Effects of dietary lipid levels on mitochondrial gene expression in low and high-feed efficient families of rainbow trout Oncorhynchus mykiss.

A 2 × 3 factorial study was conducted to evaluate the effects of dietary lipid level on mitochondrial gene expression in mixed sex rainbow trout Oncorhynchus mykiss. Practical diets with a fixed crude protein content of 42%, formulated to contain 10% (42/10), 20% (42/20) and 30% (42/30) dietary lipid, were fed to triplicate groups of either low-feed efficient (F129; mean ± s.d. = 105.67 ± 3.04 g initial average mass) or high-feed efficient (F134; mean ± s.d. = 97.86 ± 4.02 g) families of fish, to apparent satiety, twice per day, for 108 days. At the end of the experiment, diets 42/20 and 42/30 led to similar fish condition factors, which were higher than that observed with diet 42/10 (P < 0.05). F134 fish fed diet 42/10 showed the highest hepato-somatic index, while there was no significant difference among all the other treatments (P < 0.05). When the group of F134 fish fed diet 42/10 was used as the calibrator for gene expression analysis, the five genes selected for their involvement in lipid metabolism (complex I-nd1, complex III-cytb, complex IV-cox1, complex IV-cox2 and complex V-atp6) were up-regulated in the muscle and down-regulated in both the liver and the intestine. There was a significant family × diet interaction regarding nd1, cox2 and atp6 in the liver; nd1, cytb, cox1, cox2 and atp6 in the intestine, and nd1, cytb, cox1, cox2 and atp6 in the muscle (P < 0.05). The overall results of this study constitute basic information for the understanding of molecular mechanisms of lipid metabolism at the mitochondrial level in fishes.

Increased morbidity and mortality in murine cytomegalovirus-infected mice following allogeneic bone marrow transplant is associated with reduced surface decay accelerating factor expression.

Infection with cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following allogeneic bone marrow transplantation (allo-BMT). The manifestations of CMV infection can range from neurological and haematological abnormalities to diminished graft survival and, in extreme cases, death. Many clinical studies have shown a direct correlation between cytomegalovirus infection and increased morbidity and mortality post allo-BMT, yet the exact mechanism is not well understood. Although driven primarily by T cell responses, the role of complement activation in acute and chronic graft-versus-host disease (GVHD) has also become more evident in recent years. The present studies were performed to examine the effects of murine cytomegalovirus (MCMV) infection on decay accelerating factor (DAF) and MCMVs role in exacerbating morbidity and mortality post-allo-BMT. Mice infected previously with a sublethal dose of MCMV (1 × 105 plaque-forming units) have reduced expression of DAF on lung tissues and lymphocytes following allo-BMT. More importantly, mortality rates post-allo-BMT in recipient DAF knock-out mice receiving wild-type bone marrow are increased, similar to wild-type MCMV-infected recipient mice. Similarly, DAF knock-out mice showed greater intracellular interferon (IFN)-γ production by lung CD8 T cells, and infection with MCMV further exacerbated both intracellular IFN-γ production by CD8 T cells and mortality rates post-allo-BMT. Together, these data support the hypothesis that MCMV infection augments morbidity and mortality post-allo-BMT by reducing surface DAF expression.

Increased weight loss with reduced viral replication in interleukin-10 knock-out mice infected with murine cytomegalovirus.

The anti-inflammatory cytokine interleukin (IL)-10 plays an important role in the regulation of host-immune responses. Here we studied the role IL-10 plays in host responses to cytomegalovirus (CMV) infection. We demonstrate that manifestations of murine CMV (MCMV) disease are more severe in IL-10 knock-out mice, despite significantly reduced levels of viral replication. Cytokine analysis of serum revealed increased levels of interferon (IFN)-gamma, monocyte chemotactic protein 1 (MCP-1) and IL-6, all of which are potent stimulators of inflammatory responses. Depletion of IFN-gamma by monoclonal antibodies in IL-10 knock-out mice failed to improve the physical condition of the mice, while increasing viral replication. In contrast, serum levels of IL-6 in the knock-out animals were unaffected by IFN-gamma depletion and remained significantly elevated early in the course of infection. These data suggest that increased weight loss observed in IL-10 knock-out mice may be attributed to the uncontrolled production of proinflammatory cytokines, including IL-6.

Force measurement and mechanical characterization of living Drosophila embryos for human medical study.

