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Biomedical subjects

T Webb

Publications and source records attributed to T Webb.

At least 37 records · Page 2Linked to original sources
PubMed2000

Familial Prader-Willi syndrome: case report and a literature review.

Prader-Willi syndrome (PWS) is a neurobehavioural disorder arising through a number of different genetic mechanisms. All involve loss of paternal gene expression from chromosome 15q11q13. Although the majority of cases of PWS are sporadic, precise elucidation of the causative genetic mechanism is essential for accurate genetic counselling as the recurrence risk varies according to the mechanism involved. A pair of siblings affected by PWS is described. Neither demonstrates a microscopically visible deletion in 15q11q13 or maternal disomy. Methylation studies at D15S63 and at the SNRPN locus confirm the diagnosis of PWS. Molecular studies reveal biparental inheritance in both siblings with the exception of D15S128 and D15S63 where no paternal contribution is present indicating a deletion of the imprinting centre. Family studies indicate that the father of the siblings carries the deletion which, he has inherited from his mother. The recurrence risk for PWS in his offspring is 50%.

Alleles↗
PubMed2000

Reversal of rapacuronium block during propofol versus sevoflurane anesthesia.

UNLABELLED: We studied the antagonism of rapacuronium with edrophonium-atropine during propofol- or sevoflurane- based anesthesia in 60 healthy outpatients. After the induction of anesthesia with standardized doses of propofol and fentanyl, rapacuronium 1.5 mg/kg was administered to facilitate tracheal intubation. Patients were randomized to receive either a propofol infusion (100 microg. kg(-1). min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular block was monitored by using electromyography at the wrist and reversed with edrophonium 1.0 mg/kg and atropine 0.015 mg/kg when the first twitch (T(1)) response of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. The clinical duration of action (i.e., time to 25% T(1) recovery) was similar during both propofol (13.1 +/- 3.6 min) and sevoflu-rane (13.7 +/- 4.4 min) anesthesia. The time from 25% T(1) recovery to TOF ratio of 0.8 was also similar with propofol (3.4 +/- 2.1 min) and sevoflurane (5.9 +/- 8.7 min) (P > 0.05). Although none of the patients in the propofol group required more than 9 min to achieve a TOF ratio of 0. 8, two patients receiving sevoflurane required 31 min and 37 min. Adequate antagonism of rapacuronium block with edrophonium can be achieved within 10 min during propofol anesthesia. However, more prolonged recovery may occur in the presence of sevoflurane. IMPLICATIONS: We studied the reversal of rapacuronium-induced block with edrophonium and found that the residual rapacuronium block can be readily antagonized during propofol-based anesthesia. However, reversal of rapacuronium appears to be less predictable during sevoflurane-based anesthesia.

Adolescent↗
PubMed2000

Spontaneous recovery profile of rapacuronium during desflurane, sevoflurane, or propofol anesthesia for outpatient laparoscopy.

UNLABELLED: We evaluated the spontaneous recovery characteristics of rapacuronium during desflurane-, sevoflurane-, or propofol-based anesthesia in 51 consenting women undergoing laparoscopic tubal ligation procedures. After the induction of the anesthesia with standardized doses of propofol and fentanyl, 1.5 mg/kg IV rapacuronium was administered to facilitate tracheal intubation. Patients were randomized to receive either 1 minimum alveolar anesthetic concentration of desflurane, 1 minimum alveolar concentration of sevoflurane, or 100 microg. kg(-1). min(-1) propofol infusion in combination with 66% nitrous oxide in oxygen for maintenance of anesthesia. Neuromuscular blockade was monitored at the wrist by using electromyography. The degree of maximum blockade and the times for first twitch recovery (T(1)) to 5%, 25%, 50%, 75%, and 90%, as well as the recovery index, were similar in all three anesthetic groups. However, recovery times for the train-of-four ratio to achieve 0.7 and 0.8 were significantly longer with desflurane (44.4 +/- 18.9 and 53.5 +/- 22.4 min) and sevoflurane (44.8 +/- 15.1 and 53.2 +/- 15.8 min) compared with propofol (31.8 +/- 5.3 and 36.5 +/- 6.5 min). Eight patients (16%) required a maintenance dose of 0.5 mg/kg rapacuronium and reversal of rapacuronium residual block occurred in three (6%) patients. We conclude that spontaneous recovery after an intubating dose of 1.5 mg/kg rapacuronium was significantly prolonged by both desflurane and sevoflurane compared with propofol-based anesthesia. Routine monitoring of neuromuscular activity is recommended even when a single bolus dose of rapacuronium is administered during ambulatory anesthesia. IMPLICATIONS: When administered for laparoscopic surgery, the duration of action of an intubating dose of rapacuronium was prolonged 40%-50% by desflurane and sevoflurane, respectively, (versus propofol). Monitoring recovery of neuromuscular blockade produced by rapacuronium is particularly important when desflurane or sevoflurane is administered to ensure that an adequate recovery (train-of-four > or = 0.8) is achieved by the end of anesthesia.

