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Biomedical subjects

D K Williams

Publications and source records attributed to D K Williams.

At least 37 records · Page 2Linked to original sources

Isolated autosomal dominant type E brachydactyly: exclusion of linkage to candidate regions 2q37 and 20q13.

Type E brachydactyly is a digital malformation which characteristically causes an asymmetrical shortening of one or more metacarpals or metatarsals or both. Although commonly seen as part of a syndrome, it can be inherited as an autosomal dominant characteristic, the gene acting with variable expressivity, but complete penetrance. As an Albright hereditary osteodystrophy (AHO)-like syndrome including brachydactyly type E and mental retardation may be caused by (micro) deletions at chromosome 2q37, this region together with the AHO locus at chromosome 20q13 were considered as candidate loci for brachydactyly type E. In this paper we described a family with isolated autosomal dominant type E brachydactyly in whom molecular analysis excludes linkage to these regions, providing support for further genetic heterogeneity of this trait.

Chromosomes, Human, Pair 2↗

Calcium transients in growth cones and axons of cultured Helisoma neurons in response to conditioning factors.

Accumulating evidence indicates that cytosolic calcium levels regulate growth cone motility and neurite extension. The purpose of this study was to determine if intracellular calcium levels also influence the initiation of neurite extension induced by growth-promoting factors. An in vitro preparation of axotomized neurons that can be maintained in the absence of growth-promoting factors was utilized. The distal axons of cultured Helisoma neurons plated into defined medium do not extend neurites until they are exposed to Helisoma brain-conditioned medium. This provided the opportunity to study the intracellular changes associated with neurite extension. Cytosolic calcium levels were monitored with the calcium-sensitive dye fura 2 at the distal axon. In control medium calcium levels in the distal axon were constant. However, transient elevations in cytosolic calcium in the axonal growth cone occurred after addition of conditioned medium and coincident with the initiation of neurite extension. Application of calcium channel blockers showed that the transients resulted from calcium influx across the neuronal membrane. The transients, however, were not required for neurite extension, although they did influence the rate and extent of neurite outgrowth. Simultaneous extracellular patch recordings demonstrated that the calcium transients were correlated temporally with an increase in rhythmic spontaneous electrical activity of cells, suggesting that conditioned medium influences ionic membrane properties of these neurons.

Animals↗

The role of conditioning factors in the formation of growth cones and neurites from the axon stump after axotomy.

Knowledge of the cellular events that underlie initiation of outgrowth is crucial to understanding regulation of development and regeneration of the nervous system. This study utilized a culture preparation in which growth cone formation could be studied independent of cellular responses to the presence of conditioning factors. Identified neurons were removed from the buccal ganglion of the mollusc, Helisoma trivolvis, and plated into defined culture medium. A large growth cone formed at the end of the attached axon stump. Although this axonal growth cone exhibited filopodial and lamellipodial activity, it did not advance across the substrate, suggesting that growth cone formation and motility were independent of the presence of conditioning factors. Axonal growth cones of identified neurons B19 and B5 exhibited differences in their morphological and behavioral properties. In response to the addition of conditioning factors, several new neurites extended from the periphery of the axonal growth cone. Extension of outgrowth from the axonal growth cone was accompanied by a redistribution of cytoskeletal elements in the axonal growth cone. Cytoskeletal staining revealed a loss of the peripheral actin filament network and microtubules were found to extend into the peripheral lamellipodium of the axonal growth cone, an area normally devoid of microtubule staining. Thus, these experiments indicate that growth cone formation is an intrinsic property of the distal axon stump and that neurite extension from this structure involves reorganization of the neuronal cytoskeleton.

Animals↗

Impact of the Medicare fee schedule on payments to physicians.

Beginning in 1992, the Medicare program will pay physicians by the Medicare Fee Schedule, a system of geographically adjusted standardized payment rates based in part on the Resource-Based Relative Value Scale developed by Hsaio et al and in part on current Medicare payments. In our simulations of the Medicare Fee Schedule, we find that (1) redistributions of Medicare-allowed charges across specialities will be substantial but approximately only half the size projected by Hsaio, (2) there will be large redistributions among geographic areas that tend to compound the specialty redistributions, and (3) there will be wide variation within specialties as to how individual providers are affected. The majority of the redistributive impact of the Medicare Fee Schedule is attributable to implementation of a geographically adjusted system of standardized payments rather than to the particular work values developed by Hsiao et al in the Resource-Based Relative Value Scale.

Costs and Cost Analysis↗

Xylose uptake by the ruminal bacterium Selenomonas ruminantium.

Selenomonas ruminantium HD4 does not use the phosphoenolpyruvate phosphotransferase system to transport xylose (S. A. Martin and J. B. Russell, J. Gen. Microbiol. 134:819-827, 1988). Xylose uptake by whole cells of S. ruminantium HD4 was inducible. Uptake was unaffected by monensin or lasalocid, while oxygen, o-phenanthroline, and HgCl2 were potent inhibitors. Menadione, antimycin A, and KCN had little effect on uptake, and acriflavine inhibited uptake by 23%. Sodium fluoride decreased xylose uptake by 10%, while N,N'-dicyclohexylcarbodiimide decreased uptake by 31%. Sodium arsenate was a strong inhibitor (83%), and these results suggest the involvement of a high-energy phosphate compound and possibly a binding protein in xylose uptake. The protonophores carbonyl cyanide m-chlorophenylhydrazone, 2,4-dinitrophenol, and SF6847 inhibited xylose uptake by 88, 82, and 43%, respectively. The cations Na+ and K+ did not stimulate xylose uptake. The kinetics of xylose uptake were nonlinear, and it appeared that more than one uptake mechanism may be involved or that two proteins (i.e., a binding protein and permease protein) with different affinities for xylose were present. Excess (10 mM) glucose, sucrose, or maltose decreased xylose uptake less than 40%. Uptake was unaffected at extracellular pH values between 6.0 and 8.0, while pH values of 5.0 and 4.0 decreased uptake 28 and 24%, respectively. The phenolic monomers p-coumaric acid and vanillin inhibited growth on xylose and xylose uptake more than ferulic acid did. The predominant end products resulting from the fermentation of xylose were lactate (7.5 mM), acetate (4.4 mM), and propionate (5.1 nM), and the Yxylose was 24.1 g/mol.

