Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer

Even with a good surveillance program, nosocomial infections may be not recognized because of several reasons: absence of symptoms or prolonged incubation period (eg, viral bloodborne infections, tuberculosis); problems with the microbiological diagnosis, because adequate specimens may be difficult to obtain or special methods should be used (eg, fungal infections, virus, new agents); shorter hospital stays (eg, surgical-site infections); difficulty in distinguishing between nosocomial and community-acquired infections (eg, influenza); and failure to detect clinically relevant colonization (eg, multiresistant microorganisms). Because of the important potential consequences of occult nosocomial infections, specific surveillance programs should be designed to address these problems.     

Therapy of congestive heart failure in elderly persons

LVEF should be measured in all elderly persons with CHF Underlying causes and precipitating causes of CHF should be treated. Persons with CHF associated with abnormal LVEF should be treated with a low sodium diet, diuretics, and ACE inhibitors. If CHF persists, digoxin should be added. If CHF still persists, isosorbide dinitrate plus hydralazine should be added. If CHF still persists, a beta blocker should also be added. However, calcium channel blockers should not be used. Persons with CHF associated with normal LVEF should be treated with a low sodium diet, diuretics, and ACE inhibitors. If CHF persists, a beta blocker, isosorbide dinitrate plus hydralazine, or a calcium channel blocker should be added to the therapeutic regimen. If sinus rhythm is present, digoxin should not be used. Persons with CHF and abnormal or normal LVEF unable to tolerate ACE inhibitors should be treated with losartan.     

Alternatives to estrogen for the treatment of hot flashes

Postmenopausal women experiencing hot flashes in whom estrogen replacement is contraindicated have alternatives available to them; however, there is no clearly defined treatment modality. The literature addressing many of these alternatives has serious limitations, which include the small number of women enrolled and lack of comparative studies between agents. Each patient needs to be assessed in terms of her current medical status, concomitant medications, and the degree to which vasomotor instability interferes with everyday activities. The literature suggests that megestrol acetate 20 mg bid may provide significant relief. Women who opt to use megestrol acetate must be told in advance that the effects will not be felt immediately particularly if tamoxifen is used concomitantly. Clonidine and medroxyprogesterone may constitute potential alternatives, but patients may not be able to tolerate the adverse effects. Because of the lack of literature supporting their clinical use, options such as vitamin E and ginseng need to be approached cautiously. Exercise has a role in alleviating some of the complications associated with menopause, such as heart disease and osteoporosis, but its effect on neurotransmitters and hormone concentrations, and how this relates to the treatment of hot flashes have not been characterized. Patients should be told that regular physical activity, a balanced diet, avoidance of alcohol and caffeine, and stress reduction may be of additional help in decreasing vasomotor flushing.     

Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals sigma receptor binding

The mechanism of the antidepressant action of St. John's wort (Hypericum perforatum) remains unknown. A central component similar to that of the other clinically-popular antidepressants (e.g., inhibitors of 5-HT or norepinephrine reuptake or MAO) is suspected to play a role, but other mechanisms distinct from the SSRIs, NSRIs or MAOIs are possible. The extract of St. John's wort that is used clinically consists of multiple compounds. Hypericin is believed to be one of the major components responsible for the antidepressant effect. In the present study, the affinity of hypericin was determined at thirty receptor or reuptake sites. At 1.0 microM, hypericin inhibited less than 40% of specific radioligand binding at all sites except mAChR and sigma receptors. The demonstration of sigma receptor binding of hypericin is a novel finding and it might contribute to a new understanding of the clinical attributes of St. John's Wort.     

Airway subsensitivity with long-acting beta 2-agonists. Is there cause for concern?

