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We examined the convergent validity of three posttraumatic symptoms inventories, the civilian version of the Mississippi Scale for Combat-Related PTSD (CM-PTSD), the Trauma Symptom Checklist-40 (TSC-40), and the Response to Childhood Incest Questionnaire (RCIQ), in a sample of 52 adult sexual abuse survivors. The significant and moderate to strong correlations (r = .6 or higher) among these inventories supported their convergent validity. Comparison with other studies also suggests that these instruments can adequately discriminate clinical from nonclinical populations.

In the past 15 years HIV infection and AIDS have become pandemic in the world. Infectious and neoplastic complications have evolved in response to medical advances and to the appearance of HIV infection in different populations. Because AIDS patients live longer with severe immunosuppression and new treatments have controlled opportunistic infections, the spectrum of complications of AIDS has changed. New and more effective antiretroviral drugs are being developed, and physicians are learning how to use them more effectively. Currently, medical management of HIV-infected patients focuses on the appropriate use of antiretrovirals and the prevention, early diagnosis, and treatment of complicating illnesses. A coordinated continuum of care and patient education and involvement are also key elements of effective management of HIV infection.

Purpose: To increase the hematologic tolerance of interferon-alpha (IFN alpha) and zidovudine combination therapy by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF), and to evaluate the safety, tolerance, and potential efficacy of the combination in patients with Kaposi's sarcoma and AIDS., Patients and Methods: Seventeen patients with Kaposi's sarcoma associated with AIDS received zidovudine 200 mg orally every 4 hours and GM-CSF 5 micrograms/kg/d subcutaneously. Successive cohorts received IFN-alpha 2b at a daily subcutaneous dose of 5, 10, or 20 million units. The dose of GM-CSF was titrated to maintain the neutrophil count between 1 and 5 x 10(9) cells/L. Doses of all three drugs were reduced, as required, for nonhematologic toxicities., Results: GM-CSF induced leukocytosis in all patients. On average, a dose of 1.25 micrograms/kg/d was sufficient to maintain the neutrophil count within the desired range. The combination of 20 million units of IFN-alpha with zidovudine and GM-CSF induced dose-limiting toxicity in four of six patients. The major side effects were constitutional symptoms, which included malaise, anorexia, fatigue, fever, and were dose-limiting in three patients. Severe anemia and/or thrombocytopenia developed in three patients. Seven patients (41%; 95% confidence interval [CI], 18% to 64%) showed objective tumor regression that persisted for a median of 51 weeks. A rapid decrease in free-serum p24 antigen levels was observed in seven patients who had measurable levels at baseline; the mean time required to isolate human immunodeficiency virus (HIV-1) from peripheral-blood cells was increased by 7 days. The number and percentage of CD4-positive lymphocytes showed no significant change., Conclusions: GM-CSF prevents neutropenia induced by the IFN-alpha and zidovudine combination and induced no adverse effects on immune function or HIV activity. However, nonhematologic toxicity precluded a major increase in the maximum-tolerated doses of IFN-alpha and zidovudine.

An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials. Problems which might not be appreciated for months are now being resolved early, before data can be compromised unknowingly. This consensus protocol is recommended for any laboratory attempting to isolate HIV for the purpose of standardizing recovery and for accessing virologic endpoints in clinical trials.

3'-Fluoro-3'deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFN alpha) were evaluated in two- and three-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells were studied using p24 antigen production as the virologic endpoints. FLT showed 2.5-fold higher efficacy and a similar selectivity index to zidovudine. Drug interactions were evaluated by the median effect principle and the isobologram technique. FLT, CD4, and interferon alpha at noncytotoxic concentrations inhibited HIV-1 synergistically in two- and three-drug combinations with a combination index smaller than one and dose reduction index greater than one. The three-drug regimen provided greater virus suppression than the two-drug regimen. These results suggest that FLT is an alternative agent to AZT for the treatment of HIV infection either as a single agent or in combination with CD4 and/or interferon-alpha.

This article discusses the epidemiology, diagnostic methods, prevention of complications, and medical management of HIV-1 infection. Many different therapeutic strategies for HIV-1 infection are being evaluated, but until the immune suppression is eradicated, presumably through more effective antiviral therapy, complications of AIDS and HIV-1 infection will continue to be encountered.

