Hypertensive intra-arterial chemotherapy for endometrial carcinoma assessed by transvaginal Doppler ultrasound and magnetic resonance imaging

We examined the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using transvaginal Doppler ultrasound and magnetic resonance imaging. Angiotensin II, 100 mg cisplatin, and 40 mg doxorubicin were prescribed for 8 patients with endometrial carcinoma (3 stage Ia; 3 stage Ib; 2 stage II). The resistance index (RI) was obtained for intratumoral blood flow velocity waveforms by transvaginal Doppler ultrasound and changes in RI (delta RI: differences before and after chemotherapy) were calculated. The tumor volume (TV) was also evaluated, based on the T2-weighted image of magnetic resonance imaging (MRI). The decrease in tumor size [DR-T: (TV before chemotherapy--TV after chemotherapy)/TV before chemotherapy x 100] was determined. RI measurements did not correlate with TV, either before or after chemotherapy. The delta RI varied from 0.007 to 0.615 (mean: 0.207) and DR-T varied from 20.1% to 65.0% (mean: 45.5%). The correlation between delta RI and DR-T [DR-T = 23.5 + 167.2 (delta RI)-165.6 (delta RI)2; R2 = 0.772, p < 0.05] was significant. Therefore, we confirmed the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using both transvaginal Doppler ultrasound and MRI.     

Relationships between otitis media sequelae and age

OBJECTIVES: To explore relationships between age and sequelae in two groups of children treated with tympanostomy tubes for chronic otitis media with effusion (OME). STUDY DESIGN: Cross-sectional study of sequelae among children, adolescents, and adults at 4 years and 9 to 23 years after tympanostomy tube treatment. METHODS: Group I was examined with otomicroscopy, tympanometry, and audiometry two to four times a year as part of a prospective study, and they were evaluated 4 years after initial tube treatment for this study. Group II received tubes while participating in a chronic OME study, but participants were not followed prospectively after treatment. Nine to 23 years after tube treatment, they were examined with otomicroscopy, tympanometry, and hearing screening. RESULTS: Among the 5- to 28- year-old subjects, cholesteatoma (< or = 1%) and perforation (< or = 2%) were rare. In Group I, tympanosclerosis increased with age (P < .01), and OME (flat tympanograms) decreased with age in Group II (P < .01). The older cohort was more likely to have severe retractions (18% vs. 4%, P = .02), hearing loss (21% vs. 10%, P < .01), and severe atrophy (24% vs. 0%, P < .01) than the younger cohort, but they were less likely to have flat tympanograms (2% vs. 12%, P < .01). CONCLUSIONS: Although OME became less prevalent with age, important sequelae (severe atrophy, severe tympanic membrane retraction, hearing loss, cholesteatoma, and chronic perforation) may develop in children with chronic OME as they become adolescents and young adults. Long-term prospective studies are important in defining the progression of sequelae in these children.     

Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes

The food-borne carcinogenic and mutagenic heterocyclic aromatic amines undergo bioactivation to the corresponding N-hydroxy (OH)-arylamines and the subsequent N-glucuronidation of these metabolites is regarded as an important detoxification reaction. In this study, the rates of glucuronidation for the N-OH derivatives of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) by liver microsomal glucuronosyltransferase were compared to that of the proximate human urinary bladder carcinogen, N-OH-aminobiphenyl (N-OH-ABP) and the proximate rat colon carcinogen N-OH-3,2'-dimethyl-4-amino-biphenyl (N-OH-DMABP). Human liver microsomes catalyzed the uridine 5'-diphosphoglucuronic acid (UDPGA)-dependent glucuroidation of N-OH-IQ, N-OH-PhIP, N-OH-Glu-P-1 and N-OH-MeIQx at rates of 59%, 42%, 35% and 27%, respectively, of that measured for N-OH-ABP (11.5 nmol/min/mg). Rat liver microsomes also catalyzed the UDPGA-dependent glucuronidation of N-OH-PhIP, N-OH-Glu-P-1 and N-OH-IQ at rates of 30%, 20% and 10%, respectively of that measured for N-OH-DMABP (11.2 nmol/min/mg); activity towards N-OH-MeIQx was not detected. Two glucuronide(s) of N-OH-PhIP, designated I and II, were separated by HPLC. Conjugate II was found to be chromatographically and spectrally identical with a previously reported major biliary metabolite of PhIP in the rat, while conjugate I was identical with a major urinary metabolite of PhIP in the dog. Hepatic microsomes from rat, dog and human were found to catalyze the formation of both conjugates. The rat preferentially formed conjugate II (I to II ratio of 1:15), while the dog and human formed higher relative amounts of conjugate I (I to II ratio of 2.5:1.0 and 1.3:1.0 respectively). Fast atom bombardment mass spectrometry of conjugates I and II gave the corresponding molecular ions and showed nearly identical primary spectra. However, collision-induced spectra were distinct and were consistent with the identity of conjugates I and II as structural isomers. Moreover, the UV spectrum of conjugate I exhibited a lambda max at 317 nm and was essentially identical to that of N-OH-PhIP, while conjugate II was markedly different with a lambda max of 331 nm. Both conjugates were stable in 0.1 N HCl and were resistant to hydrolysis by rat, dog and human liver microsomal beta-glucuronidases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Epidemiology of sexually transmitted diseases in the catchment area of the Rostock University Dermatology Clinic after 1945

BACKGROUND: The purpose of this study is to evaluate the possibility, safety and advantages of laparoscopic approach in the diagnosis and therapy of perforated peptic ulcer. METHODS: This is a retrospective study including 69 cases of gastroduodenal perforation initially treated laparoscopically. The safety (morbidity and mortality) was estimated according to the two mortality rates fixed for laparotomies, APACHE II and Mannheimer Peritonitis Index (MPI). Sixty-nine patients (average age: 52 years), 23% of whom being over 70 years old, suffering from gastroduodenal perforation, were initially treated with laparoscopy. RESULTS: The laparoscopic diagnosis was done in 91% of cases. When the perforation was localized, the laparoscopic treatment was possible in 94% of cases. In 93% of cases a simple closure of the ulcerated perforation was performed. The conversion ratio was of 16%. One-hundred minutes (55-180) was the average operating. The morbidity was of 13%. One septic shock was reported in a patient with general purulent peritonitis diagnosed with laparoscopy and, after having converted, it was treated with laparotomy. No malignant iperCO2 was relieved. The reported mortality was of 4.3%, the theoretical mortality estimated was of 6% (MPI) and of 14% (Score APACHE II). The 3 deceased (87, 87 and 93 years old) had ASA index superior to 3. The remarkable advantage of laparoscopic approach is, in addition to diagnostic contribution, the absence of wall complications when the operation is not converted. CONCLUSIONS: The laparoscopic approach is suggested in gastroduodenal perforation, since it allows an etiological diagnosis and a treatment without conversion in 84% of cases.     

Surgical results of perforated gastric carcinoma: an analysis of 155 Japanese patients

OBJECTIVES: Free perforation of gastric carcinoma accounts for less than 1% incidence of acute abdominal crisis in Japan, and this problem occurs much less frequently in Western countries. To clarify the characteristics of patients with perforated gastric carcinoma (PGC) and to investigate a treatment of choice, we reviewed the data of Japanese patients with PGC. METHODS: A total of 155 cases of PGC reported in the Japanese literature from 1985 to 1994, including one patient of our own experience, were studied. The clinicopathologic features, including tumor stage and patient survival, were analyzed. RESULTS: There were 27 stage I tumors (19%), 16 stage II tumors (12%), 42 stage III tumors (30%), and 55 stage IV tumors (39%). Emergency gastrectomy was done in 128 patients (83%), with the mortality and 5-yr survival rate was 7 and 40%, respectively. The survival of patients was influenced by the gross type of tumor, serosal invasion, lymph node metastasis, stage of the disease, and operative curability. The 5-yr survival rate of stage I and II patients was 76% and that of curatively treated patients was 74%. CONCLUSIONS: Recent Japanese results of emergency gastrectomy for PGC are satisfactory. Long-term survival is expected in curatively treated patients with stage I and II tumors.     

