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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 199 records · Page 11Linked to original sources

An open study of the pharmacokinetics and the tolerability of raclopride extended release capsules in psychiatric patients.

Following a 4-7 day drug-free washout period, eight male inpatients took an extended-release (ER) formulation of raclopride. After the initial 8 mg dose on day 1 of the study, repeated plasma samples were collected over the ensuing 36 h. Subsequently, patients received raclopride 8 mg b.i.d. through day 7, 12 mg b.i.d. through day 14, and, if tolerated, 16 mg b.i.d. through day 21. On days 7, 14, and 21, repeated plasma samples were drawn over the 12 h following the morning dose. Relative to the previously studied immediate release form of raclopride, the ER formulation delayed and extended the absorption of raclopride, and produced lower maximum raclopride concentrations. Linear kinetics were preserved across the dose range studied. Two patients could not tolerate the highest raclopride dose because of extrapyramidal side effects.

Adult↗

Prevention and treatment of Staphylococcus aureus infections with recombinant cytokines.

Antibiotic therapy is only moderately efficacious for bovine Staphylococcus aureus mastitis. We have used recombinant bovine cytokines to activate the natural host defenses, to prevent and treat bovine mastitis. Uninfected mammary glands infused with GM-CSF or IL-2 increased the percentage of phagocytic cells in the milk by 2-3 fold. IL-1 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and had no effect on phagocytosis. Treatment with IL-2 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. GM-CSF had no effect on the number polymorphonuclear cells in the milk but enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. All cytokines were effective in preventing S. aureus infections (20-100%). 52% of all chronically infected mammary gland quarters treated with three doses of IL-2 responded to therapy and 32% of the treated quarters remained cured. 75% of all mammary glands treated with three doses of IL-1 beta responded to therapy by clearing the infection and 22% of the treated glands remained cured. These studies demonstrate that recombinant bovine cytokines can be used effectively to prevent infections as well as treat established chronic infection.

Animals↗

Efficient transmission of tick-borne encephalitis virus between cofeeding ticks.

Most of the data on oral infections of ticks with tick-borne encephalitis virus have been derived from experiments using animals infected by syringe inoculation. To mimic the natural conditions of virus transmission, tick-borne encephalitis virus-infected Ixodes ricinus (Linnaeus) or Rhipicephalus appendiculatus Neumann adults (donors) were cofed with uninfected nymphs (recipients) of either tick species on uninfected guinea pigs. Two tick-retaining cells were attached to each guinea pig: cell 1 contained uninfected nymphs and virus-infected adults, and cell 2 contained uninfected nymphs. Following engorgement, 55% of I. ricinus nymphs and 65% of R. appendiculatus nymphs were shown to have acquired the virus while cofeeding with I. ricinus donor ticks. Similarly, 66% of R. appendiculatus recipient nymphs that cofed with R. appendiculatus virus-infected adults were infected. Some of the guinea pigs on which the ticks cofed were apparently nonviremic. The results indicate that efficient transmission of tick-borne encephalitis virus can occur between cofeeding ticks even when the host on which they feed does not develop a detectable viremia.

Animals↗

Efficacy of diazepam and meperidine in ambulatory pediatric patients undergoing endoscopy: a randomized, double-blind trial.

Medications are routinely administered to children prior to upper gastrointestinal endoscopy procedures. We evaluated the efficacy and safety of four dosage regimens: meperidine 2 mg/kg (M); low-dose meperidine 1 mg/kg and diazepam 0.1 mg/kg (M low+D); high-dose meperidine 2 mg/kg and diazepam 0.1 mg/kg (M high+D); and, diazepam 0.1 mg/kg (D) in a randomized, double-blind trial in 71 pediatric patients (ages 1 to 19 years). Cooperation, emotional state, and sedation were rated. The frequency of negative behavior demonstration (i.e., crying, gagging, flailing, nervous behavior) indicating ineffective or inadequate sedation was recorded before, during, and after the procedure. Vital signs and oxygen saturation were noted. Significant differences were observed in the efficacy of the various sedation regimens. Overall, the physicians and nurses rated M most effective in children < 11 years. In these children, M high + D and D were rated least effective by the nurses, whereas physicians felt that D was least effective. In the older children, M, M low + D, and M high + D were rated similarly effective by physicians and nurses, and D was rated least effective. In both age groups, the lowest incidence of negative behaviors during the endoscopy procedure occurred in patients who received M. Combinations of D and M + D resulted in an increased incidence of negative behaviors; thus, M may be the preferred sedation regimen in children undergoing endoscopy. The addition of diazepam to meperidine may be detrimental in terms of eliciting negative behaviors.

Adult↗

Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extracts.

