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Biomedical subjects

C Pfister

Publications and source records attributed to C Pfister.

At least 19 recordsLinked to original sources
PubMed2002

[Vesicoureteric reflux and functional voiding dysfunction in children].

PURPOSE: To analyze the efficacy of the different treatments of vesicoureteric reflux (VUR) associated with reflex bladder sphincter dyssynergia (RBSD). PATIENTS AND METHODS: The medical records of 33 children (28 girls) aged 4 to 12 years presenting reflex bladder sphincter dyssynergia and vesicoureteric reflux have been reviewed. The most common clinical symptom was urinary tract infection. Voiding dysfunction included: dysuria, urinary leak, enuresia, urgency, constipation. In most cases, vesicoureteric reflux was low grade (grade 1, n=9; grade 2, n=18; grade 3, n=6) and bilateral (n=18). Three types of treatments have been utilized: reimplantation, reeducation, medical treatment (diet, antibio-prophylaxis, anti-cholinergics). RESULTS: Eleven children (2 with a solitary kidney) underwent early reimplantation which was effective on vesicoureteric reflux but 6 of them had post-operative voiding dysfunction and 5 had a new episode of urinary infection. Six had reeducation first then they underwent reimplantation. Sixteen children had an exclusive medical treatment (13 with reeducation). In 9 children vesicoureteric reflux disappeared (one child still complains of voiding dysfunction). In 7, voiding dysfunction improved but vesicoureteric reflux is still present. CONCLUSION: The management of vesicoureteric reflux associated with reflex bladder sphincter dyssynergia is complex. Surgery should certainly not be the initial treatment. However, it can remain useful if one wishes to get complete resolution of reflux.

Anti-Bacterial Agents↗
PubMed2001

Fast dynamics of halophilic malate dehydrogenase and BSA measured by neutron scattering under various solvent conditions influencing protein stability.

Protein thermal dynamics was evaluated by neutron scattering for halophilic malate dehydrogenase from Haloarcula marismortui (HmMalDH) and BSA under different solvent conditions. As a measure of thermal stability in each case, loss of secondary structure temperatures were determined by CD. HmMalDH requires molar salt and has different stability behavior in H(2)O, D(2)O, and in NaCl and KCl solvents. BSA remains soluble in molar NaCl. The neutron experiments provided values of mean-squared atomic fluctuations at the 0.1 ns time scale. Effective force constants, characterizing the mean resilience of the protein structure, were calculated from the variation of the mean-squared fluctuation with temperature. For HmMalDH, resilience increased progressively with increasing stability, from molar NaCl in H(2)O, via molar KCl in D(2)O, to molar NaCl in D(2)O. Surprisingly, however, the opposite was observed for BSA; its resilience is higher in H(2)O where it is less stable than in D(2)O. These results confirmed the complexity of dynamics-stability relationships in different proteins. Softer dynamics for BSA in D(2)O showed that the higher thermostability is associated with entropic fluctuations. In the halophilic protein, higher stability is associated with increased resilience showing the dominance of enthalpic terms arising from bonded interactions. From previous data, it is suggested that these are associated with hydrated ion binding stabilizing the protein in the high-salt solvent.

Animals↗
PubMed2001

[Expression and dynamics of peptidergic nerve fibers in granulation tissue after distance osteosynthesis].

The transmitters and/or modulators calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY) and vasointestinal polypeptide (VIP) are supposed to be involved in bone growth, fracture healing and internal remodeling. Immunohistochemical proof of neuropeptide positive fibers in normal bone let us assume that these substances effect the early phase of fracture healing. Exact time of appearance of neuropeptide positive fibers, localisation in the bone, chemospecifity and mode of genesis are unknown so fare. Research was done on a model of distance osteosynthesis of the rabbit tibia. Primary and secondary antibodies were used for indirect immunohistochemical technique. We put more strength on the concrete stereological calculation of length of the nerve fibers than on a conventional statistical evaluation. After histological preparation of tissue specimens from the interfragmental gap and the bone marrow beside the gap the neuropeptides CGRP, SP and NPY were immunohistochemically expressed. Sprouting of CGRP- and SP-positive nerve fibers has its origin in the bone marrow. A vascularisation in the early state of osteoneogenesis after fracture seems impossible without the nerval peptidergic influence and transmission.

Animals↗
PubMed2001

Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia.