The effects of 3'-azido-3'-deoxythymidine (AZT), phosphonoformate (PFA), and 2',3'-dideoxythymidine (ddT) and their combination on human immunodeficiency type 1 (HIV-1) replication were studied by measuring the HIV-1 p24 antigen expression and reverse transcriptase (RT) release in HIV-1-infected MT4 cells in vitro. RT activity was also measured in a cell-free system by using poly(rA)-oligo(dT) as the primer-template, and cell growth inhibition was measured in noninfected MT4 cells. The interactions of these two- and three-drug combinations were evaluated by the combination index (CI) method and isobologram techniques. The 50% effective concentrations (EC50s) of AZT, PFA, and ddT were 0.014 to 0.005, 9.4 to 8.8, and 8.4 to 2.5 microM, respectively, for p24 enzyme-linked immunosorbent assays (ELISAs) and 0.005 to 0.0034, 1.43 to 1.37, and 2.87 to 2.83 microM, respectively, for RT activity in vitro; for RT activity in the cell-free system, the EC50s were 0.00019 to 0.00024, 0.012 to 0.02, and 0.00074 to 0.0005 microM, for AZT-5'-triphosphate, PFA, and ddT-5'-triphosphate, respectively. AZT in combination with PFA (1:200) or ddT (1:5) as well as the combination of these three drugs (1:200:5) synergistically inhibited HIV-1 replication and RT activity in the cell-free system over a wide range of drug concentrations, with the CIs ranging from 0.5 to 0.09, in which CIs of less than 1, 1, and greater than 1 indicate synergism, additive effect, and antagonism, respectively. Three- and two-drug combinations of AZT, PFA, and ddT showed similar degrees of synergism against HIV-1 replication in p24 assays and RT release assays, whereas the combination of AZT and ddT was found to be the most selective in terms of its anti-HIV-1 effect versus cytotoxicity. Dose reduction indices calculated from both HIV-1 replication inhibition, as measured by p24 ELISA and by RT activity in the cell-free system, indicated that two- and three-drug combinations at high effect levels and the selected combination ratios allow 2- to 240-fold dose reduction over the single drug alone in terms of their anti-HIV-1 effects. The three-drug combination showed the highest dose reduction index. These finding suggest that increased efficacy and reduced toxicity may be achieved in AIDS therapy by using AZT, PFA, and ddT in two- or three-drug combinations.

Objective: To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS)., Design: Prospective cohort study., Setting: Tertiary care center., Patients: Of 1030 patients with AIDS who were followed at Memorial Sloan-Kettering Cancer Center between 1 January 1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to trauma or a pulmonary procedure., Results: Of 20 patients with AIDS who presented with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine prophylaxis (relative risk, 17.6) and those with a history of P. carinii pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically significant risk factor independent of a history of P. carinii pneumonia. The pneumothorax-related mortality rate was 10% and there was considerable morbidity., Conclusions: Patients with AIDS at the highest risk for developing pneumothorax are those with a history of P. carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk. Pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with AIDS who develops a pneumothorax.

Purpose: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly growing lymphoma, has been rare among adults in the United States, but has greatly increased in incidence with the acquired immunodeficiency syndrome epidemic. This report details the results of treatment of adult SNCL with a series of protocols originally designed for the treatment of acute lymphoblastic leukemia (ALL)., Patients and Methods: Between July 1973 and May 1987, 29 adults with newly diagnosed SNCL were treated at Memorial Hospital with intensive chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17, and L-20 protocols. Nine patients had positive serologies for human immunodeficiency virus (HIV) infection. One patient with all measurable disease resected was not evaluable for response., Results: Sixteen of 28 evaluable patients (57%) achieved a complete remission with treatment. With follow-up as long as 153 months (median, 47 months), 50% of all patients and 59% of patients with negative or unknown HIV serologies have survived and are probably cured. Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater than 500 U/L had a significantly shortened survival as compared with those with a lower serum LDH. Other pretreatment patient characteristics associated with a shortened survival of borderline statistical significance were high National Cancer Institute stage (C, D) and bone marrow involvement. These results are similar to those for ALL and lymphoblastic lymphoma and are comparable to those for American SNCL in the literature., Conclusions: Approximately one half of adults with SNCL are curable with intensive chemotherapy. More intensive chemotherapy with hematopoietic growth factor and/or autologous bone marrow or peripheral stem cell support may increase curability.

