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[Ideal treatment of malaria attack: more questions than answers? Experience of a department of infectious diseases].

The number of cases of malaria imported to western Europe from tropical areas is steadily growing, due to the increased number of people traveling to endemic regions and to the spread of Plasmodium strains resistant to chemoprophylaxis. This has prompted the WHO to frequently update its guidelines concerning preventive therapy. We report on 143 consecutive cases of benign attacks of malaria in patients returning primarily from western and central Africa. Plasmodium falciparum was responsible for 80% of the cases. Forty-one percent of the patients had followed their preventive regimen correctly; mefloquine failed in 3 of them. Three early relapses were observed after curative treatment, including 2 patients who had received intravenous quinine for more than 5 days. Because P. falciparum infection is potentially lethal, we suggest that the treatment of malaria attacks be optimized, by systematically dosing serum quinine levels, in order to adjust the administered doses, and, as a first-line therapy, by prescribing a combination of drugs to patients at high risk of resistance.

Adolescent↗

[Hepatic metastasis of unknown primary site].

In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom-oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non-toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations.

Adenocarcinoma↗

Amrinone during porcine intraperitoneal sepsis.

Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v. (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis. Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study. Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure. Intravenous amrinone modestly augmented cardiac index without altering heart rate. Mean systemic and pulmonary arterial pressures decreased. Systemic and pulmonary vascular resistance fell significantly (P less than 0.05). Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05). During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index. Consequently, cardiac output and oxygen delivery increased modestly. Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis.

Amrinone↗

Tuberculosis in patients infected with the human immunodeficiency virus.

A retrospective study of tuberculosis was undertaken among 125 patients infected with human immunodeficiency virus (HIV) who attended our regional infectious disease unit between 1986 and 1989. Nine TB-positive patients (five English, three Africans, one Indian) were identified. In three patients who presented with pyrexia of unknown origin and no objective evidence of any organ involvement, the diagnosis of TB was established from examination of sputum induced by nebulized hypertonic saline. Four other patients had extrapulmonary disease while another two had only pulmonary manifestations of TB. Chest radiographs from five patients were normal, while the other four showed cavities with consolidation, pleural effusion, miliary opacities and hilar enlargement, respectively. All but two mycobacterial isolates were fully sensitive to standard first-line chemotherapeutic drugs. Response to treatment was rapid and only complicated in one patient. There were no relapses following treatment without maintenance therapy after a mean follow-up of 22.2 months (range 9-48). Three patients died, of causes unrelated to TB. Tuberculosis may occur at any stage of HIV disease and is an important cause of fever in HIV-infected British patients, even when chest radiographs are normal and previous BCG vaccination has been performed.

Adult↗

Management of malignant ventricular arrhythmias using antitachycardia devices.

Cardioverter defibrillators were implanted in 26 patients at Charleston Area Medical Center for management of cardiac arrest (7 patients), and drug refractory sustained ventricular tachycardia (19 patients). A variety of operative approaches and concomitant surgical procedures were utilized in the implantation of these devices. No operative deaths occurred. A superficial wound infection was the only operative complication. During the follow-up period (9.3 +/- 5 months), 11 of 26 patients (46 percent) had a defibrillator discharge and one death occurred (3 percent), which was due to heart failure. Patients with malignant ventricular arrhythmias may present with sustained monomorphic ventricular tachycardia with associated syncope, pre-syncope or without any associated symptoms. Unfortunately, cardiac arrest may be the initial presentation. The use of antitachycardia devices such as implantable cardioverter defibrillators and antitachycardia pacemakers has allowed physicians to more successfully treat patients with malignant ventricular arrhythmias. In a significant number of patients with these arrhythmias, such devices are now used as first-line therapy.

Adult↗

Penicillinase-producing Neisseria gonorrhoeae in a subset of nonemergent patients: I. A trend in the Washington, DC area.

A significant increase in penicillinase-producing isolates of Neisseria gonorrhoeae has been detected and documented in the District of Columbia. Currently, the prevalence of beta-lactamase isolates is approaching 50%, with the greatest number of cases being detected in the 18- to 23-year-old age group, in both males and females. Indicators suggest that this trend, which was first noted in 1987, will become more pronounced in the future. Ceftriaxone is now the first-line drug of choice in treating suspected gonococcal infections.

Adolescent↗

Droloxifene, a new antiestrogen, in advanced breast cancer. A double-blind dose-finding study. The Droloxifene 002 International Study Group.

To determine the optimal daily dose of the new antiestrogen droloxifene for the treatment of breast cancer, a multinational, multicenter, randomized, double-blind, phase II trial was initiated. Postmenopausal women with progressive advanced breast cancer (distant metastatic cancer, inoperable recurrent or primary tumor) with positive or unknown hormone receptor status (estrogen or progesterone) were entered in the study. Droloxifene was administered in a double-blind randomized design with daily doses of either 20, 40, or 100 mg once daily as first-line systemic therapy. None of the patients had received previous systemic antitumor therapy with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Response was determined according to Union Internationale Contre le Cancer/World Health Organization criteria. Only patients with at least one measurable lesion were entered into the trial. The highest quality of data was achieved in two ways: source verification in the hospitals through monitors and peer review with subgroups of investigators determining the tumor response of each patient at adjudication meetings (evaluating parameters obtained from physical examination and reviewing X-rays and computer tomography scans). To date, 254 patients have been enrolled. Results from all these groups, without breaking the randomization code, based on 131 patients whose data have been verified are as follows: 10 complete responses (CR), 37 partial responses (PR), 47 no change, 29 progressive disease, 8 patients too early to evaluate. Thus, the overall response rate (CR + PR) was 38%. Droloxifene was well tolerated.