Regular treatment with both long- and short-acting beta 2-agonists results in tolerance to their bronchoprotective effects, although the relevance of this phenomenon in terms of long term asthma control remains unclear. However, there appears to be no appreciable difference between the 2 long-active beta 2-agonists, salmeterol and formoterol, in their propensity to induce beta 2-adrenoceptor down-regulation and subsensitivity. The degree of subsensitivity appears to be somewhat greater with indirect stimuli such as exercise and allergen challenge, compared with direct stimuli such as histamine and methacholine. This loss of functional antagonism with long-acting beta 2-agonist therapy is partial and is not prevented by concomitant inhaled corticosteroid therapy. However, the protective effects of inhaled corticosteroids on their own appear to be additive to those of long-acting beta 2-agonists when both drugs are concomitantly administered in the long term. The subsensitivity to bronchoprotection may be of clinical relevance in terms of patients who are inadvertently exposed to indirect bronchoconstrictor stimuli such as allergens or exercise, suggesting that long-acting beta 2-agonists should not be taken on a regular basis for this particular indication. There is a greater tendency for bronchodilator subsensitivity to develop with longer-acting, than with shorter-acting beta 2-agonists, and this may reflect the longer duration of beta 2-adrenoceptor occupancy and consequent downregulation. As with the bronchoprotective effects of long-acting beta 2-agonists, the development of bronchodilator subsensitivity is only partial and occurs regardless of whether patients are taking concomitant inhaled corticosteroid therapy. The long-term bronchodilator action of the long-acting beta 2-agonist itself is maintained within the twice daily administration interval. However, subsensitivity occurs in relation to a blunted response to repeated doses of short-acting beta 2-agonists, as in the setting of an acute asthma attack. There is considerable inter-individual variability in the propensity for downregulation and subsensitivity, which is determined by genetic polymorphism of the beta 2-adrenoceptor. Current international asthma management guidelines suggest that long-acting beta 2-agonists should be used on a regular basis in patients who ware inadequately controlled on inhaled corticosteroid therapy, so the addition of long-acting beta 2-agonist therapy is an alternative to using higher doses of inhaled corticosteroids. There are, however, concerns that regular long-acting beta 2-agonists might result in masking of inadequately treated inflammation in patients receiving suboptimal inhaled corticosteroid therapy. Physicians should be aware of the airway subsensitivity that develops with long-acting beta 2-agonist therapy, and patients should be warned that they may have to use higher than conventional dosages of short-acting beta 2-agonists to relieve acute bronchoconstriction in order to overcome this effect. In patients receiving an optimised maintenance dose of inhaled corticosteroid, if long-acting beta 2-agonists are to be used on an as required basis, it would seem rational to use formoterol for this purpose, due to its faster onset of action than salmeterol.     

Value of digoxin in heart failure and sinus rhythm: new features of an old drug?

Digoxin has been a controversial drug since its introduction >200 years ago. Although its efficacy in patients with heart failure and atrial fibrillation is clear, its value in patients with heart failure and sinus rhythm has often been questioned. In the 1980s, reports of some large-scale trials indicated that digoxin, with or without vasodilators or angiotensin-converting enzyme inhibitors, reduced signs and symptoms of congestive heart failure and improved exercise tolerance. This beneficial influence was mainly found in patients with more advanced heart failure and dilated ventricles, whereas the effect in those with mild disease appeared to be less pronounced. In the last few years, new data have shown that digoxin may also have clinical value in mild heart failure, either when used in combination with other drugs or when administered alone. As neurohumoral activation has increasingly been recognized to be a contributing factor in the disease progression of chronic heart failure, the modulating effects of digoxin on neurohumoral and autonomic status have received more attention. Also, there is evidence that relatively low doses of digoxin may be at least as effective as higher doses and have a lower incidence of side effects. Further, the recognition that the use of digoxin too early after myocardial infarction may be harmful and the development of other drugs, in particular angiotensin-converting enzyme inhibitors, have obviously changed the place of digoxin in the treatment of chronic heart failure. The large-scale survival trial by the Digitalis Investigators Group (DIG), whose preliminary results have recently been presented, has shown that although digoxin has a neutral effect on total mortality during long-term treatment, it reduces the number of hospital admissions and deaths due to worsening heart failure. The potentially new features of the old drug digoxin are discussed in this review.     

St. John's Wort (Hypericum Perforatum): Practical considerations based on the evidence.