Anti-p24 reactions in sera from 42 human immunodeficiency virus type 1 (HIV-1)-infected and 36 uninfected people with indeterminate Western blot antibody tests for HIV-1 were studied. Anti-p24 reactivity in HIV-1-infected people was completely blocked by HIV-1 recombinant p24 antigen, whereas the reaction in uninfected individuals with indeterminate patterns was inhibited partly or not at all. In contrast to infected individuals, anti-p24 reactivity from uninfected individuals could not be detected by an inhibition ELISA for HIV-1 p24 antibody. These results suggest a practical way to distinguish anti-p24 reactivity in sera from patients with HIV-1 infection from that seen in uninfected patients with indeterminate Western blot reactions.

An ELISA-inhibition assay based on commercially available HIV-1 p24 antigen tests was developed for detecting p24 antibodies. The test is specific and simple. p24 antibody was detectable in all p24 antigen negative Western blot positive sera, but was detectable infrequently in antigen positive sera. Sera from patients with indeterminate HIV-1 reactions (individuals without evidence of HIV-1 infection who nevertheless had p24 antibody) were p24 antigen negative and p24 antibody negative in the ELISA-inhibition reaction.

Central nervous system (CNS) toxoplasmosis is an important infectious complication of AIDS which requires prolonged treatment. Most cases occur in patients with serologic evidence of prior exposure and therefore appear to result from reactivation of a previously acquired infection. Antibody to Toxoplasma gondii was found in 130 out of 411 patients with AIDS (32%). Of these, CNS toxoplasmosis developed in 31 (24%). By survival analysis, the estimated probability of ever developing CNS infection in antibody-positive individuals was 28%, occurring in 26% of patients within 2 years of the onset of AIDS. All patients with HIV infection should be tested for antibody to T. gondii and monitored for any neurologic change. Methods of prophylaxis for CNS toxoplasmosis in these high-risk patients need to be developed.

Objective: To evaluate safety, tolerance, and potential efficacy of interferon-alpha and zidovudine combination therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS)., Design: Open, phase-I study with randomization between two preparations of interferon-alpha., Setting: Outpatient clinic of a cancer research center., Patients: Forty-three patients with Kaposi sarcoma associated with AIDS., Interventions: Patients were treated with interferon-alpha, 4.5, 9, or 18 million U/d, and zidovudine, 100 or 200 mg orally every 4 hours., Measurements and Main Results: Neutropenia was the major dose-limiting toxicity. Fatigue, liver enzyme elevation, anemia, and thrombocytopenia were dose-limiting in some patients. Maximum tolerated dosages for interferon-alpha 2a with zidovudine, respectively, were 4.5 million U/d with 200 mg every 4 hours or 18 million U/d with 100 mg every 4 hours. An interferon-alpha n1 [corrected] dosage of 9 million U/d with zidovudine dosages of either 100 or 200 mg every 4 hours induced dose-limiting toxicity in most patients. Of 37 evaluable patients, 17 (46%; 95% CI, 30% to 62%) showed complete or partial tumor regression. Antitumor effects occurred more frequently in patients with baseline CD4 counts above 200 x 10(6) cells/L (65%) than in patients with lower baseline counts (30%, P = 0.05). Effects on CD4 cells were related to both initial CD4 count and interferon dose. Increased skin test reactivity and decreased serum human immunodeficiency virus (HIV) p24 antigen and virus recovery from blood cells were seen., Conclusions: Combined therapy with interferon-alpha and zidovudine can be safely administered to patients with AIDS and Kaposi sarcoma. The observed effects on tumor growth, HIV replication, and immune function support further studies of the combination in patients at various stages of HIV infection.

A case of disseminated infection with Pneumocystis carinii is presented, and the English-language literature is reviewed for cases of documented extrapulmonary infection with this organism. In this case--with P. carinii diffusely replacing the bone marrow and causing hepatic, adrenal, and glomerular tuft necrosis--the clinical illness and multiple-organ dysfunction attributed to disseminated P. carinii were more severe than had previously been described. Because the rate of extrapulmonary P. carinii infection found at autopsy in patients with AIDS is at least 2.5% at our institution, we caution against the routine use of aerosol rather than parenteral pentamidine for treatment of P. carinii pneumonia until additional data are available.

