Claire Pomeroy

Adenovirus Infections in Hematopoietic Stem Cell Transplant Recipients

We report a 12% incidence of adenovirus infections among 532 recipients of hematopoietic stem cell transplant (HSCT) from January 1986 through March 1997. The median time from day of stem cell infusion to first positive culture was 41 days. Recipients of allogeneic stem cells, as opposed to autologous stem cell recipients, were more likely to have a culture positive for adenovirus (16% vs. 3%; P<.0001). Pediatric patients were also more likely than adults to have a positive culture (23% vs. 9%; P<.0001). Among stem cell recipients with partially matched related donors, pediatric recipients appear to be at significantly greater risk for infection than adult recipients (P<.001). Positive cultures were associated with evidence of invasion in 64% of cases (41 of 64). A multiple logistic regression analysis showed that isolating adenovirus from more than 1 site correlated with greater risk for invasive infections (P=.002). Invasive infections were associated with poorer chance of survival.

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.

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.

Medical Complications and Medical Management of Bulimia

The syndrome of bulimia is a common disorder and can be associated with serious psychological and physical morbidity. Unfortunately, many patients are reluctant to discuss their symptoms with their physicians and few clues can be found on physical examination to aid in the diagnosis. Possible physical signs include ulceration or scarring of the dorsum of the hand, salivary gland hypertrophy, and dental enamel erosion. In laboratory testing it is fairly common for patients with active bulimia to have fluid and electrolyte abnormalities, particularly hypokalemic alkalosis, and some also have elevated serum amylase levels. Rare complications include myopathies from misuse of ipecac, ruptured esophagus and pneumomediastinum associated with vomiting, and subtle abnormalities in neuroendocrine regulatory systems. Medical management including monitoring of fluid and electrolyte balance is essential during treatment.

A Placebo-Controlled, Double-Blind Crossover Study of Naltrexone Hydrochloride in Outpatients with Normal Weight Bulimia

The endogenous opioid system plays an important role in the control of feeding behavior. Previous research has shown that antagonism of endogenous opioids will suppress feeding in certain models in both human and infrahuman species. In the current study, 16 normal-weight bulimic women were treated with low-dose naltrexone, the long-acting, orally active narcotic antagonist, and placebo in a crossover design. The use of the active drug was not associated with a clinically significant reduction in binge eating or vomiting episodes. Suggestions for further research in this area are offered.

Effect of body weight and caloric restriction on serum complement proteins, including Factor D/adipsin: studies in anorexia nervosa and obesity

Complement plays important roles in host immune defences, and recent studies suggest that adipose tissue is an important site of production for some complement proteins. Starvation has been associated with low complement levels, but studied populations have usually had concomitant opportunistic infections or other conditions which might affect complement levels. To determine the impact of body weight and changes in body weight on serum complement, we investigated levels of complement proteins in otherwise healthy patients with a wide range of body weights, including patients with anorexia nervosa before and after treatment, obese dieters before and after weight loss, and normal weight controls. We found that complement proteins of the alternative pathway (C3, B, and D), alternative pathway haemolytic activity (AP50) and the inhibitors H and I were low in starving anorectics and normalized with weight gain. C3a levels were comparable in anorectics at low weight and after weight gain, indicating that low serum complement levels were attributable to hypoproduction and not complement cascade activation with consumption. Further, levels of C3, B, AP50, H and I, but not D, were higher than controls in obese patients and decreased toward normal after weight loss. Overall, percentage of ideal body weight, changes in body weight, and serum transferrin were each highly correlated with serum levels of complement proteins. We conclude that levels of alternative pathway complement components are determined in part by factors that influence body weight and by weight changes, possibly due to changes in production in adipose tissue or at other sites.

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.

Role of interleukin-6 and transforming growth factor-β in anorexia nervosa☆

Abstract 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-α (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β (TGF-β) 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-β 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-α levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.

Cognitive-behavioral group psychotherapy of bulimia nervosa: Importance of logistical variables

Although much of the psychotherapy for psychiatric disorders is conducted on a weekly basis, several researchers in the field of bulimia nervosa have utilized a more intensive approach as a means to strengthen treatment effects. A second issue concerns the amount of emphasis that should be placed on encouraging the interruption of bulimic symptoms early in treatment. In the current study we systematically studied these two issues. Subjects were randomly assigned to one of four forms of cognitive-behavioral group psychotherapy, the four cells differing on the variables of intensity and emphasis on abstinence. The results indicate that a high intensity approach, an early abstinence approach, or a combination of these two approaches are all significantly more effective in inducing remission in patients with bulimia nervosa compared with a weekly psychotherapy that uses the same manual-based cognitive-behavioral therapy approach.

Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity.

OBJECTIVE We previously reported elevated serum levels of the cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with anorexia nervosa (AN). We investigated the cellular production of these two cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa (BN), and obesity as well as in normal-weight control subjects. METHODS Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC) incubated with and without concanavalin A (ConA) were assayed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS Significant differences across the four groups were found in the stimulated cellular production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in the AN group compared to controls. IL-6 production was significantly elevated in obese subjects relative to the two normal-weight groups, BN and controls, and tended to be higher in the AN group than in the controls, but not significantly so. IL-1alpha production was greater in obese subjects. CONCLUSION The findings of increased IFN-gamma production and a tendency toward increased IL-6 production (both of which suppress food intake in animals) in individuals who severely restrict food intake suggest a potential role for these cytokines in the pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese individuals requires further investigation to determine if these cytokines contribute to the development or perpetuation of obesity.