Aberrant atrioventricular conduction triggered by antimalarial prophylaxis with mefloquine.
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Biomedical subjects
Publications and source records attributed to J Richter.
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The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (IF2). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P = 0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P = 0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P = 0.04) and p53 overexpression were associated with poor prognosis (P = 0.0021), whereas mdm-2 overexpression was not related to patient outcome (P = 0.73). A Cox regression analysis revealed tumor stage (P < 0.001) and p53 overexpression (P < 0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.
Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.
According to sonographic criteria, 55 patients underwent surgical treatment with mobilisation in a lower leg plaster or conservative treatment with early mobilisation in heel pad (3 cm) shoes when an acute Achilles tendon rupture (ATR) was diagnosed. The follow-up period in 51 patients was 2.4 years (operated group = 28 patients, conservative group = 23 patients) with clinical examination and testing of isokinetic muscle strength in knee joint flexion. After surgical treatment, minor wound infections occurred in 10.6%. Reruptures occurred in 13% of the conservative group. Following conservative treatment, the rate of stress-related achillodynia was significantly higher (P = 0.019). In the operated group mean isokinetic muscle strength was 13.7% lower than in the uninvolved leg and decreased significantly with non-operative treatment to 75.3% (P = 0.012). We recommend surgical treatment of acute ATR. The indications for conservative treatment depend on the extent of the rupture (measured by ultrasound in the equinus position), the desired level of daily activity and the patient's degree of compliance.
Eighty-one patients (83 shoulder joints) underwent surgical procedures for recurrent shoulder joint dislocations. All patients had an extra-articular osteotomy with subcapital derotation according to Weber's technique. In all, 46% of the patients underwent additional intra-articular reconstructions. After a mean follow-up of 4.6 years, redislocations (6%) were observed only when a singular derotation technique had been used. Complications were minor (2.4%). External rotation of the operated shoulder joints was normal in most patients with a mean of 48.5 degrees. Improvement in sporting activities was seen in 80% and in working activities in 70%. The mean Constantscore was 89.2. Subacromial pain was rare and correlated with reduced scores in functional strain tests postoperatively. There was no postoperative arthritis owing to the derotation technique. Because of unrestricted rotation and early functional therapy, we observed a good indication for an additional derotation technique when a Hill-Sachs defect is evident.
Sixty-three patients with rigid equinovarus contractures of the foot following ischemic episodes in the lower leg were treated at our institute from 1983 to 1994 by lengthening the Achilles tendon and the tendon of the m.tibialis posterior, release of the tendons of the m.flexor digitorum longus and the m.flexor hallucis longus and release of the dorsal capsule of the ankle joint. Patients with an equinus deformity greater than 20 degrees, with an additional hind foot varus deformity of more than 5 degrees and/or malrotation of the midfoot were not eligible for this procedure. The initial equinus deformity ranged from 7 degrees to 20 degrees (mean 14 degrees). The clinical and radiological results of 41 patients were evaluated retrospectively with a minimum follow-up of 1 year (mean 3.4 years). The overall results were evaluated according to a modified score of Angus and Cowell. Results were good in 60.9%, fair in 29.3% and poor in 9.8%. The range of motion of the ankle joint and the subtalar and midtarsal joints could not be improved. Postoperative complications were observed in 8 patients, one intraoperative lesion of the posterior tibial artery occurred, one avulsion fracture of the anterior tibial metaphysis and one compression syndrome of the tibial nerve. One patient had an initially incomplete correction with a remaining equinus deformity of 10 degrees, and two recurrences of the foot deformity after initially correct position were observed. Furthermore, two hematomas and two soft-tissue infections required surgical revision. These complications may have been due to the preoperatively scarred soft tissue at the medial aspect of the hind foot and a residual postoperative soft-tissue defect after the correction of the foot deformity had been achieved. In conclusion, the technique described is effective in correcting mild pes equinovarus deformities after ischemic episodes in the lower leg. If the pes equinus deformity is greater than 20 degrees, corrective osteotomies of the hind foot should be performed instead.
