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Comparative trials of terazosin with other antihypertensive agents.

The efficacy and safety of terazosin were compared with those of other antihypertensive drugs in three parallel-group, randomized, double-blind studies in which 133 patients with mild to moderate hypertension participated. In two studies, terazosin monotherapy was compared with placebo and prazosin (study M79-073), or with hydrochlorothiazide (study M80-012). In a third study (M80-013), the combination of terazosin plus hydrochlorothiazide was compared with the combination of prazosin plus hydrochlorothiazide. Doses of study medications were administered twice daily and were increased at weekly intervals until the average supine diastolic blood pressure was 90 mm Hg or less, with a decrease from baseline of at least 10 mm Hg, or until the maximum specified dosage of a given study drug was reached. In general, all active treatments resulted in significant decreases from baseline in supine and standing blood pressures. There was no significant difference between terazosin- and prazosin-treated patients for changes from baseline to the final visit in supine or standing blood pressure measurements (study M79-073). Hydrochlorothiazide had a significantly greater effect on supine diastolic blood pressure when compared with terazosin (study M80-012). Otherwise, there were no significant differences between active treatment groups. Overall, no regimen caused clinically important changes in pulse rates, body weights, laboratory test results, physical examinations, or electrocardiograms. The incidence of side effects was approximately the same for all drugs; the most common side effects were headache, dizziness, malaise, asthenia, and nasal congestion. The results of these studies suggest that terazosin exhibits antihypertensive activity that is quantitatively similar to that of prazosin in patients with mild to moderate hypertension, and that a dose of 1 to 10 mg twice daily is well tolerated.

Adrenergic alpha-Antagonists↗

Cumulative experience with terazosin administered in combination with diuretics.

The short-term antihypertensive efficacy and safety of terazosin when administered with a diuretic were assessed in three randomized, double-blind, placebo-controlled studies. In all studies, adding terazosin to an established diuretic regimen resulted in significant incremental decreases in blood pressure from baseline to the final visit, with an overall satisfactory response rate of 56 percent versus 29 percent for control subjects. Mean decreases in supine diastolic blood pressure in the terazosin-treated groups ranged from 4.5 to 8.9 mm Hg, compared with mean decreases of 0.4 to 5.8 mm Hg in the placebo-treated groups; these differences generally achieved statistical significance. There were no clinically or statistically significant changes in pulse rates, physical examinations, or electrocardiographic tracings. Results of clinical laboratory tests revealed no evidence of drug-induced toxicity. Patients receiving the terazosin plus diuretic combination had a slight tendency to gain weight. The most common adverse effects reported by this group were dizziness, headache, and asthenia. The results of these studies indicate that combination therapy with terazosin plus a diuretic is both safe and effective for the treatment of hypertension.

Adrenergic alpha-Antagonists↗

Long-term experience with terazosin for treatment of mild to moderate hypertension.

Two hundred twenty-six patients with mild to moderate hypertension were treated with terazosin in an open, multicenter study to determine the drug's long-term efficacy and safety. All patients had previously received terazosin in a short-term study; 66 patients entered from later short-term studies and had experienced a 7 mm Hg decrease in supine diastolic blood pressure in response to terazosin. Terazosin was administered once or twice daily either alone or in combination with a diuretic and/or a beta blocker. Supine systolic and diastolic blood pressures were significantly decreased from baseline during time intervals ending at 90, 180, 360, and 720 days of long-term therapy. No clinically significant trends were observed in pulse rate, clinical laboratory test results, physical examinations, or electrocardiograms. Patients had a tendency toward a slight weight gain. The most common adverse experiences attributed to terazosin monotherapy were dizziness and asthenia (9.7 percent and 6.6 percent, respectively). Adverse experiences were usually of mild or moderate severity. Of the 226 patients who underwent long-term therapy, 29 (13 percent) withdrew because of adverse experiences, and three (1 percent) withdrew because of uncontrolled blood pressure. This study demonstrates that terazosin is effective and safe for long-term treatment of hypertension.

Adrenergic alpha-Antagonists↗

Long-term acceptability of perindopril: European multicenter trial on 856 patients.

