Brain neurotransmitter changes in three patients who had a fatal hyperthermia syndrome.

The authors examined the autopsied brains from three patients who had a fatal hyperthermia syndrome. There was marked hypothalamic noradrenaline depletion in all three patients, severe brain choline acetyltransferase deficiency with nucleus basalis cell loss in two patients, and mild to moderate brain choline acetyltransferase loss in one patient. Striatal dopamine metabolite/dopamine ratio was below normal in two patients and not elevated, as would be expected after short-term neuroleptic administration, in the third. This suggests that reduced capability (aggravated by the cholinergic deficit) of the nigrostriatal dopamine system to respond adequately to stress and/or neuroleptic-induced receptor blockade may be important in the development and course of fatal hyperthermia syndrome.

Multicenter double-blind study of the efficacy and tolerance of roxithromycin versus erythromycin ethylsuccinate in acute orodental infection in adults. Odontogenic Infections Study Group.

A total of 194 patients with orodental infection were randomized either to roxithromycin 150 mg twice daily plus placebo or to erythromycin 1 g twice daily plus placebo for a mean duration of 8 days. The infections consisted of cellulitis, pericoronitis, and adenopathy, or any two in combination. In the 176 cases in which efficacy was evaluable, outcome was satisfactory in 94% and 91% of cases treated with roxithromycin and erythromycin, respectively (p = 0.45). Patients were evenly distributed with respect to demographic characteristics, diagnosis, and concomitant treatment. Surgery was performed in 63%, primarily for abscess formation in cellulitis (p less than 0.001); 18% of patients with an abscess did not undergo surgery. The success rate was identical irrespective of whether surgery was performed, including in those with an abscess. Tolerance was evaluated in 1986 patients. Unwanted effects, elicited by direct questioning, were reported in approximately 20% of cases per group (19% for roxithromycin and 21% for erythromycin). They consisted of mild gastrointestinal upsets which caused treatment to be withdrawn in eight cases (four per group). Thus, roxithromycin and erythromycin twice daily for orodental infection are similar in both efficacy and tolerance.

Comparison of two oral antibiotics, roxithromycin and amoxicillin plus clavulanic acid, in lower respiratory tract infections.

In a randomized, multicenter, open-label study, 490 ambulatory adult patients with lower respiratory tract infection (LRTI) were randomized to roxithromycin (ROX) 150 mg b.i.d. orally (n = 244) or amoxicillin plus clavulanic acid (AMX + CA) as 500 mg AMX + 125 mg CA t.i.d orally (n = 24). Clinical results were analyzed in 477 patients with acute bronchitis (79%), chronic bronchitis (CB) (14%), and pneumonia (7%). There were significantly more patients with underlying disease (cardiovascular diseases, p = 0.045; and alcoholism, (p less than 0.001), and more patients over the age of 65 years (p = 0.045) in the ROX group. Overall clinical efficacy was similar in both groups: 88% (206:235) in the ROX group and 85% (205:242) in the AMX + CA group. Side effects were reported in 67 cases (28%) in the AMX + CA group and in 21 cases (9%) in the ROX group (p less than 0.0001), causing withdrawal in 21 and three cases, respectively (p less than 0.001). Thus, despite being administered to a significantly older and more ill group of patients with LRTI, roxithromycin was as effective as amoxicillin plus clavulanic acid and better tolerated.

Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones: a 3-year survey in France.

OBJECTIVE: To assess trends in the susceptibility to beta-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories. METHODS: During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen beta-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum beta-lactamase (ESBL). RESULTS: Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to beta-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp. CONCLUSION: Over the 3-year study period beta-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.

[Contribution of sequential voluntary ambulatory monitoring in the diagnosis of arrhythmia. A multicenter study of 1287 symptomatic patients]. / Apport de l'enregistrement ambulatoire séquentiel volontaire à la détection des arythmies. Etude multicentrique sur 1,287 patients symptomatiques.

