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Biomedical subjects

J Mills

Publications and source records attributed to J Mills.

At least 397 records · Page 22Linked to original sources
PubMedDate not supplied

Failure of a once-daily regimen of cefonicid for treatment of endocarditis due to Staphylococcus aureus.

Cefonicid, a new long-acting cephalosporin, was evaluated for treatment of endocarditis due to Staphylococcus aureus. Four patients, all with infection of the tricuspid valve, were treated with a single daily injection. By the fifth day of therapy, three of the four patients continued to have spiking fevers and positive blood cultures, and treatment with cefonicid was discontinued. Even though peak concentrations of antibiotic in serum were greater than 20-40 times the minimum inhibitory concentration of the antibiotic for the infecting organism, serum bactericidal titers were less than 1:8 in three patients. Susceptibility testing of 52 clinical isolates in broth confirmed a marked difference between inhibitory and bactericidal concentrations for 40% of these strains. In addition, susceptibility testing performed in serum rather than broth resulted in a sixfold increase in the minimum inhibitory concentration, a result suggesting that protein binding may be in part responsible for these failures of treatment. Cefonicid administered as a single daily dose is inadequate for treatment of endocarditis due to S. aureus and should not be used for treatment of bacteremia or life-threatening infections known or suspected to be caused by this organism.

Adult↗
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Pneumocystis carinii and Toxoplasma gondii infections in patients with AIDS.

Pneumocystis carinii and Toxoplasma gondii are the commonest protozoans causing infections in patients with acquired immunodeficiency syndrome (AIDS). P. carinii is almost exclusively a pulmonary pathogen and caused the commonest serious infection experienced by AIDS patients. The clinical findings are those of progressive pneumonia. Diagnosis requires microscopic examination of lower respiratory secretions or lung tissue. Pentamidine or combinations of trimethoprim and sulfamethoxazole are equally effective (85% recovery), but about one-half of patients thus treated experience severe toxicity. T. gondii infections occur primarily in the brain; patients present with focal seizures or neurologic deficit and have focal abnormalities as assessed by computed tomography. Serologic tests for toxoplasmosis are rarely diagnostic in AIDS patients, and most patients are treated empirically with a combination of pyrimethamine and sulfonamide. Less invasive diagnostic tests and better chemotherapeutic agents are required for both pneumocystosis and toxoplasmosis.

Acquired Immunodeficiency Syndrome↗
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Passive immunotherapy for encephalitis caused by herpes simplex virus.

Passive administration of antiviral antibody has been assessed in animal models as a potential form of treatment for infections due to herpes simplex virus (HSV). Previous investigative work has demonstrated the beneficial effect of immune serum administered either before or after HSV infection of mice. In some studies the protective effect of antibody was abrogated in the absence of T lymphocytes, an observation suggesting that cellular effector mechanisms may be necessary for antibody efficacy. In the present study of a mouse model of encephalitis caused by HSV type 2, a 0.5-ml dose of human immunoglobulin (1,250 mg of immunoglobulin G/kg of body weight) prepared at pH 4.25 for intravenous administration reduced mortality and prolonged survival when administered by intraperitoneal injection 24 hr before or up to 8 hr after intranasal viral challenge. The serum titer of HSV-neutralizing antibody and the response to therapy were dose dependent. Clinical trials of passive immunotherapy for severe HSV infections may be warranted.

Animals↗
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Paromomycin therapy of endemic amebiasis in homosexual men.

A prospective evaluation was made of the therapeutic efficacy of paromomycin, an orally administered, nonabsorbable aminoglycoside, in 114 homosexual men with mild-to-moderate (nondysenteric) intestinal amebiasis. All patients received 25-35 mg/kg daily in three divided doses for seven days. Of the 80 patients with gastrointestinal complaints at the onset of therapy, 55 (80%) of 69 were asymptomatic within four to six weeks after completion of treatment; 11 patients were lost to follow-up. Paromomycin produced long-term eradication of intestinal Entameba histolytica infection in 92% of all men evaluated. The rate of microbiologic cure among patients with symptoms at the onset of therapy was comparable to that among asymptomatic individuals. Paromomycin was well tolerated, with mild diarrhea during therapy the only frequent adverse effect (67% of patients). Thus, paromomycin is an effective alternative to conventional multi-drug therapy for intestinal amebiasis, and it has the advantages of low toxicity, brief duration of therapy, and a high rate of patient compliance.

