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Biomedical subjects

D Taylor

Publications and source records attributed to D Taylor.

At least 37 records · Page 2Linked to original sources

Pharmacokinetic interactions involving clozapine.

BACKGROUND: Metabolism of clozapine is complex and not fully understood. Pharmacokinetic interactions with other drugs have been described but, in some cases, their mechanism is unknown. METHOD: Published trials and case reports relevant to the human metabolism of clozapine and to suspected pharmacokinetic interactions were reviewed. RESULTS: Metabolism of clozapine appears to be largely controlled by the function of the hepatic cytochrome p450IA2 (CYPIA2). Compounds which induce CYPIA2 activity (carbamazepine, tobacco smoke) may reduce plasma clozapine levels. Inhibitors of CYPIA2 (caffeine, erythromycin) have the opposite effect. Drugs which inhibit the hepatic cytochrome p4502D6 (CYP2D6) have also been reported to elevate plasma clozapine levels. The mechanism of this interaction is unclear. CONCLUSIONS: The co-administration of clozapine and compounds reported to alter its metabolism should be avoided where possible. A host of other interactions can be predicted and so caution should be exercised when co-administering drugs which affect the function of CYPIA2 and CYP2D6. The pharmacokinetics of clozapine require further investigation so that its safe use can be assured.

Anti-Bacterial Agents

Seeing the forests for the more than the trees.

Assessing the health effects of deforestation is difficult because of the rate at which the world's forests are disappearing. From 1990 to 1995 alone, the world lost a total area of forest cover nearly twice the size of Italy. Deforestation, which is caused by human population growth and encroachment, clearance for agricultural production, and the growing worldwide demand for wood products, has been linked with effects ranging from local changes in climatic and disease patterns to global climate change and biodiversity loss. Deforestation is responsible for about 25% of net annual releases of carbon dioxide into the atmosphere and also lessens the amount of forest available to absorb greenhouse gas emissions. Deforestation also causes a tremendous loss of biodiversity worldwide. It is estimated that over the next 50 years deforestation will rank as the single greatest cause of species loss.

Communicable Diseases

Tricuspid endocarditis following a Papanicolaou smear: case report.

Infective endocarditis is an uncommon complication of obstetrical and gynecological practice and has not been reported in the literature to be associated with Papanicolaou smears. The authors report a nonintravenous drug user who developed group B streptococcal endocarditis of the tricuspid valve following a routine Papanicolaou smear. She required surgical excision of the valve and replacement after failed antibiotic therapy.

Adult

A dominant interfering Myb mutant causes apoptosis in T cells.

The c-Myb transcription factor is required for the production of most hemopoietic lineages, but information is sparse about its mode of action and the key genes it regulates. We have made an inducible dominant interfering Myb protein, by creating a chimera comprising the DNA binding domain of c-Myb, the Drosophila Engrailed repressor domain, and a modified estrogen receptor hormone binding domain. When expressed in the murine thymoma cell line EL4, activation of this mutant results in a significant proportion of the cell population undergoing apoptosis, as assessed by nuclear breakdown and DNA fragmentation, but has no apparent effect on cell-cycle progression. The apoptotic phenotype is mirrored during thymopoiesis in transgenic mice expressing dominant interfering Myb mutants; their T cells are fragile both in vivo and in vitro. Induction of the Myb dominant interfering mutant in EL4 cells correlates with down-regulation of bcl-2, but does not affect transcription of other bcl-2 family members; conversely, overexpression of bcl-2 in the transgenic mouse model rescues thymocytes from death. Analysis of the bcl-2 promoter by run-on transcription, bandshifting, and transient expression assays shows that it is a direct target of Myb. These data suggest a new and important role for Myb proteins as regulators of cell survival during hemopoiesis.

3T3 Cells

Quality and professionalism in health care: a review of current initiatives in the NHS.

Since the start of the 1990s the NHS and the clinical professions have made significant investments in quality management in health care, and a plethora of initiatives has been aimed at service improvement. From a patient's perspective the extent to which these exercises have been cost effective is uncertain, although they have certainly involved great effort and enterprise on the part of many clinicians and managers. An important opportunity now exists to integrate this work into the mainstream of clinical and general service management. If clinicians can accept quality management concepts as central to their professional ethos and regulatory structures this could help them to maintain their professional authority and protect them and their patients from imposed decisions based on inadequate understanding of health care costs and benefits.

Health Policy

Clinical experience with preimplantation genetic diagnosis of cystic fibrosis (delta F508).

Preimplantation genetic diagnosis (PGD) was attempted in 12 couples in whom both parents carry the common delta F508 deletion causing cystic fibrosis (CF). In vitro fertilization (IVF) was followed by cleavage stage biopsy on days 2 and 3 and removal of one or two cells for genetic analysis by nested polymerase chain reaction (PCR) and heteroduplex formation. A total of 18 cycles resulted in 137 normally fertilized embryos, of which 115 developed to cleavage stages and 114 were successfully biopsied. Genetic analysis was successful in 83 embryos (73 per cent). With the remaining embryos, either results from two or more cells were discordant or amplification failed. In 15 cycles, one or two either normal or carrier embryos were transferred and five (33 per cent) clinical pregnancies were established. Five singletons have been born and at birth all five babies have been confirmed as homozygous for the normal allele. Our experience demonstrates that IVF and cleavage stage biopsy consistently provides sufficient embryos, diagnosed as unaffected, for transfer in this autosomal recessive disease and that pregnancy rates are comparable to those following IVF.