Adult↗
PubMed2000

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: To evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top-grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions on persons and coded by a systematic context-sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16 (range, 0-110). Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in 4 of 5 cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Humans↗
PubMed2000

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: The purpose of this study was to evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions upon persons and coded by means of a systematic context sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16, with a range from 1 to 110. Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in four of five cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Americas↗
PubMed1999

The cytotoxicity and mode of action of 2,3,4-trisubstituted pyrroles and related derivatives in human Tmolt4 leukemia cells.

4-Carbethoxy-1-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybenzoyl)-3-(4-methoxyphenyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g., human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase alpha, RNA polymerases, nucleoside kinase and ribonucleoside reductase.

Animals↗
PubMed1998

Cytotoxicity of substituted alkyl-3,4-bis(4-methoxyphenyl)pyrrole-2-carboxylates in L1210 lymphoid leukemia cells.

Two alkyl-3,4-bis(4-methoxyphenyl)pyrrole-2-carboxylates proved to be potent cytotoxic agents in the murine L1210 lymphoid leukemia screen. DNA synthesis was preferentially inhibited with the major target of the agents being de novo purine biosynthesis at the regulatory enzyme sites of PRPP-amido transferase and IMP dehydrogenase. Other enzymatic activities which were suppressed by the drugs were DNA polymerase alpha, RNA polymerases, ribonucleoside reductase and dihydrofolate reductase. The d[NTP] pools, nucleoside kinase and the pyrimidine pathway were not affected by the presence of drugs. The DNA molecule itself was not the target of the agents, i.e. no alkylation of nucleotide bases, intercalation between bases or cross-linking of DNA strands occurred. The agents did cause L1210 DNA fragmentation after 24 h incubation at 100 microM.

Animals↗
PubMed1998

A clinical, cytogenetic and molecular study of ten probands with supernumerary inv dup (15) marker chromosomes.

Ten probands with moderate to severe developmental delay were found to have a supernumerary inv dup (15) chromosome. These patients and their families were studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms associated with the 15p short arm suggested a maternal derivation for the marker chromosome in all informative cases. One marker was directly maternally inherited. Molecular analysis employing Southern blotting and polymerase chain reaction (PCR) of microsatellite repeats demonstrated the presence of extra alleles in the 15q11q13 region. All ten of the probands demonstrated an extra band at one or more locus without recourse to densitometry. All of the inv dup (15) markers were comparable in size to a G group chromosome but there were differences in the positions of the breakpoints in 15q. There was an inconsistent relationship between marker size, gene dosage and severity of phenotype.

Adolescent↗
PubMed1998

Prader-Willi syndrome and psychotic symptoms: 1. Case descriptions and genetic studies.

Six people with Prader-Willi syndrome (PWS) who developed psychoses are described. Along with other literature reviewed in the present paper, the results imply an association between PWS and psychotic symptoms. Genetic studies were possible in five cases and SNRPN expression was examined in three cases. Maternal uniparental disomy and 15q11q13 deletions were found, demonstrating that psychotic symptoms are not associated with a single type of genetic abnormality.

Adolescent↗
PubMed1998

Affective psychosis and Prader-Willi syndrome.

Previous studies have demonstrated that maladaptive behaviours are common amongst adults with Prader-Willi syndrome (PWS). Case reports have also previously demonstrated that psychosis can occur amongst adults with PWS. The present study was undertaken in order to gain a better understanding of the psychopathology of the psychosis of PWS. Twenty-three out of 25 adults identified with PWS living in Northamptonshire, UK, agreed to participate. Comprehensive psychiatric assessments (using the PPS-LD), and measures of adaptive and maladaptive behaviours (using the AAMR-ABS) were completed. Comparisons were made for the prevalence of psychiatric disorders against those from a previous epidemiological study of adults with intellectual disability of other aetiologies from a neighbouring county. The PWS group was found to have higher rates of affective disorders (a point prevalence of 17.4%), in which psychotic symptoms were common, but similar rates of schizophrenia/delusional disorders (4.3%) compared with the comparison group. Behaviour disorders were also common. Surprisingly, none of the PWS group was found to have generalized anxiety or phobic disorders. The diagnostic criteria for the episodes including psychotic symptoms are explored. The high rates of affective disorders is of clinical (i.e. treatment) importance as well as being of academic interest with regard to the genetics of psychiatric disorders.

