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Biomedical subjects

R Graham

Publications and source records attributed to R Graham.

At least 55 records · Page 3Linked to original sources
PubMed1998

Physical exercise and psychological well being: a critical review.

The relation between physical exercise and psychological health has increasingly come under the spotlight over recent years. While the message emanating from physiological research has extolled the general advantages of exercise in terms of physical health, the equivalent psychological literature has revealed a more complex relation. The paper outlines the research evidence, focusing on the relation between physical exercise and depression, anxiety, stress responsivity, mood state, self esteem, premenstrual syndrome, and body image. Consideration is also given to the phenomena of exercise addiction and withdrawal, and implications for exercise prescription are discussed.

Affect↗
PubMed1998

Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras.

Bisphosphonates are currently the most important class of antiresorptive drugs used for the treatment of metabolic bone diseases. Although the molecular targets of bisphosphonates have not been identified, these compounds inhibit bone resorption by mechanisms that can lead to osteoclast apoptosis. Bisphosphonates also induce apoptosis in mouse J774 macrophages in vitro, probably by the same mechanisms that lead to osteoclast apoptosis. We have found that, in J774 macrophages, nitrogen-containing bisphosphonates (such as alendronate, ibandronate, and risedronate) inhibit post-translational modification (prenylation) of proteins, including the GTP-binding protein Ras, with farnesyl or geranylgeranyl isoprenoid groups. Clodronate did not inhibit protein prenylation. Mevastatin, an inhibitor of 3-hydroxy-3-methylglutatyl (HMG)-CoA reductase and hence the biosynthetic pathway required for the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, also caused apoptosis in J774 macrophages and murine osteoclasts in vitro. Furthermore, alendronate-induced apoptosis, like mevastatin-induced apoptosis, could be suppressed in J774 cells by the addition of farnesyl pyrophosphate or geranylgeranyl pyrophosphate, while the effect of alendronate on osteoclast number and bone resorption in murine calvariae in vitro could be overcome by the addition of mevalonic acid. These observations suggest that nitrogen-containing bisphosphonate drugs cause apoptosis following inhibition of post-translational prenylation of proteins such as Ras. It is likely that these potent antiresorptive bisphosphonates also inhibit bone resorption by preventing protein prenylation in osteoclasts and that enzymes of the mevalonate pathway or prenyl protein transferases are the molecular targets of the nitrogen-containing bisphosphonates. Furthermore, the data support the view that clodronate acts by a different mechanism.

Alendronate↗
PubMed1998

Anti-tumour activity of bisphosphonates in human myeloma cells.

Multiple myeloma is a haematological malignancy characterized by an expansion of malignant plasma cells within the bone marrow and is frequently associated with bone disease involving the development of osteolytic bone lesions, pathological fractures, osteoporosis and hypercalcaemia. A class of anti-resorptive drugs known as bisphosphonates have been in use to treat osteoclast-mediated bone diseases for the past 3 decades, and are currently proving effective in the treatment of the bone disease associated with multiple myeloma. Recent studies have suggested that bisphosphonate treatment may also result in an improvement in survival in some patients with multiple myeloma. These effects on survival may reflect an indirect effect of the bisphosphonates on tumour growth, via inhibition of osteoclast activity and hence a reduction in the release of tumour growth factors. However, it is also possible that bisphosphonates may have a direct effect on myeloma cells. In support of this we have demonstrated that bisphosphonates can decrease cell proliferation and induce apoptosis in human myeloma cells in vitro, and this review discusses the possibility that bisphosphonates may have not only an anti-resorptive action, but may also have a direct anti-tumour activity.

Animals↗
PubMed1998

Evaluation of recombinant dengue viral envelope B domain protein antigens for the detection of dengue complex-specific antibodies.

