Biomedical subjects

P Coates

Publications and source records attributed to P Coates.

At least 19 recordsLinked to original sources

PubMed2006

AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons.

Programmed cell death has been linked to AMPA-receptor-mediated excitotoxicity in pyramidal neurons of the hippocampus. The intent of this study was to investigate the roles of caspase-dependent and independent nuclear death-related factors in mediating AMPA-induced nuclear changes in PyNs by use of immunohistochemistry and transmission electron microscopy (TEM). Data indicate increases in the nuclear levels of caspase-activated acinus and DNase and Endonuclease G (a caspase-independent endonuclease) in CA1 and CA3 PyN nuclei with different temporal patterns following an AMPA-insult. Hoechst staining and TEM confirm AMPA-induced chromatin condensation. The presence of active acinus in nuclei suggests it mediates chromatin condensation. Interestingly, a DNA fragmentation labeling protocol showed that there was no chromatin cleavage up to 90 min after AMPA-insult. Overall, we conclude that: 1) AMPA-induced excitotoxicity increases nuclear immunoreactivity of pro-death enzymes from multiple programmed cell death pathways, 2) differential chromatin condensation patterns occur between CA1 and CA3, and 3) there is no chromatin cleavage within our experimental timeframe.

Animals↗

PubMed2005

Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.

Acne Vulgaris↗

PubMed2003

Antibiotic-resistant acne: lessons from Europe.

BACKGROUND: Propionibacterium acnes and P. granulosum are widely regarded as the aetiological agents of inflammatory acne. Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics. Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K. OBJECTIVES: To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres. METHODS: Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary. Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics. Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA. RESULTS: Viable propionibacteria were recovered from 622 patients. A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically. The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%). Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26.4% in the U.K.). No isolates resistant to tetracycline were detected in Italy, or in Hungary. Overall, there were strong correlations with prescribing patterns. Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain. Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne. None of 27 physicians working in other outpatient departments harboured resistant propionibacteria. CONCLUSIONS: The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria. Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K. Resistant genotypes originally identified in the U.K. are distributed widely throughout Europe. Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic.

Acne Vulgaris↗

PubMed2003

Short-term effects of topical fusidic acid or mupirocin on the prevalence of fusidic acid resistant (FusR) Staphylococcus aureus in atopic eczema.

BACKGROUND: Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical fusidic acid is widely used in its treatment. There is concern that topical use of fusidic acid may be driving the selection and dissemination of fusidic acid-resistant (FusR) S. aureus. OBJECTIVES: To test the hypothesis that treatment of atopic eczema for 2 weeks with topical fusidic acid/steroid combination can increase carriage of FusRS. aureus. METHODS: Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% fusidic acid plus 0.1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0.1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. RESULTS: Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for FusRS. aureus there was no significant change in the prevalence of carriage, or population density in either group compared to baseline. Over 50% of patients carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither regimen affected either the prevalence or population density of S. aureus or FusRS. aureus in the nerves. CONCLUSIONS: In this small study there is no evidence to support the hypothesis that short-term treatment of atopic eczema with fusidic acid/steroid combination increases fusidic acid resistant S. aureus during a 2-week period.

Administration, Topical↗

PubMed2002

Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study.

BACKGROUND: Cutaneous propionibacteria are implicated in acne pathogenesis, although their exact role in the genesis of inflammation is still poorly understood. Agents, including antibiotics, that reduce the numbers of propionibacteria on skin are therapeutic. Resistance in the target organism is a well-recognized consequence of antibiotic therapy for acne but formal prevalence and distribution data are lacking. OBJECTIVES: To monitor the prevalence of skin colonization by antibiotic-resistant propionibacteria in acne patients attending the dermatology out-patient clinic at Leeds General Infirmary over a 10-year period beginning in 1991, and to examine the distribution of resistant strains on acne-prone skin and in the nares. METHODS: Propionibacterial samples were obtained from the skin surface of the worst affected site (usually the face) of 4274 acne patients using a moistened swab. The swab was used to inoculate agar plates with and without selective antibiotics. After anaerobic incubation at 37 degrees C for 7 days, the amount of growth in the presence of each antibiotic was scored on a scale from 0 to 5+. A small number of patients (72) were selected for more detailed quantitative sampling at six different sites to examine the distribution of resistant propionibacteria on acne-prone skin and in the anterior nares. RESULTS: The proportion of patients carrying strains resistant to one or more commonly used antiacne antibiotics rose steadily from 34.5% in 1991 to a peak of 64% in 1997. The prevalence dropped to 50.5% during 1999 and then rose again to 55.5% in 2000. Resistance to erythromycin was the most common and the majority of erythromycin-resistant strains were cross-resistant to clindamycin. Resistance to tetracyclines was less common in all years and with little increase over time. The more detailed quantitative study in 72 patients showed that population densities of resistant propionibacteria varied considerably between sites and between individuals. Almost invariably, patients were colonized with resistant strains at multiple sites, including the nares. CONCLUSIONS: Skin colonization with antibiotic-resistant propionibacteria is much more common now than a decade ago. Resistant propionibacteria are widely distributed on acne-prone skin and in the nares. This suggests that they will be very difficult to eradicate using existing therapeutic regimens, especially from the nasal reservoir.

