In a controlled randomized study among 48 patients undergoing 75 courses of aggressive antileukemic therapy, it was shown that cotrimoxazole was less effective than penicillin G in preventing septicemia due to viridans streptococci. Both antibiotics were given intravenously. During 35 episodes of chemotherapy in the group of patients on penicillin G only, one patient developed a streptococcal bacteremia; this contrasted with bacteremia and septicemia in seven patients during 40 episodes in the group on cotrimoxazole. In three of these seven patients, septicemia was associated with respiratory failure and it was the cause of death in one. Both aerobic gram-negative rods and streptococci which caused infection despite cotrimoxazole prophylaxis were resistant to cotrimoxazole. Side effects such as hypersensitivity and favorable or unfavorable interaction with the oral selective decontamination regimen were similar for the two drugs, with the exception of colonization with Candida spp, which occurred more often in patients on cotrimoxazole than in patients on penicillin.

Agranulocytosis↗

PubMed1992

Erysipelas-like skin lesions associated with Campylobacter jejuni septicemia in patients with hypogammaglobulinemia.

Three cases are reported of hypogammaglobulinemic males with recurrent Campylobacter jejuni septicemia and erysipelas-like cellulitis without diarrhoea. In one patient Campylobacter jejuni grew from skin biopsy specimens. The findings in another patient were strongly suggestive of osteomyelitis caused by Campylobacter jejuni. Since the susceptibility of hypogammaglobulinemic patients to infection with Campylobacter jejuni is probably related to a lack of serum bactericidal activity against Campylobacter jejuni due to lack of IgM, two patients in whom previous antimicrobial treatment failed were treated with plasma infusions. This regimen supplemented with imipenem resulted in cure of these relapsing infections. Campylobacter jejuni septicemia must be considered in hypogammaglobulinemic patients who present with periodic fever and cellulitis.

Adult↗

PubMed1992

Chronic intraperitoneal infusion of low doses of tumor necrosis factor alpha in rats induces a reduction in plasma triglyceride levels.

Single and repeated bolus injections of tumor necrosis factor alpha (TNF) in laboratory animals have been reported to result in hypertriglyceridaemia, suggesting that TNF is a mediator of hypertriglyceridaemia occurring during infection. However, as during infection production of TNF is probably chronically elevated, we determined the effects of continuous infusion of low doses of TNF on plasma levels of triglycerides and cholesterol. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps which continuously delivered TNF or saline for 7 days. Infusion of rats with doses of TNF as low as 4.0 and 8.0 micrograms/24 h resulted in significant decreases in plasma levels of triglycerides as compared with those after saline infusion. Although plasma triglyceride concentrations were persistently lower in TNF than in saline animals throughout the study period, the differences were most prominent during the first days and reached statistical significance at day 1, 3, 4 and 5 and of the 4.0 micrograms experiment and on day 1, 2 and 3 of the 8.0 micrograms experiment. This suppression of plasma triglyceride concentrations was not accompanied by changes in plasma cholesterol levels. No effects of chronic TNF treatment on food intake, body weight change and rectal temperature of the animals were observed. These findings indicate that chronic infusion of low doses of TNF induces hypotriglyceridaemia in rats. The role of TNF as a factor in mediating hypertriglyceridaemia during infectious diseases needs to be reconsidered.

Animals↗

PubMed1992

Plasma and whole blood exchange in meningococcal sepsis.

The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin. Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE. Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73%. A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62%. In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours. In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission. The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025). For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured. The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes. This is approximately the same as reported values for patients who were not treated with PEBE. It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin.

Adolescent↗

PubMed1992

Indium-111-labeled human nonspecific immunoglobulin G: a new radiopharmaceutical for imaging infectious and inflammatory foci.

Indium-111-labeled human nonspecific immunoglobulin G (111In-IgG) is a newly developed radiopharmaceutical for imaging infectious and inflammatory foci. This article presents an overview of the literature concerning 111In-IgG scintigraphy. The current theory about the mechanism of accumulation suggests that 111In-IgG accumulates in lesions as a result of enhanced vascular permeability and subsequent entrapment of the radiolabeled protein. Human studies show excellent results in imaging bone and joint, abdominal, and intravascular infection. Of special interest is the ability to depict infectious foci in granulocytopenic patients. The value of 111In-IgG scintigraphy for detection of infection is compared with that of gallium-67, labeled-leukocyte, and technetium-99m (99mTc) nanocolloid scintigraphy. The significance of differences between 111In-IgG scintigraphy and two other new scintigraphic techniques, 99mTc-labeled IgG and 99mTc-labeled murine monoclonal anti-granulocyte antibody BW 250/183, are discussed.