To increase the specificity of dengue (DEN) diagnosis based on antibody detection, we have evaluated recombinant proteins as antigens that incorporate most of the B domain of the DEN virus envelope protein fused to the trpE protein of Escherichia coli (trpE-DEN). A pooled antigen consisting of trpE-DEN proteins representing all four serotypes of DEN virus was used in an indirect ELISA for the detection of IgG or IgM antibody. This assay was compared with a standard IgG indirect ELISA and an IgM-capture ELISA using DEN virus-infected cell culture pooled antigens. The results indicated that the trpE-DEN antigens and the cell culture antigens were equally sensitive for detecting IgM and IgG antibodies in convalescent sera from Peru and Indonesia representing virus isolation-confirmed primary and secondary DEN infections, respectively. Fourteen day postinfection IgG antibody-positive sera obtained from individuals infected with DEN-1 virus who had been vaccinated with other flaviviruses were more strongly reactive with the cell culture antigen than with the recombinant antigen, but by day 21 postinfection, a strong antibody response to the trpE-DEN antigens was present. These results suggested that the early antibody response was directed predominantly towards shared flavivirus group antigens that were not detected with the trpE-DEN antigens. Comparison of the trpE-DEN-1 recombinant antigen with a DEN-1 virus-infected cell lysate antigen for the detection of IgG antibody in sera from a cohort of 55 individuals from Peru who seroconverted over a one-year period indicated greater specificity for the recombinant antigens. Also, sera from individuals with no known DEN infections that had been sequentially vaccinated with yellow fever and Japanese encephalitis reacted with the DEN virus cell culture antigen in the IgG ELISA, but did not react with the trpE-DEN pooled antigens. Similarly, YF IgM antibody positive samples that showed cross-reactivity with the DEN virus cell culture antigens, did not react with the trpE-DEN pooled antigens. These results indicated that the trpE-DEN pooled antigen provided a more specific diagnosis of dengue infections than DEN virus-infected cell culture antigen and avoided the biohazards associated with handling live virus during the preparation of diagnostic reagents. The trpE-DEN pooled antigen should permit a better approach to distinguish between past DEN and other flavivirus infections in epidemiologic surveys, and also increase the specificity of serologic diagnosis of acute DEN infections.

Antibodies, Viral↗
PubMed1998

Entry of US medical school graduates into family practice residencies: 1997-1998 and 3-year summary.

This is the 17th 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 16.6% of the 15,894 graduates of US medical schools between July 1996 and June 1997 were first-year family practice residents in October 1997, compared with 15.9% in 1996 and 14.6% in 1995. This is the highest percentage since this series of studies began in 1980-1981 (12.8%). Medical school graduates from publicly funded medical schools were almost twice as likely to be first-year family practice residents in October 1997 than were residents from privately funded schools, 19.8% compared with 11.8%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1997 at 25.8%; the Middle Atlantic and New England regions reported the lowest percentages at 11.7% and 10.7%, respectively. Nearly half of the medical school graduates (48.1%) entering a family practice residency program as first-year residents in October 1997 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. This article reports the average percentage for each medical school for the last 3 years. Also reported are the number and percentage of graduates of colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family practice residency programs, based on estimates provided by the American Association of Colleges of Osteopathic Medicine.

Career Choice↗
PubMed1998

Results of the 1998 National Resident Matching Program: family practice.

The 1998 National Resident Matching Program (NRMP) results reflect a change in the perceptions and choices of physicians entering graduate medical education in the United States. Ninety-one fewer positions were filled in family practice residency programs in 1998, as well as 21 fewer in primary care internal medicine, 12 fewer in primary care pediatrics, and 13 fewer in internal medicine-pediatric programs. In contrast, 49 more positions were filled in anesthesiology, and 12 more US seniors chose diagnostic radiology, two "marker" disciplines that have recently been market sensitive. Thirty-four more positions were also filled in each of categorical internal medicine and pediatrics programs, where trainees are "pluripotential" with perceived options for practicing as generalists or entering subspecialty fellowships, depending on the market. While the demands of managed care and the needs of rural and underserved populations continue to offer a market for family physicians, family practice may have experienced a "primary care backlash" though the 1998 NRMP.

Career Choice↗
PubMed1997

Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium mobilization by estrogen.

