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Biomedical subjects

M Whitby

Publications and source records attributed to M Whitby.

At least 37 records · Page 2Linked to original sources

Fusidic acid in septicaemia and endocarditis.

The in vitro activity of fusidic acid against Staphylococcus aureus is confirmed in clinical studies which demonstrate that this antibiotic in combination with other agents, particularly beta-lactams, is efficacious in non-MRSA septicaemia. Some reports suggest that fusidic acid when used in combination, may significantly diminish the risk of relapse after cessation of therapy. However, in spite of over 30 years of use and its recommendation in a number of guidelines, published evidence is insufficient to allow reliable comment on the efficacy of the antibiotic in the treatment of endocarditis.

Anti-Bacterial Agents↗

Fusidic acid in the treatment of methicillin-resistant Staphylococcus aureus.

The emergence of MRSA in the 1960s coincided with the introduction of fusidic acid. Since that time, the antibiotic has been widely used against this organism, both in the 1960s and 1970s and against the more modern multi-resistant version of the 1980s and 1990s. Although showing potent in vitro activity, experimental in vivo and in vitro investigations have demonstrated disappointing results. Clinical efficacy has been demonstrated in a series of small studies and case reports, particularly when fusidic acid is used in combination for the treatment of MRSA carriage. Given the widespread use of fusidic acid against MRSA, published evidence supporting its efficacy is limited and does not support the use of the agent as monotherapy.

Anti-Bacterial Agents↗

Endemic nosocomial gram-negative bacteraemias resulting from contamination of intravenous heparin infusions.

Following several cases of Gram-negative bacteraemia secondary to intravenous heparin infusion contamination, we retrospectively reviewed nosocomial bacteraemias associated with heparin infusions at our institution. Thirty-one episodes of heparin-infusion related bacteraemia occurred in 30 patients over a 23-month period affecting 2% patients receiving heparin infusions for more than 48 h. Gram-negative bacteria were responsible for all bacteraemias. The care of infusions during clinical use was prospectively surveyed, revealing that approximately 20% of lines and cannulae were left for more than 72 h before replacement, and significant discordance occurred between line replacement and syringe and cannula exchange. We concluded that contamination of the infusions was probably extrinsic and secondary to manipulations of the system during use. Prolonged usage and discordant exchange of infusion components were likely important factors in initial contamination and subsequent bacterial proliferation. The problem resolved following the introduction of a policy for routine and simultaneous replacement of lines and syringes at 24-h intervals and upon cannula exchange.

Anticoagulants↗

Three cases of dengue 1 virus infection from islands in the Gulf of Thailand.

Three Australian tourists who recently travelled to islands in the Gulf of Thailand developed febrile illnesses associated with myalgias, thrombocytopenia, and atypical lymphocytosis. Dengue 1 virus was isolated from all three patients. The patients' clinical features and serological and virological investigations are presented. These cases highlight the need for awareness of dengue amongst travellers and the preventive precautions required when visiting endemic regions. After the urgent exclusion of malaria, dengue should be considered in the differential diagnosis of febrile persons who have recently returned from endemic regions.

Adult↗

Gamma delta T cells: their immunobiology and role in malaria infections.

The status of research on gamma delta T cells is reviewed. Recent research shows that gamma delta T cells may see antigens in an immunoglobulin-like manner and that non-peptidic substance can be antigens for these cells. Considerable advances have been made in defining the immunobiology of gamma delta T cells, with evidence for sentinel, protective and immunoregulatory roles. Research on gamma delta T cells in malaria infections suggests that gamma delta T cells are mediators of protective immunity, most probably through the production of Th1 cytokines such as TNF alpha, TNF delta and IFN gamma and that excessive production of such cytokines may contribute to pathology. Our data on the features of the peripheral blood gamma delta T cells response in humans infected with Plasmodium falciparum show that there is considerable variation between individuals in the relative expansion of gamma delta T lymphocytes following primary or secondary infection. They confirm that activation of gamma delta T cells occurs during P. falciparum infection and that activated cells can persist for many weeks after treatment. The possibility that gamma delta T cells have an immunoregulatory function in malaria infections is proposed.

