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M Obradovic

Publications and source records attributed to M Obradovic.

At least 19 recordsLinked to original sources
PubMed2005

Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers.

INTRODUCTION: Pharmacological challenges with hallucinogens are used as models for psychosis in experimental research. The state induced by glutamate antagonists such as phencyclidine (PCP) is often considered as a more appropriate model of psychosis than the state induced by serotonergic hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and N,N-dimethyltryptamine (DMT). However, so far, the psychological profiles of the two types of hallucinogenic drugs have never been studied directly in an experimental within-subject design. METHODS: Fifteen healthy volunteers were included in a double-blind, cross-over study with two doses of the serotonin 5-HT2A agonist DMT and the glutamate N-methyl-D-aspartate (NMDA) antagonist (S)-ketamine. RESULTS: Data are reported for nine subjects who completed both experimental days with both doses of the two drugs. The intensity of global psychological effects was similar for DMT and (S)-ketamine. However, phenomena resembling positive symptoms of schizophrenia, particularly positive formal thought disorder and inappropriate affect, were stronger after DMT. Phenomena resembling negative symptoms of schizophrenia, attention deficits, body perception disturbances and catatonia-like motor phenomena were stronger after (S)-ketamine. DISCUSSION: The present study suggests that the NMDA antagonist model of psychosis is not overall superior to the serotonin 5-HT2A agonist model. Rather, the two classes of drugs tend to model different aspects or types of schizophrenia. The NMDA antagonist state may be an appropriate model for psychoses with prominent negative and possibly also catatonic features, while the 5-HT2A agonist state may be a better model for psychoses of the paranoid type.

Adult↗
PubMed1999

Determinants of long term survival after surgery for cancer of the lung: A population-based study.

BACKGROUND: Even if some determinants of lung cancer (LC) prognosis have been established, their independent effect on long term survival remains to be seen. The objective of the current study was to identify the prognostic indicators of long term survival among LC patients treated by surgery. METHODS: All patients with LC recorded at the Geneva Cancer Registry between 1977 and 1987 were analyzed by logistic regression, considering as cases (n = 98) those patients alive 10 years after their initial diagnosis and as controls (n = 330) all other patients, excluding those who did not undergo putative curative surgery. The effect of each prognostic factor was evaluated after accounting for age and gender ("crude" effect) and also for other a priori confounding factors (adjusted effect). Additional models considered two staging variables simultaneously to identify the strongest staging determinant. Results were presented as relative risk estimates of long term (>/=10 years) survival. RESULTS: Age, histology, and stage of disease significantly influenced prognosis regardless of the confounding factors considered. Gender also emerged as a discriminated factor in LC outcome, with a 2.1-fold increased chance (95% confidence interval, 1.6-3.5) of long term survival for women compared with men. Method of discovery, presence of symptoms, period of diagnosis, socioeconomic status, and tumor differentiation did not appear to be associated with long term survival. Extent and size of the tumor were found to be the most reliable prognostic staging factors, whereas adenopathy had no effect after accounting for extension. CONCLUSIONS: The current population-based study quantifies the independent effect of the factors modifying the chances of curability in patients with LC. In particular, it provides additional evidence that gender strongly influences long term survival.

Adult↗
PubMed1999

Treatment of anal carcinoma in the elderly: feasibility and outcome of radical radiotherapy with or without concomitant chemotherapy.

