Altered motility and bacterial flora after functional end-to-end anastomosis

The functional end-to-end technique with a gastrointestinal stapler is commonly used for small-bowel anastomosis, but the effects of this anatomically side-to-side anastomosis on motility are unknown. Fasting small-bowel myoelectric activity and culture results were compared in six animals undergoing handsewn end-to-end and functional end-to-end anastomoses. Serosal electrodes were placed at 10 cm intervals, and the small bowel was divided 25 and 55 cm from the ligament of Treitz. The functional end-to-end and end-to-end techniques were performed in each animal in random order. Fasting myoelectric recordings were obtained at weekly intervals for up to 20 weeks after operation. New electrodes were placed, and additional recordings were obtained from 29 to 39 weeks, 51 to 63 weeks, and 108 to 112 weeks after operation. The recordings were visually inspected for passage of phase 3 of the migrating myoelectric complex (MMC). By 12 to 20 weeks after operation, 91% of MMCs crossed the end-to-end anastomoses versus 22% across the functional end-to-end anastomosis (p less than 0.001). Even 2 years after surgery only 56% of MMCs crossed the functional end-to-end anastomosis. Quantitative bacterial cultures suggested a trend toward bacterial overgrowth in the functional end-to-end anastomosis. These results demonstrate that the functional end-to-end anastomosis alters small-bowel motility to a greater degree than an end-to-end anastomosis and may predispose to bacterial overgrowth.     

Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors.

From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.     

Development of a functional scoring system for rheumatoid arthritis patients with cervical myelopathy.

OBJECTIVE: To be able to measure disability objectively in rheumatoid arthritis complicated by cervical myelopathy. METHODS: The responses to the Stanford health assessment questionnaire disability index were recorded from 250 consecutive patients (group 1) referred to our unit for spinal surgery. Using principal components analysis the questionnaire was reduced from 20 questions to 10 questions. In the second part of the study, the results of the questionnaire for those patients undergoing surgery from the original group of 250 patients were analysed with respect to outcome. RESULTS: The reduction in the number of questions results in no significant loss of information, reliability (internal consistency Cronbach's alpha = 0.968) or sensitivity. The new scale, the myelopathy disability index, measures only one dimension (Eigen value 6.97) and may be more finely tuned to the measurement of disability in these myelopathic patients. When administered to the 194 patients undergoing cervical spine (group 2) surgery the myelopathy disability index was an accurate predictor of neurological and functional outcome, as well as survival following surgery (P < 0.0001). CONCLUSIONS: The myelopathy disability index provides a much needed objective and reliable means of assessing disability in patients with rheumatoid involvement of the cervical spine and also in predicting outcome following surgical intervention. It also provides information for both the patient and surgeon alike, on what to realistically expect from surgery. Its adoption should facilitate comparisons between different forms of surgical intervention.     

Outbreak of gram-negative bacteremia and pyrogenic reactions in a hemodialysis center

During the period from April 4, 1988, to April 20, 1988, nine pyrogenic reactions and five gram-negative bacteremias occurred in 11 patients undergoing dialysis. All pyrogenic reactions and gram-negative bacteremias occurred among patients in whom a reprocessed dialyzer was used. The rate of pyrogenic reactions or bacteremias per 100 sessions using a reprocessed dialyzer was higher than in sessions during which a new dialyzer was used (4.5 vs. 0; p = 0.03). Dialyzers were manually reprocessed with 2.5% Renalin germicide. The Renalin concentrations varied widely in 12 dialyzers stored after manual reprocessing during the epidemic period (0.9-4.2%); the median endotoxin concentrations varied from 0 to 246 ng/ml and were higher in dialyzers with Renalin concentrations less than or equal to 1.0% than in dialyzers with higher concentrations (p = 0.01). Experiments using a dilution technique described by a technician resulted in Renalin concentrations ranging from 1.4% at the surface to 3.5% at the bottom of the preparation container. These findings suggest that failure to adequately admix Renalin during dilution may be associated with low levels of disinfectant, high levels of bacteria and endotoxins in dialyzers, and outbreaks of pyrogenic reactions and gram-negative bacteremias in dialysis patients.     

Integrin stimulation regulates polymorphonuclear leukocytes inflammatory cytokine expression.

