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Biomedical subjects

R S Klein

Publications and source records attributed to R S Klein.

At least 19 recordsLinked to original sources
PubMed1992

Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection.

BACKGROUND AND METHODS: To examine the clinical course of human immunodeficiency virus (HIV) infection in injection-drug users, we conducted a prospective study of a cohort of patients in a methadone-treatment program in New York City from July 1985 through December 1990. The patients underwent standardized evaluations at base line and semiannually thereafter and received on-site primary medical care. Rates of progression to the acquired immunodeficiency syndrome (AIDS) and major outcomes before the development of AIDS were examined by univariate analyses; the risk of AIDS was also assessed by product-limit survival analysis and proportional-hazards regression. RESULTS: Of 318 HIV-seropositive patients who did not yet have AIDS (171 men and 147 women), 90 were black, 179 were Hispanic, and 49 were white; the median age was 33 years. Over a median of 3.0 years of follow-up, 55 (17 percent) received a diagnosis of AIDS (incidence per 100 person-years, 5.8). Major outcomes before the development of AIDS included oral candidiasis (incidence per 100 person-years, 11.2), pyogenic bacterial infections including pneumonia and sepsis (8.0), pulmonary tuberculosis (1.2), multiple constitutional symptoms (13.6), and herpes zoster (1.3). There were 41 deaths from AIDS, and 13 seropositive patients without AIDS (4.1 percent) died of bacterial infections, as compared with only 1 of 411 seronegative patients studied (P < 0.001). The incidence of AIDS was 62 percent lower among those who took zidovudine than among those who did not (P = 0.02). In the multivariate analysis, progression to AIDS was best predicted by low numbers and percentages of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis, bacterial infections, or tuberculosis. There was no consistent relation between progression to disease and the continued use of injection drugs. CONCLUSIONS: HIV-infected injection-drug users have progression to AIDS at rates comparable to those of other HIV-infected groups, but they have substantial pre-AIDS morbidity and mortality, particularly from bacterial infections, which also appear to predict disease progression.

AIDS-Related Opportunistic Infections↗
PubMed1992

Cultured astrocytes express mRNA for peptidylglycine-alpha-amidating monooxygenase, a neuropeptide processing enzyme.

Cultured astrocytes have been previously found to express several neuropeptides, as well as the neuropeptide processing enzyme carboxypeptidase E (CPE). To investigate whether cultured astrocytes contain additional peptide-processing enzymes, Northern blots were screened for peptidylglycine-alpha-amidating monooxygenase (PAM) mRNA. PAM is involved with the formation of amide groups on the C-terminus of numerous peptide hormones and neurotransmitters. Primary cultures of astrocytes contain moderate levels of PAM mRNA, as determined by Northern blot analysis. The level of PAM mRNA in cultured hypothalamic astrocytes is similar to the level expressed in cultured hypothalamic neurons. The relative abundance of PAM mRNA differs up to 6-fold between astrocytes cultured from various brain regions. Astrocytes cultured from hypothalamus have high levels of PAM mRNA, those cultured from striatum, frontal cortex, and hippocampus have moderate levels, and those cultured from cerebellum have low levels. To investigate whether all cultured astrocytes express PAM mRNA, in situ hybridization analysis of cultured astrocytes was performed. Interestingly, virtually all of the astrocytes cultured from either hypothalamus or cerebellum express PAM mRNA, in contrast to a previous finding that only 20-40% of similarly cultured astrocytes express CPE. The presence of PAM mRNA in cultured astrocytes suggests that these cells have the capacity to produce amidated neuropeptides.

Animals↗
PubMed1992

Heterogeneous expression of carboxypeptidase E and proenkephalin mRNAs by cultured astrocytes.

Cultured astrocytes have been found to express neuropeptides, neuropeptide processing enzymes and their mRNAs. Although astrocytes were shown to display regional variation in their expression of these mRNAs, it was unclear whether all astrocytes cultured from the same brain region express similar mRNA levels or if this expression is heterogeneous. We examined the individual heterogeneity of astrocytes cultured from several brain regions by in situ hybridization. Astrocytes derived from the frontal cortex, hypothalamus and cerebellum of neonatal rat brains were cultured for 3 weeks and then analyzed by in situ hybridization using 35S-labeled cRNA probes to carboxypeptidase E (CPE), proenkephalin (PE), and cyclophilin (1B15) mRNAs and an oligomeric probe complimentary to the first 45 bases of rat 18S rRNA. Frequency histograms generated by counting the grains produced over emulsion-coated cells demonstrated populations of astrocytes expressing high levels of mRNA for CPE and PE and a population expressing low to background levels of these mRNAs. In contrast, all cultured astrocytes expressed high levels of 1B15 mRNA and 18S rRNA. The percentage of cultured astrocytes expressing high levels of CPE mRNA was 42% for frontal cortex astrocytes and 23% for cerebellar astrocytes. While the percentages of cultured astrocytes expressing high levels of PE mRNA varied slightly between brain region (24-28%), the level of PE mRNA expression per cell showed greater variation between regions. The effect of culture density on the expression of PE mRNA was also examined. Approximately 55% of the cells in low density cultures expressed PE mRNA, while only 5-10% of the cells in high density cultures expressed this mRNA. These results indicate that cultured astrocytes display individual heterogeneity with regard to neuropeptide biosynthesis and that the expression of neuropeptides by these cells is regulated.

