Mechanisms of resistance to the carbapenems.
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Biomedical subjects
Publications and source records attributed to M J Gill.
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Antibodies against reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) have been detected in seropositive subjects by immunoprecipitation, Western immunoblotting, and neutralization assay. Recently, we noticed that the antibodies against RT stabilized RT upon heat inactivation, and we have developed a stabilization assay of RT antibody. Briefly, the RT of HIV-1 is completely inactivated by incubation at 56 degrees C for 20 min, but this inactivation is inhibited in the presence of a specific antibody directed against this molecule. We examined the specificity and clinical significance of this stabilization assay. HIV-1 antibody-positive sera stabilized HIV-1 RT but not HIV-2 RT, whereas half of these sera cross-neutralized HIV-2 RT. Antibody titers against RT determined by the neutralization assay and the stabilization assay were compared with clinical characteristics. Antibodies against HIV-1 RT were much more frequently detected by the stabilization assay than by the neutralization assay. Statistically significant associations were found between stabilizing antibody titer and CD4+ cell number in peripheral blood of patients and also between antibody titer and CD4+/CD8+ ratios. These results indicate that our new stabilization assay to detect specific antibodies against RT of HIV-1 is useful as a clinical marker of infection and progress of the disease.
OBJECTIVE: To determine whether previous blood donations from HIV-positive patients posed a threat to recipients. DESIGN: Interviewer-administered questionnaire survey. SETTING: Regional HIV outpatient referral clinic for southern Alberta. PATIENTS: All 478 patients attending the clinic from May 1, 1993, to Mar. 31, 1994; 366 were excluded: 335 had not donated blood, and 31 could not provide reliable information regarding possible donations. INTERVENTIONS: Patients were asked at a routine clinic visit regarding the dates, frequency and location of previous blood donations. The Canadian Red Cross was informed, with patient consent, if the previous donations posed a potential risk of HIV transmission. OUTCOME MEASURES: Number of HIV-positive patients whose donations posed a possible or definite risk to recipients. RESULTS: A total of 545 units of blood had been donated by the 112 patients in the study; 57 units (donated by 29 patients) posed a possible risk, and 12 (given by 11 patients) posed a definite risk of HIV transmission to the recipients. Thirty-two of these donors had been unknown to the Red Cross through its "look-back" and "trace-back" protocols. Only 1 of the 13 patients found to be HIV positive by the Red Cross openly admitted donating blood to undergo HIV antibody testing; the remainder were either ill-informed or did not perceive themselves to be at risk. The patients were highly mobile, 36.7% donating blood at some time in a province other than the one where they had received their positive HIV test result. CONCLUSION: Asking HIV-positive patients about their blood donation history, although subject to recall bias, is a simple and inexpensive method for identifying high-risk blood donations. The Red Cross should routinely be notified, with patient consent, of all donations posing a risk in order to enhance the prospect for identifying HIV-positive blood recipients.
The major outer membrane protein of Neisseria gonorrhoeae, Por, functions as a porin and is thought to occur as one gene with two alleles. The immunologically distinct epitopes of the two subclasses, IA and IB, have allowed the development of serotyping schemes. Clinical isolates of N. gonorrhoeae are believed to express only a single type of Por, either IA or IB. We have encountered two clusters of isolates that react with antibodies to both IA and IB Por. Isolates within the clusters are indistinguishable by the phenotypic characteristics tested. In addition, the amplification of the por gene in representative isolates showed that the por gene of the hybrids gave similar restriction digest patterns within but not between the clusters.
Novel carbohydrate antigen expressions were observed on T lymphocytes from HIV infected patients using flowcytometric analysis with four mAbs; BM-1, ACFH-18, FH-2 and C-6. These carbohydrate antigens were also expressed on oncogenic transformed cells but were either not expressed or were weakly expressed in lymphocyte populations from healthy subjects. A dramatic change in glycosylation was induced on CD8+T cells from HIV infected patients. The glycosylation change correlated with the progression of the disease. The incidence of Ley antigen expression on CD8+T cells increased as the disease progressed with the ongoing impairment of immune function. The phenotype change that occurred with Ley antigen expression might reflect the abnormal activation of T lymphocytes of some specific, but unknown, population of CD8+T cells. Thus, carbohydrate changes on the cell surface may induce immunological abnormality and accelerate the damage within the CD4+T cell subset, resulting in an impairment of the antigen specific immune system.
