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Biomedical subjects

P Friedmann

Publications and source records attributed to P Friedmann.

At least 19 recordsLinked to original sources

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.

Bowen's Disease↗

Benefits of linking primary medical care and substance abuse services: patient, provider, and societal perspectives.

Individuals with alcohol and drug use problems may receive health care from medical, mental health, and substance abuse providers, or a combination of all three. Systems of care are often distinct and separate, and substantial opportunities for benefit to patient, provider, and payer are missed. In this article, we outline (1) the possible benefits of linking primary care, mental health, and substance abuse services from the perspective of the major stakeholders-medical and mental health providers, addiction clinicians, patients, and society-and (2) reasons for suboptimal linkage and opportunities for improving linkage within the current health care system. We also review published models of linked medical and substance abuse services. Given the potential benefits of creating tangible systems in which primary care, mental health, and substance abuse services are meaningfully linked, efforts to implement, examine, and measure the real impact should be a high priority.

Adult↗

Angiogenic therapy for the chronically ischemic lower limb in a rabbit model.

The purpose of this study was to evaluate the long-term effectiveness of basic fibroblast growth factor (bFGF) in achieving neovascularization following ischemia from arterial ligation and to determine an optimal dosage level. We used an Ameroid constrictor to produce progressive occlusion of the left femoral artery of rabbits. At 2 weeks, the rabbits were randomized to receive intravenous injection of vehicle (group A, n = 15); 3 microg/kg/day bFGF (group B, n = 12); 10 microg/kg/day bFGF (group C, n = 12); or 16 microg/kg/day bFGF (group D, n = 15) for 3 days. At 1 to 37 days after surgery, we assessed limb neovascularization by transcutaneous oximetry (TCPO(2)), angiography, heart rate, arterial pressure, peripheral vascular resistance (PRU), and muscle blood flow (MBF) during steady-state intra-arterial infusion of saline (basal), acetylcholine, papaverine, or serotonin under anesthesia and capillary density (cap/mm(2)) and capillary per muscle fiber ratio (cap/F). Groups B and C showed significantly greater change in TCPO(2) over time than groups A and D (P < 0.0001). Group D showed the lowest TCPO(2) values from days 14 to 37 and group C the highest. Groups B and C showed a higher number of vessels filled with contrast agent than groups A and D (P < 0.0001). Calf cap/mm(2) and cap/F were significantly higher in groups B and C than groups A and D (P < 0.0001). Calf basal MBF values were higher in groups B and C than in groups A and D, but were not statistically significant. Group D showed the highest level in basal PRU. There were no significant differences in heart rate or blood pressure among the groups. These results show (1) treatment with bFGF has no adverse hemodynamic effects, (2) bFGF enhances angiogenesis and circulation at moderate doses, and these effects persist at least several weeks, and (3) high doses of bFGF may inhibit angiogenesis and collateral circulation.

Animals↗

Continuing medical education: a new vision of the professional development of physicians.

The authors describe their vision of what continuing medical education (CME) should become in the changing health care environment. They first discuss six types of literature (e.g., concerning learning and adult development principles, problem-based/practice-based learning, and other topics) that contribute to ways of thinking about and understanding CME. They then state their view that the Association of American Medical Colleges (AAMC) has made a commitment to helping CME be more effective in the professional development of physicians. In presenting their new vision of CME, the authors describe their interpretation of the nature and values of CME (e.g., optimal CME is highly self-directed; the selection and design of the most relevant CME is based on data from each physician's responsibilities and performance; etc.). They then present seven action steps, suggestions to begin them, and the institutions and organizations they believe should carry them out, and recommend that the AAMC play a major role in supporting activities to carry out these steps. (For example, one action step is the generation and application of new knowledge about how and why physicians learn, select best practices, and change their behaviors). Six core competencies for CME educators are defined. The authors conclude by stating that collaboration among the appropriate academic groups, professional associations, and health care institutions, with leadership from the AAMC, is essential to create the best learning systems for the professional development of physicians.