PSC 833 (Valspodar) can reverse multidrug resistance (MDR) in patients with hematologic malignancies, but alters the pharmacokinetics of concomitant anticancer agents. A phase I, dose-finding study was initiated to define a safe and effective regimen of mitoxantrone, etoposide, and cytarabine (MEC) when administered with PSC 833 to patients with early relapsed or refractory acute myeloid leukemia (AML). Poor-prognosis AML patients refractory to first-line induction therapy or relapsing within 9 months of attaining complete remission (CR) were treated with cytarabine (1.0 g/m2/day), etoposide (30 mg/m2/day), and mitoxantrone at a dose of either 3.0 mg/m2/day (cohort 1) or 4.5 mg/m2/day (cohorts 2 and 3) for 6 days plus continuous-infusion PSC 833 (10 mg/kg/24 h with a 2.0 mg/kg loading dose) for 6 or 7 days each 21-day cycle. Patients achieving CR were given a 4-day MEC plus PSC 833 consolidation cycle. Twenty-three patients were enrolled (eight with primary refractory AML and 15 in relapse). Dose-limiting toxicity occurred in one of six patients in cohort 2 (grade 4 mucositis) and one of seven patients in cohort 3 (grade 4 hyperbilirubinemia). The maximum tolerated dose of mitoxantrone was defined as 4.5 mg/m2/day. Clinically significant grade 4 hyperbilirubinemia, possibly related to PSC 833, occurred in four patients. Hematologic toxicities were as expected in this patient population, but were not dose limiting. Mild to moderate cerebellar ataxia and paresthesia occurred in six (26%) and five (22%) patients, respectively, but were not dose limiting. Overall, six of 23 (26%) patients achieved CR, including five patients with demonstrated P-glycoprotein expression and/or function. The median overall survival was 4 months. All six patients with a CR were alive and four (17%) patients were disease free at 12 months. Blood levels of PSC 833 were well above the target level of 1000 ng/ml, a concentration that is known to reverse MDR in vitro. PSC 833 reduced the clearance of etoposide by approximately two-fold. No correlation was observed between the mitoxantrone or etoposide area under the curve and response. In conclusion, the MEC plus PSC 833 tested regimen was well tolerated and the 26% CR rate warrants further testing of this regimen in a randomized, phase III trial.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[Role of helical tomodensitometry in the early diagnosis of renal infarction].

INTRODUCTION: Renal infarction is a rare and often difficult diagnosis. The objective of this study was to demonstrate that contrast-enhanced spiral CT in patients presenting features of renal colic, can establish the diagnosis by confirming the presence of infarction of the renal parenchyma. MATERIAL AND METHODS: Over a 10-month period, the authors proposed the following decision flow-chart for all patients admitted with clinical features of renal colic: plain abdominal x-ray and first-line renal ultrasound, which, in the absence of a diagnosis (stones or dilatation of cavities), were completed by unenhanced spiral CT scan. When these examinations were normal, contrast-enhanced spiral CT scan was then performed. RESULTS: 300 patients were included in this study, and CT was performed in 40 cases. This management allowed the diagnosis of infarction of the renal parenchyma in three patients, who are described here. When unenhanced CT sections do not reveal any abnormality, contrast-enhanced sections are essential to visualize the infarcted zone, seen as a triangular low density lesion with clearly defined margins and a vascular topography. CONCLUSION: Contrast-enhanced spiral CT should now be considered to be the reference examination for the assessment of non-documented renal colic. This recent imaging modality should allow the diagnosis of a greater number of infarctions of the renal parenchyma, which formerly remained undiagnosed.

Humans↗
PubMed2001

[Ischemic orchiditis: review of 5 cases diagnosed by color Doppler ultrasonography].

PURPOSE: To study color-doppler ultrasoundfeatures of testicular infarction caused by orchiepididymitis, a severe complication of orchiepididymitis. MATERIAL: and Methods. Five patients were included over a 2 year period. All presented with more than 24 hours of pain. A final diagnosis of testicular infarction caused by orchiepididymitis and color doppler ultrasound was available in all cases. RESULTS: All patients showed doppler ultrasound signs of testicular ischemia. Either vascularisation was not detectable or intratesticular resistive index was increased with a negative diastolic flow. Orchidectomy was performed in all patients. CONCLUSION: Color doppler examination of the scrotum should include measurement of intratesticular resistive index. An elevated RI can be suggestive of ischemia.