Animals↗

PubMed1992

Dietary fish-oil supplementation in experimental gram-negative infection and in cerebral malaria in mice.

Dietary fish-oil supplementation interferes with eicosanoid production and appears to decrease production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). The effect of fish oil was investigated in an intramuscular Klebsiella pneumoniae infection in Swiss mice and in cerebral malaria induced by Plasmodium berghei in C57B1/6 mice. After a low inoculum of K. pneumoniae, 90% of fish oil-fed mice survived; survival in control mice fed equal amounts of corn or palm oil or normal chow was 30%, 40%, and 0, respectively. Cerebral malaria occurred in only 23% of fish oil-fed mice; in the controls, cerebral malaria developed in 61%, 81%, and 78%, respectively. Contrary to what was expected, lipopolysaccharide-induced ex vivo production of IL-1 alpha and TNF alpha by peritoneal cells was significantly enhanced in fish oil-fed mice compared with controls. Indomethacin treatment did not alter the outcome in these two infections, thus arguing against reduced prostaglandin synthesis as an explanation for the increase in resistance to infection.

Animals↗

PubMed1992

Optimizing antimicrobial therapy. A method for antimicrobial drug use evaluation.

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Anti-Bacterial Agents↗

PubMed1992

Use of immune modulators in nonspecific therapy of bacterial infections.

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Adjuvants, Immunologic↗

PubMed1992

Interleukin-1-induced nonspecific resistance to bacterial infection in mice is not mediated by glucocorticosteroids.

Preexposure to a low dose of interleukin-1 (IL-1; 3 to 30 micrograms/kg) 24 h before a lethal gram-negative bacterial infection prolonged survival in normal and granulocytopenic mice. To examine whether this protective effect is mediated by glucocorticosteroids, we first measured corticosterone concentrations in mice after administration of 80 and 800 ng of IL-1. IL-1 induced a dose-dependent increase in corticosterone levels in plasma. Next, the corticosterone peak induced by a protective dose of IL-1 (800 ng) was simulated by administration of synthetic human adrenocorticotropic hormone 1-24 (ACTH) in normal and neutropenic mice. Although corticosterone levels induced by pretreatment with IL-1 or ACTH were virtually identical, the ACTH-induced corticosterone peak was not associated with protection against Klebsiella pneumoniae infection in normal mice and Pseudomonas aeruginosa infection in neutropenic mice. This indicates that the protective effect of IL-1 pretreatment against gram-negative bacterial infection is not mediated by elevated levels of glucocorticosteroids. In addition, we found that plasma corticosterone concentrations during K. pneumoniae infection were significantly lower after pretreatment with IL-1 than after pretreatment with ACTH or vehicle, probably reflecting the better physical condition of IL-1-treated mice.

Animals↗

PubMed1992

Continuous infusion of interleukin-1 beta in rats induces a profound fall in plasma levels of cholesterol and triglycerides.

During infectious diseases, striking alterations in plasma concentrations of cholesterol (hypocholesterolemia) and triglycerides (hypertriglyceridemia) may occur. It has been suggested that interleukin-1 is a mediator of these alterations. We studied the effects of continuous administration of recombinant human interleukin-1 beta (rhIL-1 beta) on plasma levels of cholesterol and triglycerides. A total of 42 rats were equipped with minipumps loaded with either rhIL-1 beta (delivery rate of 0.5, 2.0, or 4.0 micrograms/day i.p. for 1 week) or saline. After 1 day of treatment with rhIL-1 beta, plasma cholesterol levels had not changed. On day 2 a remarkable decrease of plasma cholesterol levels was observed in rats treated with 2.0 micrograms rhIL-1 beta/day (1.49 +/- 0.13 versus 2.23 +/- 0.08 mmol/l, p less than 0.005; rhIL-1 beta versus saline) or 4.0 micrograms rhIL-1 beta/day (1.46 +/- 0.04 versus 2.18 +/- 0.04 mmol/l,p less than 0.0005). This decrease persisted until the end of the experiment and occurred in all major lipoprotein fractions. Triglycerides in plasma (and in very low density lipoprotein) decreased almost concomitantly with plasma cholesterol, although to a lesser degree. Infusion of 2.0 micrograms rhIL-1 beta/day did not affect either cholesterol esterification or total postheparin lipolytic activity in plasma. Long-term infusion with 4.0 micrograms rhIL-1 beta/day induced prolonged fever, whereas at the lower doses temperatures were elevated only the first 2 days. rhIL-1 beta at a dose of 2.0 and 4.0 micrograms/day induced a transient decrease of food intake and a suppression of body weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Chronic stimulation of the pituitary-adrenal axis in rats by interleukin-1 beta infusion: in vivo and in vitro studies.

