Genetic factors in septic shock.
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Biomedical subjects
Publications and source records attributed to J Short.
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We evaluated the distribution of apolipoprotein E (apoE) immunoreactivity in mouse and human olfactory bulbs. ApoE immunoreactivity was present in the olfactory nerve and around the glomeruli. Immunoreactivity was seen in somata that appeared to be glial. No neuronal staining was seen. The apoE immunoreactivity was also present in the mouse olfactory bulb subependymal layer. The specificity of immunoreactivity was confirmed with apoE-deficient mice (apoE gene knock-out mice, apoE KO) which did not display any immunoreactivity. The presence of apoE around glomeruli and nerve suggest that apoE is associated with the continuous degeneration and regeneration processes that occur in the olfactory nerve. Experimental manipulation of the olfactory nerve may be a useful technique to determine the functions of apoE in a well-defined neural system.
The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.
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BACKGROUND: The spleen plays a central role in the generation of both cellular and antibody responses during graft rejection. Although changes in lymphocyte function have been extensively analyzed in vitro, there have been limited attempts at quantitating the structural changes in the lymphoid compartments within the spleen during graft rejection. METHODS: We describe here a means of quantitating the histological changes in the spleen using immunohistochemical techniques and computerized image analysis. RESULTS: Allograft rejection at 6 days after transplant is characterized by a threefold increase in the T cell-rich areas of the periarteriolar lymphoid sheaths (PALs). The follicular areas are enlarged and germinal centers appear in 55% of the white pulp regions. Acute xenograft rejection, 4 days after transplant, is specifically accompanied by a 2.3-fold increase in the marginal zone (MZ) and an increase in the numbers of B cells in the red pulp of the spleen. The expansion of both PALs and follicular/germinal centers during xenograft rejection is comparable to that observed during allograft rejection. We also investigated the effect of two immunosuppressants, leflunomide and cyclosporine, on the spleen of rats with hamster hearts. Leflunomide, which prevents acute xenograft rejection, prevented the increase in PALs and significantly reduced the areas comprising the MZ and follicles. Cyclosporine, which does not alter the tempo of xenograft rejection and only partially inhibited xenospecific antibody production, inhibited the increase in PALs and the appearance of germinal centers, while permitting a modest increase in the area of MZ and follicles. CONCLUSIONS: These observations collectively suggest that both T cell-dependent and T cell-independent responses are stimulated by the transplanted xenograft. However, the T cell-independent responses that initiate xenograft rejection are characterized by very modest increases in the area of MZ and follicles within the white pulp of the spleen.
The first step in redesigning the health care delivery process for ambulatory care begins with the patient and the business processes that support the patient. Patient-related business processes include patient access, service documentation, billing, follow-up, collection, and payment. Access is the portal to the clinical delivery and care management process. Service documentation, charge capture, and payment and collection are supporting processes to care delivery. Realigned provider networks now demand realigned patient business services to provide their members/customers/patients with improved service delivery at less cost. Purchaser mandates for cost containment, health maintenance, and enhanced quality of care have created an environment where every aspect of the delivery system, especially ambulatory care, is being judged. Business processes supporting the outpatient are therefore being reexamined for better efficiency and customer satisfaction. Many health care systems have made major investments in their ambulatory care environment, but have pursued traditional supporting business practices--such as multiple access points, lack of integrated patient appointment scheduling and registration, and multiple patient bills. These are areas that are appropriate for redesign efforts--all with the customer's needs and convenience in mind. Similarly, setting unrealistic expectations, underestimating the effort required, and ignoring the human elements of a patient-focused business service redesign effort can sabotage the very sound reasons for executing such an endeavor. Pitfalls can be avoided if a structured methodology, coupled with a change management process, are employed. Deloitte & Touche Consulting Group has been involved in several major efforts, all with ambulatory care settings to assist with the redesign of their business practices to consider the patient as the driver, instead of the institution providing the care.
The finding of a large discordance between animal species in their response to a carcinogenic challenge, has led to the realization that the useful extrapolation of animal test data to humans requires a better understanding of animal interspecies differences. With the development of transgenic shuttle vector based animal systems we are now able to study mutation of the same genetic target in both mice and rats. We have begun to analyze mutants recovered from rat lines carrying low copy numbers of the same lambda/lacI constructs carried by the Big Blue mouse. A large database on mutations in lacI transgenic mice is already available for comparison. The data indicate that the differences between the mutations recovered from rat liver and germ cell tissues are similar to those recovered from transgenic mice, but when compared with a large database of mutations available for mice, some site-to-site differences may exist. This study represents the first interspecies look into the molecular nature of mutations in the lacI transgenic rodents.
The development of anorexia nervosa in a high-functioning, early adolescent, autistic female is described. This case raises the issue of co-occurrence of childhood-onset disorders sharing the phenomena of obsessions and compulsions. The role of dysregulation of the serotonergic neurotransmitter system as a common underlying mechanism in these disorders is suggested. Psychoactive agents affecting the serotonin system and in particular the atypical neuroleptic risperidone may be of value in these disorders. There is added benefit to the combined use of biological and behavioral therapies.