The objective of this paper is to investigate and characterize the force behaviour and mechanical properties of living Drosophila embryos using an in situ polyvinylidene fluoride (PVDF) piezoelectric microforce-sensing tool with a resolution in the range of sub-micro newtons. The Drosophila embryo is one of the most studied organisms in biological research, medical research, genetics, and developmental biology and has implications in the cure of human diseases. It is also used to study the wiring of the human brain and the nervous system. For a highly efficient and accurate microinjection of genetic material into a Drosophila embryo, it is absolutely necessary to allow close monitoring of the magnitude and direction of microinjection and other biomanipulation forces acting on the embryo during the injection process. In this paper, a networked microrobotic biomanipulation platform integrating a two-axis (two-dimensional) PVDF microforce-sensing tool is used to implement force sensing and injection of living Drosophila embryos. Based on the event synchronization for the feedback of injection video and microforce, the developed networked microrobotic platform can greatly advance operations in microinjection and biomanipulation. Through experiments, quantitative relationships between the applied force and membrane structural deformation of embryos in different stages of embryogenesis and their microinjection force behaviours were investigated. Ultimately, the technology will provide a critical and major step towards the development of automated biomanipulation for batch injection of living embryos in genetic and developmental studies, which will facilitate the development of medicine for the cure of human diseases.

A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.

Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.

Leptin in anorexia nervosa.

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa.

Anorexia nervosa is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. To determine the potential role of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in anorexia nervosa, serum concentrations of these cytokines were measured in patients with anorexia nervosa during starvation and after weight gain. Serum IL-6 and TGF-beta concentrations were both significantly elevated during starvation and returned to levels comparable to those of normal-weight controls by the end of therapy. In contrast, serum TNF-alpha levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.

Maintenance treatment and 6-month outcome for bulimic patients who respond to initial treatment.

Bulimic subjects who responded to intensive group psychotherapy plus imipramine or placebo or to imipramine alone (N = 68) were assigned to 4-month maintenance with weekly support groups and/or medication (placebo or imipramine) and were evaluated 6 months after initial treatment (N = 61). Thirty percent of the subjects relapsed during the 6 months. Initial treatment with group psychotherapy plus placebo or imipramine was associated with a lower relapse rate than initial treatment with imipramine alone. Neither attendance at the maintenance group sessions nor imipramine maintenance was associated with better outcome.

HIV antibody testing: the gap between policy and practice.

In response to recent laws regulating human immunodeficiency virus (HIV) antibody testing practices in all federal hospitals, our university-affiliated Veterans Affairs Hospital instituted several interventions designed to increase appropriate testing. Specific hospital policy requiring restriction of testing to high-risk individuals, provision of pre- and posttest counseling, and documentation of written consent was instituted. In addition, an education campaign to inform physicians of hospital policy and training of counselors as physician extenders was undertaken. To determine the efficacy of these interventions, we reviewed all HIV antibody tests performed during a subsequent six-month period (n = 221). Only 14% of tests met all hospital policy requirements. The decision to test was prompted by identification of a risk factor or other acceptable reason for testing for only 31% of patients. Risk reduction counseling was provided for only 28% of patients. Written consent was documented for 62% of patients. Health care providers on surgical services were less likely than others to comply with hospital policy (p < 0.0001). We conclude that an interventional program including specific hospital policy mandates, physician education, and provision of trained counselors was not adequate to ensure optimal HIV antibody testing practices. If this gap between policy and practice is to be closed, additional interventions, or alternatively modification of policy guidelines, will be needed.

Renal manifestations of hepatitis C infection.

Hepatitis C is an important cause of renal disease, and renal complications may be the presenting manifestation of hepatitis C infection. About half of patients present with evidence of renal insufficiency, and up to one quarter present with nephrotic syndrome. Others present with proteinuria or evidence of diminished renal function. The pathogenesis of hepatitis C-associated renal disease remains incompletely defined, but most evidence suggests that glomerular injury results from deposition of circulating immune complexes in the subendothelium and mesangium. Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, is the most common renal lesion. Interferon alpha-2b is currently the treatment of choice. However, success is limited, with many patients failing to respond or suffering relapse upon discontinuation of therapy. Studies of newer treatment modalities, such as longer courses of interferon or the use of ribavirin or immunosuppressive agents, are underway. Hepatitis C-associated renal disease may progress to end-stage renal failure requiring dialysis in about 10% of patients.

Infection in the myelodysplastic syndromes.

PURPOSE: To determine the incidence, characteristics, and outcome of infection in patients with myelodysplastic syndromes (MDS) and risk factors that may lead to infection. PATIENTS AND METHODS: We reviewed infections that occurred in 86 consecutive patients with MDS who received care from 1968 to 1986 at a university-affiliated Veterans Affairs Medical Center. Time lines charting the course of each patient with MDS were created and included infections, MDS subgroup at the time of presentation and at the time of each infection, peripheral neutrophil counts, and therapies for MDS. RESULTS: Infections occurred at a rate of nearly one per patient year of observation. Infection rates were associated with MDS subgroup as follows: refractory anemia with or without ringed sideroblasts (RA +/- RS) less than refractory anemia with excess blasts (RAEB) less than RAEB in transformation (RAEB-T). The group of RA +/- RS patients who had erythroid abnormalities but minimal or no dyspoiesis of other cell lines had the lowest rate of infections. Infection rates were higher in patients with less than or equal to 1,000 neutrophils/microL blood than in patients with greater than 1,000 neutrophils/microL blood for each classifiable MDS subgroup. Neutrophil concentration and MDS subgroup were independent risk factors for infection in patients with MDS. Bacterial pneumonias and skin abscesses were the most common infections. Infection was the most common cause of death during MDS, accounting for 64% of deaths, and was more common than transformation to acute leukemia as a cause of death. CONCLUSION: Infection is a common, life-threatening problem in patients with MDS. Neutropenia and MDS subgroup are each risk factors for infection. Clinicians should aggressively evaluate patients with fever and MDS for infection, especially pneumonia and skin infections.

