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Biomedical subjects

R Graham

Publications and source records attributed to R Graham.

At least 109 records · Page 6Linked to original sources
PubMed1994

Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling.

The prevalence of asymptomatic hyperuricaemia among Polynesian women (Maoris, Cook Islanders, Samoans, Tongans) was high--44%. This hyperuricaemia resulted from a reduced fractional uric acid clearance (FEur: uric acid clearance factored by creatinine clearance x 100--6.7 +/- 1.5%) compared with the FEur in healthy UK women (12.8 +/- 2.9%). This reduction in FEur was not as great as that in young UK women with familial juvenile hyperuricaemic nephropathy (FJHN: 5.1 +/- 1.5%) and was not associated with impaired renal function. The FEur in the normouricaemic Polynesians (9.7 +/- 1.9%) was also lower than that in healthy UK women (12.8 +/- 2.9%). The reduced FEur in these Polynesian women supports the hypothesis that indigenous Pacific races share a similar genetic defect in renal urate handling to that reported as the basis for the susceptibility to hyperuricaemia in Maori men. Neither alcohol nor hypertension contributed to this. This study also confirmed that, compared with their European counterparts, Polynesian women have a high purine intake and a strong tendency to obesity which increases with age. These factors, together with the reduced FEur, put them at added risk for gout. However, the reduction in FEur was not as great as that reported for the normouricaemic or asymptomatic hyperuricaemic Maori male (4.9 +/- 1.5% and 3.9 +/- 1.4%, respectively), confirming the same sex difference in renal urate handling in adult Polynesians as in caucasians.

Adult↗
PubMed1994

Entry of US medical school graduates into family practice residences: 1993-1994 and 3-year summary.

This is the 13th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each US medical school's graduates entering family practice residency programs. Approximately 12.3% of the 15,564 medical school graduates between July 1992 and June 1993 were first-year family practice residents in October 1993, compared with 10.8% the previous year. This is the highest percentage since 1983-1984. Medical school graduates from publicly funded medical schools were more than twice as likely to be first-year family practice residents in October 1993 as were residents from privately funded schools, 15.9% compared with 7.1%. The Mountain region again reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1993 at 19.1%; the Middle Atlantic and New England regions continued with the lowest percentages at 7.7% and 6.6%, respectively. At least one in four graduates from nine medical schools during the reporting period was in a family practice residency program in October 1993; only two medical schools had this distinction in 1992. Approximately one in two medical school graduates entering a family practice residency program as first-year residents in October 1993 entered a program in the same state where they graduated from medical school. The percentages for each medical school have varied substantially from year to year since the AAFP began reporting this information. The average percentage for each medical school for the last 3 years is reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Career Choice↗
PubMed1994

Results of the 1994 National Resident Matching Program: family practice.

The 1994 National Resident Matching Program results reveal a 14% increase in positions filled in family practice residencies, compared with 1993 (2,293 vs 2,002) and a 13% increase in positions filled by US seniors (1,850 vs 1,636). Similarly, 9% more positions were filled on July 1, 1994, than 1993 (3,040 vs 2,798). For the first time, in 1994 more than 3,000 first-year residency positions were filled in family practice. One hundred more US seniors matched in internal medicine, and 74 more US seniors matched in pediatrics. Given the anticipated career choices of students entering residency training in the generalist disciplines, it is expected that 31% of the class of 1994 (Liaison Committee on Medical Education (LCME)-accredited medical schools) will practice as generalists. An 8% increase in first-year positions offered, and the development of 10% new Accreditation Council for Graduate Medical Education-accredited family practice residency programs could accommodate 20% of the nation's graduates of LCME- and American Osteopathic Association-accredited medical schools. With increasing interest in family practice careers, increased support for the nation's family practice residency programs is critical.

Accreditation↗
PubMed1993

An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily.

