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Biomedical subjects

J K Griffiths

Publications and source records attributed to J K Griffiths.

28 records · Page 2Linked to original sources

Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children.

OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.

Adjuvants, Immunologic↗

Temporal changes in permeability and structure of piglet ileum after site-specific infection by Cryptosporidium parvum.

BACKGROUND/AIMS: Cryptosporidiosis is an important enteric infection associated with diarrhea in humans. The structural and functional basis for diarrhea is poorly understood. The aim of the study was to determine the structural and functional basis of diarrhea in cryptosporidiosis during evolving host cell-parasite interactions in the intestine. METHODS: We used the piglet model for temporal studies of alterations in intestinal epithelial structure and function that occurred 12-48 hours postinoculation. Segments of intestine were directly inoculated in vivo, harvested, and studied in vitro using Ussing chamber techniques. RESULTS: Villus architectural alterations corresponded to the extent of infection. Increased numbers of lamina propria inflammatory cells were evident at 36 hours postinoculation. Solute and macromolecular permeability was not increased. Glucose-responsive short-circuit current was diminished at 48 hours postinoculation. The short-circuit current response to theophylline was the same in control and infected tissues. CONCLUSIONS: We conclude that passive solute and macromolecular permeability in infected tissues is not significantly increased during parasite-host cell interactions 12-48 hours postinoculation. Electrogenic glucose stimulated Na+ absorption, a function principally of villus absorptive cells, is impaired, and electrogenic Cl- secretion, a function of crypt epithelial cells, remains the same. These findings parallel structural observations that include loss of the Na+/glucose-transporting villus epithelium without loss of crypt epithelium.

Animals↗

Spectrum and significance of bacteremia due to Moraxella catarrhalis.

Fifty-eight cases of bacteremia due to Moraxella catarrhalis, including seven that occurred in patients treated at our facilities, are analyzed. The host's medical history plays a major role in the presentation and outcome of M. catarrhalis bacteremia. Bacteremia is typically accompanied by pneumonia in adults with underlying respiratory disease. Many neutropenic patients do not manifest a focus of infection; in contrast, the source identified in healthy, immunocompetent patients is usually the upper airway or the ears. In the recent literature, it has been reported that a rash is typically absent in adults with bacteremic pneumonia and in immunocompetent hosts and that only some neutropenic patients have a rash. The prognosis is grave for patients with endocarditis and for patients with immunoglobulin deficiency or neutropenia not related to a hematologic malignancy. In addition, mortality is substantial among bacteremic patients with respiratory conditions or other chronic debilities, especially when respiratory copathogens are present. The prognosis is good for febrile neutropenic patients with underlying leukemia or lymphoma when the neutropenia resolves. When healthy, immunocompetent individuals are affected with M. catarrhalis bacteremia, their presentations range from self-limited febrile illness to life-threatening disease.

Adult↗

Shigellosis in neonates and young infants.

To determine the clinical features and outcome of shigellosis in young infants, we reviewed the hospital records of 159 infants < or = 3 months of age (including 30 neonates) and 159 children 1 to 10 years of age with shigellosis who were admitted to the Diarrhoea Treatment Centre in Dacca, Bangladesh. Infants more commonly had a history of nonbloody diarrhea (82.8% vs 42.7%; p < 0.001), moderate or severe dehydration (59.9% vs 32.1%; p < 0.001), or bacteremia (12.0% vs 5.0%; p = 0.027) and less commonly had fever (32.7% vs 58.6%; p < 0.001), abdominal tenderness (1.9% vs 12.6%; p < 0.001), or rectal prolapse (0% vs 8.3%; p = 0.001). Infections caused by Shigella boydii (20.8% vs 6.3%; p < 0.001) and Shigella sonnei (7.5% vs 1.3%; p = 0.006) were more common, and Shigella dysenteriae type 1 (9.4% vs 31.4%; p < 0.001) infections were less common in infants than in older children; the proportion of Shigella flexneri infections was equivalent in the two groups (59.1% vs 60.4%). Infants were twice as likely to die as older children (16.4% vs 8.2%; p = 0.026). Only 17 infants (14.3%) were being exclusively breast fed at the onset of their illness. In a multiple logistic regression analysis, independent predictors of death in infants were gram-negative bacteremia, ileus, decreased bowel sounds, hyponatremia, hypoproteinemia, and a lower number of erythrocytes detected on microscopic examination of stool specimens. Diarrhea management algorithms that rely only on clinical findings of dysentery to diagnose and treat shigellosis are likely to be unreliable in this high-risk age group.

Age Factors↗

Cryptosporidium parvum infection of Caco-2 cell monolayers induces an apical monolayer defect, selectively increases transmonolayer permeability, and causes epithelial cell death.