Animals↗
PubMed1992

Secretion of carboxypeptidase E from cultured astrocytes and from AtT-20 cells, a neuroendocrine cell line: implications for neuropeptide biosynthesis.

Cultured astrocytes have recently been shown to produce certain neuropeptides, as well as neuropeptide processing enzymes. To characterize the secretory pathway in cultured astrocytes, we used the neuropeptide processing enzyme carboxypeptidase E (CPE) as a marker for neuropeptide secretion. Cultured astrocytes and AtT-20 cells, a mouse pituitary-derived neuroendocrine cell line, were labeled with [35S]Met for 15 min and then chased with unlabeled Met. CPE was isolated from either medium or cell extracts using a substrate affinity column. The time course of secretion of radiolabeled CPE was significantly different for cultured astrocytes as compared with AtT-20 cells. CPE was rapidly secreted from the astrocytes after a 30-min lag time, presumably reflecting transport through the endoplasmic reticulum and Golgi apparatus, followed by constitutive secretion. The secretion of radiolabeled CPE was essentially complete by 2 h. In contrast, only a portion of the radiolabeled CPE was secreted from AtT-20 cells over a 2-3-h period, indicating that the majority of newly synthesized CPE is stored, presumably in secretory granules within the AtT-20 cells. The regulation of CPE secretion from astrocytes was also examined. CPE secretion is stimulated two- to threefold by prolonged treatment (3-48 h) with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) but not by treatment with other secretagogues that stimulate CPE secretion from AtT-20 cells (forskolin, isoproterenol, A23187, and vasoactive intestinal peptide) or short (less than 3 h) exposure to TPA. Taken together, these results indicate that the secretory pathway for CPE, and presumably neuropeptides, is substantially different in astrocytes than the secretory pathway for CPE in neuroendocrine cells.

Animals↗
PubMed1992

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents.

Animals↗
PubMed1991

High risk of human papillomavirus infection and cervical squamous intraepithelial lesions among women with symptomatic human immunodeficiency virus infection.

We investigated the relationship of human papillomavirus (by cervicovaginal lavage and Southern blot), human immunodeficiency virus, and squamous intraepithelial lesions in 96 high-risk women in the Bronx, New York. Antibodies for human immunodeficiency virus were detected in 51 (53%) women. Of the 33 women with symptomatic human immunodeficiency virus infection, 23 (70%) had human papillomavirus infection compared with 4 of 18 (22%) asymptomatic women who were human immunodeficiency virus seropositive and 10 of 45 (22%) uninfected women (p less than 0.0001). The rate of squamous intraepithelial lesions was 52% (14 of 27) for women with both viruses detected, 18% (6 of 34) for women with either virus detected, and 9% (3 of 35) for uninfected women. Among symptomatic human immunodeficiency virus-infected women, a strong association between human papillomavirus infection and squamous intraepithelial lesions was demonstrated (odds ratio, 12; 95% confidence interval, 1.3 to 108). Risk was highest for younger women from ethnic or racial minority groups. Advanced human immunodeficiency virus-related disease, with its associated immunosuppression, seems to exacerbate human papillomavirus-mediated cervical cytologic abnormalities. Public health measures are needed to provide Papanicolaou smear screening and appropriate clinical follow-up and treatment for women at high risk for human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Major aphthous-like ulcers in patients with AIDS.

This report describes persistent, painful oral ulcers that occurred in nine patients with the acquired immunodeficiency syndrome (AIDS). These ulcers resembled major aphthous ulcers in clinical appearance and response to therapy. They occurred less frequently in patients with AIDS than those caused by herpes simplex and were found in 4 of 346 (1.1%) patients with AIDS at one medical center. Lesions were typically painful. Identification and treatment with topical tetracycline and steroids led to resolution with relief of symptoms. Further study is necessary to understand the etiology and pathogenesis of these ulcers.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Periodontal disease in heterosexuals with acquired immunodeficiency syndrome.

We studied the prevalence and severity of periodontal disease among 181 heterosexual men and women with AIDS. Included were 167 (92%) intravenous drug users (IVDU) and 14 sexual partners of persons at risk for AIDS. Periodontal disease was seen in 71 of 78 (91%) women compared to 75 of 103 (73%) men. Gingivitis was the most severe form of periodontal disease in 7 (9%) women and 15 (15%) men. Increased severity of periodontal disease was seen in women as compared with men (P less than .001); among subjects with periodontitis, 48 (75%) of 64 women had moderate to advanced disease compared to 32 (53%) of 60 men. For individuals with periodontitis, the extent of involvement was associated with severity; 90% of subjects with advanced periodontitis had all 4 quadrants affected. Concurrent oral manifestations of AIDS, including candidiasis, hairy leukoplakia, ulcers and Kaposi's sarcoma were present in 167 (92%) subjects. We conclude that HIV-associated gingivitis and HIV-associated periodontitis are common in heterosexual men and women with AIDS and are often accompanied by other oral manifestations of AIDS. The reason periodontal disease is more severe in women is not known. Clinicians should be aware that these disorders occur in heterosexuals as well as in homosexual men. Further study will be necessary to delineate the pathogenesis of these disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Survival differences in patients with AIDS.

