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Neighborhood social disorder as a determinant of drug injection behaviors: a structural equation modeling approach.

Neighborhood environments are increasingly recognized as a contextual determinant of health, behaviors, and disease; however, the pathways through which neighborhood characteristics impact health behaviors are poorly understood. This article examines pathways to elucidate how neighborhood social disorder may lead to HIV transmission. Data are from a baseline survey of 701 injection drug users from the Self-Help in Eliminating Lethal Diseases Study, an HIV prevention intervention in Baltimore. Structural equation modeling was used to examine the pathways among social disorder, psychological distress, and drug injection behaviors. The relationship between disorder and injection behaviors in the models tested suggests that psychological distress is higher in more socially disordered neighborhoods, that distress leads to greater injection frequency and equipment sharing, and that injection frequency predicts equipment sharing.

Adolescent↗

Diagnosis and management of dysfunctional voiding.

PURPOSE OF REVIEW: This review will focus on the diagnosis and management of voiding dysfunction in neurologically and anatomically normal children. The discussion will highlight recent developments and research in the clinical approach as well as the etiology and classification of these disorders. RECENT FINDINGS: Voiding dysfunction in children encompasses a wide spectrum of clinical entities, recently classified collectively as dysfunctional elimination syndromes. Voiding dysfunction typically presents after toilet training and may originate from behavioral issues that arise around this time in childhood development. The spectrum of disorders includes urge syndrome, dysfunctional voiding with an uncoordination between the detrusor and urinary sphincter, and enuresis. Clinical symptoms may vary from mild incontinence to severe disorders with endpoints of irreversible bladder dysfunction with vesicoureteral reflux, urinary tract infection and resulting nephropathy. Diagnosis relies heavily on a good history and physical examination, but also includes radiologic and urodynamic evaluation. Treatment generally consists of medical therapy, primarily with anticholinergics as well as behavioral therapy to modify learned voiding patterns that contribute to the voiding dysfunction. SUMMARY: This overview of voiding dysfunction in children outlines the established approaches to its diagnosis and treatment and highlights the most recent developments in the field.

Biofeedback, Psychology↗

Drug treatment of phobias. Efficacy and optimum use.

In the last decade anxiety disorders have been the focus of intensive research in the psychiatric community, resulting in a rapid growth in our understanding of these illnesses. Diagnostic, biological, and psychopharmacological investigations have revealed important distinctions among these disorders which enable the clinician to make well-informed therapeutic choices and frequently ameliorate or even eliminate anxiety symptoms and related phobic behaviour. The principles of treatment can be simply stated: 1. Careful diagnostic evaluation through history and exclusion of medical and psychiatric conditions which mimic anxiety disorders. 2. Treatment selection based on diagnosis and formulation with the patient of the goals and expected outcome of pharmacotherapy. 3. Systematic application of each drug treatment in sufficient dosage and for an adequate duration permitting progression to the next agent when results are not optimal. 4. Addition of non-pharmacological interventions, usually behavioural therapy, to decrease phobic behaviour. 5. Development of a maintenance or discontinuation strategy tailored to the needs of the patient.

Adrenergic beta-Antagonists↗

[Pharmacokinetic comparison of propranolol and atenolol in people with primary hypertension].

The influence of primary hyperlipidemia on the pharmacokinetics of lipophilic propranolol and hydrophilic atenolol was studied. Thirty patients with hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia and healthy subjects were enrolled. A single dose of 80 mg propranolol or 100 mg atenolol was administered orally using a cross-over study design. Pharmacokinetic parameters were calculated according to the noncompartmental open model. The results reflect the general tendency to altered pharmacokinetics of lipophilic and hydrophilic drugs in patients with disorders of lipid metabolism. In the case of lipophilic propranolol, the most pronounced changes were observed in mixed hyperlipidemia, with a tendency to reduced steady state distribution volume, decrease in the elimination rate constant and total body clearance. In conclusion, the present study revealed an influence of lipid disorders on the pharmacokinetics of beta-blockers, with the most significant alterations seen in mixed hyperlipidemia. The dosage of beta-blockers should be modified in patients with an abnormal lipid profile in serum.

