Studies for estimating the biologic behavior and prognosis of paragangliomas in the head and neck

Despite a large number of histopathologic and immunohistochemical studies, the biologic behavior and prognosis of paragangliomas (glomus tumors) of the head and neck still remain uncertain. In the present study 36 specimens from 32 patients who underwent surgery for a paraganglioma were examined. The examinations included routine histology, quantitative DNA analysis based on image cytometry, immunohistochemical detection of the proliferating cell nuclear antigen (PCNA) along with visualization of nucleolar organizer regions (AgNOR). According to LeCompte, the paragangliomas were histologically divided into three subcategories: 16 patients had a paragangliomatous tumor. 14 patients had an adenomatous tumor, and 6 patients had an angiomatous tumor. Quantitative DNA analysis revealed three categories of tumors with characteristical DNA pattern; DNA type I tumors were pure diploid, DNA type II tumors had stemlines at 2c and 4c and were therefore recognized as diploid-tetraploid. Aneuploid cells were not apparent in these two groups. DNA type III tumors had stemline ploidies exceeding 2c and 4c. Aneuploid cells were present in all of these tumors. The biologic behavior of these lesions therefore must be recognized as suspicious. DNA type III tumors and adenomatous tumors showed the highest values for the PCNA scores, indicating a higher proliferation rate and a more rapid growth pattern in these lesions. Twenty patients could be followed over a period of up to 110 months. Five of these patients developed a recurrent tumor. All of them had DNA type III tumors. The DNA indices showed significantly higher values in the recurrent tumor group. The 2c deviation index (DI) and the entropy value had the highest prognostic significance. No correlation to clinical follow-up was found for the AgNOR score. Based on these results, prognostic indices for paragangliomas were developed: patients with a tumor having a 2c DI exceeding 2.0, entropy value of more than 4.0. 5c exceeding rate more than 8.0, and a PCNA score more than 20.0% can be recognized as being at high-risk for developing recurrent disease.     

Nutrient Intake following Vertical Banded Gastroplasty or Gastric Bypass

Background: This study explored eating habits, nutrient intake, and blood vitamin and mineral levels to determine whether severely obese subjects (BMI 40-50 kg m⁻²) post-vertical banded gastroplasty (VBG) or gastric bypass Roux-en-Y (GBR) are at risk of developing compounded under-nutrition. Methods: A dietary follow-up of 36 VBG and 19 GBR was maintained for 18 months via 7-day food intake diaries and 24-h recalls. Food intake was analysed for energy and nutrient composition and for its relative amount to recommended dietary allowances (RDA). Results: Weight loss was greatest during the first 6 months, continued at a slower rate for the next 6 months, nearly ceasing thereafter. The results following GBR were not substantially different from those following VBG 18 months postoperatively. The median weight loss at 1 year postoperatively was 48, 46, 48 and 36 kg; expressed as residual excess body weight: 0.2, 16, 13 and 22% for GBR Men, Women, VBG Men, Women, respectively. According to the classification proposed by Reinhold, all subjects achieved excellent treatment outcomes 18 months postoperatively. Despite the relatively low reported energy intake (20-50% below RDA), no correlation was found between rate of weight loss and energy intake at 6 months postoperatively. The intake of most vitamins and minerals was below 50% of RDA during the 18 months follow-up. The increase in energy intake did not improve the level of the nonenergy-contributing nutrients. Compliance to multivitamin and mineral supplement intake deteriorated with time. Conclusion: The low to within-normal range of blood vitamin and mineral levels 12 months postoperatively suggests the slow development of subclinical nutritional deficiency which could jeopardize the subjects' long-term health status.     

Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men

BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.     

The Toxicity of Glyphosate and Several Glyphosate Formulations to Four Species of Southwestern Australian Frogs

The acute toxicity of technical-grade glyphosate acid, glyphosate isopropylamine, and three glyphosate formulations was determined for adults of one species and tadpoles of four species of southwestern Australian frogs in 48-h static/renewal tests. The 48-h LC₅₀ values for Roundup? Herbicide (MON 2139) tested against tadpoles of Crinia insignifera, Heleioporus eyrei, Limnodynastes dorsalis, and Litoria moorei ranged between 8.1 and 32.2 mg/L (2.9 and 11.6 mg/L glyphosate acid equivalent [AE]), while the 48-h LC₅₀ values for Roundup? Herbicide tested against adult and newly metamorphosed C. insignifera ranged from 137–144 mg/L (49.4–51.8 mg/L AE). Touchdown? Herbicide (4 LC-E) tested against tadpoles of C. insignifera, H. eyrei, L. dorsalis, and L. moorei was slightly less toxic than Roundup? with 48-h LC₅₀ values ranging between 27.3 and 48.7 mg/L (9.0 and 16.1 mg/L AE). Roundup? Biactive (MON 77920) was practically nontoxic to tadpoles of the same four species producing 48-h LC₅₀ values of 911 mg/L (328 mg/L AE) for L. moorei and >1,000 mg/L (>360mg/L AE) for C. insignifera, H. eyrei, and L. dorsalis. Glyphosate isopropylamine was practically nontoxic, producing no mortality among tadpoles of any of the four species over 48 h, at concentrations between 503 and 684 mg/L (343 and 466 mg/L AE). The toxicity of technical-grade glyphosate acid (48-h LC₅₀, 81.2–121 mg/L) is likely to be due to acid intolerance. Slight differences in species sensitivity were evident, with L. moorei tadpoles showing greater sensitivity than tadpoles of the other four species. Adult and newly emergent metamorphs were less sensitive than tadpoles. Received: 19 February 1998/Accepted: 16 August 1998     