Cytokines↗

Experimental human Plasmodium falciparum infections: longitudinal analysis of lymphocyte responses with particular reference to gamma delta T cells.

The kinetics of the gamma delta T-cell response was analysed in the context of the overall haematological response in subjects experimentally infected with sporozoites of Plasmodium falciparum. Numbers of gamma delta and alpha beta T cells and NK cells declined markedly during infection to reach minimum values 12-13 days post-infection when the patients were ill. This decline commenced from the beginning of the erythrocytic cycle and well before parasites could be detected microscopically and clinical symptoms developed. Platelet numbers also declined. In vivo activation of gamma delta T cells was evident with sequential up-regulation of the activation markers CD69 and HLA-DR. gamma delta T cell numbers were highest after treatment with the majority being CD4-CD8-, HLA-DR+ and showing reduced CD45RA expression. Contrary to some published observations gamma delta T-cell percentages remained within the normal range. Little evidence of upregulation of activation or memory markers was observed in the alpha beta T-cell population. In vitro proliferative responses to malaria antigen which involve gamma delta T cells were lost as the infection progressed and the lymphocyte count declined but these could be restored with the addition of exogenous IL-2 to cultures. The authors findings are consistent with a protective and/or immunomodulatory role for gamma delta T cells in malaria.

Adult↗

Tick-borne diseases in Australia.

Tick bites are a common problem in Australia and an important cause of morbidity in medical and veterinary practice. Complications include local inflammation and infection, paralysis and transmission of various pathogens. Over the past three decades, several new tick-borne diseases have been recognised both in Australia and overseas. The importance of these diseases has also increased, in part due to greater recreational activities occurring in tick infested areas. However, our understanding of the microbiology and epidemiology of many of these diseases is incomplete.

Australia↗

Effect of OKT3 in steroid-resistant renal transplant rejection.

Between January 1, 1982, and November 1, 1986, 169 cadaver renal graft transplantations were performed at this hospital with CsA as induction therapy. OKT3 was not available in this period. Of these grafts, 15.9% were lost within 6 months, 10.7% from acute rejection (AR). Between November 1, 1986, and October 1, 1992, 483 cadaver renal graft transplantation were performed. Induction therapy included CsA and OKT3 was available. Of these grafts, 8.7% were lost inside 6 months, 3.1% from AR. Of these last 483 grafts, 113 received 125 courses of OKT3. Ten courses were prophylactic, and 115 courses in 103 patients were for rejection resistant to steroid therapy (biopsy proven in all but 2 cases. Ninety-three percent of rejection episodes treated with OKT3 responded, at least initially. Graft survival in OKT3-treated patients was 81%, 77%, and 76% at 6 months, 1 year, and 2 years, respectively. In contrast, graft survival in steroid-resistant rejection during the first period (without OKT3) was 59%, 57%, and 57% at these intervals. There were 8 infective deaths within 6 months in the 113 OKT3-treated patients, compared with 2 in the 343 who did not receive OKT3 (P < 0.001). There were 7 viral deaths in the OKT3 group compared with none in those not receiving OKT3 (P < 0.001). Prophylaxis with oral acyclovir and cotrimoxazole was instituted in October 1990 in OKT3-treated patients and ganciclovir use was increased. Since this change, no further viral deaths have occurred. OKT3 is a very effective antirejection agent, but its use is associated with an increased mortality from viral infections. With appropriate prophylaxis and treatment, however, this mortality can be reduced.

Cyclosporine↗

Phialophora corneal ulcer.

BACKGROUND: A corneal fungal ulcer which appeared to be quite superficial clinically, was found by histologic examination to unexpectedly involve the full thickness of the cornea. METHODS: A patient with an apparent superficial corneal fungal ulcer due to Phialophora species was resistant to topical and intravenous antifungal therapy. RESULTS: Penetrating keratoplasty cured the condition with retention of normal vision with a follow-up of two years. CONCLUSIONS: If keratomycosis is unresponsive to topical and intravenous antifungal therapy, penetrating keratoplasty may be required to eliminate the infection. Resistance to medical therapy might suggest presence of fungus far deeper in the cornea than suspected clinically.