Adrenergic beta-Antagonists↗

[Methodological aspects of bone marrow research using 111In-citrin].

A study of 111In-citrin distribution and kinetics in the body of patients without hemopoietic disorder showed the accumulation (up to 20%) of the injected drug in the bone marrow. Organ fixation, elimination and other pharmacokinetic indices confirming 111In-citrin functional applicability for investigation of the red bone marrow were determined shortly after intravenous injection and in 24 h using a total body meter. These data formed the basis for the calculation of radiation exposures and the solution of methodological problems related to a radionuclide study of the bone marrow in cancer and leukemic patients. 111In concentration in the pelvic bones determined with the help of the total body meter, reflected the total red bone marrow functional activity and was in reverse correlation with a RP elimination value. Total body scintigraphy 24 h after the drug administration made it possible to visualize the bone marrow distribution in the body and to reveal signs of general or local disorders of bone marrow functional activity in leukemias or malignant tumors after combination therapy.

Bone Marrow↗

Report from the Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) and the Domino Liver Transplant Registry (DLTR).

Familial amyloidotic polyneuropathy (FAP) is a fatal disease, belonging to a group of systemic disorders caused by an amyloidogenic transthyretin (TTR) variant. Orthotopic liver transplantation (OLT) eliminates the source of the variant TTR molecule, and is presently the only known curative treatment. A fascinating consequence of this treatment is the possibility of retransplanting the removed FAP liver into another non-FAP patient, which created the so-called domino liver transplantation (DLT) procedure. The Familial Amyloidotic Polyneuropathy World Transplant Registry (FAPWTR) was initiated in 1995, and in 1999 a Domino Liver Transplantation Registry (DLTR) was created. Herein data from these Registries are presented. A total number of 56 centers in 16 countries have performed OLT for FAP, and, today, approximately 65-70 OLTs are performed annually worldwide. During the last decade, a total of 623 patients have undergone 660 OLTs. Patient survival is excellent and comparable to the survival with OLT performed for other chronic liver disorders. Twenty-six centers in 12 countries have reported recipients of DLT grafts and presently 30-35 DLTs are performed annually. The FAPWTR and DLTR have become useful tools in evaluating the potential risks and benefits of these relatively new therapeutic options, in addition to encouraging a rewarding collaboration between centers involved in the management of these patients.

Amyloid Neuropathies, Familial↗

Ontogeny of susceptibility to experimental febrile seizures in rats.

Two experiments were conducted using microwave hyperthermia (MHT) to induce seizures among limited numbers of Long-Evans rat pups. The MHT model of febrile seizures eliminates several methodological complications inherent in previous animal models of the disorder. In Experiment 1, rat pups were rendered hyperthermic with MHT or were sham-irradiated on Days 11, 13, 15 or 17 postpartum. The results indicate a statistically significant decline in seizure susceptibility with age. In Experiment 2, rats were subjected to either single or multiple hyperthermic episodes on Days 11, 13, 15, or 17 postpartum. The results indicate an increase in susceptibility to seizures attributable to prior seizure history. In both experiments, seizures were induced with increases in rectal temperature of 1 to 3 degrees C. The results parallel many clinical features of febrile seizures and argue the efficacy of the MHT model.

Animals↗

Unexplained Nausea and Vomiting.

Nausea and vomiting are debilitating symptoms for patients, and can be challenging problems in diagnosis and management for physicians. Initial efforts must be made to establish a specific diagnosis that represents the pathophysiological cause of the nausea and vomiting. If a specific diagnosis is made (for example, antral ulceration), then specific therapy for the lesion will usually eradicate the nausea and vomiting associated with the specific disease. When standard gastrointestinal diseases are eliminated as a cause of nausea and vomiting, then gastric neuromuscular disorders (disorders of motility) should be considered as potential causes of these symptoms. Gastric neuromuscular disorders range from gastric dysrhythmias and abnormalities of gastric accommodation to frank gastroparesis. Treatments for nausea and vomiting due to gastric neuromuscular dysfunction include: 1) patient education and dietary counseling; 2) gastrokinetic drugs; 3) visceral, sensory afferent and CNS drugs; 4) gastrostomy for stomach venting; 5) jejunostomy for enteral feeding access; and 6) acustimulation and gastric pacemaker therapies. Treatment approaches based on the pathophysiology of gastric neuromuscular dysfunction(s) and on patient education aid in the successful management of unexplained nausea and vomiting.

