Search PubMed⌕ Search

Biomedical subjects

A Halpern

Publications and source records attributed to A Halpern.

At least 19 recordsLinked to original sources
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

Skin cancer in the elderly.

This article describes the clinical features, treatment options, and prognosis of the most common skin cancers: basal cell carcinoma, squamous cell carcinoma, and melanoma. Emphasis is placed on specific issues that need to be considered when dealing with cancers of the skin in the elderly population. In addition, issues surrounding the early detection and prevention of skin cancer are addressed.

Aged↗
PubMed2001

Muscle metaboreflex control is diminished in normotensive obese women.

There is no information about the muscle metaboreflex control in obese individuals. In 40 normotensive obese women (OW; body mass index 33.5 +/- 0.4 kg/m2, age 32.4 +/- 1.1 yr) and 15 age-matched, normotensive lean women (LW; body mass index 22.7 +/- 0.8 kg/m2, age 34.4 +/- 1.4 yr), we measured muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) in the nonexercising forearm during static exercise at 10 and 30% of maximal voluntary contraction (MVC). Baseline MSNA (38 +/- 2 vs. 31 +/- 1 bursts/min, P = 0.001) and mean blood pressure were significantly higher in OW compared with LW. FBF was significantly lower, whereas forearm vascular resistance was significantly higher in OW. During 10% MVC, MSNA increased similarly in both groups, but during 30% MVC, MSNA was higher in LW. FBF and forearm vascular resistance responses during both 10 and 30% MVC were similar between groups. During posthandgrip circulatory arrest, MSNA remained significantly elevated compared with baseline in both groups, but this increase was significantly lower in OW (3.8 +/- 0.82 vs. 9.4 +/- 1.03 bursts/min, P = 0.002). In conclusion, muscle metaboreflex control of MSNA is blunted in OW. MSNA responses are not augmented during selective activation of central command/mechanoreceptors and metaboreceptors, despite increased MSNA levels in OW. Muscle vasodilatory response during graded handgrip isometric exercise is preserved in OW.

Adult↗
PubMed2001

Contribution of Doppler echocardiography to the evaluation of systolic and diastolic function of obese women versus a control group.

OBJECTIVE: To study by doppler echocardiography the cardiac systolic and diastolic functions of health, uncomplicated obese subjects. METHODS: Fifty-nine obese women with an average body mass index (BMI) of 35 kg/m2 were evaluated and compared with 19 subjects with an average BMI of 23 kg/m2 (control group). RESULTS: In the obese group, a clear tendency was observed toward higher systolic pressure, increased wall thickness and, consequently, myocardial mass, elevation on the circumference stress of the left ventricular wall, and an indisputable presence of diastolic abnormalities. Filling abnormalities were observed with impaired relaxation, with prolonged isovolumic relaxation time (IVRT) and augmented atrium contribution representing early indexes of cardiac dysfunction when systolic performance is still normal. CONCLUSION: Obesity is generally a chronic condition, and doppler echocardiography can be used as a noninvasive instrument for early evaluation of left ventricular diastolic indexes.

Adult↗
PubMed2001

Interaction of glutathione S-transferase M1 and T1 genotypes and malignant melanoma.

The mu and theta classes of glutathione S-transferases (GST) may affect the development of cutaneous malignant melanoma (CMM) by decreasing cellular oxidative stress in skin. These isozymes are absent in a large proportion of the population because of germ-line homozygous deletions in the genes encoding GSTM1 and GSTT1. To determine the association between GSTM1 and GSTT1 homozygous deletions (GSTM1 null and GSTT1 null, respectively) and CMM, we studied 212 patients with CMM, 150 patients with CMM and dysplastic nevi (DN), 147 patients with DN alone, and 124 healthy persons without CMM or DN. Comparing CMM cases (n = 362) to participants without CMM (n = 271), we found no association with GSTM1 null [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.86-1.6] or GSTT1 null (OR, 0.82; 95% CI, 0.56-1.2), either independently or in combination (OR, 1.4; 95% CI, 0.81-2.2), after adjusting for age. However, among the subset of participants with red or blond hair, those with CMM were twice as likely to carry GSTM1 null (OR, 2.2; 95% CI, 1.2-4.2) and nearly 10-fold more likely to carry both GSTM1 null and GSTT1 null (OR, 9.5; 95% CI, 1.2-73) compared with those without CMM. These data suggest that among persons with hair colors traditionally associated with increased risk for melanoma, absence of both GSTM1 and GSTT1 may act to further elevate CMM risk.

Adult↗
PubMed2001

Agminated atypical (dysplastic) nevi: case report and review of the literature.

