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99mTc-DTPA aerosol for same-day post-perfusion ventilation imaging: results of a multicentre study.

A multicentre study was performed in an attempt to evaluate a submicronic technetium-99m diethylene triamine penta-acetic acid aerosol generated by a newly developed delivery system, the aerosol production equipment (APE nebulizer), for same-day post-perfusion ventilation imaging in patients with clinically suspected pulmonary embolism. Quantitative comparison between the DTPA aerosol and krypton gas demonstrated a close correlation with respect to regional pulmonary distribution of activity and peripheral lung penetration (n = 14, r = 0.94, P < 0.001 and r = 0.75, P < 0.0025, respectively). In 169 consecutive patients, DTPA aerosol images performed immediately following perfusion (inhalation scan I) were compared to those carried out on the next day (inhalation scan II) with respect to image quality and assessment of perfusion-ventilation matches or mismatches. Agreement between inhalation scans I and II with respect to perfusion defects matched or mismatched to ventilation was found in 166/169 (98%) studies. The image quality of inhalation scan I was equal to that of scan II in 72%; inhalation scan I was superior in 11% of cases, while scan II was superior in 17%. This submicronic 99mTc-labelled DTPA aerosol is well suited for fast same-day post-perfusion ventilation imaging in patients with clinical suspicion of pulmonary embolism.

Aerosols↗

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yielding r = 0.909 (P less than 10(-6)), and in 22 cases with regard to the right ventricular ejection fraction, yielding r = 0.712 (P less than 0.001). The comparison between the first-pass study using 99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, with r = 0.937 (P less than 10(-6)), and for the right ventricular ejection fraction in 15 subjects, with r = 0.783 (P less than 0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of 99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of 99mTc-Sestamibi.

Coronary Disease↗

Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study.

A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of 99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good correlation with semiquantitative ratio indices for 99mTc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15). Q and Rmax also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage), Q was reduced in the moderate and severe groups, while Rmax was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results for Q and Rmax. Acquisition times of 15 or 30 min provided the same results. The multicompartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate that Q and Rmax are useful general indices for evaluating the functional reserve capacity of the liver.

Asialoglycoprotein Receptor↗

Failed partial nephrectomy: local recurrence vs. multicentric disease.

Candidates for partial nephrectomy for renal cell carcinoma include those with (1) bilateral synchronous lesions, (2) tumour in a solitary kidney and (3) renal mass and borderline renal function. Present imaging techniques aid in the identification of appropriate candidates for partial nephrectomy and in the preoperative assessment for technical feasibility of the operation. Studies have shown that the postoperative local recurrence rate ranges from 9 to 13%. We submit a case report in which a 65-year-old male with a history of colon carcinoma four years earlier was found to have a 3 cm left lower pole lesion on his follow-up abdominal CT scan. Upon intended partial nephrectomy, a small synchronous upper pole mass was noticed as well as numerous cortical lesions despite extensive preoperative imaging to the contrary. It is our feeling that finer imaging techniques including thinner CT cuts, additional imaging planes and continued use of renal ultrasound will aid in the identification of ipsilateral, synchronous lesions and draw further distinction between local recurrence and multicentric disease.

Aged↗

Late sequelae of foreign body inhalation. A multicentric scintigraphic study.

A multicentre European study on foreign body inhalation has been organized by the Pediatric Task Force covering both the SNME and the ENMS. Among the 100 cases which could be collected in a 2 year period, about 40% of scintigraphic abnormalities were found 6 months after relief of the foreign body. The frequency of these defects was clearly related to the time interval between aspiration and removal. Factors like the localization of the foreign body and the site of the early scintigraphic defects could be related to the further scintigraphic outcome, but this could not be proven statistically. Similarly, the absence of bronchial tree inspection after removal of the foreign body seemed to be associated with more permanent scintigraphic lesions. Finally, it is obvious that a large number of patients demonstrated scintigraphic alterations 6 months or more after removal of the foreign body, although the chest X-rays were considered normal.

Child↗

A randomised multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children.

