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Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial.

The efficacy of the benzodiazepine antagonist flumazenil has been assessed clinically in a double blind, randomised, placebo-controlled multicentre study in patients with grade I-III portosystemic encephalopathy. In an ancillary study reported here the effect of flumazenil on the electroencephalogram (EEG) was analysed in 32 patients who had EEG grading according to protocol. Following the baseline observation period, patients were randomised to receive (at 1 min interval) 3 sequential bolus injections of flumazenil (0.4, 0.8 and 1 mg) or placebo followed by infusions of flumazenil (1 mg/h) or placebo for 3 h. Patients were monitored for 5 h after infusion. A positive response was defined as 1 point improvement in EEG grade. After independent analysis of the EEG gradings 5 out of 17 (29%) flumazenil treated patients showed an improvement in EEG grading (3 after bolus, 2 during follow-up) compared to 2 out of 15 (13%) placebo treated patients (1 after bolus, 1 during follow-up) (95% confidence interval of difference: -12% to + 50%). Of the 5 EEG responders after flumazenil, 3 also had an improvement in clinical PSE grading (none after bolus, 2 during infusion, 1 during follow-up), compared to neither of the 2 EEG responders after placebo. EEg responders did not differ from non-responders with respect to Child-Pugh score, basal EEG, PSE grade and positivity for benzodiazepines. In conclusion, treatment perspectives for flumazenil in portosystemic encephalopathy appear to be present for only a minority of patients; however, this study yields no support for a major role of benzodiazepine antagonists in the treatment of hepatic encephalopathy.

Adult↗

Splenic injury--a prospective multicentre diagnostic study.

One hundred and forty-seven patients with splenic injury were entered in a prospective multicentre study including 18 hospitals. The diagnosis was made by scintigraphy in 55 patients, ultrasonography in 51 and computed axial tomography in 31. Exploratory laparotomy was performed in 52 patients, in 23 of these after a positive peritoneal lavage. Splenic injury was found in 33 per cent of the ultrasound examinations, indicated in another 20 per cent and not indicated in 16 per cent. In 31 per cent increased intraperitoneal effusion was the only finding. There was a tendency towards an underestimation of the injury by ultrasonography. Peritoneal lavage was positive in all examinations.

Adolescent↗

Italian Multicentre Study on Dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease.

For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress.

Aged↗

Prediction and detection of ovulation by the measurement of urinary pregnanetriol-3 alpha-glucuronide. A multicentre study.

The urine excretion pattern of pregnanetriol 3 alpha-glucuronide (PT-3G) throughout the menstrual cycle in 26 normal ovulating women was evaluated in a multicentre study. The concentration of PT-3G was measured by radioimmunoassay in daily samples of early morning urine (EMU) from 20 women for three consecutive cycles and from 6 women who conceived during the period of study. PT-3G was also measured in 24-h urine samples from 5 additional women. The peak of urine LH was used as a reference point for ovulation (Day 0). The EMU concentration of PT-3G in the follicular phase of 60 normal ovulatory cycles was 5.10 mumol/l +/- 0.11 (arithmetic mean +/- SE). The first PT-3G defined rise (CUSUM analysis) occurred during the late follicular phase (Days -3 to 0) with a PT-3G maximum excretion (9.69 mumol/1 +/- 0.55) on Day 0, whereas a PT-3G excretion peak occurred during mid-luteal phase (Days +5 to +9). The overall PT-3G excretion during the luteal phase (8.06 mumol/1 +/- 0.17) was significantly higher than that of the follicular phase (P less than 0.001). A further sustained increase in PT-3G excretion was noted after day +11 in the conceptional cycles. The 24-h excretion profile of PT-3G was similar to that obtained in EMU samples. No inter-centre significant variation was noticed in terms of PT-3G concentration values. The results were interpreted as demonstrating that the PT-3G excretion profile throughout the cycle exhibits a close resemblance to that of serum 17-OH progesterone. The data also indicates that although the immunoanalytical measurement of this urine steroid metabolite does not give an early sign for the occurrence of ovulation, it can be used for both the immediate prediction and the detection of ovulation.

Adolescent↗

A comparison of fluconazole and ketoconazole in the oral treatment of vaginal candidiasis; report of a double-blind multicentre trial.

One hundred and eighty three patients with vaginal candidiasis were randomly allocated to treatment with either fluconazole in a single oral 150 mg dose, or ketoconazole, 200 mg twice daily for 5 days. Favourable clinical responses were obtained in 92% of the patients in the fluconazole group and in 89% of those in the ketoconazole group after 5-16 days. Long-term evaluation at 27-62 days showed favourable clinical responses in 86 and 88%, respectively. Candida was eradicated from the vagina in 77% of both treatment groups at the long-term evaluation. The relapse or reinfection rate was similar for both groups, ranging between 4-8%. One hundred and thirty two of the 160 patients who had rectal swabs cultured for yeast at baseline, gave positive results. Of the 27 patients in the fluconazole group whose rectal cultures remained negative at the long-term evaluation, 26 maintained mycological cure of their vaginal candidiasis. In contrast, patients with positive rectal cultures at this time were much less frequently associated with mycological cure. The results were similar for the patients in the ketoconazole group. Treatment-related side effects in both groups were few and minor. This double-blind multicentre study showed that a single oral 150 mg dose of fluconazole was as effective as 5 days of oral ketoconazole medication in the treatment of vaginal candidiasis.

