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Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 91 records · Page 5Linked to original sources

Community screening to reveal iron deficiency in healthy menstruating women in Israelian suburbs.

OBJECTIVE: To determine the incidence of iron deficiency among healthy women of child-bearing age, study the predictive value of blood hemoglobin level for this condition and assess the efficacy of a community screening program. METHOD: All healthy women aged 18-45 years registered with one community outpatient clinic were requested to complete a questionnaire on present and past medical history; one-third also completed a second questionnaire on symptoms related to anemia. All underwent a blood test for hemoglobin, serum-saturated transferrin and ferritin levels. RESULTS: Of the 163 women who complied (83% of the targeted population), 25.8% were diagnosed as having iron deficiency; of these 40.5% had a hemoglobin level of 12 g% or higher. The most sensitive indicator proved to be serum ferritin level. Iron deficiency was more prevalent in women with a personal history of anemia. Only 34.1% of the study group completed follow-up. CONCLUSION: There is a high incidence of iron deficiency among women of childbearing age. However, because of the surprisingly low compliance with follow-up visits, preventive periodic screening of healthy menstruating women using routine blood tests is not recommended at this time, except for those with specific complaints or who are at high risk.

Adolescent↗

Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing.

OBJECTIVES: This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders. BACKGROUND: To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women. METHODS: We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women. RESULTS: The patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women. CONCLUSIONS: Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.

Bias↗

Infant feeding patterns on Mauritius Island, 1991.

The 1991 Mauritius Contraceptive Prevalence Survey (CPS) included a special module on infant feeding patterns in Mauritius. Since 1985, when a similar CPS was conducted, the incidence of breast-feeding has fallen from 86% to 72%. The duration of any breast-feeding among those breast-fed remained constant at 13.6 months. The module allowed for an assessment of the World Health Organization (WHO) breast-feeding indicators on exclusive breast-feeding, timely complementary feeding and continued breast-feeding. Only 16% of infants 0-3 months old are exclusively breast-fed; only 29% on infants 6-9 months old receive breast milk and complementary foods and only 27% of children 12-15 months are still breast-fed. These patterns of limited breast-feeding and early supplementation may signal future declines in breast-feeding for other African and Asian countries.

Adolescent↗

Rectal carcinoma metastatic to the thyroid gland.

Clinically evident metastases to the thyroid gland are rarely found antemortem. A case of a 59-year-old woman with a history of rectal carcinoma, who presented with low back pain and a mass in the right lobe of her thyroid gland, is presented. The tumour of the thyroid was found to be metastatic adenocarcinoma from her previous rectal cancer. Other synchronous metastases were noted in her lumbar spine and kidneys. The clinical finding of metastases to the thyroid gland is rare, particularly from a colorectal primary. One must consider, however, the possibility of a tumour of the thyroid gland representing a secondary malignancy in any patient with a prior history of cancer.

Adenocarcinoma↗

Serum leptin levels in the acquired immunodeficiency syndrome.

Leptin, a hormone that is secreted by adipose tissue in proportion to fat stores, regulates energy balance and appetite. Recently, tumor necrosis factor and interleukin-1, cytokines that regulate the host response to infection, have been shown to acutely increase leptin levels, raising the possibility that leptin could mediate the anorexia of some infections. We measured leptin levels in patients with the acquired immunodeficiency syndrome and found that leptin levels were not increased relative to body fat in patients who were anorectic, were losing weight, or had a history of weight loss. Furthermore, leptin levels were not increased during secondary infection, suggesting that elevations in leptin do not play a key role in the anorexia of infections associated with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Stable activation and desensitization of beta 2-adrenergic receptor stimulation of adenylyl cyclase by salmeterol: evidence for quasi-irreversible binding to an exosite.

