Biomedical subjects
K Sutton
Publications and source records attributed to K Sutton.
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
P-type and Q-type calcium channels mediate neurotransmitter release at many synapses in the mammalian nervous system. The alpha 1A calcium channel has been implicated in the etiologies of conditions such as episodic ataxia, epilepsy and familial migraine, and shares several properties with native P- and Q-type channels. However, the exact relationship between alpha 1A and P- and Q-type channels is unknown. Here we report that alternative splicing of the alpha 1A subunit gene results in channels with distinct kinetic, pharmacological and modulatory properties. Overall, the results indicate that alternative splicing of the alpha 1A gene generates P-type and Q-type channels as well as multiple phenotypic variants.
Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation.
The fluoroquinolone antibiotic ciprofloxacin has been encapsulated into large unilamellar vesicles (LUV) at efficiencies approaching 100%. Drug accumulation proceeded in response to a transmembrane gradient of methylammonium sulfate and occurred concomitantly with the efflux of methylamine. A mechanism for the encapsulation process is described. LUV composed of dipalmitoylphosphatidylcholine-cholesterol (DPPC/chol), distearoylphosphatidylcholine-cholesterol (DSPC/chol), or sphingomyelin-cholesterol (SM/chol) increased the circulation lifetime of ciprofloxacin after intravenous (i.v.) administration by > 15-fold. The retention of ciprofloxacin in liposomes in the circulation decreased in the sequence SM/chol > DSPC/chol > DPPC/chol. Increased circulation lifetimes were associated with enhanced delivery of the drug to the livers, spleens, kidneys, and lungs of mice. Encapsulation of ciprofloxacin also conferred significant increases in the longevity of the drug in the plasma after intraperitoneal administration and in the lungs after intratracheal administration in comparison to free ciprofloxacin. The efficacy of a single i.v. administration of an SM/chol formulation of ciprofloxacin was measured in a Salmonella typhimurium infection model. At 20 mg of ciprofloxacin per kg of body weight, the encapsulated formulation resulted in 10(3)- to 10(4)-fold fewer viable bacteria in the livers and spleens of infected mice than was observed for animals treated with free ciprofloxacin. These results show the utility of liposomal encapsulation of ciprofloxacin in improving the pharmacokinetics, biodistribution, and antibacterial efficacy of the antibiotic. In addition, these formulations are well suited for i.v., intraperitoneal, and intratracheal or aerosol administration.
Challenging communication: people with learning disabilities who challenge services.
This paper describes a project designed to equip direct care workers with the knowledge and skills to address communication as a central factor in the lives of people with learning disabilities who challenge services. The elements of the approach taken--'Challenging Communication'--are described, outcomes discussed and possible implications for the speech and language therapy profession briefly considered.
Inductively coupled plasma mass spectrometric detection for chromatography and capillary electrophoresis.
Inductively coupled plasma mass spectrometry (ICP-MS) is now a well established detection technique for liquid chromatography, gas chromatography, supercritical fluid chromatography and capillary electrophoresis. A review of the literature with particular regard to ICP-MS as a chromatographic and capillary electrophoretic detector is presented. The various modes of chromatography and capillary electrophoresis are discussed and practical descriptions for hyphenating the techniques with the ICP mass spectrometer are given. Sample introduction systems and data acquisition methods are reviewed along with the numerous applications of ICP-MS as a chromatographic detector. In addition, alternative plasma sources, such as the atmospheric and reduced pressure helium microwave-induced plasmas for chromatographic detection are described.
Personal characteristics associated with episodes of injury in a residential facility.
Number of episodes of injury and personal characteristics of 412 individuals living in a state-operated ICF/MR during 1994 were examined. Results indicated that 16% of the facility population experienced 67% of the injuries. Discriminant functions were created using chlorpromazine equivalent level combined with maladaptive behavior, medical, and adaptive behavior factors to classify individuals into high and low injury groups. Individuals taking antipsychotics, having higher maladaptive behavior scores, and having relatively higher levels of adaptive behavior were most likely to be in the high injury group. We concluded that episodes of injury were not evenly distributed across the individuals and certain personal characteristics discriminated high from low risk groups.