Administration, Oral↗

Multiosseous osteosarcoma involving the mandible: metastatic or multicentric?

A case of multiosseous osteosarcoma in a 15-year-old girl is presented. Neoplastic foci were initially diagnosed in the right ilium and left mandible. The clinical course was complicated by pregnancy and chemotherapeutic side effects. Postmortem examination revealed multiple tumor emboli in the lungs. The literature concerning metastatic and multicentric origins of multiosseous osteosarcomas is reviewed. The case presented probably represents mandibular metastasis from the ilium.

Adolescent↗

Multicentric reticulohistiocytosis.

A case of multicentric reticulohistiocytosis with prominent oral manifestations is described. The case is presented to emphasize the oral involvement since there appear to be no reports of this entity in the dental literature.

Adult↗

Multicentric development of pancreatic intraductal carcinoma through atypical papillary hyperplasia.

We report a case of multiple intraductal carcinomas of the pancreas associated with diffuse atypical papillary hyperplasia. A 67-year-old Japanese man with a complaint of epigastric pain was examined by endoscopic retrograde pancreatography, which demonstrated multiple dilated branches of the pancreatic duct in the body and tail of the pancreas. Histologic examination on the resected pancreas showed diffuse atypical papillary hyperplasia in multiple dilated ducts associated with multiple intraductal carcinomas. Histologic features are described and multicentric carcinogenesis through atypical papillary hyperplasia is discussed.

Aged↗

Multicentric Kaposi's sarcoma in a 5-year-old human immunodeficiency virus-negative renal allograft recipient.

We describe the clinical and pathologic features of a case of pediatric multicentric Kaposi's sarcoma (KS) associated with allograft transplantation in a human immunodeficiency virus (HIV)-negative child. A lethal polyadenopathic and visceral KS occurred in a 5-year-old Caribbean boy who had undergone an allogenic renal transplantation for diffuse mesangial sclerosis with end-stage renal failure 4 months previously. The HIV-1 and HIV-2 serologies were negative. Despite its rarity, KS must be considered as a differential diagnosis in posttransplantation polyadenopathic or multisystemic syndromes in children.

Autopsy↗

Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the "Société Française de Biologie Clinique".

The laboratory heterogeneity of the lupus anticoagulant (LA) was investigated in a multicentre study using a panel of 78 plasma samples diagnosed as containing a LA. Consecutive samples were collected by 12 participants using various screening tests, and sent to 7 laboratories which performed one or more clotting assays among the following: activated partial thromboplastin time (APTT), dilute Russell viper venom time, kaolin clotting time (KCT), dilute tissue thromboplastin time (dTTI) and a platelet neutralization test. For APTT and dTTI, 10 versions of these tests including standard and mixing procedures were carried out. They varied by reagents, phospholipid concentration or methodology. Cut-off times were determined for each test by comparing the results of the panel to those of a control population. When the data of all clotting assays were pooled, 70 of the 78 selected plasmas were considered to contain LA, 15 of them having a low-titer inhibitor. Sensitivity, defined as the proportion of positive results among LA-containing plasmas, varied from 62 to 100% and was positively related to responsiveness (defined as the mean ratio of clotting time to cut-off time). Laboratory heterogeneity of LA-containing plasma was illustrated by a star symbol plot analysis. Different populations of samples, with LA preferentially recognized by one assay (or group of assays) irrespective of the overall sensitivity of this assay, were identified. Multiple component analysis demonstrated the heterogeneity of low-titer inhibitors, which complicates their recognition in routine laboratory investigation.

Adult↗

Multicentric hemangioblastomas in the cerebellum.

An 18-year-old female patient who had been diagnosed as having von Hippel-Lindau disease was admitted to our hospital with signs of increased intracranial pressure. Computed tomographic examination and vertebral angiography revealed the presence of five multicentric cerebellar nodules, of which three had newly occurred in the opposite hemisphere, probably sometime during the 3 years before admission. This case gives us some insights into the biological multipotentiality of cerebellar hemangioblastoma. We stress that close observation is absolutely necessary for this unique group of tumors, even after total excision.

Adolescent↗

Repeated multifocal recurrence of grade I, grade II, and grade III meningiomas: regional multicentricity (primary new growth) or metastases?