Serum antibodies to human Pneumocystis carinii antigens were measured in greater than 400 specimens from different population groups by the immunoblotting technique. Serologic responses varied during the first 2 years of life, but in children greater than or equal to 2 1/2 years and in adults antibodies to a 40-kDa band were found in greater than 85% of the specimens; antigens to bands of 66, 92, and 116 kDa were also detected frequently. The prevalence of serum antibodies in immunosuppressed patients varied at different institutions and was usually lower than that of healthy controls. Seven (41%) of 17 patients with single episodes of pneumocystosis and 13 (93%) of 14 patients with recurrent episodes followed sequentially developed active serum IgM and/or IgG antibody responses to the 40-kDa antigen. Serologic responses to P. carinii were also detected, though less frequently, by immunofluorescence. These data suggest that the 40-kDa antigen is a major marker of P. carinii infection and that immunoblotting is useful in measuring serum antibody responses to the organism in both normal and immunocompromised hosts.

To determine the emotional impact of serological testing for HIV, 218 physically asymptomatic adults were evaluated in a confidential clinical setting 2 weeks before HIV test notification, immediately before and after notification, and 2 and 10 weeks later. All received extensive pre- and post-test counseling. The 179 seronegatives reported one or more HIV risk behaviors: homosexual intercourse (n = 111), heterosexual intercourse with possibly infected partners (n = 62), intravenous drug use (n = 20). Immediately after notification, seronegatives had significant decreases in visual analogue scale (VAS) measures of anxiety, depression, fear of getting AIDS, and fear of having infected others. Reductions were sustained at both follow-up assessments and were complemented by significant reductions on standardized self-reported measures of anxiety (Spielberger State Anxiety Inventory, SAI), depression (Beck Depression Inventory, BDI), and psychiatric symptoms (Brief Symptom Inventory, BSI) as well as by clinical ratings of depression (Hamilton Depression Rating Scale, HDRS). Of 39 seropositives, 35 had homosexual risk behaviors, seven had been intravenous drug users (IVDUs; four of whom were homosexual men), and one was a female partner of an IVDU. Immediately after notification, VAS measures of their anxiety were not significantly increased, and at 10 weeks after notification, their VAS measures of distress and mean scores on BDI, SAI and BSI were significantly lower than at entry. Their HDRS ratings were not significantly increased.

Antibody to Mycobacterium avium-Mycobacterium intracellulare antigen was measured by immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and indirect immunofluorescence in sera from 30 patients with acquired immunodeficiency syndrome (AIDS), 10 patients with hairy cell leukemia, and 33 hospitalized and healthy controls. Ten patients with AIDS and three patients with hairy cell leukemia in the study population had disseminated M. avium-M. intracellulare infection. Patients with AIDS and disseminated infection had antimycobacterial antibody levels, demonstrated by ELISA, that did not differ significantly from those in uninfected patients with AIDS or controls. Infected patients with hairy cell leukemia had significantly higher levels of antimycobacterial antibody, demonstrated by ELISA, than did uninfected patients with hairy cell leukemia or controls (P less than .001). One patient with hairy cell leukemia, studied serially, showed a greater than 100-fold rise in antibody titer with the onset of infection. These results further demonstrate that AIDS involves a functional defect in humoral immunity, in addition to impairment of cellular immune function.

The clinical features and laboratory results of 63 patients with or at risk for AIDS with lymphoid neoplasias seen from November 1980 through November 1986 are reviewed. Forty-three had systemic non-Hodgkin's lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkin's disease (HD), and one had plasmacytoma evolving to myeloma. Those with systemic NHL included 40 (93%) with intermediate or high-grade histologies, 35 (81%) with advanced stage (III, IV), and 28 (65%) with extranodal disease at presentation (predominantly marrow and meninges). Overall survival was short (median, 10.5 months from diagnosis) with the majority of deaths attributable to AIDS-related opportunistic infections (OI). However, 17 patients with diffuse NHL achieved a complete clinical remission, and nine now have been disease-free for more than 1 year (median follow-up, 28 months; range, 12 to 73 months). Early stage and lack of systemic symptoms were features associated with prolonged disease-free survival. Primary brain NHL was a uniformly lethal manifestation of AIDS, being diagnosed at postmortem in seven of nine severely immunosuppressed homosexual men. As with NHL, a propensity towards advanced disease and extranodal involvement was also observed in HD, suggesting that the atypical clinical behavior of HD may be an additional epiphenomenon of AIDS. This experience tends to argue for the use of intensive therapy in at least some patients with AIDS-related systemic NHL since it has resulted in a proportion of long-term disease-free survivors.