BACKGROUND: Patients with the atypical mole syndrome have multiple dysplastic nevi that appear to be randomly distributed on certain preferred anatomical sites such as the upper back. These dysplastic nevi are thought to be acquired melanocytic nevi that begin appearing at puberty. To our knowledge, the presence of agminated atypical (dysplastic) nevi has not been reported. OBSERVATION: We describe a patient with the atypical mole syndrome who has more than 100 melanocytic nevi, many of which are clinically atypical and one of which proved to be a melanoma. Among his many melanocytic nevi is a cluster of approximately 50 nevi that are distributed in an area measuring 5 x 3 cm. The histopathologic features of these nevi are consistent with the diagnosis of "dysplastic nevus." CONCLUSIONS: To our knowledge, agminated atypical (dysplastic) nevi have not been described previously. The presence of agminated atypical (dysplastic) nevi in a patient with the atypical mole syndrome can be theorized to arise because of loss of heterozygosity.

Adult↗
PubMed2000

Decreased androgen levels in massively obese men may be associated with impaired function of the gonadostat.

OBJECTIVE: In obese men, sex hormone-binding globulin (SHBG) as well as total testosterone (TT) levels are decreased. Data concerning serum free testosterone (FT) levels in obese men are discordant. FT levels are decreased in only some morbidly obese men, consistent with an impairment of the feedback regulatory mechanism. In this study we aimed to verify serum levels of TT and FT in two groups of obese men (BMI < 35.0 kg/m2 and BMI > 35.1 kg/m2) before and after weight loss. DESIGN: Two groups of obese men (group 1: BMI < or = 35 kg/m2; and group 2: BMI > or =35.1 kg/m2) were studied before and after 6 months of a low energy diet (1200 kcal/day). Every patient received a therapeutic prescription of dexfenfluramine (15 mg b.i.d.) that was maintained for 6 months. SUBJECTS: Thirty-seven obese men and 20 normal weight men. MEASUREMENTS: Serum sex hormones (TT and FT), serum luteinizing hormone (LH) and insulin were analyzed by RIA assays. Plasma insulin levels, serum TT, FT and LH concentrations were obtained before and after weight loss. RESULTS: Moderately obese men (BMI = 32.3+/- 1.9 kg/m2) presented significantly decreased TT levels (390+/-120ng/dl) as well as FT (mean+/-s.d.:16.0+/-4.8pg/ml) as compared with normal controls. FT serum levels had a significant and negative correlation with body mass index (BMI), whereas for TT concentrations this correlation was not significant. Serum LH concentrations (4.5+/-2.9mlU/ml) were normal. Insulin levels were elevated in all patients (46.3+/-30.1 microU/ml). After weight loss there was a significant (P< 0.01) increase in TT, FT and LH levels, whereas insulin concentrations significantly decreased. In massively obese men (BMI = 43.0 6.7 kg/m2), TT (320+/-110ng/dl), FT (11.0+/-2.1 pg/ml) and LH (3.1+/-1.3mlU/ml) were decreased and significantly lower as compared with the previous group and normal controls. As expected, after weight loss TT, FT and LH levels increased significantly while insulin concentrations decreased. CONCLUSIONS: We concluded that FT levels are dependent on the degree of obesity, massively obese men (BMI > or =35.1 kg/m2) being considered as candidates for consistently low FT levels. A functional decrease of LH pulse amplitude and serum LH levels as well as a possible negative action of excess of circulating leptin on the steroidogenesis may be related to the decreased androgens levels in massively obese men.

Adult↗
PubMed1999

A study of 'crisis cards' in a community psychiatric service.

OBJECTIVE: 'Crisis cards' state patients' treatment details and preferences in anticipation of a later occasion when the patient might be too ill to express them directly. We assessed the feasibility of introducing 'crisis cards', or a collaborative form of them, 'joint crisis plans', into a sectorized community psychiatric service. METHOD: All patients with a psychosis and at high risk of crisis were invited to participate. Follow-up examined patients' satisfaction and how the cards were used. RESULTS: In total, 106 eligible patients were identified and offered a card, and 40% agreed to participate. Patients with an affective psychosis, past suicide attempts and less frequent admissions were over-represented among those who agreed to take part. Patients chose to include a wide range of information. For participants, admissions fell by 30% in the follow-up year. CONCLUSION: Crisis cards serve both a 'manifest', practical function (to provide important information when the patient is too ill to do so) and a 'latent' psychological one (positive effects on the patient's attitude to self, their illness and treatment, and their relationship with the clinical team).

Adult↗
PubMed1998

A study of patients with Nelson's syndrome.

OBJECTIVE: The prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome. PATIENTS AND METHODS: We have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceded the adrenalectomy. RESULTS: The comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro-ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group. DISCUSSION: The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.

Adolescent↗
PubMed1997

Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma.

OBJECTIVE: To investigate the relationship of number and type of nevi to the development of melanoma. DESIGN: Case-control study. SETTING: Outpatient clinics in referral hospitals. PATIENTS: Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus. MAIN OUTCOME MEASURES: Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners. RESULTS: Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma. CONCLUSIONS: Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention.

Adult↗
PubMed1997

Pheochromocytoma: study of 50 cases.

