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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

Syntheses, structures and anorectic effects of human and rat amylin.

Amylin, a 37-residue polypeptide with a single disulfide bond originally isolated from the pancreas of type-II diabetic patients, has been shown to cause peripheral insulin resistance and to attenuate the inhibition of hepatic glucose output by insulin. We have also shown that amylin is present in the rat hypothalamus and that it inhibits food intake by rats. In order to further investigate the anorectic properties we synthesized both human and rat amylin by the solid phase method and purified to homogeneity in an overall yield of 10-20%. Structural analyses indicated that human amylin exhibited predominantly a beta-sheet structure at both acidic and alkaline pH, whereas no ordered structure was evident in the case of rat amylin. Intrahypothalamic injection of rat amylin resulted in a potent dose-dependent inhibitory effect on the food intake by rats adapted to eat their daily ration of food in an eight-hour period. Human amylin was less effective as an anorectic agent. Furthermore, rat amylin completely blocked the potent orexigenic effect of neuropeptide Y (NPY). These investigations show that there is a fundamental difference in the secondary structures of human and rat amylin and that rat amylin is a potent inhibitor of both basal and NPY-induced feeding by rats.

Amino Acid Sequence↗
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Structure-activity studies of peptide YY(22-36): N-alpha-Ac-[Phe27]PYY(22-36), a potent antisecretory peptide in rat jejunum.

Peptide YY (PYY) and its homologous peptide, neuropeptide Y (NPY), are known to exhibit potent antisecretory effects in the intestine. To determine the structural requirements to elicit antisecretory effects, we have synthesized several analogs of the PYY active site, PYY(22-36), and compared their binding affinities and antisecretory potencies in rat jejunum. These investigations revealed that the hydroxyl groups of Ser23 and Thr32, as well as the imidazole group of His26, are important for activity in the intestine. N-alpha-acetylation of PYY(22-36) increased both the binding affinity and antisecretory potency. Structure-activity studies with N-alpha-Ac-PYY(22-36) showed that substitution of His26 with parachlorophenylalanine (pCl-Phe) or Tyr36 with N-Me-Tyr reduced receptor affinity, while replacement of Tyr27 with Phe increased the activity substantially. Furthermore, acylation of the alpha-NH2 group with hydrophobic groups, myristic and naphthaleneacetic acids, substantially reduced the antisecretory potencies but not the binding affinities. Further modification of N-alpha-Ac-[Phe27]PYY(22-36) may lead to the development of more potent agonist compounds, which may provide a framework for the design of a new class of antidiarrheal drugs.

Animals↗
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Benign extraovarian mimics of ovarian cancer. Distinction with imaging studies.

Imaging of the pelvis via computed tomography (CT), ultrasound, or magnetic resonance (MR) provides excellent anatomical detail and superb resolution. Despite this, radiologists often have difficulty reaching a specific diagnosis in evaluating adnexal masses. A wide spectrum of benign extraovarian pathology may closely resemble ovarian cancer. Fallopian tube disease such as hydrosalpinx, tuboovarian abscess, and chronic ectopic pregnancy may mimic cystic or solid ovarian neoplasm. Pedunculated uterine leiomyomas may imitate ovarian lesions. Gastrointestinal causes of adnexal masses include mucocele, abscess, and hematoma. These entities may appear similar to ovarian lesions, thus requiring close attention to specific anatomical detail in order to help differentiate them. Similarly, peritoneal disease including tuberculous peritonitis and peritoneal pseudocyst may simulate ovarian tumor. While ultrasound represents the initial imaging modality in the evaluation of most pelvic disease, MR's multiplanar capability and improved tissue characterization make it a valuable modality in many circumstances.

Adult↗
PubMedDate not supplied

Young Investigator Award. Percutaneous facet joint fusion: preliminary experience.