Serum arabinitol concentrations and arabinitol/creatinine ratios were determined in 25 cancer patients with invasive candidiasis, 73 severely ill cancer patients who did not have invasive candidiasis, and 15 uninfected patients with chronic renal failure. Elevated arabinitol concentrations were found in patients with renal failure and invasive candidiasis. Serum arabinitol concentrations exceeded 1.19 micrograms/ml in 13 of 18 patients with invasive candidiasis who were studied when renal function was normal and in three of 52 control patients. Among patients with renal failure, 10 of 14 with invasive candidiasis but only four of 36 control patients had serum arabinitol concentrations of greater than 5.85 micrograms/ml. Serum arabinitol and creatinine concentrations were strongly correlated. The arabinitol/ creatinine ratio exceeded 1.5 in 16 of 25 patients with invasive candidiasis but in only three of 88 control patients. Increased serum arabinitol concentrations appear to reflect increased production of arabinitol by yeast in individuals with invasive candidiasis.

Sheep red cells treated with concanavalin A and sensitized with a partially purified aspergillus antigen were used to detect antibody to Aspergillus by passive hemagglutination (PHA). Sera from eight patients with aspergillomas or allergic aspergillosis had PHA titers of greater than or equal to 1:800 and antibody detectable by immunodiffusion (ID). Of 122 hospitalized cancer patients without invasive aspergillosis, 118 had titers of less than or equal to 1:80, 86 of < 1:10, two of 1:160, and two of 1:320. None had antibody by ID. Antibody was detectable by PHA in sera from 12 of 14 healthy microbiology laboratory workers. Of 55 cancer patients who had sera available for testing within two weeks before diagnosis of invasive aspergillosis, 18 patients seroconverted: 13 by both PHA and ID, two by PHA alone, and three by ID alone. PHA titers rose from < 1:10 to between 1:40 and 1:1,280. In immunosuppressed patients who were at risk of developing invasive aspergillosis, the appearance of antibody correlated with the diagnosis of invasive aspergillosis.

Diarrhea due to enteric pathogens is an important complication of advanced human immunodeficiency virus infection. Whereas numerous bacterial and parasitic agents have been implicated, the role of pathogenic enteric viruses is less clear. Stools from 153 human immunodeficiency virus seropositive men were tested by electrophoresis, enzyme-linked immunosorbent assay, and immune electron microscopy for the presence of rotaviruses (group A and non-group A), adenoviruses, and Norwalk agent. Virus was detected in 9% of the patients with acquired immunodeficiency syndrome, 3% of the patients with acquired immunodeficiency syndrome-related complex, and none of the seropositive men without these diagnoses. Virus detection was not more likely in stool from patients with diarrhea.

Gossypol, a polyphenolic aldehyde extracted from cottonseed, is a male anti-fertility agent which has been reported to have anti-viral activity. In this paper we report that gossypol inactivates human immunodeficiency virus (HIV) in an in vitro system. Following exposure of cell-free incubates of HIV to 100 uM gossypol, ultracentrifugation and inoculation of the washed pellet onto H9 cells, there is no evidence of elevated reverse transcriptase activity over 21 days. Treatment with lower concentrations of gossypol reduces the peak and lengthens the time to maximal reverse transcriptase activity compared with control cultures. These observations suggest that gossypol could be used as a vaginal spermicidal/virucidal agent. The mechanism of the in vitro anti-viral action as well as the effect of orally administered gossypol on the infectivity of semen of HIV-seropositive men warrant further study.

