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Biomedical subjects

R S Klein

Publications and source records attributed to R S Klein.

At least 145 records · Page 8Linked to original sources
PubMed1985

Anaerobic mediastinitis complicating median sternotomy.

Two cases of mediastinitis and bacteremia caused by Bacteroides species following median sternotomy are described. In both patients, purulent sternal drainage and signs of systemic toxicity led to the diagnosis. Surgical reexploration and administration of appropriate antibiotics effected clinical cure. Although there is only a single previous case of anaerobic mediastinitis following median sternotomy incision reported, these two cases suggest that this unusual infection may not be so rare as previously thought.

Adult↗
PubMed1985

Cervical osteomyelitis caused by Pseudomonas cepacia in an intravenous-drug abuser.

We report a case of vertebral osteomyelitis caused by Pseudomonas cepacia in a patient with a history of intravenous-drug abuse. P. cepacia infections are usually nosocomial, although community-acquired infections occur more commonly in intravenous-drug abusers than in the general population. Vertebral osteomyelitis caused by P. cepacia has not previously been reported.

Cervical Vertebrae↗
PubMed1985

Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome.

Depressed T cell immunity is a universal characteristic of the acquired immunodeficiency syndrome (AIDS). In the present study, 25 patients with AIDS and opportunistic infections, 22 individuals with AIDS-related complex (ARC, or chronic lymphadenopathy syndrome), and 20 healthy homosexuals were evaluated by means of the T cell colony assay. Forty-seven healthy heterosexual controls showed an average of 3964 +/- 319 colonies/7.5 X 10(5) cells, with a range of 880 to 9340. The mean in the 20 healthy homosexuals (3173 +/- 483) did not differ significantly from the controls; in this group, only three patients had values less than 1000 colonies/plate. By contrast, all AIDS patients and 14 ARC patients had colony counts less than 1000. The mean value for the AIDS patients was only 24 +/- 15 (p less than 0.0005 compared with either controls or healthy homosexuals); values in the ARC group were intermediate (1180 +/- 360). The addition of interleukin 2 to the plates promoted correction of the proliferative abnormality in ARC patients. This interleukin increased colony scores in the AIDS group, but the mean value was still significantly less than controls. Comparison indicated that the colony assay is a more sensitive indicator for detecting proliferative abnormalities than responses to PHA, Con A, or pokeweed mitogen in suspension cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

Forty-four episodes of Pneumocystis carinii pneumonia (PCP) occurred in 36 of 70 patients with the acquired immunodeficiency syndrome. Thirty-four patients with 40 episodes of PCP were treated with trimethoprim-sulfamethoxazole. Therapy was successful in 18 episodes (45%), but was unsuccessful in 15 episodes (37.5%). In the latter cases, two patients died within 72 hours; 13, of whom nine died, had therapy changed to pentamidine. In seven additional episodes (17.5%), trimethoprim-sulfamethoxazole was changed to pentamidine due to adverse reactions; all patients survived. Seven patients (26% of survivors) developed recurrent PCP. Twenty-two patients (65%) developed adverse reactions to trimethoprim-sulfamethoxazole, including leukopenia (20), hepatotoxicity (12), fever (eight), rash (six), and immediate reactions (two). Reactions were most common during the second week of therapy. Patients with the acquired immunodeficiency syndrome who have PCP have a high trimethoprim-sulfamethoxazole failure rate, due either to adverse reactions or unresponsive infection. Late recurrence is common.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Intravenous drug abusers and the acquired immunodeficiency syndrome (AIDS). Demographic, drug use, and needle-sharing patterns.

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended "shooting galleries," where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome.

We studied the frequency with which unexplained oral candidiasis led to unequivocal acquired immunodeficiency syndrome (AIDS) in patients at risk. Twenty-two previously healthy adults with unexplained oral candidiasis, of whom the 19 tested had a reversed T4/T8 ratio and 20 had generalized lymphadenopathy, were compared with 20 similar patients with a reversed T4/T8 ratio and generalized lymphadenopathy who did not have oral candidiasis. All were intravenous-drug abusers, homosexual or bisexual men, or both. Thirteen of the 22 patients with oral candidiasis (59 per cent) acquired a major opportunistic infection or Kaposi's sarcoma at a median of three months (range, 1 to 23) as compared with none of 20 patients with generalized lymphadenopathy and immunodeficiency but without candidiasis who were followed for a median of 12 months (range, 5 to 21) (P less than 0.001). AIDS developed in 12 of 15 patients with candidiasis and T4/T8 ratios less than or equal to 0.51, as compared with none of four with ratios equal to or greater than 0.60 (P less than 0.01). We conclude that in patients at high risk for AIDS, the presence of unexplained oral candidiasis predicts the development of serious opportunistic infections more than 50 per cent of the time. Whether the remainder will have AIDS is not yet known.