Adult

Biochemical epidemiology of gallbladder cancer.

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.

Adult

Immunogenicity and reactogenicity of a combined DTPw-hepatitis B vaccine in Lithuanian infants.

UNLABELLED: A total of 120 healthy Lithuanian infants were enrolled in a double-blind, randomized trial to receive one of two lots of SmithKline Beecham Biologicals' combined diphtheria, tetanus, whole cell Bordatella pertussis hepatitis B (DTPw-HB) candidate vaccine administered according to a 0, 1.5, 3-month, primary immunization schedule (beginning at approximately 3-4 months of age). The immunogenicity (based on the antibody responses elicited by each of the four vaccine components) and the reactogenicity (based on documented solicited and unsolicited symptoms) of this candidate vaccine were evaluated. Of the 120 subjects enrolled, 100 were included in the analysis of immunogenicity. One month after the third vaccine dose, all infants had protective levels of antibodies against HBsAg and tetanus toxoid and all, except one infant, had protective levels of antibodies against the diphtheria toxoid (98.9%). At this time all subjects had responded to the B. pertussis component with antibody titres greater than or equal to the assay cut-off. Data collected for all enrolled infants were included in the analysis of reactogenicity. Most local symptoms were mild and occurred within the first 48 h following vaccination. Redness was the most frequently reported local symptom and irritability was the most frequently reported general symptom. One vaccine-related serious adverse event was reported (fever, diarrhea, vomiting and irritability). This event resolved within 20 h without any complications. CONCLUSION: The combined DTPw-HB vaccine was safe, well-tolerated and immunogenic for all four antigens when administered to a population of healthy infants beginning at 3-4 months of age.

Antibody Formation

Vaginography--investigation of choice for clinically suspected vaginal fistulas.

PURPOSE: Vaginal fistulas are rare but can cause extremely distressing symptoms for patients and prove difficult to define anatomically. Barium studies have been reported as having a maximum sensitivity of only 34 percent for detection of vaginal fistulas. Vaginography is an alternative method for diagnosis and evaluation of suspected vaginal fistulas, which has been reported to have a sensitivity of 100 percent. We reviewed our total experience of vaginography to fully assess its capabilities. METHODS: Twenty-seven patients with clinically suspected vaginal fistulas were investigated with vaginography during a six-year period. Results of vaginograms were compared with final operative or clinical diagnosis and with results of other radiologic investigations. RESULTS: Vaginography successfully identified 19 of 24 fistulas, giving a sensitivity of 79 percent. In our series, barium enema was only able to identify 9 percent of fistulas arising from the colon. CONCLUSIONS: In this, the largest series of vaginograms, apparent reduction in sensitivity from the 100 percent quoted in earlier series to 79 percent probably represents a more accurate assessment of vaginography as a diagnostic investigation. Even allowing for this reduction, vaginography is still the most sensitive, economic, and informative investigation for identification and delineation of vaginal fistulas. We recommend that vaginography be the initial investigation of choice in patients with clinically suspected vaginal fistulas.

Adult

Delayed visual maturation in infants: a disorder of figure-ground separation?

Delayed visual maturation (DVM) is characterised by visual unresponsiveness in early infancy, which subsequently improves spontaneously to normal levels. We studied the optokinetic response and recorded pattern reversal VEPs in six infants with DVM (aged 2-4 months) when they were at the stage of complete visual unresponsiveness. Although no saccades or visual tracking with the eyes or head could be elicited to visual objects, a normal full-field rapid buildup OKN response occurred when viewing biocularly or during monocular stimulation in the temporo-nasal direction of the viewing eye. Almost no monocular OKN could be elicited in the naso-temporal direction, which was significantly poorer than normal age-matched infants. No OKN quick phases were missed, and there were no other signs of "ocular motor apraxia." VEPs were normal in amplitude and latency for age. It appears, therefore, that infants with DVM are delayed in orienting to local regions of the visual field, but can respond to full-field motion. The presence of normal OKN quick-phases and slow-phases suggests normal brain stem function, and the presence of normal pattern VEPs suggests a normal retino-geniculo-striate pathway. These oculomotor and electrophysiological findings suggest delayed development of extra-striate cortical structures, possibly involving either an abnormality in figure-ground segregation or in attentional pathways.

Attention

Use of occlusive dressings on central venous catheter sites in hospitalized children.