The acceptability of perindopril in the long-term treatment of patients with mild to severe essential hypertension was assessed in a large European multicenter trial including 856 patients. Diastolic blood pressure (DBP) at inclusion was 95-125 mm Hg after 1 month of placebo. Normalization of blood pressure was defined as a DBP less than or equal to 90 mm Hg. Treatment was started with perindopril 4 mg once daily and increased when necessary to 8 mg daily. If DBP was not controlled, a second drug (hydrochlorothiazide) and finally a third drug were added. After 1 year of treatment in all 690 evaluable patients, supine systolic and diastolic blood pressure decreased by 29 mm Hg (from 172 +/- 1 to 143 +/- 1 mm Hg, p less than 0.001) and 19 mm Hg (from 105 +/- 1 to 86 +/- 1 mm Hg, p less than 0.001), respectively. Perindopril monotherapy normalized blood pressure in 55% of patients and total percentage of normalization was 78%. The overall incidence of withdrawals for side effects was 6.8%, the most common side effect being cough (2.2%). The most frequent complaints reported were cough (7.0%), headache (5.6%), asthenia (5.1%), mood and/or sleep disturbance (5.1%), and dizziness (3.2%). The small changes observed in hematologic and biochemical parameters were not clinically relevant.

Adolescent↗

Water intoxication associated with oxytocin administration during saline-induced abortion.

Four cases of water intoxication in connection with oxytocin administration during saline-induced abortions are described. The mechanism of water intoxication is discussed in regard to these cases. Oxytocin administration during midtrimester-induced abortions is advocated only if it can be carried out under careful observations of an alert nursing staff, aware of the symptoms of water intoxication and instructed to watch the diuresis and report such early signs of the syndrome as asthenia, muscular irritability, or headaches. The oxytocin should be given only in Ringers lactate or, alternately, in Ringers lactate and a 5 per cent dextrose and water solutions. The urinary output should be monitored and the oxytocin administration discontinued and the serum electrolytes checked if the urinary output decreases. The oxytocin should not be administered in excess of 36 hours. If the patient has not aborted by then the oxytocin should be discontinued for 10 to 12 hours in order to perform electrolyte determinations and correct any electrolyte imbalance.

Abortion, Induced↗

Pirprofen-induced fulminant hepatitis.

We report the cases of 2 female patients aged 69 and 61 yr, suffering from fulminant hepatitis induced by pirprofen, a new nonsteroidal antiinflammatory drug. The duration of pirprofen administration before the onset of hepatitis was long, 7 and 9 mo, respectively. Hepatitis was not preceded or accompanied by hypersensitivity manifestations. The liver lesion consisted of massive, predominantly centrilobular hepatic cell necrosis and microvesicular steatosis. One patient died of liver failure. Although the risk of fulminant hepatitis is very low, we recommend that, in patients taking pirprofen for more than 2 mo and complaining of asthenia, nausea, or vomiting, serum aminotransferase levels should be measured and administration of the drug should be interrupted as soon as an increased level is noted.

Aged↗

Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis.

Antinuclear antibodies giving a perinuclear fluorescence and directed to a 200-kilodalton polypeptide of the nuclear envelope have been described in primary biliary cirrhosis. The purpose of this study, based on a series of 150 patients with primary biliary cirrhosis, was to ascertain the prevalence of these antibodies and to compare patients with and without these antibodies. Antinuclear antibodies giving a perinuclear fluorescence were demonstrated in 43 of the 150 patients (29%); antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope were found in 40 of these 43 patients. Asthenia, arthralgia, associated extrahepatic diseases, Raynaud's phenomenon, and other antinuclear specificities were significantly less common, and titers of antimitochondrial antibodies were significantly lower in patients with antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope than in patients without these antibodies. Clinical outcome, liver tests, and histological lesions did not significantly differ in patients with and without these antibodies.

Antibodies, Antinuclear↗

Combination chemotherapy for patients with advanced carcinoma of the cervix: trial of mitomycin-C, vincristine, bleomycin, and cisplatin.

Sixteen patients with metastatic or recurrent carcinoma of the cervix were treated with combination chemotherapy consisting of mitomycin-C, vincristine, bleomycin, and cisplatin. Seven of 14 (50%) evaluable patients responded. In 2 patients all measurable disease resolved. Median duration of response was 4.5 months. Toxicity was severe and consisted of myelosuppression, pulmonary fibrosis, nausea, vomiting, stomatitis, asthenia, and fever. Two treatment-related deaths occurred. This combination chemotherapy regimen appears to have a response rate similar to other cisplatin containing regimens. Response durations were short and toxicity was severe.

Adult↗

Clinical determinants of long-term mortality in elderly patients with heart disease.

