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[Antibiotic therapy in maternal-fetal infections].

The selection of first-line antimicrobial therapy in neonates with maternofetal infection is based on probability data from epidemiologic studies of bacterial infections. Because of the high prevalence of ampicillin-resistant E. coli strains and of the lack of susceptibility of Listeria and group D streptococci to cephalosporins, combined use of two complementary drugs, such as amoxicillin and cefotaxime with an aminoglycoside, is recommended. Each dose should be increased twofold in patients with meningeal involvement. The interval between aminoglycoside doses depends on the degree of renal maturity and therefore on gestational age. Discontinuation of treatment on the third day when clinical and biologic monitoring disproves the suspected infection avoids the occurrence of untoward effects, especially on the intestinal flora. In other cases, administration of two drugs selected on the basis of bacteriologic findings is needed beyond the third day. Specific therapy is required in infrequent infections (Candida, tuberculosis, syphilis, Helicobacter). The dosage of antimicrobials with narrow therapeutic margins (vancomycin, aminoglycosides) should be adjusted on the basis of serum assays performed at four-day intervals. Duration of therapy is usually ten days but may reach 21 days in neonates with meningitis. Prevention, in the absence of specific vaccines, rests on antenatal and perinatal treatment of women at high risk for infection. Management of neonates with group B streptococcal infection is controversial; close clinical and biologic monitoring over 48 hours may allow to reduce the use of antimicrobials.

Anti-Bacterial Agents↗

[Antibiotic treatment of acute otitis media].

The strategy of antimicrobial therapy in acute otitis media rests on bacteriologic and pharmacokinetic data. Pneumococci and Haemophilus are still the two most prevalent pathogens in acute otitis media and raise problems regarding susceptibility: 25% of Haemophilus beta-strains produce beta-lactamases and 6 to 12% of pneumococci are intermediate or resistant to penicillin. Pharmacologic features required of antimicrobials used in acute otitis media include good penetration in the ear and sustained supra-MIC levels in middle ear fluid. Kinetics of drugs in the ear are still often incompletely understood. The last selection criterion is analysis of comparative trials. Available data do not point to superiority of any drug over the others. Amoxicillin should no longer be given as first-line therapy. Amoxicillin combined with clavulanic acid (Augmentin) is effective on the entire spectrum of causative organisms. Higher levels of amoxicillin may be needed (concomitant use of amoxicillin and (Augmentin). First-generation cephalosporins are effective but may prove unsuccessful in patients with large inocula. Pediazole is clinically effective although penetration of erythromycin in the ear is delayed. The new oral third generation cephalosporins are effective in infections due to beta-lactamase-producing Haemophilus strains. A bacteriologic study should be performed routinely whenever otitis media occurs in an infant under three months of age.

Acute Disease↗

Leadership behaviors of pediatric nurse managers.

PURPOSE: To determine the leadership behaviors of firstline managers in pediatric hospital organizations. METHOD: A descriptive survey of 34 first-line managers in pediatric hospitals was done. A demographic questionnaire provided information about the nurses and their units. The Fiedler Leader Match Scales were used to collect data about the nurse manager's leadership behaviors. RESULTS: The nurse managers were slightly more task-oriented than people-oriented. The majority of the nurse managers perceived themselves to have high situational control. The match between the scales indicated that 21 of the managers were considered effective leaders. CONCLUSIONS: The majority of the nurse managers possessed effective leadership behaviors and were motivated by the completion of tasks.

Adult↗

[Bactericide activity of cefadroxil comparated with amoxicillin-clavulanic acid, cefaclor and josamycin].

Betalactamase-producing organisms are responsible for an increasing number of ENT and lower respiratory tract infections. Or cephalosporins and the combination of amoxicillin with the beta-lactamase inhibitor clavulanic acid are alternatives to ampicillin therapy. The killing activity of cefadroxil on the organisms most often responsible for ENT and respiratory infections was evaluated in vitro using a viable bacteria count method, comparatively with cefaclor, josamycin, and amoxicillin-clavulanic acid. Killing activity was found to be time-dependent for all the antimicrobial agents studied. Cefadroxil exhibited the same bactericidal effect on Streptococcus pyogenes and S. pneumoniae than the other agents. Haemophilus influenzae and an increasing number of Pneumococcus strains were resistant to josamycin which is therefore not appropriate for first-line therapy. As compared with amoxicillin and amoxicillin-clavulanic acid, cefadroxil was less active on H. influenzae and more active on Staphylococcus aureus. Production of beta-lactamase failed to influence the killing activity of cefadroxil. These bacteriologic data, together with results of pharmacologic studies (long half-life and good penetration within tissues) can explain the clinical successes obtained with cefadroxil in ENT and lower respiratory tract infections.

