Transmission of the human immunodeficiency virus.
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Biomedical subjects
Publications and source records attributed to R S Klein.
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Oral examinations of 103 consecutive patients with acquired immunodeficiency syndrome (AIDS) were performed. Of these patients, 74 (72%) were heterosexuals and 29 (28%) were homosexual or bisexual men. Lesions that were identified on subsequent examination were recorded separately. Oral candidiasis was the most common finding, occurring in 94 patients. Other findings were herpes simplex ulceration (ten patients), exfoliative cheilitis (nine patients), xerostomia (ten patients), "hairy" leukoplakia (seven patients), and Kaposi's sarcoma (four patients). A patchy, depapillated tongue was seen in six patients, and ulcers with uncertain cause were seen in three patients. Gingival bleeding, perioral molluscum contagiosum, and brown hairy tongue each occurred in one patient. In this study, "hairy" leukoplakia and Kaposi's sarcoma occurred exclusively in homosexual and bisexual men with AIDS, and occurred significantly more frequently in this group than in heterosexual patients with AIDS. There was no significant difference between these groups in the frequency of occurrence of other findings.
An inosine analog, 9-deazainosine, has previously been demonstrated to inhibit Pneumocystis carinii in culture with WI-38 cells. The present study shows that it is also effective against Pneumocystis carinii in immunosuppressed Sprague-Dawley rats with Pneumocystis carinii pneumonia. After 8 wk of immunosuppression, rats that developed severe Pneumocystis carinii pneumonia were treated with either 9-deazainosine or served as controls. After 15 days of therapy, animals were sacrificed and severity of infection determined by morphologic examination of lungs for numbers of Pneumocystis carinii. Treated animals had greatly reduced numbers of Pneumocystis carinii trophozoites and cysts, compared with controls. This drug shows promise for therapy of Pneumocystis carinii pneumonia and should be studied further.
Ninety adult patients with acquired immunodeficiency syndrome (AIDS) and 27 with AIDS-related complex were seen consecutively, when available, either as inpatients or in AIDS clinics and given complete cutaneous examinations. Skin disease was common both in patients with AIDS and in those with AIDS-related complex. The most common cutaneous findings were candidiasis in 55 patients (47.0%), dermatophytosis in 35 (30%), herpes simplex infections in 26 (22%), molluscum contagiosum in 11 (9%), seborrheic dermatitis in 37 (32%), and acquired ichthyosis or xerosis in 36 (30%). Several cutaneous conditions previously reported in association with AIDS were infrequently seen: Psoriasis was seen in only one patient, and deep fungal infections and basal and squamous cell carcinomas were seen in none. No significant differences were noted in the prevalence of skin disease between patients with AIDS and those with AIDS-related complex, although xerosis and ichthyosiform skin changes tended to be more common in those with AIDS. The yellow nail syndrome and "a papular eruption" associated with AIDS were seen. Skin diseases also tended to be widespread and severe in the patients studied.
The dose of orally administered 9-deazainosine calculated to suppress 50% of Leishmania donovani amastigotes in hamster livers was 19 mg/kg (body weight) per day; 96 to 99% of Leishmania organisms were eliminated from the liver and spleen of squirrel monkeys by 50 mg/kg per day. Because these activities were greater than that of the experimental clinical agent allopurinol and comparable to that of the classical agent parenteral pentavalent antimony, 9-deazainosine should be considered for clinical development for visceral leishmaniasis.
Kinetoplastid hemoflagellates are sensitive to growth inhibition by various purine analogs. In this study the activities of 9-deazainosine (9-DINO), formycin B, and sinefungin were compared in experimental murine Trypanosoma brucei subsp. brucei infections, both singly and in combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine). Used singly, all of the purine analogs were able to suppress an acute T. brucei subsp. brucei infection. 9-DINO and formycin B were the most active. None of the purine analogs was curative when used singly against a strain causing chronic central nervous system infection. 9-DINO was highly effective when used in combination with DFMO in curing this central nervous system infection and another more stringent experimental infection. Neither sinefungin nor formycin B was active in combination with DFMO in curing the central nervous system experimental infection. 9-DINO was metabolized to phosphorylated derivatives of 9-deazaadenosine and 9-deazaguanosine by bloodstream trypomastigotes, but not by murine erythrocyte suspensions or kidney or liver homogenates--a potential rationale for the selectivity of the analog. These studies indicate that 9-DINO is a potent, nontoxic purine analog which, in combination with DFMO, is capable of late-stage cures of African trypanosomiasis.
Since previous studies have shown an increased fecal carriage rate of Streptococcus bovis in patients with carcinoma of the colon, a study was undertaken to determine the fecal carriage rate of this organism in patients with gastrointestinal carcinoma of noncolonic origin. Organisms identified as S. bovis were isolated on fecal culture from 10 of 82 (12%) controls, 19 of 94 (20%) individuals with noncolonic gastrointestinal carcinoma, and 12 of 80 (15%) patients with other gastrointestinal disorders. Subjects with noncolonic gastrointestinal carcinoma did not have a fecal carriage rate of S. bovis significantly different from that in controls. A literature review of 251 patients with S. bovis septicemia identified at least 89 (35%) with neoplasms of the colon. Only nine patients (4%) with gastrointestinal neoplasms of other than colonic origin were noted. At present, the indication for an intensive evaluation of the upper gastrointestinal tract in individuals with S. bovis bacteremia is substantially less than that for the colon.