The effects of renal function on serum concentrations of the candidal metabolite arabinitol were studied by examining the accumulation and elimination of arabinitol in animals and humans. Serum concentrations of arabinitol rose sharply and in direct proportion to creatine concentrations after nephrectomy in rats. The serum half-life of exogenous arabinitol was 20.8 hr in anephric rats but only 0.62 hr in sham-nephrectomized control animals. The mean +/- SD apparent space of distribution of arabinitol was 419 +/- 26 ml/kg. The fraction of exogenously administered arabinitol recovered in the urine was 0.73 +/- 0.13 in uremic rats, 0.85 +/- 0.28 in control rats, and 0.95 +/- 0.10 in normal dogs. The arabinitol/creatinine clearance ratio was 0.99 +/- 0.08 in normal dogs and 0.99 +/- 0.25 in 22 critically ill patients with cancer. Thus arabinitol is eliminated by nearly quantitative urinary excretion and its cleared at virtually the same rate as creatinine. Therefore, the rate of arabinitol appearance in the body from any source equals the urinary arabinitol excretion rate and is directly proportional to the concentration ratio of arabinitol to creatinine in serum or urine.

We analyzed 67 adenovirus isolates from 48 patients with AIDS. The isolates included 5 of subgenus A (all Ad31), 23 of subgenus B, 4 of subgenus C (all Ad5), and 35 of subgenus D. The subgenus A and C strains were from liver, lung, blood, urine, and stool and were unremarkable in their antigenic characteristics. The subgenus B strains were mostly from urine and were serotyped by neutralization (SN) and hemagglutination-inhibition (HAI) tests as Ad11 (12 isolates), Ad16 (1), Ad35 (3), and Ad21/H21 + 35 (1) plus new intermediate strains 34/H11 (3), 35/H11 (1), and 11 + 35/H11 (2). The subgenus D serotypes from 24 patients were mostly from stool specimens and consisted of 8 isolates of known serotypes, 16 of antigenically intermediate strains, and 11 of five new adenovirus types with distinct antigenic and restriction enzyme characteristics. The new serotypes were described as candidate types 43-47 in accordance with currently accepted taxonomic criteria. Ad45, 46, and 47 showed a major relation by HAI with Ad29, 24, and 20, respectively. Four intermediate types were related to the new serotypes. The plethora of serotypes from patients with AIDS suggests that no epidemiological significance can be attached to any one serotype.

An outbreak of Kaposi's sarcoma in homosexual men has recently been observed in New York and California which differs from the "classic" North American disease with regard to younger age of onset and clinical prognosis. Although the exact mechanism for initiation of either disease is still unknown, a viral mechanism has been suggested in both cases. In order to investigate the possible role of HLA-associated variations in genetic susceptibility, 39 patients with histologically documented Kaposi's sarcoma were typed for HLA-A,B,C antigens. Most of these patients were also typed for HLA-DR antigens and for Gm allotypes. A significant increase in DR5 occurred in both groups. Decreases in B8 and DR3 and an increase in homozygosity for the Gm haplotype 3;5,13 were also noted. These results suggest that HLA and Gm linked immune response factors may play a role in the induction of both these forms of the disease.

Cryptosporidium is a coccidial protozoan of the intestinal tract; cryptosporidiosis in veterinarians has been reported as a cause of diarrhea. It has also been reported as a cause of diarrhea in marrow transplant recipients. Cryptosporidiosis has gained attention recently because of its occurrence in patients with the acquired immune deficiency syndrome (AIDS). A healthy intensive care unit nurse who acquired cryptosporidiosis from a bone marrow transplant recipient with diarrhea caused by cryptosporidiosis is described. Results of laboratory examination, including T lymphocyte subsets, were normal. She was treated with bed rest and a liquid diet and her symptoms completely resolved after 15 days. Health care workers should be aware that cryptosporidiosis can be transmitted to them from patients and should follow precautions to avoid acquiring the disease.

The cause of AIDS is unknown. In the absence of a specific etiologic agent or diagnostic test, a case can only be recognized when complications of the immune deficiency such as infection or Kaposi's sarcoma occur. Defective T-cell function is the principal immunologic defect; there are also defects, however, in B-cell function that may have some clinical significance. It has not yet been possible to reverse the immunologic deficiency, and this failure has been the principal prognostic factor in this illness. A number of the infectious complications of AIDS, however, can be diagnosed and successfully treated.