BACKGROUND: For most cancers, information on treatment tolerance and results for elderly patients is quite limited. This study was conducted to investigate the feasibility and results of curative nonsurgical treatment of patients age 75 years or older with anal carcinoma. METHODS: From January 1976 through June 1996, invasive anal squamous cell carcinoma was diagnosed in 58 patients age > or = 75 years. Curative treatment was administered to 47 patients (81%), of whom 42 received radiotherapy (RT), either used alone (21) or associated with concomitant chemotherapy (CT). RT was administered in two sequences, the first in which a median dose of 39.6 gray (Gy) was delivered with megavoltage photon beams, followed (after a median interval of 43 days) by a boost with either brachytherapy or external beam (median dose, 20 Gy). CT started on Day 1 and generally consisted of 1 cycle of mitomycin C (MMC; median dose, 9.5 mg/m2) and a 96-hour infusion of 5-fluorouracil (5-FU; median dose, 600 mg/m2/day). The median follow-up for all patients was 48 months (range, 5-163 months). RESULTS: Of 40 patients (95%) who completed curative treatment, acute toxicity resulted in shortening of the planned first irradiation sequence in 2 patients (1 in each group) and an unplanned treatment break in 11 patients (4 in the RT group and 7 in the RT-CT group). Grade 2 and 3 acute reactions (RTOG) were observed in 43% and 54% of patients, respectively. Among all Grade 3 reactions, 32% occurred in the RT group and 68% in the RT-CT group. In patients receiving RT-CT, Grade 2-3 leukopenia was observed in 25% of patients, Grade 2-3 fatigue was observed in 58% of patients, and Grade 2 cardiac toxicity related to 5-FU occurred in 1 patient. At 5 years, the overall survival was 54% (49% and 59% for the RT and RT-CT groups, respectively, P = 0.28), and the actuarial local control rate was 78.5% (73% and 83% for the RT and RT-CT groups, respectively, P=0.36). Five patients presented with Grade 3-4 late complications, all of them in the RT-CT group. CONCLUSIONS: The current series confirms the feasibility of sphincter-conserving treatment for elderly patients who present with anal carcinoma. Rates of acute or late complications appeared similar to those observed in younger patients, and the oncologic results were at least as favorable as those commonly reported.

Aged↗
PubMed1998

Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. EUROCARE Working Group.

The EUROCARE Study is a European Union project to assemble survival data from population-based cancer registries and analyse them according to standard procedures. We investigated and compared liver, pancreatic and biliary tract cancer survival in 17 countries from 1985 to 1989. Time trends in survival over the 1978-1989 period were also investigated in 12 countries. The overall European mean 1 year relative survival was 16% for primary liver cancer, 26% for biliary tract cancer and 15% for pancreatic cancer. The corresponding 5-year relative survival was 5, 12 and 4%, respectively. Taking the European average as the reference, the relative risk (RR) of death was at least 20% higher for the three cancers in Denmark and Estonia. Survival tended to be higher in Spain for primary liver cancer and biliary tract cancer. Gender had little influence on survival whilst age at diagnosis was inversely related to prognosis. There was an improvement in 1-year relative survival rate for primary liver cancer: relative risk (RR) of 0.68 (95% confidence interval (CI) of 0.60-0.77) for 1987-1989 versus 1978-1980 and biliary tract cancer (RR 0.77, 95% CI 0.68-0.87). There was less variation in 5-year relative survival rate over time. Some intercountry survival differences for primary liver, biliary tract and pancreatic cancers exist over Europe. Differences in quality of care, in particular treatment aggressiveness, may explain some of these differences in survival. New approaches to the management of these cancers need to be found.

Adolescent↗
PubMed1994

Isolation of a Puumala-like virus from Mus musculus captured in Yugoslavia and its association with severe hemorrhagic fever with renal syndrome.

An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in 1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children and 1 adult, and 1 of the children died. Rodents were captured from the same area and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung tissues of hantavirus antigen-positive Mus musculus. Serology and restriction enzyme digestion of polymerase chain reaction-amplified segments from this virus showed that it was a strain of Puumala (PUU) virus, the causative agent of nephropathia epidemica. While Clethrionomys glareolus is the major rodent host for PUU virus, these results suggest that M. musculus may also play an important role in harboring and transmitting PUU-like viruses. The serologic association of this virus with patients with severe HFRS reaffirms that PUU-like viruses may cause severe disease in addition to the generally mild form normally associated with nephropathia epidemica.

Animals↗
PubMed1993

[Multiple tumors of colon and rectum].

