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Osteoporosis: screening, prevention, and management.

OBJECTIVE: To present clinical recommendations for osteoporosis prevention that include new support for routine bone mass screening of asymptomatic perimenopausal high-risk women. Technological advances make it conceivable that osteoporosis, a metabolic bone disorder rather than a true disease, can be prevented on a wide scale and eventually eliminated. Effective prevention requires that advanced screening procedures be easily accessible and reimbursable as a wise healthcare investment. STUDY SELECTION: This article reviews research bearing on clinical management of women potentially at risk for osteopenia and osteoporosis. Background includes the pathogenesis of osteoporosis and known risk factors such as heredity, life-style, gynecological history, eating disorders, endocrinopathies, and scoliosis. Studies of bone mass measurement favor dual-energy roentgenographic absorptiometry as the bone densitometry method of choice for screening women at risk and for use with roentgenograms in evaluating bone health. The balance between bone formation and resorption can be assessed by a number of biochemical markers, which are reviewed. Other factors known to affect bone mass are discussed. CONCLUSIONS: Primary care physicians, especially gynecologists, can play a pivotal role by [1] identifying women with higher risks for osteoporosis at earlier ages; [2] stressing the importance of developing maximal bone mass before menopause; and [3] developing individualized patient prescriptions for bone mass determinants under personal control: exercise, nutrition (e.g., calcium and vitamin D), life-style, and hormone replacement therapy.

Bone Density↗

Routine prothrombin time determination before elective gynecologic operations.

The prothrombin time (PT) test is routinely ordered to identify unsuspected bleeding disorders in patients before elective operations. We evaluated the usefulness of screening PT tests before elective gynecologic operations over a 6-month period at Women's Hospital in Los Angeles, California. Of 1546 patients, 1516 (98.1%) had normal test results. Charts of 25 of the 30 patients with abnormal values were available for review: 20 did not benefit from the test results, and five had indications for coagulation testing on history or physical examination. In the absence of specific indications, routine preoperative PT testing before elective gynecologic operations does not contribute to patient care and should be eliminated.

Anticoagulants↗

Elimination of posttraumatic symptomatology by relaxation and visual-kinesthetic dissociation.

Five patients suffering from posttraumatic stress disorder and experiencing persistent intrusive imagery were treated with two sessions of relaxation training followed by two sessions of the visual-kinesthetic dissociation technique. Outcome was monitored using a multiple baseline design. Despite the briefness of the intervention, three of the patients showed an almost complete reduction in the frequency of their intrusive images and substantial changes on other measures of psychopathology. One patient showed partial improvement and one patient showed no improvement at all.

Adult↗

Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models.

Parkinson disease is a common neurodegenerative disorder that leads to difficulty in effectively translating thought into action. Although it is known that dopaminergic neurons that innervate the striatum die in Parkinson disease, it is not clear how this loss leads to symptoms. Recent work has implicated striatopallidal medium spiny neurons (MSNs) in this process, but how and precisely why these neurons change is not clear. Using multiphoton imaging, we show that dopamine depletion leads to a rapid and profound loss of spines and glutamatergic synapses on striatopallidal MSNs but not on neighboring striatonigral MSNs. This loss of connectivity is triggered by a new mechanism-dysregulation of intraspine Cav1.3 L-type Ca(2+) channels. The disconnection of striatopallidal neurons from motor command structures is likely to be a key step in the emergence of pathological activity that is responsible for symptoms in Parkinson disease.

Animals↗

Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release.

STUDY OBJECTIVES: Hypocretins (orexins) are involved in the sleep disorder narcolepsy. While hypocretin-1 has a daily oscillation, little is known regarding the relative contribution of circadian and homeostatic components on hypocretin release. The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined. DESIGN: SCN-ablated (SCNx) and sham-operated control rats were implanted with activity-temperature transmitters. Animals were housed individually under 1 of 3 lighting conditions: 12-hour:12-hour light:dark cycle (LD), constant light (LL), and constant darkness (DD). Lesions were verified histologically and shown not to affect hypocretin-containing cells. Hypocretin-1 concentrations in the CSF were determined every 4 hours using radioimmunoassays. MEASUREMENTS AND RESULTS: Control animals displayed robust circadian (LL, DD) and diurnal (LD) fluctuations in CSF hypocretin-1, locomotor activity, and temperature. Peak CSF hypocretin-1 was at the end of the active period. Activity, temperature, and CSF hypocretin-1 were arrhythmic in SCNx animals in LL and DD. In LD, a weak but significant fluctuation in activity and temperature but not CSF hypocretin-1 was observed in SCNx animals. We also explored correlations between CSF hypocretin-1, CSF corticosterone, and locomotor activity occurring prior to CSF sampling in arrhythmic SCNx rats under constant conditions. Significant correlations between hypocretin-1 and activity were observed both across and within animals, suggesting that interindividual and time-of-the-day differences in activity have significant effects on hypocretin release in arrhythmic animals. No correlation was found between CSF hypocretin-1 and corticosterone. CONCLUSIONS: Hypocretin-1 release is under SCN control. Locomotor activity influences the activity of the hypocretin neurons.