Education, Medical, Continuing↗

HIV incidence among injection drug users in New York City, 1992-1997: evidence for a declining epidemic.

OBJECTIVES: We assessed recent (1992-1997) HIV incidence in the large HIV epidemic among injection drug users in New York City. METHODS: Data were compiled from 10 separate studies (N = 4979), including 6 cohort studies, 2 "repeat service user" studies, and 2 analyses of voluntary HIV testing and counseling services within drug treatment programs. RESULTS: In the 10 studies, 52 seroconversions were found in 6344 person-years at risk. The observed incidence rates among the 10 studies were all within a narrow range, from 0 per 100 person-years at risk to 2.96 per 100 person-years at risk. In 9 of the 10 studies, the observed incidence rate was less than 2 per 100 person-years at risk. The weighted average incidence rate was 0.7 per 100 person-years at risk. CONCLUSIONS: The recent incidence rate in New York City is quite low for a high-seroprevalence population of injection drug users. The very large HIV epidemic among injection drug users in New York City appears to have entered a "declining phase," characterized by low incidence and declining prevalence. The data suggest that very large high-seroprevalence HIV epidemics may be "reversed."

Adult↗

Prevalence and risk factors for positive tuberculin skin tests among active drug users at a syringe exchange program.

OBJECTIVES: To evaluate the prevalence and predictors of tuberculin skin test (TST) reactions > or =10 mm among active injection drug users (IDUs) at a syringe exchange program in New York City. METHODS: From August 1995 to January 1996, participants were offered TB screening, an interview, and received $15.00 upon returning for skin test interpretation. RESULTS: 610/650 (94%) consented to screening. Of the 566 (93%) who returned for skin test readings, skin test data were available for 564 (99.8%); 14% (95% CI 11.6-17.4) had TSTs > or =10 mm. When the > or =5 mm threshold for interpretation of TST among HIV-infected persons was used, the prevalence of TST positivity increased by only 1%. In univariate analysis, the prevalence of TST > or =10 mm increased with age and with increasing years of IDU (both P = 0.001). Because of a strong correlation between age and duration of IDU, two logistic regression models were examined. In the model with age alone, a history of self-reported TST positivity (OR 8.88; 95% CI 4.9-16.09; P = 0.0001) and increasing age (OR per 10 years increase in age, 1.69; 95% CI 1.24-2.29; P = 0.0008) were independent predictors of TSTs > or =10 mm. In the model with duration of IDU, a history of TST positivity (OR 8.82; 95% CI 4.74-16.41; P = 0.0001) and duration of IDU (OR per 10 years of IDU, 1.46; 95% CI 1.10-1.94; P = 0.0081) were independent predictors of TST > or =10 mm. CONCLUSIONS: Use of the reduced cutoff point for TST positivity from 10 mm to 5 mm did not significantly affect the prevalence of positive TSTs in this cohort of active drug users. Increased prevalence of TB infection with age suggests a high annual incidence of TB infection in this population, and the increased risk of TB infection with increasing duration of IDU suggests that the duration spent in IDU environments may increase infection risk.

Adult↗

Knowledge of tuberculosis among drug users. Relationship to return rates for tuberculosis screening at a syringe exchange.

Tuberculosis is an important health issue among drug users. We sought to evaluate active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the relationship between TB knowledge and attitudes and tuberculin skin test (TST) return rates at a syringe exchange program. DUs were recruited at a syringe exchange program in New York City, were interviewed and offered TSTs, and received $15.00 upon returning for TST reading. The questionnaire evaluated knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV infected. Almost all knew that TB is contagious and more than two thirds knew that TB is treatable and that TB preventive therapy existed. However, fewer than half knew that HIV-related TB could be treated, 30% thought TB could be treated without a medical doctor, and the majority (70%) thought a reactive TST implied infectivity. The rate of return for TST reading was 93%. In multivariate analysis, those who knew that HIV-related TB was curable were more likely to return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p = .03). The high acceptance and return rates suggest that TB services can be incorporated into syringe exchange programs. However, several important gaps in TB knowledge existed in this population at high risk of TB, which may impact on adherence and which support the need for TB education for drug users.