The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was 1.1% and that of metachronous carcinomas 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinoma was observed. The 5-year actuarial survival in case of curative resection was 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions.

Actuarial Analysis↗
PubMed1993

[Multiple tumors of the colon and rectum].

The possible occurrence of multiple synchronous or metachronous malignant lesions in patients with a carcinoma of the colon and rectum is a well known event. In this population-based study in the Geneva area from 1970 to 1986, the frequency of synchronous colorectal carcinomas was of 1.1% and that of metachronous carcinomas of 1%. The relative risk of metachronous colorectal carcinoma is higher than in the general population (colon after rectum 1.2, colon after colon 1.7 and rectum after rectum 1.4). A high association of adenomatous polyps with multiple colorectal carcinomas was observed. The 5-year actuarial survival in case of curative resection was of 87% for metachronous carcinomas, 35% for single carcinomas and 33% for synchronous carcinomas. We conclude that complete preoperative colonoscopy, whenever possible, should be performed to screen patients with synchronous carcinomas. Finally, a lifelong follow-up of the residual colon or rectum should be planned to detect metachronous lesions.

Aged↗
PubMed1992

Hemorrhagic fever with renal syndrome in Yugoslavia: epidemiologic and epizootiologic features of a nationwide outbreak in 1989.

A nationwide epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in Yugoslavia in 1989. Sera from 609 hospitalized patients, from all six Republics (Bosnia and Hercegovina, Croatia, Macedonia, Montenegro Serbia, Slovenia) and two Provinces (Kosovo and Vojvodina), who had signs and symptoms suggestive of HFRS, and sera and lung tissues from 544 small mammals belonging to 13 species were studied for evidence of hantavirus infection. Of the 226 patients with serologically confirmed HFRS, 182 resided in Bosnia and Hercegovina or in Serbia. The severity of disease differed from region to region, with an overall fatality of 6.6% (15/226). Patients from southern Yugoslavia tended to have more severe disease and exhibited two types of antibody patterns, while approximately equal numbers of clinically severe and mild cases of HFRS were registered in central Yugoslavia, where four types of antibody patterns were found. Two of these antibody patterns suggested the existence of hantaviruses which are antigenically distinct from those reported to date. Two seasonal peaks of disease, one during the summer and the other in late autumn, were found. Hantaviral antibodies and/or antigens were detected most often in the yellow-necked mouse (Apodemus flavicollis) (88/189), the wood mouse (Apodemus sylvaticus) (28/146), the striped field mouse (Apodemus agrarius) (10/64), the bank vole (Clethrionomys glareolus) (36/63), the house mouse (Mus musculus) (14/29), and the Norway rat (Rattus norvegicus) (14/21). Five other species of rodents and insectivores were infrequently infected.

Animals↗
PubMed1992

Belgrade virus: a new hantavirus causing severe hemorrhagic fever with renal syndrome in Yugoslavia.

Two biologically and genetically distinct hantaviruses were isolated from blood and urine specimens collected from four Yugoslavian patients with clinically severe hemorrhagic fever with renal syndrome (HFRS). Viral isolates from three patients, designated strains Belgrade 1-3, were distinct from Hantaan, Seoul, Puumala, and Prospect Hill viruses as determined by plaque-reduction neutralization tests and restriction analysis of enzymatically amplified M-segment fragments. The fourth isolate, called Kraljevo, was indistinguishable from Hantaan virus. Strains Belgrade 1 and 2, like the Kraljevo strain, caused a fatal meningoencephalitis in newborn mice inoculated with 100 pfu of virus intracerebrally and intraperitoneally. Strain Belgrade 3 was much less neurovirulent, requiring 30,000 pfu of virus to cause fatal disease in mice. These data indicate that two distinct hantaviruses, one of which constitutes a new serotype, cause clinically severe HFRS in Yugoslavia.

Adult↗
PubMed1990

The risk of second cancer (SC) in patients treated for testicular seminoma.

