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Biomedical subjects

J Foy

Publications and source records attributed to J Foy.

18 recordsLinked to original sources
PubMed1998

Paraspinal abscess associated with epidural in labour.

A 24-year-old presented in labour requesting an epidural. She had been diagnosed as having "pelvic arthropathy" at 37 weeks. After an uneventful epidural and instrumental delivery, she discharged herself home. She re-presented 19 days later with left hip pain and abnormal neurological signs in the lower limbs. On MRI, there was a large paraspinal abscess with an epidural granulation mass compressing her spinal cord. She had an urgent surgical decompression. In hindsight, it is likely that the paraspinal mass was present at the time of epidural insertion. The discussion highlights that complications are sometimes not what they seem.

Abscess↗
PubMed1997

Clinically used antimicrobial drugs against experimental pneumocystosis, singly and in combination: analysis of drug interactions and efficacies.

We analyzed single drugs and combinations of drugs used clinically in the treatment of opportunistic infections and other conditions for their activities against Pneumocystis carinii pneumonia in immunosuppressed rats. When they were used alone, atovaquone, rifabutin, and dapsone were more active than clarithromycin or trimethoprim. Drug combinations were evaluated for synergistic activity by an analysis of variance model for two-way factorial experiments and a response surface model. Atovaquone combined with trimethoprim trimethoprim and some combinations of dapsone and clarithromycin was synergistic; however, the activities of combinations of atovaquone and rifabutin, atovaquone and clarithromycin, and atovaquone and dapsone were simply additive. Lovastatin, which inhibits 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive whether it was used alone or in combination with other agents. None of the synergistic drug combinations was as effective as trimethoprim-sulfamethoxazole. We conclude that the rat model can be used to test combinations of anti-P. carinii agents for synergistic activity by well-established statistical techniques. While some combinations of clinically used antimicrobial drugs have enhanced anti-P. carinii activity, further studies are needed before clinical trials can be contemplated.

Animals↗
PubMed1994

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.

Animals↗
PubMed1993

Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis.

We compared Ro 11-8958, an analog of trimethoprim (TMP) with improved antimicrobial and pharmacokinetic properties, other dihydrofolate reductase (DHFR) inhibitors, sulfamethoxazole (SMX), and dapsone (DAP) in the treatment of Pneumocystis carinii pneumonia in an immunosuppressed rat model. In contrast to previous reports, high dosages of the DHFR inhibitors were used in combination with fixed, low dosages of SMX (3 mg/kg of body weight per day) or DAP (25 mg/kg/day). When administered alone at these dosages, SMX and DAP reduced the median P. carinii cyst count about 5- to 15-fold. Ro 11-8958, TMP, and diaveridine used at a dosage of 20 mg/kg/day with SMX were only slightly more effective than SMX used alone. However, administration of these DHFR inhibitors at a dosage of 100 mg/kg/day with SMX lowered the cyst count about 500- to 1,000-fold, indicating a synergistic effect. Little or no synergism was found when other DHFR inhibitors (pyrimethamine, cycloguanil, and tetroxoprim) were combined with SMX. Regimens of Ro 11-8958 at a dosage of 20 mg/kg/day with DAP and of TMP or diaveridine used at a dosage of 100 mg/kg/day with DAP showed comparable anti-P. carinii activity, lowering the cyst count 100- to 200-fold. By contrast, Ro 11-8958 administered at a dosage of 100 mg/kg/day with DAP reduced the cyst count > 1,000-fold. Thus, the experimental approach used here enables the rat model of pneumocystosis to be used to compare synergistic combinations of antifolate drugs. The favorable results achieved with Ro 11-8958 indicate that it should be considered for clinical trials.

AIDS-Related Opportunistic Infections↗
PubMed1992

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

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

Animals↗
PubMed1992

Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.

Over a 7-year period, we analyzed 261 dose regimens of antimicrobial drugs in the treatment and prevention of Pneumocystis carinii pneumonia in an immunosuppressed rat model. These compounds ranged from drugs in clinical use to newly synthesized agents. Drug efficacy was expressed as the magnitude of the reduction in median P. carinii cyst or nucleus counts on a scale ranging from inactive (less than 5-fold) to very markedly active (greater than or equal to 1,000-fold). The classification system was reproducible and allowed drugs studied at different times to be compared with each other. The system demonstrated a hierarchy of anti-P. carinii activity not only among classes of compounds but also among individual members of a drug class. Sulfonamides, sulfones, and diamidines were the most active agents; some purine nucleosides and nitrofurans also showed promising activity; and most antiparasitic, antifungal, antibacterial, and antiviral drugs were inactive. We conclude that this classification system represents a simple, quantitative method of comparing the activities of antimicrobial drugs against P. carinii. Information gained from this system should be helpful in developing new anti-P. carinii compounds and establishing standard procedures for their evaluation.

Animals↗
PubMed1991

Furazolidone and nitrofurantoin in the treatment of experimental Pneumocystis carinii pneumonia.

