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Biomedical subjects

R Graham

Publications and source records attributed to R Graham.

At least 73 records · Page 4Linked to original sources

Specialty practice of family practice residency graduates, 1969 through 1993. A national study.

OBJECTIVE: To describe demographic and practice characteristics of physicians who graduated from family practice residency training programs. DESIGN: Information was obtained from the databases of the American Academy of Family Physicians, the American Board of Family Practice (ABFP), and the American Medical Association. Data sets were cross-referenced, and quantitative data from medical membership organizations and the certifying board were summarized. Information regarding medical school graduation and family practice residency completion was reported by the participating residency programs, and data on practice specialty were self-designated by the participating physicians. SUBJECTS: Physician graduates of Accreditation Council for Graduate Medical Education-accredited family practice residency programs from 1969 through 1993. MAIN OUTCOME MEASURES: Practice specialty designation by graduates of family practice residency programs. RESULTS: Of the 38659 physicians who graduated from family practice residency programs from 1969 through 1993, 8780 (23%) were women, 2181 (6%) were graduates of colleges of osteopathic medicine, 4777 (12%) were international medical graduates, and 33484 (87%) were certified by the ABFP. Of the 36088 family practice residency graduates who designated a practice specialty, 32764 (91%) identified their specialty as family practice, including 32608 physicians who identified family practice, 129 general practice, 21 family practice-geriatric medicine, and six family practice-sports medicine. Among the 3324 family practice residency graduates (9%) who identified themselves as practicing in another specialty, the most common specialties were emergency medicine (1446 physicians [4%]) and preventive medicine (386 physicians [1%]). No other practice specialty was designated by more that 0.5% of family practice residency graduates. CONCLUSION: The vast majority of family practice residency graduates are self-designated as practicing family medicine. These data suggest that family practice residency programs are an effective mechanism for the production of generalist physicians.

Data Collection↗

An assessment of pain and return to normal activity. Laparoscopic herniorrhaphy vs open tension-free Lichtenstein repair.

BACKGROUND: Laparoscopic herniorrhaphy is controversial and deserves critical evaluation. METHODS: In a randomized prospective study transabdominal preperitoneal laparoscopic herniorrhaphy (n = 24) was compared in patients to the tension-free Lichtenstein repair (n = 29) utilizing validated and reliable pain and activity assessment tools. The Sickness Impact Profile (SIP) was used to compare preoperative normal activity to postoperative activity. A Pain-O-Meter (visual analogue scale plus affective and sensory pain descriptors) assessed intensity of pain. The total pain assessment score and SIP were compared across time (postoperative day 1-42). Analgesic medication was used as a covariate. RESULTS: The total pain score was less for laparoscopic herniorrhaphy but this did not reach statistical significance. Similarly, the SIP showed modest improvement for laparoscopic herniorrhaphy. No differences between groups were noted for morphine equivalents of administered analgesics or length of hospitalization. CONCLUSION: Further investigation of laparoscopic herniorrhaphy is warranted.

Adult↗

A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer.

Studies in animal models of mouse mammary carcinoma have shown that ovine submaxillary mucin, which carries multiple sialyl-Tn (STn) epitopes, is effective in stimulating an immune response and inhibiting tumour growth. In similar studies using carbohydrate antigens, pretreatment with low-dose cyclophosphamide has been shown to be important in modulating the immune response to antigen possibly by inhibiting suppresser T-cell activity. In a clinical trial assessing the efficacy and toxicity of synthetic STn, patients with metastatic breast cancer were randomised to receive 100 micrograms STn linked to keyhole limpet haemocyanin (KLH) with DETOX-B adjuvant given by subcutaneous injection at weeks 0, 2, 5 and 9 with or without low-dose cyclophosphamide (CTX, 300 mg m-2) pretreatment, 3 days before the start of immunotherapy. Patients with responding or stable disease after the first four injections were eligible to receive STn-KLH at 4 week intervals. The main toxicity noted was the development of subcutaneous granulomata at injection sites. Of 23 patients randomised, 18 received four injections, 5 patients having developed progressive disease during the initial 12 week period. Two minor responses were noted in the 18 patients who received four active specific immunotherapy (ASI) injections and a further five patients had stable disease. Six patients continued ASI at 4 week intervals and a partial response was noted in a patient who had previously had stable disease. All patients developed IgG and IgM responses to sialyl-Tn and levels of IgM antibodies were significantly higher in those patients who were pretreated with CTX. Measurable tumour responses have been recorded following ASI with STn-KLH plus DETOX and the immunomodulatory properties of low-dose CTX have been confirmed.

Adjuvants, Immunologic↗

Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript.

The mutation underlying Huntington disease (HD) is CAG expansion in the first exon of the HD gene. In order to investigate the role of CAG expansion in the pathogenesis of HD, we have produced transgenic mice containing the full length human HD cDNA with 44 CAG repeats. By 1 year, these mice have no behavioral abnormalities and morphometric analysis at 6 (one animal) and 9 (two animals) months age revealed no changes. Despite high levels of mRNA expression, there was no evidence of the HD gene product in any of these transgenic mice. In vitro transfection studies indicated that the inclusion of 120 bp of the 5' UTR in the cDNA construct and the presence of a frameshift mutation at nucleotide 2349 prevented expression of the HD cDNA. These findings suggest that the pathogenesis of HD is not mediated through DNA-protein interaction and that presence of the RNA transcript with an expanded CAG repeat is insufficient to cause the disease. Rather, translation of the CAG is crucial for the pathogenesis of HD. In contrast to that seen in humans, the CAG repeat in these mice was remarkably stable in 97 meioses. This suggests that genomic sequences may play a critical role in influencing repeat instability.