Reviews the available data on hypericum perforatum, an herbal remedy known as St. John's wort commonly used for psychological and psychiatric symptoms, such as anxiety, depression, cognitive dulling, and insomnia. Specifically, data regarding hypericum's efficacy, tolerability, and potential for interactions is examined. It is hoped that this review will allow clinicians to draw their own conclusions regarding this herb and provide them with information for educating and guiding discussions with patients. It is noted that the ethical, legal, and practice issues related to psychologists recommending—or even discussing—the use of herbal preparations remain complex, and that psychologists should be aware that this is not a risk-free area. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fatality due to intravenous diltiazem for acute ventricular rate control

Progressive, sustained bradycardia resulting in asystole and subsequent death is reported in a 70-year-old woman with hyperkalemia and suspected digoxin toxicity following a 0.25 mg/kg intravenous diltiazem dose for treatment of atrial fibrillation with a rapid ventricular response. The possible pharmacodynamic and pharmacokinetic interactions between diltiazem, digoxin, and an elevated plasma potassium concentration are discussed and related to the outcome of the case. The routine practice of concomitant administration of diltiazem for rapid ventricular rate control and digoxin for long-term control may be dangerous in a subset of patients.     

Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options?

The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean fever. Azathioprine can be used when the maternal condition requires a cytotoxic drug during the first trimester. Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.     

Antidiarrheal agents for the management of treatment-related diarrhea in cancer patients

The efficacy and use of antidiarrheal agents in patients who diarrhea associated with cancer treatments are reviewed. Diarrhea is common in cancer patients and may interfere with cancer treatment. Diarrhea may be induced by chemotherapy, radiation therapy, surgery, graft-versus-hot disease (GVHD) or infection after bone marrow transplantation, and other causes. The general goal of antidiarrheal therapy is to reduce fluid loss in the stool by inhibiting intestinal secretion, promoting absorption, and decreasing intestinal motility. Antidiarrheal agents may be classified as intestinal transit inhibitors, intraluminal agents, proabsorptive agents, and antisecretory drugs. Opiate agonists are the most commonly used intestinal transit inhibitors; they can be effective in treating cancer treatment-related diarrheas but must be used cautiously. Intraluminal agents include clays, activated charcoal, and cholestyramine; these adsorbents and other binding resins can interfere with the absorption of orally administered antidiarrheals and other drugs and are unlikely candidates for use in most cases of diarrhea in cancer patients. Clonidine, a proabsorptive agent, should be used only in patients with secretory diarrhea refractory to opiate agonist treatment. Octreotide is an antisecretory drug that has shown considerable efficacy in clinical trails as a treatment for diarrhea caused by chemotherapy of GVHD; its use for radiation therapy-induced diarrhea, although not studied clinically, is nevertheless an option. In general, opiate agonists and octreotide appears to offer the most efficacy and flexibility. Opiate agonists and octreotide are effective agents for cancer treatment-related diarrhea.     

A possible interaction of potential clinical interest between digoxin and acarbose

This case report describes a 69-year-old woman with diabetes mellitus and heart failure who repeatedly had unusual subtherapeutic levels of plasma digoxin. When the drug therapeutic regimen was checked it was found that a new drug, acarbose, had been added to the therapeutic regimen before the unexpected laboratory reported results. Because other drugs included in her therapeutic menu were rejected as being responsible for decreased levels of digoxin, it was recommended to discontinue acarbose to evaluate its role. In the absence of acarbose, the plasma concentration of digoxin increased to the therapeutic range. We concluded that acarbose may be responsible for a pharmacokinetic interaction with digoxin by a still unknown mechanism. Although discontinuation of acarbose was recommended, the attending physician discontinued administration of digoxin because the clinical condition of the patient did not get worse during subtherapeutic levels of digoxin.     

Biochemical evaluation of digoxin dosage in patients with heart failure

The investigations were carried out in 56 patients aged 54 to 84 years, treated with a supporting dosage 0.25 mg of digoxin because of chronical insufficiency of the heart, according to the NYHA classification II and III degree, in whom the functions of liver and kidneys have not been ascertained. A fourfold determination of digoxin concentrations in the blood was established in the time of distribution balance. From among the examined patients three groups were separated: receiving the drug chronically at 8.00 a.m. (group A), receiving it at 8.00 p.m. (group B) and group C, for which the sacral method was used. Depending on medical indications the patients received during the examination other drugs. In group C the therapy was limited to diuretic drugs. In no clinical symptoms of digitalism could be observed. Subtherapeutic levels of digoxin (< 0.8 ng/ml) were found in the three groups on an average in 50% of the patients. The high percentage of patients with nontherapeutic concentration in blood serum confirms once more, that treatment with digoxin without checking their concentration in the serum does not give the certainty of suitable dosage. The results of the studies show that the optimalization of digoxin therapy from the point of pharmacological view should be based on a penetrating estimation of the whole of the clinical image, the checking of the image with the help of the concentration determinations of the drug.     

