Epidemiology and clinical manifestations of human immunodeficiency virus infection.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
I Frank
Publications and source records attributed to I Frank.
Screening surgeons for HIV infection: assessment of a potential public health program.
OBJECTIVE: To develop a model to assess the impact of a program of testing surgeons for human immunodeficiency virus (HIV) on the risk of HIV acquisition by their patients. DESIGN: A Monte Carlo simulation model of physician-to-patient transmission of human immunodeficiency virus (HIV) infection using three different rates of physician-to-patient transmission per percutaneous exposure event (0.15%, 0.3%, 0.6%). Data from the model were developed from a review of the medical literature and from subjective probability estimates when data were not available. We used this model to estimate on a national basis the annual number of cases of HIV transmission from surgeons to patients with and without surgeon testing and practice limitations. RESULTS: The annual number of transmitted cases would range from 0.5 (+/- 0.3), assuming a surgeon HIV prevalence of 0.1% and a surgeon-to-patient transmission rate of 0.15%, to 36.9 (+/- 11.6), assuming a surgeon HIV prevalence of 2% and a surgeon-to-patient transmission rate of 0.6%. After one screening cycle, a mandatory screening program would be expected to reduce the annual transmissions to 0.05 (+/- 0.03) and 3.1 (+/- 1.1), respectively. CONCLUSION: Patients are at low risk of acquiring HIV infection from an infected physician during an invasive procedure. The potential costs of such a program extended beyond the costs of testing and counseling. In communities with high HIV prevalence, screening surgeons and limiting their practices may decrease patient access to care. A disability insurance program also would be required to protect surgeons and trainees performing invasive procedures. Screening surgeons for HIV infection would be a costly undertaking that would reduce but not completely eliminate this risk.
AIDS Serodiagnosis↗
Pulmonary aspergillosis in patients with AIDS. Clinical and radiographic correlations.
OBJECTIVE: To evaluate the clinical and radiographic features of pulmonary aspergillosis as they present in AIDS patients; in particular, to determine similarities and differences between Aspergillus infection in patients with AIDS vs those without AIDS. SUBJECTS AND METHODS: Six new cases of confirmed or probable pulmonary aspergillosis were discovered during a search of hospital records. These are reviewed with 30 previously reported cases with special attention to radiographic appearance of disease and how radiographic appearance influences clinical outcome. RESULTS: Symptoms of pulmonary aspergillosis in AIDS were nonspecific, most often including fever, cough, and dyspnea, and less commonly, chest pain or hemoptysis. Major risk factors for the development of pulmonary aspergillosis in patients with AIDS were steroid administration and neutropenia. Neutropenia was often a complication of therapies for AIDS, in particular, ganciclovir and zidovudine. Radiographic appearance of disease could be divided into three general categories. One third of the patients (13/36) presented with cavitary upper lobe disease resembling noninvasive or chronic necrotizing aspergillosis. Fatal hemoptysis occurred in 42 percent of patients with this form of disease. Twenty-two percent (8/36) of the cases presented as a nondescript focal alveolar opacity similar to invasive aspergillosis. In several patients, the focal infiltrate remained stable for several months, a feature that is unusual for aspergillosis in non-AIDS patients. The air crescent sign was present in none of the 36 reported cases. Patients with only focal disease had the best prognosis of patients with pulmonary aspergillosis. Bilateral alveolar or interstitial disease similar to invasive aspergillosis was present in 23 percent (9/36) of the patients. Bilateral disease appears to be a marker for disseminated infection and was associated with a high mortality due to aspergillosis. Two new forms of bronchial aspergillosis (5/36 cases) have been described previously. These patients presented with either obstructing fungal casts or bronchial pseudomembranes demonstrated bronchoscopically. In some patients with the bronchial forms of aspergillosis, transient alveolar opacities were seen on chest radiographs. These opacities may represent regions of atelectasis due to airway obstruction. One patient who had bilateral pneumothoraces without parenchymal opacities did not correspond to any of the three previously mentioned categories. Mortality due to aspergillosis was greater than 50 percent among AIDS patients. Death was subsequent to fatal hemoptysis or widespread pulmonary or systemic infection. CONCLUSION: Unlike other risk groups that tend to contract only one form of pulmonary aspergillosis, AIDS patients can develop the whole spectrum of aspergillosis-related pulmonary disorders, including chronic cavitary, invasive, and bronchial forms of aspergillosis. Clinical symptoms are nonspecific and major risk factors include neutropenia, which is often a side effect of various therapies for AIDS, and steroid administration. Patients with the chronic cavitary form of disease have an unusually high mortality due to fatal hemoptysis. Patients with bilateral pulmonary infiltrates and aspergillosis have a high mortality due to disseminated infection.