Voluntary sequential ambulatory recording is a diagnostic method of recording per-critical electrocardiographs in symptomatic patients with the aid of a portable solid-state technology recorder. In order to assess the value of this technique in the detection of arrhythmias, a multicenter study was performed in 1,287 symptomatic patients suspected of having paroxysmal arrhythmias (palpitations in 86.5% of cases). The quality of the sequential ambulatory recording was judged to be good in 54.9% and mediocre in 40.2% of cases: only 4.9% of recordings were uninterpretable. This technique allowed identification of a cardiac arrhythmia related to symptoms in 42.5% of the 1,091 cases which were analysed; sustained supraventricular tachycardia (11.7%), ventricular extrasystoles (14.9%) and simple sinus tachycardia (9.5%) were the principal abnormalities. The per-critical recording was negative in 57.5% of patients, suggesting a purely functional origin of symptoms in these cases. Atrial fibrillation was more common in hypertensive patients (11.3% vs 5.5% in normotensives, p less than 0.01) as were ventricular extrasystoles (23.1% vs 13% in normotensives, p less than 0.001). Voluntary sequential ambulatory recording seems to be a technique well adapted to the detection of symptomatic arrhythmias and a useful complement to Holter recording.

[Action of trandolapril on the blood glucose balance and microalbuminuria in hypertensive diabetics]. / Action du trandolapril sur l'équilibre glycémique et la microalbuminurie chez l'hypertendu diabétique.

The aim of this study was to evaluate the action of trandolapril on blood glucose control and microalbuminuria in mild to moderate hypertensive in patients with non-insulin-dependent diabetes. Sixty-seven patients, aged between 33 and 79, were enrolled. After a two week placebo run-in period, treatment with trandolapril as monotherapy was given for 3 months. The dose of trandolapril was adjusted between 1 and 4 mg/day according to antihypertensive response. Patients were assessed clinically and by laboratory investigations each month. Two patients were excluded from efficacy analysis because of major protocol deviations. Mean DBP fell, under the influence of treatment, from 101 +/- 5 mmHg to 82 +/- 7 mmHg (p < 0.0001) and mean SBP from 171 +/- 9 mmHg tp 147 +/- 11 mmHG (p < 0.0001). At three months, 54 patients (84%) had a DBP < or = 90 mmHg. Microalbuminuria decreased significantly (p = 0.03) during treatment. Microalbuminuria returned to normal in 11 of the 13 patients in whom the baseline value was above 21 micrograms/min and increased to above normal in 2 of the 26 patients who had a normal baseline value. Blood glycosylated hemoglobin, fructosamine, glucose and creatinine, and creatinine clearance remained stable. Plasma potassium rose slightly in 7 patients. Six adverse events were reported (4 coughs, 1 peripheral edema, 1 plantar mal perforans). One patient died from pulmonary embolism. In conclusion, trandolapril is an effective antihypertensive agent in hypertensive diabetics. Trandolapril causes a significant decrease in microalbuminuria and does not interfere with blood glucose control in these patients.

[Evaluation of thiocolchicoside as monotherapy in low back pain. Results of a randomized study versus placebo]. / Evaluation du thiocolchicoside en monothérapie dans le lumbago douloureux. Résultats d'une étude randomisée contre placebo.

Thiocolchicoside is a muscle relaxant which, due to its mainly spinal GABA-agonist activity, is used by the oral and intramuscular routes in the ambulatory treatment of painful contracture of the skeletal muscles. The effectiveness and acceptability of this drug in the treatment of acute low-back pain were evaluated in a multicentre, randomized, double-blind, drug versus placebo trial involving 98 patients. The effectiveness of thiocolchicoside was assessed on the following criteria: patients' overall opinion, pain intensity, number of analgesic tablets taken, vertebral rigidity and ability to resume ordinary daily tasks. The results obtained showed that thiocolchicoside significantly improves the principal criterion by the second day of treatment and the other criteria within 5 days.

[Efficacy and tolerability of tiaprofenic acid (Surgam) in acute sinusitis in adults. Results of a randomized study versus paracetamol and placebo]. / Efficacité et tolérance de l'acide tiaprofénique (Surgam) dans les sinusites aiguës de l'adulte. Résultats d'une étude randomisée contre paracétamol et contre placebo.

