Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Thirteen standardbred horses were trained as follows: phase 1 (endurance training, 7 wk), phase 2 (high-intensity training, 9 wk), phase 3 (overload training, 18 wk), and phase 4 (detraining, 12 wk). In phase 3, the horses were divided into two groups: overload training (OLT) and control (C). The OLT group exercised at greater intensities, frequencies, and durations than group C. Overtraining occurred after 31 wk of training and was defined as a significant decrease in treadmill run time in response to a standardized exercise test. In the OLT group, there was a significant decrease in body weight (P < 0.05). From pretraining values of 117 +/- 2 (SE) ml.kg-1.min-1, maximal O2 uptake (VO2max) increased by 15% at the end of phase 1, and when signs of overtraining were first seen in the OLT group, VO2max was 29% higher (151 +/- 2 ml.kg-1.min-1 in both C and OLT groups) than pretraining values. There was no significant reduction in VO2max until after 6 wk detraining when VO2max was 137 +/- 2 ml.kg-1.min-1. By 12 wk detraining, mean VO2max was 134 +/- 2 ml.kg-1.min-1, still 15% above pretraining values. When overtraining developed, VO2max was not different between C and OLT groups, but maximal values for CO2 production (147 vs. 159 ml.kg-1.min-1) and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLT group. Overtraining was not associated with a decrease in VO2max and, after prolonged training, decreases in VO2max occurred slowly during detraining.     

DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: thirteen-year follow-up study on a cohort of patients

Intestinal metaplasia identifies Barrett's esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual-parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia-free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia-free BE patients, followed up since 1985 once every 1-2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual-parameter analysis only. Twenty-one patients were diploid. Twelve (group II) also had an abnormally high G1-phase protein content compared to group I (nine patients), which were diploid with a low-moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low- and a high-grade dysplasia were observed at 3 and 6 years follow-up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia-free BE and assist in understanding the various stages of malignant transformation in long-term follow-up studies.     

Effects of environment on growth, efficiency of feed utilization, carcass fatness, and their association

The effects of environmental factors (house type, temperature, and type of watering system) on gain (G), feed consumption (FC), feed conversion (FCR), accumulation of abdominal fat (AF), and the association between FCR and AF of broilers were studied in a series of seven experiments. In addition, the adjustment of broilers to new housing environments and the factors affecting this adjustment were evaluated. The 4- to 7-wk G and FC were greater in groups raised at 21.1 C than 26.7 C. There were no consistent effects of environmental temperature on FCR (significantly reduced in 21.1 C groups compared with the 26.7 C groups in two of four trials) or in AF (significantly greater in 21.1 C groups than in 26.7 C groups in one of four trials). Environmental temperatures had no consistent effect on the relationship between FCR and AF. Both waterer types and environmental temperature affected the adjustment of broilers to placement in individual cages. Adjustment was better (less mortality and shorter periods of reduced FC) in the 21.1 C environment and when cup instead of trough waterers were provided. The 4- to 6-wk G and FC were reduced in the caged birds compared with the floor pen birds, but the FCR and AF were not consistently different. The initial (4-wk) BW significantly affected the 6-wk BW, G, FC, and FCR, but was not correlated with AF.     

Can the ventilatory equivalent for carbon dioxide predict the severity of functional impairment in patients with cardiac insufficiency?

OBJECTIVE: To evaluate whether the changes in the ventilatory equivalent for carbon dioxide (VE/VCO2), during the early stages of cardiopulmonary exercise testing, can predict maximal oxygen consumption (VO2max) in patients with chronic heart failure. METHODS: We studied 38 patients (30 males, mean age 56 +/- 11 years) with chronic heart failure. All patients performed maximal symptom limited, treadmill exercise test with breath-by-breath respiratory gas analysis. They were divided in two groups according to their maximal oxygen consumption (group I-VO2max above 14 ml/kg/min and group II-VO2max below 14 ml/kg/min). In both groups, we analysed VE/VCO2 at rest, at the anaerobic threshold (AT) and at peak exercise, and the percentage of VE/VCO2 reduction from rest to AT. RESULTS: Eleven patients had a VO2max below 14 ml/kg/min (group II). At rest VE/VCO2 = 53 +/- 13 in group II versus 47 +/- 10 in group I (p = 0.048), at the AT VE/VCO2 = 46 +/- 12 in group II versus 36 +/- 7 in group I (p = 0.001) and at peak exercise VE/VCO2 = 46.2 +/- 13 in group II versus 36.2 +/- 6 in group I (p = 0.0002). There was a 24% reduction in the VE/VCO2, from rest to AT in group I, compared to a 16% reduction in group II (p = 0.004). A reduction in the VE/VCO2 from rest to AT less than 16% predicted a VO2max below 14 ml/kg/min with a sensitivity of 60% and a specificity of 93%. CONCLUSIONS: Patients with severe functional impairment have higher values of VE/VCO2 in all exercise stages. A reduction of VE/VCO2 from rest to anaerobic threshold of less than 16% is a high specific predictor of a VO2max below 14 ml/kg/min.     

