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Most large comparative trials of therapeutic agents are now conducted as multicentre studies. Some of the major studies designed by Bradford Hill were also multicentre, and his methods of design and conduct remain valid today, even though improved methods for analysing the data have appeared subsequently.
Profound immunodeficiency in multicentric Castleman's disease has already been elucidated. In the present study, we investigated CD45RO and Fas antigen expression and apoptosis by T cells in three patients with this disease. T cell expression of CD45RO and Fas antigen was increased in two of the three patients, indicating in vivo lymphocyte activation. Apoptosis of T cells from the two patients with increased CD45RO and Fas antigen expression occurred after overnight culture in the presence of pokeweed mitogen. Occurrence of apoptosis was indicated by DNA laddering and nuclear chromatin condensation. Peripheral blood mononuclear cells from the two MCD patients revealed spontaneous apoptosis following 3 days of culture by quantitative assay using flow cytometry. These findings show that T cells are activated in some patients with multicentric Castleman's disease and suggest that this activation may promote apoptosis.
BACKGROUND: The most common entrapment in the lower extremity is peroneal mononeuropathy (PM) at the fibular head. Several studies of this condition have been published but, until now, no wide multicenter clinical-neurophysiological studies on PM are available. In recent years, multicenter studies have been suggested; moreover it is commonly accepted that a multiperspective approach provides more comprehensive results. METHOD: The Italian CTS and other entrapments Study Group has designed a strict clinical and neurophysiological protocol to carry out a wide multicentre study on PM at the fibular head. In addition to traditional clinical-neurophysiological evaluation, the group has also adopted validated disability and patient-oriented measurements in order to obtain more comprehensive and reliable data about this entrapment. The study was designed: 1) to identify predisposing factors; 2) to better assess the clinical picture; 3) to evaluate relationships between etiological, clinical and neurophysiological findings; 4) to evaluate the natural evolution of the entrapment. Study design is described. FINDINGS: During the period from November 2002 to January 2004, 69 patients were enrolled consecutively in eleven Italian centres. Our preliminary data show that PM involves men more frequently than women (M:F = 3.9:1). With regard to the predisposing factors, PM is idiopathic (16%) or due to surgery (21.7%), prolonged posture (23.2%), weight loss (14.5%), external compression (5.8%), arthrogenic cyst at the fibula (1.4%), trauma (10.1%); it also occurred in bedridden patients (7.3%). Unexpectedly, peroneal nerve lesions were due not only to surgical operation close to the peroneal region, but were also associated with thoracic-abdominal surgery. Usually PM involves both terminal branches; patients complain of motor deficit in 99.5% of cases, sensory symptoms in 87.9% and pain in 19.7%. CONCLUSIONS: Our preliminary results provide some interesting information and confirm the usefulness of multicentre and multiperspective studies to standardise the approach to nerve entrapment.
A case of multicentric metachronous GCT was presented. The clinical and radiographic features of multicentric GCT as reported in the literature and in the present case were discussed. The multiple bone involvement made therapeutic assessment difficult. The surgical stage as well as the location of each lesion were important in planning surgery.
The typical giant cell tumor (GCT) is a solitary neoplams that occurs in the epiphysis or epimetaphysis of long bones. GCT is seen with a slightly increased frequency in females, and 70% of patients are between 20 and 40 years of age at the time of presentation. Multicentric giant cell tumor (MGCT; two or more centers) is an unusual variant of GCT. Patients with MGCT are likely to be younger than those with a solitary lesion. The multicentric variety is often of a higher stage at diagnosis and is more often associated with a pathological fracture than the unifocal tumor. We are reporting five new cases of MGCT, with a total of 21 tumors seen over a period of 25 years from 1967 to 1992.