To determine which of the many clinical parameters routinely collected influence mortality in patients with low left ventricular ejection fraction (LVEF) (< 45% at radionuclide ventriculography), 128 elderly patients (mean age 79 +/- 3 years) with various heart diseases were prospectively followed for 3 years. Twenty-eight-percent had coronary heart disease, 16% hypertensive heart disease, 7% valvular heart disease. The remaining 62 patients (48%) made up a group comprising patients with primitive cardiomyopathy, cor pulmonary with no evidence of coronary heart disease, valvular disease or hypertensive heart disease. Thirty-four-percent of all patients were classified as having congestive heart failure (CHF). Age, sex and 37 clinical variables were analyzed using a Cox proportional model. Forty-four patients died, 36 (82%) of sudden cardiac death. Ten characteristics at study entry predicted an increased mortality risk: S3 gallop, number of clinical signs >or= 3, LVEF or= III, dyspnea, digoxin treatment, rales, number of symptoms >or= 4, asthenia, associated pulmonary disease. Long-term survival of very elderly patients with low ejection fraction is related to the functional capacity, the severity of symptoms and the number of clinical signs. Moreover a LVEF <or= 25% selects a subgroup of patients at higher risk. Our results suggest that these variables may influence the long-term survival of elderly patients with heart disease. Further studies with a greater number of patients are necessary to better delineate the prognostic value of the clinical and instrumental variables routinely collected in these patients.

Journal Article↗

[Diabetes insipidus disclosing metastasis of breast adenocarcinoma].

We are reporting on a case of diabetes insipidus (DI) and anterior pituitary failure revealing a breast cancer metastasis. Ten years after being diagnosed with a unilateral breast cancer, the patient presented with asthenia, thirst, polyuria and nocturia improved by subcutaneous DDAVP. MRI revealed a thickened pituitary stalk. DI is uncommon, late and usually asymptomatic in breast cancer. The association with an anterior pituitary failure is even more rare. In our patient the metastasis is in the pituitary stalk and seems to be due to meningeal deposits. MRI appears to be the best procedure to perform, showing a thickening stalk. Extension to the pituitary gland is related to direct tumor invasion from adjacent structures rather than haematogenous spread.

Adenocarcinoma↗

[Kikuchi-Fujimoto necrotizing histiocytic lymphadenitis: apropos of 2 cases and review of the literature].

The Kikuchi-Fujimoto's syndrome is an histiocytic necrotizing lymphadenitis which is observed at any ages but preferentially among young adults. The sex ratio is about 4:1 in favour of women. It is clinically characterized by cervical lymph nodes in a context of fever and asthenia. Sometimes, there is transitory leucopenia and an increase of the erythrocyte sedimentation rate. The course of the disease is spontaneously favourable in 1 or 3 months but recurrence is possible. The histology of the lymph node could mimic a malignant lymphoma and the immunohistochemical findings are of a great importance (Ki-M1P or KP1 antibody). The etiology remains unknown but some infectious diseases have been suspected (toxoplamosis, Epstein-Barr virus). Its association with a systemic lupus erythematous had been described and this set the problem of its physiopathology. We report two new cases of Kikuchi-Fujimoto's syndrome which one was attributed to Epstein-Barr virus primo-infection and the other associated with a systemic lupus erythematous.

Adult↗

Development of countermeasures for medical problems encountered in space flight.

By the turn of this century, long-duration space missions, either in low Earth orbit or for got early planetary missions, will become commonplace. From the physiological standpoint, exposure to the weightless environment results in changes in body function, some of which are adaptive in nature and some of which can be life threatening. Important issues such as environmental health, radiation protection, physical deconditioning, and bone and muscle loss are of concern to life scientists and mission designers. Physical conditioning techniques such as exercise are not sufficient to protect future space travellers. A review of past experience with piloted missions has shown that gradual breakdown in bone and muscle tissue, together with fluid losses, despite a vigorous exercise regimen can ultimately lead to increased evidence of renal stones, musculoskeletal injuries, and bone fractures. Biological effects of radiation can, over long periods of time increase the risk of cancer development. Today, a vigorous program of study on the means to provide a complex exercise regimen to the antigravity muscles and skeleton is under study. Additional evaluation of artificial gravity as a mechanism to counteract bone and muscle deconditioning and cardiovascular asthenia is under study. New radiation methods are being developed. This paper will deal with the results of these studies.

Aerospace Medicine↗

Phase II study of 9-hydroxy-2N-methylellipticinium acetate.

A broad phase II trial of elliptinium was conducted in 105 evaluable patients with advanced solid tumors. The drug was given as a 60-90-min i.v. infusion at a weekly dose of 100 mg/m2. Of 36 breast cancer patients, one achieved complete and six achieved partial response for an overall response rate of 19%. Responses lasted for 12-56 weeks from initiation of therapy. There was also one partial response among 21 patients with squamous cell carcinoma of the lung. No response could be obtained in 17 patients with colon cancer, 13 patients with head and neck cancer and 18 patients with a wide variety of other malignancies. Myelosuppression was minimal. Nausea and vomiting were the most frequent toxic effects. The drug also produced serious xerostomia and acute intravascular hemolysis. Asthenia was common. Other adverse reactions included fever and chills, transient neurologic and cardiovascular manifestations and renal function impairment. Additional work is needed to define optimal modes of drug administration.