Acne Vulgaris↗

PubMed2001

Intraperitoneal hypothermia during surgery enhances postoperative tumor growth.

BACKGROUND: Recent work has shown that intraoperative hypothermia is a significant source of surgical trauma, with wide-ranging physiological and immunological sequelae. The aim of this study was to examine the effects of intraperitoneal hypothermia during laparoscopy on tumor growth in an animal model. METHODS: Thirty WAG rats were randomized to undergo anesthesia alone (n = 10), insufflation with cold carbon dioxide (CO2) (n = 10), or insufflation with warm CO2 (n = 10). During insufflation, 1 x 105/ml CC531s colon cancer cells in suspension were injected into the peritoneal cavity. The control group was anesthetized and tumor cells were injected without insufflation. After 3 weeks, total tumor weight and the extent of tumor spread, as assessed by the modified Peritoneal Cancer Index (PCI), were compared at autopsy. RESULTS: Laparoscopy with cold CO2 resulted in a significant reduction in local and core body temperatures (p <0.05). Tumor growth in both groups that underwent CO2 pneumoperitoneum was significantly increased compared with the group that did not (p <0.0001, control vs warm CO2 and cold CO2). There was significantly more tumor growth in the rats insufflated with unwarmed CO2 than in the normothermic group (mean total tumor 0.01 g +/- 0.03 vs. 0.043 g +/- 0.07; p = 0.025 Mann-Whitney U test). Tumor spread as shown by the PCI scores was less in the warm gas group than it was in the animals insufflated with cold gas (151 vs 266). CONCLUSIONS: These data demonstrate that the peritoneal insufflation of CO2 enhances tumor growth and that the prevention of perioperative hypothermia during laparoscopy attenuates tumor growth. This effect may be partially mediated by the increased peritoneal trauma that results from insufflation with cold gas.

Animals↗

PubMed2001

Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine.

BACKGROUND: Some comparative trials of selective serotonin 1B/ID-agonists in migraine have reported -15% lower efficacy for sumatriptan tablets than that reported in placebo-controlled trials. OBJECTIVE: This study was designed to test the hypothesis that the encapsulation methods used to mask active drug may delay absorption of sumatriptan from dosing to 2 hours after dosing (the traditional end point in clinical trials of migraine treatment), an effect that may be enhanced by migraine-associated gastric stasis. METHODS: Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was assessed by calculating the area under the plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentration. Data for the AUC from time zero to infinity and maximum plasma concentration were used to assess standard bioequivalence, which is considered to occur when the 90% CIs for the geometric mean treatment ratios (test/reference) fall between 0.8 and 1.25. RESULTS: Study 1 included 26 healthy subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30 patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours after dosing, particularly during a migraine. AUC2 values with encapsulated sumatriptan compared with the conventional tablet were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI, 0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy volunteers and patients experiencing a migraine. CONCLUSIONS: Encapsulation delayed absorption of sumatriptan 0 to 2 hours after dosing, particularly during a migraine. This delay in absorption of the encapsulated form may account for the lower efficacy of sumatriptan in some comparative studies.

Adult↗

PubMed2001

Modeling and stimulation for clinical trial design involving a categorical response: a phase II case study with naratriptan.