Borderline hepatocellular nodules (BHN), atypical adenomatous hyperplasia, macroregenerative nodule type II or dysplastic nodules in the cirrhotic liver are considered to be important prcancerous lesions transforming to hepatocellular carcinoma (HCC). In order to evaluate the uni- or multicentric origin of BHN and HCC arising from BN, we surveyed 30 cirrhotic livers with BHNs that had been surgically resected or autopsied during 1973-1993. Among the 30 cirrhotic livers with BHNs, two or more BHNs were present in a single cirrhotic liver in 10 (33%) cases, while only one BHN was present in a single cirrhotic liver in the remaining 20 (67%) cases. The mean number of BHN in a cirrhotic liver with multiple BHNs was 3.5. Carcinomatous foci were present within BHN in 6 (60%) of the 10 cirrhotic livers with multiple BHNs, while they were present in 4 (20%) of the 20 cirrhotic livers with a single BHN; this difference was statistically significant (P < 0.05). Coexistance of HCC was noted in 8 (80%) of the 10 cirrhotic livers with multiple BHNs, and in 3 (15%) of the 20 cirrhotic livers with a single BHN; this difference was statistically significant (P < 0.01). There were no significant differences in age, sex, aetiology and morphology between cirrhotic livers with multiple BHNs and those with a single BHN. These data suggest that BHN and HCC arising from BHN may be of multicentric origin.
An extremely rare case of multicentric periosteal osteoid osteoma in a child was presented. The lesions were found to be embedded in a narrow elliptical strip, suggesting the possibility that lesional tissue was stretched in a longitudinal fashion as a result of the rapid skeletal growth. In young patients with stretched periosteal reaction who complain of pain, multicentric osteoid osteoma should be suspected. These nidi can be obscured by the exuberant periosteal reaction. Accurate evaluation of the radiographic findings is very important.
A transformed cell line, B1, of cerebral endothelial origin from the Wistar-Kyoto male rat has chromatid and chromosome type bridges in virtually every cell. It exhibits various dicentric and polycentric chromosomes. Most dicentrics are symmetric isochromosomes. Certain isodicentrics are present in a fair segment of the cell population; however, almost all cells have some newly arising isodicentrics. The live cells show a lengthened prometaphase. Anaphase is also retarded possibly due to the occurrence of bridges. At anaphase some multicentrics split at only one centromere. When pulled to the two poles the unsplit centromeres and the distal chromosome segment form a side arm bridge. Another mechanism appears to be a total lack of separation of daughter centromeres at meta-anaphase ('meiotic-like' behavior of mitotic chromosomes). This is realized by the pulling of each of the two unsplit centromeres to opposite poles and results in bridges with both sister chromatids running parallel to each other. A break at corresponding weak points in the two sister chromatids followed by rejoining can form a dicentric isochromosome. A third mechanism, the breakage-fusion-bridge cycle, is also operative but would not produce isodicentrics. In the case of the first two mechanisms some or all centromeres apparently split between telophase and onset of the following DNA synthesis rather than at the usual time at late metaphase. These observations may suggest some previously unknown behavior of multicentric chromosomes during mitosis.
During the 7 years from 1984 to 1990, 36 patients underwent liver resection for solitary hepatocellular carcinoma (HCC) measuring less than 5 cm in diameter, with no intrahepatic vascular invasion on imaging diagnoses and no macroscopic infiltration into the tumor capsule or surrounding tissues. Although HCC is less likely to cause intrahepatic adjacent metastasis to the cut liver surface, an analysis revealed the possibility of intrahepatic distant metastasis and metachronous multicentric occurrences, even after complete removal of the primary tumor. The 5-year cumulative survival rate was 53%, while the 5-year cumulative recurrence-free survival rate was 19%. Of the 36 patients, 18 (50%) had suffered a recurrence by April, 1992, one with extrahepatic metastasis. Recurrence of intrahepatic metastasis was multifocal in 5 patients, single and adjacent in 1, and single (or a few) and distant in 11. Multifocal recurrence was observed within 1 year after liver resection. The sole single and adjacent metastatic case occurred in one of eight patients in the recurrent group in whom distance of the surgical margin was less than 1 cm [TW(+)]. Multicentric occurrence was found in 6 of 13 patients (46%) whose recurrent tumors were examined histologically, and all belonged to the "single (or a few) and distant" type of recurrence. In this report, we also present two typical cases of metastasis, one being multifocal metastasis occurring within 3 months after liver resection and the other being intrahepatic metastasis occurring after a 4-year-dormant state, to demonstrate the complicated nature of the intrahepatic metastatic pattern.