Animals↗

Sperm chromatin structure assay of bulls qualified for artificial insemination.

The goal of our study was to find the relationship between fertility of bulls qualified for AI and the percentage of spermatozoa with abnormal chromatin structure as an independent parameter. We used the frozen semen of 8 mature bulls from one AI center. Each bull was represented by 3 ejaculates collected with at least 2-week intervals. Bull fertility was calculated on the basis of non-return ratio and was expressed as a scale where 100 points represented the average fertility of all the AI center's bulls. Bulls with lower or higher fertility received a lower or higher score respectively. Fertility scores of bulls used in the study ranged from 83 to 104 . Semen was processed according to the SCSA (sperm chromatin structure assay) method and was analyzed by flow cytometry. "Artificial" alpha(t) (alpha(t)=red/green+red fluorescence) and red fluorescence histograms were used for calculation of COMPalpha(t), SDalpha(t), %Red, %PeakR and MeanR parameters. The percentage of spermatozoa with abnormal chromatin ranged from 1.2% to 23.8%. A large variation among ejaculates was found for bulls with lower fertility. Fertility correlated significantly with COMPalpha(t) (-0.50, P < 0.05), SDalpha(t) (-0.55, P < 0.01), %Red (-0.53, P < 0.01), %PeakR (-0.58, P < 0.01) and MeanR (-0.45, P < 0.05). The SCSA method has a practical application in analyzing spermatogenesis disorders in bulls. If regularly applied, it allows us to identify and eliminate ejaculates with a high level of sperm chromatin abnormalities.

Acridine Orange↗

The effects of ante- and postnatal hypoxia on the central nervous system and their correction with peptide hormones.

Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.

Adrenocorticotropic Hormone↗

Rheopheresis for age-related macular degeneration: a novel indication for therapeutic apheresis in ophthalmology.

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly. Successful therapy is not yet available for the majority of patients, especially not for patients with dry AMD. AMD at cellular and molecular levels is at least in part a microcirculatory disorder of the retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders and represents a novel treatment option for patients with dry AMD. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, cholesterol, von Willebrand factor, and alpha 2-macroglobulin results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as a series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation and recovery of retinal function. Two controlled randomized clinical trials demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD patients, especially for those with the dry form. Recently the interim analysis of the sham-controlled, double blind, randomized multicenter Multicenter Investigation of Rheopheresis for AMD (MIRA-I) trial confirmed these results. The framework of completed and still ongoing controlled clinical trials in combination with postcertification studies including the RheoNet registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. The development and continuous update of guidelines for the precise indication of Rheopheresis for AMD follows the requirements of evidence-based medicine.

Adolescent↗

The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis is a disease entity in which patients have (1) elevated eosinophils on esophageal biopsy and (2) symptoms of gastroesophageal reflux. The symptoms do not improve on aggressive acid blockade but do improve on elimination diet or corticosteroid treatment, which tentatively links food allergies to this disorder. OBJECTIVE: The purpose of this study was to identify potential food antigens in eosinophilic esophagitis. METHODS: Patients with eosinophilic esophagitis were identified by biopsy. Potential food antigens were identified prospectively by skin prick testing and patch testing, which were performed through use of standard methods. Atopic tendencies, demographics, and potential food allergies were identified. Repeat esophageal biopsies were reviewed when possible. RESULTS: A total of 26 patients (22 male, 4 female) with a biopsied-confirmed diagnosis of eosinophilic esophagitis underwent both skin prick testing and patch testing to identify potential causative foods. Milk and egg were the most common positive foods with skin prick testing. Wheat was the most common positive food with patch testing. The patients were advised to avoid positive foods as identified by skin prick testing and patch testing. In all, 18 patients had resolution of their symptoms, 6 patients had partial improvement, and 2 were lost to follow-up. Overall, after intervention, esophageal eosinophil counts improved from 55.8 to 8.4 eosinophils per high-power field. The foods most commonly identified by patients as causing symptoms were milk and egg. CONCLUSION: The combination of skin prick testing and patch testing can identify potential causative foods that might contribute to the pathogenesis of eosinophilic esophagitis.

