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Biomedical subjects

K R Brown

Publications and source records attributed to K R Brown.

At least 19 recordsLinked to original sources
PubMed1992

Concentrations of copper, zinc and lead in the Sydney rock oyster, Saccostrea commercialis (Iredale and Roughley) from the Georges River, New South Wales.

Copper, zinc and lead were analysed from samples of non-commercially grown Sydney rock oysters collected from the Georges River estuary in spring 1987. The results, when compared with previous data from 1975, indicated a marked increase in the concentration of copper (up to 40%) and zinc (up to 300%). For several sites, the recommended (National Health and Medical Research Council) levels for copper and zinc (70 micrograms g-1 and 1000 micrograms g-1 respectively) were exceeded. There appears to be a decrease in the concentration of lead since 1975. The gradient of increasing copper and zinc concentrations with increasing distance upstream from the mouth of the estuary reported in 1975 could not be statistically validated. A significant correlation was found between copper and zinc loadings in the oysters. It was noted that data collected in 1975 were based on commercially grown oysters. The use of commercially grown oysters, rather than indigenous oysters, to examine interaction of contaminant load and distance upstream, is complicated as commercial oysters are moved within the estuary and between estuaries to maximise growth potential.

Animals↗
PubMed1991

Blunt trauma-induced pacemaker failure.

A 54-year-old man with an artificial pacemaker sustained blunt trauma to his chest when he was struck with a baseball bat. Within 15 minutes after the injury, the patient experienced cardiovascular collapse. His pacemaker failed, and he required insertion of a temporary transvenous pacemaker. At surgery, the defect was traced to failure of the pulse generator, a rare cause of pacemaker failure. Emergency department evaluation should include prompt and continuous ECG monitoring, an overpenetrated chest radiograph, and telemetry evaluation after discharge.

Cardiac Pacing, Artificial↗
PubMed1990

The regulation of biological products.

The purpose of regulations for biological products is the same as that for any other medicinal or related products: the protection of recipients of the products. The entry into the age of molecular biology with its attendant development and manufacturing technology has placed new demands on regulatory agencies and related industry personnel. While the general goals of regulations remain the same, the scientific bases by which biological products must be reviewed and registered vary from those traditionally used for drugs or even older vaccines produced by conventional methods of growth, harvesting and purification. New regulations must be developed which take into account the new science involved in molecular biology and recombinant technology; new definitions must be provided and widely understood. The regulation of biologic products on an international basis is complicated by issues such as national interests superceding individual patient needs, bureaucracies being driven primarily by regulation and secondarily by science, industry expecting priority treatment for innovative products while having to absorb costs related to lost regulatory review time, and agencies or industry relying upon outdated regulations and/or archaic tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotechnology↗
PubMed1990

Norfloxacin versus trimethoprim-sulfamethoxazole in the treatment of urinary tract infections.

In a controlled, randomized trial of 133 patients with proven urinary tract infections (UTIs), significantly more pathogens were found to be susceptible to norfloxacin than to trimethoprim-sulfamethoxazole (TMP-SMZ) (p less than 0.01). Among patients with pathogens susceptible to both drugs, more of those treated with norfloxacin were cured or improved (p = 0.06). When at least one patient variable, i.e., prior history of therapy, was corrected for, this difference became significant (p = 0.03). Norfloxacin eradicated 11 of 13 infections due to Pseudomonas aeruginosa and 6 of 7 due to enterococci. Five patients treated with norfloxacin and two treated with TMP-SMZ had relapses within 6 weeks. Significantly fewer adverse experiences occurred in patients receiving norfloxacin (p less than 0.01).

Adult↗
PubMed1990

Ivermectin--clinical trials and treatment schedules in onchocerciasis.

