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Biomedical subjects

P Paterson

Publications and source records attributed to P Paterson.

At least 19 recordsLinked to original sources

Oral ciprofloxacin plus colistin: prophylaxis against bacterial infection in neutropenic patients. A strategy for the prevention of emergence of antimicrobial resistance.

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].

Adolescent↗

MRSA pyomyositis complicating sickle cell anaemia.

A patient being treated for sickle cell crisis developed swollen, painful, indurated, discoloured thighs after several days in hospital. Imaging revealed the presence of multiple small abscesses in the muscle and methicillin resistant Staphylococcus aureus (MRSA) was cultured from aspirated fluid. Pyomyositis usually occurs in association with damaged muscle and impaired host defences. Staphylococcus is the most frequent organism involved. It is not a common complication of sickle cell disease, although it may be under diagnosed. Availability of advanced imaging techniques facilitates early diagnosis of pyomyositis.

Adult↗

Donor finger morbidity in cross-finger flaps.

We reviewed 16 patients who had cross-finger flap procedures carried out between 1991 and 1996 at the West Midlands Regional centre for Plastic and Reconstructive Surgery. We looked specifically at the donor finger morbidity of each patient with a median follow up interval of 43 months.At follow up there were 10 patients with cold intolerance, eight patients with subjective joint stiffness and a documented reduced range of finger joint movement. Skin graft reconstruction of the secondary defect was associated with poor colour match in eight cases (seven hyperpigmented, one hypopigmented) and visible contour deformity in eight cases. There were no clinically significant differences between split skin graft or full thickness skin graft for donor finger reconstruction. Although cross-finger flaps may provide soft tissue cover in a variety of finger pulp injuries, these results show an alarming incidence of donor finger morbidity associated with such procedures.

Adolescent↗

Defining a normal finger web in children.

We calculated the interdigital web ratios for children between the ages of 5 and 6 and 10 and 11 years. We compared these ratios with those seen in adults and conclude that there is a change in finger web morphology with age. We found that a photocopier provided images of similar quality to conventional photography.

Child↗

A multicenter, randomized, prospective study of endoscopic laser ablation versus transurethral resection of the prostate.

OBJECTIVES: To assess the safety and efficacy of endoscopic laser ablation of the prostate (ELAP), performed with the Urolase fiber and the neodymium:yttrium-aluminum-garnet laser, compared to transurethral resection of the prostate (TURP) in patients with bladder outflow obstruction secondary to benign prostatic hyperplasia (BPH). METHODS: In this multicenter, prospective, randomized study, a total of 151 patients were treated (ELAP, 76; TURP, 75) of whom 137 completed 1 year follow-up (ELAP, 67; TURP, 70). Safety parameters included measurement of preoperative and 24-hour postoperative sodium, hematocrit, and hemoglobin values and careful monitoring of adverse events. Efficacy was assessed with the American Urological Association symptom score (6), urinary flow rates, and residual urinary volume measurements. RESULTS: There was 1 death in each group during the study period unrelated to the treatment procedure. There was a clinically significant improvement in all efficacy parameters in both groups. Between group comparisons favored TURP in maximum flow rate, residual urinary volume, and symptom score. ELAP had a better safety profile than TURP in the defined safety parameters of drop in hemoglobin and hematocrit values. In 16% of patients, a blood transfusion was required after TURP compared with no transfusions in the ELAP group. Urinary tract infections and dysuria were more frequent in the ELAP group. CONCLUSIONS: ELAP performed with the Urolase fiber is a useful alternative therapy to TURP in patients presenting with bladder outflow obstruction secondary to BPH.

Aged↗

Is the treatment of urgency incontinence a placebo response? Results of a five-year follow-up.

The treatment and symptomatic outcome were reviewed in 50 women who had presented with urgency incontinence as their main symptom 5 years previously. All had idiopathic urgency incontinence and, on the basis of urodynamic investigation, 40 were considered to have detrusor instability and 10 sensory urge incontinence. The results indicate that the natural history of sensory urgency is one of spontaneous resolution; all treatments of detrusor instability (including surgery) produced an unsustained short-term symptomatic response. This pattern of response to therapy may be interpreted as being largely of a placebo nature and this emphasises the need for long-term follow-up in the assessment of new treatment modalities.