Tiaprofenic acid (Surgam) is a non steroidal anti-inflammatory drug used for acute inflammation during episode of upper respiratory tract infection in adults. Its efficacy in association was already demonstrated in tonsillitis. The efficacy and tolerance of tiaprofenic acid for the treatment of inflammation occurring in the course of adult acute sinusitis were evaluated by a randomized study versus paracetamol and placebo. 139 patients were included in the study. 134 patients were evaluated for efficacy. They received either tiaprofenic acid or paracetamol or placebo during seven days together with amoxicillin. We used evaluation criterion taking into consideration inflammatory physical indications of sinusitis and opinions of investigators and patients. After 7 days of treatment the efficacy of tiaprofenic acid (Surgam) was significantly superior to placebo on all principal criterion studied. Amelioration with paracetamol was lower, but no statistical difference was found between paracetamol and tiaprofenic acid (Surgam) groups. Tolerance was good in every group.

Comparison of resilon and gutta-percha filling materials on root canal fracture resistance following restoring with quartz fiber posts.

OBJECTIVE: Bacterial leakage and root fractures are the most important reasons of root canal treatment failure. Due to the lack of adhesion of gutta percha to the canal walls, Resilon has been introduced as a root-filling material able to bond to the root walls. Metal posts may predispose the tooth walls to oblique and vertical fracture which usually leads to tooth loss; whereas, fiber posts may reinforce the remaining tooth structure. The purpose of this study was to compare the effect of Resilon and gutta-percha on the fracture resistance of root canal following restoring with quartz fiber posts. MATERIALS AND METHODS: Forty-four maxillary incisor root canals were chemo-mechanically prepared, then randomly divided into three groups: 1-Control group (n=20), 2-Experimental group (n=20) and a negative control group (n=4). Root filled teeth were restored with quartz fiber posts and composite resin cores. Four teeth with a conservative prepared access cavities and without any further post preparation were used as a negative control group. After simulating the clinical situation, specimens were loaded in the Universal Testing Machine for compressive strength test. All data were statistically analyzed by the T-test. RESULTS: The mean compressive strengths for group 1 was 535.8 ± 155.23 N and 645.93 ± 182.98N for group 2, which were statistically significant (p-value= 0.047). CONCLUSION: Root canals filled with Resilon were significantly more resistant than that of gutta-percha, following restoration with quartz fiber posts.

An evaluation of tolerance of roxithromycin in adults.

This review deals with tolerance of a new macrolide, roxithromycin from data collected from a number of studies in adults. A total of 2917 adults, 2519 given roxithromycin 150 mg bid, were recruited into 17 multicentre comparative or non-comparative studies. Nine studies were double-blind, against doxycycline, erythromycin estolate (EES), lymecycline or cephradine. Overall the drug was well tolerated: side-effects possibly or probably related to roxithromycin were noted in only 4.1% (120/2917) of all patients, and in 3.1% (15/480) of elderly subjects. The gastrointestinal tolerance of roxithromycin was significantly better than that of doxycycline in four trials, and better than that of erythromycin ethylsuccinate in one study. The incidence of drug-related liver function test abnormalities following roxithromycin therapy was low and compared favourably with data published on erythromycin. Roxithromycin shows a satisfactory safety profile at the recommended daily dosage of 150 mg bid in adults.

Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience.

In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method. The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects. We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy.

Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women.

We report the results of a large-scale trial with mifepristone (RU 486) followed by the administration of a prostaglandin (PG) analogue for the medical termination of early pregnancy. Altogether, 16,173 patients from 300 centers were evaluated. 48 women (0.3%) were lost to follow-up prior to, and 416 (2.6%) after the PG administration, and therefore the efficacy was evaluated in 15,709 women. Overall, the success rate was 95.3%, with no statistical difference regarding the nature and dose of PG used. The median duration of bleeding was 8 days, being 12 days or less in 89.7% of the women. Bleeding was significant enough to necessitate a vacuum aspiration or a dilatation and curettage in 0.8% of the cases. A blood transfusion was necessary in 0.1% of the women (11 patients). Serious cardio-vascular side-effects were reported in 4 cases after the PG (sulprostone) injection: they consisted of one acute myocardial infarction attributed to a coronary spasm, and in marked hypotension in the other 3 women. All patients recovered uneventfully. In conclusion, RU 486 followed by a PG analogue provides an efficient and safe medical alternative to surgery for early pregnancy termination, provided that the recommended protocol is adequately followed and the contraindications to prostaglandins are respected.