RT-PCR was undertaken on total RNA extracts from bone and scales of the rainbow trout, Oncorhynchus mykiss. The rainbow trout estrogen receptor (ER)-specific primers used amplified a single product of expected size from each tissue which, using Southern blotting, strongly hybridized with a 32P-labelled rtER probe under stringent conditions. These data provide the first in vivo evidence of ER mRNA in bone and scale tissues of rainbow trout and suggest that the effects of estrogen observed in this study (increased bone mineral and decreased scale mineral contents, respectively) may be mediated directly through ER.

Animals↗
PubMed1997

The value of breast lumpectomy margin assessment as a predictor of residual tumor burden.

PURPOSE: Margin assessment is commonly used as a guide to the relative aggressiveness of therapy for breast conserving treatment (BCT), though its value as a predictor of the presence, type, or extent of residual tumor has not been conclusively studied. Controversy continues to exist as to what constitutes a margin that is "positive," "close," or "negative." We attempt to address these issues through an analysis of re-excision specimens. PATIENTS AND METHODS: As part of an institutional prospective practice approach for BCT, 265 cases with AJCC Stage I/II carcinoma with an initial excision margin that was < or = 2 mm or indeterminate were subjected to re-excision. The probability of residual tumor (+RE) was evaluated with respect to tumor size, histopathologic subtype, relative closeness of the measured margin, the extent of margin positivity graded as focal, minimal, moderate, or extensive, and the extent of specimen processing as reflected in the number of cut sections per specimen volume (S:V ratio). The amount of residual tumor was graded as microscopic, small, medium, or large. The histopathologic subtype of tumor in the re-excision specimen was classified as having an invasive component (ICa) or pure DCIS (DCIS). RESULTS: The primary excision margin was positive, > 0 < or = 1 mm, 1.1-2 mm, and indeterminate in 60%, 18%, 5%, and 17%, respectively. The predominant histopathologies in the initial excision specimens were invasive ductal (IDC) (50%) and tumors with an extensive intraductal component (EIC) (43%). The histopathology of the initial excision specimen was highly predictive of the histopathology of tumor found on re-excision, as residual DCIS was found in 60% of +RE specimens with initial histopathology of EIC compared to 26% for IDC (p = 0.001). Neither the extent of margin positivity nor the extent of tumor in the re-excision were significantly related to the initial histopathologic subtype; however, a +RE was seen in 59% of EIC, 43% of IDC, and 32% of invasive lobular ILC cases (p = 0.01). The extent of margin positivity was significantly related to the size of the tumor such that tumor size < or = 20 mm was associated with a greater probability of focal or minimal margin involvement. Positive margins graded as focal, minimal, moderate/extensive were associated with a +RE in 26%, 58%, and 84%, respectively (p = 0.001). Further, the extent of positivity was significantly correlated with the extent of residual tumor such that focal/minimal positivity was more commonly associated with micro/small +RE, whereas moderate/extensive positivity was associated with medium/large +RE. When the closest margin of the initial excision specimen was positive, > 0 < or = 1 mm, or 1.1-2 mm, a +RE was found in 56%, 41%, and 17%, respectively (p = 0.01) but did not correlate with the amount of residual tumor. The extent of specimen processing as reflected in the S:V ratio did not correlate with the probability of defining a measured margin as positive nor the probability of a +RE. In a univariate model, the extent of tumor in the re-excision and the histologic type of tumor in the re-excision were significantly associated with margin status and initial histopathology, respectively. The probability of finding a +RE, based on a multivariate model, was associated with the closeness and extent of margin involvement and initial histopathology of an EIC. CONCLUSION: The relative closeness of tumor to the specimen edge and the extent of margin positivity are predictive for residual tumor, though with an error consistent with its limitations as a sampling procedure. The histopathology of tumor in the initial excision is predictive of the type of residual tumor and the extent of margin positivity was correlated with the amount of residual tumor.

Adult↗
PubMed1997

Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes.