Antineoplastic Agents↗

Attention-deficit hyperactivity disorder.

The epidemiology, etiology, pathogenesis, clinical presentation, diagnostic criteria, and clinical course of attention-deficit hyperactivity disorder (ADHD) are described and the role of pharmacotherapy in the management of this disorder is discussed. ADHD is a behavioral disorder of unknown etiology characterized by inattention, impulsiveness, and hyperactivity. The behavior, which may be manifest at home, at school, or in social situations, is generally worse in settings requiring sustained attention; as a result, academic underachievement is frequently an associated problem. Although the onset usually occurs before the age of four years, ADHD is most commonly diagnosed when the child enters school. It is up to six times more common in boys than in girls. Nearly one third of all children with ADHD continue to show symptoms of the disorder in adulthood. While many questions about the pathophysiology of ADHD remain unanswered and a cure has not yet been found, pharmacotherapy can effectively control the symptoms of the disorder in most patients. Three psychostimulant medications--dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline--are considered the drugs of first choice for management of the behavioral manifestations of ADHD. Dextroamphetamine and methylphenidate are equally effective in improving the symptoms of ADHD. Pemoline, a newer agent, may be tried in patients who cannot tolerate or do not respond to these two first-line agents. Common adverse effects associated with stimulant medications include anorexia, insomnia, stomach pain, and weight loss; these are generally transient and decrease with time. Imipramine hydrochloride and desipramine hydrochloride are less effective and may produce more serious adverse effects than the psychostimulants and are therefore considered second-line agents for the treatment of ADHD. Dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline have been shown to effectively control the behavioral symptoms of ADHD. For maximum impact, pharmacotherapy should be accompanied by behavioral, educational, and psychosocial intervention.

Attention Deficit Disorder with Hyperactivity↗

Medical management of unstable angina. What have we learned from the randomized trials?

Because of the absence of a generally accepted definition of unstable angina, the clinical context of drug trials for this condition has varied from trial to trial. Early- versus late-entry trials must be distinguished, and the possibility of a modification of effect caused by the nature of drug therapy already given when the patient became unstable or by concomitant treatment in addition to experimental treatment must be taken into account. These factors cannot be overlooked when the results from a limited number of reported trials are pooled together. The largest early-entry trial with a beta-blocker and a calcium antagonist was the Holland Interuniversity Nifedipine/metoprolol Trial (HINT), which enrolled patients with suspected unstable angina diagnosed at coronary care unit admission. HINT results showed that unstable angina cannot be reliably differentiated from evolving myocardial infarction (MI) in this particular context and that there are few early MIs that could have been prevented. In patients who were not already taking a beta-blocker, metoprolol reduced the incidence of acute MI or recurrent ischemia, and there was no benefit of nifedipine. On the other hand, the addition of nifedipine was effective in patients whose conditions became unstable despite maintenance treatment with a beta-blocker. Thus, previous beta-blockade modified the effect of the calcium antagonist studied. Based on evidence from HINT and other trials, it is concluded that beta-blockers should be used as the first-line treatment in patients with unstable angina and that a calcium antagonist should be added when patients remain unstable despite beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Cardiac contractility and conduction: a comparison of antihypertensives.

The four classes of first-line antihypertensive agents recommended in the 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure are reviewed here. Particular consideration is given to the effects of these agents on heart rate, atrioventricular nodal conduction, and myocardial contractility in patients with other cardiovascular diseases. Diuretics and angiotensin-converting enzyme inhibitors have no significant direct effects on cardiac function. beta-Blockers inhibit catecholamine stimulation of the heart and may be particularly beneficial in treating patients with a history of myocardial infarction. Calcium channel blockers reduce blood pressure by dilating arterial resistance vessels. They are structurally heterogeneous and highly selective in their sites of action. As a consequence, cardiac effects can be minimized by selecting a calcium channel blocker with more potent peripheral vasodilatory effects. A new calcium channel blocker, isradipine, currently undergoing clinical trials, is highly selective for arterial smooth muscle and appears to be a safe and effective antihypertensive agent.

Adrenergic beta-Antagonists↗

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↗

Present state of cardiovascular community control programme in the Czech Socialist Republic.

The high incidence, great import, and long duration of cardiovascular diseases are reflected in high demands placed on the health services. Experience shows that utilization of the results of research in general practice is lagging behind. The application of any improvement in the diagnosis, therapy, and prevention in health care waits several years for its accomplishment. In order to improve this situation, the Ministry of Health of the CSR constituted, in line with WHO recommendations, a Department for Cardiovascular Diseases Control. The Department has worked out a programme of prevention and control of the major cardiovascular diseases, in particular, ischaemic heart disease, systemic hypertension and its complications, rheumatic heart disease, congenital cardiac and vascular defects, and cor pulmonale. New diagnostic, therapeutic, and preventive procedures are first tried out in so-called model areas and are only after this introduced into the national health care of people suffering from or endangered by cardiovascular diseases. In parallel, organizational measures necessary for comprehensive care are implemented. The authors report on the experience gained so far with the realization of the programme of care of people suffering from IHD and acute myocardial infarction. They emphasize the importance of continual schooling of medical personnel and of health education of the entire population. They describe the implementation on a national scale of postgraduate cardiological courses intended especially for first-line doctors.

Cardiovascular Diseases↗

Buccal administration of fenoterol aerosol in young children with asthma.

A new technique for the administration of a bronchodilator aerosol, fenoterol, in young children with asthma is described. Rapid and effective bronchodilatation can be obtained in many patients simply by directing the jet of the bronchodilator aerosol onto the buccal mucosa. This method will frequently obviate the need for painful or potentially dangerous injections of adrenaline or aminophylline as a first-line treatment in children with acute attacks of asthma.

Aerosols↗