To investigate the role of ticks in TBE virus transmission, salivary gland extract (SGE) was derived from partially fed female Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus appendiculatus ticks. Guinea-pigs were infested with uninfected R. appendiculatus nymphs and inoculated with a mixture of TBE virus and SGE or with virus alone. The number of ticks which on average acquired virus from feeding on animals inoculated with TBE virus and SGE from partially fed ticks was 4-fold greater than the number that became infected by feeding on animals inoculated with virus alone or virus plus SGE from unfed I. ricinus. Viraemia was detected in 67% of guinea-pigs inoculated with virus plus SGE compared to 30% of guinea-pigs inoculated with virus alone. Virus titres in the blood were similar for both groups of animals [range 2.0-2.8 log10 plaque-forming units (PFU)/ml of blood]; however, the number of ticks that became infected was significantly higher on animals inoculated with virus plus SGE from partially fed ticks. No significant difference was observed with respect to the tick species used to derive SGE. The results indicate that TBE virus transmission is enhanced by factor(s) associated with the salivary glands of feeding ticks, and that these factor(s) may facilitate efficient transmission of TBE virus between infected and uninfected ticks even when they feed on hosts that have no detectable viraemia.

Animals↗

School health education in the European Community.

The School Health Education Commission of the European Community is making efforts to improve school health education in the European Community countries. While past efforts have involved single issue causes, current activities emphasize a holistic perception of school health education. Radical education reforms throughout the European Community advocate improved health education. The movement toward quality health education in the European Community countries uses a model called the Health Promoting School, a cooperative effort involving schools, families, and communities. The model is being promoted through three stages: 1) national conferences held in each European Community country, 2) summer schools to provide teacher training, and 3) national projects, supported by the World Health Organization, agreement conducted to determine the efficacy of the Health Promoting School Model.

Europe↗

Retrieval and allocation of organs for transplantation: the Michigan experience.

The Organ Procurement Agency of Michigan (OPAM) is now in its twenty-third year of service to the transplant community in Michigan. From a beginning with one coordinator in 1971, it now employs 53 individuals, including 8 laboratory technologists for its own on-site histocompatibility laboratory, a dozen procurement coordinators stationed throughout the state, 6 organ placement coordinators in the main office, 6 screening coordinators who provide around-the-clock coverage at the office, a tissue recovery section, as well as additional finance, education, and administrative support staff. This chapter outlines the history and growth in organ recoveries of the organization. More importantly, the chapter also analyzes the Michigan experience regarding racial distribution of kidneys. While African-Americans comprise 14% of the general population of the state, they comprise 40% of the waiting kidney recipients and only 26% of the actual recipients. Depending upon blood type, average waiting time for a kidney for African-Americans can be up to 4 months longer than for Whites. The analysis attributes this variance primarily to the allocation methodology for kidney distribution, which is largely driven by antigen matching and secondarily to the generally greater frequency and higher degree of blood sensitization among African-Americans, which causes a substantially higher frequency of positive-crossmatch results between potential donor and recipient. The authors conclude that changes in the present allocation system could be made to achieve greater equity for African-American patients, without removing the advantages inherent in transplanting kidneys with closely matched antigens.

ABO Blood-Group System↗

Characterization of phycocyanin produced by cpcE and cpcF mutants and identification of an intergenic suppressor of the defect in bilin attachment.

Mutants of the cyanobacterium Synechococcus sp. PCC 7002 constructed by the insertional inactivation of either the cpcE or cpcF gene produce low levels of spectroscopically detectable phycocyanin. The majority of the phycocyanin produced in these strains appears to lack the alpha subunit phycocyanobilin (PCB) chromophore (Zhou, J., Gasparich, G. E., Stirewalt, V. L., de Lorimier, R., and Bryant, D. A. (1992) J. Biol. Chem. 267, 16138-16145). Purification of the phycocyanin produced in the mutants revealed two fractions each with an aberrant absorption spectrum. Tryptic peptide maps of the major fraction showed that the alpha-84 PCB peptide was absent. The two PCB peptides derived from the beta subunit were normal. Tryptic digests of the less abundant phycocyanin fraction contained a family of bilin peptides derived from the alpha subunit. Several distinct bilin adducts were present. A major component was a mesobiliverdin adduct, a previously described product of the in vitro reaction of PCB and apophycocyanin. The same results were obtained with both the cpcE mutant and the cpcF mutant. In vitro reactions with PCB and the fractions containing apo alpha subunit showed that the alpha-84 bilin attachment site was unmodified and competent for adduct formation. Pseudo-revertants of both strains were observed to arise at high frequency. Analysis of the phycocyanin from a cpcE pseudo-revertant, which produced a near wild-type level of phycocyanin with alpha subunit carrying PCB, revealed a single amino acid substitution, alpha-Tyr129----Cys. This residue, which is conserved in all phycocyanins sequenced to date, forms part of the alpha-84 bilin binding site and lies within 5 A of alpha-Cys84. A mutated cpcA gene containing this substitution was constructed by site-directed mutagenesis and transformed, along with cpcB, into a cpcBAC deletion strain containing an insertionally inactivated cpcE. This strain produces high levels of phycocyanin and the majority of the alpha subunit carries PCB at alpha-Cys84.