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Gastrointestinal symptoms are commonly seen in patients with established AIDS. We examined the charts of 258 HIV-infected patients attending our HIV outpatient clinic to determine: (1) the frequency of gastrointestinal symptoms in unselected HIV-infected patients and (2) if there are any predictors of the development of symptoms in initially asymptomatic patients. We found the overall frequency of gastrointestinal symptoms at initial presentation in our ambulatory, predominantly homosexual population of HIV-infected patients was 35% (95% CI 30-40%) with 19% having anorexia, 15% weight loss, 14% diarrhea, and 5% dysphagia. There was no association between the presence of symptoms and stool parasites, which were found in 51% of patients. In 165 patients who were initially asymptomatic, 72% subsequently developed symptoms over 36 months of actuarial follow-up. Patients with initial T4 counts < 500 were more likely to develop symptoms. Patients with a greater degree of immunosuppression as indicated by a lower T4 count, are more likely to develop gastrointestinal symptoms.
The bioavailability of zidovudine was evaluated in 16 HIV seropositive patients using a prospective standardized study. Symptomatology, D-xylose absorption and immune status were also measured to determine indicators of poor bioavailability. Zidovudine was rapidly absorbed (Tmax: 0.82 +/- 0.39 h) with a large variation in peak serum concentrations (Cmax: 1.21 +/- 0.64 mg/L). The mean elimination half-lives after intravenous and oral administration were 1.5 +/- 0.4 h and 1.3 +/- 0.2 h, respectively. Mean zidovudine bioavailability was 64.0 +/- 21.3% and was not associated with D-xylose absorption values. Five h urine D-xylose excretion was abnormal in seven patients but only three (43%) had zidovudine bioavailabilities below the mean for the group. Conversely, only five of nine patients (56%) with normal D-xylose absorption tests had zidovudine absorption values below the mean. The presence of a mild alteration in bowel habits, defined as up to four unformed or semi-solid stools per day, showed a highly significant relationship to low bioavailability (P < 0.0001, Student's t-test). Lower CD4 lymphocyte counts were also associated with a low bioavailability (R-squared, 0.36, P = 0.0143). Patients with lower CD4 lymphocyte counts or with mild diarrhoea may be at risk for erratic zidovudine absorption.
An increased incidence of lymphoma has been reported in patients with the acquired immunodeficiency syndrome. Malignant lymphomas that develop within this setting of impaired immune surveillance have distinctive clinical, histologic, and molecular biologic characteristics. Histologically, the majority of these lymphomas are small noncleaved cell or immunoblastic lymphomas, and are B-cell phenotype by immunophenotypic and immunoglobulin gene rearrangement studies. In contrast with malignant lymphoma occurring in the general population, extranodal origin is common in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas, with the central nervous system, bone marrow, gastrointestinal tract, and liver being the most common sites. To the best of our knowledge, there has been no description in the literature of primary renal lymphoma occurring in patients with the acquired immunodeficiency syndrome. We report an unusual case of primary non-Hodgkin's lymphoma (diffuse B-cell immunoblastic type) of the kidney in a patient with the acquired immunodeficiency syndrome.
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The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.