The exact risk of second cancer (S.C.) following treatment of testicular seminoma is not well determined in most series. At our institution, 122 patients with pure seminoma were treated by orchidectomy followed by radiation therapy from 1951 to 1986. Six were lost to follow-up. For the 116 remaining patients, the overall 5-, 10-, 15- and 20-year survival probability was 95%, 90%, 87%, and 84%, respectively. Eleven patients developed 12 second cancers, with a cumulative risk of 7%, 16%, and 16% at 10, 15, and 20 years, respectively. Overall, the risk of second cancer was increased (O/E = 1.97, p = 0.023). There were 3 controlateral seminoma (O/E = 50, p = 0.001), 2 transitional carcinoma of the bladder (O/E = 6.9, p = 0.035), 2 non-Hodgkin's lymphoma (N.S.), 1 acute myeloblastic leukemia, 1 chronic lymphocytic leukemia, 1 intracranial dysgerminoma, 1 rectal and 1 lung adenocarcinoma. Four tumors developed within the previously irradiated field (O/E = 2.2, N.S.). Excluding second seminoma, the overall risk of second cancer was not significant (O/E = 1.33). Five of the 11 patients with second cancer are currently alive without recurrent cancer. We conclude that patients treated for seminoma have an increased risk of second cancer but the overall prognosis remains excellent. The potential factors responsible for second cancer, including irradiation, are discussed.

Combined Modality Therapy↗
PubMed1989

Incidence and morbidity of cancer of the cervix in Geneva, Switzerland.

The incidence and mortality rates of invasive carcinoma of the cervix in the state of Geneva, Switzerland, is reported for the time periods 1970-1973 and 1980-1983. A reduction in mortality (7 to 4.3/100,000) occurred as well as a considerable decrease in the overall incidence (20.3 to 11.4/100,000). This decrease is particularly marked in the age group of 35-64 years. It is less marked between the ages of 60 and 69 and did not appears before 35 years or after 70 years of age. In the time period 1980-1983, more than one half of the cases were found after age 60 years, two thirds of them in stage 2 or worse. It is therefore essential that screening programs recruit a high enough proportion of older women.

Female↗
PubMed1988

[Prognostic factors in survival after cancer: epidemiological model].

Quality of care assessment is one of the principal issues considered when studying the survival of cancer patients. Survival rates based on hospital series ("clinical survival") essentially aim at evaluating the impact of therapy, taking into account the stage of the tumor. When, on the other hand, survival rates refer to a demographically defined population ("epidemiologic survival") they depend not only on quality of therapy but also on differentials in access to health services which in turn condition partly the stage at time of diagnosis and therapy selection. Since these patterns of access can vary according to socio-cultural characteristics, the epidemiologist is tempted to focus the prognostic analysis of survival on these characteristics. In a cancer registry setting, clinical indicators (stage of the lesions, type of health care institution and therapy) must not be neglected. Rather, these must be analyzed both as co-factors of survival and as phenomena to be explained in their own right. Issues relating to this topic are discussed using the example of breast cancer in Geneva.

Aged↗
PubMed1988

[Swiss interregional epidemiologic study of the risk of cancer in the contralateral breast].

This epidemiologic investigation in three Swiss regions (Geneva, St. Gall-Appenzell, Vaud) included 5,193 women diagnosed as having a first primary breast cancer. The patients were followed up for ten years (the observation totalled 24,994 women-years). Overall, these results confirmed that the relative risk of a second breast cancer was greatly increased during the first year following the primary diagnosis, but this was largely due to simultaneously discovered contralateral tumours. Beyond the first year of follow-up, the relative risk of a second tumour was lower but still significantly greater than unity. No significant diminution of the excess risk was observed in the first 10 years of follow-up. Relative risk of a second breast cancer was generally higher before age 50, independently of the latency. The relative risk of a second breast cancer differed significantly from one region to another, possibly due to specific techniques of registration.

Adult↗