Craniofacial abnormalities in sleep apnoea syndrome

Each year, 15 transvestibular transseptal transsphenoidal hypophysectomies are performed in Lausanne. The aim of the study was to determine the complications rate of our procedure and their influence on the life quality of patients. Questionnaires were sent to 178 patients, operated between 1984 and 1995. 125 questionnaires were returned. Out of those, 73 patients accepted to undergo a control rhinoscopy. The most frequent complains were nasal obstruction and crusting (38% each), whistling while breathing through the nose (12%), and stuffiness of the upper lip or teeth (7%). Endoscopically, we detected an anterior septal perforation in 10 cases (13.7%), 8 (80%) of which were symptomatic and a posterior septal perforation in 6 cases, all of them being asymptomatic. Finally, 36% of the patients had no complains and 19% of them had an improvement of respiration after the operation. Of the whole series of 178 patients, only 5% had complications requiring an ENT follow-up for longer than 6 months after having been operated.     

Expression of ribonucleolytic toxin restrictocin in Escherichia coli: purification and characterization

OBJECTIVES: To define the incidence and severity of ovarian hyperstimulation syndrome (OHSS) occurring in oocyte donors. METHODS: Women (n = 149) aged 31.3 +/- 4.8 years (mean +/- S.D., range 21-41 years) participated as designated oocyte donors and underwent 400 consecutive cycles of controlled ovarian stimulation using human menopausal gonadotropin following pituitary downregulation with gonadotropin-releasing agonist. Patients were monitored by serial transvaginal ultrasound examinations and serum estradiol (E2) determinations. Oocytes (15.6 +/- 7.5 per aspiration; range 2-57) were harvested by ultrasound-directed transvaginal follicle aspiration 36 h following the intramuscular injection of human chorionic gonadotropin (hCG). Follow-up examination occurred 1 and 2 weeks post-aspiration. RESULTS: On the day of hCG injection E2 levels ranged from 512 to 13,502 pg/ml (mean 2902.7 +/- 1486.9 pg/ml). Over the next few weeks the degree of hyperstimulation in donors was staged: mild 65% (grade I, n = 98; grade II, n = 162); moderate 33.5% (grade III, n = 120; grade IV, n = 14); severe 1.5% (grade V, n = 6; grade VI, n = 0). Associated preaspiration E2 levels were: grade I, 1120 +/- 424 pg/ml; grade II, 2084 +/- 613 pg/ml; grade III, 3785 +/- 1713 pg/ml; grade IV, 5370 +/- 1264 pg/ml; grade V, 4286 +/- 1100 pg/ml. Worsening OHSS was associated with increasing levels of E2. There were no serious complications and hospitalization was not required. All symptoms resolved within 30 days of aspiration, disappearing by the time of the first menstrual flow in women of grade-III or lower stage. CONCLUSION: Although oocyte donors commonly experienced exaggerated levels of serum E2 they rarely (< 2%) developed severe OHSS. This may be attributable to their lack of embryo transfer which avoids exacerbating the illness.     