Coordinated effects of electromagnetic field exposure on erythropoietin-induced activities of phosphatidylinositol-phospholipase C and phosphatidylinositol 3-kinase

Initial studies with the erythropoietin-sensitive human hematopoietic cell line, TF1, demonstrated both multifarious effects of pulsed electromagnetic field (EMF) exposure on lipid signal transduction and antiproliferative effects of EMF. Stimulation of TF1 cells with erythropoietin resulted in increased phosphatidylinositol 3-kinase activity within 2 min. Addition of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, produced a decrease in cell proliferation as measured by accumulation of cells in the G0/G1 phase of the cell cycle and suppression of erythropoietin-induced DNA synthesis. Similar effects on cell proliferation were seen under EMF treatment. Phosphatidylinositol 3-kinase activity in erythropoietin-stimulated TF1 cells, measured in whole-cell extracts, increased 34% within 2 min and remained above basal levels for at least 20 min. EMF decreased erythropoietin-stimulated phosphatidylinositol 3-kinase activity to lower than basal levels. Additionally, translocation of the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase to the membrane was prevented by EMF. Phosphatidylinositol-specific phospholipase C was activated, as reflected by increases in diacylglycerol and inositol trisphosphate at 15-60 s after EMF treatment. These results provide the first evidence of subtle coordinated changes by EMF associated with loss of phosphatidylinositol 3-kinase activity, inhibition of the translocation of p85 to the membrane, and activation of phosphatidylinositol-phospholipase C.     

Comparative nutritive value of winged bean (Psophocarpus tetragonolobus (L) DC) and other legumes grown in Tanzania

BACKGROUND: In order to assess the efficiency of flow-controlled shunts in reducing shunt failure in the treatment of adult hydrocephalus (with a special focus on overdrainage complications), a series of 289 patients was analyzed through a retrospective and comparative study performed in three neurosurgical departments. METHODS: A group of 142 adult patients suffering from hydrocephalus were operated on using a conventional differential pressure (DP) shunt and compared with a group of 147 adult patients operated on using flow-controlled (FC) system (Orbis-Sigma, Cordis). Only the first complication, which required a surgical revision within the first 2 years after shunt implantation, was taken into account for each patient and analyzed using life-table methods. RESULTS: The actuarial risk of shunt infection in the two groups is respectively 8.3% and 10.9% at 1 year (nonsignificant difference). The actuarial risk of mechanical complications at 1 year is 38% for the DP patients and 10% for the FC patients (p = 0.0001); this difference is largely due to a decrease of complications related to overdrainage phenomenon (14/142 subdural collections were observed in the DP group versus 1/147 in the FC group) (p = 0.0001). CONCLUSION: The conclusion of this cooperative and retrospective study is that the use of a flow-controlled system decreases the risk of mechanical complications related to the hydrodynamic properties of the shunts used in the treatment of adult hydrocephalus, especially those related to overdrainage.     

Effect of deoxycholate on immunoglobulin G concentration in bile: studies in humans and pigs

Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.     

