Brad M. Dworkin

Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS)

UNLABELLEDnSelenium is required for activity of the enzyme glutathione peroxidase, and selenium deficiency may be associated with myopathy, cardiomyopathy and immune dysfunction including oral candidiasis, impaired phagocytic function and decreased CD4 T-cells. We assessed selenium status in 12 patients with AIDS compared to normals and found significantly low plasma and red blood cell levels. Plasma selenium in AIDS was 0.043 +/- 0.01 microgram/ml vs 0.095 +/- 0.016 in controls (P < 0.001). Selenium status correlated with serum albumin (r = 0.77; P < 0.001) and 60% had documented GI malabsorption as determined by abnormal D-Xylose tests. In a subsequent study blood selenium and glutathione peroxidase were diminished in 12 AIDS and 8 ARC patients compared with normals (all P < 0.001). For glutathione peroxidase the mean levels were decreased by 45% in AIDS and 27% in ARC versus controls (P < 0.001). Both plasma selenium and glutathione peroxidase significantly correlated with total lymphocyte counts (r = 0.65; P < 0.001; glutathione peroxidase and lymphocyte counts). This occurred in both homosexuals and drug users with AIDS and irrespective of the presence or absence of diarrhea or GI malabsorption. To determine if tissue levels of selenium were also depleted we studied cardiac selenium levels in autopsy AIDS hearts compared to age and sex matched controls. Cardiac selenium in AIDS was 0.327 +/- 0.082 micrograms/g dry weight versus 0.534 +/- 0.184 in controls (P < 0.01). Two cases had histologic cardiomyopathy pathologically consistent with the cardiomyopathy described in Keshan disease associated with low selenium blood levels. To further assess mechanisms of nutrient and selenium deficiency in AIDS we studied dietary intake in outpatients and inpatients with various stages of HIV infection. Inadequate selenium intake based on a computer (Nutritionist 3) analysis of 72 h diet records was present in only 17% of clinically stable HIV positive outpatients and 71% of inpatients with AIDS.nnnCONCLUSIONSnSelenium deficiency is common in HIV positive patients as documented by low plasma and red blood cell levels of selenium, diminished activity of glutathione peroxidase, and low cardiac selenium levels in AIDS hearts. Patients with AIDS tend to have more severe deficits than those with earlier stages of HIV infection. The selenium deficit in blood does correlate with serum albumin levels and total lymphocyte counts. Poor dietary intake and malabsorption could lead to this condition which has important implications for both cardiac and immune functions in HIV positive patients.

Abnormalities of blood selenium and glutathione peroxidase activity in patients with acquired immunodeficiency syndrome and aids-related complex

Severe protein-calorie malnutrition is common in patients with AIDS and could contribute to the progressive deterioration characteristic of that disease. Selenium deficiency could also have a negative impact on immune function and other organ functions vital for recovery from infectious diseases. Therefore, to assess any role for selenium in AIDS, we determined plasma and erythrocyte selenium levels and glutathione peroxidase activity in 13 patients with AIDS compared to 8 patients with AIDS-related complex (ARC) and 14 healthy controls. Plasma selenium levels were significantly reduced in AIDS patients compared to controls (p<.0001) and to ARC (p<.02). Erythrocyte selenium levels in both AIDS and ARC were also reduced compared to controls (p<.02), but not to each other. Glutathione peroxidase activity in AIDS was 28.9±1.4 U/g Hb vs 38.4±6.9 in ARC (p=NS) and 52.3±1.7 in controls (p<.0001 vs AIDS;p<.02 vs ARC). When all groups were combined, there were significant correlations between total lymphocyte count and both plasma selenium (r=.53;p<.002) and erythrocyte glutathione peroxidase activity (r=.65;p<.0001). In addition, strong correlations were noted between plasma selenium and serum albumin (r=.68;p<.0001), plasma selenium and glutathione peroxidase (r=.77;p<.0001), and glutathione peroxidase and hematocrit (r=.66;p<.0001). In AIDS or ARC, no correlations between selenium with disease duration or weight loss were present. We conclude that, in comparison to normals, patients manifesting infection with human immunodeficiency virus have evidence of selenium deficiency as determined by diminished plasma and erythrocyte levels and glutathione peroxidase activity. These abnormalities are most marked in patients with AIDS, but are also present in patients with AIDS-related complex. Selenium deficiency has important implications for the progression and pathogenesis of clinical disease in AIDS.