OBJECTIVE: To determine the prevalence of HIV in endoscopic biopsies from the esophagus, stomach, duodenum, and rectum of homosexual and bisexual men at various stages of HIV infection as part of a comprehensive study of gastrointestinal dysfunction in HIV infection. METHODS: After repeated washings and mechanical disruption, biopsies obtained from 58 volunteers were individually cocultured with pooled peripheral blood lymphocytes from healthy HIV-seronegative blood donors. RESULTS: HIV was isolated from at least one site in 40 out of 49 patients. Esophageal biopsies were most frequently found positive (46%), followed by duodenal biopsies (44%), rectal biopsies (43%), and gastric biopsies (27%). Recovery of HIV was not related to any gastrointestinal signs or symptoms. HIV was recovered in the biopsies both from asymptomatic patients with CD4 lymphocyte counts greater than 500 x 10(6)/l and also from patients with more advanced disease receiving zidovudine therapy. CONCLUSIONS: The entire gastrointestinal tract appears to be a target site throughout the course of HIV infection in homosexual and bisexual men.
Blood sampling on filter paper has many advantages for the detection of perinatal human immunodeficiency virus (HIV) infection by the polymerase chain reaction (PCR). However, if the method is to be widely used, an assessment of its performance under field conditions is required. To simulate conditions in the field, 50-microliters aliquots of whole blood containing low levels of HIV proviral DNA (4 to 1,024 copies per 100,000 nucleated cells) were spotted onto filter paper; dried; and subjected to heat, humidity, and prolonged storage at room temperature. After exposure, the DNA was recovered and amplified with primers to human leukocyte antigen DQ alpha- and HIV-specific sequences. Treatment at 37 degrees C and 60% humidity for 7 days, storage for 12 weeks at 22 degrees C, and freeze-thawing twice had no adverse effect on PCR reactivity when compared with the results obtained with reference spots stored at -20 degrees C. The lower limits of HIV detection in all tests ranged from 4 to 16 HIV copies per 100,000 cells. Fixation in 70% ethanol improved the amplification of low levels of HIV DNA and reduced biohazard risks. These findings suggest that dried blood spots will provide a powerful new resource for testing for HIV by PCR, especially in remote areas where refrigeration and immediate sample processing are unavailable.
A psychiatric examination was conducted on 144 patients at various stages of HIV infection and on 29 controls found to be seronegative. One-half of the control group had at least one DSM-III-R Axis I diagnosis, most commonly cannabis abuse, alcohol abuse, or adjustment disorder. Compared to this baseline, HIV-infected subjects had higher rates of adjustment disorder. AIDS patients were also more likely to suffer from organic mental disorder. The rate of unemployment increased as the disease progressed. Major depression was seen in only ten patients, and there were no differences between controls and HIV-infected subjects. Formal assessment of mood state and feelings of pessimism also showed no differences among the groups. The importance of helping improve the patient's lifestyle through the control of alcohol and drug abuse is underscored.
49 gay men confirmed to be infected with the human immunodeficiency virus (HIV) and 9 HIV seronegative gay men participated in a pilot study comparing clinical status and enteric parasite load with gastrointestinal structure, function and symptomatology. Cases included 16/49 (33%) men who were CDC stage II, 7/49 (14%) who were CDC stage III, and 26/49 (53%) who were CDC stage IV. The mean CD4-lymphocyte count was 476 +/- 199 (SD)/microliter. The prevalence of enteric parasitic flora was similar in HIV seropositive patients and controls. Seven cases had enteric infection with pathogenic agents including 3 patients with Entamoeba histolytica, and 4 patients with Giardia lamblia, one of whom also had cryptosporidiosis. Other cases were most frequently colonized with Blastocystis hominis (44%) and Endolimax nana (41%) regardless of the HIV clinical status. HIV seropositive patients with enteric parasitic colonization tended to have lower mean levels of serum IgA than cases without parasites. Duodenal morphometric mucosal changes demonstrated a significant decrease in the mean villous height (p < 0.01) with no elongation of the crypt depth in HIV-infected patients with and without diarrhea compared to controls. Despite gastrointestinal symptoms including diarrhea and weight loss being more prevalent in HIV infected individuals than controls, no correlations were found between the presence of particular enteric parasites, gastrointestinal symptomatology, the clinical HIV status of the CD4-lymphocyte count, the malabsorption of D-xylose or morphometric changes in the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)
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