Amoxicillin↗

The role of atopy in asthma.

Allergy plays an important role in chronic asthma. Aeroallergens, both indoor and outdoor, provide a constant source of bronchial inflammation that increases bronchial hyperreactivity. This increased reactivity lowers the threshold of response to nonspecific triggers of asthma flares such as viral infections, pollutants, and cold air. Asthma is a chronic inflammatory disease in much the same way that the rheumatic diseases are. In that respect, therapy should be directed at reducing inflammation, as it is in the rheumatic diseases. Along these lines, newer approaches to asthma therapy should emphasize steroids as first-line treatment. In this way, therapy is targeted against the underlying inflammation that causes the bronchial obstruction, rather than treating with bronchodilators such as theophylline and B agonists. The effect of such continuous antiinflammatory therapy is decreased airway hyperresponsiveness, which has obvious clinical benefit.

Age Factors↗

Beneficial effects on serum lipids in noninsulin dependent diabetics by acarbose treatment.

Acarbose (Bay g 5421, Glucobay; CAS 56180-94-0) inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. It is therefore efficient as a first-line drug in the treatment of noninsulin-dependent diabetics (NIDDM) insufficiently treated with diet alone. Information is scarce whether under acarbose treatment the lipid metabolism can also be improved. Therefore the changes of triglycerides, cholesterol and HDL-cholesterol were analyzed in a randomized double-blind placebo-controlled trial. In brief, 94 NIDDM aged 43 to 70, after a pretreatment period of at least 3 months, were treated with 100 mg acarbose t.i.d. or placebo for 24 weeks. The patients were recruited after a 4-week screening phase with reinforcement of diet. The most impressive results of acarbose treatment were lowering of blood glucose and insulin, especially in the postprandial state, and of HbA1 (glycosylated hemoglobin). Results on lipids: The initial serum cholesterol levels showed a broad spectrum. Low concentrations remained unchanged under acarbose, while high concentrations (the upper tercile) decreased from 273 to 251 mg/dl. This effect was statistically significant compared to placebo. HDL-cholesterol levels increased continuously under acarbose and placebo as well thus indicating some study effect. Similarly, fasting triglycerides leveled down under acarbose and placebo. However, drastic differences appeared in postprandial triglycerides which were checked 1 and 5 h after a test meal given at entry and at finish of the study. The lowering by acarbose compared to placebo was highly significant for the 1 h postprandial concentrations. It is concluded that acarbose treatment can reduce elevated cholesterol concentrations and postprandial triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗

[Study of vinorelbine (V) combined with hexamethylmelamine (H) (combination V-H) in adenocarcinoma of the ovary: results a phase I-IIA trial, NHO-88, of ARTAC "ovarian" group].

The lack of decisive progress in ovarian cancer chemotherapy in recent years led the ARTAC "Ovary" group to initiate a study based on the hypothesis of collateral sensitivities. In this phase I-II trial, NHO-88, the V-H combination (associating vinorelbine (VNB) and hexamethylmelamine (HMM) was studied in patients with advanced ovarian adenocarcinomas, most of which had become resistant to previous chemotherapy. The aim of the study was to find an active combination without complete cross resistance with first-line platinum salt based combinations, such as CAP, FAP or CACb-300. A pilot feasibility study was first carried out to determine the maximum tolerated weekly dose (MTWD) of VNB (20 mg/m2/week), HMM being administered per os on days 1-14 of every 28-day cycle at a standard dose of 250 mg/m2/day. An open phase II-A study was further carried out according to a 2-step sequential analysis method for phase II clinical trials. We observed: 1), a good tolerance of the V-H combination apart from frequent neutropenia; 2), a response rate of 35% (95% confidence interval: 23-47%); 3), a median response duration of 4 months (range: 1-7 months); 4), in some cases, the absence of a complete cross-resistance between the V-H regimen and the previously administered platinum-based combinations. These results, which are currently being validated (phase II-B ongoing), constitute the first step in the search for active systems of sequential or alternate chemotherapeutic regimens for the treatment of advanced carcinomas.

Adenocarcinoma↗

From stepped care to tailored therapy.