Urinary stress incontinence. Comparison of the Raz technique and the Bologna technique. Analysis of a series of 188 patients

OBJECTIVE: Our purpose was to evaluate and compare the perioperative morbidity and the long-term results of the Raz colposuspension and the Bologna operation for the treatment of stress urinary incontinence in women. STUDY DESIGN: Data of 188 women who underwent either a Bologna operation (group 1) or a Raz colposuspension (group 2) for the treatment of stress urinary incontinence between January 1, 1987 and December 1, 1995 were analysed retrospectively regarding history, preoperative evaluation, associated surgical procedures, complications and cure and failure rate. POPULATION AND METHODS: 80 patients were treated with the Bologna operation and 108 with the Raz colposuspension. Patients with prior anti-incontinence surgery, and patients with a preoperative diagnosis of urge incontinence were excluded from the study. Success was defined both subjectively (complete absence of complaint of stress urinary incontinence) and objectively (no evidence of loss of urine on cough provocation during physical examination). Survival curves were generated in each group for time to event data: "time to recurrent stress incontinence" and compared by the logrank test. A multivariate analysis using a Cox proportional hazards regression model was performed to indentify possible outcome predictors. RESULTS: The success rate of group 1 was significantly higher than that of group 2 (p = 0.00001). The median of success was 51 months in group 1 and 21 months in group 2 (p = 0.00001). The incidence of intraoperative complications in each group (inadvertent cystostomy, hemorrhage) did not differ. The multivariate analyses using the Cox regression model showed that the most highly correlated variable with the surgical cure rate was the type of surgical anti-incontinence procedure adopted: Bologna or Raz (p = 0.00001) CONCLUSION: In our hands, the Bologna operation has a higher cure rate than the Raz colposuspension. For us, when treating patients with stress urinary incontinence by the vaginal route, the Bologna operation is indicated when sufficient anterior vaginal tissue is available to create vaginal bands.     

Long-term results of two schedules of treatment for toxic multinodular goitre with radioiodine therapy

Results of the long-term effects of two schedules of radioiodine therapy I131 in 130 toxic multinodular goitre patients were evaluated. Seventy five patients (group I) were treated with low doses and 55 patients (group II) with calculated high doses adjusted for thyroid weight (0.5-1 mci/g) and radioiodine uptake. Follow up (mean +/- SEM) was 4.5 +/- 0.4 years and 4.8 +/- 0.6 years respectively (P > 0.1). At the end of follow up, hyperthyroidism was successfully reversed in 78% (Group I) and 82% (Group II). In group I hypothyroidism was present in 5% of patients, while it was 12.5% in group II patients. The total dose per gram of thyroid tissue was not significantly different in both the groups (.058 mci +/- .0054 VS .073 +/- .0054 mci/g). However in group II the number of I131 administration was significantly lower (1.5 +/- 0.2) than in group I (3.2 +/- 0.4). The percentage of patients who were adequately treated in Group II with single dose was more as compared in group I (62% in group II versus 40% in group I). Euthyroidism was reached in a shorter time after treatment in group II (median time 0.8 year in group II Vs 1.1 yrs in group I) It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a significant low incidence of post therapy hypothyroidism in patients treated with low doses as compared to higher doses of radioiodine therapy.     

Goal attainment scaling: Planning and outcome.

T. J. Kiresuk and R. E. Sherman's (1968) goal attainment scaling (GAS) and a non-scaled goal-setting (NGAS) approach were compared in terms of their impact on case planning and treatment outcome. Exp I tested the hypothesis that 9 GAS clinicians would formulate more specific indicators of treatment goal progress and set goals more relevant to identified case needs than would 9 NGAS clinicians, while both groups would be equally adept at identifying case needs. Exp II hypothesized that GAS cases would receive higher scores than NGAS cases on standardized measures of treatment outcome, and that GAS scores would correlate significantly with global measures of improvement. Exp I provided support for the contribution of GAS to greater indicator specificity, but not goal relevance. Exp II indicated that GAS cases were perceived by teachers as showing more change than NGAS cases. Improvement on GAS goals was not related to improvement on global measures of treatment outcome. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reamed interlocking intramedullary nailing of open fractures of the tibia

