Kidney transplantation with ureteral implantation in a neurogenic bladder.
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Biomedical subjects
Publications and source records attributed to M Hall.
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A protein responsible for clot formation was isolated from plasma of the crayfish Pacifastacus leniusculus, by repeated precipitation at low ionic strength, pH 6.0. The protein, here named clotting protein (CP), is a lipoglycoprotein, which consists of two 210-kDa subunits, covalently associated by disulfide bonds. Preparations of the CP can form stable clots in the presence of crayfish haemocyte lysate supernatant, which contains endogenous, Ca(2+)-dependent transglutaminase (TGase) activity. The covalent, TGase-mediated polymerization of CP could clearly be visualized in SDS/PAGE under reducing conditions, where the 210-kDa subunit is covalently cross-linked into dimeric, trimeric and higher polymeric forms. The CP was shown to be a substrate for transglutaminases, since two different fluorescent TGase substrates, namely dansylcadaverine and a dansylated glutamine-containing peptide, were incorporated into the CP subunit by active TGase. This indicates the presence of both glutamine and lysine residues in the CP, accessible for TGase cross-linking. The amino acid composition and the N-terminal amino acid sequence of the clotting protein was determined.
The binding characteristics of [3H]cytisine, a putative CNS nicotinic receptor ligand, were examined in 4 regions of the human brain. [3H]Cytisine was found to bind non-cooperatively with high affinity to a single site in tissue homogenates and to exhibit low non-specific association. The binding characteristics of this ligand were evaluated in thalamus at 4 degrees C and 24 degrees C. The association constants were found to be 0.234 and 0.308 min-1 nM-1, while the dissociation constants were 0.007 and 0.098 min-1, respectively. Saturation analysis of thalamus revealed the equilibrium Kd to be 147 pM (4 degrees C) and 245 pM (24 degrees C), values in good agreement with those determined kinetically. The Hill coefficient varied slightly between brain regions; however, the mean values in all regions examined were close to 1.0 at 0.95 +/- 0.03 (4 degrees C) and 0.91 +/- 0.04 (24 degrees C). [3H]Cytisine binding could be displaced using both nicotinic agonists and antagonists. Cytisine was the most potent displacer of [3H]cytisine binding with an Ki of 250 pM. Nicotine and acetylcholine were also potent displacers with Ki values of 1.8 and 8.1 nM, respectively. The nicotinic antagonists alpha-bungarotoxin and mecamylamine were ineffective competitors for the [3H]cytisine binding site while dihydro-beta-erythroidine had an Ki value of 109 nM. Thalamus showed the highest density of cytisine binding sites of all the regions examined (48 fmol/mg protein) while the hippocampus, cingulate gyrus and the cortex showed Bmax values of 18.9, 19.3 and 8.8 fmol/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Coeliac disease is strongly associated with HLA-DQ2, but it is possible that additional major histocompatibility complex genes also confer disease susceptibility. Encoded close to HLA-DQ are two genes, TAP1 and TAP2, whose products are believed to transport antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 81 coeliac disease patients with caucasoid controls revealed an increased frequency of the alleles TAP1A and TAP2A in the patient population. However, no significant difference was found when patients were compared with HLA-DR and -DQ matched controls, indicating linkage disequilibrium between TAP1A, TAP2A, and HLA-DQ2. The TAP gene products do not have a major influence on susceptibility or resistance to coeliac disease in a Northern European Caucasoid population.
The human papillomavirus (HPV) has been shown to be associated with neoplasms of the human colon using immunohistochemistry and in situ hybridization. We now report our use of the polymerase chain reaction and Southern blotting to investigate that same association. We selected 38 carcinomas, 21 adenomas, and 24 normal mucosal samples for the current study. Tissue sections were prepared, and then DNA was extracted and subjected to 40 cycles of amplification using Thermus aquaticus DNA polymerase and a set of degenerate primers. Amplified products were analyzed by agarose gel electrophoresis and Southern blotting. The L1 region of the HPV genome was identified in 13 of 38 carcinomas (32%), 8 of 21 adenomas (38%), and 2 of 24 normal biopsy specimens (8%). These observations validate our previous results and confirm the presence of HPV in human colon mucosa and tumors of that mucosa.