Adult↗
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Treatment of gonorrhea with first- and second-generation cephalosporins and other new beta-lactam antibiotics.

Aqueous procaine penicillin, ampicillin, and amoxicillin have been used successfully in treatment of gonococcal infections for many years. Many of the new beta-lactam antimicrobial agents subsequently have proved effective for treating these infections as well. First-generation cephalosporins are less active (by weight) than second-generation cephalosporins, which, in turn, are less active than third-generation drugs. Single-dose therapy of uncomplicated mucosal gonococcal infections with first-generation cephalosporins has resulted in generally unacceptably low cure rates of less than 90% in most studies, whereas parenterally and orally administered second-generation cephalosporins show good clinical efficacy. Both second- and third-generation cephalosporins are active against beta-lactamase-producing Neisseria gonorrhoeae. The extended-spectrum and ureido-penicillins are active in vitro against non-beta-lactamase-producing N. gonorrhoeae and have parallel activity in vivo. Single doses of aztreonam, the first monobactam studied in humans, have also shown excellent clinical efficacy.

Anti-Bacterial Agents↗
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Recurrent herpes labialis in skiers. Clinical observations and effect of sunscreen.

Recurrent orofacial herpes infection may be triggered by high altitude skiing, presumably because of solar ultraviolet radiation exposure. Six (12%) of a group of 51 subjects with a history of skiing-triggered herpes observed during 1 week of high altitude skiing experienced reactivations of orofacial herpes a median of 3 1/2 days after exposure. Within this group, application of a sunscreen with a sun protection factor (SPF) of 15 failed to influence the reactivation rate as compared with a placebo. Reactivation of herpes triggered by skiing is common. As application of a sunscreen with an SPF of 15 did not appear to influence the reactivation rate, alternate approaches to the control of recurrent orofacial herpes are needed.

Adult↗
PubMedDate not supplied

Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid space: a preclinical study for the treatment of cancer pain.

Chromaffin cells have been shown to release a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. The allogeneic transplantation of chromaffin cells in the subarachnoid space has been shown to alleviate pain in various rodent models and possibly in terminal cancer patients. Because of the shortage of human cadaver donor tissue, we are investigating the possibility of transplanting xenogeneic cells in polymer capsules. In this technique, cells are surrounded by a permselective synthetic membrane whose pores are suitably sized to allow diffusion of nutrients, neurotransmitters and growth factors, but restrict the diffusion of the large molecules of the immune system and prevent contact with immunocompetent cells. The encapsulation technique therefore allows transplantation of xenogeneic tissue between species as well as retrieval of transplanted cells. Previously we have reported that encapsulated bovine chromaffin cells survive and alleviate pain in various rodent models. The purpose of the present study was to assess the feasibility of implanting a human sized device in a large animal model. Adrenals from 5 calves were surgically removed; chromaffin cells were isolated from these glands using a collagenase-based digestion-filtration technique. Cells were loaded into acrylic-based tubular (5 cm long, 920 microns wide) permselective capsules attached to silicone tethers. The capsules were maintained in vitro for at least 7 days following the encapsulation procedure. Nicotine evoked release was analyzed in a defined subgroup from each batch. One capsule was then implanted using a guiding cannula system in the lumbar subarachnoid space of each sheep for 4 (n = 5) and 8 (n = 1) wk. All capsules were retrieved intact by gentle pulling on the silicone tether. Except for one capsule, the evoked catecholamine release of the retrieved capsules was in the same range as that of other capsules from the same cohort that had been maintained in vitro. All retrieved capsules were devoid of host cell reaction. Clusters of viable cells dispersed in an alginate immobilizing matrix were observed throughout all the implanted capsules. This study demonstrates the feasibility of transplanting functional encapsulated xenogeneic chromaffin cells into the cerebrospinal fluid of a large animal model using a capsule of appropriate dimensions for human implants. We believe that these results suggest the appropriateness of human clinical trials in patients suffering from refractory terminal cancer pain.