Ras-p21,p53在阴茎癌腹股沟淋巴结中的表达及临床意义

Objective: The aim of this study was to investigate the expression and clinical significance of ras-p21 and p53proteins in inguinal lymph nodes with penis carcinoma. Methods: The clinical data of 44 patients of penis (squamous) carcinoma and 40 non-tumor patients from 1990 to 2002 in our hospital were added to our research, 84 inguinal lymph nodes were got by lymph node biopsy from each patient at random. Pathological examination showed that 18 cases of cancer group were metastatic carcinoma as group A, the other 26 cases were inflammatory affection as group B. 20 cases of non-tumor group were nonspecific inflammatory inguinal lymph nodes as group C and the other 20 cases were normal lymph nodes as group D, all the 84 cases in our research were investigated by immunohistochemistry to detect the expression of ras-p21 and p53protein. Results: Immunohistochemistry demonstrated that the expression of as-p21 and p53 protein were significantly higher in cancer group A (88.89%, 72.22%) and B (30.77%, 23.08%) than in control group C (5%, 0%) and group D (0%, 0%.). The expression of two proteins showed significant differences between group A and group B (P ＜ 0.01), and no significant differences between group B and group C (P ＞ 0.05). The expression of two proteins showed significant difference between group A and control group (C + D) (P ＜ 0.01). The expression of two proteins showed significant differences between cases of cancer groups (A + B) and control groups (C + D) (P ＜ 0.01). Significant differences were showed between group (A + B) and group D with the expression of ras-p21 and p53 (P ＜ 0.01). The expression of ras-p21 and p53 in three different differentiated groups were G1 (well-differentiated) group: (22.73%, 13.64%), G2 (moderate-differentiated) group: (81.25%, 68.75%), G3 (poorly differentiated) group: (100%, 83.33%). There was significant differences between G1 group and G3 group (P ＜ 0.05), and no significant differences between G1 group and G2 group, G2 group and G3 group (P ＞ 0.05). There was significant differences between three clinical stages with the expression of ras-p21 and p53 (P ＜ 0.05). Conclusion: Ras-p21 and p53 protein werehighly expressed in cancer groups in this study, while, two proteins hardly detected from control groups. If the inflammatory lymph nodes of penile cancer patients show the positive expression of p21 and p53 protein, the inguinal lymph nodes also need dissection, which is important to improve the diagnosis of inguinal lymph node metastasis rate and patient survival of penile cancer. Ras-p21 and p53 protein detection can act an objective indicator of tumor metastasis and prognosis, and also for our treatment of penile cancer in the inguinal lymph node dissection surgery provides determine indicators.     

Quantification of Gordona amarae strains in foaming activated sludge and anaerobic digester systems with oligonucleotide hybridization probes

Previous studies have shown the predominance of mycolic acid-containing filamentous actinomycetes (mycolata) in foam layers in activated sludge systems. Gordona (formerly Nocardia) amarae often is considered the major representative of this group in activated sludge foam. In this study, small-subunit rRNA genes of four G. amarae strains were sequenced, and the resulting sequences were compared to the sequence of G. amarae type strain SE-6. Comparative sequence analysis showed that the five strains used represent two lines of evolutionary descent; group 1 consists of strains NM23 and ASAC1, and group 2 contains strains SE-6, SE-102, and ASF3. The following three oligonucleotide probes were designed: a species-specific probe for G. amarae, a probe specific for group 1, and a probe targeting group 2. The probes were characterized by dissociation temperature and specificity studies, and the species-specific probe was evaluated for use in fluorescent in situ hybridizations. By using the group-specific probes, it was possible to place additional G. amarae isolates in their respective groups. The probes were used along with previously designed probes in membrane hybridizations to determine the abundance of G. amarae, group 1, group 2, bacterial, mycolata, and Gordona rRNAs in samples obtained from foaming activated sludge systems in California, Illinois, and Wisconsin. The target groups were present in significantly greater concentrations in activated sludge foam than in mixed liquor and persisted in anaerobic digesters. Hybridization results indicated that the presence of certain G. amarae strains may be regional or treatment plant specific and that previously uncharacterized G. amarae strains may be present in some systems.     

Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group

We performed electrophysiological and serological testing within 15 days of symptom onset on 369 patients with Guillain-Barré Syndrome (GBS) enrolled in a trial comparing plasma exchange, intravenous immunoglobulin, and both treatments. Patients were classified into five groups by motor nerve conduction criteria; 69% were demyelinating, 3% axonal, 3% inexcitable, 2% normal, and 23% equivocal. Six of 10 (60%) patients with axonal neurophysiology had had a preceding diarrheal illness compared with 71 of 359 (20%) in other groups. Antiganglioside GM1 antibodies were present in a higher proportion of patients with axonal physiology or inexcitable nerves than other patients. The number dead or unable to walk unaided at 48 weeks was greater in the group with initially inexcitable nerves (6 of 12, 50%) compared with the rest (52 of 357, 15%), but was not significantly different between the axonal (1 of 10, 10%) and demyelinating (44 of 254, 17%) groups. Sensory action potentials and clinical sensory examination were both normal in 53 of 342 (16%) patients, and these "pure motor GBS" patients were more likely than other GBS patients to have IgG antiganglioside GM1 antibodies and to have had preceding diarrhea but had a similar outcome. The axonal group was more likely than other groups to have normal sensory action potentials. The outcomes in response to the three treatments did not differ in any subgroup (including patients with pure motor GBS or preceding diarrhea) or any neurophysiological category.     

Epilepsy diagnosis and localization in patients with antecedent childhood febrile convulsions

PURPOSE: A history of febrile convulsions (FC) is often obtained in patients presenting for surgical treatment of temporal lobe epilepsy (TLE), but it is not clear that preferential temporal localization of epilepsy is associated with antecedent FC. METHODS: We prospectively inquired about FC and their characteristics in all patients presenting to an epilepsy clinic through a patient questionnaire and interview. We studied the incidence of antecedent childhood febrile convulsions in relation to epilepsy diagnosis. RESULTS: FC were reported by 133 of 1005 study patients (13.2%). TLE was more likely to be preceded by FC (78/310, 25.2%) than extratemporal epilepsy (ETE) (12/216, 5.6%) (p < 0.000001) or generalized epilepsy (GE) (16/146, 11.0%) (p < 0.001). Patients with GE were more likely than patients with TLE to have had simple FC (p < 0.00005). Prolonged duration was the most common FC complex feature in TLE patients. CONCLUSIONS: We demonstrated a preferential association of FC with temporal lobe foci and a weaker association between FC and GE. FC does not appear to be a clear risk factor for ETE.     

Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross-sectional longitudinal study

The aim of this mixed cross-sectional longitudinal study covering a total age range of 11-17 years, i.e. the entire pubertal growth period, was (1) to specify the changes in maximal breathing pattern during incremental exercise; (2) to determine what parts of the changes are due to anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength; and (3) to determine if the role of these variables is identical before, during and after pubertal growth spurt. This study was conducted in 44 untrained schoolboys separated into three groups, with an initial age of 11.2 +/- 0.2 years for group A, 12.9 +/- 0.25 years for group B, and 14.9 +/- 0.26 years for group C. These children were subsequently followed for 3 years, during the same time period each year. The maximal inspiratory and expiratory pressures (PI max and PE max) were used as an index of the respiratory muscle strength. During an incremental exercise test, maximal ventilation (VE max), tidal volume (VT max), breathing frequency (fmax), inspiratory and expiratory times (tI max and tE max) and mean inspiratory flow (VT/tI max) were measured at maximal oxygen uptake (VO2max). Our study showed that there was a marked increase with age in VE max, VT max, and VT/tI max, and no significant changes in fmax, tI max and tE max. PI max and PE max showed a general trend towards an increase between 11 and 17 years. The study of the linear correlations between maximal breathing pattern and the anthropometric characteristics, physical fitness and inspiratory or expiratory muscle strength showed that, in the three groups of children, (1) lean body mass was the major determinant of VE max, VT max and VT/tI max and the relationships were significantly different before, during and after the pubertal growth spurt; (2) physical fitness was the main determinant of tI max, tE max and fmax before and after the pubertal growth spurt; and (3) maximal respiratory strength did not play a significant role. In conclusion, this mixed cross-sectional longitudinal study showed, at maximal exercise, a significant increase in VE max during growth due only to a significant increase in VT max and VT/tI max, and that the relationships of anthropometric characteristics and physical fitness with maximal breathing pattern change during growth.     