PURPOSE: The overall aim of the present study was to investigate retrospectively the feasibility and utility of model-based clinical trial simulation as applied to the clinical development of naratriptan with effect measured on a categorical scale. METHODS: A PK-PD model for naratriptan was developed by using information gathered from previous naratriptan and sumatriptan preclinical and clinical trials. The phase IIa naratriptan data were used to check the PK-PD model in its ability to describe future data. A further PK-PD model was developed by using the phase IIa naratriptan data, and a phase IIb trial was designed by simulation with the use of Matlab. The design resulting from clinical trial simulation was compared with that derived by using D-optimal design. RESULTS: The PK-PD model showed reasonable agreement with the data observed in the phase IIa naratriptan clinical trial. Clinical trial simulation resulted in a design with four or five arms at 0 mg, 2.5 and/or 5 mg, 10 mg, and 20 mg, PD measurements to be taken at 0, 2, and 4 or 6 h and at least 150 patients per arm. A sub-D-optimal design resulted in two dosing arms at 0 and 10 mg and PD measurements to be taken at 1 and 2 h. CONCLUSIONS: Clinical trial simulation is a useful tool for the quantitative assessment of the influence of the controllable factors and is the only tool for the quantitative assessment of the uncontrollable factors on the power of a clinical trial.

Administration, Oral↗

PubMed2001

In the midst of confusion lies opportunity: fostering quality science in dietary supplement research.

The Office of Dietary Supplements (ODS) was established at the National Institutes of Health (NIH) by Congress through the Dietary Supplement Health and Education Act (DSHEA) of 1994. The mission of the ODS is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results and educating the public, all in an effort to foster an enhanced quality of life and health for the U.S. population. In pursuit of this mission, ODS takes into account an array of dietary supplement ingredients and products. This includes vitamin and mineral supplements and botanicals, as well as non-nutrient supplements. Toward that end, ODS has taken a number of steps. In collaboration with other Institutes and Centers at NIH, ODS has established a network of Dietary Supplement Research Centers around the country that provide the focus for multidisciplinary research efforts; it supports research activities and scientific conferences, it supports evidence-based reviews of supplements, and it maintains a public database of scientific literature on dietary supplements. The lack of credible information from well-controlled studies of many dietary supplements raises issues of caution and concern. The ODS is committed to providing and disseminating accurate and reliable scientific information on dietary supplements.

Consumer Product Safety↗

PubMed2000

HPA-1a-mediated platelet interaction with monocytes in vitro: involvement of Fcgamma receptor (FcgammaR) classes and inhibition by humanised monoclonal anti-FcgammaRI H22.

To gain insight into mechanisms of platelet destruction and its possible inhibition during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) the binding to monocytes (Mo) of anti-HPA-1a-sensitised platelets, the initial step in IgG-mediated destruction by effector cells, was evaluated in an in vitro assay. Neonatal Mo were compared with adult Mo as effectors in the assay. Moreover, the potential involvement of Fcgamma receptor (FcgammaR) classes during platelet destruction in the disease was tested by using FcgammaR class-specific reagents as inhibitors of the binding reaction. Neonatal Mo were 37% less active than adult Mo in their interaction with anti-HPA-1a-sensitised platelets (p < 0.05). The FcgammaRI-specific reagents human monomeric IgG and humanised anti-FcgammaRI monoclonal H22 caused virtually complete inhibition of platelet binding to Mo. When compared to an intravenous immunoglobulin preparation the inhibitory activity of H22 was 10-100 x greater than that of the latter compound. Monoclonal anti-FcgammaRII IV.3 and anti-FcgammaRIII 3G8 decreased platelet binding by 70% and 64%, respectively, but only the anti-FcgammaRII inhibition was statistically significant (p < 0.001). Finally, anti-HPA-1a-sensitised platelets bound to 131H- but not to 131R- FcgammaRIIa transfected 3T6 mouse fibroblasts (p < 0.01), in an anti-HPA-1a-concentration-dependent manner. The results suggest that FcgammaRI and FcgammaRIIa may be involved in anti-HPA-1a-mediated platelet destruction by mononuclear phagocytes during FAIT/NAIT. Moreover, the much greater potency ofmonoclonal H22 than of intravenous immunoglobulin as an inhibitor of anti-HPA-1a-mediated Mo-platelet interaction, might render it superior to the latter agent in the maternal therapy of the disorder.