Initial clinical trials with ivermectin were performed in patients with both roundworm infestation and onchocerciasis. Obvious clinical safety allowed for rapid progression through 5-30-50-100-150-200 mcg/kg in infected patients. Initial studies showed some effect at 50 mcg/kg; subsequent double-blind controlled studies, either with placebo or diethylcarbamazine (DEC), confirmed the efficacy of ivermectin as well as further defining its safety profile. Absence of adverse eye findings or serious systemic reactions justified the further open trials. Studies of patients treated at 6, 12, or 18 month intervals showed a long lasting effect of ivermectin in reducing skin microfilaria counts. Phase III studies confirmed safety and efficacy and further refined the dose to 150 mcg/kg every 12 months. Large trials in Liberia and other countries in West Africa, and subsequently under Onchocerciasis Control Program (OCP), included approximately 120,000 persons carefully followed during which few patients with serious adverse experiences were reported. These extensive field trials confirmed the relative safety allowing for broad distribution of ivermectin in programs not able to provide physician monitoring.

Animals↗
PubMed1989

The role of cytochrome c4 in bacterial respiration. Cellular location and selective removal from membranes.

The cellular location of cytochrome c4 in Pseudomonas stutzeri and Azotobacter vinelandii was investigated by the production of spheroplasts. Soluble cytochrome c4 was found to be located in the periplasm in both organisms. The remaining cytochrome c4 was membrane-bound. The orientation of this membrane-bound cytochrome c4 fraction was investigated by proteolysis of the cytochrome on intact spheroplasts. In P. stutzeri, 78% of the membrane-bound cytochrome c4 could be proteolysed, whilst 82% of the spheroplasts remained intact, suggesting that the membrane-bound cytochrome c4 is on the periplasmic face of the membrane in this organism. Cytochrome c4 was not susceptible to proteolysis on A. vinelandii spheroplasts, in spite of being digestible in the purified state. Cytochrome c5 was shown to have a similar cellular distribution to cytochrome c4. Selective removal of cytochrome c4 from membranes of P. stutzeri was accomplished by the use of sodium iodide and propan-2-ol, with the retention of most of the ascorbate-TMPD (NNN'N'-tetramethylbenzene-1,4-diamine) oxidase activity associated with the membrane. Sodium iodide removed most of the cytochrome c4 from A. vinelandii membranes with retention of 62% of the ascorbate-TMPD oxidase activity. Cytochrome c4 could be returned to the washed membranes, but with no recovery of this enzyme activity. We conclude that cytochrome c4 is not involved in the ascorbate-TMPD oxidase activity associated with the membranes of these two organisms.

Azotobacter↗
PubMed1989

Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States.

Imipenem-cilastatin was evaluated for tolerability and efficacy in a multicenter open, noncomparative trial involving 178 infants and children with bacterial infections. Imipenemcilastatin was administered in total daily dosages of 100 mg/kg for patients up to 3 years of age and 60 mg/kg for those more than 3 years of age. Favorable clinical response was achieved in 98 of 100 patients judged evaluable for efficacy. Adverse effects were generally mild and reversible and included diarrhea alone or with vomiting (5.1%), irritation of intravenous infusion site (3.3%) and rash (2.2%). Changes in laboratory test values reported most frequently were thrombocytosis (8.9%), elevations in aspartate aminotransferase (7.9%) and alanine aminotransferase (5.6%) and eosinophilia (8.4%). This safety profile appears to be comparable to that of other beta-lactam antibiotics. Moreover imipenem-cilastatin was effective in infections caused by a broad spectrum of pathogens that include Haemophilus influenzae, Staphylococcus aureus, P. aeruginosa and anaerobes. These attributes suggest that imipenem-cilastatin should be safe and effective in selected pediatric patients.

Adolescent↗
PubMed1988

Free and membrane-bound forms of bacterial cytochrome c4.