OBJECTIVE: The purpose of these studies is to investigate the role of integrin binding on the regulation of polymorphonuclear leukocyte (PMN) cytokine receptor expression. SUMMARY BACKGROUND DATA: Current knowledge in this area revolves around the ability of beta 2 integrins to mediate PMN adherence and chemotaxis. The role of alpha 1-6/beta 1 integrins in regulating cytokine receptor expression has not been probed. METHODS: Purified human PMN were adhered on plastic, fibronectin, or laminin-coated surfaces followed by the addition of iodine 125 (125I) monoclonal antibodies (mAbs) directed against tumor necrosis factor-alpha R (TNF-alpha R) p60, p80, or interleukin-1 beta R (IL-1 beta R) types I, II. Receptor expression was calculated based on the counts per minute (cpm) bound. The role of individual beta 1 integrins was assessed using mAbs directed against the alpha 1-6 subunit of the beta 1 complex, and integrin cross-linkage was achieved using secondary goat antimouse F(ab')2 antibodies. Polymorphonuclear leukocytes were pretreated with herbimycin A to determine the role of protein tyrosine kinase in mediating the effect of the beta 1 integrins. RESULTS: Adherence of PMN to Ln decreased IL-1 beta types I, II receptor expression, whereas adherence to Fn increased TNF-alpha R p60 and p80 expression. Anti-VLA-5 (CD49e) but not anti-VLA-1 through VLA-4 and VLA-6, blocked the effect of Fn on TNF-alpha receptors, whereas anti-VLA-6 but not anti-VLA-1 through VLA-5 blocked the effect of Ln on IL-1 beta receptors. Modulation of IL-1 beta and TNF-alpha receptors by VLA-5 and VLA-6 required protein tyrosine kinase activation as herbimycin A (10 micrograms/mL) blocked the affect of Fn and Ln. Changes in PMN cytokine receptor expression led to parallel changes in functional activity as assessed by the binding of 125I IL-1 beta and TNF-alpha. CONCLUSIONS: Integrin stimulation regulates the cell surface expression of PMN cytokine receptors. Ligation of CD49e upregulates TNF-alpha receptor expression, whereas binding of CD49f downregulates IL-1 beta receptor expression. Both processes are protein tyrosine kinase dependent. Changes in PMN cytokine receptor expression led to corresponding changes in functional activity. These results provide the first demonstration that chemotaxis of PMN into the interstitium provides a mechanism for ongoing participation in the local inflammatory response and is regulated by matrix protein integrin receptors.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Understanding family variables in outcome research in schizophrenia

Outcome studies in schizophrenia research consistently show the importance of family variables in predicting patient relapse. The concept of expressed emotion (EE) is clinically relevant, though concerns remain about its precise meaning. The history of the EE studies is reviewed in the light of other family research, and an alternative model of family emotional environment is proposed. A number of clinical implications are considered.     

Membrane flow within the myelin sheath in IDPN neuropathy

This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.     

Effects of tumor necrosis factor on system ASC-mediated glutamine transport by human fibroblasts.

The effects of tumor necrosis factor-alpha (TNF) on glutamine GLN transport by cultured human fibroblasts were studied. Uptake of 3H-GLN was assayed in both the presence and absence of sodium in order to differentiate Na(+)-dependent and Na(+)-independent transport systems. GLN transport was linear (r = 0.99) for at least 15 min and occurred predominantly via a single Na(+)-dependent pathway, consistent with System ASC. Incubation of fibroblasts with TNF (1000 units/ml) for 12 hr resulted in a significant decrease in system ASC-mediated glutamine transport activity. TNF did not alter cell morphology or protein content. Kinetic studies indicated that the decrease in carrier-mediated Na(+)-dependent GLN transport was not due to a change in transporter affinity (Km = 117 +/- 23 microM in controls vs 86 +/- 23 microM in TNF, P = NS), but instead to a 45% decrease in maximal transport rate (Vmax = 4088 +/- 354 pmole/mg protein/30 sec in controls vs 2230 +/- 510 in TNF, P less than 0.05). TNF also decreased Na(+)-independent transport by 50% (mean uptake of 50 microM GLN = 94 +/- 13 pmole/mg protein/30 sec in controls vs 46 +/- 6 in TNF, P less than 0.02). In human fibroblasts, the activity of System ASC, which has generally been viewed as a hormonally unresponsive carrier, is decreased by TNF. This impairment in glutamine transport may result in inadequate amounts of intracellular glutamine to support fibroblast metabolism and possibly function.     

Effects on birthweight of alcohol and caffeine consumption in smoking women.

STUDY OBJECTIVE--Previous work found no effect on birthweight of alcohol and caffeine consumption in non-smokers but such an effect was found in smokers. This report investigates further the effects on birthweight of alcohol and caffeine at three stages of pregnancy in smoking women. DESIGN--This was a prospective population study. SETTING--District general hospital in inner London. PARTICIPANTS--Out of 1309 women who completed all pregnancy interviews, 895 were excluded because they did not smoke, leaving a sample of 414 smokers. MEASUREMENTS AND MAIN RESULTS--Number and brand of cigarettes smoked, and quantity of alcohol and caffeine consumed were obtained by interview at booking, 28, and 36 weeks gestation. Birthweight was corrected for gestation and adjusted for maternal height, sex of infant and parity. The effect on birthweight of alcohol consumption was not explained by the amount smoked in terms of quantity and yield. Similarly the effect of caffeine was independent of smoking. When alcohol, caffeine, and smoking were analysed together, alcohol and caffeine were both associated with reductions in birthweight. Alcohol was associated with a reduction of up to 8% after adjusting for tobacco and caffeine intake, and caffeine was associated with a reduction of up to 6.5% after adjusting for tobacco and alcohol intake. Women who at booking were heavy smokers (greater than or equal to 13 cigarettes/day or greater than or equal to 15 mg carbon monoxide/cigarette), heavy drinkers (greater than or equal to 100 g/week alcohol), and had high caffeine intake (greater than or equal to 2801 mg/week) had a predicted reduction in mean birthweight of 18% (95% CI 11% to 24%). CONCLUSIONS--It is well known that women who smoke in pregnancy have smaller babies than non-smokers. Our study suggests that if these women also drink alcohol and high quantities of caffeine then the risk of poor fetal growth is increased even further.