A randomised control multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children is reported. One hundred and fifty children of either sex (age range: 2-10 years) were randomised to receive either a single dose of 400 mg of albendazole suspension, or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5 consecutive days. At the end of therapy, majority of children in both treatment groups were symptom free. Two days after completion of therapy, 97% of children in both treatment groups were giardia free in the stools. Side effects were noted in 3 children in the albendazole group, and in 20 children in the metronidazole group. We conclude that albendazole suspension is as effective as metronidazole in the treatment of giardial infection in children. It is safe and has fewer side effects as compared to metronidazole.

Albendazole↗

Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

Anemia↗

A multicentric study for serotyping and susceptibility to antibiotics of pneumococci in Italy.

A multicentric study of the incidence of pneumococcal serotypes was recently carried out in five different geographical areas in Italy. Two hundred and sixty-seven strains were typed using the quellung reaction with monospecific antisera, but only 28 of these were isolated directly from the site of infection. The most frequent serotypes were 19, 6, 3, 9, 4, 1 and 18 without remarkable differences regarding the area, age of patients and site of isolation. It was found that 60.3% of the serotypes isolated from all sources and 67.8% of those isolated from the sites of infection are contained in the currently used antipneumococcal vaccine. Antibiotic resistance was found versus aminoglycosides (34.9%), tetracycline (28.3%), chloramphenicol (5.2%) and penicillin (3.3%). Cefoxitin appeared to be the antibiotic to which the pneumococci were most susceptible. Only two types, 19 and 16, resulted resistant to all the antibiotics.

Anti-Bacterial Agents↗

Risk Factors for AIDS Associated Kaposi's Sarcoma. An European Multicentre Case Control Study.

EURO-SHAKS, European study on HIV associated Kaposi's sarcoma, is a BIOMED 1 project financed by the European Union (DG XII). The Spanish side of the project has been financed by FISS (Fondo de Investigaciones Sanitarias). The aims of this study are to identify possible genetic, behavioural, biological and environmental risk factors for HIV associated Kaposi's sarcoma through a multicentre case-control study. An extensive personal questionnaire, a clinical data form and blood sample is required from all participants. In addition, a cutaneous biopsy is request from KS patients. The presence of several European groups in this project implies a large and diverse sample size and will allow to correlate the behaviour, clinical and biological data in different geographical areas, and therefore study the possible transmission routes as well as the natural history of the putative causal agent of KS. One of the main objectives of EURO-SHAKS is to create a European Bank of AIDS biological samples for possible future investigations.

Journal Article↗

Factor VIII-related activities after 1-deamino-8-D-arginine vasopressin in multicentric reticulohistiocytosis.

A woman with multicentric reticulohistiocytosis, having symptoms including bleeding and a borderline level of factor VIII, was given an i.v. infusion of DDAVP as a pharmacological test to evaluate the release of factor VIII-related properties from storage sites. The results show a reduced response to DDAVP in the patient in comparison with a normal control subject. This could be due either to a defect in the release of the factor VIII complex after DDAVP or to a reduced synthesis and/or storage capacity by the storage cells.

Adolescent↗

Reduced-osmolarity oral rehydration salts solution multicentre trial: implications for national policy.

World Health Organization (WHO) recommended standard ORS solution has sodium (90 mmol/L) and glucose (111 mmol/L) almost in the ratio of 1:1 and a total osmolarity of 311 mmol/L. There are concerns that the sodium or glucose concentration and the overall osmolarity in the formulation is not appropriate. Therefore, the efficacy of standard and reduced-osmolarity ORS solutions in young children with acute diarrhea was evaluated in a recent WHO supervised multicentre trial conducted in India (New Delhi), Brazil, Mexico and Peru. The implications of trial results are discussed. In non-cholera diarrhea, both the standard and reduced osmolarity ORS solutions were effective in achieving clinical rehydration. The stool output was 39% higher in the standard ORS solution group as compared to the reduced-osmolarity ORS solution group. The duration of diarrhea was 22% higher in the standard ORS solution group. The risk of requiring supplementary intravenous infusion was increased in children treated with standard ORS solution [relative risk 1.4 (0.9-2.4)]; this benefit was not observed in Indian patients due to high breast feeding rate. The mean sodium concentration at 24 hours after admission was lower in the reduced osmolarity ORS solution group [135 (134-136) vs 138 (136-139), p < 0.01). The low osmolarity ORS deserves to be evaluated in adult cholera to determine its efficacy and any excess hyponatreamia. Meanwhile, it is reassuring that the WHO formulation was effective and its use was not associated with hypenatremia even in young children. Efforts must continue to be made to promote WHO-ORS while research to improve it further is welcome.