Journal Article↗

Pharmacokinetics of vinpocetine and its metabolite, apovincaminic acid, in plasma and cerebrospinal fluid after intravenous infusion.

The pharmacokinetics of vinpocetine (ethyl apovincaminate, Cavinton) and its metabolite, apovincaminic acid, was studied in patients with cerebrovascular disorders. Vinpocetine (1 mg/kg) was infused intravenously over 25 min. The elimination half-life of the parent drug in plasma was 4.7+/-2.13 h. Total clearance of vinpocetine was 0.79+/-0.1 1 h(-1) kg(-1). The presence of vinpocetine in cerebrospinal fluid shows that the drug is able to pass through the blood-brain barrier and reach the central nervous system which is a possible site of action. The maximum increase of cerebral blood flow (25%) was measured at 32 min after the start of the infusion.

Journal Article↗

Effects of ethylcholine mustard azirinium ion (AF64A) on the choline acetyltransferase and nitric oxide synthase activities in mesopontine cholinergic neurons of the rat.

The choline analogue, ethylcholine mustard azirinium ion (AF64A), has been proposed as a selective neurotoxin that produces degeneration of central cholinergic neurons. However, the mechanisms of action and the specificity or non-specificity of this toxin are still undefined. In this study, we have investigated the effects of AF64A, in comparison with kainic acid, on cholinergic neurons of the mesopontine formation (pedunculopontine and laterodorsal tegmental nuclei), a neuronal population also expressing nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide. We used choline acetyltransferase immunohistochemistry as a marker of acetylcholine activity, and nitric oxide synthase immunohistochemistry and NADPH-diaphorase histochemistry as markers of nitric oxide synthase activity. Our results show that the injection of low doses of AF64A produces: (1) an area of cavitation in the injection site of pedunculopontine tegmental nucleus (local non-specific effect), and (2) a transient decrease in choline acetyltransferase immunoreactivity in choline acetyltransferase-nitric oxide synthase neurons in both the ipsilateral laterodorsal tegmental nucleus and the perilesional area of the pedunculopontine tegmental nucleus, while their morphology and nitric oxide synthase immunoreactivity remain unaltered (post-diffusion specific effect). These findings indicate that the loss of choline-related enzymatic activity is not necessarily associated with degeneration of cholinergic neurons, and that the recovery of choline acetyltransferase immunoreactivity may arise from neurons whose activity is diminished during the first postinjection weeks. Taking into account that AF64A is a suitable tool to develop a reversible model of neurological disorders related to cholinergic deficit, further efforts should be directed toward elimination of its local non-specific effect.

Animals↗

Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria.

OBJECTIVES: The main objectives of this study were to assess whether the use of different definitions of irritable bowel syndrome (IBS) could influence measurements of its prevalence and characterize the patient population fulfilling these different diagnostic criteria. METHOD: A telephone survey was carried out by contacting 8,221 subjects aged >or=18 Years representative of the French population. A "screening" questionnaire based on three algorithms of IBS classification (Manning, with or without a notion of a minimal duration of symptoms, Rome I and Rome II) was used by specialised inquirers. RESULTS: Twenty three percent of the subjects interviewed stated that they had suffered from abdominal pain during the previous 12 Months. The prevalence of IBS considerably varied, depending on the diagnostic criteria used: 12% based on Manning criteria without reference to the duration of symptoms; 2.5% if the notion of duration of symptoms was added to the Manning criteria, and 2.1% and 1.1% based on the Rome I and Rome II criteria, respectively (the latter including the same notion of duration). In total, 212 subjects (2.6%) met at least one of the criteria including a minimal duration of symptoms, with a predominance for women (sex-ratio close to 2). CONCLUSION: The prevalence of IBS is strongly dependent on the classification algorithm employed. The requirement of a minimum duration of symptoms eliminates IBS in a large number of subjects complaining of abdominal disorders. Once these methodological variations were taken into account, the prevalence of IBS in France was found to be comparable to that published in international literature.