Fibro-osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods

BACKGROUND: Asthma patients are frequently exposed to antiallergic and antitussive medications, in addition to their respiratory treatment. These medications interfere with inflammatory pathways common to all atopic diseases and could affect asthma. OBJECTIVES: To investigate associations between antiallergic and antitussive medications and the occurrence of asthma exacerbations and to assess the extent of use of these medications in asthma. METHODS: Regular users of anti-asthma medications were identified in a drug dispensing database. A base-cohort of asthma patients was identified using age and exposure criteria. A nested case-control study was performed within the base-cohort: the outcome was defined as a new dispensing of oral corticosteroids and matched cases and controls were compared regarding exposure to antiallergic medications. Odds ratios (OR) were computed by conditional logistic regression and adjustment incorporated markers for asthma severity. RESULTS: 680 asthma patients were followed in the base-cohort for an average duration of 1390 days. Antitussives, antihistamines and nasal corticosteroids were used by respectively 40, 30 and 13 per cent of the asthma population. Among the patients, 134 cases were pair matched with controls. In these pairs, antitussives showed a significant association with asthma exacerbations, with an OR of 3.1. The association had borderline significance for antihistamines and was not significant for nasal corticosteroids. The results were not modified by adjustment for disease severity. CONCLUSIONS: This study confirms that antitussives and antihistamines are commonly used by asthmatics and indicates that both classes are associated with increased occurrence of asthma exacerbations; assessing causality from present data is, however, difficult. Nasal corticosteroids are used less often and are not associated with the outcome. Antihistamine and antitussive medications should be more thoroughly investigated in asthma patients.     

Cross-reactivity of TDX and OPUS immunoassay systems for serum digoxin determination

The properties of the widely used TDX Analyzer and recently developed OPUS Immunoassay System were compared using 403 serum specimens taken from patients who did or did not take digoxin. Of the 210 specimens from patients not treated with digoxin, a false- positive digoxin concentration was detected in 15 specimens (7%) by TDX and in only 2 specimens (1%) by OPUS because of the cross-reactivity with structurally similar drugs. Potassium canrenoate, digitoxin, deslanoside, and methyldigoxin exhibited marked concentration-dependent cross-reactivity in the TDX assay method, whereas deslanoside and methyldigoxin only showed cross-reactivity with the antibody used in the OPUS method. Although a poor correlation was observed between these two methods for the determination of 193 samples from patients treated with digoxin, the correlation was remarkably improved (r = 0.914) and the slope approximated unity when excluded the data from patients who were treated concurrently with the cross-reactive compounds. In routine TDM of digoxin, the authors experienced two cases in which cross-reactivity of the assay system caused a clinical problem. Concurrent administration of intravenous canrenoate apparently interfered with the digoxin assay by TDX, but this problem was solved by using the OPUS system. The authors found OPUS more useful for monitoring serum digoxin concentrations in patients because of its superior specificity.     

Congestive heart failure

The differentiation between systolic and diastolic CHF is clinically important because it allows one to formulate an appropriate therapeutic regimen. As a rule, ACE inhibitors have become a major component in the treatment of systolic heart failure; diuretics, digoxin, and other vasodilators are used in conjunction with them. Optimal therapy for diastolic heart failure remains to be defined. Further research is required for this subset of patients. Numerous other support measures, such as counseling, activity, diet, patient knowledge of medications, and compliance, all affect the patient's outcome.     