In 1977 the National Heart, Lung and Blood Institute in the USA drew together a panel of experts as the first 'Joint National Committee' to provide guidelines on the detection, evaluation and management of hypertension. This was the birth of 'stepped care', which was internationally adopted, and consisted of: step 1--a diuretic; step 2--if step 1 is inadequate, add a beta-blocker; step 3--if step 2 is inadequate, add a vasodilator (e.g. hydralazine). With the evolution of a broader, multiple risk factor approach to the management of hypertension, and the development of newer agents, this simple system was modified during the 1980s. The relative importance of non-pharmacological intervention resulted in step 1 becoming drug-free, and alternative agents necessitated wider 'steps'. The interaction of hypertension with other coronary heart disease (CHD) risk factors, the disappointing effect of thiazides and beta-blockers on CHD events in intervention trials, and the increasingly large list of potential drug combinations meant that by 1989 several international consensus bodies no longer considered stepped care to be viable. Stepped care has been replaced by 'tailored therapy'. That is, based on an assessment of the patient's overall cardiovascular risk profile, the choice of first-line drug therapy has been broadened beyond diuretics and beta-blockers to include ACE inhibitors, calcium antagonists and selective alpha 1-blockers. Many hypertension experts are now of the opinion that, except in limited circumstances, diuretics and beta-blockers should only be used as second-line or third-line agents.

Antihypertensive Agents↗

Oral lesions in the systemic mycoses.

Oral lesions have rarely been reported in systemic mycoses, though over the past few years they have been recorded particularly in immunocompromised individuals. The dramatic increase in numbers of immunocompromised persons, especially those infected with human immunodeficiency virus, has almost certainly been responsible for the increase in reports of oral disease caused by systemic mycoses, particularly aspergillosis, cryptococcosis, and histoplasmosis. However, reports of coccidioidomycosis, blastomycosis, and paracoccidioidomycosis have, as yet, increased little in this population. Dentists, when they observe chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions (particularly in immunocompromised patients) should be aware of the possibility of a systemic mycosis. Amphotericin remains the standard therapy for most deep mycoses, while the newer azoles are the first-line agents for superficial mycoses, such as candidiasis, and are increasingly used in the deep mycoses.

Antifungal Agents↗

Idarubicin in blastic crisis of chronic myelogenous leukemia.

BACKGROUND: Blastic crisis (BC) is the terminal event in the natural history of most chronic myelogenous leukemia (CML) patients. Depletion of the normal stem cell compartment, as well as the proliferative advantage and frequent pharmacoresistance of the blastic clone, contribute to the poor prognosis of CML patients in this phase. Recent clinical trials have shown that idarubicin (IDR) in combination with cytosine arabinoside (ARA-C) is more active than daunorubicin at comparable doses in acute myelogenous leukemia (AML). Furthermore, IDR alone also exhibits antitumoral activity in the BC of CML. METHODS: Twelve Ph+ CML patients in BC (male 8, female 4; median age 45 yrs., range 19-55 yrs.) were treated with IDR 12 mg/m2/die for 3 consecutive days in sequential combination with Ara-C (1 hour i.v. infusion) 120 mg/m2/12 hrs. for 7 consecutive days. BC exhibited a myeloid phenotype in 9 and a lymphoid phenotype in 3 cases. Median duration of the previous chronic phase had been 36 months (range 6-180). RESULTS: Clearing of peripheral and bone marrow blasts was achieved in all but one patient. Three other patients were classified as resistant because of blastic regrowth, and 3 died of infection during postchemotherapeutic aplasia. Two patients achieved complete remission (CR) and 3 partial remission (PR). The median duration of response was 11 months (range 6-32). CONCLUSIONS: In BC of CML the IDR/Ara-C combination led to an encouraging rate of either partial or complete responses. The relatively long duration of unmaintained response was even more interesting, with the duration of PR approaching that of CR. These data suggest that IDR should be considered as one of the first-line drugs in the treatment of BC of CML.

Adult↗

[Obstruction of pulmonary arteries. Contribution of the scanner and MRI. Apropos of 10 cases].

We present a retrospective study of ten patients presenting non specific clinical manifestations in whom the diagnosis of pulmonary embolism was documented by CT scan and/or MRI. Results of CT scan and/or MRI were compared to DSA bi-selective pulmonary angiography findings. In a large number of cases, CT scan and MRI allowed the detection of the obstruction within the right and left pulmonary arteries (RPA and LPA). Although these techniques did not permit the diagnosis of peripheral clots, pulmonary infarcts were usually depicted by these two procedures. CT scan and/or MRI could be performed as first-line investigations in case of atypical clinical symptoms because of their high relevance for proximal pulmonary artery obstruction, although these two non-invasive procedures cannot indicate the aetiology of the obstruction etiology.

Evaluation Studies as Topic↗

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Drug prescribing in rheumatoid arthritis in Otago.