Adolescent↗

How to choose antimicrobials for surgical prophylaxis.

For many of today's clean-contaminated surgical operations antibiotic prophylaxis is a generally accepted and proven procedure. On the basis of a literature survey the parameters to be considered are analyzed: bactericidal spectrum, pharmacokinetics (peak plasma and tissue concentrations, tissue penetration, persistence at high-risk sites and elimination), minimal toxicity, absence of (above all, serious) adverse drug reactions (coagulation disorders, etc.), avoidance of resistance, suitability for single-dose prophylaxis even when the operation is unforeseeably delayed after the administration of the antibiotic, or when the operation lasts a very long time. Finally, the antimicrobial chosen must be cost-effective. The decisive factor, however, remains the proven clinical efficacy for the procedure concerned. There should be no prejudging of any issue until the relevant data have been collected, especially in the case of facts suggesting that single-dose antimicrobial agents are effective even in colorectal surgery, and that cephalosporins of the third generation might offer advantages over those of the first.

Anti-Bacterial Agents↗

Ceftazidime in serious hospital-acquired infections.

Thirty-four patients, most of them immunocompromised, with severe hospital-acquired infections, including septicaemia, respiratory tract and complicated urinary tract infections were treated with ceftazidime 1-2 g intravenously 8-hourly. Twenty-six patients were cured or improved (76%). The most common pathogens were Enterobacteriaceae and Pseudomonas aeruginosa; Gram-positive organisms were isolated from nine patients. Failure were observed in eight patients (24%), four of them had infections caused by resistant organisms, one had infection with Ps. aeruginosa which became resistant during therapy. Superinfection occurred in 11 patients (32%). Mean peak serum levels after 1 g intravenously were 86.2 +/- 30.3 mg/l; after 2 g intravenously 151.6 +/- 52.2 mg/l. The half-life of serum elimination was 1.8-1.9 h, 2 h in patients with liver function disorders and 3 h in patients with renal impairment. Side effects were mild. Ceftazidime is useful in treating Gram-negative infections, but the gaps in its spectrum, the high rate of superinfection and emergence of resistance are matters of concern.

Adult↗

Review article: systemic and topical steroids in inflammatory bowel disease.

Steroids are still widely used in the treatment of inflammatory bowel diseases. Pharmacological studies have shown that there is no major abnormality in the pharmacokinetics of steroids in these disorders. Foam preparations with rectal application decrease the bioavailability to low levels, eliminating systemic complications. For oral use, 'nonsystemic' steroids have been developed. In ulcerative colitis, steroids are rarely needed as 5-aminosalicylates are effective in the majority of patients. This is true for rectal application in distal colitis, as well as in more extensive disease. In Crohn's disease, steroids are more often used; however, in population-based studies, less than 50% of patients have been treated with steroids, as there are alternative treatments available for the large group of patients with mild to moderate activity. For those patients needing steroid treatment, budesonide seems to be a good choice in active disease, but has not shown convincing effects in the maintenance of remission over longer periods of time. There is no place for long-term steroid treatment in ulcerative colitis and very little in Crohn's disease--immunosuppression with azathioprine or related drugs is certainly the better alternative.

Administration, Topical↗

Slow oscillatory activity of rat globus pallidus neurons in vitro.

The neurons in the external segment of the pallidum in the primate develop a characteristic firing pattern consisting of alternately occurring long, 2-20 s, strongly active phases and long completely silent phases when the subthalamo-pallidal excitatory inputs are blocked. The induction of the activity might be a factor in the development of dyskinesias after the loss of subthalamic output. In this study, we used globus pallidus (GPe) slice preparations obtained from juvenile rats to examined the conditions that support the alternatively occurring long depolarized and hyperpolarized phases which we refer to as the slow oscillation (SO). SO was not induced by the blockade of glutamatergic inputs but was induced by treatments that depolarized dendrites and, at the same time, hyperpolarized the somata with current injections. The treatments included elevation of extracellular K(+), application of K-current blockers and the lowering of extracellular Ca(2+). Application of TTX or intracellular BAPTA injection blocked the SO, while the SO could be maintained in hyperpolarization-activated inward current blockers, organic Ca-current blockers and up to 200 microm CdCl(2). These results suggest that Na currents play a major role in the generation of SO in vitro. It can be speculated that Na currents are involved in the development of active phases observed in the GPe after blockade of the glutamatergic inputs in vivo and that the unique property of GPe neurons in maintaining strong activity after the elimination of the glutamatergic driving force contributes to the development of motor disorders such as dyskinesia.