IgM immunoblotting and polymerase chain reaction (PCR) were evaluated for use in diagnosing congenital syphilis, and the prevalence of central nervous system (CNS) invasion by Treponema pallidum during congenital infection was examined. The results of rabbit infectivity testing (RIT) on serum and cerebrospinal fluid (CSF) of 19 infants born to mothers with untreated early syphilis were compared with results of PCR and IgM immunoblotting. Seven infants had clinical evidence of congenital syphilis supported by positive serum IgM immunoblot (7/7), PCR (6/7), and RIT (3/3). Six symptomatic infants (86%) had T. pallidum isolated from CSF by RIT; 5 of 6 RIT-positive CSF samples were positive by PCR, and 2 also were reactive by IgM immunoblot. In 12 asymptomatic infants, 5 (42%) had a reactive serum IgM immunoblot and in 4 of these IgM reactivity was the only evidence of congenital infection. CNS invasion by T. pallidum was uncommon among asymptomatic infants; only 1 (8%) was positive by CSF RIT. The excellent agreement between RIT and PCR further substantiates the use of PCR as a surrogate for RIT. Our data indicate that the diagnosis of asymptomatically infected neonates will require a comprehensive approach using assays for both specific neonatal IgM and T. pallidum DNA in serum and CSF.
A young college student was found unresponsive, head down in his pillow with a metal canister containing ethyl chloride in or beside his right hand. Resuscitative efforts failed. Qualitative screening detected ethyl chloride in the vitreous fluid and antemortem and postmortem blood. Quantitation was carried out on available fluids with the following results: hospital blood, 20 mg/dL; postmortem blood, 65 mg/dL; and vitreous fluid, 41.7 mg/dL. No other drugs or volatiles were found. Death was subsequently attributed to an overdose or adverse reaction to this product.
Two elderly men, one with definite and one with probable malignancy, presented with severe back pain. Both had osteomyelitis of the lumbar spine due to Group G streptococci which responded to chemotherapy.
On the basis of a preliminary observation that sodium-lithium countertransport showed different intra-individual variations when calculated by two standard methods despite using the same sets of lithium efflux data, we decided to compare values by the two methods in a much larger number (50) of volunteers. Although there was significant correlation between the two sets of values (r = 0.936), mean value by M-1 was significantly higher than that by M-2 (P < 0.007). Using appropriate statistical methodology, the limits of agreement between M-1 and M-2 values (-0.066 to 0.096 mmol L cell-1 h-1) were considerable; and the 95% confidence limits of the bias (i.e. mean difference) did not include zero. Furthermore, neither the 95% confidence interval for the correlation coefficient nor that for the slope of regression line included 1.0. These suggest lack of agreement between the two sets of values. The probable cause of this difference is discussed.
Population screening for carriers of cystic fibrosis (CF) is now possible. Such screening may have both advantages and disadvantages and hence must be evaluated before it becomes routine practice. As the potential benefits of screening are wide and the drawbacks may include psychological effects, a combination of approaches is needed to assess screening thoroughly instead of only counting numbers of terminations or carrier tests. We describe the issues concerned and our methodology for a rigorous evaluation of population antenatal carrier screening for cystic fibrosis.
OBJECTIVE: To derive clinical standards for singleton birthweight in a population based on area of residence. DESIGN: Analysis of variables recorded in Aberdeen Maternity and Neonatal Databank, calculating for each birth a standardised birthweight score, taking account of determining factors. SUBJECTS: All singleton live births of 32 to 42 weeks gestation to Aberdeen City District residents from 1979 to 1983. RESULTS: Basic standards of birthweight are presented correcting for gestational age, sex of the baby and parity of the mother. Birthweight is not normally distributed and empirical data are presented rather than smoothed curves. Adjustment for maternal height is straightforward but adjustment for maternal weight must take account of the gestation at which the woman was weighed. A method of calculating the appropriate correction for height and weight is described in detail. CONCLUSION: Birthweight is not normally distributed at each week of gestation. Standardisation for parity, gestation and sex of the baby is essential, but adjustment for maternal size is complex.