Adolescent↗

What proportion of couples undergoing unrestricted in vitro fertilization treatments can expect to bear a child?

A 200-patient cohort has been established so that longitudinal analysis can determine the likelihood of an individual in vitro fertilization (IVF) entrant achieving a viable uterine pregnancy or a live baby. After a minimum of 39 months of access to repeated treatment cycles, 24% have achieved at least one viable pregnancy by undergoing an average of 2.48 treatment cycles per cohort member. Life-table analysis shows that most of these pregnancies have occurred in the first year after entering the program. Many members have undergone only one or two treatment cycles. In the future, greater emphasis will need to be placed on factors which encourage couples to undergo additional cycles of treatment. This, as much as technical advances, may increase outcome figures.

Actuarial Analysis↗

Mechanisms of butylated hydroxytoluene-mediated modulation of 2-acetylaminofluorene mutagenicity in rat and human hepatocyte/Salmonella assays.

Salmonella typhimurium (TA98) mutagenesis assays were used to study the influence of the antioxidant butylated hydroxytoluene (BHT) on 2-acetylaminofluorene (2-AAF) mutagenesis, in search of the mechanism of the anticarcinogenic effects of BHT. Rats pre-treated with BHT in the diet (0.5% w/w for 10 days) provided hepatocytes and hepatocyte S9 which were more efficient in the activation of 2-AAF than were similar preparations from control rats. The increased release of mutagens from hepatocytes might explain the reported increase in the incidence of bladder tumours in BHT-treated rats. In contrast, the mutagenic activity of 2-AAF was inhibited by the in vitro addition of BHT into incubations where human or rat liver S9 and intact hepatocytes were used for metabolic activation. Both competitive and un-competitive inhibition by BHT of 7-ethoxycoumarin O-deethylation was observed in hepatocytes which suggested that the antimutagenic activity may be mediated by one or more mechanisms of cytochrome P-450 inhibition. BHT inhibition of the mutagenicity of N-OH 2-AAF and of rat urinary metabolites of 2-AAF indicated that effects other than those mediated by cytochrome P-450 also occur e.g. scavenging of reactive metabolites. It was concluded that BHT-modulation of 2-AAF metabolic activation and mutagenesis (which may relate to BHT-protection against hepatocarcinogenicity) involves multiple mechanisms.

2-Acetylaminofluorene↗

Activation of 2-amino-3-methylimidazo (4,5-f) quinoline in rat and human hepatocyte/Salmonella mutagenicity assays: the contribution of hepatic conjugation.

The capacity of human liver S9 and hepatocytes to metabolically activate 2-amino-3-methylimidazo (4,5-f) quinoline (IQ) in Salmonella mutagenicity assays more closely resembles that of preparations from Aroclor-induced rat than control rat. The extent to which hepatocyte conjugating enzymes contribute to activation in these assays has been studied. Omission of sulphate or addition of a 'specific' sulphotransferase inhibitor (2,6-DCNP) did not significantly reduce mutagenicity, nor did PAPS enhance S9-mediated bacterial mutagenicity. Conversely, mutagenicity was significantly inhibited by PCP (an inhibitor of both sulphotransferase and acetyltransferase) and an acetylation-deficient Salmonella (TA98/1,8DNP6) was unresponsive to the mutagenicity of IQ. These data suggest that acetylation but not sulphation is important in IQ bacterial mutagenesis. The addition of acetyl CoA, PAPS-generating system or ATP paradoxically reduces the mutagenicity of IQ in S9/Salmonella TA98 assays. Therefore, activation by esterification in hepatocytes does not contribute to the mutagenicity of IQ in Salmonella typhimurium possibly due to restricted access of conjugates into the bacterial cell.

Animals↗

Sex differences in the effects of microsomal enzyme inducers on hepatic phase I drug metabolism in the rat.

This study investigates the sex-dependence of the effects of microsomal enzyme inducers (phenobarbitone, isosafrole and ethanol) on the hepatic phase I metabolism of lignocaine and imipramine. It is shown that all of the inducers exert sex-dependent effects on the enzymes activities known to be sex related in the rat, e.g. lignocaine N-deethylase activity is decreased by phenobarbitone pretreatment in the male but increased by the same treatment in the female. The inducers tend to decrease the sex differences seen in untreated animals. Ethanol may give this effect by its action of decreasing serum testosterone levels but the mechanism of action of the other compounds is uncertain. It is possible that the sex-dependent cytochrome P-450 species are selectively sensitive to the action of the compounds in terms of induction, repression or inhibition. It is clear, however, that the effects of the pretreatments are related to the sex differences in phase I metabolism in the rat.

