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Biomedical subjects

A Halpern

Publications and source records attributed to A Halpern.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Dysplastic nevi as a melanoma risk factor in patients with familial melanoma.

BACKGROUND: Familial melanoma has been associated with "clinically atypical moles" or "dysplastic nevi," (DN) which are markers for increased melanoma risk. In addition, melanomas in these kindreds present at a younger age, and tend to be multiple. METHODS: Melanoma incidence rates were determined for 710 members of 311 melanoma families, defined as kindreds in which melanoma had occurred in two or more blood relatives. Patients were classified either clinically or histologically as expressing DN. Melanomas that occurred before the first examination were recorded, and patients were followed prospectively for new melanomas. RESULTS: In prospective follow-up, the age-adjusted melanoma incidence rate was 1710/100,000 patient-years in family members with DN. In contrast, the rate was zero (no melanomas occurred) in family members without DN. For family members with DN, but without a history of melanoma, the age-adjusted incidence rate of melanoma was 413/100,000 patient-years, whereas the rate was 2779/100,000 patient-years in family members with DN and a history of melanoma. CONCLUSIONS: Dysplastic nevi and a history of melanoma are strong risk factors for subsequent melanoma. Prognostic factors are greatly improved for patients with melanomas diagnosed in follow-up compared with the first two melanomas in each kindred. These findings warrant surveillance of individuals with DN who are members of familial melanoma kindreds.

Adult↗

Legal landmark for community care of former psychiatric patients.

A recent judgment of the Lands Tribunal has set an important precedent which should decrease the potential for restrictive covenants to thwart the development of the government's care in the community programme. In 1989 a Worthing couple were permitted to convert their own house into a residential care home for former psychiatric patients. Judge B Marder, QC, ruled on 12 January 1993 that the "public interest" outweighed a contractual stipulation that the property should be used only for residential, non-business purposes. This is a radical change in the Lands Tribunal's view of mental illness.

Community Mental Health Services↗

Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets.

Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to contain predominantly PKC alpha, beta I, beta II, and delta with minor immunoreactivity for PKC epsilon, zeta, and eta. In intact platelets, sodium oleate caused a time-dependent redistribution of PKC alpha, beta II, and delta from cytosol to membrane fractions with little effects on PKC beta I. On the other hand, PMA and thrombin induced translocation of all four isoenzymes of PKC. In vitro, oleate partially activated (50% of Vmax) purified calcium-dependent PKC (alpha, beta I, and beta II) with an EC50 of 50 microM whereas it fully activated (100% of Vmax) purified calcium-independent PKC (predominantly delta) with an EC50 of 5 microM. The selective effects of oleate on PKC isoenzymes were investigated in platelet cytosol which contains endogenous PKC and its physiologic substrates. Under these conditions, oleate potently activated calcium-independent PKC causing the phosphorylation of the 40-kDa substrate. Activation of calcium-dependent isoforms occurred only at higher concentrations of oleate. Thus, oleate activates multiple isoenzymes of PKC with predominant effects on calcium-independent PKC.

Amino Acid Sequence↗

Strand breaks in plasmid DNA, natural and brominated, by low-energy X-rays.

Single- and double-strand breaks were measured in Col E1 plasmid DNA, natural and partially brominated, irradiated with monoenergetic X-rays (from a synchrotron radiation source) on both sides of the K-absorption edge for Br. The fraction of the undamaged supercoiled form decreased exponentially with the photon dose; its yield in the brominated DNA did not exhibit any energy-dependence. This result is consistent with the calculated relative contributions of photoelectric interactions with individual component atoms which show that an electron flux originating in light atoms outweighs that from bromine. However, X-rays of energy above the Br K-edge appear slightly more efficient in producing double-strand breaks. This result, as well as those reported in the literature on the Auger enhancement of different biological endpoints in cells containing brominated DNA, seem to suggest that the positive charge and submolecular effects associated with the photo-absorption in bromine play some role in damaging processes, besides the initial distribution of deposited electron energy.

Bromine↗

Screening and surveillance of patients at high risk for malignant melanoma result in detection of earlier disease.

Screening, surveillance, and educational programs have been recommended for members of hereditary melanoma kindreds with dysplastic nevi, who are at very high risk for melanoma. For melanomas detected in a surveillance program offered to 555 such persons, the average thickness was 0.52 mm for 28 surveillance incident melanomas, 0.55 mm for 64 nonsurveillance incident melanomas, and 1.44 mm for 48 index lesions (p less than 0.001). The proportion of cases with level I or II invasion was 60.8%, 58.3%, and 36.2% respectively (p = 0.002). The nonsurveillance incident melanomas were diagnosed before entry into the surveillance program, but these patients were presumably aware of the earlier occurrence of two index melanomas in their families. These findings are consistent with a favorable effect of surveillance and education in a high-risk population and suggest that patient factors as well as physician factors may contribute to early diagnosis.

Dysplastic Nevus Syndrome↗

A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.

Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.

Antibodies, Anti-Idiotypic↗

Reduced serum thyroglobulin response to bovine TSH in malignant hypofunctioning solid thyroid nodules: comparison to benign nodular disease.

Forty-three euthyroid patients with a single, solid, nonfunctioning thyroid nodule were submitted to fine needle aspiration biopsy and serum thyroglobulin (Tg) was measured before and after (48h) 10 U of bovine TSH. Twenty-two normal subjects were also submitted to the bTSH test. Patients with nonfunctioning nodules were divided in two groups: (I) Benign or Suspicious Cytology (n = 32), (II) Malignant tissue (n = 11). In the latter group all patients underwent surgery and the pathology findings confirmed the presence of thyroid carcinoma. Twenty-one patients with benign or suspicious cytology were also operated upon and the diagnosis was colloid goiter (n = 16) and follicular adenoma (n = 5). In eleven other patients the nodule reduced significantly in size (8) or was no longer palpable after suppressive therapy (3). Normal individuals had a basal serum Tg mean +/- SD value of 12 +/- 7.2 ng/ml and a peak Tg value of 44 +/- 47 ng/ml. Serum Tg values were significantly higher (p less than 0.01) in patients with benign and malignant nodules. However the mean absolute increment (delta Tg) after bTSH was significantly lower (p less than 0.01) in patients with malignant nodules (7.2 +/- 4.8 ng/ml) as compared with normal subjects (22 +/- 16 ng/ml) or subjects with benign nodules (31 +/- 30 ng/ml). The relative (%) serum Tg increment was also significantly lower in patients with malignant tissues (14 +/- 11) as compared to those with benign nodules (77 +/- 86) or normal subjects (247 +/- 173).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Adenylyl Cyclases↗