Research and patient care: what needs review and by whom?
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Biomedical subjects
Publications and source records attributed to B Evans.
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The bioavailability of phenytoin from ACC-9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC-9653 to healthy volunteers. Absolute bioavailability of phenytoin derived from ACC-9653 in each subject was calculated as the ratio of the phenytoin area under the plasma concentration time curve for time 0 to infinity [AUC(0-inf)] after ACC-9653 divided by the phenytoin AUC(0-inf) after intravenous sodium phenytoin. The mean absolute bioavailability of ACC-9653 was 0.992 after intravenous administration and 1.012 after intramuscular administration. These data establish that the bioavailability of ACC-9653 is complete following intravenous or intramuscular administration in single-dose volunteer studies. The absolute bioavailability of phenytoin derived from ACC-9653 in subjects with therapeutic plasma phenytoin concentrations is being studied in patients given simultaneous infusions of stable isotope-labeled tracer doses of ACC-0653 and sodium phenytoin.
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Response to second-line therapy in relapsing patients with small cell lung carcinoma (SCLC) is often claimed to be evidence in favour of non-cross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were retreated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 2-4 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.
Blood samples were obtained from two male and two female platypuses at various times after capture and anaesthesia for other experimental purposes. In samples obtained during ketamine-xylazine or pregnanediol anaesthesia 15-24 h after capture, the concentration of total glucocorticoids, measured as 'cortisol equivalent' in a radioligand assay, was 207-620 nmol/l. In samples taken 14-35 h after injection of dexamethasone (0.2 mg/kg) total glucocorticoid concentration was 79-88 nmol/l. Individual glucocorticoids were isolated on columns of Sephadex LH-20 and measured separately against appropriate standards. In all except two haemolysed samples obtained from a male that died 25 h after capture, the major glucocorticoid behaved as cortisol, contributing 77-94% of the total. The remainder was made up of varying proportions of substances behaving as corticosterone, 11-deoxycortisol and cortisone. In the haemolysed samples from the moribund animal the major reactive substance, contributing 52-54% of the total, behaved as cortisone. The total adrenal gland weight of this animal was 747 mg, compared with 200-286 mg in two others, suggesting preceding exposure to stress. Equilibrium dialysis and polyacrylamide gel electrophoresis (PAGE) revealed no evidence for a transcortin-like glucocorticoid- and progesterone-binding protein in platypus plasma. However, as in the echidna, there was a heat-labile, high-capacity binding system migrating with albumin on PAGE. Glucose was undetectable in the plasma of the moribund animal and only 1.7-2.8 mmol/l in the initial plasma samples from the others. In two animals, injection of glucose i.p. and dexamethasone i.m. was followed by an increase in the plasma concentration of glucose to the range 3.8-9.9 mmol/l and commencement of normal swimming and feeding activity for the next 36-48 h.
The purpose of the present study was to describe the relations among various perinatal, environmental, and demographic measures in a sample of low birth weight infants and to relate those measures to 1-year developmental status. Perinatal variables included birth weight, gestational age, Apgar scores, and summary measures of respiratory distress and morbidity. Home visits provided ratings of the infants' environment at 7 and 12 months corrected age. The Bayley Scales of Infant Development were given at the 12-month home visit. A principal components factor analysis revealed four factors. The first factor was labeled an immaturity-illness factor, since it was primarily composed of gestational age, birth weight, and the respiratory distress and morbidity summary scores. Ratings of the infant's home environment loaded on the second factor, the demographic variables on the third factor, and the 1- and 5-minute Apgar scores comprised the fourth factor. The four factor scores together with the number of delays on the Denver Developmental Screening Test, given at 7 months corrected age, were entered as independent variables in four multiple regression analyses with the corrected and uncorrected mental development index index (MDI) and psychomotor development index (PDI) Bayley scores as the dependent variables. These regression analyses indicated that 1-year developmental status is a reflection of the infant's immaturity and neonatal morbidity, the quality of his or her home environment, and freedom from sensorimotor delays.
Twenty patients with previously untreated ovarian cancer received intensive chemotherapy after initial surgery. Treatment comprised two courses of cyclophosphamide at 7 g/m2 with mesna, re-evaluation with second-look laparotomy where appropriate, followed by five courses of cisplatin at 100 mg/m2. Three patients achieved pathologically documented complete remission (PDCR) with high-dose cyclophosphamide, and eight patients achieved partial remission. Fifteen patients went on to receive cisplatin. Nine of these patients had no assessable disease; of six patients who were assessed for response two achieved PDCR and three achieved partial remission. The overall response rate to the sequential regimen was 14/20 (70%). High-dose cyclophosphamide was associated with marked haematological toxicity, which was cumulative and fatal in two patients. The median duration of first remission was 14 months, and the median duration of survival was 20 months. It is concluded that sequential treatment with high-dose cyclophosphamide and cisplatin appears to be no more effective than conventional treatment in advanced ovarian cancer, judging by the PDCR rate and median survival achieved.