Cytochrome c4 was isolated from cells of Pseudomonas aeruginosa, Pseudomonas stutzeri and Azotobacter vinelandii. The dihaem nature, Mr of approx. 20,000 and ferrohaem spectra in the region of the alpha- and beta-peaks define this family of cytochromes c. The behaviour of the holocytochromes in SDS was atypical, but removal of the haem groups resulted in a normal migration. In all three organisms most of the cytochrome c4 was tightly bound to the membrane, but some free cytochrome was detected. The membrane-attached cytochrome could be extracted with butanol, and this solubilized form was then indistinguishable in properties from the free form. Denitrifying rather than aerobic growth conditions hardly affected the total cytochrome c4 in the two pseudomonads, but there was slightly more free form and less membrane-attached form in denitrifying growth. The nature of the attachment of cytochrome c4 to the membrane is discussed and a model is proposed for the process of solubilization.

Amino Acids↗
PubMed1988

The efficacy results and safety profile of imipenem/cilastatin from the clinical research trials.

Imipenem/cilastatin is highly effective for infections in many body sites against a broad range of gram-positive and gram-negative aerobic and anaerobic bacteria. During therapy, development of resistance is uncommon except in the case of Pseudomonas aeruginosa in which the incidence appears similar to that for other beta-lactam antibiotics. There appears to be a very low probability of cross-resistance. The clinical and laboratory adverse reactions are similar in type to those for other beta-lactam antibiotics. The frequency of colonization and superinfection during treatment with imipenem/cilastatin has been comparable to other antibiotics in comparative trials and to literature reports for other antibiotics for noncomparative trials.

Bacterial Infections↗
PubMed1987

Imipenem/cilastatin treatment of lower extremity skin and soft tissue infections in diabetics.

The efficacy and safety profile of imipenem/cilastatin was investigated in 94 patients with diabetes mellitus with infections of the lower extremity. Ninety-eight percent of the pathogens were susceptible to imipenem; this was higher than to other antibiotics tested. Ninety-two percent of the patients were cured (47%) or improved (45%). Bacterial eradication was achieved for 79% of the pathogens. Adverse experiences were similar to those reported previously. Imipenem-cilastatin proved to be a very effective antibiotic with a good safety profile for use in diabetic patients with lower extremity infections.

Anti-Bacterial Agents↗
PubMed1986

The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients.

The relative safety of imipenem/cilastatin for 3470 patients was reviewed to see if the safety profile was similar to that seen for the first 1723 patients treated. The most common clinical adverse experiences were local ones related to the site of intravenous infusion. Gastrointestinal adverse experiences included nausea, vomiting, or diarrhoea. The frequency of pseudomembranous colitis was low (0 X 1%). The most common central nervous system abnormality was seizure. The most common background factor was central nervous system abnormality including prior history of seizure. Dermatological adverse experiences included rash, pruritus and urticaria. Bleeding and decreased renal function were uncommon. The most common laboratory changes included transient increased liver function values, eosinophilia, positive Coombs' test (not associated with haemolysis) and increased platelets. The current clinical and laboratory safety data are similar to those obtained in the early part of the clinical trials.

Bacterial Infections↗
PubMed1985

Complexity in the redox titration of the dihaem cytochrome c4.

Redox titration of the dihaem, two domain cytochromes c4 from Pseudomonas aeruginosa, Pseudomonas stutzeri and Azotobacter vinelandii showed complex behaviour indicative of the presence of two redox components. In the case of the P. stutzeri cytochrome c4, two spectroscopically distinct components were present during the redox titration. In contrast, cytochrome c-554(548) from a halophilic Paracoccus species is a stable dimer of a monohaem cytochrome which shows close homology to cytochrome c4, but does not show complexity in its redox titration. The presence of chemically distinct haem environments or anti-cooperative interactions between identical haem groups are two possible explanations for the redox complexity of cytochrome c4. The simple redox titration of cytochrome c-554(548) shows that haems situated relatively close together need not interact, but direct cleavage, separation and study of the domains will be necessary to decide whether they do or do not interact in the case of cytochrome c4.