Ninety-one patients with documented invasive infections due to an Aspergillus species were identified at Memorial Sloan-Kettering Cancer Center from July 1, 1971, through December 31, 1976. Of the 29 patients in whom the diagnosis was made during life, 10 had successful treatment and survived the Aspergillus infection by two to 17 months. An immunodiffusion test was useful in the early diagnosis of invasive aspergillosis, and in 11 patients in whom the diagnosis was supported by seroconversion and who underwent treatment, the survival rate was 64 percent. Cultures of respiratory secretions were not reliable because they often reflected only colonization. In one year, only 9 percent of he patients with Aspergillus species isolated from the sputum had an invasive infection. The lung was the commonest site of involvement, 91 percent of the patients having pulmonary lesions. The most frequently affected extrapulmonary organ was the brain (18.3 percent). Eight patients had nonpulmonary aspergillosis as the only manifestation of this infection. Most of the 91 patients had hematologic neoplasms as the underlying disease, and neutropenia and antibacterial therapy preceded the diagnosis of aspergillosis in the majority of cases.

Renal colony counts, total arabinitol appearance, and the arabinitol/creatinine ratios in the serum and urine of rats with lethal candidiasis were measured. Total arabinitol appearance and the arabinitol/creatinine ratios increased significantly after infection. The serum arabinitol/creatinine ratio was high (2 SD above the mean value in normal animals) in five of six infected rats at 24 hr, in eight of eight at 48 hr, and in none of the control animals. The urinary arabinitol/creatinine ratio was high in 14 of 19 infected rats by 24 hr, in 11 of 11 by 48 hr, and in none of the control animals. Total arabinitol appearance and the arabinitol/creatinine ratios were highly correlated with renal colony counts. Arabinitol production in vitro was sufficient to account for the increased arabinitol appearance observed in vivo in 12 of 14 rats. Thus it is concluded that the excess arabinitol that appeared in vivo was produced by the infecting fungus and that arabinitol is a quantitative marker substance for candidiasis.

Chronic pneumonitis due to Hemophilus influenzae developed in a 68-year-old woman. The unusual aspects of this manifestation and the patient's chest roentgenographic findings are discussed. Hemophilus influenzae was isolated from lung tissue obtained at an open lung biopsy. The isolate was sensitive to ampicillin sodium, and therapy resulted in clinical and roentgenographic resolution of the infection.

A patient with human immunodeficiency virus (HIV) type 1 infection developed chronic iridocyclitis and anterior vitritis that were poorly responsive to topical and systemic corticosteroid therapy. Anterior chamber paracentesis was performed and HIV was isolated from culture of aqueous humor. Subsequent treatment with oral zidovudine resulted in resolution of the iridocyclitis and vitritis and full functional recovery of the eye. This case suggests that HIV may be a cause of uveitis responsive to systemic zidovudine therapy.

Concentrations of amphotericin B (AmB) in tissues obtained at autopsy from eight patients were measured by high-performance liquid chromatography (HPLC). The patients had received doses of 101-2,688 mg of antibiotic. Highest concentrations of the drug were found in the liver; in one patient the amount of AmB in the liver was 41% of the total dose. No evidence of metabolism of the drug was observed, and bioassay of ethanol extracts of tissue showed that the drug retained activity. Three of the patients had histologic evidence of aspergillar or candidal infection in tissues with concentrations of AmB ranging from 2.5 to 166 micrograms/g. With two patients, the concentrations of the drug in the tissues exceeded by greater than or equal to 10-fold the minimum inhibitory concentrations of the drug in isolates that had been obtained from the same tissues. Unknown factors present in tissues appear to limit the in vivo activity of AmB.

Mycobacterium tuberculosis was detected by the Isolator lysis-centrifugation blood culture system from the blood of a patient with tuberculosis of the breast. The organism also grew on conventional laboratory media inoculated with pleural fluid from the patient.