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To determine the risk of transmission of human T-cell lymphotropic virus Type III/lymphadenopathy-associated virus (HTLV-III/LAV) to close but nonsexual contacts of patients with the acquired immunodeficiency syndrome (AIDS), we studied the nonsexual household contacts of patients with AIDS or the AIDS-related complex with oral candidiasis. Detailed interviews, physical examinations, and tests for serum antibody to HTLV-III/LAV were performed on 101 household contacts of 39 AIDS patients (68 children and 33 adults), all of whom had lived in the same household with an index patient for at least three months. These contacts had shared household items and facilities and had close personal interaction with the patient for a median of 22 months (range, 3 to 48) during the period of presumed infectivity. Only 1 of 101 household contacts--a five-year-old child--had evidence of infection with the virus, which had probably been acquired perinatally rather than through horizontal transmission. This study indicates that household contacts who are not sexual partners of, or born to, patients with AIDS are at minimal or no risk of infection with HTLV-III/LAV.
The association of Streptococcus bovis septicemia with abnominal neoplasms has been well-documented. The case of a man who presented with vertebral osteomyelitis due to S. bovis is reported; he was subsequently found to have bacteremia and colonic polyps. It is recommended that patients who present with localized as well as generalized S. bovis infections undergo yearly colonoscopy.
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Three analogs of inosine, formycin B, allopurinol ribonucleoside, and 9-deazainosine, were tested for their ability to suppress proliferation of Pneumocystis carinii in culture with WI-38 cells. The organism was inhibited by 9-deazainosine at 10 micrograms/ml, and there was some inhibition at 1 microgram/ml. Formycin B was effective only at 40 micrograms/ml. Allopurinol ribonucleoside had little effect.
The radiologic features were examined in a retrospective review of 25 patients with gastrointestinal complications of acquired immunodeficiency syndrome (AIDS). Factors of risk for AIDS present in these patients included homosexuality (n = 10), intravenous drug abuse (n = 7), multiple blood transfusions (n = 1), and unconfirmed or unknown factors (n = 7). Gastrointestinal abnormalities identified on radiologic studies (including upper gastrointestinal, small bowel, and barium enema studies) were correlated with histopathologic specimens and the results of bacteriologic, viral, fungal, and parasitologic studies. The most common disorders (88%) were candidal esophagitis and cytomegaloviral colitis; neoplastic involvement of the gastrointestinal tract was far less common (12%), with only two patients (8%) having Kaposi sarcoma. Gastrointestinal studies, which can provide useful if not always definitive diagnostic information, are recommended to precede more invasive diagnostic studies in evaluating patients with suspected AIDS.
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We reviewed the clinical data, hepatic histology, and microbiological features of 21 patients with previously documented acquired immune deficiency syndrome who had liver biopsies. Diagnoses of specific infections were made on liver biopsy in 11/21 patients (57%). Granulomas were found in 10/21 patients (48%) and were most often a manifestation of infection with Mycobacterium avium-intracellulare. Elevated levels of serum alkaline phosphatase and longer duration of diagnosed illness were significantly associated with the presence of granulomatous disease.
9-Deazapurine ribonucleosides constitute a new class of noncleavable purine nucleoside phosphorylase inhibitors that have at least 30-fold greater affinity for the enzyme than the corresponding C-nucleosides of the formycin B series. 9-Deazaguanosine, 9-deazainosine, and 5'-deoxy-5'-iodo-9-deazainosine competitively inhibited human erythrocytic purine nucleoside phosphorylase with Ki values of 29, 20, and 1.8 X 10(-7) M. The last compound is the most potent nucleoside inhibitor of the enzyme presently available and its synthesis is described. In contrast, 7,9-dideaza-7-thiainosine is a very weak inhibitor of the enzyme. When tested as an inhibitor of 2'-deoxyguanosine phosphorolysis in intact human erythrocytes and MOLT-3 human T-cell lymphoblastic leukemia cells, 5'-deoxy-5'-iodo-9-deazainosine was equipotent with 8-aminoguanosine (which is a precursor for 8-aminoguanine, Ki = 2 X 10(-7) M). Similarly, 5'-deoxy-5'-iodo-9-deazainosine and 8-aminoguanosine both potentiated the growth inhibition of human T-lymphocytic MOLT-3 cells by 2'-deoxyguanosine, reducing the 50% inhibitory concentration from approximately 2 X 10(-5) to approximately 2 X 10(-6) M.
We studied a hospital-based pneumococcal immunization program. Ninety (66%) of 136 patients on the study unit (group 1) and 97 (80%) of 122 patients on the control unit (group 2) were candidates for pneumococcal vaccine based on age of 65 years or older or underlying medical condition, or both, and absence of prior vaccination. In group 1, an infection control nurse identified candidates at the time of discharge and offered vaccine. No intervention was made in group 2. Seventy (78%) of vaccine candidates in group 1 were vaccinated at the time of hospital discharge compared with none of 97 candidates in group 2 (P less than .001). A hospital-based program offering vaccine at the time of hospital discharge can significantly improve immunization rates and successfully immunize the majority of hospitalized individuals at high risk from pneumococcal infection.