Statewide variation in the treatment of patients hospitalized with spleen injury

HYPOTHESIS: Surgeons' treatment decisions for patients with spleen injuries in Washington State from January 1, 1990, through December 31, 1994, were different in rural compared with urban communities. DESIGN AND SETTINGS: Retrospective cohort analyses using the Death and Illness History Database for the state of Washington, which provides a cross-linked record of an individual's sequential hospitalizations. Counties were defined as metropolitan, urban, or rural on the basis of population density. PATIENTS: A total of 1905 patients (1927 hospitalizations) with an International Classification of Diseases, Ninth Revision, Clinical Modification, discharge diagnosis code of 865. MAIN OUTCOME MEASURES: Physician management decisions (perform a celiotomy or repair the spleen) were stratified by geographic region. RESULTS: Throughout the state, there was substantial variability in the treatment of spleen-injured patients. Factors associated with higher odds of splenectomy included older age, overall severity of injury, treatment in rural hospitals, and treatment in the earlier years of study. While the frequency of splenic salvage increased over time, hospital length of stay, rehospitalization, and 30-day mortality did not increase. CONCLUSIONS: Injury to the spleen is a common problem for which management decisions vary by geographic region, indicating that a single management protocol does not universally apply. To evaluate appropriateness of care by process measures, such as splenic injury management, will require that decision makers grant some latitude in management variability based on factors such as practice setting.     

Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer's disease and frontotemporal dementia

OBJECTIVES: The diagnosis of Alzheimer's disease (AD) is now reliant on the use of NINCDS-ADRDA criteria. Other diseases causing dementia are being increasingly recognised--for example, frontotemporal dementia (FTD). Historically, these disorders have not been clearly demarcated from AD. This study assesses the capability of the NINCDS-ADRDA criteria to accurately distinguish AD from FTD in a series of pathologically proved cases. METHODS: The case records of 56 patients (30 with AD, 26 with FTD) who had undergone neuropsychological evaluation, brain imaging, and ultimately postmortem, were assessed in terms of whether at initial diagnosis the NINCDS-ADRDA criteria were successful in diagnosing those patients who had AD and excluding those who did not. RESULTS: (1) The overall sensitivity of the NINCDS-ADRDA criteria in diagnosing "probable" AD from 56 patients with cortical dementia (AD and FTD) was 0.93. However, the specificity was only 0.23; most patients with FTD also fulfilled NINCDS-ADRDA criteria for AD. (2) Cognitive deficits in the realms of orientation and praxis significantly increased the odds of a patient having AD compared with FTD, whereas deficits in problem solving significantly decreased the odds. Neuropsychological impairments in the domains of attention, language, perception, and memory as defined in the NINCDS-ADRDA statement did not contribute to the clinical differentiation of AD and FTD. CONCLUSION: NINCDS-ADRDA criteria fail accurately to differentiate AD from FTD. Suggestions to improve the diagnostic specificity of the current criteria are made.     

Interleukin-10 (IL10) promoter polymorphisms and multiple sclerosis

Interleukin-10 (IL10) is an anti-inflammatory cytokine which may modulate disease expression in multiple sclerosis (MS). Three dimorphic polymorphisms within the IL10 promoter region at positions - 1082, -819 and -519 have previously been identified. The - 1082*A allele has been associated with low and the - 1082*G allele with high in vitro IL10 production. We have genotyped 185 Caucasian MS patients and 211 ethnically matched controls for each of these three dimorphisms. MS patients were stratified for severity of disease outcome. No associations were found for any IL10 promoter polymorphisms when the MS cases were compared with controls or with disease outcome with regards to disability. IL10 polymorphism does not appear to be associated with MS or to influence disease progression.     

Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group

OBJECTIVE: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas. METHODS: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test. RESULTS: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result. CONCLUSIONS: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum.     

The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions

Objectives: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. Methods: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1β, IL-6 and IL-8 and prostaglandin E₂ (PGE₂) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire. Results: Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1β 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0.01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged. Conclusion: The interleukins measured proved to be sensitive indicators of irritating effects of 1,1,1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa. Received: 3 March 1999 / Accepted: 14 June 1999