Adult↗

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning.

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC)were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2)at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were < 5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exlcusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (P<0.1). UMBC tended to occur more frequently in quadrant B with an average histologic tumor size significantly smaller than that in MONBC (P <0.01). The histologic types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.

Journal Article↗

Clinical and immunological assessment in HIV+ subjects receiving inosine-pranobex. A randomised, multicentric study.

Inosine-pranobex (methisoprinol, isoprinosine; INPX) is the p-acetamidobenzoic salt of N,N-dimethylamino-2-propanol and inosine in a 3:1 molar ratio. In early studies, INPX was found to partially inhibit human immunodeficiency virus (HIV) and to increase the immunocompetence of HIV-infected subjects in vitro. We report the results of a randomised, multicentric clinical trial carried out on 553 HIV+ patients. 261 individuals were treated with INPX (two 500 mg tablets every 6 h for 3 months) and the remaining 292 constituted the untreated control group. INPX treatment was associated with a slightly improved clinical condition or with a trend in that direction, as compared to the untreated group. A preservation of the CD4/CD8 cell ratio values, a decrease in the CD8+ cells and an increase in the Leu 2-7+ cell number better than in the untreated individuals was also observed in the patients taking INPX. No serious or adverse effects of INPX have been observed.

Acquired Immunodeficiency Syndrome↗

Most critically ill patients are perceived to die in comfort during withdrawal of life support: a Canadian multicentre study.

PURPOSE: Most deaths in intensive care units (ICUs) follow a withdrawal of life support (LS). Evaluation of this process including the related perspectives of grieving family members is integral to improvement of palliation in the ICU. METHODS: A prospective, multicentre, cohort study in six Canadian university-affiliated ICUs included 206 ICU patients (length of stay >or=48 hr) who received mechanical ventilation (MV) before LS withdrawal. We recorded modes, sequence and time course of LS withdrawal and drug usage (4 hr before; 4-8 hr and 8-12 hr before death). We asked a specified family member to assess patient comfort and key aspects of end-of life care. RESULTS: MV was withdrawn from 155/206 (75.2%) patients; 97/155 (62.6%) died after extubation and 58/155 (37.4%) died with an airway in place. The most frequently used drugs and the cumulative doses [median (range)] in the four hours before death were: morphine 119/206, 24 mg, (2-450 mg); midazolam 45/206, 24 mg, (2-380 mg); and lorazepam 35/206, 4 mg, (1-80 mg). These doses did not differ among the three time periods before death. Of 196 responses from family members most indicated that patients were perceived to be either totally (73, 37.2%), very (48, 24.5%), or mostly comfortable (58, 29.6%). Times to death, morphine use and family members' perceptions of comfort were similar for each type of change to MV. CONCLUSIONS: Most patients were perceived by family members to die in comfort during a withdrawal of LS. Perceptions of patient comfort and drug use in the hours before death were not associated with the mode or sequence of withdrawal of LS, or the time to death.

Analgesics, Opioid↗

Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the Canadian Multicentre Trial.