One hundred twelve open tibial fractures were treated by reamed interlocking nailing in 108 patients. There were 31 (28%) Grade I fractures, 38 (34%) Grade II, 23 Grade IIIA (21%), and 20 (18%) Grade IIIB fractures. Early amputation was performed in 2 (10%) Grade IIIB fractures for severe crushing injuries. Compartment syndrome complicated 8 (7%) fractures. Mean time to union was 29 weeks for Grade I fractures, 32 weeks for Grade II, 34 weeks for Grade IIIA, and 39 weeks for Grade IIIB. Nonunion complicated 9 (8%) fractures: 1 (3%) Grade I fracture, 2 (5%) Grade II fractures, 3 (13%) Grade IIIA fractures, and 3 (17%) Grade IIIB fractures. Deep infection complicated 4 Grade II fractures (10%) and 2 (11%) Grade IIIB fractures. Reamed locking intramedullary nailing is a safe and effective technique for management of open tibial fractures.     

Efficacy of combination chemotherapy with miconazole and G-CSF in deep mycosis accompanying hematological diseases

In order to examine the efficacy of the combination chemotherapy with miconazole and G-CSF, patients with deep mycosis and suspected deep mycosis were divided into 3 groups. Group I: miconazole and G-CSF were administered simultaneously. Group II: miconazole was administered later during G-CSF administration. Group III: only miconazole was administered. Of a total of 117 cases 105 cases were analyzed including group I 37 cases, group II 39 cases and group III 29 cases, excluding 12 dropout and inadequate cases. Of the 105 cases, deep mycosis were 31 and suspected deep mycosis were 74, and underlying diseases were hematological malignancies such as leukemias. Efficacy judged mainly by the change of fever was 62.2% (23/37) in group I, 43.6% (17/39) in group II, and 41.4% (12/29) in group III, respectively. Efficacy was better in the patients whose neutrophil counts increased from less than 500/microliters to more than 500/microliters (group I 75.0%, group II 72.7%) than in the patients whose neutrophil counts were less than 500/microliters throughout the time of miconazole administration (group I 33.3%, group II 33.3%). Adverse effects were minimal in 3 groups (group I 15.4%, group II 17.4%, group III 15.6%). It is concluded that the combination with miconazole and G-CSF is effective in the treatment of deep fungal infections.     

Resection as elective treatment of hilar cholangiocarcinoma (Klatskin tumor)

A retrospective analysis of our experience in the treatment of hiliary cholangiocarcinoma or Klatskin tumor was performed with the aim of evaluating the morbi-mortality and prognosis of its treatment to thereby determine the usefulness of the different therapeutic options. From 1989 to 1997, 51 patients diagnosed with hiliary cholangiocarcinoma were treated in our hospital. Surgery was indicated in 16 with curative aims (group I) while palliative treatment with percutaneous biliary drainage was indicated in 35 (group II). Biliary resection was carried out in 8 patients being associated with hepatic resection in 4 (group IA) and in 8 patients undergoing liver transplantation (group IB). Clinico-epidemiologic data and hospital stay were similar in all the groups. The frequency of complications was similar in groups I and II although the frequency of cholangitis (49%) in group II was noticeable. The percentage of readmissions was also greater in group II (12 vs 46%, respectively; p = 0.03) with prosthesis obstruction being the most frequent cause. Accumulated survival at 1, 2, and 3 years in group I was 84, 64 and 48% with a median survival of 33 months, while in group II the median survival was of 6 months with no patient surviving more than 2 years (p = 0.0001). When groups IA and IB were compared, greater frequency of complications in groups IA (100 vs 37%; p = 0.002), similar frequency of readmissions (87 vs 75%; p = NS), median survival greater in group IB (12.5 months vs 48 months) and significantly higher actuarial survival in group IB (48% in 2 years vs 83% to 2 years; p = 0.02) was observed. In conclusion, surgery is the treatment of choice in hiliary cholangiocarcinoma whenever possible, given the greater survival without a significant increase in morbimortality. Likewise, we consider that liver transplantation is a useful option in the treatment of patients with cholangiocarcinoma type IV of Bismuth.     