Animals↗

Influence of cytochrome P-450 type on the pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl or 4-methoxybiphenyl.

The rate of production of 4-hydroxybiphenyl from 4-methoxybiphenyl in hepatocytes isolated from untreated rats was essentially identical to that from biphenyl in hepatocytes isolated from rats pretreated with beta-naphthoflavone at 40 mg/kg. Similar results were obtained using liver microsomes isolated from untreated or treated rats. The selective inhibition of these reactions by metyrapone, alpha-naphthoflavone and ethanol demonstrated that different forms of cytochrome P-450 are responsible for O-demethylation of 4-methoxybiphenyl in livers of untreated rats and 4-hydroxylation of biphenyl in livers of pretreated rats. The pattern of conjugation of 4-hydroxybiphenyl generated from biphenyl in hepatocytes isolated from pretreated rats was different from that for 4-hydroxybiphenyl generated from 4-methoxybiphenyl in hepatocytes isolated from untreated rats, there being a 60% decrease in sulphation measured after 60 min incubation with biphenyl. Glucuronidation of 4-hydroxybiphenyl was not affected. The sulphation of 4-hydroxybiphenyl added directly was significantly decreased in hepatocytes isolated from pretreated rats. The initial rate of glucuronidation of 4-hydroxybiphenyl added directly was not altered by the pretreatment, but there was a significant decrease in overall glucuronidation measured over a 60 min incubation. Similar results were obtained using liver slices. beta-Naphthoflavone added directly to liver slices significantly decreased the extent of sulphation of 4-hydroxybiphenyl but did not influence glucuronidation. There was evidence of a late decrease in biphenyl 4-hydroxylase activity in hepatocytes isolated from pretreated rats. It is concluded that the differences observed in the cellular metabolism of biphenyl and 4-methoxybiphenyl can be ascribed to competition between beta-naphthoflavone and/or its metabolites retained within the cells following pretreatment, and biphenyl and/or its metabolites for the pathways common to their metabolism. It is also concluded that the type of cytochrome P-450 involved in the generation of 4-hydroxybiphenyl does not, per se, influence the subsequent pattern of conjugation.

Animals↗

Influence of cytochrome P-450 type on the pattern of conjugation of 7-hydroxycoumarin generated from 7-alkoxycoumarins.

Pretreatment of rats with phenobarbitone increased hepatic microsomal 7-methoxy-and 7-ethoxy-coumarin O-dealkylase activities. Pretreatment with beta-naphthoflavone increased only the 7-ethoxycoumarin O-dealkylase activity. The addition of metyrapone in vitro inhibited the O-dealkylations to different extents. Similar results were obtained with diphenyloxazole and ethanol. These results are taken to indicate that different forms of cytochrome P-450 are involved in the O-dealkylation of these two substrates. The pattern of metabolism (Phase I and Phase II) of each alkoxycoumarin in rat isolated hepatocytes was very similar. The sulphate conjugate was the major metabolite produced, the amount of which approached a plateau as the rate of O-dealkylation increased. It is concluded that the type of cytochrome P-450 involved in the initial Phase I metabolism does not influence the subsequent pattern of conjugation.

Animals↗

The effect of ascorbic acid on the conjugation of 4-hydroxybiphenyl in rat isolated hepatocytes.

Ascorbic acid at high non-physiological levels inhibited the sulphation of 4-hydroxybiphenyl by rat isolated hepatocytes. Glucuronylation of 4-hydroxybiphenyl, formed from 4-methoxybiphenyl, was increased at ascorbic acid levels which inhibited sulphation. The glucuronylation of 4-hydroxybiphenyl added directly to the cells was enhanced at concentrations of ascorbic acid which did not inhibit sulphation. Ascorbic acid did not influence the cytochrome P-450-dependent O-demethylation of 4-methoxybiphenyl or the level of cellular lipid peroxidation.

Animals↗