Synchronous multicentric aggressive fibromatosis does not appear to have been previously reported. Two such cases are described. The tumors were identified by magnetic resonance (MR) imaging. The incidence of synchronous multicentric aggressive fibromatosis is not known. It is anticipated that increased use of coronal MR imaging will reveal more tumors of this type, both synchronous and metachronous. In a patient with known or suspected aggressive fibromatosis, every other soft tissue nodule or mass in the same limb has to be regarded as an additional tumor of the same histology.
Our study examined 166 patients with breast cancer with a mean age of 63 years. Each patient underwent mastectomy with the organ being investigated by histological giant sections and additional small sections from the nipple. Nipple involvement was found in 64 cases (38%). Multifocal carcinoma occurred in 76 patients. Further multicentric carcinomatous foci (36 cases) demonstrated a significant increase in affected nipples. Additional atypical ductal or lobular hyperplasia was observed in 53 cases and showed involvement in 34. Nine carcinomas of ductal origin were combined with lobular carcinoma in situ, all cases proved to have carcinomatous changes in the nipple. It is concluded that apart from the well-known influence of advanced tumor stages and tumor localization, nipple involvement correlates with multicentricity and multifocality of breast cancer as a disease of the whole organ.
Although multicentric glioblastomas are relatively rare, their occurrence is not an extreme rarity. A multicentric lesion should always be thought of when the symptoms cannot be related to a single focus and when the special investigations do not confirm a single lesion. In our opinion the brain scintigram and the computer tomogram offer the best diagnostic possibilities at present. If the preoperative diagnosis has been made, then an indication for operation can be justified only if multiple tumours can be removed through one approach and, what is even more important, at one sitting. The cases demonstrated prove that this procedure can be successful. If, on the other hand, only one of several tumours is excised, then a fatal outcome is almost certain.
This study aims to evaluate the clinical significance of the nuclear DNA index (DI) for identification of multicentrically occurring (MC) hepatocellular carcinoma (HCC). In 14 multinodular HCC patients, the DI of 30 HCC specimens and 14 non-cancerous liver tissues were analyzed by flow cytometry. Histological studies of the 30 HCCs revealed MC in 6 cases and intrahepatic metastasis (IM) in 7 cases except for a histologically undetermined case who was found to be a hepatitis B virus (HBV) carrier, and the MC of this case was determined by a clonal study using the HBV integration pattern. In four of the seven specimens with MC HCC, the DI of all the intrahepatic tumors was 1.0 (diploid pattern), while the remaining three were different. On the other hand, five of the seven IM cases were identical (3 diploid and 2 aneuploid), one similar level (DI = 1.17-1.18) and one different (1.0 and 1.24). Moreover, in one IM case, the possibility of an alteration of the DI during the course of HCC development was investigated. Although the DI of the recurrent main tumor (DI = 1.17) of this case, which was identified as metastasis of the primary tumor by a clonal study, was also similar to that of subsequent metastatic lesions (DI = 1.18), the DI of the primary tumor was 1.0. These results indicate that DI analysis was not enough to make a differential diagnosis of the multicentric occurrence of HCC.
We describe a 42-year-old man with a five-year history of arthritis mutilans-like destructive joint changes and with a one-year history of nodules on the fingers, ears, oral mucosa, pharynx, larynx, vocal cords, some being ulcerated and haemorrhagic. He was diagnosed as having rheumatoid arthritis; however, biopsies from the nodules on the oral mucosa and ear revealed multicentric reticulohistiocytosis. The large nodule over the olecranon process, simulating a rheumatoid nodule but diagnosed as multicentric reticulohistiocytosis with biopsy; ulcerated and haemorrhagic nodules on the oral mucosa; and rapidly progressive joint destructions make our case interesting.
Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.