Animals↗

A waterborne outbreak of hepatitis E virus transmission in southwestern Vietnam.

A hepatitis outbreak affecting primarily adults occurred in southwestern Vietnam, along the Hau river bordering Cambodia, in June and July 1994. One month after the outbreak, sera and epidemiologic information were collected from 150 subjects: 50 patient cases, 50 matched, healthy community controls, and 50 geographic controls living 50 km upriver. The prevalence of immunoglobulin G (IgG) to hepatitis E virus (HEV) was significantly (P < 0.001) higher (76%) among cases than among the matched (38%) and geographic (38%) control populations. Immunoglobulin M to HEV was detected by enzyme-linked immunosorbent assay and Western blot in 16% of sera collected from patients one month after the outbreak. Hepatitis E virus RNA was detected with the polymerase chain reaction in 6% of sera from patients; RNA was not detected in either control group. These results indicate that HEV was the etiologic agent responsible for the outbreak. Children were under-represented among clinical cases. River water served as the principal source for drinking and bathing among most (96%) of the case and control study populations. Boiling of drinking water was negatively associated (P < 0.05) with IgG anti-HEV seropositivity. Unusually heavy rainfall likely contributed to conditions that favored the outbreak. This is the first recognized outbreak of epidemic HEV transmission in Indo-China.

Adolescent↗

Entry of US medical school graduates into family practice residencies: 1995-1996 and 3-year summary.

This is the 15th 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 14.6% of the 16,124 graduates of US medical schools between July 1994 and June 1995 were first-year family practice residents in October 1995, compared with 13.4% in 1994 and 12.3% in 1993. This is the highest percentage since 1980-1981 (12.8%), when this series of studies began. Medical school graduates from publicly funded medical schools were almost twice as likely to be first-year family practice residents in October 1995 than were residents from privately funded schools, 18% compared with 9.7%. The West North Central region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1995 at 24.8%; the Middle Atlantic and New England regions continued with the lowest percentages at 7.6% and 9.3%, respectively. Approximately one in two medical school graduates (46.7%) entering a family practice residency program as first-year residents in October 1995 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. In addition, the number and percentage of graduates from colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family practice residency programs are reported.

Censuses↗

Results of the 1996 National Resident Matching Program: family practice.

The results of the 1996 National Resident Matching Program (NRMP) set records in the number of positions filled in family practice residencies, with a 10.8% increase over 1995 (2,840 vs 2,563) and a 9.4% increase in positions filled with US seniors (2,276 vs 2,081). This is the largest number of US seniors choosing family practice in the history of the NRMP. A total of 196 (6.7%) more positions were offered in family practice through the NRMP, compared with 1995 (3,137 vs 2,941). Thus, 195 of these additional 196 positions were filled with US seniors. In keeping with the trend begun in 1992, 242 more positions were filled on July 1, 1996, than 1995 (3,494 vs 3,252), for a fill rate of 97.8%. Internal medicine residencies matched 67 fewer US seniors in 1996, while pediatric residencies matched 85 more US seniors. During the past 4 years, family practice has been the choice of 82.6% of the additional US seniors choosing a primary care residency. With continued record increased interest in family practice as a career choice and the need for more family physicians, priority support for the nation's family practice residency programs continues to be of critical importance.

Family Practice↗

A non-invasive assessment of hepatitis B virus carrier status using saliva samples.

A non-invasive testing method to determine hepatitis B virus (HBV) carrier status in pregnant women was evaluated. Paired serum and saliva samples were collected and assessment of hepatitis B markers were performed. Of the 502 women enrolled, 5.6% (28/502) of their sera were found to be positive for HBV surface antigen (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the saliva reactive samples were matched to the serum reactive samples (50% sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were non-reactive for HBeAg. This report found a non-invasive saliva testing method to be a possible alternative approach for determining chronic HBV carrier status if the sensitivity of the test can be improved.

Carrier State↗

Identification of the acid/base catalyst in Agrobacterium faecalis beta-glucosidase by kinetic analysis of mutants.

The catalytic mechanism of the retaining beta-glucosidase (Abg) from Agrobacterium faecalis involves a double-displacement process in which an alpha-glucosyl-enzyme intermediate is formed with general acid catalytic assistance and then hydrolyzed with general base assistance. Glu170 was identified as an important residue, possibly the acid/base catalyst, on the basis of sequence alignments. This glutamate is conserved in almost all enzymes in family 1 of glycoside hydrolases. Detailed pre-steady-state and steady-state kinetic analyses of the mutant E170G suggested very strongly that Glu170 is the acid/base catalyst. First, kcat values were invariant with pH over the range of 5.0-9.0. Secondly, rates of formation of the glycosyl-enzyme, calculated from kcat/Km and k2, were similar to those of wild-type enzyme for substrates not requiring protonic assistance but dramatically reduced for those needing acid catalysis. Thirdly, addition of azide as a competitive nucleophile increased kcat values 100-300-fold for substrates whose rate-limiting step is deglycosylation, yielding beta-glucosyl azide, but had no effect on the wild-type enzyme. Other anionic nucleophiles had similar, but less dramatic effects. Previous results [Gebler, J.C., et al. (1995) 34, 14547-14553] had indicated that Tyr298F is important for catalysis. The kinetic consequences of the mutations in the double mutant E170G-Y298F are additive, resulting in a 10(6)-fold reduction in kcat values and allowing the accumulation of a stable (t1/2 > 7 h) glucosyl-enzyme intermediate. Thus, Glu170 and Tyr298 function independently, and a possible role for Tyr298 in modulating the pKa of the catalytic nucleophile is proposed.

Amino Acid Sequence↗