The drug therapy prescribed for a group of 50 patients with rheumatoid arthritis in Otago prior to specialist referral was examined. Thirty-two patients were receiving some first-line anti-inflammatory drugs and six were receiving no therapy at the time of their first hospital clinic visit. Salicylates had been prescribed first in only 16 of the 50 patients while this drug had been withdrawn because of side effects in about one-third of the patients who had been treated with it prior to specialist referral. Seven patients had received phenylbutazone and six corticosteroids as the first treatment for their rheumatoid arthritis. About one-third of the patients were receiving more than one anti-inflammatory drug at the time of their initial clinic visit.

Adult↗

Bretylium tosylate: a review.

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic agent, are reviewed. Bretylium tosylate is used to treat life-threatening ventricular arrhythmias, principally ventricular fibrillation and ventricular tachycardia, that have not responded to treatment with first-line antiarrhythmic agents. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission. The drug is poorly absorbed orally, requiring either i.m. or i.v. administration. Drug excretion occurs primarily through the kidney, necessitating dosage modification in renal disease. Hypotension is the most commonly observed adverse reaction to bretylium tosylate. Rapid i.v. administration may cause severe nausea and vomiting, and i.m. injection at the same site may cause atrophy and necrosis of muscle tissue. Quinidine and procainamide may potentiate the hypotensive effects of bretylium. Bretylium will aggravate digitalis-induced arrhythmias. Bretylium's use in resistant ventricular tachyarrhythmias requires close clinical monitoring.

Arrhythmias, Cardiac↗

[Current chemotherapy of pulmonary tuberculosis].

Tuberculosis has today lost much of its dread for mankind: in 1976, 1823 persons contracted tuberculosis and 182 died of pulmonary tuberculosis in Switzerland. In contrast, 1375 died of pneumonia, 1309 of non-specific airway disease and 2202 of bronchial cancer in the same year. The present data on morbidity and mortality in Switzerland resemble those of the other industrial European countries or the USA. The decrease in morbidity and mortality of pulmonary tuberculosis was caused-among other factors-by chemotherapy. Chemotherapy not only profoundly changed the infectivity of tuberculous patients and made ambulatory, domiciliary treatment possible, but cured pulmonary tuberculosis. The introduction of the bactericidal rifampicin led to the latest major landmark in the chemotherapy of tuberculosis in the past 20 years: namely, short-course chemotherapy. Together with the other first-line drugs (isoniazid, streptomycin, ethambutol), rifampicin shortened the duration of chemotherapy from 18--24 to 9--12 months. Short-course chemotherapy is today the therapy of choice for most patients with pulmonary tuberculosis.

BCG Vaccine↗

[Tics and Tourette Syndrome].

Tics disorders and Tourette syndrome (TS) are neurodevelopmental conditions characterized by motor and/or vocal tics with onset in childhood. Their clinical presentation is heterogeneous and fluctuating over time, with exacerbations related to emotional, environmental, and medical factors. Diagnosis is clinical and based on medical history and neurological examination, following DSM-5-TR criteria, with ancillary testing rarely required. The prevalence of TS is estimated at 0.7%, while transient tic disorders affect up to 10% of children. The natural history is generally favorable, with symptom improvement during adolescence, although a subset of patients continues to experience tics into adulthood. Most individuals with TS present psychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, which significantly impact quality of life and should be prioritized in management decisions. Treatment is recommended only when tics cause functional impairment and follows a stepwise approach including psychoeducation, behavioral interventions, and individualized pharmacological therapy. Comprehensive behavioral intervention for tics is considered first-line treatment when available. Alpha-2 adrenergic agonists and dopamine antagonists are the most commonly used pharmacological options. Neuromodulation therapies are reserved for severe, refractory cases. These recommendations from the Ibero-American Academy of Pediatric Neurology summarize current evidence and provide a practical, updated framework for the diagnosis and management of tic disorders and Tourette syndrome in pediatric patients.

Humans↗

Rheumatoid arthritis.

Management should help relieve symptoms, increase or maintain function, produce few side effects and keep the cost to a minimum. Aspirin remains the first-line drug; other nonsteroidal anti-inflammatory drugs may be useful when aspirin cannot be tolerated. Symptoms and signs of rheumatoid disease may be suppressed by corticosteroids, but only gold compounds, penicillamine and cytotoxic therapy have been shown to decrease disease activity and lessen permanent joint damage.

Adrenal Cortex Hormones↗

Role of DTIC (NSC-45388) in the chemotherapy of sarcomas.

DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.

Clinical Trials as Topic↗