Diminished Blood Selenium Levels in Renal Failure Patients on Dialysis: Correlations with Nutritional Status

Selenium deficiency has been implicated as contributing to the development of cardiovascular disease, skeletal muscle myopathy, anemia, increased cancer risk, and deranged immune function. Since these problems may also be associated with renal failure, and the kidney plays an important role in selenium homeostasis, we measured selenium and compared it with nutritional status in 24 stable hemodialysis patients, 12 chronic intermittent peritoneal dialysis patients, and 29 healthy controls. Whole blood and plasma selenium was determined by a spectrofluorometric method. For whole blood the mean (±SD) selenium levels were 0.11 ± 0.02 ug/ml in controls vs. 0.071 ± 0.01 ug/ml in hemodialysis cases and 0.052 ± 0.006 ug/ml in peritoneal dialysis (p < 0.005). Significant decreases were seen also for plasma and red blood cell selenium in all groups respectively. Pre- and postdialysis plasma and whole blood selenium levels showed no significant changes in both dialysis groups. However, predialysis residual peritoneal fluid did contain selenium (0.029 ± 0.005 ug/ml).Some evidence of protein-energy undernutrition was noted in both dialysis groups compared with controls. However, no significant differences in nutritional parameters were noted between hemodialysis and peritoneal dialysis patients. When all groups were combined, significant correlations were found between whole blood selenium and serum albumin (r = 0.61; p < 0.001), triceps skin fold in females (r = 0.62; p < 0.001), and midarm muscle circumference in males (r = 0.71; p < 0.001).We conclude that low blood selenium is present in renal failure patients undergoing hemodialysis. This abnormality is even greater in peritoneal dialysis cases. Although pre- and postdialysis selenium levels do not change appreciably, peritoneal fluid contained selenium and represents a source of loss. Poor proteincalorie nutritional status was also evident in both dialysis groups and probably contributed to this abnormality.

Decreased hepatic selenium content in alcoholic cirrhosis

Selenium deficiency has been implicated as contributing to hepatic injury in alcoholics. The mechanism by which this occurs is most likely lipoperoxidation secondary to decreased activity of the selenoenzyme glutathione peroxidase. To further assess this relationship, we measured selenium content in autopsy livers in 12 patients with alcoholic cirrhosis compared to 13 patients matched for age and sex dying from other causes, mostly with cardiopulmonary diseases. The mean (±sem) hepatic selenium content in cirrhosis was 0.731±0.077 Μg/g dry weight versus 1.309±0.166 Μg/g in controls (P< 0.005; Students t test). Clinical and biochemical indices of significant hepatic dysfunction, including encephalopathy, ascites, and elevations of serum bilirubin or prothrombin time, were only present in the cirrhotic group. A significant inverse correlation between hepatic selenium content and the prothrombin time was noted (r=−0.50; Ps<0.02). No significant relationships between hepatic selenium and the abnormalities of bilirubin, albumin, or aspartate aminotransferase were found. We conclude that significantly decreased hepatic selenium stores are present in patients with severe alcoholic cirrhosis compared to controls. The magnitude of that selenium deficit does correlate with some indices of hepatic function, specifically the prothrombin time. These data lend further support to a true selenium deficiency state in alcoholic cirrhosis. It is highly possible that selenium deficiency represents an important link, synergistically joining the nutritional and hepatotoxic backgrounds of alcoholic liver injury and cirrhosis.

Persistence of multiply antibiotic-resistant campylobacter jejuni in a patient with the acquired immune deficiency syndrome

Chronic diarrhea due to Campylobacter jejuni has been described in patients with hypogammaglobulinemia. A patient with the acquired immune deficiency syndrome (AIDS) and normal total serum immunoglobulins had persistent diarrhea and C. jejuni on stool culture for seven and a half months despite repeated antibiotic therapy. Antibiotic sensitivity studies revealed the C. jejuni to be multiply antibiotic-resistant. Evaluation of the mechanism of resistance showed the organism harbored a conjugative plasmid capable of transferring resistance to tetracycline, but not to other antibiotics. It is concluded that C. jejuni infection may rarely result in chronic diarrhea in patients with AIDS. The combination of an immune deficiency state including abnormal B cell function previously described in AIDS and multiple antibiotic resistance may have contributed to the persistence of the organism in this case.