The relaxation of tracheal smooth muscle by the beta 2-adrenergic receptor (beta AR) agonist salmeterol displays several unusual properties: (i) slow onset of action (t1/2 = 5-15 min), (ii) prolonged activation (t1/2 = 8-14 hr), and (iii) the ability to recover from beta AR blockade. These properties led to the hypothesis that salmeterol binds with very high affinity to an exosite in addition to the beta AR activating site. Despite extensive characterization of salmeterol-induced bronchodilation, little is known about the molecular actions of salmeterol. We report the unique properties of salmeterol binding to the beta AR, activation of adenylyl cyclase, and desensitization of the hamster beta AR expressed in L cells. First, we found that salmeterol activation of adenylyl cyclase, although rapid and potent (low EC50 relative to epinephrine), was nevertheless remarkably inefficient relative to the full agonist epinephrine. Reduced coupling efficiency of salmeterol was demonstrated using formulations recently introduced by our group. Second, we found that pretreatment of L cells with salmeterol led to a stable activation of adenylyl cyclase that survives extensive wash procedures and sucrose step gradient purification of plasma membrane fractions. This activation of basal adenylyl cyclase did not require salmeterol binding to the classic active site during pretreatment, as it occurred in the presence of an excess of a beta AR antagonist. Third, we found that the rapid phase of salmeterol-induced desensitization was much reduced relative to epinephrine, consistent with its poor coupling efficiency and with its prolonged activation of adenylyl cyclase. These unique properties of salmeterol support the proposal that it binds reversibly to the activating or active site and as well to an extremely high affinity exosite from which it has access to the active site.

Adenylyl Cyclases↗

Collagen gene expression in the neomatrix of carcinoma of the breast.

Excessive deposition of extracellular matrix or neomatrix is a characteristic of desmoplastic invasive breast carcinomas. Type I and III collagens are abundant neomatrix components. Archival breast tissue sections were studied using 35S-labeled cDNA probes for alpha 1(I) and alpha 1(III) procollagen and in situ hybridization. Among the 33 invasive breast cancers, hybridization was seen forming a gradient-like pattern in fibroblasts closest to tumor cells. In the 10 ductal carcinomas in situ studied, a ring-like pattern of hybridization was seen in proximity to the basement membrane zone. Adjacent normal and benign tissues did not demonstrate the patterns of hybridization described in malignant tissues. Gene expression for neomatrix interstitial collagens occurs before there is evidence of invasion in carcinoma of the breast.

Breast Neoplasms↗

Familial cutaneous malignant melanoma and tumors of the nervous system. A hereditary cancer syndrome.

BACKGROUND: Excessive risk of cutaneous melanoma as a second cancer has been associated with benign or malignant tumors of the nervous system. Cutaneous melanoma and nervous system tumors may independently aggregate in families. There are, however, no previous reports of increased likelihood of tumors of the nervous system in families of patients with cutaneous melanoma or--of cutaneous melanoma in families with tumors of the nervous system. METHODS: The occurrence of nervous system tumors as second cancers was examined in a series of 904 patients with cutaneous melanoma and/or their family members. RESULTS: Fifteen families with 17 members with cutaneous melanoma from this series had one or more additional relatives with tumors of the nervous system, including astrocytoma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma, meningioma, and acoustic neurilemmoma. Another subgroup of 10 patients with cutaneous melanoma had either a meningioma (n = 9) or acoustic neurilemmoma (n = 1) as a second tumor. The pattern of atypical melanocytic nevi occurring in the majority (20/25) of cutaneous melanoma patients in our series and in additional first degree relatives of 9 of 11 of the affected families, has been previously associated with the Familial Atypical Multiple Mole-Melanoma syndrome. CONCLUSIONS: This unusual familial and personal occurrence of tumors, showing differentiation toward tissues of the neural crest, neuroepithelium, and/or mesenchymal derivation, supports a putative association with a hereditary cancer susceptibility trait.

Adolescent↗

Pramipexole in patients with early Parkinson's disease.

We evaluated the efficacy, safety, tolerability, and pharmacokinetics of pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease (PD). The study design was a parallel, placebo-controlled trial using an ascending dose of 4.5 mg/day pramipexole maximum. All subjects received selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who received at least one dose of the study medication, all but one, in the placebo group, completed the trial, which was 9 weeks in duration. The primary efficacy endpoints were changes in scores from baseline to final measurement on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The pramipexole group had a significantly greater improvement (p = 0.002) than the placebo group on UPDRS Part II (Activities of Daily Living). The change in score from baseline to final measurement on UPDRS Part III (Motor Examination) was not significantly different (p = 0.10) between the pramipexole and placebo groups, although the trend favoured the pramipexole group. All subjects in both the pramipexole and the placebo groups experienced one or more episodes of asymptomatic orthostatic hypotension; there was no significant difference between the pramipexole and the placebo groups in the number of subjects experiencing symptomatic orthostatic hypotension. The adverse events profile of pramipexole was similar, in general, to that of other dopamine receptor agonists. Plasma pramipexole levels increased linearly with dose. Pramipexole appears to be promising agent in the treatment of early PD.