Acquired Immunodeficiency Syndrome↗
PubMed1984

9-Deazaadenosine--a new potent antitumor agent.

-Deazaadenosine (9-DAA), a novel purine analog, was found to be a potent inhibitor of the growth of nine different human solid tumor cell lines in vitro and of pancreatic carcinoma (DAN) in antithymocyte serum (ATS)-immunosuppressed mice. In culture, IC50 values ranged from 1.1 to 8.5 X 10(-8)M. Ovarian carcinoma (MR) was the only cell line in which the activity of 9-DAA was potentiated (about 10-fold) by pretreatment with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF). After incubation of cultured pancreatic DAN cells with 9-DAA (10(-5)M) for 2 hr, a peak appeared in the triphosphate region of HPLC nucleotide profiles that was identified tentatively as 9-deazaATP. Under the same incubation conditions, the incorporation of [3H]uridine into RNA and of [3H]thymidine into DNA was inhibited by 34 and 80% respectively. In vivo studies using ATS-immunosuppressed mice showed that 9-DAA at 0.4 mg/kg/day for 3 consecutive days reduced pancreatic carcinoma (DAN) tumor weights to approximately 50% of untreated controls. The nucleoside transport inhibitor p-nitrobenzyl-6-thioinosine (NBMPR) was shown to selectively protect host tissues from 9-DAA toxicity and, thereby, potentiated the antitumor activity of 9-DAA in vivo at optimal dosages.

Animals↗
PubMed1984

Biological action of inosine analogs in Leishmania and Trypanosoma spp.

Previous investigations have suggested that inosine analogs would be good models for the development of chemotherapeutic agents active against pathogenic hemoflagellates. We have systematically modified the five-membered heterocyclic ring of six inosine analogs and tested them for their antiprotozoal activities and toxicity to a mammalian cell line. All six analogs were very active against the three protozoan pathogens Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. Two of the six, 9-deazainosine and allopurinol ribonucleoside, had very little toxicity for mouse L cells and offer promise as potential chemotherapeutic agents.

Animals↗
PubMed1984

In vitro susceptibility of Streptococcus bovis to six antibiotics.

A recent report of two isolates of Streptococcus bovis resistant to killing by low levels of penicillin G prompted this study of the in vitro susceptibility of 100 clinical isolates of S bovis to six antibiotics. Using a microdilution method, we found the minimum bactericidal concentrations for 99% of the isolates to be as follows: penicillin G, 0.5 microgram/ml; methicillin, 16 micrograms/ml; ampicillin, 0.5 microgram/ml; cephalothin, 2 micrograms/ml; clindamycin, 2 micrograms/ml; and vancomycin, 2 micrograms/ml. The high-level resistance of S bovis to penicillin G previously described was not seen. This study suggests that penicillin G can still prove effective in treating most infections caused by S bovis, including infective endocarditis, and that cephalothin and vancomycin are useful alternative agents.

Ampicillin↗
PubMed1983

Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome.

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Inhibition of lymphocyte function by 9-deazaadenosine.

9-Deazaadenosine (c9Ado), a novel C-nucleoside, has been found to inhibit lymphocyte-mediated cytolysis (LMC) in a time-dependent manner. c9Ado inhibited LMC by 50% at concentrations of 10 and 0.07 microM after drug-pretreatment periods of 3 and 22 hr, respectively, although a 1-hr pretreatment of cytolytic lymphocytes with 100 microM c9Ado had no effect upon this lymphocyte function. c9Ado was metabolized rapidly and extensively to 9-deazaadenosine 5'-triphosphate (c9ATP) both by mouse cytolytic lymphocytes and by human erythrocytes. Adenosine kinase purified from rabbit liver phosphorylated c9Ado with a Km of 200 microM and a Vmax of 8% that for adenosine. The metabolic buildup of c9ATP in lymphocytes was accompanied by a large, time-dependent decrease in cellular ATP and by smaller percentage decreases in CTP, UTP and GTP. Among other biochemical effects examined, c9Ado was found to cause a decrease in lymphocyte cAMP content and appeared to be neither an inhibitor nor a substrate for S-adenosylhomocysteine hydrolase. Consistent with this latter result, L-homocysteine thiolactone had no effect on the inhibition of LMC by c9Ado. Neither the inhibition of LMC by c9Ado nor the metabolic formation of c9ATP in lymphocytes was affected by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), indicating that c9Ado is not a substrate for adenosine deaminase. 5-Iodotubercidin, a non-competitive inhibitor (Kis = 9 nM, Ku = 20 nM) of adenosine kinase, prevented the above effects of c9Ado on lymphocyte function, c9ATP formation, and ATP levels. Either complete preservation (with coformycin) or partial replenishment (with adenosine plus EHNA) of ATP levels in c9Ado-treated lymphocytes resulted in partial restoration of cytolytic function to cells containing large amounts of c9ATP. These results suggest that c9Ado is inhibitory to LMC both because it causes a decrease in the absolute concentration of ATP within the cytolytic lymphocytes and because it permits the establishment within these cells of an unfavorable c9ATP:ATP ratio which impedes the utilization of ATP in a reaction essential to the execution of this lymphocyte function.