Action Potentials↗

Differential drug response of panic and agoraphobic avoidance in a case of panic disorder.

A case is presented of a patient with severe panic disorder and agoraphobia in whom initial treatment with clomipramine resulted in complete elimination of panic attacks, with no improvement in agoraphobic avoidance. The addition of phenelzine to the pre-existing clomipramine treatment resulted in rapid and complete disappearance of the agoraphobic avoidance. The possible implications of this case for our understanding of the neurobiological relationship between panic attacks and agoraphobia are discussed.

Adult↗

Serum neutralizing activity against Actinobacillus actinomycetemcomitans leukotoxin in juvenile periodontitis.

A relatively high incidence of infection by Actinobacillus actionomycetemcomitans can be shown in subgingival plaque samples obtained from patients with juvenile periodontitis. These organisms possess a potent leukotoxin(s) which rapidly destroys isolated human polymorphonuclear leukocytes (PMNs) and monocytes. If such leukotoxins operate in vivo, they could deprive the gingival crevice area of an essential antibacterial defense mechanism. We have found that sera from juvenile periodontitis patients consistently (greater than 90%) contain antibodies which neutralize Actinobacillus actinomycetemcomitans leukotoxin(s). On the other hand, sera from normal individuals or patients with other types of periodontal disease usually amplified rather than inhibited the leukotoxic reaction. Many patients with juvenile periodontitis have demonstrable defects in PMN or monocyte chemotaxis and this may place them at risk to gingival infection by Actinobacillus actinomycetemcomitans. The immune response against these organisms could be a crucial determinant in the course of juvenile periodontitis. While this disease is relatively rare, it does cause immeasurable emotional, physical and economic hardship for patients and their families. The identification of Actinobacillus actinomycetemcomitans as a potential pathogen in this disorder may eventually lead to specific forms of therapy to prevent and eliminate infection by this organism in these patients.

Actinobacillus↗

Amyloidosis.

Amyloidosis is not a single disease but a series of diseases in which there is extracellular deposition of a protein which, although it may be derived from different and unrelated sources, folds into a beta pleated sheet. There have recently been significant advances in elucidating the pathogenesis and in the treatment of this group of disorders. By identifying the source of precursor protein, treatment is aimed at eliminating or reducing the extent of deposition and is tailored for each patient. Early diagnosis is required for the optimal effect of treatment on patient survival and quality of life. An increased awareness among physicians of the spectrum of the disease and tools to aid its diagnosis is of increasing importance.

Amyloidosis↗

Expression of IP-10/CXCL10 is upregulated by double-stranded RNA in BEAS-2B bronchial epithelial cells.

BACKGROUND: Interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10/CXCL10) is a potent chemoattractant for activated T and NK cells, and elevated levels of IP-10 are identified in bronchoalveolar lavage fluids from patients with pulmonary disorders related to Th-1-type immunity, which is a prerequisite for elimination of viral pathogens. Bronchial epithelial cells play an important role in respiratory infections as the initiator of airway inflammation by releasing chemokines and expressing cell surface membrane molecules involved in leukocyte adhesion. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and induces antiviral reactions in cells. OBJECTIVES: We investigated the regulation of IP-10 in BEAS-2B bronchial epithelial cells in response to poly IC, and also addressed the possible role of retinoic-acid-inducible gene-I (RIG-I) and IFN-regulatory factor 3 (IRF-3), two genes involved in the signaling induced by viral infection. METHODS: The expressions of IP-10 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The overexpression of RIG-I or IRF-3 was performed by transfection of BEAS-2B cells with each cDNA. RESULTS: Poly IC enhanced the expression of IP-10 mRNA and protein in concentration- and time-dependent manners. Overexpression of RIG-I or IRF-3 potentiated the poly-IC-induced upregulation of IP-10. CONCLUSIONS: IP-10 may contribute to antiviral activity through the activation of Th-1-type immunity, and RIG-I and IRF-3 may be involved in this reaction.

Bronchi↗

Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders.

OBJECTIVE: To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations. CASE SUMMARY: A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175-188 micrograms/d. After taking a high dose of calcium carbonate (1250 mg three times daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate. DISCUSSION: Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyrodism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption. CONCLUSIONS: Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction.

Antacids↗