PURPOSE: The synovium-lined apophysial joint is an important cause of back pain through facet arthrosis and nerve root pressure. The short-term results of two relatively noninvasive treatments--facet block and facet rhizotomy--have been better than their long-term results. The authors propose treatment with fusion of the posterior facet joints in the lumbar spine by means of a simple percutaneous procedure performed under local anesthetic with use of radiologic guidance. MATERIALS AND METHODS: In the first phase of this study the technical feasibility of the concept was established in human cadaver spine. In the second phase a canine model was tested in which bone grafts were surgically inserted into lumbar facet joints. Five male and two female mongrel dogs, weighing 18-25 kg (mean, 20.3 kg), were operated on. Each procedure was done in three steps: First, preoperative computed tomographic (CT) scans were obtained to measure facet depth. Second, surgery was performed under fluoroscopic guidance with use of a threaded guide wire, a small cannulated coaxial drilling system, and hydroxyapatite cancellous bone plugs. Third, early postoperative CT scans were obtained to verify bone plug location. CT was repeated at 4 and 6 months after surgery to check for fusion. The dogs were killed at 6 months, and histologic examination was performed. RESULTS: Successful insertion of the bone plug was achieved in 12 of the 14 facets (86%). One dog died as a complication of the procedure. Fusion occurred in five of the 12 surgically treated facets (42%). CONCLUSION: Drilling and surgical insertion of bone plugs into facet joints of dogs were feasible. The fusion results are promising and may improve with future modifications of the technique.

Anesthesia, Local↗
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Increased mortality with intravenous supplemental feeding in severely burned patients.

Patients with large cutaneous burns are characterized by an elevated metabolic rate and lose up to 25% of their body weight within 3 weeks. A previous study suggested that intravenous supplementation to attain nutritional requirements was of no benefit in patients with cutaneous burns covering greater than 50% of their total body surface area. In this study 39 patients with burns greater than 50% of their total body surface area were randomly assigned to receive intravenous supplementation of enteral calories (n = 16) or enteral calories alone (n = 23). Intravenous supplementation decreased the amount of enteral calories that patients with burns could tolerate. The mortality rate was significantly higher (p less than 0.05) in the intravenously supplemented group at 63% as compared with 26% in the group receiving enteral calories alone. Both groups showed significant decrease in natural killer cell activity when compared with controls at both 0 to 7 and 7 to 14 days after injury. T cell helper/suppressor ratios were depressed in both groups when compared with controls; however, the intravenously supplemented group was significantly depressed at 7 to 14 days after burn. Both groups demonstrated hepatomegaly, moderate fatty infiltration, and cholestasis. It is suggested that intravenous supplementation should be carefully evaluated and used only in patients with total enteral failure.

Adult↗
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Is a history of depressive symptoms associated with an increased risk of infertility in women?

Researchers have reported an association between self-reported antidepressant use and increased risk of ovulatory infertility but could not control for confounding by the drug indication. We evaluated the role of depressive symptoms in the development of infertility. We recontacted a population-based sample of Pawtucket Heart Health Program (PHHP) health survey respondents to perform this case-control study. Self-reported infertility was defined as an inability to conceive after 12 months of unprotected intercourse. Controls were women who reported at least one pregnancy. The index age for infertile women was the age at which they first experienced fertility problems, and for the fertile women it was the age of their first pregnancy. History of depressive symptoms was based on self-report before the index age. Women with a history of depressive symptoms were nearly twice as likely to report infertility relative to women without a history of depressive symptoms before the index age after controlling for potential confounders (90% confidence interval: 0.9-3.2). Our data suggest that depressive symptoms as well as the drugs used to treat these conditions may play an important role in the pathogenesis of infertility. The association between depressive symptoms and infertility should be explored further.

Adolescent↗
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Nursing diagnoses for the postpartum woman.

A descriptive, correlational study was undertaken to identify nursing diagnoses selected by mothers during the first 72 hours after birth. The convenience sample of 231 women completed questionnaires listing 34 diagnoses. On average, each mother selected nine diagnoses of concern to her since the birth. Alteration in comfort, potential for growth, alteration in body fluids, impaired mobility, and sleep pattern disturbance were the most frequently selected diagnoses. Only 34.5% of the mothers identified knowledge deficit as a concern. Parity, type of delivery, and length of postpartum time influenced the diagnoses selected. The data suggest modifications in the focus of hospital-based, postpartum nursing care.