Incidence of Toxoplasma and Toxocara antibodies among out-patients in the Ophthalmic Research Institute, Egypt

Infection by Toxoplasma gondii and Toxocara canis is getting much important nowadays. Both are soil transmitted infections. The present study was planned to detect the incidence of T. gondii and T. canis antibodies among 100 patients attending the outpatient clinics in Research Institutes of Ophthalmology (RIO), whose urine and stool were free from other parasitic stages. Patients were classified into two groups, group I; (70 ocular cases) and group II, (30 non-occular cases). Control group (group III); 30 healthy persons. Sera from all individuals were subjected to IFAT and IHAT to detect Toxoplasma antibodies and IFAT to detect Toxocara antibodies. By using IFAT for Toxoplasma revealed, 25% as a total incidence, 21.4% in group I, 33.3% in group II and 6.6% in group III. While IHAT revealed 51% as a total incidence, 51.4% in group I, 50% in group II and 23.3% in group III. Among group I, retinochoroiditis cases showed the highest incidence and titre. While hydrocephalic cases showed highest incidence and titre in group II. T. canis antibodies revealed 23% as a total incidence, 14.3% in group I, 43.3% in group II and 5% in group III. Cases presented with retinal detachment showed the highest incidence and titre in group I while in group II hepatomegalic cases gave the highest incidence and titre. Concomitant infection of both Toxoplasma and Toxocara was detected in 8% of positive cases.     

Human parainfluenza virus type 3 up-regulates major histocompatibility complex class I and II expression on respiratory epithelial cells: involvement of a STAT1- and CIITA-independent pathway

Human parainfluenza virus type 3 (HPIV3) infection causes severe damage to the lung epithelium, leading to bronchiolitis, pneumonia, and croup in newborns and infants. Cellular immunity that plays a vital role in normal antiviral action appears to be involved, possibly because of inappropriate activation, in the infection-related damage to the lung epithelium. In this study, we investigated the expression of major histocompatibility complex (MHC) class I and II molecules on human lung epithelial (A549) and epithelium-like (HT1080) cells following HPIV3 infection. MHC class I was induced by HPIV3 in these cells at levels similar to those observed with natural inducers such as beta and gamma interferon (IFN-beta and -gamma). MHC class II was also efficiently induced by HPIV3 in these cells. UV-irradiated culture supernatants from infected cells were able to induce MHC class I but not MHC class II, suggesting involvement of released factors for the induction of MHC class I. Quantitation of IFN types I and II in the culture supernatant showed the presence of IFN-beta as the major cytokine, while IFN-gamma was undetectable. Anti-IFN-beta, however, blocked the HPIV3-mediated induction of MHC class I only partially, indicating that viral antigens, besides IFN-beta, are directly involved in the induction process. The induction of MHC class I and class II directed by the viral antigens was confirmed by using cells lacking STAT1, an essential intermediate of the IFN signaling pathways. HPIV3 induced both MHC class I and class II molecules in STAT1-null cells. Furthermore, MHC class II was also induced by HPIV3 in cells defective in class II transactivator, an important intermediate of the IFN-gamma-mediated MHC class II induction pathway. Together, these data indicate that the HPIV3 gene product(s) is directly involved in the induction of MHC class I and II molecules. The induction of MHC class I and II expression by HPIV3 suggests that it plays a role in the infection-related immunity and pathogenesis.     

Regeneration of adrenal cortical tissue after adrenal autotransplantation

OBJECTIVE: This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. METHODS: Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. MAIN OUTCOME MEASURES: The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. RESULTS: The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. CONCLUSIONS: Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.     

Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.     