Peptide-mediated regulation of the allergic immune response

The objective of our study was to investigate if there are abnormalities in signal transducing G proteins in patients with panic disorder. We utilized selective antibodies to quantitate the levels of the G protein alpha subunits that regulate adenylyl cyclase activity (G alpha s and G alpha i2) and phosphoinositide turnover (G alpha q/11) in platelet membranes (and leukocyte membranes for G alpha s), and also carried out pertussis toxin (PT) catalyzed [32P]ADP-ribosylation in platelet membranes from a group of 13 untreated panic disorder patients, 10 untreated social phobia patients, and 12 healthy subjects. There were no significant differences among the three groups in the immunolabeling of G alpha s in platelets or leukocytes, or in the immunolabeling of G alpha i1/2, G alpha q/11, or PT-catalyzed [32P]ADP-ribosylation in platelets. Within the constraints imposed by using peripheral blood cells to reflect brain composition, our results do not provide support for G protein abnormalities in patients with panic disorder. These results contrast with those obtained using identical methodology in bipolar affective disorder, where elevated G alpha s in leukocytes has been reported (Manji et al. 1995).     

Use of diuretic renogram in evaluation of patients before and after endopyelotomy

OBJECTIVES: Endopyelotomy is a widely accepted alternative in the treatment of ureteropelvic junction (UPJ) obstruction, with success rates between 63% and 88%. However, various methods have been used to evaluate patients with UPJ obstruction, making it difficult to compare results. Diuretic renography has the potential to unify the evaluation if performed in standard ways. In this report, we present a standardized protocol for diuretic renography. METHODS: Nineteen endopyelotomies were performed by one surgeon (E.B.K.) at our institution. The 16 patients were evaluated with technetium 99m MAG-3 diuretic renography. The presence or absence of obstruction was classified according to the differential renal function, time activity curves, and Tmax to T 1/2max time. Three patients had a postoperative Whitaker's test. RESULTS: Eight patients had pre- and postoperative diuretic renograms at our institution. This group was stratified by their differential renal function. Among 4 patients with differential renal function greater than 35%, 3 of 4 showed progressive improvement in renal function postoperatively, 4 of 4 had a Tmax to T 1/2max time less than 10 minutes, and 3 of 4 ha d unobstructed time activity curves. Five patients had postoperative renograms only. Of these 5 patients, 4 had differential renal function greater than 35% and 3 of 5 had normal-appearing curves and normal Tmax to T 1/2max time. Three patients required a second endopyelotomy and 2 of these underwent a dismembered pyeloplasty. CONCLUSIONS: Standardized diuretic renography should be used as an objective test for the evaluation of patients with UPJ obstruction. The successful outcome of an endopyelotomy depends on the preoperative renal function of the involved kidney. Whitaker's test may be used for equivocal cases.     

Indoor radon prediction from soil gas measurements

We have studied the intubating conditions in 60 ASA I or II patients, after induction of anaesthesia with propofol 2 mg kg-1, allocated to one of the following three groups: group 1, remifentanil 1 microgram kg-1; group 2, remifentanil 1 microgram kg-1 and lignocaine 1 mg kg-1; group 3, remifentanil 2 micrograms kg-1. No neuromuscular blocking agents were administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Overall intubating conditions were acceptable in 35% of patients in group 1, 100% of patients in group 2 and 85% of patients in group 3. There was a statistically significant drop in blood pressure after induction in groups 2 and 3, and two patients in each group required ephedrine 6 mg i.v. boluses, as dictated by the intervention criteria (mean arterial pressure fall > 25% from baseline). Similarly, there was a drop in heart rate in groups 2 and 3, but this did not reach statistical or clinical significance, and no patient required atropine.     

Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors

Gaucher disease is the most common lysosomal storage disease with a high prevalence in the Ashkenazi Jewish population but it is also present in other populations. The presence of eight mutations (1226G, 1448C, IVS2+1. 84GG, 1504T, 1604T, 1342C and 1297T) and the complete deletion of the beta-glucocerebrosidase gene was investigated in 25 unrelated non-Jewish patients with Gaucher's disease in Germany. In the Jewish population, three of these mutations account for more than 90% of all mutated alleles. In addition, relatives of two patients were included in our study. Restriction fragment length polymorphism analysis and sequencing of PCR products obtained from DNA of peripheral blood leukocytes was performed for mutation analysis. Gene deletion was detected by comparison of radioactively labelled PCR fragments of both the functional beta-glucocerebrosidase gene and the pseudogene. Among the unrelated patients, 50 alleles were investigated and the mutations identified in 35 alleles (70%), whereas 15 alleles (30%) remained unidentified. The most prevalent mutation in our group of patients was the 1226G (370Asn-->Ser) mutation, accounting for 18 alleles (36%), followed by the 1448C (444Lcu-->Pro) mutation, that was found in 12 alleles (24%). A complete gene deletion was present in two alleles (4%). The IVS1+2 (splicing mutation), the 1504T (463Arg-->Cys) as well as the 1342C (409Asp-->His) mutations were each present in one allele (2%). None of the alleles carried the 84GG (frame-shift), 1604A (496Arg-->His) or the 1297T (394Val-->Leu) mutation. This distribution is different from the Ashkenazi Jewish population but is similar to other Caucasian groups like the Spanish and Portuguese populations. Our results confirm the variability of mutation patterns in Gaucher patients of different ethnic origin. All patients were divided into nine groups according to their genotype and their clinical status was related to the individual genotype. Genotype/phenotype characteristics of the 1226G, 1448C, and 1342C mutations of previous studies were confirmed by our results.     