Adrenal Glands↗
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Horner's syndrome after carotid endarterectomy--a case report.

Horner's syndrome is described in a patient with anisocoria and unilateral lid ptosis 48 hours after an ipsilateral carotid endarterectomy. This case illustrates a rare iatrogenic complication of sympathetic nerve dysfunction following elective surgery.

Aged↗
PubMedDate not supplied

Correlation between specific immunity to a metabolite of halothane and hepatic lesions after multiple exposures.

A correlation between the use of halogenated anesthetic agents and liver necrosis is not yet established in man. In an attempt to resolve this dilemma, guinea pigs were immunized with a complex of guinea-pig albumin and trifluoroacetate (TFA), a common metabolite of halothane and fluorexene, and then exposed to halothane on multiple occasions. Histology and liver-function tests showed no difference in the incidence of liver damage between groups of animals immune to TFA with cellular immunity and untreated control animals. However, a difference in the liver enzyme levels was seen between controls and animals showing humoral immunity.

Animals↗
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Hantavirus reservoir hosts associated with peridomestic habitats in Argentina.

Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping (2,299 rodents of 32 species during 27,780 trap nights) at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas.

Animals↗
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Views of mixed sex wards: a survey of patients, carers and nurses.

This paper describes the design and implementation of a survey carried out at Wharfedale General Hospital, related to the potential development of mixed sex wards. The survey of patients, carers and ward nurses, carried out in December 1992, demonstrated a general consensus of views on mixed sex ward options, and identified a number of key areas which need to be addressed before both sexes can be nursed satisfactorily on wards which have historically been used for males or females only. The recommendations arising from the survey are now being taken up by the hospital managers for further action.

Adult↗
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Management of heart failure.

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Angiotensin-Converting Enzyme Inhibitors↗
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Expression and characterisation of the ovine respiratory syncytial virus (ORSV) G protein for use as a diagnostic reagent.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in children and calves. Antibodies to ovine RSV (ORSV) are common in sheep, but the clinical disease is not well defined. There is no report of ORSV infection in Australian sheep although respiratory distress syndrome has been described. This discrepancy may be due to the lack of a suitable diagnostic test. In this report, we have characterised the ORSV G protein in an attempt to study its relatedness to human and bovine RSV (HRSV, BRSV) and for use in the development of a suitable diagnostic assay. Full length and a truncated variant of ORSV G protein were expressed in mammalian cells and the expressed proteins characterised by indirect immunofluorescence and radioimmunoprecipitation assays. Our results indicate that like HRSV, the ORSV G protein is heavily glycosylated. The expressed protein was membrane bound as well as secreted and could be purified from culture supernatants and may be suitable for use in development of a diagnostic assay.

Animals↗
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Collaborative care.

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Aged↗
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Forecasting the future of HIV epidemics: the impact of antiretroviral therapies & imperfect vaccines.

Mathematical models can be used as health policy tools and predictive tools. Here we review how mathematical models have been used both to predict the consequences of specific epidemic control strategies and to design epidemic control strategies. We review how models have been used to evaluate the potential impact on HIV epidemics of (i) combination antiretroviral therapies (ART) and (ii) imperfect vaccines. In particular, we discuss how models have been used to predict the potential effect of ART on incidence rates, and to predict the evolution of an epidemic of drug-resistant HIV. We also discuss, in detail, how mathematical models have been used to evaluate the potential impact of prophylactic, live-attenuated and therapeutic HIV vaccines. We show how HIV vaccine models can be used to evaluate the epidemic-level impact of vaccine efficacy, waning in vaccine-induced immunity, vaccination coverage level, and changes (increases or decreases) in risky behavior. We also discuss how mathematical models can be used to determine the levels of cross-immunity that vaccines will need to attain if they are to be used to control HIV epidemics in countries where more than one subtype is being transmitted.

AIDS Vaccines↗