PIP: Between May 1988 and September 1989, physicians administered 600 mg of RU-486 followed by either 1 mg gemeprost vaginal pessary or im injection of 0.125-1.0 mg sulprostone to 16,369 11-48 year old women attending 30 centers in France to evaluate this regimen's safety and efficacy and whether trained prescribers could adequately comply with recommended protocol. 13.6% patients whose gestational age was greater than the recommended 50 days, underwent RU-486 and prostaglandin (PG) analogue administration. 78% of 571 patients did not receive a PG analogue because they expelled the conceptus after RU-486 administration. The remaining 126 women did not receive RU-486 even though they had not expelled the conceptus. Clinicians administered to PG analogue to 88.4% of all women within the recommended 36-48 hours after RU-486 administration. The RU-486 and PG analogue regimen had a success rate of 95.3%. Women who received the PG analogue within the recommended time period had a higher success rate than those who received it either too early or too late (95.8% vs. 92.8% and 93.9%, respectively; p = .001). In those women who did not receive the PG analogue, RU-486's success rate was considerably lower (88.6%; p .001). The nature and does of the PG analogue greatly influenced expulsion within 4 hours after its administration (44.1% after 1 mg gemeprost vs. 57.3%, 55.8%, 73.5%, and 67.6% after 0.125, 0.25, 0.375, and 0.5 mg sulprostone respectively; p .001). The higher doses of sulprostone had a significant effect on duration of bleeding (e.g., 9.1 days for 0.5 mg vs. 7.1 days for 0.125 mg p .001). 89.7% of the women bled for no more than 12 days. The bleeding was so profuse in 0.8% of the cases that either vacuum aspiration or dilatation and curettage was needed. 11 women required 1-3 units of blood. 8.5% experienced at least 1 side effect, the most common being uterine cramps (1.6% of all cases). 4 women suffered from grave cardiovascular effects (myocardial infarction in 1 case, severe hypotension in 3 cases). As long as prescribers consider contraindications and follow the protocol, this regimen is a viable alternative to surgical abortion.

[Antipyretic effect of tiaprofenic acid in children. Comparative study with paracetamol]. / Effet antipyrétique de l'acide tiaprofénique chez l'enfant. Etude comparative au paracétamol.

The authors report the results of a randomised, multi-centric study comparing the antipyretic activity of tiaprofenic acid to that of acetaminophen. Seventy nine children of both sexes, aged 8 months to 9 years, having an average temperature at inclusion of 38.5 degrees C (+/- 0.5 degree C), received as a single dose 50 mg of tiaprofenic acid (3.7 +/- 0.9 mg/kg) (40 children) or 100 mg of acetaminophen (7.7 +/- 1.7 mg/kg) (39 children) for upper respiratory tract infection. The rectal temperature was taken regularly over a 6-hour period. Whatever the criteria considered (gradient between the initial temperature and the lowest temperature observed, difference of temperature at the different time points between the two groups), tiaprofenic acid appeared as effective an antipyretic as acetaminophen. Tolerance was good in both groups. Tiaprofenic acid appears as an interesting alternative to acetaminophen in the treatment of fever in upper respiratory tract infections in children.

Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study.

A prospective, randomized, multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin (150 mg b.i.d. orally) and penicillin (2.5 MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of hospitalized adult patients with erysipelas. Seventy-two patients entered the study. Thirty-one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial. The overall efficacy rates (cure without additional antibiotics) were 84% (26/31) in the roxithromycin group and 76% (29/38) in the penicillin group (P = 0.43). No side-effects were observed in the roxithromycin-treated patients whereas rashes occurred in two cases in the penicillin group, leading to exclusion from the study. Oral roxithromycin can thus be considered an effective and well-tolerated treatment for erysipelas in adult hospitalized patients.