In this study 48 patients with histologic grade I and 41 with grade II/III meningiomas were reviewed retrospectively for the occurrence of multifocal tumor masses in relation to recurrence. Regional multicentric tumor masses were increasingly seen in progressive disease with repeated recurrence and occurred significantly more frequently in grade II/III compared to grade I meningiomas. Small microscopic tumor extensions along the subdural space around the tumor bulk, defined as tumor spurs, could be documented as an alternative form of multifocal disease. The occurrence of these spurs was associated with recurrence. In nearly all cases the multifocal disease was limited to the vicinity of the primary or previous tumor site. In three patients with grade III meningiomas however, at recurrence distant tumors could be found. These were interpreted as drop, cerebrospinal fluid and hematogenic metastases, respectively. In these three cases tumor spurs were documented in previous operations. It is concluded that not only primary new growth in a tumor that virtually from the beginning already has a regional multifocal origin, but also the spread of tumor cells along the subdural space forming tumor spurs, as well as distant metastases, plays an important role in recurrent meningioma.

Brain Neoplasms↗

Multicentric glioma studied with positron emission tomography: a case report.

Positron emission tomography (PET) studies of a multicentric glioma case were undertaken using 11C-methionine (Met) and 18F-fluorodeoxyuridine (FUdR). Met-PET revealed high accumulating lesion in both the left and right hemispheres, whereas in the FUdR-PET, the lesion on the right showed marked accumulation, but not that on the left. For both foci, the histologic diagnoses were anaplastic astrocytoma, but the lesion on the right showed higher density of undifferentiated tumor cells than that on the left. PET studies using Met and FUdR are effective in delineating the proliferative potential of glioma cells, which otherwise cannot be determined by histopathologic studies.

Brain↗

Multicentric basal cell carcinoma of penile skin.

A multicentric basal cell carcinoma of the penile skin is reported. The skin adjacent to the tumor showed changes similar to those observed in sun-damaged skin. Inasmuch as the patient denied sunbathing in the nude, causation is unclear, but sun may have played a role in the genesis of the tumor.

Adult↗

Multicentric angiomyolipoma: renal and lymph node involvement.

A retrospective review of 6 patients with renal angiomyolipoma treated surgically revealed regional lymph node involvement in 2--an incidence of 33 per cent. The clinical behavior in these patients suggests that nodal involvement is an expression of multicentricity rather than metastatic disease.

Child↗

Multicentric study of beclomethasone dipropionate nasal aerosol in adults with seasonal allergic rhinitis.

A double-blind, parallel-design multicentric study, in two phases, was conducted to examine the safety and efficacy of 2-wk treatment with various doses of beclomethasone dipropionate nasal aerosol (BDNA) and placebo in adults with seasonal allergic rhinitis. In phase I, 162 patients received BDNA, 33.5 micrograms/burst (o.d.,b.i.d., t.i.d., q.i.d.), or placebo; in phase II, 189 patients received BNDA 42, micrograms/burst (b.i.d. q.i.d.), or placebo. In both phases, statistically significant (p less than 0.05) differences favoring BDNA over placebo were found for all efficacy measures (global evaluation and total and individual symptom scores). In phase I, response to treatment increased as BDNA dosage increased, with a leveling off at t.i.d. dosage. In both phases, marked improvements were seen by week 1, with maximum improvement during week 2. Eighty-seven patients had adverse reactions-sneezing and nasal burning were most common. No suppression in morning cortisol levels was seen, nor were Candida infections promoted. A 2-wk treatment with BDNA was safe and effective in the treatment of seasonal allergic rhinitis in adults.

Adult↗

Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Northern Italian Cooperative Study Group.

A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

Actuarial Analysis↗

Multicentre study of gestrinone in cyclical breast pain.

Although the aetiology of cyclical mastalgia is poorly understood, the consistent finding of an increased prolactin stimulation response probably due to oestrogen dominance has led to the use of treatment with prolactin-lowering drugs and antioestrogens. The efficacy and safety in cyclical mastalgia of gestrinone, which has androgenic, anti-oestrogenic, and antiprogestagenic properties, were investigated in a multicentre study. In a double-blind randomisation procedure, 72 patients were allocated placebo and 73 treatment with gestrinone (2.5 mg twice a week) for 3 months. The patients recorded the severity of breast pain on a visual analogue scale before and during treatment and scored other breast symptoms as not present (0), mild (1), moderate (2), or severe (3). The gestrinone group had significantly greater reductions than the placebo group in breast pain score at months 1, 2, and 3 of treatment (mean reduction 59.5 [SD 22.6] to 11.7 [17.0] vs 58.2 [17.6] to 36.7 [23.0] at month 3; p less than 0.0001). All six breast symptoms had lower scores in the gestrinone than in the placebo group by the end of treatment. In a subset of 30 participants (15 from each group), serum concentrations of oestradiol, progesterone, and tri-iodothyronine were significantly lower than baseline after 3 months of gestrinone, but concentrations of luteinising hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and thyroxine did not change. 41% of gestrinone-treated and 14% of placebo-treated patients reported at least one side-effect; most of these were androgen-mediated. 11 placebo-treated patients and 4 on gestrinone discontinued treatment. Thus, gestrinone was very effective in the treatment of cyclical mastalgia and was well tolerated.

Adolescent↗