Adult↗

PubMed2000

Antibiotic resistance patterns of aerobic coryneforms and furazolidone-resistant Gram-positive cocci from the skin surface of the human axilla and fourth toe cleft.

Samples of skin surface bacteria from 28 healthy subjects plated directly on to selective and non-selective media revealed that the proportion of aerobic coryneforms and furazolidone-resistant Gram-positive cocci (FURECs) resistant to erythromycin was significantly greater in the fourth toe cleft than in the axilla (P < 0.05). There were more erythromycin-resistant bacteria than tetracycline-resistant bacteria at both sites (P = 0.001 for the toe cleft; P < 0.01 for the axilla). In total, 160 distinct isolates were obtained, of which 42 were FURECs and 118 were aerobic coryneforms. Of these, 153 (96%) were resistant to erythromycin and 66 (41%) to tetracycline. All except seven of the tetracycline-resistant strains were also resistant to erythromycin. The resistant isolates belonged to a variety of species. CDC group ANF corynebacteria were most numerous and composed 31% of all isolates. The majority (76%) of FURECs were identified as Micrococcus luteus. MIC determinations on selected strains revealed that tetracycline-resistant FURECs were sensitive to doxycycline and minocycline, as were most tetracycline-resistant coryneforms. Nine coryneform isolates were cross-resistant to all three tetracyclines. Only a minority of erythromycin-resistant FURECs (21%) demonstrated a macrolide-lincosamide-streptogramin type B (MLS)-resistant phenotype with inducible or constitutive cross-resistance to clindamycin and the type B streptogramin, pristinamycin IA. Twenty-nine erythromycin-resistant FURECs had a novel phenotype distinct from MLS and macrolide-streptogramin type B resistance. In contrast, most coryneforms (79%) were MLS resistant. Among the remainder, two unusual erythromycin resistance phenotypes were apparent, both of which differed from the unusual phenotype in FURECs. This study has revealed that the non-staphylococcal aerobic flora of skin contains a considerable reservoir of tetracycline and erythromycin resistance determinants. The three unusual macrolide resistance phenotypes may be associated with novel resistance mechanisms.

Actinomycetales↗

PubMed1999

A pharmacokinetic model for tenidap in normal volunteers and rheumatoid arthritis patients.

PURPOSE: To develop a pharmacokinetic model for tenidap and to identify important relationships between the pharmacokinetic parameters and available covariates. METHODS: Plasma concentration data from several phase I and phase II studies were used to develop a pharmacokinetic model for tenidap, a novel anti-rheumatic drug. An appropriate pharmacokinetic model was selected on the basis of individual nonlinear regression analyses and an EM algorithm was used to perform a nonlinear mixed-effects analysis. Scatter plots of posterior individual pharmacokinetic parameters were used to identify possible covariate effects. RESULTS: Predicted responses were in good agreement with the observed data. A bi-exponential model with zero order absorption was subsequently used to develop the mixed-effects model. Covariate relationships selected on the basis of differences in the objective function, although statistically significant, were not particularly strong. CONCLUSIONS: The pharmacokinetics of tenidap can be described by a bi-exponential model with zero order absorption. Based on differences in the log-likelihood, significant covariate-parameter relationships were identified between smoking and CL, and between gender and Vss and CLd. Simulated sparse data analyses indicated that the model would be robust for the analysis of sparse data generated in observational studies.

Adult↗

PubMed1999

A variety of gram-positive bacteria carry mobile mef genes.

The mefE gene codes for a membrane bound efflux protein, which confers resistance to macrolides, and has been identified in Streptococcus pneumoniae. A variety of gram-positive organisms were examined. Twenty-six isolates of S. pneumoniae carried mefE and were resistant to erythromycin (MIC of 2-16 mg/L). Two additional isolates of Emr S. pneumoniae carried both ermB and mefE(MIC of 16-128 mg/L). One Micrococcus luteus, one Corynebacterium jeikeium, three Corynebacterium spp., two viridans streptococci and seven Enterocccus spp. also carried mef genes. It was possible to move the mef gene from all 11 S. pneumoniae tested to susceptible S. pneumoniae and/or Enterococcus faecalis recipients. The addition of DNase (1 g/L) did not affect the gene transfer. It was also possible to move the mef gene from donor Enterococcus spp., viridans streptococci, M. luteus, C. jeikeium and Corynebacterium spp. to E. faecalis recipients. Transconjugant isolates were resistant to erythromycin (MIC = 16 mg/L). Hybridization with a labelled mef oligonucleotide probe against Southern blots and bacterial dot blots confirmed the presence of the mef genes. This is the first time that a mobile mef gene has been identified in four different genera, from three distinct geographical locations.