Adult↗
PubMed1998

Linkage analysis in Rett syndrome families suggests that there may be a critical region at Xq28.

A whole X chromosome study of families in which Rett syndrome had been diagnosed in more than one member indicated that the region between Xq27 and Xqter was the most likely region to harbour a gene which may be involved in the aetiology of the disease. Further, more detailed studies of Xq28 detected weak linkage and a higher than expected sharing of maternally inherited alleles. It is suggested that there may be more than one gene involved in the aetiology of this syndrome, particularly as the very rare families in which more than one girl is affected often show variable clinical symptoms.

Alleles↗
PubMed1998

Pneumothorax and pneumomediastinum during colonoscopy.

A case of bowel perforation during diagnostic colonoscopy is reported. This resulted in the sudden appearance of massive subcutaneous emphysema of the neck, causing acute upper airway obstruction which necessitated urgent endotracheal intubation. Large bilateral pneumothoraces and pneumomediastinum were also present.

Aged↗
PubMed1997

Protease digestion studies of an equilibrium intermediate in the unfolding of creatine kinase.

Protease digestion experiments have been used to characterize the structure of an equilibrium intermediate in the unfolding of creatine kinase (CK) by low concentrations (0.625 M) of guanidine hydrochloride (GdnHCl). Eighteen of the major products of digestion by trypsin, chymotrypsin and endoproteinase Glu-C have been identified by microsequencing after separation by SDS/PAGE and electroblotting on poly(vinylidene difluoride) membranes. The C-terminal portion (Gly215 to Lys380) was much more resistant to digestion than the N-terminal portion (Pro1 to Gly133), although the area most sensitive to proteolysis was in the middle of the CK sequence (Arg134 to Arg214). These experiments are consistent with the two-domain model for the CK monomer. The structure of the intermediate is proposed to consist of a folded C-terminal domain and a partly folded N-terminal domain separated by an unfolded central linker. Protease susceptibility is clustered within two N-terminal regions and one central region. These regions are evidently exposed as a result of the partial unfolding and/or separation of the N-terminal domain. Further evidence for the structure of this intermediate comes from gel filtration studies. Treatment of CK with 0.625 M GdnHCl resulted in slow aggregation at 37 degrees C, but not at 12 degrees C, a phenomenon previously reported for phosphoglycerate kinase. The aggregation did not occur at higher GdnHCl concentrations and was unaffected by a reducing agent. It is proposed that aggregation is a consequence of non-specific interactions between hydrophobic regions, possibly domain/domain interfaces, which become exposed in the intermediate.

Amino Acid Sequence↗
PubMed1996

Prevalence of fragile X syndrome.

The much-quoted prevalence figure of 1:1,000 males for fragile X syndrome is an overestimate in a mixed ethnic population. A reexamination of the individuals from whom those data were derived using molecular diagnostic techniques demonstrates a more realistic figure of 1:4,000 males.

Female↗
PubMed1996

Long-term benefits of aggressive treatment for primary colorectal cancer.

The long-term follow up of 128 colorectal cancer patients is reported. Seventy-nine percent (101/128) of the patients had curative resections: 70 patients had radical lymphadenectomies with wide removal of tumor-adjacent nodes, and 31 patients had standard resections. The 5-year overall survival rates for Dukes' stage B and C patients and for all rectosigmoid cancer patients significantly favored radical resection (60% vs. 38%, 57% vs. 29%, respectively, P < 0.05). Tumor-free survival rates were also higher after radical lymphadenectomy but did not reach statistical significance. Eleven percent (14/128) of the patients required multiorgan resections, and/or preoperative radiation to render fixed cancers resectable, and these patients had a 10-year tumor-free survival rate of 45%, compared to zero % 5-year survival for the 27 patients who underwent palliative procedures (P < 0.01). These results confirm that many colorectal cancer patients will be cured with aggressive treatment and they support the need for a controlled trial for evaluation of lymphadenectomy for this disease.

Adult↗