Animals↗
PubMed1985

Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin.

The clinical and laboratory data relating to the adverse experiences and tolerability of imipenem/cilastatin in the first 2,516 patients treated with the antibiotic are reviewed, with special reference to the last 793. Clinical adverse experiences were predominantly related to the gastrointestinal system (nausea and vomiting), local injection site, and allergy (rash). A low frequency of drug-related seizures was also reported. The most frequent adverse laboratory experiences were transient elevations of liver function test values. In general, the safety profile was similar to that of other beta-lactam antibiotics.

Adolescent↗
PubMed1985

Comparison of the sensitivity of the vaginal mucous membranes of the albino rabbit and laboratory rat to nonoxynol-9.

Studies were conducted to compare the sensitivities of the vaginal mucous membranes of the albino rabbit and albino rat to irritation by the surfactant nonoxynol-9. The purpose of this comparison was to evaluate the rat as a model for screening vaginal products for their potential irritancy. Nonoxynol-9 at various concentrations in distilled water was administered intravaginally by lavage once a day for four consecutive days. On day 5, the animals were killed and the vaginal tissues were processed and examined histopathologically. Using a predetermined semiquantitative scoring system, it was found that the intensity of irritation was concentration dependent in both species. In the rabbit, the irritation was significantly greater than that in the rat, being mild with concentrations of 2.5 and 5% and moderate to severe at 12.5 and 25%. In the rat, irritation was negligible up to 12.5%, becoming mild at 25% and more moderate at 75%. Thus the vaginal mucosa of the rabbit is more sensitive than that of the rat and may be expected to give a more exaggerated representation of the irritation potential of a compound to the human vagina than would the rat mucosa.

Animals↗
PubMed1985

Photochemical binding of photoallergens to human serum albumin: a simple in vitro method for screening potential photoallergens.

A simple procedure employing UV spectroscopy is described for testing the ability of chemicals to form covalent conjugates with proteins after irradiation with the appropriate wavelength of light. A range of known photoallergens of widely differing structure has been tested using this procedure; results of these experiments, together with evidence from the scientific literature, provide a correlation between compounds known to be photoallergens and their ability to form covalent conjugates with proteins on irradiation with the appropriate wavelength of light. The method is proposed as an in vitro screening procedure for potential photoallergens.

Allergens↗
PubMed1985

Imipenem/cilastatin therapy of serious infections: a U.S. multicenter noncomparative trial.

Imipenem/cilastatin, which combines a broad-spectrum antibiotic derived from thienamycin with a specific enzyme inhibitor, was administered in dosages of 1 to 4 gm/day to 717 patients in a multicenter noncomparative trial. Ninety-nine percent of the bacterial pathogens tested were susceptible to imipenem, and 86% were eradicated. Clinical outcome was favorable in 85% or more of the cases when assessed according to the site of infection, and 92% of the cases responded to treatment overall. Development of resistance was rare except for Pseudomonas aeruginosa, which became resistant in 19% of the patients infected with that organism. More than half the patients with resistant P aeruginosa had a favorable clinical outcome, however. Superinfection occurred in approximately 4% of all patients. The adverse clinical experiences occurring most frequently were related to gastrointestinal function (nausea, vomiting, and diarrhea). In general, the safety profile of imipenem/cilastatin was similar to that of other beta-lactam antibiotics.

Anti-Bacterial Agents↗
PubMedDate not supplied

Safety of cefoxitin: an approach to the analysis of laboratory data.

The safety of cefoxitin, in terms of values obtained in laboratory tests during and after therapy, was estimated by three methods for analysis of data derived from controlled clinical comparisons of cephalothin and cefoxitin. Both antibiotics were found to be safe with respect to hematologic, renal, and hepatic function and did not differ significantly from each other. Laboratory data confirmed by tests performed serially and by paired related tests were analyzed by a novel method of comparison.

Cefoxitin↗