The Pem homeobox gene: rapid evolution of the homeodomain, X chromosomal localization, and expression in reproductive tissue.
A hallmark of homeobox genes is their high degree of sequence conservation in distantly related species. Here, we report the chromosomal localization, sequence, and expression pattern of an orphan homeobox gene, Pem, that encodes a homeodomain (HD) that has undergone a surprisingly high rate of evolutionary change. The N-terminal portion of the Pem HD, which includes the first two alpha-helices, exhibits only 44% sequence identity between rat Pem (r.Pem) and mouse Pem (m.Pem). This N-terminal subdomain exhibited an extremely high frequency of nonsynonymous substitutions, severalfold higher than other regions of the Pem protein. In contrast, the third helix, which is known to confer most of the base-specific contacts of HDs with DNA, was almost identical in r. Pem and m.Pem. Several lines of evidence suggested that the rat and mouse genes that we identified as Pem genes are true homologues: (1) the r.Pem and m.Pem genes both reside on the X chromosome; (2) they possess identical exon/intron splice junctions; (3) they both encode a distinctive motif upstream of the HD that is unique to Pem; and (4) the only m.Pem-like gene we were able to identify in the rat genome other than r.Pem was a pseudogene, r.Pem-ps, whose sequence and chromosomal localization indicated that it was derived by reverse transcription and reinsertion into the genome. The functional r.Pem gene is selectively expressed in placenta, testis, epididymis, and ovary. This expression pattern is of interest since other genes transcribed in reproductive tissue have also been shown to undergo high rates of sequence divergence. The high rate of amino acid substitutions in the N-terminal region of the Pem HD suggests the possibility of species-specific directional selection.
A follow-up study of patients hospitalized after minor head injury.
Minor head injury accounts for 95% of all head injury. In this study 62 patients, hospitalized after minor head injury, were assessed within 48 h, and invited to attend for review and retesting 3 months later. Thirty-five patients were followed up in this way and 11 more were interviewed over the telephone. There was significant improvement on all psychometric tests between initial evaluation and follow-up. Between 51% and 86% reported troublesome late post-concussional symptoms, of which headaches and tiredness were the most frequently reported symptoms. Length of post-traumatic amnesia (PTA) was related to severity of symptoms. Clinical levels of anxiety and stress were noted in approximately one-third of the whole group; 95% of the group had returned to work by 3 months with a mean absence rate of 9.4 days. The therapeutic implications of these results are discussed.
Flexible sigmoidoscopy or colonoscopy for colorectal screening: a randomized trial of performance and acceptability.
In a randomized clinical trail to assess acceptability, yields, costs, and unwanted effects of screening procedures, 232 subjects (137 with family history of colorectal carcinoma or adenoma, 95 without) were offered either flexible sigmoidoscopy or colonoscopy. Subjects with polyps found on sigmoidoscopy were followed up by colonoscopy. The two procedures were similar in compliance (65%) and yield (19% adenoma, 15% hyperplastic polyps). Polyps of either type were more common in those with a family history (prevalence: 41% compared with 24% without family history, p = 0.04). Costs per procedure were 60% lower for sigmoidoscopy, but follow-up colonoscopy reduced this cost advantage to 20% per subject. The subjects found the preparation for sigmoidoscopy easier, but the procedure more uncomfortable and embarrassing, as colonoscopy was performed under sedation. In this hospital-based study, colonoscopy was as acceptable to subjects, and only slightly more costly than sigmoidoscopy. Advantages of sigmoidoscopy would be greater for use outside hospitals and with less intensive follow up.
