Biomedical subjects
Publications and source records attributed to T Roman.
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Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Several investigations have reported associations between ADHD and both the 7-repeat allele of the 48 bp VNTR at the DRD4 gene and the 10-repeat allele of the 40 bp VNTR at the DAT1 gene, but the results have been inconsistent. A sample of 81 Brazilian ADHD children and adolescents and their parents were screened for these DRD4 and DAT1 VNTRs. An excess of the DRD4 7-repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample (chi-square = 11.55, P = 0.03; chi-square = 12.17, P = 0.03, respectively). However, haplotype relative risk (HRR) analysis showed no preferential transmission of the DRD4 7-repeat allele. No evidence of association with the DAT1 polymorphism was detected by both approaches. Nevertheless, an interaction effect of both genes on ADHD hyperactive/impulsive dimension was observed (F = 4.68; P = 0.03). These results add to the group of studies that together suggest a small effect of these genes in the susceptibility to ADHD.
After the initial report in 1976 of a trichinellosis epidemic caused by the consumption of infected horsemeat, 12 other outbreaks have been described in Europe. Since the first serious human outbreak several experiments have confirmed the susceptibility of horses to Trichinella species and the rapid disappearance of specific antibodies in this host that prevents the use of serological methods for routine screening. A review of the distribution of parasite burdens in muscles of naturally or experimentally infected horses indicates that the tongue is the most likely sample to contain detectable numbers of Trichinella larvae in low level infections. Requirements for testing of horsemeat are specified in legislation of the European Union, and other recommendations are published elsewhere. The EEC directives have evolved into very specific requirements which specify the testing of at least 5g of tongue, masseter or diaphragm per horse using a pooled digestion assay. More recently, France has revised the requirement for sample size to 10g for horsemeat originating from countries with high prevalence of Trichinella. To address the continuing outbreaks of human trichinellosis due to infected horsemeat, the development and implementation of a quality assurance system for testing is being considered.
The presence of the seven-repeat allele of the VNTR in the exon 3 of the dopamine D4 receptor gene (DRD4) has been associated in healthy subjects to the personality trait of novelty seeking. The present study focuses these observations on a sample of Brazilian male alcoholics, evaluated on the temperament dimensions originally described by Cloninger. The genotypes observed are in agreement with those expected under Hardy-Weinberg equilibrium. Subjects with the seven-repeat allele manifest lower harm avoidance scores. No significant differences between subjects with or without the seven-repeat allele in the scores of novelty seeking or reward dependence were observed. The lack of association between novelty seeking and the DRD4 exon 3 polymorphism is further corroborated by the fact that the comorbid antisocial personality disorder is not associated to the presence of the seven-repeat allele. These results could be explained by a biological connection between the personality dimensions of novelty seeking and harm avoidance.
PURPOSE: Results of treatment of patients with Stage I seminoma with orchiectomy and radiotherapy are excellent. Even without adjuvant radiotherapy, the relapse rate is only 15-20%; most of the patients fail in the retroperitoneum, with rare failures observed in the pelvis (0.5-2%). In 1991, we began a prospective study evaluating para-aortic lymph node radiation as the only adjuvant treatment for such patients. This paper reports our preliminary results. MATERIALS & METHODS: Between March 1991 and January 1996, 35 patients with histologically proven Stage I seminoma were entered in the study. Median age was 37.9 years (range: 27-65 years). A radical inguinal orchiectomy was performed in all patients. Staging workup consisted of a chest X-ray; B-HCG, alpha-fetoprotein, and CT scan of the abdomen and pelvis in all patients. Lymphangiogram was done in 23 (66%) of 35 patients for further evaluation of the retroperitoneal lymph nodes. Radiotherapy consisted of treatment to the para-aortic region only. Parallel opposed fields extending from the top of T11 to the bottom of L5 were used. The median field size was 8.7 x 21.8 cm (range: 7-11 x 18-26 cm). The median total dose, prescribed at midpoint, was 25 Gy given in 15 daily fractions of 1.66 Gy. Follow-up was performed every 3 months for the first year, every 4-5 months for the second and third years, and every 6 months thereafter. Chest X-ray, tumor markers, and CT scan of the pelvis were performed routinely as part of the follow-up investigation. RESULTS: At a median follow-up of 39.7 months (range: 16-74 months), 34 (97.1%) of 35 patients are alive with no evidence of disease for an overall actuarial survival rate of 97.1% at 5 years and a cause-specific actuarial survival rate of 100%. Treatment morbidity was limited to Grade I-II acute side effects in 18 (51.4%) of 35 patients. No late side effects were seen. CONCLUSION: From our preliminary results, adjuvant radiation treatment limited to the para-aortic lymph node region, without ipsilateral pelvic irradiation, appears to be adequate treatment for Stage I seminoma. Such an approach in our patients resulted in minimal toxicity and excellent disease-free survival.