Abdominal Pain↗

Risk of discovering endometrial carcinoma or atypical hyperplasia during hysteroscopic surgery in postmenopausal women.

STUDY OBJECTIVE: To assess the risk of diagnosing endometrial carcinoma or atypical hyperplasia in tissue resected during hysteroscopy performed for intrauterine pathology presumed benign in postmenopausal women. DESIGN: A single-center prospective study (Canadian Task Force classification II-2). SETTING: Department of Gynecology, La Conception Hospital, Marseille, France. PATIENTS: Three hundred twenty-five women with intrauterine pathology, presumed benign, causing postmenopausal bleeding or bleeding related to hormone replacement therapy. INTERVENTION: All women had an endometrial biopsy after diagnostic hysteroscopy to exclude endometrial carcinoma or atypical hyperplasia. Then they underwent hysteroscopic surgical resection (203, 62.5%) or endometrial ablation (122, 37.5%). MEASUREMENTS AND MAIN RESULTS: Two cases each (0.6%) of endometrial carcinoma and endometrial atypical hyperplasia were discovered that were missed by preoperative evaluations. CONCLUSION: Outpatient hysteroscopy and endometrial biopsy do not eliminate the finding of carcinoma or endometrial atypical hyperplasia, as these disorders may be discovered during hysteroscopic surgery.

Aged↗

Phenytoin intoxication in critically ill patients.

Phenytoin intoxication can result in major and possibly life-threatening disorders. Furthermore, the hepatic clearance can become saturated, thus, shifting the elimination from first- to zero-order kinetics. This results in a slow elimination of the compound in case of intoxication. The treatment modalities for phenytoin overdose are limited. Taking into account the high level of protein binding, the molecule is not easily eliminated from the body by means of extracorporal epuration. Although reports exist on the use of MARS (molecular adsorbents recirculating system) dialysis, peritoneal dialysis, and standard dialysis for the elimination, in practice, hemoperfusion, is the most often applied technique. The authors report the case of a hypoalbuminemic patient with severe neurologic signs of phenytoin intoxication (total concentration moderately elevated, free fraction high). A combination of high-flux dialysis and hemoperfusion resulted in a considerable extraction of the drug, accelerating the natural clearance from the body and ameliorating clinical signs of intoxication. In selected patients (with a high free fraction of phenytoin), high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion.

Epilepsy↗

Eating disorders.

Anorexia nervosa and bulimia nervosa present special challenges for physicians. Considerable skill and flexibility, as well as a collaborative spirit, are required to address the important physical, psychological, and social dimensions of these eating disorders. The ideal treatment is an individualized program designed to (1) eliminate the multifaceted effects of a body weight driven well below the biologic set point, (2) develop self-esteem, including a healthy attitude toward the body, and (3) strengthen those aspects of the individual and the family that orient the patient to health instead of illness.

Anorexia Nervosa↗

Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.

BACKGROUND: Men with chronic renal failure evaluated for transplantation are often tested for prostate specific antigen (PSA) to detect prostate cancer. PSA occurs in several different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA to tPSA (%fPSA) is widely used to enhance discrimination of benign disorders from prostate cancer. The low molecular mass of fPSA suggests elimination by renal glomerular filtration and that renal failure may significantly influence %fPSA. We evaluated whether established reference levels for %fPSA are applicable also to patients treated with haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 20 men on intermittent haemodialysis with low-flux membranes and 25 men on CAPD, without known history of prostate cancer. The control group included 3129 men without known prostate cancer. We analysed fPSA and tPSA in serum by dual-label immunofluorometric assays, from which we calculated %fPSA and cPSA. Serum levels of different PSA forms were adjusted for age and presented as geometric means. RESULTS: Percent fPSA was significantly higher in patients on either haemodialysis (39.5%) or CAPD (39.6%) compared with controls (28.1%). Haemodialysis patients, but not CAPD patients, had significantly higher mean levels of fPSA. Levels of tPSA and cPSA for haemodialysis or CAPD patients did not differ significantly compared with controls. CONCLUSIONS: Recommended reference ranges for %fPSA, based on men with normal renal function, do not apply to uraemic men on dialysis. In these men, a high %fPSA should not be considered as a sign of benign disease. This is clinically important in the evaluation of dialysis patients for transplantation, as %fPSA is often used as a tool for detection of prostate cancer.