The Bacillus subtilis pnbA gene encoding p-nitrobenzyl esterase: cloning, sequence and high-level expression in Escherichia coli.
p-Nitrobenzyl esters serve as protecting groups on intermediates in the manufacture of clinically important oral beta-lactam antibiotics; de-esterification of the intermediates is required for synthesis of the final product. A Bacillus subtilis PNB carboxy-esterase (PNBCE) catalyzes hydrolysis of several beta-lactam antibiotic PNB esters to the corresponding free acid and PNB alcohol. This communication (i) describes cloning the pnbA gene, which encodes PNBCE, (ii) provides the nucleotide sequence of the pnbA open reading frame (ORF) and (iii) describes a method for efficiently expressing the ORF in Escherichia coli. The amino acid (aa) sequence, deduced from the nucleotide sequence of the pnbA ORF, matched an experimentally determined N-terminal aa sequence of B. subtilis PNBCE and also matched an active site sequence previously identified by biochemical analyses. Specific activity of PNBCE in crude extracts was more than 90-fold greater in recombinant E. coli, as compared to B. subtilis. This increase in expression led to more than a 500-fold improvement in the efficiency of purification of PNBCE.
G protein modulation of voltage-dependent calcium channels and transmitter release.
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Effects on cardiac performance of atrioventricular node catheter ablation using radiofrequency current for drug-refractory atrial arrhythmias.
Patients with atrial fibrillation or atrial flutter (AF) are candidates for radiofrequency (RF) catheter ablation of the atrioventricular (AV) node with the aim being to control heart rate. As patients with AF can have markedly impaired ventricular function, information concerning the hemodynamic effects of AV node ablation using RF current would be valuable. Fourteen consecutive patients (mean age 65 +/- 3 years) with drug-resistant AF underwent AV node catheter ablation with RF current and had permanent pacemaker implantation. The mean left ventricular ejection fraction (EF) by two-dimensional echocardiography immediately before ablation was 42 +/- 3% (range 14%-54%) and their mean exercise time was 4.4 +/- 0.4 minutes. Complete AV block was achieved in all 14 patients with 6 +/- 2 RF applications (range 1-18). There was no evidence of any acute cardiodepressant effect associated with delivery of RF current, and EF 3 days after ablation was 44 +/- 4%. By 6 weeks after ablation, the left ventricular EF was significantly improved compared to baseline (47 +/- 4% postablation vs 42 +/- 3% preablation; P < 0.05), and this modest increase in EF was accompanied by an improvement in exercise time (5.4 +/- 0.4 min). In conclusion, delivery of RF current for AV node catheter ablation in patients with AF and reduced ventricular function is not associated with any acute cardiodepressant effect. On the contrary, improved control of rapid heart rate following successful AV node ablation is associated with a modest and progressive improvement in cardiac performance.
Red flags on the quality road.
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Self-scheduling in a CVICU (cardiovascular intensive care unit).
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The presenting ECG pattern in survivors of cardiac arrest and its relation to the subsequent long-term survival. Brain Resuscitation Clinical Trial I Study Group.
In a prospective multi-center study, 262 patients were given general intensive care therapy following cardiopulmonary resuscitation if they were still comatose and unresponsive to pain 10 min after restored spontaneous circulation. Mortality (mainly cardiac) was 53.4% over the first 10 days, and 49% of the remaining survivors died between 10 days and 6 months. In the subsequent 6 months few patients died. Presenting electrocardiograms (ECG) showed ventricular fibrillation (VF) in 54.2%, asystole in 29.8% and electromechanical dissociation (EMD) in 9.2% of the patients. One-year survival, 14.1% for asystole, 4.2% for EMD and 26.0% for VF and VT (ventricular tachycardia), differed significantly (P less than 0.01). VF/VT patients were older and had more cardiovascular disease. Adjustments of these and other covariates increased the significance of difference between ECG groups. Successful resuscitations from asystole or EMD appeared to be more common than has previously been reported, but this group of patients experienced an extremely high cardiac mortality over the first 6 months following resuscitation.
Progress in the human geography of the Maghreb.
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A proposal for a combined family practice--internal medicine residency.
Both family practice and internal medicine currently train graduates for primary care. A single, four-year program is proposed that combines the strengths of family practice and internal medicine, incorporates community needs into the curriculum, and addresses the physician's changed role in a revolutionized health care provision system. Specific training recommendations and the societal and professional advantages of such a program are detailed.
A clinical method to assess food retention, development of a standard food portion mass and food debris disclosure.
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