The use of pulse oximetry during pre-hospital cardiopulmonary resuscitation was prospectively investigated in 23 cases. The question was whether the measurement of oxygen saturation during pre-clinical resuscitation is useful and what conclusions are possible. We were able to obtain confidential data for oxygen saturation in 82.6% (n = 19) of cases. Our results show that pulse oximetry could be used as a means of quality control during resuscitation. It is a useful part of pre-hospital monitoring and should be used during resuscitation as early as possible.
BACKGROUND: Due to the increasing use of pharmacologic stress tests and the lack of comparative studies on ventricular function, this study was designed to establish the average limits in ventricular function with different kinds of stress, and to compare the response among them. METHODS: A randomized, open, controlled phase II clinical trial in 4 parallel groups was designed. Forty healthy male volunteers between 18 and 25 years were randomized into 4 groups of 10 individuals each: physical exercise (group 1), dobutamine (group 2), adenosine triphosphate (ATP) (group 3) and dipyridamole (group 4). Each volunteer underwent equilibrium radionuclide angiography, at rest and during stress. RESULTS: The global and regional ejection fraction increased significantly with the 4 kinds of stress. The maximal increase was reached with dobutamine and the minimal with dipyridamole. Physical exercise induced an increase in global ejection of 13 +/- 5%; dobutamine 16 +/- 6%; ATP 9 +/- 3% and dipyridamole 4 +/- 3%. CONCLUSIONS: The global and regional ejection fraction increases significantly more with dobutamine than with the other stress tests. Dipyridamole elicits the minimal increase.
Gastroesophageal reflux (GER) occurs in 22-66% of patients with noncardiac chest pain (NCCP). Although open-label investigations have shown beneficial effects of antireflux therapy in NCCP, no double-blind, prospective, placebo-controlled studies have been conducted. The purpose of this study was to evaluate the effects of omeprazole compared to placebo in a prospective, double-blind, randomized trial of patients with NCCP and GER. Thirty-six consecutive patients with NCCP and GER documented by 24-hr ambulatory pH testing entered this study. The subjects were randomized to omeprazole, 20 mg by mouth twice a day (17 patients), or placebo (19 patients) for eight weeks. Patients on omeprazole obtained significantly more improvement in the fraction of chest pain days (P = 0.006) and severity (P = 0.032) when compared to placebo. More patients in the omeprazole group reported improvement in individual daily pain scores (81% vs 44%, P = 0.03) and individual severity scores (81% vs 50%, P = 0.057). Thirteen (81%) of the subjects in the treatment arm reported overall symptomatic improvement versus one (6%) in the placebo group (P = 0.001). The results of this study indicate that acid suppression with omeprazole effectively improves chest pain in patients with NCCP and GER.
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Almost all investigations concerning the relationships between sibship size, sibship position and psychiatric disorders addressed more formal aspects, i.e. frequency and position, with contradictory and inconsistent results. Analyses considering sibship size and birth order as mediating factors between parental rearing and psychopathological manifestations in adults are lacking. The present results of an investigation of 1,013 psychiatric inpatients and 251 healthy volunteers support a systematic association between sibship size and parental rearing, mainly in terms of a reversed relationship between emotional warmth, overprotection and number of siblings. An excess of psychiatric patients in the middle position of a sibling seems to be related to specific unfavourable rearing patterns. A validation of our preliminary results would be required in terms of preventive measures for children of risk populations.