PURPOSE: To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma following total abdominal hysterectomy and bisalpingo-oophorectomy (TAH BSO). MATERIALS AND METHODS: Twenty patients originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or II) following TAH BSO developed isolated vaginal recurrences and were referred to our radiation oncology department for definitive treatment. The median time between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Median prescribed dose was 3500 cGy to the vagina mucosa surface for the HDRB only group. These patients were followed for a median duration of 47.5 months following treatment for isolated vaginal recurrence. RESULTS: Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications. Three patients developed grade 2 late complications from treatment; all 3 were from the combined modality group (HDRB + EBRT). CONCLUSION: The use of HDRB resulted in high complete response rates and durable long-term disease-specific survival in a substantial percentage of patients. To our knowledge, this study represents the first published results on treatment of vaginal recurrences with HDRB. Although the number of patients in this study is small, treatment results compare favorably to those obtained from patients treated with low-dose-rate brachytherapy +/- EBRT from other studies.
STUDY OBJECTIVE: We evaluated bronchoscopic tumor appearance and tumor location as determinants of response to high-dose rate brachytherapy (HDR-BT) in patients with symptomatic unresectable bronchogenic carcinoma previously treated with external-beam irradiation. PATIENTS AND METHODS: Thirty patients with symptomatic endobronchial bronchogenic carcinoma who had previously completed external irradiation were divided into two groups based on whether the initial bronchoscopic appearance showed an endoluminal mass or submucosal infiltration/extrinsic compression. Furthermore, patients were also classified based on tumor location: central (trachea or mainstem bronchi) and peripheral (lobar or segmental bronchi). Patients underwent three treatments of 800 cGy intraluminal irradiation at 2-week intervals, with follow-up evaluation 4 weeks later. We evaluated response in tumor extent based on bronchoscopic and chest radiograph appearance, as well as symptoms with standardized scales. RESULTS: Fifteen of 24 patients who underwent follow-up bronchoscopy had reductions in the degree of endobronchial obstruction. Seven of 24 patients had radiographic improvement in the extent of atelectasis. Patients with both tumor appearances (endoluminal and submucosal/extrinsic compression) had significant improvements following HDR-BT with regard to hemoptysis. Patients with submucosal disease also had improvement in cough. Patients with peripheral tumors had better rates of response for hemoptysis and cough than did those with central tumors. CONCLUSION: HDR-BT may result in symptomatic improvement in patients with bronchogenic carcinoma, whether characterized endoscopically as endoluminal projection or submucosal infiltration/extrinsic compression. Peripheral tumors have better rates of response than central tumors, possibly on the basis of less extensive disease.
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BACKGROUND: External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disase are common following external irradiation. The impact of high dose rate (HDR) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated. METHODS: A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic determination of degree of endobronchial obstruction. RESULTS: One hundred and eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients had radiographic improvement in the extent of atelectasis. Positive response rates ranged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. Two patients died before completion of the study protocol. Short term complications included one episode of non-fatal, massive haemoptysis, five of minor haemoptysis, and one pneumothorax. CONCLUSIONS: HDR brachytherapy may improve the degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.
The immunoglobulin heavy chain repertoire in fish was investigated by cloning a total of 88 rearranged VDJ junctions from the head kidney B cell mRNA of a salmonid, the rainbow trout (Oncorhynchus mykiss). Trout DH segments are short and cannot be classified into independent DH families. Several of the ten identified putative DH segments had stretches of nucleotide sequence identity with mouse (DQ52, DFL 16.2 and Dsp 2.1), human (DM1) and chicken (DH4) DH. There was a clear preference for one or two of the three putative DH reading frames and a stop codon is often present in the less used reading frame. Four of the six JH segments are preferentially used, and analysis of the VH-DH and DH-JH junctions suggest the presence of N-nucleotides. The absolute size and size heterogeneity of the rainbow trout CDRH3 are smaller than those of the Xenopus, mouse and human CDRH3. About 75% of the 84 in-frame trout CDRH3 have 8, 9 or 10 residues and none of them have more than 11 residues. This homogeneization of the CDRH3 loop size may partly explain the restricted antibody diversity in lower vertebrates.