Central-nervous-system toxoplasmosis developed in 7 of 269 patients with the acquired immunodeficiency syndrome reported to the New York City Health Department through July 1982. Focal neurologic abnormalities, mass lesions on computed-tomographic brain scans, lymphocytic cerebrospinal fluid pleocytosis, and detectable IgG antibody to Toxoplasma gondii were common; but IgG titers of 1:1024 or more, IgM antibody to T. gondii, and positive open brain biopsies were uncommon. Serologic findings suggested that the disease resulted from recrudescent rather than primary infection. Four of five patients improved when treated with sulfonamides and pyrimethamine, but 2 had relapses. An aggressive diagnostic approach and sometimes even empiric therapy are warranted when central-nervous-system toxoplasmosis is suspected in a seropositive patient with the acquired immunodeficiency syndrome.

Serial quantitative blood cultures were performed before and during treatment in four patients with the acquired immune deficiency syndrome (AIDS) and Mycobacterium avium-intracellulare bacteremia. Initial colony counts were 350 to 28,000 cfu/ml, the counts declined substantially with treatment in two patients, and they declined modestly with treatment but rose when it was stopped in the other two. In one patient who was studied in detail, most of the circulating organisms were within the leukocytes, colony counts in blood subjected to lytic agents were 1.9- to 5.2-fold higher than in unlysed blood, and there were 10(5) to 10(6) times more organisms per gram in several tissue specimens obtained at autopsy than per milliliter of blood. It is concluded that continuous high-grade bacteremia is common in patients with AIDS and severe M. avium-intracellulare infections and that serial quantitative blood cultures provide a potential means for studying treatment in these patients.

Among 211 adults with leukemia who received multiple transfusions, 6 were found to be seropositive for human T-cell leukemia virus Type I (HTLV-I). Before the positive serum specimens were obtained, these patients received a mean of 14 units of red cells and 78 units of platelets. Seroconversion could be documented in three patients. None of the 6 patients seropositive for HTLV-I had a T-cell leukemia, other illnesses attributable to HTLV-I infection, or risk factors for HTLV-I infection other than transfusion: none were seropositive for human immunodeficiency virus. Patients with leukemia who receive multiple transfusions appear to be at risk for HTLV-I infection.

The Mycobacterium avium complex, only rarely described as an invasive pathogen in humans, has recently been reported to frequently cause disseminated disease in patients with the acquired immune deficiency syndrome. Between February 1981 and February 1984 at Memorial Sloan-Kettering Cancer Center, 30 patients with acquired immune deficiency syndrome, 3 patients with leukemia, and 2 patients with congenital severe combined immunodeficiency syndrome developed disseminated M. avium complex infection. Mycobacteria were often found in multiple sites both antemortem and postmortem. Blood cultures were a reliable method for detecting disseminated infection, and the new lysis blood culture systems provided an efficient technique for determining the number of organisms per milliliter of blood. Acid-fast stains and cultures of fecal specimens were also helpful in diagnosing infection. Most of the mycobacteria were serovar 4 (77%), and most (86%) produced a deep yellow pigment. All isolates were susceptible to standard concentrations of clofazimine, cycloserine, and ansamycin, but tended to be resistant to isoniazid, streptomycin, ethambutol, ethionamide, and rifampin.

Defects in T-cell function have been seen in patients with the acquired immunodeficiency syndrome. Although the cellular immune system plays a key role in host defense against Salmonella, there have been no detailed reports of salmonellosis in patients with this syndrome. We report our experience with salmonella infections in six patients. Salmonellosis in these patients was unusually severe, characterized by widespread infection, bacteremia, and relapse, despite standard antibiotic treatment. Because of the difficulty in eradicating salmonella infection in patients with the acquired immunodeficiency syndrome, long-term suppressive treatment with antibiotics seems warranted.

Opportunistic infections with yeast and molds are increasingly common in patients with neoplastic diseases. Candida species, Aspergillus species, Phycomyces, and Cryptococcus neoformans remain most common, but other organisms are being encountered as pathogens. With the exception of Cryptococcus, most opportunistic fungal infections are difficult to diagnose. New diagnostic tests for these diseases are being evaluated. Amphotericin B remains the antifungal agent of choice. In certain patients, the addition of 5-fluorocytosine may improve the outcome. Experience with cryptococcosis in severely immunocompromised cancer patients at Memorial Sloan-Kettering Cancer Center suggests that those who are treated with amphotericin B intravenously and intraventricularly via an Ommaya reservoir along with 5-fluorocytosine do better than those treated with amphotericin B alone.