It has been shown that acute administration of interleukin-1 (IL-1) to rats elicits a transitory increase in plasma ACTH and corticosterone (B) levels. To investigate the effects of chronic administration of IL-1 on plasma ACTH and B levels, in the present study rats were equipped with Alzet osmotic minipumps loaded with either IL-1 (delivery rate 0.5, 2.0, or 4.0 micrograms/24 h, ip, for 1 week) or saline. At the end of the treatment the rats were decapitated, the adrenals were weighed, and the in vitro release of beta-endorphin (beta E) by the anterior pituitary and that of B by the adrenal gland were measured. Continuous administration of 2.0 and 4.0 micrograms IL-1/24 h resulted in a persistent increase in plasma ACTH and B concentrations compared to the levels in saline-infused rats, with peak levels on the first day of administration. In addition, adrenal weights of IL-1 rats were significantly higher than those of saline rats. The 4.0-micrograms IL-1/day in vivo treatment induced an increase in spontaneous in vitro secretion of beta E and B, while the in vitro responses of the pituitary (to CRF) and the adrenal (to ACTH) of animals treated in vivo with IL-1 were significantly diminished. IL-1 at a dose of 0.5 microgram failed to affect plasma ACTH and B values, adrenal weight, and in vitro beta E and B secretion. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at lower doses of IL-1 (2.0 and 0.5 micrograms), temperatures were elevated only on the first 2 days of infusion. IL-1 at doses of 2.0 and 4.0 micrograms/day induced suppression of body weight gain on the first 2 days of the treatment period compared to saline treatment. Plasma norepinephrine and/or epinephrine concentrations were raised only on day 1 of the 2.0- and 4.0-micrograms IL-1 experiments. Thus, the observed effects of IL-1 on the hypothalamo-pituitary-adrenal axis probably do not result merely from stress induced by the treatment. Taken together, our data show the potential of IL-1 to induce a dose-dependent and long term activation of the pituitary-adrenal axis.

Adrenal Glands↗

PubMed1992

Gastric abnormalities in humoral immune deficiency syndromes.

Patients with late-onset hypogammaglobulinaemia have a very high risk of developing gastric cancer. In such patients there is a high frequency of atrophy of the gastric mucosa. This is reflected in low gastrin content of the antral mucosa, low serum pepsinogen A level and pepsinogen A/C ratio, and reduced serum gastrin secretion in response to bombesin stimulation. There is no evidence to support a role of Helicobacter pylori infection in the aetiopathology of these gastric abnormalities, although prior infection cannot be excluded with certainty. Since patients with early-onset hypogammaglobulinaemia and X-linked agammaglobulinaemia do not show this increased frequency of gastric abnormalities, it is unlikely that the immunoglobulin deficiency per se is responsible for the development of the gastric abnormalities found in patients with late-onset hypogammaglobulinaemia. Because of the very high risk of gastric cancer, regular endoscopic screening is warranted in patients with late-onset hypogammaglobulinaemia.

Agammaglobulinemia↗

PubMed1992

Psychogenic periodic fever.

The present report concerns a 35-yr-old Caucasian male who had suffered from episodic fever of unknown origin over a period of 13 yr. Extensive investigation covering all the known causes of fever of unknown origin did not yield a diagnosis. Finally, a psychogenic cause was considered, and treatment with a psychotropic drug and relaxation therapy led to complete disappearance of the febrile periods.

Adult↗