AIDS-Related Opportunistic Infections↗
Proton MR spectroscopy of brain abnormalities in neonates born to HIV-positive mothers.
PURPOSE: To examine the sensitivity of proton MR spectroscopy for detecting early central nervous system abnormalities in neonates born to human immunodeficiency virus (HIV)-positive mothers. METHODS: Asleep, unsedated, and continuously monitored by electrocardiography, 10 newborns, 5 with HIV-positive and 5 with HIV-negative mothers, were studied within the first 10 days of life in a 1.5-T scanner. After T1- and T2-weighted images were obtained, proton spectra were performed using voxels of interest (3.4 cm3) in the deep parietooccipital white matter. Peaks were identified as N-acetyl-aspartate (2.0 ppm), creatine and phosphocreatine (3.0 ppm), choline (3.2 ppm), and inositol (3.5 ppm). Peak areas were used to calculate metabolic ratios: N-acetyl-aspartate to creatine, inositol to creatine, and creatine to choline. RESULTS: All newborns of HIV-positive mothers had abnormal proton spectra compared with control infants; a nonspecific amino acid peak in the 2.1- to 2.6-ppm area was elevated, broad, and overlapping the N-acetyl-aspartate peak in all the HIV-exposed newborns and in only 1 of the 5 control newborns. The choline-to-creatine ratio was higher in HIV-exposed newborns at 2.3 +/- 0.4 (normal term, 0.9 +/- 0.3), as was the N-acetyl-aspartate-to-creatine ratio at 2.6 +/- 0.9 (for control subjects, 1.2 +/- 0.4). MR images from these brain regions were all considered normal. Because acquired immunodeficiency syndrome develops in only a small fraction of neonates born to HIV-seropositive mothers, the above spectral abnormalities found in all our subjects may result from indirect effects of HIV, such as intrauterine growth retardation. CONCLUSIONS: These findings indicate that proton MR spectroscopy might play an important role in detecting early central nervous system complications in newborns of HIV-seropositive mothers.
AIDS Dementia Complex↗
[Delayed effects of calcium].
Some extracardial effects of a calcium chloride solution were analysed for a period of one week after infusion in cattle, sheep and rabbits. Effects upon the heart occur during the infusion or immediately after it (peracute calcium toxicity) and are related to a hypercalcaemia. They consist in disturbances of some metabolic processes, in particular of the skeletal musculature (myopathia). Marked increases of the activities of creatin-kinase of the serum show delayed effects of calcium, which are dose dependent. During the time of maximal effects the calcium concentrations in the serum of treated animals are normal. So the situation can be called a toxic normocalcaemic (post-hypercalcemic) calcium effect. An additional application of calcium in a large dosage within a period of 72 hours after the first application may increase the toxic effects of calcium.
Animals↗
Nurse practitioner managed care for persons with HIV infection.
This exploratory study examined whether outcomes of care for HIV-infected patients are related to whether the patient's primary provider is a physician (MD) or a nurse practitioner (NP). Functional status, symptom occurrence, self management, health service use and patients' assessment of their care were evaluated for 87 HIV-infected patients in a teaching hospital outpatient setting. NP patients were three times as likely to report their health status as only fair or poor (odds-ratio = 3.06, p = .028), and reported significantly more unpleasant symptoms over a four-week period. Despite being in poorer health than patients cared for by physicians, NP patients functioned at comparable levels and used no more health care services than MD patients. NP patients reported 45 percent fewer problems with their care (p = 0.003). Findings suggest that more extensive use of nurse practitioners could safely enhance access to care for persons with HIV-related illnesses.
Adult↗
Proton MR spectroscopy of HIV-infected patients: characterization of abnormalities with imaging and clinical correlation.