Quantitative analysis of rapid pointing movements in Cree subjects exposed to mercury and in subjects with neurological deficits

To quantify rapid alternating movements (RAMs) we used a simple prototype developed in our laboratory that requires the subject to rotate two hand-held foam spheres connected to optical encoders via flexible rods. Ninety-six participants, including 30 control subjects, 36 Cree subjects exposed to methylmercury, 21 subjects with Parkinson's disease, 6 subjects with cerebellar deficits, and 3 subjects with essential tremor, were involved in the study (though data for 5 were later removed). Twelve characteristics were developed and calculated from the raw data. Conditions examined included two hands at natural cadence (NC2), right and left hands separately at fast cadence (FCl), and both hands at fast cadence (FC2). Two ratios (FC2/NC2) and (FC2/FC1) combining these conditions were also examined. Test-retest reliability was >0.80 for most characteristics but was <0.70 for some characteristics, especially in the conditions executed at normal cadence. Correlations between characteristics and numbers of outliers with respect to the control group distribution were used to reduce the set of characteristics from 12 to 7 (i.e., duration, range, maximum slope, similarity in shape, smoothness, sharpness, and coherence). ANOVAs on the three largest groups generated significant results for most characteristics in the three conditions and the two ratios for Cree subjects and subjects with Parkinson's disease. ANOVAs on 3 age-matched groups (n=6) suggest that methylmercury affects the performance of the Cree subjects with the higher exposure, especially in terms of smoothness, sharpness, and coherence. These preliminary results suggest that this test is sufficiently specific and sensitive to characterize the performance of different groups of subjects. Ratios tend to improve discrimination for Cree subjects in a few characteristics but not for patients with Parkinson's disease.     

Survival in stage T2-T3A bladder cancer treated with radical cystectomy

OBJECTIVE: The optimal treatment for patients with localized muscle-infiltrating urothelial carcinoma (Jewett stage B or T2-T3a of the TNM classification, UICC 1992) continues to be a controversy. The present study analyzed the survival rate in patients with stage T2-T3a bladder cancer who had been treated by radical cystectomy. METHODS: The records of 50 patients with T2-T3a NO tumor, submitted to pelvic lymphadenectomy and radical cystoprostatectomy, were reviewed to determine the prognosis in this group of patients. Seventeen patients (34%) received three courses of systemic chemotherapy (CMV) prior to cystectomy. RESULTS: The overall 5-year survival rate was 73%; 76% for those with T2 (n = 30) and 67% for those with T3a (n = 20) (log-rank, p = 0.27). No statistically significant differences were observed for age (less than or over 65 years), tumor growth pattern (papillary or flat), tumor size (less or greater than 5 cms) or treatment (with or without induction CMV). However, patients with G1-2 tumor had a better survival rate (94% at 5 years) than those with G3 tumor (51%), a difference with statistical significance (log-rank, p = 0.047). The Cox regression analysis showed no independent variable of prognostic significance. CONCLUSION: Muscle-infiltrating urothelial carcinoma is highly curable by radical surgery. Some authors believe it is unnecessary to distinguish T2-T3a lesions; therefore a critical review of the TNM classification appears to be warranted. We are unable to distinguish patients with a better prognosis that might benefit from less aggressive therapeutic options. Similarly, the therapeutic benefits of induction chemotherapy prior to cystectomy in patients with stage T2-T3a tumor could not be demonstrated.