Alu repetitive elements represent the most common short interspersed elements (SINEs) found in primates, with an estimated 500,000 members in the haploid human genome. Considerable evidence has accumulated that these elements have dispersed in the genome by active transcription followed by retroposition, and that this process is ongoing. Sequence variation between the individual elements has lead to the hierarchical classification of Alu repeats into families and subfamilies. Young subfamilies that are still being actively transposed are of considerable interest, and the identification of one such subfamily (designated 'PV') has lead to the hypothesis that the most recent retroposition events are due to a single master Alu source gene. In the course of our search for the gene causing Huntington disease, we have detected an Alu retroposition event in two families. Sequence analysis demonstrates that this Alu element is not a member of the PV subfamily, but is similar to 5 other Alu elements in the GenBank database. Together, these Alu elements, all of which contain a 7 base-pair internal duplication, define a distinct subfamily, designated as the Sb2 subfamily, providing evidence for a second actively retroposing Alu source gene. These data provide support for multiple source genes for Alu retroposition in the human genome.

Base Sequence↗
PubMed1993

Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease.

Huntington's disease (HD) is a late-onset autosomal dominant neuropsychiatric disorder presenting in mid-adult life with personality disturbance and involuntary movements, cognitive and affective disturbance, and inexorable progression to death. The underlying genetic defect has been mapped to chromosomal band 4p16.3 (refs 2, 3). Analysis of specific recombination events in some families with HD has further refined the location of the HD defect to a 2.2 megabase DNA interval. Using a direct complementary DNA selection strategy we have identified at least seven transcriptional units within the minimal region believed to contain the HD gene. Screening with one of the cDNA clones identified an Alu insertion in genomic DNA from two persons with HD which showed complete cosegregation with the disease in these families but was not found in 1,000 control chromosomes. Two genes including the previously identified alpha-adducin gene and another that encodes for a 12-kilobase transcript, map in close proximity to the Alu insertion site. The 12-kilobase transcript should be regarded as a strong candidate for the HD gene.

Base Sequence↗
PubMed1993

Regulation of the phosphate (Pi) concentration in UMR 106 osteoblast-like cells: effect of Pi, Na+ and K+.

Osteoblast-like cells possess Na-dependent transporters which accumulate orthophosphate (Pi) from the extracellular medium. This may be important in bone formation. Here we describe parallel measurements of Pi uptake and cellular [Pi] in such cells from the rat (UMR 106-01 and UMR 106-06) and human (OB), and in non-osteoblastic human fibroblasts (Detroit 532 (DET)). In UMR 106-01, cellular [Pi] was weakly dependent on extracellular [Pi] and higher than expected from passive transport alone. [32Pi]-uptake was inhibited by Na deprivation, but paradoxically increased on K deprivation. With Na, 87 per cent of cellular 32P was found in organic phosphorus pools after only 5 min. Na deprivation also decreased cellular [Pi], in both UMR 106-01 and DET, but the decrease was smaller than that in [32Pi]-uptake. Ouabain decreased [32Pi]-uptake and cellular [Pi] in DET, but not in UMR 106-01. Regulation of cellular [Pi] is therefore at least partly dependent on Na/Pi co-transport, but this does not seem to be an exclusive property of osteoblasts.

Animals↗
PubMed1993

A transcription map of the region containing the Huntington disease gene.

A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hybridization to overlapping YACs from this region. These cDNA clones were aligned into transcription units by hybridization to specific mRNAs, by sequence overlap and by physical mapping onto overlapping YAC clones. Nine separate transcription units spanning approximately one megabase were detected by RNA hybridization. They represent a minimum number of genes in this region and do not include those genes expressed specifically in tissues not used for the hybridization. The transcription map that is provided by the cDNA segments will lead to the generation of a detailed gene map of this region.

Base Sequence↗
PubMed1993

Safety of intracavitary urokinase with percutaneous abscess drainage.