Adult↗

Basic fibroblast growth factor stimulates angiogenesis in the hindlimb of hyperglycemic rats.

Angiogenic growth factors including basic fibroblast growth factor (bFGF) have therapeutic value for chronic ischemia in nondiabetic animals. However, angiogenic therapy for chronic ischemia in a background of diabetes remains unexplored. In the present study, we evaluated the effects of exogenous bFGF on angiogenesis in streptozotocin-induced diabetic rats with ischemic and nonischemic limbs. We produced ischemia of the left lower limb by excising the superficial femoral artery. At 2 weeks, the rats received an intramuscular injection of vehicle (group A), 0.3 microg bFGF/day (group B), or 1 microg bFGF/day (group C), daily for 2 weeks. At 4 weeks, we assessed limb angiogenesis by skeletal muscle capillary density (cap/mm2) and capillary per muscle fiber ratio (cap/F) counts. Group C had significantly higher mean levels compared to group A for calf capillary density (P < 0.0024) and capillary per muscle fiber ratio in both thigh (P < 0.0015) and calf (P < 0.0001). There was a trend toward increased mean capillary per muscle fiber ratio with increasing dose. This trend was significant in the calf (P < 0.0015) and just missed statistical significance in the thigh. There was a similar trend in calf capillary density. We conclude that exogenous bFGF enhances angiogenesis and, possibly, collateral circulation in ischemic limbs of diabetic rats.

Animals↗

Papanicolaou and Kruger assessment of sperm morphology: thresholds and agreement.

The current World Health Organization guidelines (1992) suggest that the presence of > or = 30% normal sperm forms (i.e. PAP criteria) is consistent with normal semen quality. Critical evaluation of sperm morphology (CE; Kruger classification) has shown an excellent correlation with human in vitro fertilization. Utilizing Kruger criteria, > 14% normal sperm forms has been proposed as indicative of normal semen quality. We have performed a retrospective analysis on 261 individuals to assess the agreement between PAP and Kruger criteria for normal sperm morphology (NSM). When the threshold for NSM by PAP was set at 30%, a significant agreement was found between the percentage normal forms of both criteria (Kappa coefficient = 0.37; p < 0.001). Sixty-seven (92%) of the 73 men found to have abnormal sperm morphology by PAP had abnormal semen by Kruger classification. When the threshold for NSM by PAP was established at 50%, the Kappa coefficient was 0.48 (p < 0.001). Sixty of the 72 samples (83%) classified as normal by PAP staining were normal by Kruger criteria. Interestingly, when NSM by PAP was between 30 and 50%, the specimen was just as likely to have normal or abnormal sperm morphology by Kruger (40 vs. 60%, respectively). These results strongly suggest that a high or low percentage of NSM by PAP is in agreement with the Kruger classification. The excellent agreement of Kruger and WHO criteria at the extremes (< 30% and > 50%) may obviate the need for Kruger assessment. However, when WHO morphology is between 30 and 50%, the addition of Kruger evaluation may provide meaningful information to help better diagnose a patient and plan his treatment.

Humans↗

A method to track surgical site infections.

We present an approach to assessing the impact of surveillance for surgical site infections and providing feedback to surgeons on their progress, as part of continuous quality improvement. Adjusting for patient risk factors using the Standardized Mortality Ratio, there was a marked decrease over time in both SMR (1.3 to 0.27) and crude infection rates (32 to 10 per thousand operations per year). These declines cannot be explained by decreased length of hospital stay.

Benchmarking↗

"Why I am not infected with HIV": implications for long-term HIV risk reduction and HIV vaccine trials.