Adult↗

Treatment of diabetes mellitus to reduce its chronic cardiovascular complications.

Cardiovascular complications are a major cause of morbidity and mortality in patients with diabetes mellitus. Diabetes is a heterogeneous, complex metabolic disorder, and it is unlikely that control of hyperglycemia alone will eliminate the excess of cardiac, cerebral, and peripheral vascular diseases found in diabetic patients. In the care of the diabetic patient, glucose levels should be reduced to normal if possible. In addition, however, it is crucial to evaluate and, if necessary, to correct abnormalities in lipids, blood pressure, and hemostasis. The importance of reducing levels of insulin and insulin resistance is not yet clear. Although many questions remain to be answered, available data strongly suggest that patients with diabetes benefit from more aggressive and comprehensive treatment.

Blood Coagulation↗

The structure of T6 human insulin at 1.0 A resolution.

The structure of T(6) human insulin has been determined at 120 K at a resolution of 1.0 A and refined to a residual of 0.183. As a result of cryofreezing, the first four residues of the B chain in one of the two crystallographically independent AB monomers in the hexameric [Zn(1/3)(AB)(2)Zn(1/3)](3) complex undergo a conformational shift that displaces the C(alpha) atom of PheB1 by 7.86 A relative to the room-temperature structure. A least-squares superposition of all backbone atoms of the room-temperature and low-temperature structures yielded a mean displacement of 0.422 A. Omitting the first four residues of the B chain reduced the mean displacement to 0.272 A. At 120 K, nine residues were found to exhibit two discrete side-chain conformations, but only two of these residues are in common with the seven residues found to have disordered side chains in the room-temperature structure. As a result of freezing, the disorder observed at room temperature in both ArgB22 side chains is eliminated. The close contact between pairs of O( epsilon 2) atoms in GluB13 observed at room temperature is maintained at cryotemperature and suggests that a carboxylate-carboxylic acid centered hydrogen bond exists [-C(=O)-O.H.O-C(=O)-] such that the H atom is equally shared between the two partially charged O atoms.

Crystallization↗

Mechanism of anti-asialo GM1 prevention of graft-vs-host disease: identification of allo-antigen activated T cells.

The purpose of this study was to begin to dissect the mechanism whereby anti-asialo GM1 (alpha ASGM1) prevents otherwise lethal graft-vs-host disease (GVHD) across multiple minor histocompatibility barriers in mice. Phenotypic characterization of cells from the peak proliferative time of the graft-vs-host reaction (C57BL/6J lymph node cells----irradiated LP/J, days 5-7) revealed the alpha ASGM1 and alpha Thy 1.2 identified cells with an approximate 80% concordance and that NK-1.1 staining was negligible. Because resting T cells do not label with alpha ASGM1, the epitope recognized by alpha ASGM1 on GVHR T cells is an activation antigen. Because asialo GM1 has been previously found on the surface of activated macrophages, we wanted to distinguish between the two most likely targets for the in vivo effect of alpha ASGM1 infusions (T cells or macrophages). We compared the effects of alpha ASGM1 infusions on alloantigen-stimulated T-cell proliferation versus antigen presentation: T-cell proliferation was markedly reduced by alpha ASGM1 infusions, whereas antigen presentation function was not diminished. We conclude that the mechanism whereby alpha ASGM1 prevents GVHD does not involve NK cells or antigen presenting cells, but does involve activated donor T cells. The potential therapeutic advantage of such an antibody for use in human disorders compared to pan-immunosuppression lies in its ability to eliminate selectively those T cells involved in the immunologic process (i.e. activated T cells) while sparing the remainder of the T-cell repertoire.

Animals↗