Contact allergy to topical corticosteroids and systemic contact dermatitis from prednisolone with tolerance of triamcinolone

We report the case of a 27-year-old female who had an allergic contact dermatitis to topical corticosteroids belonging to the corticosteroid groups A and D. Upon oral treatment with prednisolone a disseminated exanthema began within 24 h. Patch tests revealed sensitization to corticosteroids of group A, C and D, including prednisolone-21-acetate and betamethasone valerate, but not of group B corticosteroids such as triamcinolone. After intradermal testing of corticosteroids the exanthema flared again and the patient was treated with oral triamcinolone, with rapid improvement of her symptoms. A literature review revealed that exanthematous reactions after systemic treatment with corticosteroids have been rarely reported. Since corticosteroids are essential emergency drugs, a safe corticosteroid should be identified for such patients. Patch and intradermal tests may be used for that purpose.     

Pathogenesis and treatment of liver fibrosis in alcoholics: 1996 update

Fibrosis is a common end stage for most chronic liver diseases. It results from an imbalance between collagen production and degradation. One promising approach for prevention and treatment is the stimulation of collagenolytic processes. In nonhuman primates it was found that polyenylphosphatidylcholine (PPC), extracted from soybeans, protects against alcohol-induced fibrosis and cirrhosis and prevents the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2-containing PC species; it also attenuates the transformation of lipocytes into collagen-producing transitional cells. Furthermore, it increases collagen breakdown, as shown in cultured lipocytes enriched with pure dilinoleoyl PC (18:2-18:2 PC), the main PC species present in the extract, which may be the active ingredient. Since PC appears to promote the breakdown of collagen, there is reasonable hope that this treatment may affect not only the progression of the disease, but may also reverse preexisting fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat. Therefore, PPC may be useful for the management of fibrosis of alcoholic and nonalcoholic etiologies as well. S-Adenosylmethionine opposes CCl4-induced fibrosis and can affect some of the consequences of the ethanol-induced oxidative stress in experimental animals and in man. Anti-inflammatory medications (corticosteroids, colchicine) are also being used and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are being tested.     

The case against using ordinal numbers for gestational age

OBJECTIVE: Use of ordinal numbers (eg, twelfth) instead of cardinal numbers (eg, twelve) to measure gestational age often leads to clinical confusion. We conducted this study to document the prevalence of ambiguous or contradictory use of ordinal numbers for gestational age and to discuss some clinical implications. MATERIALS AND METHODS: We reviewed a convenience sample of standard texts in obstetrics and in abortion and examined a random sample of articles on abortion. RESULTS: Imprecise or incorrect use of ordinal numbers for gestational age was common: Eight of nine (89%) obstetrics texts and all six abortion texts had this problem. The corresponding figure for the abortion articles was 32 of 88 (36%). CONCLUSION: Use of ordinal numbers for gestational age introduces information bias (misclassification) into the scientific literature. More importantly, it may lead to clinical errors related to the timing of administration of antenatal corticosteroids and the upper limit for induced abortions. Gestational age measurements should use only cardinal numbers (eg, twelve) of completed days or weeks from the last menstrual period. Clinicians should abandon use of ordinal numbers for gestational age.     

Therapy of resistant psoriasis with topical corticosteroids and dimethylsulfoxide

The sequential application of full-strength dimethylsulfoxide (DMSO) and potent topical corticosteroid preparations was very effective in resistant plaque-type psoriasis. Complete clearing may be achieved in 3-4 weeks. Lower strengths of DMSO were less beneficial. Irritation from the solvent was effectively controlled by corticosteroids and was limited to transient burning or stinging. Resistance to topical corticosteroids may be overcome by the concomitant use of DMSO.     

New and emerging drug treatments for hypertension

BACKGROUND: Existing antihypertensive therapies are effective in lowering blood pressure, however, they are associated with adverse effects that may contribute to medication non-compliance. Furthermore, morbidity and mortality benefits have not been established with commonly used agents such as ACE inhibitors and calcium channel blockers. OBJECTIVE: Newer antihypertensive therapies offer similar efficacy with fewer adverse effects and may be of benefit in a number of concomitant disease states. DISCUSSION: This article examines the promise of the newer therapies: angiotensin II antagonists, T-type calcium channel blockers, dual metalloprotease inhibitors and endothelin receptor antagonists.