The purpose of this study was to characterize the proton magnetic resonance (MR) spectroscopic findings in the brains of patients infected with human immunodeficiency virus (HIV). Peak areas were used to calculate metabolite ratios. Spectra were analyzed by blinded readers who calculated areas under metabolite peaks. MR images were evaluated by blinded readers, with both white and gray matter being rated as normal or abnormal. An aggregate index that combined N-acetylaspartate/creatine (Cr), choline/Cr, and marker peak/Cr ratios resulted in mean scores for patients and control subjects of 4.4 +/- 1.5 (standard deviation [SD]) and 2.5 +/- 0.4, respectively (P = .001). Eight of 11 patients (73%) had abnormal MR images versus four of 11 control subjects. Thirteen of 15 patient spectra (87%) were abnormal (> 2 SDs from the mean of the control subjects), while only one of 10 control spectra was abnormal. These initial results indicate that proton MR spectroscopy is a potentially useful modality for detecting HIV involvement in the central nervous system.
AIDS Dementia Complex↗
Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients.
Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a heterodimeric lymphokine produced by B cells that has multiple effects on T and NK cell functions. NKSF at concentrations as low as 0.4 pM enhances the spontaneous cytotoxic activity of peripheral blood lymphocytes (PBL) against a variety of tumor-derived target cell lines and virus-infected target cells. The combined treatment of PBL with NKSF and IL-2 results in a less than additive enhancement of cytotoxicity. NKSF enhances the cytotoxic activity of spontaneously cytotoxic CD16+CD5- NK cells and does not confer cytotoxic activity to CD16-CD5+ T cells. PBL from patients infected with human immunodeficiency virus (HIV) have significantly lower cytotoxic activity against tumor-derived target cells and virus-infected target cells than PBL from control healthy donors. Treatment of PBL from HIV-infected patients with NKSF and/or IL-2 results in an increase of NK cell cytotoxicity against both types of target cells to levels similar to or higher than those of untreated PBL from healthy donors. PBL from HIV-infected patients produce interferon gamma in response to NKSF and/or IL-2, although at levels 5- or 10-fold lower than those produced by PBL from healthy donors. The multiple biological effects of NKSF, its activity at very low molar concentrations, and its ability to synergize with other physiological stimuli suggest that NKSF/IL-12 is a lymphokine likely to have physiological importance and considerable therapeutic potential.
Adult↗
Efficacy and tolerance of intermittent versus daily cotrimoxazole for PCP prophylaxis in HIV-positive patients.
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Drug Administration Schedule↗
Interaction of terbinafine with human serum and serum proteins.
The allylamine antimycotic terbinafine acts by inhibition of ergosterol biosynthesis at the level of squalene epoxidase. Using this mechanism in Candida parapsilosis cells, a functional assay was developed to investigate the effects of serum and serum proteins on the antifungal action of terbinafine and related drugs in vitro. Inhibition of ergosterol biosynthesis by terbinafine was antagonized by human serum in a dose-dependent non-saturable manner. The results were not affected by varying the period of pre-incubation of serum with the drug or with the fungal cells, or by performing the test in other species of Candida, Aspergillus and Trichophyton. Qualitatively similar effects were observed with the related allylamine compounds naftifine and SDZ 87-469, the extent of antagonism correlating with their lipophilicity. The effect appeared to be caused by non-specific binding of the drug to major serum components, including albumin and the lipoproteins (both LDL and HDL). Reduced bioavailability resulting from binding by serum may at least partly account for the low efficacy of terbinafine in experimental models of systemic infection, in contrast to its high efficacy in infections of the skin, nails and hair.
Antifungal Agents↗
Antibody-dependent cellular cytotoxicity (ADCC) is directed against immunodominant epitopes of the envelope proteins of human immunodeficiency virus 1 (HIV-1).
In this study, epitopes of HIV envelope proteins that are involved in ADCC were identified. Peripheral blood mononuclear cells (PBMC) were obtained from adults with asymptomatic HIV infection or early symptoms of AIDS. These PBMC, which were reported to be "armed" in vivo with HIV-specific antibodies, were used as effector cells in 51Cr release assays. Target cells consisted of CD4 lymphocytes from healthy seronegative donors, coated with the IIIB strain of HIV-1 or with one of seven synthetic peptides. Cytotoxicity was detected against CD4 lymphocytes coated with HIV-1 IIIB or with the peptides env aa 507-518, corresponding to the carboxy-terminus of gp120, and env aa 597-611, corresponding to the region of the cysteine loop of gp41. The magnitude of target cell lysis was directly related to the quantity of peptide used. In contrast, target cells coated with the peptide gag aa 129-135, corresponding to the p17/p24 cleavage region of the gag precursor, were not killed. The same immunodominant regions which were involved in ADCC were recognized in enzyme-linked immunoabsorbent assays (ELISA) by the majority of 107 sera from HIV-infected adults. We conclude that the immunodominant epitopes located at the carboxy-terminus of gp120 and the cysteine loop of gp41 serve as recognition structure for antibodies, capable of mediating ADCC against HIV-infected cells.
