pressure (MAP) was seen only with timolol, although the difference between the two groups was not significant. Pulse, pupil size, and basal tear secretion were unchanged in both groups. Burning upon instillation of the drops was more frequent with betaxolol.     

Is cranial radiation necessary for CNS prophylaxis in pediatric NHL?

The records of 95 consecutive children less than or equal to 21 years of age with previously untreated diffuse histology NHL registered in our protocols from 1978 to 1983 were reviewed. Seventy-nine patients were considered eligible for analysis. The histologic subtypes represented included lymphoblastic (LB) 37%; histiocytic (DHL) 29%; undifferentiated (DU) 19%; poorly differentiated (DPDL) 9%; and unclassified (UNHL) 6%. Distribution of the patients according to stage showed Stage I, 0%; Stage II, 11%; Stage III, 53%; Stage IV, 36%. Four different Memorial Hospital protocols for systemic chemotherapy were used (LSA2L2 73%; L10 9%; L17 10%; L17M 8%); however, the IT (intrathecal) chemotherapy was uniform (Methotrexate: 6.0-6.25 mg/M2 per treatment course) and was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was included in the induction, consolidation, and maintenance phases of all treatment protocols. Cranial radiation was not included in the CNS prophylaxis program. The overall median time of follow-up was 43 months. The overall CNS relapse rate was 6.3%, however, the incidence of CNS lymphoma presenting as the first isolated site of relapse in patients in otherwise complete remission (minimum follow-up of 19 months with 97% of patients off treatment) was only 1/58 (1.7%). Our data suggests that IT chemotherapy when given in combination with modern aggressive systemic combination chemotherapy, and without cranial radiation appears to be a highly effective modality for CNS prophylaxis regardless of stage, histology, or bone marrow or mediastinal involvement. Therefore, with the commonly used aggressive combination chemotherapy for the management of all stage diffuse pediatric NHL, and the known increased risk of leukoencephalopathy with combination of cranial radiation and intensive systemic and intrathecal chemotherapy, we believe that cranial radiation may not be indicated for CNS prophylaxis in pediatric NHL.     

Chemotactic inhibitors in sera of patients with neoplastic disease

Our objective was to define the functional characteristics of chemotactic inhibitors in sera of patients with various neoplastic diseases. Fifty-nine patients were studied: lung cancer (15), breast cancer (11), lymphoma (20), leukemia (13). Chemotaxis and random motility were measured using a modified agarose technique with C5a and a bacterial filtrate of E. coli as the chemoattractants. Two types of inhibitors were found: chemotactic factor inhibitors and cell-directed inhibitors. The type of inhibitor as well as the specificity of the inhibitor for the chemoattractant (C5a or bacterial filtrate) varied depending upon the underlying neoplasm. Cell-directed inhibitors were reversible and none of the inhibitors affected random motility. Contrary to previous reports, the chemotactic factor inhibitors were heat-stable (p less than 0.001). Morphometric analysis of inhibited and non-inhibited cells using scanning electron photomicrographs showed a significant alteration in shape of the inhibited cells (p less than 0.003). The results indicate greater heterogeneity of the chemotactic inhibitors than was previously thought, as well as a tumour-dependent specificity of the inhibitors for the chemoattractants.     

A multicenter evaluation of safety of early extubation in liver transplant recipients.

Small single-institutional studies performed prior to the introduction of organ allocation using the Model for End-Stage Liver Disease (MELD) suggest that early airway extubation of liver transplant recipients is a safe practice. We designed a multicenter study to examine adverse events associated with early extubation in patients selected for liver transplantation using MELD score. A total of 7 institutions extubated all patients meeting study criteria and reported adverse events that occurred within 72 hours following surgery. Adverse events were uncommon: occurring in only 7.7% of 391 patients studied. Most adverse events were pulmonary or surgically related. Pulmonary complications were usually minor, requiring only an increase in ambient oxygen concentration. The majority of surgical adverse events required additional surgery. Analysis of a limited set of perioperative variables suggest that blood transfusions and technical factors were associated with an increased risk of adverse events. In conclusion, while early extubation appears to be safe under specified circumstances, there are performance differences between institutions that remain to be explained.