To define the clinical, demographic, and behavioral variables that may influence survival in patients with AIDS, we studied 526 patients with AIDS diagnosed through September 1987 who were cared for at a single medical center. A diversity of racial and ethnic backgrounds, ages, both men and women, and all risk behaviors except hemophilia were well represented. The initial AIDS defining diagnosis was the most powerful predictor of survival. The median survival was 12.8 months for patients presenting with Kaposi's sarcoma (p less than 0.001), 10.9 months for patients presenting with Pneumocystis carinii pneumonia (p less than 0.001), and 4.8 months for patients presenting with other infections or neoplasms (p less than 0.02). For the entire series, male sex and younger age were associated with more favorable survival (p less than 0.025). For those presenting with Pneumocystis carinii pneumonia, in addition to younger age (p less than 0.025), black race (p less than 0.025) and the combination of male sex and intravenous drug use (p less than 0.005) were associated with a more favorable survival. Within a setting of comparable clinical care, survival from the point of diagnosis of AIDS is associated most strongly with the initial AIDS diagnosis, but differences in age, gender, race, and risk behavior also exert an influence on survival.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Gastrointestinal malignancy in patients with AIDS.

To clarify the prevalence and characteristics of gastrointestinal malignancy in patients with AIDS, we reviewed the demographics and clinical features of patients with AIDS and gastrointestinal neoplasms seen at North Central Bronx Hospital and Montefiore Medical Center during the past 8 yr. Malignant neoplasia complicated AIDS in 108/869 (12%) of the cases in our study. Most common was Kaposi's sarcoma (KS) (60%), followed by lymphoma (35%) and miscellaneous tumors (6.5%). The gastrointestinal tract was involved in 35/108 (32%) of patients with AIDS and neoplasia. Gastrointestinal tract involvement with KS usually was silent, although present, in every patient with KS who underwent autopsy. Lymphoma was most commonly non-Hodgkin's, and often produced symptoms. Uncommonly, the gastrointestinal tract was the primary site of neoplasms other than KS or lymphoma.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The recovery of Mycobacterium avium complex and Mycobacterium tuberculosis from blood specimens of AIDS patients using the nonradiometric BACTEC NR 660 medium.

The ability of the nonradiometric BACTEC NR 660 aerobic 6A blood culture medium to support mycobacterial growth was investigated. During a 19-month period blood cultures from 140 AIDS patients were sent to the microbiology laboratory. After the cultures were incubated for seven days, aliquots of medium from the vials were centrifuged, sediments examined microscopically for mycobacteria, and cultured to mycobacterial media. Seventy-one AIDS patients (51%) had at least one blood culture positive for mycobacteria. There was a significant difference in the percent of female AIDS patients positive for mycobacteria compared to male patients (72% vs. 44%, P less than 0.01). Forty-four percent of all subsequently positive cultures were detected by an acid fast stain of the specimen sediment. Subcultures from the BACTEC 6A suspensions were positive on mycobacterial media at one-seven weeks (mean three weeks) after planting. Sixty-nine of the isolates were Mycobacterium avium complex, while two were Mycobacterium tuberculosis. Some bacteremias with M. tuberculosis may have been undetected because growth experiments with a reference strain showed that, in contrast to M. avium complex, M. tuberculosis did not increase in concentration in 6A medium.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Additional evidence for lack of transmission of HIV infection by close interpersonal (casual) contact.

To further study the possibility of transmission of HIV infection by close personal but non-sexual, non-parenteral contact we have continued to enroll and evaluate household contacts of adult patients with AIDS. Two hundred and six household contacts of 90 patients with AIDS were evaluated with detailed interviews, physical examinations, and detection of HIV antibodies and p24 antigen from 1984 to 1987; 118 of these contacts were re-evaluated 6-12 months after cessation of household contact or death of the patient. The median duration of household contact from 18 months prior to symptoms in the AIDS patients to last contact was 23 months (range 3-101 months). The median time elapsed from first contact during this period to the last evaluation was 38 months (range 13-66 months). No household contact had signs or symptoms suggesting HIV infection. All 206 were negative for serum antibodies to HIV and HIV p24 antigen, despite extensive sharing of household facilities and items and personal interactions with AIDS patients. This study continues to show that household members without other risks remain at minimal to no risk for HIV transmission (95% confidence interval, 0-1.44) despite prolonged and substantial close non-sexual contact with AIDS patients, and after re-evaluation at a median of 10.9 months after initial evaluation.

Acquired Immunodeficiency Syndrome↗