An Igh-V library was constructed from the head kidney cytoplasmic RNA of an 8.5-month-old non-immunized rainbow trout, Oncorhynchus mykiss, using the 5' RACE polymerase chain reaction. Six new Igh-V segments were identified, bringing to nine the number of Igh-V families actually defined in that species. A phylogenetic analysis shows that these nine Igh-V families can be classified into three major groups. The first includes the Igh-V1, Igh-V3, Igh-V4, and Igh-V7 families, and is homologous to the human and mouse Group III Igh-V families. The second includes the Igh-V5, Igh-V8, and Igh-V9 families and is more closely related to the Group I and Group II human and mouse Igh-V families. The third group includes the Igh-V2 and Igh-V6 families, which are not closely related to any other vertebrate Igh-V gene. Six Igh-J segments were characterized. They can recombine with Igh-V segments belonging to different families and there is a high level of junctional diversity between the Igh-V and Igh-J segments.
A retrospective review of 69 patients with testicular seminoma, stage I and II, treated by orchiectomy and adjuvant irradiation at McGill University Hospitals from 1972 to 1987 was performed. All patients underwent either lymphangiogram or computed axial tomography scan for evaluation of retroperitoneal disease. There were 52 stage I (75%), 13 stage IIA (11%), 2 stage IIB (3%), and 2 stage IIC (Royal Marsden Hospital staging criteria). Median follow-up time was 6.2 years. The 10-year actuarial survivals were 94% and 93% for stages I and II, respectively. Only two stage I patients failed treatment, and both died from metastatic disease. Interestingly, both developed biopsy-proven metastatic brain disease and had no evidence of intra-abdominal recurrence. In stage II disease, only one patient failed the treatment. There was no serious acute toxicity and no late complications have been encountered. Radiation therapy following orchiectomy is the treatment of choice for stage I and for most stage II patients with testicular seminoma. The controversial aspects of radiographic retroperitoneal staging, the use of prophylactic mediastinal irradiation for stage II patients, and the role of surveillance only for stage I patients are discussed.
The role of intracavitary therapy in combination with external pelvic radiotherapy for endometrial carcinoma remains controversial. To determine the pelvic failure rat in patients receiving only external pelvic radiotherapy following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) for carcinoma of the endometrium, we undertook a retrospective review of all patients referred to the Radiation Oncology Department from January 1977 through December 1984. Patients with grade I, superficially invading tumors were excluded from this analysis. 52 patients were eligible for the study. Three patients who were lost to follow-up immediately after completion of external beam irradiation were excluded, leaving a total of 49 evaluable patients. The median follow-up time is 61 months. Pelvic failure was seen in only 2 patients (4%), both of them occurring concurrent with distant disease. No vaginal vault failures were observed. Overall actuarial survival at 5 years was 82%. We conclude that external beam pelvic radiotherapy alone without intracavitary boost appears to be an adequate treatment for patients undergoing TAHBSO for carcinoma of the endometrium.
Measurement of 75Se-cholesterol (Scintadren) uptake and computed tomography (CT) of the adrenal glands were compared as a means of differentiating the cause of Cushing's syndrome in 11 patients over a 2-year period. Quantitative Scintadren imaging differentiated adrenocorticotrophic hormone (ACTH)-dependent disease from local adrenocortical lesions as the cause of Cushing's syndrome in all the patients studied. CT of the adrenal glands rapidly and accurately detected the adrenal mass lesions in 2 cases and was effective in documenting bilateral hyperplasia due to ectopic ACTH-dependent disease. However, in entopic ACTH (pituitary)-dependent disease the adrenal glands were of normal thickness in all but 2 patients, who had bilateral hyperplasia. Scintadren imaging and CT are useful non-invasive procedures for differentiating local adrenal disease from ACTH-dependent disease as the cause of Cushing's syndrome and should be the initial investigations once a firm clinical and biochemical diagnosis of Cushing's syndrome has been made.
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Our initial experience of 50 patients who underwent fine-needle aspiration biopsy for suspected abdominal malignant disease confirms the safety and effectiveness of the technique. A positive diagnosis of malignant tumour was made in 36 out of 42 patients who were finally shown to have malignant disease. The correct diagnosis was made on 13 out of 17 patients with a pancreatic tumour; in 17 out of 17 with a liver tumour; in 3 out of 3 with renal masses; and in 3 out of 5 with other malignant lesions. Ultrasound was used for localization of the aspiration site in 38 patients, angiography in 11 patients and direct puncture in 2. During the biopsy of 55 sites, the needle was inserted into the abdomen 190 times and the only significant complication was the development of retroperitoneal haematoma in 2 patients.