Adult↗

Barriers to condom use among women attending planned parenthood clinics.

Assessed condom use, barriers to condom use, oral contraceptive use, partnership status and STD history in 457 15-30 year-old women attending four family planning clinics. Subjects were classified into three condom use groups: Non Users (37%); Current Users (33%); and Past Users (30%). Factor analysis revealed five barriers to condom use: Partner's Perception, Peer's Perception, Pleasure/Intimacy, Communication, and Low Perceived Need. Multivariate analyses revealed significant group differences on only two barrier factors: Pleasure/Intimacy and Low Perceived Need. Low Perceived Need accounted for 13.5% of the variance in condom use. Women with low perceived need to use condoms were more likely to use oral contraceptives.

Adolescent↗

cAMP-dependent protein kinase and protein kinase C consensus site mutations of the beta-adrenergic receptor. Effect on desensitization and stimulation of adenylylcyclase.

Activation of cAMP-dependent protein kinase (cAPK) or protein kinase C (PKC) causes a rapid desensitization of beta 2-adrenergic receptor (beta AR) stimulation of adenylylcyclase in L cells, which previous studies suggest involves the cAPK/PKC consensus phosphorylation site in the third intracellular loop of the beta AR, RRSSK263. To determine the role of the individual serines in the cAPK- and PKC-mediated desensitizations, wild type (WT) and mutant beta ARs containing the substitutions, Ser261-->Ala, Ser262-->Ala, Ser262-->Asp, and Ser261/262-->Ala, were constructed and stably transfected into L cells. Results showed that serine 262 was the primary site of the cAPK-induced desensitization, whereas either serine 261 or serine 262 was sufficient to confer the 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA)/PKC-mediated desensitization. Coincident stimulation of cAPK and PKC caused an additive desensitization (6-8-fold increase in the EC50) which was significantly reduced (80%) only by the double substitution mutation. Quantitative evaluation of the coupling efficiencies and the GTP-shift of the WT and mutant receptors demonstrated that only one of the mutants, Ser262-->Ala, was partially uncoupled. The Ser262-->Asp mutation did not significantly uncouple, demonstrating that introducing a negative charge did not appear to mimic the desensitized state of the receptor. The beta AR expression level played a critical role in determining the pattern of beta AR desensitization; i.e. while the overall desensitization was unaltered within a large range of beta AR expression level (10-300 fmol/mg), the increase in EC50 and decrease in Vmax were differentially affected by the change in the receptor level.

Adenylyl Cyclases↗

Pharmacologic stress dual-isotope myocardial perfusion single-photon emission computed tomography.

Separate-acquisition rest thallium-201/exercise technetium-99m sestamibi (sestamibi) dual-isotope single-photon emission computed tomography (SPECT) has been shown to be effective for assessment of myocardial perfusion and viability. The present study was designed to validate the dual-isotope approach when used in conjunction with pharmacologic stress. All patients had rest 201TI SPECT followed immediately by adenosine (n = 82) or dipyridamole (n = 50) infusion and sestamibi injection. Sestamibi SPECT was performed 1 hour later. The entire study lasted < 2.5 hours. The patient population was categorized into three groups: 51 consecutive patients with coronary angiography and no previous myocardial infarction (group I), 58 consecutive patients with a low prescintigraphic test likelihood of coronary artery disease (group II), and 23 consecutive catheterized patients with remote Q-wave myocardial infarction (group III). For group I patients, the sensitivity and specificity for dual-isotope SPECT were 92% (35 of 38) and 85% (11 of 13), respectively, when > or = 50% coronary artery narrowing was considered significant and were 97% (34 of 35) and 81% (13 of 16) respectively, when > or = 70% narrowing was considered significant. The normalcy rate among the 58 patients of group II was 96%. Comparisons for pattern of stress-defect reversibility demonstrated that of the 97 stress defects within the infarct zones (group III), 15% were reversible and 85% were nonreversible. In contrast, of the 227 stress defects within the diseased (> or = 50% stenosis) vessel zones of the group I patients, 93% were reversible and 7% were noreversible (p < 0.001 vs group III). In conclusion, separate acquisition rest 201-TI/pharmacologic stress sestamibi dual-isotope SPECT is an efficient myocardial perfusion imaging protocol with high accuracy for detection and assessment of angiographically significant coronary artery disease.

Adenosine↗