Using resting chondrocytes derived from human articular femoral head and a conditionally immortalised human articular chondrocyte cell line we have studied the expression of members of the novel metalloproteinase/disintegrin family termed ADAM. Using RT-PCR we can detect the expression of ADAM-12 a novel family member isolated from myeloma cells [1]. We also find expression of ADAM 10 a functional metalloproteinase/disintegrin first isolated from bovine brain and ADAM-15 a metallodisintegrin isolated from mammary derived epithelial cells. Northern blotting was used to confirm expression. One main transcript is visible for ADAM-12 whereas both ADAM-10 and ADAM-15 have multiple transcripts indicating possible RNA variants potentially derived from alternative splicing or alternative use of polyadenylation sites. Since chondrocytes are proposed as an important source of metalloproteinase enzymes involved in joint pathology the potential relevance of the expression of these molecules to connective tissue disorders is discussed.

ADAM Proteins↗
PubMed1997

Pityriasis rubra pilaris: an unusual cutaneous complication of AIDS.

Pityriasis rubra pilaris is an uncommon hyperkeratotic, papulosquamous disorder that has been reported in patients infected by HIV. We recount a case of pityriasis rubra pilaris in an HIV-seropositive man. A 36-year-old man with a history of ulcerative colitis and recurrent otitis externa had diffuse psoriaform erythroderma. He was treated initially with methotrexate and isoretinoin without clinical improvement. Skin examination showed large, erythematous, orange, scaly patches on the upper extremities and thickening of the nail beds. The palms and soles were hyperkeratotic. Skin biopsy revealed changes that were consistent with pityriasis rubra pilaris. Six months before the onset of symptoms, results of an enzyme-linked immunosorbent assay (ELISA) and Western Blot assay for HIV were negative. Six months after symptoms, results of repeat enzyme-linked immunosorbent assay and Western blots for HIV were positive (CD4+ T-cell count = 200 cells/ mm3). Clinical course had been complicated by episodes of Staphylococcus aureus bacteremia, mucocutaneous candidiasis, and development of localized squamous cell carcinoma of the skin. The increased severity of pityriasis rubra pilaris should prompt clinicians to consider coinfection with HIV in patients who have disease that is refractory to treatment. Clinicians also should remain vigilant for the development of squamous cell carcinoma.

AIDS-Related Opportunistic Infections↗
PubMed1997

Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia.

A cross-sectional survey was conducted in West Kalimantan (Borneo), Indonesia to geographically profile hepatitis E virus (HEV) prevalence in the riverine areas recognized as the foci of epidemic HEV transmission in 1987. Additionally, a contiguous, although distinct, population with no identifiable historical exposure to epidemic HEV was surveyed downstream for comparative purposes. Eight hundred eighty-five sera were assayed by enzyme immunoabsorbent assay for anti-HEV IgG and anti-hepatitis A virus (HAV) IgG markers. A very high percent (90%) of both the outbreak and comparison populations was anti-HAV IgG positive by the age of nine years. In contrast, the prevalence of anti-HEV IgG in the outbreak area (50%) was significantly higher than in the comparison area (23%) (P < 0.0001). In both the outbreak and comparison areas, anti-HEV IgG prevalence increased with age ( < 0.0001), except for the group > or = 50 years of age. The prevalence (53%) of antibody to HEV in the population > or = seven years of age from the outbreak area (alive during the actual 1987 outbreak) was significantly (P < 0.0001) greater than among the children < seven years of age (born after the outbreak) (15%). However, anti-HEV IgG prevalence among the population from the comparison area did not differ significantly between the > or = seven- (23%) and < seven- (20%) year-old age groups. The percentage of anti-HEV IgG-positive individuals among males (47%) from the outbreak area was lower (P < 0.05) compared with females (55%). While overall usage of river water for drinking purposes was not universal, dependence on river water as a primary source was significantly higher (P < 0.001) in households from the outbreak area (60%) compared with the comparison area (30%). This study indicates persistence of an anti-HEV IgG response in a large percentage of the population seven years after an epidemic of HEV infections. Also, the relatively high prevalence (15%) of anti-HEV in children < seven years of age from the outbreak area reflects continuing, sporadic infections.

Adolescent↗
PubMed1997

Indium-111-leukocyte imaging: a case of peritonitis mimicking inflammatory bowel disease.