OBJECTIVE: Percutaneous drainage of abscesses is an effective treatment, but the success rate is lower for abscesses that have septa and are multilocular. Several clinical and in vitro studies suggest urokinase may be useful in such cases. Our study was designed to determine the safety of urokinase administered into an abscess cavity during the course of percutaneous drainage. SUBJECTS AND METHODS: Our study included 26 consecutive patients with 31 abscesses treated with percutaneous drainage. Exclusion criteria included age less than 18 or more than 95 years, CNS disorders (e.g., tumor, vascular problems), coagulation impairments, hepatic failure, pregnancy, and abscesses in the spleen, pancreas, or interloop area. Three doses were used: group 1 (nine patients), 1000 IU of urokinase per centimeter of abscess diameter; group 2 (11 patients), 2500 IU of urokinase per centimeter of abscess diameter; and group 3 (nine patients), 5000 IU of urokinase per centimeter of abscess diameter. These doses were administered every 8 hr for 3 days along with percutaneous drainage. Charts were reviewed to determine success and to detect adverse clinical events. Studies included sequential CT scans; serial serum determinations of hematocrit, prothrombin time, partial thromboplastin time, platelet count, fibrinogen levels, and levels of fibrin degradation products; and serial laboratory analysis of purulent material for fibrinogen and fibrin degradation products. Percutaneous drainage was considered successful if no surgical intervention was required. RESULTS: Our results showed no significant change in hematologic studies and no bleeding complications. Analysis of purulent material indicated that urokinase remained active in the abscess milieu. Drainage was successful in seven of 11 patients in group 1, all nine patients in group 2, and 10 of 11 patients in group 3. All eight abscesses with septa were successfully drained. CONCLUSION: Intracavitary urokinase can be given safely during percutaneous drainage of an abscess, with no associated bleeding complications or changes in coagulation parameters.

Abscess↗
PubMed1993

Active specific immunotherapy: PEM as a potential target molecule.

An understanding of the mechanisms involved in a biological phenomenon increases its potential for clinical exploitation. Thus, the simultaneous identification of TAA and the molecular mechanisms involved in antigen presentation and recognition by the immune system make the use of ASI a real possibility. The polymorphic epithelial mucin is expressed on most carcinomas and is highly immunogenic. Furthermore, it has many characteristics that make it potentially an ideal target molecule for ASI: (a) not only is it expressed, but it is upregulated by most carcinomas; (b) it is aberrantly glycosylated by carcinomas, resulting in the exposure of cryptic epitopes; (c) its tandem repeat structure results in there being many epitopes per molecule; (d) its extended structure at the surface means it is one of the first molecules the cells of the immune system encounter; and (e) its apparent ability to elicit HLA unrestricted killing already demonstrated in cancer patients makes it applicable to all individuals.

Amino Acid Sequence↗
PubMed1993

Entry of US medical school graduates into family practice residencies: 1992-1993 and three-year summary.

This is the 12th report prepared by the American Academy of Family Physicians (AAFP) on the percentage of each medical school's graduates entering family practice residency programs. Approximately 10.8% of the 15,466 graduates of LCME-accredited US medical schools between July 1991 and June 1992 were first-year residents in family practice in October 1992. This compares to 10.3% the previous year. This is the first increase since 1989. Medical school graduates from publicly funded medical schools were more than twice as likely to be first-year residents in family practice in October 1992 than were residents from privately funded schools, 13.8% compared to 6.4%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1992 at 18.3%; the Middle Atlantic and New England regions continued with the lowest percentages, 5.6% and 7.8%, respectively. Approximately one in two medical school graduates entering a family practice residency program as a first-year resident in October 1992 entered a program in the same state as that of his or her medical school of graduation. The percentages for each medical school have varied substantially from year to year since the AAFP has reported this information. The average percentage for each medical school for the last three years is reported. In addition, the number and percentage of graduates from colleges of osteopathic medicine who entered ACGME-accredited family practice residency programs are reported.

Accreditation↗
PubMed1993

Results of the 1993 National Resident Matching Program.

The 1993 NRMP results reveal a 19% increase in positions filled in family practice residencies compared to 1992 (2,002 versus 1,658) and a 17% increase in positions filled by US seniors (1,636 versus 1,398). Similarly, 11% more positions were filled on July 1, 1993, than 1992 (2,798 versus 2,530). This confirms a trend begun in 1992 of increased interest in careers in family practice, reversing four years of declining interest from 1988 to 1991. Two hundred one fewer US seniors matched in internal medicine, while 36 more chose pediatrics. Of students entering residency training in the generalist disciplines, it is expected that 27% of the class of 1993 (LCME-accredited medical schools) will practice as generalists. An increase of 9% of first-year positions offered, and the development of 15% new ACGME-accredited family practice residency programs, could accommodate 20% of the nation's graduates of LCME- and AOA-accredited medical schools. With increasing interest in careers in family practice, increased support for the nation's family practice residency programs is critical.

Career Choice↗