A multicentre trial was designed to determine the dose-response and side-effects of esmolol when administered as a single iv bolus prior to induction of anaesthesia for controlling the haemodynamic response to tracheal intubation. Five hundred and forty-eight patients from 12 university-affiliated centres across Canada were randomized prospectively to receive either placebo (PLAC) or esmolol (E) in a dose of 100 mg (E100) or 200 mg (E200). Study medication was given immediately before induction of anaesthesia with thiopentone 3-5 mg.kg-1 and succinylcholine 1.5 mg.kg-1. Low-dose narcotic (fentanyl 2-3 micrograms.kg-1 or sufentanil 0.3 micrograms.kg-1) or moderate dose narcotic (fentanyl 4-7 micrograms.kg-1) was also given at five of the participating centres, whereas patients in the remaining seven centres received no narcotic. Patients who received PLAC and no narcotic had greater HR and SBP values after tracheal intubation than patients who received either E100 or E200 (P less than 0.005). The proportion of patients whose maximum HR exceeded 110 min-1 was also greater in the PLAC group (22/180) than in either the E100 (10/187) or E200 (9/181) groups (P less than 0.05), but was not different when comparing E100 with E200. Esmolol was less effective in controlling blood pressure, but, in combination with low-dose narcotic, esmolol suppressed the SBP response to tracheal intubation. In the presence of moderate-dose narcotic, however, a decrease in SBP occurred in all three groups following induction of anaesthesia (P less than 0.003), with the largest decrease (17 +/- 4%) occurring in patients who had received E200. The overall incidence of hypotension (SBP less than 90 mmHg) was greater in the E200 group (33%) than either the E100 (25%) or PLAC (16%) groups (P less than 0.05). Other side-effects, such as bradycardia, bronchospasm or pain on injection, occurred no more frequently in either esmolol group than with placebo. It is concluded that a 100 mg bolus of esmolol is safe and effective for controlling the haemodynamic response to tracheal intubation. This dose of esmolol combined with a low dose of narcotic (fentanyl 2-3 micrograms.kg-1 or equivalent) results in effective control of both heart rate and blood pressure, while avoiding important side-effects.

Adrenergic beta-Antagonists↗

Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization.

The Syst-Eur Trial is a concerted action of the European Community's Medical and Health Research Programme. The trial is carried out in consultation with the World Health Organization, the International Society of Hypertension, the European Society of Hypertension and the World Hypertension League. This article describes the objectives and the protocol of Syst-Eur, a multicentre trial designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality. Secondary endpoints include cardiovascular events, such as myocardial infarction and congestive heart failure. To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized to active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/day), combined with enalapril (5-20 mg/day) and hydrochlorothiazide (12.5-25 mg/day), as necessary. The patients of the control group receive matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per-protocol comparison of the outcome in the 2 treatment groups. A one-year pilot trial (1989) showed that the protocol is practicable. The Ethics Committee therefore decided to start the definite study (1990), in which randomized patients will be followed for 5 years. Recruitment of new centres and of the required 3,000 patients will last 3 years (until 1993).

Aged↗

Epidemiology of infection with HIV-1 in Sardinia: a multicentre prospective study.

To study the spread of human immunodeficiency virus type 1 (HIV-1) in Sardinia, we conducted a multicentre prospective study of the prevalence of antibody to HIV-1 (anti-HIV-1) in various populations during 1985-1989. The highest anti-HIV-1 prevalence (61.4%) was found in intravenous drug users. Anti-HIV-1 was found in 32% of haemophiliacs, 4.2% of thalassemics and less than 1% in the other groups. We conclude that control of HIV infection in Sardinia will require a major expansion of prevention and treatment programs for drug addiction.

Adolescent↗

An European open multicentre trial with auranofin in rheumatoid arthritis.

In 8 European countries a multicentre trial was started in 672 patients with RA. The safety and efficacy of Auranofin (oral gold), was evaluated. There seems to be no difference in response to treatment between patients treated with Auranofin 3 mg twice daily or 6 mg once daily. From the fourth month of treatment there is a statistically difference in improvements for following parameters : activity index of Chalkins, articular index of Lansbury, ESR, pain, morning stiffness, grip strength, number of swollen joints and number of tender joints. These data suggest that Auranofin can be considered as a valuable disease modifying antirheumatic drug (DMARD) in RA and that early onset of therapy can be advised. In most cases the treatment is well tolerated.

Anti-Inflammatory Agents↗