Adult↗

Comparison of fleroxacin and amoxicillin in the treatment of uncomplicated urinary tract infections in women.

Fleroxacin, 400 mg, was compared with amoxicillin, 3,000 mg, each administered orally in a single dose, for the treatment of women with acute uncomplicated symptomatic urinary tract infections. A total of 142 patients were randomized to receive fleroxacin, and 147 patients to receive amoxicillin. Of these, 33 in the fleroxacin group and 39 in the amoxicillin group were considered bacteriologically evaluable. Cure at 5-9 days after treatment was achieved in 32 (97%) of the fleroxacin-treated patients and in 22 (56%) of the amoxicillin-treated patients (p < 0.001). For the most frequently isolated pathogen (Escherichia coli), all 24 isolates were eradicated in the fleroxacin group, as were 11 of 25 in the amoxicillin group. At 6 weeks after therapy, bacteriologic cure was maintained in 20 (95%) of the 21 evaluable patients who received fleroxacin and in 8 (89%) of 9 evaluable patients who received amoxicillin. There were no reinfections in either group. A total of 280 patients were assessed for safety. Clinical adverse events were reported in 32 (23%) of 137 patients in the fleroxacin group and in 19 (13%) of the 143 patients in the amoxicillin group. In both groups, the most common adverse effects were gastrointestinal, while adverse events involving the central nervous system were more frequent in patients who received fleroxacin. On the basis of this study, it appears that fleroxacin is demonstrably more effective than amoxicillin as single-dose therapy for uncomplicated urinary tract infection.

Adolescent↗

Evaluation of a novel fluorescence polarization immunoassay for teicoplanin.

A fluorescence polarization immunoassay (FPI) for teicoplanin that uses the TDx Instrument System (Abbott, Irving, Tex.) as an automated analyzer has been developed by Innotron of Oregon Inc. and was evaluated in patients with staphylococcal infections enrolled in a clinical trial of the antibiotic. The assay proved accurate in estimating concentrations of between 5 and 100 mg/liter. The intraassay coefficient of variation was < 7.3%, while the interassay variance was < 11.6% against three commercially prepared standards at known concentrations of approximately 5, 35, and 75 mg/liter. Against routinely prepared standards at 10 concentrations between 5 and 100 mg/liter analyzed in a single run, the coefficient of variance did not exceed 4.3%. Compared with bioassay, the FPI demonstrated good correlation in terms of reliability (r = 0.909) in samples containing teicoplanin only and specificity (r = 0.916) in samples containing both teicoplanin and gentamicin. With a turnaround time of 20 min and with only 50 microliters of serum needed for estimation of the amount of drug in a sample, the FPI described here should provide a useful method of teicoplanin measurement in routine diagnostic laboratories.

Biological Assay↗

Spontaneous Clostridium perfringens lung abscess unresponsive to penicillin.

Clostridial necrotising pneumonia is a rare complication of aspiration, bronchial tumour or foreign body, pulmonary infarction, trauma and debilitating medical conditions. Although spontaneous clostridial pneumonia has been reported previously, close scrutiny of those case reports suggests that most of the patients had a recognised predisposing cause. We report a case of true spontaneous Clostridium perfringens pneumonia complicated by septic shock, pneumothorax and pulmonary necrosis. The patient responded poorly to conventional treatment with benzylpenicillin, and although the addition of metronidazole produced dramatic resolution of the sepsis, lobectomy was required to effect cure.

Clostridium Infections↗

The febrile patient.

Fever has long been recognised as a manifestation of infection; on occasions, it may be a pointer to other underlying diseases including immune-mediated and neoplastic conditions. This article explores the causes of fever, especially prolonged fever, and provides a management plan.

Anti-Bacterial Agents↗