Evaluation of phagocytic cell function in an ex vivo model of hemodialysis

An ex vivo model of hemodialysis was used to evaluate the effect of dialysis membranes on phagocytic cell function. Blood was withdrawn continuously from healthy, non-uremic donors, heparinized, and pumped, single pass, through membrane modules under conditions which simulated normal dialysis conditions. The membrane modules contained membranes of cellulose, DEAE-substituted cellulose, or polysulfone. Blood was obtained from the module outlets for determination of complement activation, phagocyte elastase release, zymosan-induced phagocyte chemiluminescence, and monocyte interleukin-1 production. Significantly less complement activation occurred with the polysulfone and DEAE-substituted cellulose membranes than with cellulose membranes. Normal monocyte interleukin-1 production was not stimulated by any of the membranes used. In contrast, the cellulosic, but not the polysulfone, membranes primed the oxidative burst of the phagocytes and caused them to release elastase. DEAE-substituted cellulose had a lesser effect on elastase release than did cellulose and elastase release correlated significantly with the degree of complement activation. However, the correlation between complement activation and priming of phagocyte oxidative burst was weak, suggesting that membranes affect phagocyte oxidative metabolism through more than one mechanism. We conclude that some dialysis membranes stimulate the bacteriacidal functions of normal phagocytic cells, in part through complement-dependent mechanisms.     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.     

The effect of nimodipine on ICP and CBF in patients with normal-pressure hydrocephalus

Eight patients with normal-pressure hydrocephalus (NPH) were studied. The resting mean arterial blood pressure (MABP) was 100 (90-125) mmHg and the mean intracranial pressure (ICP) was 11 (5-17) mmHg. ICP and MABP were continuously measured intraventricularly and intra-arterially, respectively. Changes in global cerebral blood flow (CBF) were estimated by the arteriovenous oxygen difference method. Intravenous nimodipine (15 microgram/kg/hour) was given in the first 2 hours and 30 microgram/kg/hour in the next 2 hours. MABP was reduced 23 (4-47) mmHg (p less than 0.05). ICP was increased 3 (0-10) mmHg (p less than 0.05). CBF was unchanged in the group on the whole, but in 4 of patients a major drop in perfusion pressure was seen, and CBF decreased 6, 11, 23 and 34%, respectively. Thus these findings underline the importance of maintaining the perfusion pressure under treatment with nimodipine.     

Post-prostatectomy urinary incontinence: response to behavioral training

Urinary incontinence after prostatectomy can be psychologically and socially disabling. We reviewed our experience with 27 patients who were incontinent between 5 and 198 months after either radical retropubic, total perineal or transurethral prostatectomy. These patients were entered into our bladder behavior clinic, which was administered by nursing staff with physician supervision. Patients were strongly encouraged to discontinue the incontinence devices, and were then evaluated for the type and extent of incontinence. Perineal exercises were demonstrated in detail, tested for their correct use via simultaneous rectal and abdominal examination, and applied to the pattern of incontinence. Patients were evaluated frequently for compliance and their progress was followed with instruction repeated as needed. Pharmaceutical agents were not used. Among the 24 patients evaluable over-all improvement in the number of incontinent episodes was 56.6% (p less than 0.001). Two patients (8.3%) achieved total continence, 10 (42%) improved greatly, 4 showed moderate improvement and 8 (33%) showed essentially no change. Transurethral and perineal prostatectomy patients improved by 74 and 61%, respectively, versus only 33% in the radical retropubic group (p = 0.14). In addition, patients who previously underwent transurethral resection before total prostatectomy did worse (18%) than did those who did not (67%). We conclude that a significant number of patients who are incontinent after prostatectomy (especially those without a prior transurethral resection) can improve dramatically with a behavioral training program that provides a strong support system.     

A comprehensive survey for polymorphisms in the bovine IFN-gamma gene reveals a highly polymorphic intronic DNA sequence allowing improved genotyping of Bovinae.

This study aimed to identify interferon-gamma (IFN-gamma) gene variants in cattle for diagnostic purposes. Therefore, the entire bovine IFN-gamma gene (BoIFNG) and 2605 bp of its promoter DNA were sequenced. The BoIFNG DNA sequence conforms to the published part of Bo-IFN-gamma cDNA. Primer extension experiments show the presence of a 5' extension of exon 1 by 42 nucleotides (nt). One SINE element (Bov-A2) is located in the 5'-region, and two SINE elements (Bov-tA, Bov-B) are contained in the 3'-region of BoIFNG. The variants were detected by comparative sequence analysis of PCR amplicons from different bovine species. Four polymorphic mononucleotide repeats are situated in the promoter and in intron 1. Four distinct series of single nucleotide polymorphisms (SNP) were found in functionally important regions of BoIFNG. The region between the two intron 1 microsatellites contains the highest density of SNPs in Bos taurus breeds. One G-T transversion in the coding region of exon 1 causes a Gly(14) to Val(14) exchange in the BoIFNG signal peptide of different bovine species. A G-A transition in exon 2 encodes a Ser(19) to Asn(19) change in the mature protein of the Tibetan yak. Genotyping of randomly sampled Holstein Friesian cows at selected SNPs and of both intron 1 microsatellites revealed two dominant BoIFNG microhaplotypes. The detected SNPs improve the recently reported genotyping system of cattle.     

Hypothyroidism and hyperprolactinemia as a possible cause of androgenetic alopecia in the female

31 female patients suffering from androgentic alopecia were examined by means of the TRH test with regard to hypothyroidism and hyperprolactinemia. Before, as well as 20 and 40 minutes after, application of thyroxine releasing hormone (TRH), the serum concentrations of the hypohyseal thyroxine stimulating hormone (TSH) and prolactin (PRL) were measured by radioimmunoassay (RIA). In 7 of the patients (23%), we found increased TSH levels after stimulation with TRH--indicative of hypothyroidism. In 9 of the patients (29%), we observed increased PRL levels after TRH stimulation, indicating prolactinemia. TSH and PRL can interact with androgen metabolism at various levels. Thyroxine may influence the unbound, metabolically active testosterone via the sex hormone binding globulin (SHBG). Prolactine, which is stimulated by TRH, promotes the suprarenal cortisol and androgen production. In 48% of the patients, we found either hypothyroidism or hyperprolactinemia. This suggests that both conditions may contribute to the clinical picture of female androgenetic alopecia, as they interfere with the androgen metabolism.