Anti-Bacterial Agents↗

PubMed1997

Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus.

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.

Absorption↗

PubMed1997

Does oral isotretinoin prevent Propionibacterium acnes resistance?

Oral and topical antibiotics play a major role in acne therapy. Physicians base treatment choices on personal perceptions of efficacy, cost-effectiveness or risk-benefit ratios and rarely take bacterial resistance into account. Propionibacterium acnes isolates resistant to one or more anti-acne antibiotics have been reported in Europe, the USA, Japan and New Zealand. Therapeutic failure on some but not all antibiotic regimens is an increasing management problem. In Leeds, UK, resistant strains are found in 60% of acne patients and 50% of close contacts. Recommendations for the use of antibiotics in acne therapy to help prevent the emergence of resistance in P. acnes include the implementation of antibiotic usage policies and the encouragement of improved prescribing habits. Strategies to reduce the resistant P. acnes population are necessary. This paper reports preliminary data demonstrating that oral isotretinoin (Roaccutane/Accutane) significantly reduces total numbers of resistant P. acnes on the skin of all patients.

Acne Vulgaris↗

PubMed1996

Influence of liver cirrhosis on sertraline pharmacokinetics.

Sertraline is a serotonin reuptake inhibitor. The enhancement of serotoninergic transmission is associated with antidepressant activity. In order to determine the pharmacokinetics of sertraline in patients with chronic stable hepatic insufficiency, 10 patients were matched (age, weight, sex) with 10 healthy subjects in an open study. Each participant received a single capsule containing the equivalent of 100 mg sertraline base. Blood samples were taken during 264 h after administration for measurement of plasma concentrations of sertraline. The results confirm that the oral clearance of sertraline is reduced with a 1.7-fold increase in Cmax and a significant prolongation in elimination half-life in hepatically impaired patients.

1-Naphthylamine↗

PubMed1995

Familial tremulous and myoclonic dystonia with white matter changes in brain magnetic resonance imaging.

We report two families with a disorder, probably autosomal recessive, characterized by tremor of juvenile onset, dystonia, and myoclonus with preserved cognitive, cerebellar, and peripheral nervous system functions. During 4 years' follow-up, mild spasticity appeared. Magnetic resonance imaging (MRI) revealed mild diffuse changes in the white matter. Central conduction times for visual, motor, and sensory systems were all prolonged. Extensive metabolic work-up failed to reveal lysosomal, peroxisomal, mitochondrial, or other metabolic abnormalities.

Adolescent↗

PubMed1993

Urinary growth hormone measurements as a marker of renal tubular function in diabetes mellitus.

Urinary growth hormone (UGH) excretion was assessed in 44 adult subjects (10 control, 21 insulin dependent diabetics (Group I), 13 diabetics in poor glycaemic control (Group II)). UGH was markedly elevated in the diabetic population. The UGH excretion in (1) control subjects ranged from undetectable levels to 0.7 microU/h, mean 0.4, (2) Group I 73-422 microU/h, mean 250 and (3) Group II 10-5,283 microU/h, mean 705. There was a significant correlation between UGH excretion and albumin excretion rate (AER) (r = 0.38, P < 0.05) in the subjects studied although only 50% of patients had an AER of > 20 micrograms/min. A stronger correlation was observed between beta 2-microglobulin and UGH excretion (r = 0.7, P < 0.01). There was no significant change in the 6-h serum GH levels following treatment in the patients in Group II. However a 23-79% decline in UGH excretion was observed following improvement of glycaemic control, although UGH levels failed to revert to normal. We conclude that the major factor responsible for increased UGH excretion in DM appears to be reduced tubular reabsorption of the hormone. This test may therefore prove useful as an additional marker for screening for diabetic nephropathy and may help in the understanding of the contribution of renal tubular abnormalities to the nephropathic process.

Adult↗