PURPOSE: To report the perioperative management and the serious hemodynamic fluctuations during manipulation of an organ of Zuckerkandl tumour in a patient undergoing resection of multicentric extraadrenal pheochromocytomas. CLINICAL FINDINGS: A 28-yr-old man who had undergone at age 12 a laparotomy for excision of an extraadrenal pheochromocytoma complained of paroxysmal headache, occasional sweating and palpitations. The arterial blood pressure (BP) was 200/100 mmHg. A 24-hr-urine collection showed catecholamines 5076 microg x 24 hr(-1) (normal < 25 microg x 24 hr(-1)). Computed tomography of the abdomen revealed two retroperitoneal masses, one adjacent to the lower pole of the right kidney and a second larger mass located at the aortic bifurcation in the region of the organ of Zuckerkandl. The patient was scheduled for excision of multiple extraadrenal pheochromocytomas. He was prepared preoperatively for two weeks with prazosin 1 mg po q six hours and propranolol 10 mg tid. Manipulation of the infrarenal tumour was uneventful but manipulation of the Zuckerkandl tumour resulted in severe hypertensive episodes with BP ranging from 200/100 to 320/120 mmHg. Surgery was interrupted temporarily; the hypertensive crisis was controlled by the infusion of sodium nitroprusside and by iv phentolamine and esmolol. CONCLUSION: In a patient undergoing resection of recurrent multicentric extraadrenal pheochromoctyomas, severe hypertensive episodes occurred during manipulation of one tumour but not during manipulation of the other. This may be attributed to inadequate preparation of the patient, difficult surgical dissection of the large Zuckerkandl pheochromocytoma, and/or secondary to an excessive and different pattern of release of catecholamines during manipulation of the Zuckerkandl tumour.
AIMS/HYPOTHESIS: For use in future drug development for diabetic polyneuropathy, we conducted multicentre trials to assess the reproducibility of nerve conduction studies. METHODS: All measurements were repeated twice at a time interval of 1-4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic polyneuropathy. Using a standardised method, 32 centres participated in the study of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and recording the compound action potential from abductor policis and adductor hallucis for measuring amplitude, terminal latency and minimal F-wave latency. For sensory conduction studies, sensory nerve action potentials were recorded antidromically from the second digit and the posterior aspect of the lateral malleous after distal stimulation of the left median and sural nerves. We also calculated motor conduction velocity, F-wave conduction velocity and sensory conduction velocity. The relative intertrial variation and intraclass correlation coefficient were used as an index of reproducibility. RESULTS: Of all the measurements, F-wave latency yielded the highest intraclass correlation coefficient with the smallest relative intertrial variation for both median and tibial nerves in both groups. CONCLUSION/INTERPRETATION: Median and tibial F-wave latency provide the most reproducible measures for a nerve conduction study, serving as one of the best measures in multicentre drug trials for diabetic polyneuropathies.
BACKGROUND: National suicide statistics show remarkable differences in the frequencies of various methods used for completed suicide. The WHO/EURO Multicentre Study on Parasuicide makes possible for the first time an international comparison of the frequencies of methods used in attempted suicide, because the data are based on geographical catchment areas of medical institutions. METHOD: Ongoing standardized monitoring of attempted suicide in all medical institutions serving the catchment areas was performed in 14 centres in 12 European countries. The data analysis is based on 20,649 events involving 15,530 persons, recorded between 1989 and 1993. RESULTS: The comparison of rates per 100,000 shows striking differences between the centres. The highest rates for drug overdoses were found for female attempters in Oxford (347/100,000), Helsinki (238/100,000) and Stockholm (221/100,000). Guipuzcoa had the lowest rates (61/100,000). The differences were most prominent in the age group 15-24, with outstanding rates for women in Oxford (653/100,000), which was mainly due to the frequent use of analgesics. Szeged had outstandingly high rates for pesticides and solvents. In some centres the use of multiple methods was frequent. CONCLUSIONS: There is a need, especially for areas with high frequencies for certain methods, to understand the factors involved and to develop new and specific prevention projects and to monitor their effects. The WHO/EURO Multicentre Study on Parasuicide has proved to be a useful and reliable instrument for continuous monitoring of trends in parasuicide.