PURPOSE: We studied the clinical picture, sensitivity of the biochemical tests and imaging studies, pathological findings, surgical results and followup of patients with pheochromocytoma. MATERIALS AND METHODS: The records of 50 patients with pheochromocytoma were identified. Hyperadrenergic symptoms and signs; urinary dopamine, epinephrine, norepinephrine and vanillylmandelic acid levels; serum dopamine, epinephrine and norepinephrine levels; ultrasonography; computerized tomography; magnetic resonance imaging and 131iodine-metaiodobenzylguanidine images were analyzed. The size, weight and malignancy of the tumors, as well as the operative mortality, survival rate and clinical condition of the patients were also studied. RESULTS: The hyperadrenergic syndrome alone was found in 90% of the patients, Cushing's syndrome alone in 2%, both syndromes in 4%, a palpable abdominal tumor only in 2% and incidental tumors in 2%. The sensitivities of the urinary evaluation in the diagnosis were metanephrines 97%, vanillylmandelic acid 90%, epinephrine 64%, norepinephrine 93% and dopamine 66%. For serum assessment the sensitivities were epinephrine 67%, norepinephrine 93% and dopamine 63%. The sensitivities of the localization examinations were 89, 94, 100 and 88% for ultrasonography, computerized tomography, magnetic resonance imaging and 131I-metaiodobenzylquanidine, respectively. There was only 1 operative death. Of the patients with benign tumors 88% were cured and 12% remained hypertensive with no clinical or biochemical evidence of a hyperadrenergic profile. Of the 8 patients with malignant pheochromocytoma 1 was lost to followup and 3 died of widespread disease (1 without surgery and at 2, 24 and 78 months postoperatively). Of the 4 living patients 3 had no evidence of disease and 1 was well, although with pulmonary metastases.

Adolescent↗
PubMed1997

Melanoma epidemiology.

New data show plateaus and even declines in rates of incidence and mortality due to melanoma among some age groups. Increased rates persist among older men, creating needs for health care planning. Early detection presents a paradox: screening activities, which may be more prevalent among those with higher socioeconomic status, may both increase incidence and decrease mortality (by diagnosing melanoma earlier and through the removal of precursor lesions). Studies of the development of nevi show that they are robust risk markers for melanoma and share some epidemiologic features with melanoma. Multiple primary melanomas develop in 5% to 10% of subjects with melanoma and may reflect genetic predisposition. Combined analyses and methodologic studies have refined estimation of the effects of risk factors.

Age Factors↗
PubMed1996

The addition of dexfenfluramine to fluoxetine in the treatment of obesity: a randomized clinical trial.

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n = 13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n = 20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean +/- SEM 6.2 +/- 2.8 kg and Group II 13.4 +/- 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m2. However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.

Adult↗
PubMed1996

Melanoma awareness and self-examination practices: results of a United States survey.

BACKGROUND: Skin cancers are common and there has been a dramatic increase in their incidence, particularly melanoma. However, little is known about awareness of melanoma and early detection practices in the general U.S. population. OBJECTIVE: In 1995, the American Academy of Dermatology increased their efforts to promote awareness of melanoma. This study was conducted to document current knowledge of melanoma and self-examination practices. METHODS: In February 1995, a telephone survey was conducted in a nationally representative sample of 1001 persons at least 18 years of age (3% margin of error) that included questions on knowledge, attitudes, and practices regarding early detection of melanoma. RESULTS: Almost 42% of those surveyed were unaware of melanoma, and only 26% of those who were aware could identify its specific signs. Most recognized at least one common risk factor for melanoma (e.g., sun exposure, fair skin). However, many did not distinguish melanoma from other skin cancers in terms of risk factors, signs of early disease, and body site distribution. The lowest measures of melanoma knowledge and attitudes were found among those who are male, nonwhite, and parents, and those with the lowest level of education and income. More than half (54%) did not conduct a self-examination. This practice was most frequently reported by women, white persons, and the elderly, as well as those with a greater knowledge of melanoma. CONCLUSION: Our research documents deficiencies in knowledge and practices related to early detection of melanoma in the general U.S. population and supports the need for public education about melanoma.

Adult↗
PubMed1996

Neoplastic progression and prognosis in melanoma.

Most melanomas evolve through an initial stage known as radial growth phase (RGP), encompassing in situ and microinvasive malignancies in which the probability of cure approaches 100%. At the present time, despite a shift toward earlier recognition of melanoma, by the time of diagnosis roughly 70% of melanomas have evolved to a point, known as vertical growth phase (VGP) or tumorigenic melanoma, at which cure is not certain, and prognosis depends upon certain attributes of the neoplasm and the host. Attempts have been made to assemble these attributes into prognostic models to permit estimation of the probability of cure for individuals and for groups of patients. Attributes that have been identified as independent prognostic variables include thickness of the primary neoplasm, the numbers of mitotic figures, and the presence of tumor-infiltrating lymphocytes (TIL). Other biologically important prognostic variables are on the horizon, and some will likely be based on molecules (markers) expressed on neoplastic cells that show functional significance in mechanisms of metastasis.

Disease Progression↗