Cesarean Section↗
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Thermal effects of hooding incubators.

OBJECTIVE: To determine the effect of covering infant incubators on incubator wall and air temperatures, as well as on infant temperatures. DESIGN: A within-subject ABA design, in which blankets covering the incubators were removed for a 30-minute period and then replaced. SETTING: A neonatal intensive-care unit. PARTICIPANTS: Eight medically stable infants (gestational age, 28-33 weeks; birth weight, 913-1,947 g; and postnatal age, 2-39 days). INTERVENTIONS: Incubator wall and air temperatures as well as infant temperatures were measured during three study conditions: incubators covered (30 minutes), uncovered (60 minutes), and re-covered (30 minutes). MAIN OUTCOME MEASURES: Incubator air and wall temperature; infant temperature. RESULTS: All incubator walls decreased in temperature after being uncovered; the decrease ranged from 0.6-2.2 degrees C. CONCLUSION: Although infants maintained relatively stable body temperatures during the uncovered period, the energy cost to their thermoregulatory efforts is unknown.

Body Temperature↗
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Neurologic complications in pediatric solid tumors.

The cases of 61 children, consecutively diagnosed during 1986-1990 as having malignant solid tumors (but excluding those with brain tumors and lymphoproliferative diseases), were reviewed. Neurologic complications occurred in 19 (31%), most often in association with neuroblastomas and sarcomas. Complications observed in order of frequency were: brain metastases in 6 children, spinal cord compression in 5, peripheral or cranial neuropathies in 4, and seizures in the remaining 4. Early recognition of neurologic compromise and rapid initiation of treatment are mandatory in order to prevent permanent disability.

Adolescent↗
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Negative bone scans in impending tibial stress fractures. A report of three cases.

Three highly motivated military recruits who presented with tibial pain on exertion are reported. Their initial bone scan assessments to rule out stress fracture were normal, and the recruits were returned to demanding training. One month later, because of persistent and increasing tibial pain, they were rescanned and focal activity representative of tibial stress fractures was found in each case. Until now it has been assumed that a negative bone scan ruled out a stress fracture unequivocally. Our reported cases show that bone pain may in fact precede scintigraphic evidence of a stress fracture. Persistent and increasing bone pain during demanding physical activity, even in the presence of a prior normal bone scan, may represent stress fracture and repeat bone scan may be indicated.

Humans↗
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Behavioral health benefits in employer-sponsored health plans, 1997.

Data for 1997 show that three-quarters or more of employer-sponsored health plans continue to place greater restrictions on behavioral health coverage than on general medical coverage. The nature of these restrictions varies by plan type. Some improvement in the treatment of mental health/substance abuse (MH/SA) benefits in employer plans may be occurring, however. Comparisons with data from 1996 show that the proportion of plans with benefits for "alternative" types of MH/SA services, such as nonhospital residential care, has increased. Further, the proportion with special limitations on these benefits shows a modest decrease.

Data Collection↗
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Pharmacotherapy of panic disorder: proposed guidelines for the family physician.

BACKGROUND: Efforts to improve the recognition and treatment of panic disorder in the primary care setting have not resulted in better outcomes. Studies show that even when physicians recognize panic disorder, they do not treat it adequately. Family physicians need specific diagnostic and treatment guidelines when they encounter a patient who has possible panic disorder. METHODS: Four psychiatrists with expertise in the pharmacotherapy of panic disorder and experience working in the primary care setting reviewed the available treatment literature and developed a consensus treatment algorithm for panic pharmacotherapy in the primary care setting. These proposed guidelines were reviewed for accuracy by 3 additional psychiatric experts and for their applicability to the primary care setting by 2 leading experts on the treatment of mental disorders in primary care. RESULTS: Guidelines for medication selection, dosing, titration, side-effect management, and maintenance treatment are proposed. Modifications for patients already on psychotropic medication are provided, and indications for psychiatric consultation are specified. CONCLUSIONS: Panic disorder is a highly treatable condition, and primary care physicians can deliver effective pharmacotherapy if specific guidelines are carefully followed.

Anti-Anxiety Agents↗