Amino Acid Sequence↗

Comparison of laparoscopic cholecystectomy versus elective open cholecystectomy.

Laparoscopic cholecystectomy has essentially replaced open cholecystectomy as the procedure of choice for gallbladder disease. This rapid shift to laparoscopic cholecystectomy, however, has resulted more from marketing forces than from prospective clinical trials. To evaluate the safety and efficacy of laparoscopic cholecystectomy, the first 486 laparoscopic cholecystectomies at two institutions were studied. These results were then compared to the results of the last 6 months of elective open cholecystectomy cases prior to the introduction of laparoscopic surgery. The age, sex, height, and weight were similar in both groups. The mean operative time was 78.8 +/- 1.8 min for laparoscopic cholecystectomy and 62.7 +/- 2.6 min for open cholecystectomy (p < 0.01). The mean time for tolerating a regular diet was 1.23 +/- 0.04 days in the laparoscopic group versus 2.44 +/- 0.07 days in the open group (p < 0.01). Laparoscopic cholecystectomy patients required only oral pain medications by a mean of 1.22 +/- 0.03 days postoperatively compared to 2.55 +/- 0.07 days postoperatively for those undergoing open cholecystectomy (p < 0.01). The mean length of hospitalization was 1.58 +/- 0.07 days for laparoscopic patients and 3.55 +/- 0.11 days for open patients (p < 0.01). Thirty-one patients undergoing laparoscopic cholecystectomy were converted to open cholecystectomy (6.4%). The most common reasons for conversion to open cholecystectomy were acute inflammation, adhesions, and bleeding. For the laparoscopic patients, the morbidity rate was 8.4% and the mortality rate 0.2% (1 death). In the open cholecystectomy group the morbidity rate was 8.0% and there were no deaths. The most troublesome complication in laparoscopic cholecystectomies continues to be bile leaks and bile duct injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Saliva activated transmission (SAT) of Thogoto virus: relationship with vector potential of different haematophagous arthropods.

Tick saliva (or salivary gland extract) potentiates the transmission of Thogoto (THO) virus to uninfected ticks feeding on a non-viraemic guinea-pig. This phenomenon has been named saliva activated transmission (SAT). To investigate the potential of different haematophagous arthropods to mediate SAT, guinea-pigs were infested with uninfected R.appendiculatus Neumann nymphs and inoculated with THO virus and salivary gland extract (SGE) derived from a range of ixodid (metastriate and prostriate) or argasid ticks, or mosquitoes; control guinea-pigs were inoculated with virus alone. Enhancement of THO virus transmission was observed only when SGE was derived from metastriate ticks. Comparison with the vector potential of these various arthropod species revealed that enhancement of THO virus transmission was specific for ticks which were competent vectors of the virus. The data indicate a correlation between vector competence and the ability of haematophagous arthropods to mediate SAT of THO virus.

Aedes↗

The core promoter region of the tumor necrosis factor alpha gene confers phorbol ester responsiveness to upstream transcriptional activators.

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

Base Sequence↗

99mTechnetium-labelled red blood cell scintigraphy as an alternative to angiography in the investigation of gastrointestinal bleeding: clinical experience in a district general hospital.

99mTechnetium-labelled red blood cell scintigraphy (99mTc RBC scintigraphy) was used as the second-line investigation to localise bleeding in 23 patients (11 male, 12 female; mean age 67 years) presenting with active bleeding per rectum. Scintigraphy was available on a 24 h basis. A total of 18 patients had positive scans (78%). Surgery was performed urgently in 11 patients and the site of bleeding, as predicted by scintigraphy, was confirmed in 9 (82%). 99mTc RBC scintigraphy was less useful in patients who were not bleeding actively or who were being investigated for chronic anaemia. This study suggests that 99mTc RBC scintigraphy can play a useful role in the preoperative localisation of unexplained gastrointestinal bleeding in hospitals with nuclear medicine facilities, but confirms it has little place in the management of patients unless they are bleeding actively.

Adult↗

The surgical significance of Persian Gulf sand.

Foreign bodies, in particular sand and soil particles, can cause considerable reaction in wounds and remain in tissues indefinitely. The introduction of foreign material as a contaminant in wounds and intracavitary injuries to military personnel deployed in the Persian Gulf region can be a complicating factor in treatment. Samples of desert sand from the military operational areas of the Persian Gulf were analyzed and the acute local and systemic responses of intraperitoneal contamination determined in an experimental rat model.

Animals↗