A study of brain MRI findings and clinical response of bladder emptying failure in brain bladder

In 45 patients (38 males and 7 females; average age: 78 years) with brain bladder, who did not have any peripheral neuropathies and spinal disturbances, cerebral findings of MRI (1.5 T) T2 enhanced image were analyzed in comparison with those of 7 control patients with normal urination after BPH operations. Patients with neurogenic bladder were divided into three groups as follows: 33 patients with a chief complaint of urinary disturbance (Group I), 9 patients with urinary incontinence (Group II) and 3 patients with balanced bladder (Group III). High frequency of lacune (24%) of the globus pallidus and low signalling of the corpus striatum (30%) was found in Group I patients, but low frequency in other Group patients and control patients. Furthermore, pathologic changes with various grade in the globus pallidus were observed in 91% of Group I patients. In the treatment of urinary disturbance, a high improvement rate of micturition disorder (77%) was obtained in patients treated with a combination of dantrolene and TURp (TUIbn for females). However, patients which had clear lacune of the globus pallidus showed the low improvement rate. It should be possible that the globus pallidus contributes to control the movement of the external sphincter and the pelvic base muscles as well as other striated muscles. Moreover, lacune was rarely found in the urination center of the brain-stem on MRI.     

A G protein is involved in the angiotensin AT2 receptor inhibition of the T-type calcium current in non-differentiated NG108-15 cells

In non-differentiated NG108-15 cells, both angiotensin II (Ang II) (100 nM) and CGP 42112 (100 nM) decreased the T-type calcium current amplitude by 24 +/- 2% and 21 +/- 3%, respectively. cGMP is not a mediator of the Ang II effect, since loading of cells with 50 microM cGMP did not prevent the inhibitory effects of Ang II. The effects of Ang II involves a non-identified GTPase activity since incubation with GDP beta S (3 mM) completely reversed the inhibitory effect of Ang II while GTP gamma S mimicked its effect. However, Ang II binding was not affected by GTP gamma S, and the effect of Ang II was not modified in pertussis toxin-treated cells. The inhibitory effect of Ang II on the T-type Ca2+ current involves a phosphotyrosine phosphatase activity since sodium orthovanadate prevented the effects of Ang II, although microcystin-LR, a selective Ser/Thr phosphatase 1 and 2A inhibitor, did not modify the effect of Ang II. These results provide the first evidence of a modulation of membrane conductance by Ang II through the AT2 receptor and demonstrate the involvement of a phosphotyrosine phosphatase and a G protein in the AT2 transduction mechanism in NG108-15 cells. Moreover, our data suggest that phosphotyrosine phosphatase activation is proximal to receptor occupation, since sodium orthovanadate inhibits both GTPase activity and T-type current blockage induced by Ang II or CGP 42112, while GTP gamma S inhibition of the T-type calcium current is not impaired.     

Comparison of vena contracta width by multiplane transesophageal echocardiography with quantitative Doppler assessment of mitral regurgitation

OBJECTIVE: To compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension. PATIENTS: Eight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three. METHODS: All patients underwent right heart catheterisation. Mean (SEM) right atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm Hg, cardiac index 1.75 (0.13) l/min/m2 and mixed venous oxygen saturation 59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI2) or iloprost was given for phase I (three to six weeks); the patients were then crossed over to receive the alternate drug in an equivalent phase II. MAIN OUTCOME MEASURES: Exercise tolerance was measured at baseline and at the end of phase I and II with a 12 minute walk; distance covered, rest period, percentage drop in arterial oxygen saturation (delta Sao2%) and percentage rise in heart rate (delta HR%). RESULTS: Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m with PGI2 (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI2 (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). Delta HR% was 37.5(6)% at baseline, 35(3)% on PGI2, and 24(6)% on iloprost (p = 0.04). CONCLUSIONS: Both intravenous PGI2 and iloprost caused significant improvement in exercise tolerance. Iloprost offers an alternative to PGI2 treatment of severe pulmonary hypertension.