Caco-2 cells were grown on permeable filters and infected with Cryptosporidium parvum. Infection rates exceeded 50% of target cells with a sufficient inoculum dose of parasites. Infection induced a dose- and time-dependent fall in transmonolayer resistance, which was closely related to both the inoculum dose and the number of parasites detected by immunofluorescence. Caco-2a, MDBK, and MDBK subclone F5D2 evidenced similar declines in resistance when grown and infected under similar circumstances. Caco-2 monolayers became permeable to molecules of < or = 1,000 Da but continued to remain impermeable to exogenously added, or endogenously produced, proteins of > or = 1,881 Da. We found that infected monolayers released up to 50% of the total cellular lactase dehydrogenase into apical media, but not basal media, and that the vital dye propidium iodide avidly stained infected cells, and often parasites, when added to the apical reservoir. Cryptosporidium infection of Caco-2 monolayers increases transmonolayer permeability, induces an apical cellular and monolayer defect, and causes cell death.

Animals↗

Interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist, and TNF alpha production in whole blood.

The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production can make such evaluation impractical in some clinical situations. We report a method for stimulating whole blood to produce cytokines that can be implemented in laboratories without tissue culture facilities and requires minimal sample preparation. IL-1 beta and TNF alpha production in whole blood samples was stimulated with endotoxin and/or phytohemagglutinin in standard EDTA-containing vacuum collection tubes. After incubation, plasma was removed and frozen for later assay. Comparison of this whole blood method with isolated mononuclear cell cultures indicated a significant correlation for IL-1 beta production (r = 0.746, P = 0.005). This technique also produced the newly described cytokine, IL-1 receptor antagonist. We conclude that the whole blood method is an acceptable alternative to isolated cell culture methods for measuring IL-1 beta in situations that preclude the standard in vitro approach.

Adult↗

Two cases of endocarditis due to Lactobacillus species: antimicrobial susceptibility, review, and discussion of therapy.

Endocarditis caused by lactobacilli may lead to death or to relapse of infection, despite antimicrobial treatment. We report two cases of lactobacillus endocarditis in individuals with native bicuspid aortic valves who survived without relapse and review the 39 other cases reported in the literature. In only 15 previously reported cases have patients been cured with medical therapy alone. One of our patients, who was infected with Lactobacillus acidophilus, was cured by medical therapy alone, and our other patient, who was infected with Lactobacillus casei subspecies rhamnosus, required surgical replacement of his aortic valve. L. acidophilus was tolerant and L. casei subspecies rhamnosus was resistant to many antibiotics tested. Combinations of penicillin or daptomycin and gentamicin were synergistic by time-kill assay. Synergistic therapy with a penicillin and an aminoglycoside was effective clinically and appears to provide optimal medical treatment on the basis of microbiological data.

Adult↗

Use of passive surveillance data to study temporal and spatial variation in the incidence of giardiasis and cryptosporidiosis.

OBJECTIVE: The goal of this study was to evaluate temporal and spatial variations in the reporting of cases of giardiasis and cryptosporidiosis to a passive surveillance system, and to assess the relationship of those variations to source of drinking water, adjusting for socioeconomic variables. METHODS: The authors analyzed temporal and spatial patterns for 4,058 cases of giardiasis and 230 cases of cryptosporidiosis reported to the Massachusetts Department of Public Health for 1993-1996. They linked each reported case to a database containing information on source of residential water supply and socioeconomic characteristics and evaluated the association between these factors and reporting rates using regression techniques. RESULTS: Reports of giardiasis and cryptosporidiosis were highest for the mixed unfiltered drinking water supply category. Reports of giardiasis were associated with income levels. Increases in reporting for both giardiasis and cryptosporidiosis were seen in summer to early fall. During a suspected outbreak of cryptosporidiosis n the city of Worcester in 1995, a significant increase in reported cases was also observed in the Boston metropolitan area. Following the suspected outbreak, weekly giardiasis rates increased slightly in Worcester and the Boston metropolitan area, while reporting of cryptosporidiosis increased dramatically. CONCLUSIONS: Consistently collected passive surveillance data have the potential to provide valuable information on the temporal variation of disease incidence as well as geographic factors. However, passive surveillance data, particularly in the initial period of surveillance, may be highly sensitive to patterns of diagnosis and reporting and should be interpreted with caution.

Adolescent↗

Fever, jaundice, and histiocytic erythrophagocytosis: fulminant infection or malignancy?

Some of the problems which we see on the infectious disease consultation service can be quite frustrating. This is one such case. A middle-aged man presented to our medical service with fever and dyspnea. His fulminant downhill course was characterized by anemia, jaundice, hypercalcemia, pulmonary abnormalities, and a lack of responsiveness to conventional antimicrobial therapy. At autopsy, malignant-appearing histiocytes were present in several organs including spleen, lymph nodes, and lung. Histopathological examination of tissues obtained at autopsy confirmed the presence of phagocytized erythrocytes within such histiocytes. This case aptly illustrates the hazy dividing line which sometimes exists between infectious and/or malignant processes which are, at present, still of undetermined etiology.

Diagnosis, Differential↗