Leukocytes labeled with 99mTc-HMPAO and 111In have been used extensively in imaging inflammatory disorders, including inflammatory bowel disease (IBD), which has the appearance of tubular bowel activity. Peritonitis is inflammation of the serosal surfaces lining the peritoneal cavity which envelopes the bowel, giving a pattern of diffuse abdominal uptake on imaging. We present a case of an elderly man with surgically and pathologically confirmed peritonitis whose preoperative leukocyte scan mimicked the findings of IBD. Our findings suggest that diffuse peritonitis can mimic IBD on an 111In-leukocyte scan.

Abdomen↗
PubMed1997

Entry of US medical school graduates into family practice residencies: 1996-1997 and 3-year summary.

BACKGROUND AND OBJECTIVES: This is the 16 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 15.9% of the 16,029 graduates of the US medical schools between July 1995 and June 1996 were first-year family practice residents in October 1996, compared with 14.6% in 1995 and 13.4% in 1994. 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 1996 than were residents from privately funded schools, 19.1% compared with 11.2%. The Mountain region reported the highest percentage of medical school graduates who were first-year residents in family practice programs in October 1996 at 24%; the Middle Atlantic and New England regions reported the lowest percentage at 11.4% and 9.9%, respectively. Nearly half of the medical school graduates (48.4%) entering a family practice residency program as first-year residents in October 1996 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. This article reports the average percentage for each medical school for the last 3 years. Also reported are the number and percentage of graduates from colleges of osteopathic medicine who entered Accreditation Council for Graduate Medical Education-accredited family practice residency programs.

Career Choice↗
PubMed1997

Results of the 1997 National Resident Matching Program: family practice.

The 1997 National Resident Matching Program (NRMP) results reveal all-time highs for the number of positions filled in family practice residencies (2,905) and the number of positions filled with US seniors (2,340). This is the largest number of US seniors choosing family practice in the history of the NRMP. Of the 65 additional positions filled through the NRMP, compared with 1996 (2,905 versus 2,840), 64 were filled with additional US seniors (2,340 versus 2,276). Continuing a trend begun in 1992, the 1997 results showed more positions filled in family practice residencies on July 1 than in the previous year, with 3,570 in 1997, compared with 3,494 in 1996. Internal medicine residencies matched 128 more US seniors in 1997, and pediatric residencies matched 63 more US seniors. Of the US seniors matching through the NRMP, only 37.5% are predicted to practice as generalists. In the past 5 years, family practice has been the choice of 71.5% of additional US seniors choosing primary care. The continued record increased interest in family practice as a career, coupled with the nation's need for more family physicians, demands increased support for the nation's family practice residency programs.

Career Choice↗
PubMed1997

Second report of AIDS related attitudes and sexual practices of the Jakarta Waria (male transvestites) in 1995.

As the second part of a community based educational campaign to convey the risk of HIV/AIDS to commercial sex workers in Jakarta, from May-July 1995, a total of 253 male transvestites (WARIA) were questioned about their sexual behavior patterns and their knowledge and attitude toward HIV/AIDS. In the previous report, 1991-1993, there was one out of 830 WARIA found HIV positive in November 1993. In this study, 1995, a total of two out of 253 WARIA were confirmed of HIV infection in July 1995. Most of them still have incorrect knowledge on HIV/AIDS transmission mode, they are still practicing high risk sexual attitudes such as an exchange partner rate of 5 men per three weeks, low condom use (1.2 out of the last 5 sexual contacts). The reasons for not using condoms were forgetfulness 35.3% and partner does not like condom 38.2% Most of WARIA know about condoms (94.5%), but it is difficult to access condom use from small shops around them. Therefore, to prevent further spread of HIV/AIDS in WARIA, condom should be used constantly and properly. It has been shown from another study, that more information, better availability and better promotion of condoms can increase condom use. Thus, attention should be placed on various ways of distributing condoms for WARIA in Jakarta, especially community-based distribution by peer leaders, social marketing and commercial sales.

Adolescent↗