Although the use of occlusive dressings in adults has been criticized in the literature, there has been little written on their use in the pediatric population. Management of dressing sites requires nursing judgement unique to this population. This study focused on the progression of microbial colonization and signs of inflammation occurring beneath repeated occlusive dressings applied to central venous catheter (CVC) insertion sites among 104 hospitalized children (neonate to 18 years). A noninvasive skin culture was obtained within 24 hours of CVC placement, 3 to 7 days later before the next routine dressing change, and at the time the CVC was discontinued or the child was discharged, whichever occurred first. Results showed a significant increase in microbial growth (p < or = .001) at the second dressing change, when serosanguinous drainage was heaviest, and continued significant growth (p < or = .001) when the dressing was discontinued. This microbial growth pattern was curious in the face of a 0.3% systemic sepsis rate. When neonates under 1,800 g were excluded from calculation, the pattern was not notable (p = .2119). Findings suggest the use of occlusive dressings during prolonged hospitalization for tunnelled CVCs does not lead to increased site infections in children over 1,800 g.

Adolescent

The effectiveness of papilledema as an indicator of raised intracranial pressure in children with craniosynostosis.

Craniosynostosis management partially depends on the detection and treatment of elevated intracranial pressure (ICP). Examination for papilledema is considered to be the most reliable screening method for identifying raised ICP, but its effectiveness has not been defined. One hundred and twenty-two children with craniosynostosis who underwent funduscopic examinations and then Camino ICP monitoring were studied. All eye examinations were performed by an ophthalmologist after pharmacological pupillary dilation. Fifteen patients (12%) had papilledema. Subsequent ICP monitoring showed that the median ICP was 12.7 mm Hg, with 41 patients (34%) having elevated ICPs (> 15 mm Hg). Those with papilledema had higher ICPs (17.5 +/- 3.2 versus 12.7 +/- 5.5 mm Hg), were older (5.9 +/- 4.7 versus 1.9 +/- 2.6 years), and were more likely to have craniofacial syndromes (73 versus 41%) than those without papilledema (P < 0.05). Patients with both elevated ICPs and papilledema were older (5.9 +/- 4.7 versus 1.6 +/- 1.4 years) and more likely to have multiple-suture synostosis (92 versus 61%) than those with elevated ICPs and no papilledema (P < 0.05). The presence of papilledema was a specific (98%) indicator of raised ICP, but its sensitivity was age-dependent. It was 100% sensitive in children older than 8 years, but it indicated elevated ICP in only 22% of younger patients. These results suggest that ICP monitoring to document elevated ICP is unnecessary in children older than 8 years who have detailed ophthalmological examinations. In the younger child, the presence of papilledema reliably indicates elevated ICP but its absence does not rule out elevated ICP; formal ICP measurement has a greater role in detecting elevated ICP in these patients.

Adolescent

Clinical manifestations and molecular epidemiology of five cases of diarrhoea in children associated with Vibrio metschnikovii in Arequipa, Peru.

In April 1994, Vibrio metschnikovii was isolated from five infants with watery diarrhoea in Arequipa, Peru, as part of a passive cholera surveillance system. The children ranged in age from 11 to 20 months and had acute diarrhoea, with two cases showing moderate dehydration. Two children also had traces of blood in liquid stool. The children were seen at two different hospitals, and no evidence of a common source of infection was found. No additional V. metschnikovii isolates were identified in the remaining surveillance period that covered the rest of 1994 and 1995. However, stool samples were not screened for enteric pathogens other than vibrios. V. metschnikovii strains isolated from stool samples produced opaque and translucent colonies on agar plates, suggesting capsular material. All isolates were resistant to ampicillin, erythromycin and streptomycin. Plasmid analysis revealed a common 200-kb plasmid in isolates from all cases and an additional 2.7-kb plasmid in three of the isolates. Ribotyping of each isolate after restriction with BglI and HindIII endonucleases demonstrated identical ribotyping patterns. The cases reported suggest that V. metschnikovii may be associated with diarrhoea in man by mechanisms so far unknown.

Acute Disease

Breast MRI: early experience with a 3-D fat-suppressed gradient echo sequence in the evaluation of breast lesions.

The early clinical experience with a 3-Dimensional Fourier Transform Gradient Echo sequence with fat suppression in the evaluation of breast masses is reported. Ten female patients with breast malignancies were pre-operatively evaluated with this sequence and the results compared with the pathological specimens. The scanning protocol included a non-contrast sequence followed by an immediate post-contrast sequence (completed 4.5 min after intravenous contrast injection) and a delayed sequence. Images were assessed for maximum lesion and parenchymal enhancement, lesion size and additional enhancing abnormalities. In six patients, malignant masses enhanced maximally on the immediate post-contrast sequence with parenchyma enhancing maximally on delayed images. In three cases, there was preferential enhancement of malignant lesions over normal parenchyma but to a similar degree on both post-contrast sequences. In one case, both the lesion and parenchyma enhanced maximally on the delayed sequence. Magnetic resonance assessed lesion size accurately and also detected satellite malignancies in one case. However, lesion grade, associated in situ carcinoma and lymphovascular invasion did not impact on lesion enhancement. In this small series, a contrast-enhanced, fat-suppressed 3-D Gradient Echo Sequence detected breast carcinoma with high sensitivity. The technique holds promise but further evaluation is required.

Breast