Conical devices placed in the alveolar ridge after tooth extraction have been used clinically for several years to maintain the ridge morphology. In this way, the bone atrophy which occurs after extractions is minimized, and denture fit and function are enhanced. A system using such cones made from Bioglass (registered trademark of the University of Florida) and matching burs has been developed and tested clinically. Average four-year data show a retention rate of over 90%, which compares favorably with other systems using other materials (see Hench et al., 1991). Stanley et al. (to be published), in a review of the four-year clinical data, point out that a few of the cones, although firmly positioned within the alveolar ridge, have a radiolucent zone around the implant. In a clinical study, it is not possible to determine whether this radiolucent zone represents areas of fibrous capsule which are not attached to the implant and therefore compromise its long-term stability, or whether the soft tissue is adherent to the implant and thus contributes to its long-term stability. In a recent study, conical implants identical to those in the clinical trial were placed in the alveolar ridges of dogs and evaluated for up to two years. The adhesion of bone and soft tissue was measured and the development and stabilization of the reactive gel layer monitored. The findings in this animal study support the clinical observations and contribute to an explanation of the success of the Bioglass system in patients.
Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic tumors from both chromosome 17p, in 18/26 (69%) cases, and chromosome 17q, in 15/22 (68%) cases. In the three familial tumors studied, allele loss also occurred on chromosome 17 (in 2/3 cases for 17p markers and in 2/2 cases for a 17q allele). Allele loss on chromosome 18q, at the DCC (deleted in colorectal carcinomas) locus, was not as common (6/16 cases [38%]) in sporadic ovarian tumors but had occurred in all three familial tumors. The results of linkage analysis on the breast/ovarian cancer family suggested linkage between the disease locus and 17q markers, with a maximum lod score of 1.507 obtained with Mfd188 (D17S579) polymorphism at 5% recombination. The maximum lod score for DCC was 0.323 at 0.1% recombination. In this family our results are consistent with a predisposing gene for breast/ovarian cancer being located at chromosome 17q21.
Standard pharmacologic management of cystic fibrosis is discussed and the role of new agents in the treatment of this disease is explored. Cystic fibrosis is a recessive, fatal genetic disease involving multiple organ systems, in which patients develop pancreatic insufficiency, malabsorption, and repeated pulmonary infections. Pharmacotherapy to date has included broad-spectrum antimicrobials and aggressive nutritional management with microencapsulated pancreatic enzymes. Acute pulmonary exacerbations, caused by Pseudomonas aeruginosa, require combination i.v. antimicrobial therapy for 14 to 21 days. With the recent discovery of the genetic defect responsible for cystic fibrosis, as well as the cellular mechanism, new pharmacologic approaches are being explored to improve treatment. Aerosolized amiloride is being tested to modify the basic defect in the chloride channel. Dornase, a new mucolytic, is used to decrease sputum viscosity and increase mucociliary clearance. Leukoprotease inhibitors are currently being evaluated for decreasing the acute inflammatory reaction in the lung. Gene therapy has been promising, but its role in the management of cystic fibrosis is many years away. Drug therapy for cystic fibrosis has been primarily directed at treating infections with antibiotics and supplementing digestive enzymes and vitamins. New agents and gene therapy may substantially change the morbidity and mortality of this disease.
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Two hundred and twenty-three cases of acute overdosage associated with thioridazine were reviewed. The most frequent feature was impairment of consciousness which was linearly dose-related and occasionally resulted in life-threatening complications. Arrhythmia was the most frequently reported serious toxic effect. Patients presenting with anoxia were at risk for arrhythmia, as were patients ingesting a high dose. Arrhythmia may, by decreasing cardiac output, predispose to the occurrence of all other observed complications (ie, pulmonary edema, severe hypotension and renal failure). Therefore, treatment of arrhythmias should be the keystone of management of thioridazine overdosage. Torsade de pointes was reported only once with overdosage. Isolated ventricular arrhythmias (VA) occurred at high doses (median 12 g). At lower doses (median 5 g), VA were frequently associated with conduction disturbances, which were not, as such, statistically predictive of arrhythmias. Since thioridazine in high doses exhibits a beta-adrenoceptor and a verapamil-like calcium channel blocking effect, drugs with these types of properties are contraindicated. VA may be refractory to lidocaine or recur after such therapy. Transient cardiac pacing appears to be the most appropriate management of VA. Although its efficacy is established for the treatment of phenothiazine-induced arrhythmias, its use remains rare (only 3/50 cases).
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