Antibody-Dependent Cell Cytotoxicity↗
Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1.
The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.
Adult↗
Treatment of cryptosporidiosis with paromomycin. A report of five cases.
Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.
AIDS-Related Opportunistic Infections↗
Simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder.
Simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon. Twenty-two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between January 1970 and July 1986. The overall five-year survival was 40 percent, with patients presenting with prostate cancer doing better (50%) than those with bladder cancer (32%). Retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and, when indicated, radiation therapy added postoperatively for the bladder cancer. Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated for their bladder cancer. Treatment was usually radical cystoprostatectomy with or without postoperative radiation. None died of prostate cancer. Patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer.
Adenocarcinoma↗
Herpes simplex virus type 1 Fc receptor protects infected cells from antibody-dependent cellular cytotoxicity.
Recent studies indicate that the herpes simplex virus type 1 (HSV-1) Fc receptor (FcR) can bind antiviral immunoglobulin G by participating in antibody bipolar bridging. This occurs when the Fab domain of an immunoglobulin G molecule binds to its antigenic target and the Fc domain binds to the HSV-1 FcR. In experiments comparing cells infected with wild-type HSV-1 (NS) and cells infected with an FcR-deficient mutant (ENS), we demonstrate that participation of the HSV-1 FcR in antibody bipolar bridging reduces the effectiveness of antibody-dependent cellular cytotoxicity.
Animals↗
Decisions in P. carinii pneumonia.
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Acquired Immunodeficiency Syndrome↗
Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization.
Glycoprotein gC1 of herpes simplex virus type 1 (HSV-1) binds complement component C3b. To determine if gC1 modifies the interaction of complement with virus-infected cells or cell-free virus, ns-1, a mutant HSV-1 strain that does not express gC1 at the cell surface and does not bind C3b, was compared with its parental strain, NS. Cells infected with the gC1 mutant were more susceptible to cytolysis mediated by antibody and complement or complement alone. The gC1 or gD1 genes were expressed in mammalian cells under the control of an inducible promoter. Cells induced to express gC1 resisted complement cytolysis, while cells expressing gD1 did not. gC1 modified cytolysis of virus-infected or -transfected cells by blocking alternative complement pathway activation. gC1 also modified complement-dependent virus neutralization, which was mediated by inhibiting the classical complement pathway. These results indicate a protective role for gC1 on the virion and at the cell surface.
Antibody-Dependent Cell Cytotoxicity↗
Herpes simplex virus type 1 encodes two Fc receptors which have different binding characteristics for monomeric immunoglobulin G (IgG) and IgG complexes.
Two herpes simplex virus type 1 glycoproteins, gE and gI, have been shown to form a complex that binds the Fc domain of immunoglobulin G (IgG). We demonstrate that this complex is required for the binding of monomeric nonimmune IgG but that gE alone is sufficient for binding polymeric IgG in the form of IgG complexes. Evidence that gE but not gI is required for binding IgG complexes is as follows. IgG complexes bound equally well to cells infected with gI-negative mutants or with wild-type virus, whereas cells infected with gE-negative mutants did not bind IgG complexes. Furthermore, L cells transiently transfected to express gE bound IgG complexes. Additional evidence that gI fails to augment binding of IgG complexes comes from experiments in which the gI gene was inducibly expressed in cells after infection. Inducible gI expression failed to increase binding of IgG complexes to infected cells in comparison with cells not capable of inducible gI expression. In contrast, expression of both gE and gI was necessary for binding of monomeric IgG, as demonstrated by flow cytometry using cells infected with gE-negative and gI-negative mutants. These observations demonstrate that herpes simplex virus type 1 Fc receptors (FcRs) have different binding characteristics for monomeric IgG and IgG complexes. Furthermore, it appears that gE is the FcR for IgG complexes and that gE and gI form the FcR for monomeric IgG.
Animals↗