Adenosine Triphosphate↗
PubMed1983

Pneumococcal vaccine in the hospital. Improved use and implications for high-risk patients.

A randomized trial of a program to improve pneumococcal immunization was undertaken. Also studied were the prevalence of high-risk conditions for serious pneumococcal disease among hospital admissions and prior hospitalization of patients with pneumococcal bacteremia. During two successive winters, 56% of 1,062 medical patients were identified by admission diagnosis or age as having a high-risk condition. None had received prior vaccination. During the trial period, identifying candidates for vaccination increased immunization from two (2.1%) of 95 to ten (10.4%) of 96 in year 1 and from two (2.1%) of 96 to 19 (20%) of 95 in year 2. Among adults with pneumococcal bacteremia, 33 (54%) of 61, including 32 (64%) of 50 with high-risk conditions, had documentation of prior hospitalization within five years. A hospital-based program can increase pneumococcal immunization rates and would be directed at patients in whom serious pneumococcal disease is likely to develop.

Adolescent↗
PubMed1983

Community-acquired opportunistic infections and defective cellular immunity in heterosexual drug abusers and homosexual men.

Fourteen previously healthy young patients with unusual community-acquired opportunistic infections were seen over a period of three years. They differ from patients previously described in that 11 were heterosexual drug abusers (including two women) and only three were homosexual men. There were eight Puerto Ricans, five blacks, and one white. Infections included Pneumocystis carinii pneumonia (seven), disseminated Mycobacterium intracellulare infection, histoplasmosis, cryptococcosis, and cytomegalovirus infection (one each), oral thrush (13), and Candida esophagitis (two). All patients had impaired cellular immunity manifested by cutaneous anergy and lymphopenia, and all 11 tested had a markedly decreased ratio of T helper/inducer cells to T suppressor/cytotoxic cells. Twelve had evidence of associated viral infection (Epstein-Barr virus in nine, cytomegalovirus in five, Herpes simplex type 2 in two). Clinical presentation was with a severe opportunistic infection or with a prodrome consisting of oral thrush and nonspecific findings including malaise, fever, lymphadenopathy, or cough. The syndrome of immunodeficiency and opportunistic infection occurs in nonwhite heterosexual drug abusers, not exclusively in white homosexual men, and patients may present for medical care before the onset of a severe opportunistic infection.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Spermatogenesis in the unilateral cryptorchid testis after orchiopexy.

We herein examine the role of orchiopexy in the child with unilateral cryptorchidism and specifically discuss whether this operation produces a testis capable of good sperm production. Contralateral vasectomy was performed in subjects who previously had undergone unilateral orchiopexy. Semen analysis from the previously operated testes showed marked diminution in spermatogenesis.

Adolescent↗
PubMed1983

Nucleosides. 123. Synthesis of antiviral nucleosides: 5-substituted 1-(2-deoxy-2-halogeno-beta-D-arabinofuranosyl)cytosines and -uracils. Some structure-activity relationships.

The syntheses of several 2'-halogeno-5-substituted-arabinofuranosylcytosines and -uracils are described, and relationships of structure to anti herpes virus activity in vitro were examined. Those arabinonucleosides containing the 2'-fluoro function exhibit, generally, more potent anti herpes virus (HSV) activity than do their 2'-chloro of 2'-bromo analogues. The importance of the fluorine in the 2'-"up" (arabino) configuration for enhancement of antiviral effectiveness is demonstrated by the superior activity of 2'-fluoro-5-iodo-ara-C [3a, FIAC] to that of 2'-fluoro-5-iodo-ribo-C. Of all the nucleosides tested herein, FIAC exhibited the most potent in vitro activity against HSV. 2'-Chloro-5-iodo- and -5-methyl-ara-C (3b and 4b) were 37 to greater than 500 times more effective in vitro against HSV type 2 than against type 1, suggesting that these latter derivatives might serve clinically as useful probes to distinguish between HSV types 1 and 2 in the diagnosis of HSV infections in man.

Animals↗