Animals↗

Vitamin and mineral supplementation practices of adults in seven western states.

Seven western states (Arizona, California, Idaho, Nevada, New Mexico, Oregon, and Wyoming) were surveyed in 1986 to determine the extent of vitamin/mineral supplementation and dosage levels of single supplements. Questionnaires were mailed to 3,500 individuals. A 57.8% response rate was obtained from the deliverable surveys, with a sample size of 1,730. The sample consisted of 54% women and 46% men and was predominantly white (88.9%). Fifty-four percent of the sample consumed some type of supplement; multiple vitamin/minerals were consumed with the greatest frequency. For single supplements, vitamin C was reported with the greatest frequency (23.1%), followed by some type of calcium supplement (22.5%) and vitamin E (11.1%). More than 80% of the vitamin C users indicated a dosage of 250 mg/day. Most respondents consumed calcium dosages of less than 1,000 mg/day. For vitamin E, 75% of the users consumed more than 200 IU/day. The data suggest that the potential for toxicity due to excess supplementation levels exists in the western states studied.

Adolescent↗

Assessing hospital-associated deaths from discharge data. The role of length of stay and comorbidities.

To assess the meaning of hospital-associated death rates, we studied whether mortality within 30 days of hospital admission (30-day mortality) is more informative than inpatient mortality and whether detailed assessment of additional discharge diagnoses helps in understanding death rates. We examined hospitalizations for elderly Medicare patients with principal diagnoses of stroke, bacterial pneumonia, myocardial infarction, and congestive heart failure; these conditions account for 30.8% of Medicare 30-day mortality. Average hospital stays for these conditions were 99.0% longer, and inpatient mortality was 25.0% higher in New York than in California, but 30-day mortality was 1.6% higher in California. We conclude that inpatient death rates depend on length-of-stay patterns and give a biased picture of mortality. Additional diagnoses such as shock and pneumonia were strongly associated with increased mortality, but Medicare data do not reveal which patients had these conditions at the time of admission. Recorded diagnoses of chronic diseases such as hypertension, diabetes mellitus, obesity, benign prostatic hypertrophy, and osteoarthritis were commonly associated with reduced risk of death; such reduced risk is not clinically plausible. Several lines of evidence suggest that chronic disorders are underreported for patients with life-threatening disorders. We recommend great caution in using discharge diagnoses of comorbid conditions to adjust hospital death rates for clinical differences in the patient populations.

Aged↗

Physician incomes and work patterns across specialties: 1975 and 1983-84.

Survey data on physician income and work patterns are examined and compared for 1975 and 1983-84. Specialty, hours and weeks worked, location, practice size, and incorporation status are examined. Dollar figures for 1975 are adjusted to show real-dollar income changes over the period. Incomes for surgical specialties were highest. In real-dollar terms, nonsurgical specialties exhibited sluggish growth or even fell. Urban-rural differences in real income and hours worked narrowed over time. Incorporation and group affiliation were positively related to income levels in both surveys, but number of hours worked was not. Limitations and interpretation of these data are discussed last.

Data Collection↗

Strong proposals make easy going on solicitation road.

"Just get out a proposal," is a command that is heard all too frequently from the officers of an institution, notes this author. The result is a slap-dash replica of what should have been a carefully constructed piece. With advise on the do's and don'ts of proposal writing, the author explains how any fund raiser can reach what at first seemed an unobtainable goal.

Dancing↗

Splenectomy for hypersplenism.

The five-year experience with 75 consecutive splenectomies has been reviewed. Special detail was given to eight critically ill hypersplenic patients. Their diagnoses included Hodgkin's disease, lymphoma, leukemia, myelofibrosis and Felty's syndrome. Three presented with sepsis, two with anemia not responsive to transfusion, three had pathologic bleeding and two could not receive additional needed therapy of underlying disease because of low counts. All cases responded to splenectomy favorably. Hypersplenism is primarily a loss of balance between the splenic destruction-sequestration and bone marrow production. The demonstrated rapid consumption of transfused cells and some degree of functional reserve of the bone marrow is the prerequisite and clue for splenectomy response in critically ill patients.

Adult↗

Aneurysmal rupture following resection of abdominal malignancy.

Four cases of ruptured abdominal aortic aneurysms as a postoperative complication are reported. This represents a 24 per cent mortality for elective operation in patients with known abdominal aortic aneurysm. Three cases followed resection of abdominal malignancy. The possibility exists that subtle trauma during operative manipulation may have heightened the risk of rupture. The risk to life from large abdominal aortic aneurysms (more than 6 cm) exceeds the risk of most malignancies. Abdominal aortic aneurysm should be resected first when co-incidental to a malignancy, unless the malignancy is complicated by hemorrhage, obstruction or perforation.

Abdominal Neoplasms↗