Prophylactic antibiotics for the prevention of early infection in multiple myeloma.

PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.

Diuretic use as a marker for eating problems and affective disorders among women.

Fourteen female symptomatic volunteers between the ages of 18 and 40 who used diuretics on a regular basis for reasons that were not medically necessary were evaluated. Seven (50%) were diagnosed as having a current or past syndromal or subsyndromal eating disorder, and 9 (64%) were diagnosed as having a current or past affective disorder. The results of this pilot study suggest that chronic diuretic use in young women should signal to the clinician the possibility of an unrecognized eating problem and/or an affective disorder.

Cytomegalovirus: epidemiology and infection control.

Cytomegalovirus (CMV) causes asymptomatic infection in most individuals but can produce devastating illness in immunocompromised hosts and in a small proportion of congenitally infected babies. New techniques in molecular biology have provided insights into the epidemiology and transmission of CMV. Children in day care, their parents, and sexually active individuals, especially homosexual men, are now known to be at particular risk for acquiring CMV. Recent studies show that the risk of CMV acquisition by health care workers is similar to the risk to the general public. Health care workers should be aware of the wide range of clinical manifestations, methods of laboratory diagnosis, and current limitations of treatment of CMV. Careful handwashing and avoidance of excretions and secretions are recommended to decrease the transmission of CMV in the hospital.

Human immunodeficiency virus drug resistance testing: state of the art in genotypic and phenotypic testing of antiretrovirals.

Antiretroviral drugs have significantly reduced death rates from the acquired immunodeficiency syndrome in the United States. They are highly effective in reducing viral replication, but their utility is threatened by rapid development of drug resistance. Although antiretroviral drug resistance testing is available by either genotyping or phenotyping, no consensus guidelines have been published regarding the appropriate use or interpretation of these new tests. Even though their role in clinical practice is not defined, it is important for clinicians to become familiar with relative advantages and disadvantages of genotypic and phenotypic testing and various mechanisms of antiretroviral resistance.

Hydroxyurea to inhibit human immunodeficiency virus-1 replication.

Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations.

Revising appointment, promotion, and tenure procedures to incorporate an expanded definition of scholarship: the University of Kentucky College of Medicine experience.

Scholarly activity and scholarly productivity are key features of the academic health center (AHC) and the work of college of medicine faculty. Recent changes in the academic environment of the University of Kentucky (UK) College of Medicine led to an examination of its appointment, promotion, and tenure procedures. This, in turn, led to a re-examination of the college's definition of scholarship. This article describes three of UK's scholarship-related challenges, particularly those related to clinical departments. The authors describe some of the new procedures being implemented to address these challenges; these include new faculty designations, clearer articulation of promotion procedures, explicit recognition of multiple forms of scholarship, expectations for investment in junior faculty, and mandatory discussion of faculty success in chairs' annual reviews. Faculty reactions, positive and negative, to these changes in procedures are also presented.

Selenomonas bacteraemia--case report and review of the literature.

Selenomonas species are crescent shaped Gram-negative bacilli with a characteristic tuft of flagella located on the concave surface. They are normally found in human gingiva or the rumen of herbivores. The first case of Selenomonas bacteraemia to be reported in a patient immunocompromised by malignant disease is described and the two previously reported cases of Selenomonas bacteraemia as reviewed. The importance of careful anaerobic culturing to recover the organism and special diagnostic techniques to classify the bacteria as Selenomonas species are emphasised. These organisms may cause serious human disease including bacteraemia.

Prenatal HIV prevention practices in a low seroprevalence state.

The purpose of this study was to build understanding of prenatal HIV counseling and testing practices in low seroprevalence states. Responses from a 1998 population-based survey of Kentucky prenatal care providers (67% response; 312 analyzed) were compared with findings from patient focus groups. Sixty-two percent of clinicians said they routinely counsel prenatal patients with risk factors, but only 46% routinely counsel patients without risk factors. The proportions routinely offering HIV testing to patients with and without risk factors were 94% and 84%, respectively. Prenatal patients identified "fear of a positive test result" as the major barrier to test acceptance. This fear was fueled by lack of knowledge regarding the benefits of early detection. The study concludes that achieving universal prenatal HIV testing will require new strategies, such as the distribution of a standardized protocol, that address clinicians' concerns about "time burdens" without depriving patients of the opportunity to receive individualized counseling.

Preventing secondary infections among HIV-positive persons.

Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children.