Open label study of long-term effectiveness of cisapride in patients with idiopathic gastroparesis

Cisapride induces acetylcholine release in cells of the myenteric plexus, thus promoting gastrointestinal motility. We studied the effects of cisapride on 11 patients with idiopathic gastroparesis. All had negative gastrointestinal endoscopy, normal glucose, and took no drugs capable of influencing motility. Most (9/11) were prior metoclopramide treatment failures. Patients symptoms were scored (0–60) for pain, satiety, bloating, nausea, vomiting, and heartburn. All underwent a solid gastric emptying study using a Technetium-99-labeled egg meal and received placebo prior to cisapride. There were 10 females and one male with a mean (±se) age of 37.8±2.6 years. Disease duration was 7.9±2.8 years. The dose of cisapride was 30–60 mg/day and the duration of therapy was 12.6±2.6 months (range 2.5–25 months). The symptom score improved on cisapride from 30.9±3.6 to 14.4±2.7 (P<0.002 signed rank test). Emptying half-time improved from 113±4 min to 94±6 min, and 46.9±2.4% food remaining at 120 min decreased to 35.5±3.6% (bothP<0.05). Emptying half-time in normals was 68±5 min with 16.9±2.9% remaining at 120 min. Nine of 11 patients gained weight, with a mean increase of 6.7±1.6 lb (range 2–12 lb). We conclude that cisapride significantly reduces gastrointestinal symptoms and promotes weight gain in patients with idiopathic gastroparesis and is associated with improvement in solid gastric emptying. The drug is useful in patients who previously failed metoclopramide.

Severe intrahepatic cholestasis in patients treated with recombinant interleukin-2 and lymphokine-activated killer cells

SummaryImmunotherapy with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK) has become a new form of therapy that has been shown to induce remissions in patients with renal cell carcinoma and melanoma. Despite encouraging results, this form of therapy has been associated with increasing toxicity, often requiring therapy in an intensive-care unit. In this report severe intrahepatic cholestasis occurred in two patients receiving rIL-2 and LAK cells. This form of cholestasis appeared to be directly related to rIL-2 administration at a doses of 2×106 U/m2 and 3x106 U/m2 t.i.d. A liver biopsy showed moderate hepatocellular bile stasis, with lobular and portal inflamation. All other studies for potential cause of this cholestasis were negative, including studies for metastatic disease. When therapy was discontinued, evidence for cholestasis and bile stasis resolved. We conclude that rIL-2 is a drug with a potential to induce severe hepatic injury that is reversible upon cessation of therapy with rIL-2. Further care should be exercised when rIL-2 is administered to patients with abnormal liver function.

Upper gastrointestinal bleeding following open heart surgery. Predominant finding of aggressive duodenal ulcer disease.

We reviewed our experience with endoscopically evaluated severe upper gastrointestinal hemorrhage following open heart surgery. Of 4892 patients undergoing open heart surgery, 18 (0.4%) sustained upper gastrointestinal hemorrhage requiring endoscopic evaluation. Endoscopy identified the source of bleeding in all cases. No significant complications of endoscopy were observed. Duodenal ulcers (DUs) were found in 16 (89%) of cases and were felt to be the source of bleeding in 15 (83%). Aggressive features, such as multiplicity, large size, or distal location were associated with 13 (81%) of the DU cases. Complications necessitated endoscopic or surgical therapy in eight (44%) patients with DUs. We conclude that aggressive DU disease accounts for the majority of severe upper gastrointestinal bleeding following open heart surgery.

Hemolysis, elevated liver enzymes, and low platelets in pregnancy (HELLP syndrome) a case report and literature review

The chnical syndrome of hemolysis, elevated liver enzymes and low platelets in pregnancy was first described in 1954 by Pritchard, et al (1). Since then, a total of about 300 patients have been reported (2-9). Controversy surrounding the definition, diagnosis, incidence, cause, and management of H E L L P still remains (7-12). Because the prompt recognition and management of this condition is critical to the survival of both the mother and fetus, and because the presentation may be subtle, gastroenterologists are frequently called by obstetricians to assist in the management of these patients. We report a case of HELLP and review the literature.

Nutritional Support of the Geriatric Patient

The past two decades have witnessed a dramatic change in our ability to provide adequate nutrition for our patients. At the present time, this frequently involves the use of enteral tube feedings or intravenous alimentation. This chapter will provide a practical background for the use of these advanced enteral and parenteral nutritional support techniques in the geriatric patient.