Adult↗

A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder.

Benzodiazepines have been prescribed for the treatment of Generalized Anxiety Disorder (GAD) for nearly three decades due to their proven anxiolytic efficacy, despite a considerable side effect and abuse liability profile. A new class of compounds, the azapirones, have been developed as an alternative to benzodiazepine treatment. Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone. The present 5-week study investigated three doses of ipsapirone (2.5mg, 5.0mg and 7.5mg tid) versus placebo in 267 GAD outpatients. Efficacy was evaluated using the Hamilton Anxiety Rating Scale (HAM-A), Zung Anxiety Scale (Zung-A), and Clinical Global Impression (CGI). The study design consisted of a 1-week placebo run-in, a 4-week double-blind treatment period, and a 1-week placebo washout. The 5.0mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period, with significant differences (p < 0.05) from placebo and, at times, the 2.5mg and 7.5mg groups. Incidence of adverse events, primarily dizziness, nausea, sedation, and asthenia, was found to be dose proportional, with significant increase in the 7.5mg group, which may account for the diminished effectiveness seen with this dose. Our results suggest that ipsapirone may represent a viable treatment for GAD.

Adult↗

Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial.

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.

Adolescent↗

[The individualization of care practices for twins during the first year].

BACKGROUND: Mothers of twins have some difficulties to individualize their child-raising activities during the first year. This study was aimed to determine factors influencing such activities. POPULATION AND METHODS: Thirty-seven pairs of twins born after 36 weeks of gestation and weighing more than 2,000 g were included in the study. Relationships between the parents and their children were studied from questionnaires concerning activities during the first trimester and the end of the first year of age. Each item concerning organization of meals and sleeping was graded 1 to 3 according to the degree of individualization of the care. Items concerning support of the mother by the father or other people were graded 1 to 3 according to the degree of this assistance. The physical and psychological status of the mother was also graded according to the presence or not of asthenia and/or depression. Home activities of the mother were also observed. RESULTS: The state of the mother during the first few months had an impact on her mothering behavior: tired or depressed mothers tend to treat the twins collectively and simultaneously. No link was found between social, paternal or general familial support and the degree of individualization in the maternal behaviors. CONCLUSIONS: Several factors can interfere with the psychological repercussions of a twin birth on the mother and subsequent psychoemotional development of children. Further studies are necessary to understand how each parent contributes to the organization of the family system.

Family Practice↗

[Transient erythroblastopenia in early childhood].

BACKGROUND: Transient erythroblastopenia is rare in young children although its frequency is increasing. POPULATION AND RESULTS: Six infants (four boys, two girls), aged 29-41 months (mean: 33) were admitted for polar and asthenia. Only one displayed infectious episode two months earlier. Hemoglobin ranged from 40 to 67 g/l and reticulocyte number from 1 to 10 G/l. Mean corpuscular volume was normal as was Coombs' test. There was a profound erythroblastopenia in the bone marrow in five of the six patients. Parvovirus B19 infection was excluded in all. The white cell and platelet counts were normal. All patients were given an unique blood transfusion. Reticulocytosis spontaneously appeared within a few weeks in three patients. Another patient had normal number of erythroid precursors in the bone marrow 1 month after admission. CONCLUSION: Diagnosis of transient erythroblastopenia can only be made after exclusion of known causes such as drugs, virus, immune deficiency, leukemia and of Blackfan-Diamond disease. Its persistence must lead to search for another cause.

Age Factors↗

[Severe hyponatremia associated with anorexia nervosa: role of inappropriate antidiuretic hormone secretion?].

BACKGROUND: Anorexia nervosa may be revealed by hyponatremia or associated with it. This hyponatremia can be due to diuretics or laxatives abuse, potomania or inappropriate secretion of antidiuretic hormone as in the case reported here. CASE REPORT: A 15 year-old girl was admitted for anorexia nervosa. She had secondary amenorrhea and asthenia and had lost 14 kg during the preceding 4 months. Her natremia ranged from 112 to 130 mEq/l with normal urinary sodium excretion, serum hypoosmolality (252 mosm/kg) and inappropriately elevated urinary osmolality (698 mosm/kg). Renal, adrenal and thyroid functions were normal. After water loading, patient remained euvolemic, with a negative free water clearance and an increased plasma ADH level with concomitant hyposmolality. A diagnosis of inappropriate secretion of antidiuretic hormone was made, after excluding other conditions such as potomania, drug abuse, vomiting, tumor and chronic lung disease. CONCLUSIONS: Hyponatremia sometimes seen in anorexia nervosa must lead to the search of inappropriate antidiuretic hormone secretion.

Adolescent↗