OBJECTIVE: To describe beliefs about remaining HIV-seronegative in injecting drug users in two high-seroprevalence cities, and to consider implications of these beliefs for ongoing risk reduction efforts and for HIV vaccine efficacy trials. DESIGN: Cross-sectional survey with open- and closed-ended questions. SUBJECTS: 58 HIV-seronegative injecting drug users participating in HIV vaccine preparation cohort studies in New York City, New York, U.S.A., and Bangkok, Thailand. MAJOR FINDINGS: Large majorities of subjects in Bangkok (90%) and in New York (89%) believed their "own efforts" to practice safer injection methods and safer sex were very important in avoiding HIV infection. More Bangkok subjects (30%) believed that they would "probably" become infected with HIV in the future than New York subjects (4%). Three percent of Bangkok subjects and 70% of New York subjects believed "having an immune system strong enough to avoid becoming infected with HIV despite exposure to the virus" was very important in avoiding HIV infection. This belief in New York subjects was associated with having previously engaged in high-risk behaviors (i.e., sharing injection equipment, unprotected sex, or both) with partners known to be HIV-seropositive. CONCLUSIONS: Risk reduction programming for high-HIV-seroprevalence populations and within HIV vaccine trials should address not only specific HIV risk behaviors, but also the complex belief systems about avoiding HIV infection that develop within such groups. The person's "own efforts/self-efficacy" appears to be central in the psychology of risk reduction. Members of some high-risk populations may overestimate greatly the frequency of any possible natural immunity to becoming infected with HIV. Prevention programs for these populations will need to address explicitly the probabilistic nature of HIV transmission.

AIDS Vaccines↗

Response of routine semen analysis and critical assessment of sperm morphology by Kruger classification to therapeutic varicocelectomy.

PURPOSE: We studied the effect of varicocelectomy on Kruger morphology and semen parameters. MATERIALS AND METHODS: A total of 33 subfertile men diagnosed with varicoceles was evaluated 3 months before, and 3 to 4 and 6 to 8 months after varicocelectomy. Evaluation involved routine semen analysis and sperm morphology using Kruger classification. RESULTS: Significant improvement in sperm concentration and count was found after varicocelectomy (sperm count preoperatively 117.1 +/- 29, 3 to 4 months postoperatively 162.5 +/- 41 and 6 to 8 months postoperatively 139.8 +/- 25 million sperm, p = 0.0095). Using Kruger classification, evaluation of sperm morphology revealed overall significant increase in percentage of normal A forms at 3 to 4 and 6 to 8 months after surgery (from 9.8 +/- 5.8% A forms, 13.6 +/- 7.7% A forms, and 14.5 +/- 7.5% A forms, respectively, p = 0.0002, normal greater than 14%). Twelve of the 26 patients (46%) with abnormal sperm morphology preoperatively and greater than 4% A forms reached normal levels 3 months postoperatively. Six months after surgery only 6 patients maintained normal values and 3 of the initial 14 nonresponders became normal (9 of 26, 36%). Three patients with severe teratozoospermia (less than 4% A forms) showed improvement in sperm morphology. Four patients with normal sperm morphology preoperatively were not affected by varicocelectomy. CONCLUSIONS: Surgical correction of varicocele was associated with significant improvement in sperm morphology evaluated using Kruger classification. Concentration and count improved after varicocelectomy. Changes were observed as early as 3 months after surgery.

Humans↗

An investigation into the effect of ischaemia and pressure on irritant inflammation.

Reports of chemical burns beneath tourniquets during orthopaedic procedures led us to explore the irritant effects produced by the skin antiseptics used during such procedures. A sphygmomanometer and tourniquet, at a pressure of 200 mmHg for 30 min, was used to created pressure and ischaemia which were then examined separately for their respective effects on irritant inflammation in normal subjects and those with atopic eczema. As no inflammation could be demonstrated with the antiseptics, we subsequently used the known irritant chemical anthralin to examine the effect of ischaemia with and without pressure. Site-related variation in anthralin-induced inflammation was observed but there was no demonstrable effect of either pressure or ischaemia on the inflammatory response. Therefore, as we are unable to show a relationship between ischaemia with or without pressure and irritant inflammation, we conclude that burns under tourniquets are likely to be idiosyncratic reactions and their further investigation requires examination of the individuals affected.

Anthralin↗