OBJECTIVE: Our purpose was to define a simple technique for timing a barium swallow by which radiologists can assess esophageal emptying in patients with achalasia before and after minimally invasive therapy. Our purpose was also to determine the best method of quantifying the degree of emptying using this timed technique. MATERIALS AND METHODS: In the barium swallow technique, upright frontal spot films of the esophagus are obtained at 1, 2, and 5 min after ingestion of 100-200 ml of low-density (45% weight in volume) barium sulfate (volume of barium determined by patient tolerance). Forty-two of these barium swallows done by 23 patients with achalasia were retrospectively reviewed. The examination served either as a baseline study or as a 1-month follow-up study after patients had undergone pneumatic dilatation or Clostridium botulinum toxin injection. The spot films were digitized, and a region of interest was drawn around the column of barium by two observers. The change in area seen in the region of interest on the 1- and 5-min films served as the gold standard for percentage of emptying. The spot films were then analyzed by four other observers, each of whom independently, subjectively, and qualitatively estimated the percentage of emptying between the 1- and 5-min spot films. Percentages were divided into quintiles. On a separate occasion, each of these four observers also independently measured the height and width of the barium column on the 1- and 5-min spot films. The product of height times width seen on the 1- and 5-min films became the quantitative estimate for percentage of emptying. RESULTS: We found no statistically significant difference between the percentage of emptying as measured on the digitized images by the two observers and the height-times-width calculations or qualitative emptying percentage as estimated by the four observers. Interobserver agreement for the area evaluated on the digitized films as well as the height-times-width measurements and qualitative estimates of emptying was almost perfect (the correlation coefficients being 0.99, 0.87, and 0.93, respectively). CONCLUSION: The timed barium swallow is a simple and reproducible technique. Both qualitative assessment and estimated change in area based on height-times-width measurements of the barium column are accurate methods of estimating esophageal emptying.
B16-melanoma-bearing mice were treated with four different formulations containing equivalent doses of the highly effective antineoplastic drug mitoxantrone. The formulations were: A mitoxantrone solution, a negatively charged liposome preparation (small unilamellar vesicles), a 14C-labeled polybutylcyanoacrylate- (PBCA) nanoparticle suspension, and a suspension of poloxamine 1508-coated 14C-PBCA-nanoparticles. After 1, 4 and 24 hr, three animals of each group were killed and the mitoxantrone concentrations in the blood, tumor, liver, spleen, heart and bone marrow were determined using an high performance liquid chromatography technique. Additionally, the concentrations of PBCA particles in the same tissues were measured by scintillation counting to compare the mitoxantrone distribution with the corresponding PBCA nanoparticle distribution. Each formulation led to a different body distribution profile of the drug. Liposomes drastically increased the blood level of mitoxantrone even after 24 hr, although free drug was cleared quickly. Liposomes also raised the concentration in the liver and spleen, but not the drug level in the tumor. PBCA-nanoparticles considerably increased the mitoxantrone concentrations in tumor, heart and spleen. However, the increase in tumor concentrations was not statistically significant due to the high variability. Nevertheless, the tumor growth was reduced significantly (P < .05) compared to both, the liposome and the solution preparation. The nanoparticle polymer concentrations did not completely mirror those of the drug concentrations. Especially in the heart, where no nanoparticle polymer radioactivity was found, the particle concentration did not completely correspond to the mitoxantrone concentration, revealing that a part of the drug was lost from the particles. These pharmacokinetic results correspond to parallel therapeutic effects obtained with mitoxantrone-loaded nanoparticles and liposomes in the B16 melanoma.