PURPOSE: A prospective cohort study was done to determine the efficacy and clinical outcome of a new technique for anterior vaginal wall sling construction to treat urinary incontinence due to intrinsic sphincter dysfunction or anatomical incontinence. MATERIALS AND METHODS: Preoperative evaluation included lateral cystography, video urodynamics, cystoscopy and incontinence staging. Postoperative subjective and objective staging outcome measures were prospectively assigned at predetermined regular intervals by a third party. RESULTS: Of the patients 95 had intrinsic sphincter dysfunction and 65 had anatomical incontinence. The repair failed in 7% of the 160 patients who had recurrent incontinence during followup and 9% had de novo urgency incontinence. Time to failure comparing patients with intrinsic sphincter dysfunction and anatomical incontinence was modeled using Kaplan-Meier survival curves, and the log rank test showed no significant difference between the groups (p > 0.05). Logistic regression covariates revealed no significant predictive factors for postoperative failures. Preoperative patient age was the only predictive factor for de novo instability (logistic regression model p < 0.05). CONCLUSIONS: Our initial results indicate that the 2 groups are indistinguishable to date based on current clinical and experimental statistics except for time to full recovery of postoperative voiding and incidence of postoperative instability (regression model p < 0.05).
Chronic rejection, characterized by a progressive obliterative arteriopathy, is a major cause of graft failure in long-surviving human transplants for which there is no effective treatment. Leflunomide, an isoxazol derivative, has been shown to be a novel immunomodulatory drug that profoundly suppresses the immune response. In this study, 58 Fisher-344 rats received cardiac transplantation from Lewis rats. All the recipients were given CsA at 2.5 mg/kg for 5 days postoperatively. Without further treatments, the arterial intima was progressively injured by mononuclear cell infiltration and Ab deposition. Smooth muscle cell and fibroblast proliferation in the intima became a predominant phenomenon by day 90. CsA was ineffective in controlling the progress of arterial intimal thickening when treatment began on day 30. Leflunomide at 5 mg/kg failed to control arterial intimal thickening by day 60 when therapy began on day 30. However, the progress of arterial intimal thickening was significantly inhibited by day 90 when the dosage of leflunomide had been increased to 10 mg/kg on day 60. Combined therapy with leflunomide and CsA at 5 mg/kg for 30 days dramatically reversed the arterial thickening by day 60. After increasing the dosages of both leflunomide and CsA to 10 mg/kg on day 60, the combination therapy steadily controlled the chronic rejection. Only the combination therapy significantly down-regulated circulating antidonor IgM and IgG titers. In rat smooth muscle cell culture, this same drug combination had a synergistic inhibitory effect on proliferation. Therefore, the combination therapy of leflunomide and CsA could reverse and control the progress of chronic rejection, while leflunomide, at higher dosage as a monotherapy, could stabilize chronic rejection in this model. The mechanism of the regression of chronic rejection by leflunomide and cyclosporine may be related to their in vitro abilities to control not only lymphocyte but smooth muscle cell proliferation, as well. The synergistic effect of these two drugs on vascular smooth muscle cell proliferation in vitro may be an important part of this novel activity. This unique feature holds intriguing possibilities for treating established chronic rejection.
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1. Development of CE programs for occupational health nurses is integral to professional development. Occupational health nurses are constantly being required to increase and upgrade skills. 2. Evolving issues in health care reform reflect an emphasis on the cost effective, quality care provided by well prepared occupational health nurses. Thus, the need for providing high quality programs and resources for occupational health nurses becomes a challenge for CE providers. 3. The Model for Health Education Planning (MHEP) is used to describe the development of a program. The MHEP includes six phases: initiation, needs assessment, goal setting, planning/programming, implementation, and evaluation. 4. Use of the MHEP ensures that the program planning process is achieved in an appropriate manner. The focus is on meeting the needs of the learner.
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The nature of the plans for change detailed in the National Health Service review White Paper, Working for Patients, which was presented to the British Parliament on 1 February 1989, are examined in this paper. Seven key measures are identified and outlined. The author extrapolates from the nature of the plans contained within the White Paper, the types of problems within the NHS that are attracting government attention. Questions are raised as to the appropriateness and likelihood of success of the White Paper plans in view of the problems currently besetting the NHS.
The Hemopump is a new 7-mm diameter left ventricular assist device that provides as much as 3.5 l/min of nonpulsatile cardiac output after fluoroscopic placement into the left ventricle through a femoral artery cutdown. The purpose of this study was to measure the effects of Hemopump assist on hemodynamics, left ventricular function, and perfusion in the presence and absence of ischemia. Eight dogs were instrumented under pentobarbital anesthesia with left ventricular, left atrial, and aortic catheters, a loose silk ligature around the midleft anterior descending coronary artery, and sonomicrometer crystals in midwall myocardium within the left anterior descending and circumflex perfusion territories. Hemodynamic variables, regional systolic fractional shortening, and myocardial perfusion after left atrial injection of 15-microns radiolabeled microspheres were measured in the presence and absence of Hemopump assist before and after left anterior descending artery occlusion. In the absence of ischemia, Hemopump left ventricular assist resulted in reduced left ventricular end-diastolic pressure while aortic mean pressure was maintained, and there was significant reduction in regional systolic fractional shortening (reflecting systolic unloading) that correlated with an 18% decline in regional myocardial perfusion. During left anterior descending artery occlusion, left ventricular systolic and diastolic pressures were reduced during Hemopump assist while aortic mean pressure was maintained. Perfusion rose in the ischemic territory (from 13.0 +/- 8.7% to 26.2 +/- 19.8% of nonischemic flow, p = 0.045). Reduced fractional shortening was again seen in nonischemic tissue with Hemopump assist during left anterior descending artery occlusion, and this was often correlated with reduced perfusion (r = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)