Furazolidone and nitrofurantoin, oral nitrofuran derivatives with broad-spectrum antimicrobial properties already in clinical use, were compared for activity against Pneumocystis carinii in an immunosuppressed rat model of P. carinii pneumonia. Furazolidone exhibited only slight activity as a prophylactic agent but was moderately effective in the therapy of pneumocystosis. The median histologic score and organism count fell from 4+ and 10(8) to 10(9) cysts per lung, respectively, in the controls to 1+ to 2+ and 10(7) to 10(8) cysts per lung, respectively, in the furazolidone-treated groups. However, these results were not as good as those obtained with the standard drug, trimethoprim-sulfamethoxazole (0+, 10(6) to 10(7) cysts per lung). Nitrofurantoin showed little anti-P. carinii activity despite different doses or drug preparations. The high doses of furazolidone used here and their toxic effects on the rats will probably discourage investigation of this drug in the treatment of pneumocystosis in humans. Nevertheless, since many nitrofurans have been synthesized, further exploration of this class of compounds might be helpful in developing new anti-P. carinii agents or in studying structure-activity relationships.

Animals↗
PubMed1989

Clinical implications of positive tests for antibodies to human immunodeficiency virus type 1 in asymptomatic blood donors.

Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.

AIDS-Related Complex↗
PubMed1988

Cationic antitrypanosomal and other antimicrobial agents in the therapy of experimental Pneumocystis carinii pneumonia.

Cationic compounds used in the treatment of veterinary African trypanosomiasis have structural properties similar to those of pentamidine, which has been used in the therapy of human trypanosomiasis and infection with Pneumocystis carinii. We have compared the activities of these drugs and other antimicrobial agents in an immunosuppressed rat model of P. carinii pneumonia. Diminazene, imidocarb, amicarbalide, quinapyramine, and isometamidium showed efficacy greater than or equal to that of pentamidine in the therapy of P. carinii infection, whereas ethidium and methylglyoxal bis(guanylhydrazone) were only slightly active against the organism. Diminazene and pentamidine also exhibited comparable efficacy in P. carinii prophylaxis, alpha-Difluoromethylornithine (DFMO), a polyamine inhibitor, was ineffective therapy when used alone and did not improve the effectiveness of pentamidine or diminazene. Quinine, quinidine, quinacrine, chlorpromazine, spiramycin, Pentostam, Astiban, dehydroemetine, ampicillin, gentamicin, chloramphenicol, and spectinomycin also showed little or no activity against the organism. Thus, in this model anti-P. carinii activity appears to be a common property of veterinary cationic trypanocidal compounds. This should be important in studying structure-activity relationships and in developing new drugs for the treatment of P. carinii infection in humans.

Amidines↗
PubMed1984

Doxorubicin, cyclophosphamide, and whole body hyperthermia for treatment of advanced soft tissue sarcoma.

Eleven patients with advanced soft tissue sarcoma were treated with whole body hyperthermia (41.8 degrees C-43.0 degrees C) for 2 hours, doxorubicin (45 mg/m2) at the beginning of peak temperature and cyclophosphamide (1000 mg/m2) 6 hours after doxorubicin. Warming was accomplished with a nylon and vinyl mesh water perfused suit and heating blankets under barbiturate anesthesia. Thirty-five thermochemotherapy treatments were administered after an initial baseline euthermic course. There were two complete and two partial responses including three of three liposarcomas and one of two leiomyosarcomas, and there were two disease stabilizations . Morbidity included anasarca, nausea and vomiting, diarrhea, myalgias, mild surface burns, perioral herpes simplex, reversible neuropathy, hypotension, and cardiac arrythmias . Hyperglycemia and hypophosphatemia were found during heating, and normalized at 24 hours. Liver enzyme elevations occurred 24 hours after heating and normalized within 1 week. A uniform platelet decrease (mean, 107,000/microliter) was found at 24 hours. Thermochemotherapy was found to be a feasible approach for selected patients with advanced soft tissue sarcoma for the subset of liposarcomas and leiomyosarcomas.

Adult↗
PubMed1984

Arresting development arrests aging in the nematode Caenorhabditis elegans.

Larval development of the nematode, Caenorhabditis elegans, can be arrested by either of two different treatment: (1) complete starvation, or (2) growth in a partially defined culture medium (axenic medium) of strains adapted to bacterial growth. The developmental arrest is complete under total starvation and the starved populations live about 10 days. The developmental block is incomplete in axenic medium; most animals mature but maturation takes 10 times longer than normal. If developmentally arrested cultures are returned to growth on E. coli, both the completely starved and the axenically arrested cultures mature at normal rates. Life-span is prolonged by 1 day for each day of complete starvation; life-span is prolonged by 0.7 days for each day of axenic arrest. These results suggest that aging and development are closely coupled in this system. The results are discussed in terms of previous observations on nutritional deprivation in other invertebrates and caloric restriction in mammals and are interpreted in light of theoretical models of senescence.

Aging↗