Accurate type assignment of the different HPV types which infect the female genital tract, is essential in view of the differing pathological potential of the common virus types present in the cervix. We have developed hybridisation, washing and autoradiography conditions that minimise cross-hybridisation on filters and so allow clear-cut type assignment. We describe the conditions in this paper and have used this method to screen for HPV infection in clinical populations.
A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, we constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the "CCAAT box." Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene.
ABH antigens have been demonstrated in the posterior root ganglia (PRG) of 3 primate species (marmoset, baboon and man). Their expression corresponded to the ABO phenotype of the individual and was independent of the secretor gene. In marmosets more cells were positive for H (33 +/- 9%) than for A (19 +/- 6%). In baboons A or B antigens were more easily detected (66 +/- 9%) than the H antigens (48 +/- 5%). In humans more than two-thirds of PRG cells were positive for H but only a small proportion of these were positive for A or B. The ABH antigens were found mainly in the small and intermediate-size neurons whose central processes project to lamina II of the spinal cord posterior horn. Unipolar neurons of the Gasserian ganglion, neurons of the mesencephalic nucleus of the trigeminal nerve and of some visceral ganglia have also been shown to express these antigens which are also present in the fibre layer and glomeruli of the olfactory bulbs.
In an outbreak of gastroenteritis on board a cruise ship 251 passengers and 51 crew were affected and consulted the ship's surgeon during a 14-day period. There was a significant association between consumption of cabin tap water and reported illness in passengers. Enterotoxigenic Escherichia coli were isolated from passengers and crew and coliforms were found in the main water storage tank. Contamination of inadequately chlorinated water by sewage was the most likely source of infection. A low level of reported illness and late recognition of the outbreak delayed investigation of what was probably the latest in a series of outbreaks of gastrointestinal illness on board this ship. There is a need for a national surveillance programme which would monitor the extent of illness on board passenger cruise ships as well as a standard approach to the action taken when levels of reported illness rise above a defined level.
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Sixty-one patients with FIGO stage III ovarian carcinoma and 30 patients with stage IV ovarian carcinoma were randomized to receive either high-dose cisplatin (100 mg/m2) or low-dose cisplatin (20 mg/m2) and chlorambucil. Overall response rates were similar in both arms, with 68% and 49% of stage III patients and 61% and 72% of stage IV patients responding to high-dose cisplatin and the combination, respectively. There was a strong trend for better survival in stage III (P less than .05) but not in stage IV patients treated with cisplatin alone. The toxicity suffered by patients treated with high-dose cisplatin was severe, and in 15 patients cisplatin therapy was stopped because of unacceptable toxicity.
A cDNA library from lamprey liver was constructed in pBR322 and screened with a synthetic mixed oligonucleotide probe, the sequence of which was based on a partial amino acid sequence of the lamprey fibrinogen gamma chain determined by conventional procedures. Among the positive clones was one containing a 600-base insert that covered the carboxy-terminal third of the chain and another with a 1950-base insert that stretched more than full length. The two inserts were sequenced by the Maxam-Gilbert procedure. The DNA sequencing was corroborated by reference to the amino acid sequences of five cyanogen bromide peptides that compose the carboxy-terminal 130 amino acids, as well as to a number of tryptic peptides from elsewhere in the molecule. The clone with the smaller insert (6G) contained 594 nucleotides (not counting G and C tails), 435 of which are coding and correspond to residues 264-408 of the gamma chain. The remaining 159 nucleotides included the terminator codon followed by a noncoding segment. The larger clone (2E) coded for 408 amino acids that could be readily aligned with the 411-residue human gamma chain. A 24-residue signal peptide adjacent to the proposed amino terminal was also inferred. The amino acid sequence of the fibrinogen gamma chain has been differentially conserved during evolution, the lamprey and human sequences being more than 70% identical in certain key regions but dropping to less than 25% in other sections, including the segment thought to be a part of the "coiled coils". Overall, the resemblance amounts to 50% identity. Of the 10 cysteines found in mammalian chains, 9 are at identical positions, but the tenth, which in mammalian fibrinogens is a part of the interdimeric bridging, is absent in the lamprey.
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Afferent pupillary defects may accompany asymmetric primary open-angle glaucoma, though the exact incidence has not been reported. Charts were reviewed on 89 patients attending the Glaucoma/Uveitis Clinic at the North Carolina Memorial Hospital in Chapel Hill, North Carolina over a five-year period. All patients had primary open-angle glaucoma diagnosed by: (1) increased ocular tensions (22 mmHg) in the presence of open-anterior-chamber angles and (2) optic-nerve cupping and atrophy compatible with (3) pressure-dependent, visual-field loss. No subjects with secondary glaucomas, primary-angle-closure glaucoma, or ocular hypertension are included.The presence of the relative afferent pupillary defect was noted in 21 of 89 patients (23 percent). Sixteen of 70 black patients had relative afferent pupillary defect in the more severely affected eye, while five of 19 white patients demonstrated afferent pupils. Other demographic characteristics of this population are described. Two typical primary-open-angle glaucoma patients are discussed to demonstrate comparable changes within the optic nerves and Goldmann visual fields. The presence of the relative afferent pupillary defect best correlates with asymmetric, visual-field loss in the more severely affected eye.