PURPOSE: We conducted a randomized, double-blind, multicenter clinical trial to determine whether lansoprazole was superior to continued therapy with histamine H2-receptor antagonist therapy in healing erosive reflux esophagitis. METHODS: Investigators from nine medical centers enrolled 159 patients with endoscopically documented esophageal erosions and/or ulcers that had failed to heal with 12 or more wk of at least standard dosages of histamine H2-receptor antagonist therapy. Patients received ranitidine 150 mg b.i.d. for 8 wk or lansoprazole 30 mg for 4 wk followed by either lansoprazole 30 mg or lansoprazole 60 mg for another 4 wk of treatment. Patients underwent endoscopy at screening and at weeks 2, 4, and 8. RESULTS: At 2, 4, and 8 wk of therapy, healing rates were significantly higher in the lansoprazole group compared with the ranitidine group (p < 0.001). By 8 wk, 84% of the lansoprazole group were healed as opposed to only 32% of the ranitidine group. Lansoprazole was superior to ranitidine in providing relief of upper abdominal burning and daytime heartburn (p < 0.001) and reducing the need for antacids (p < 0.001). Lansoprazole patients had less interference with sleep and less day time drowsiness than ranitidine patients (p = 0.05). The percentages of patients with adverse events were similar in both groups. Fasting serum gastrin levels at weeks 4 and 8 were significantly higher in the lansoprazole group compared with the ranitidine group. CONCLUSION: Eight weeks of lansoprazole therapy is safe, superior to continued ranitidine therapy, and effective in healing more than 80% of patients with erosive reflux esophagitis previously resistant to histamine H2-receptor antagonist therapy.
Alterations of chromosome 8, including deletions of 8p, occur frequently in many tumors. In this study, fluorescence in situ hybridization was used to study the relationship between 8p deletions, 8q gains, and phenotype in bladder cancer. Cells from 87 tumors were examined by dual-labeling fluorescence in situ hybridization with a centromere 8 probe (pJM12) and P1 probes for 8p22, 8p12, 8q12, and 8q24. Both 8p22 deletions and 8q24 gains were strongly associated with tumor phenotype. There was a marked difference in 8p22 deletions between noninvasive (pTa) tumors (3/33) and minimally invasive (pT1) tumors (8/19; P = 0.005) whereas there was no significant difference between pT1 and muscle-invasive (pT2-4) tumors (19/35; P = 0.3926). Six tumors with 8p22 deletion were examined at 8p12. Three of these tumors showed no 8p12 deletion, narrowing down the site of a putative tumor suppressor gene distal to 8p12. In one other case, there was a marked increase in 8p12 copy number (> 40 per cell; amplification), suggesting the presence of an oncogene involved in bladder cancer at 8p12. The marked difference in 8p22 deletions between noninvasive (pTa) and minimally invasive (pT1) tumors is consistent with a role of a putative tumor suppressor gene on 8p for development of invasive tumor phenotype.
The haematopoietic stem cells in the bone marrow have long been considered, at least in theory, as an ideal target for gene therapy. Of the more than 250 clinical gene transfer protocols reported from around the world up to December 1996, almost one in three involves manipulation of haematopoietic cells. This includes both marketing trials and trials with a therapeutic intent. The human gene transfer trials targeting haematopoietic cells, the knowledge gained from them and their limitations are briefly summarized.
In a group of women who gave birth to a foetus with marked growth retardation and 27 women who were delivered of eutrophic neonates the lead, cadmium, zinc and lysozyme levels in placental tissue were assessed. The investigation revealed the following results: the lead level was in the investigated group significantly higher than in the control group (15.24 ng/g vs. 11.31 ng/g). Conversely the zinc levels were significantly higher in the control group (20.52 micrograms/g vs. 14.3 micrograms/g of placental tissue). The lead, cadmium and lysozyme values rise with the womens' age in the examined placentae, while the zinc levels decline. With the elevated zinc level the lead and cadmium content in the placentae of the exposed group declines. The lysozyme values increase along with the rise of all investigated elements with the exception of zinc, where the dynamics are reversed. The findings justify the recommendation of zinc supplementation during pregnancy.
In the submitted review the authors present basic information on immunization against viral hepatitis B (VHB) in patients with chronic renal failure. These patients have a significantly lower response to the vaccine against VHB, due in particular to secondary immunodeficiency. Possible correction of this adverse situation can be achieved by modification of the immunization pattern (type and dosage of vaccine, the period and early time of vaccination, route of administration) and adjuvant immunomodulating therapy.