Adult↗
PubMed2000

Insights into the molecular relationships between malate and lactate dehydrogenases: structural and biochemical properties of monomeric and dimeric intermediates of a mutant of tetrameric L-[LDH-like] malate dehydrogenase from the halophilic archaeon Haloarcula marismortui.

L-Malate (MalDH) and L-lactate (LDH) dehydrogenases belong to the same family of NAD-dependent enzymes. LDHs are tetramers, whereas MalDHs can be either dimeric or tetrameric. To gain insight into molecular relationships between LDHs and MalDHs, we studied folding intermediates of a mutant of the LDH-like MalDH (a protein with LDH-like structure and MalDH enzymatic activity) from the halophilic archaeon Haloarcula marismortui (Hm MalDH). Crystallographic analysis of Hm MalDH had shown a tetramer made up of two dimers interacting mainly via complex salt bridge clusters. In the R207S/R292S Hm MalDH mutant, these salt bridges are disrupted. Its structural parameters, determined by neutron scattering and analytical centrifugation under different conditions, showed the protein to be a tetramer in 4 M NaCl. At lower salt concentrations, stable oligomeric intermediates could be trapped at a given pH, temperature, or NaCl solvent concentration. The spectroscopic properties and enzymatic behavior of monomeric, dimeric, and tetrameric species were thus characterized. The properties of the dimeric intermediate were compared to those of dimeric intermediates of LDH and dimeric MalDHs. A detailed analysis of the putative dimer-dimer contact regions in these enzymes provided an explanation of why some can form tetramers and others cannot. The study presented here makes Hm MalDH the best characterized example so far of an LDH-like MalDH.

Anilino Naphthalenesulfonates↗
PubMed2000

Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes.

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.

Aged↗
PubMed2000

Dose-finding study of valspodar (PSC 833) with daunorubicin and cytarabine to reverse multidrug resistance in elderly patients with previously untreated acute myeloid leukemia.

INTRODUCTION: This trial was designed to determine the maximum tolerated dose of intravenous daunorubicin (DNR) in combination with valspodar and to test the feasibility of P-glycoprotein modulation using valspodar in elderly patients with previously untreated acute myelogenous leukemia receiving standard induction chemotherapy. METHODS: Patients > or =60 years of age with previously untreated AML received valspodar (10 mg/kg/24 h by continuous intravenous infusion [CIV] on days 1-4 with a 2-mg/kg loading dose on day 1) in conjunction with two cycles of induction chemotherapy consisting of cytarabine (200 mg/m(2) CIV on days 1-7), and DNR (35 mg/m(2) [cohort 1] or 45 mg/m(2) [cohort 2] on days 1-3, intravenous bolus). Patients were assessed for dose-limiting toxicities (DLT), response rate, event-free and overall survival, and pharmacokinetics of valspodar and DNR. RESULTS: Valspodar was well tolerated at the lower DNR dose level (ie, 35 mg/m(2)) resulting in a 21% rate of DLT and only three toxic deaths. Treatment-related mortality was unacceptably high at the 45 mg/m(2) DNR dose level. The complete response rate was 49% overall and similar in both cohorts. The median overall survival of patients was 333 days in cohort 1 compared to 98 days in cohort 2. At baseline, 70% of assessable patients were P-glycoprotein positive. CONCLUSION: Substantial inhibition of P-glycoprotein activity can be achieved in this patient population at clinically tolerable doses of valspodar and DNR. The maximum tolerated dose of DNR was established as 35 mg/m(2). This regimen is being further evaluated in phase III trials.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Genes, p53↗
PubMed2000

Total bilateral ureteral replacement for stenosing ureteritis in Henoch-Schönlein purpura.

Stenosing and calcified ureteritis occurring in Henoch-Schönlein purpura remains a rare urological complication. The authors describe their own experience of the diagnosis and treatment of this rare pathology along with a review of the literature. Recognition and early surgical management may prevent serious renal outcome. In cases of ureteral replacement, different procedures using ileal segment have been proposed. We report the results of the Cockett and Goodwin procedure with a follow-up of more than 25 years.

Child↗
PubMed2000

[Contribution of lumboscopy in the treatment of pyeloureteral junction syndromes. Report of 25 cases].

OBJECTIVE: Evaluation of the results of lumboscopic repair of ureteropelvic junction syndromes. MATERIAL AND METHOD: Retrospective study of 25 consecutive lumboscopic retroperitoneal pyeloplasties performed over 3 years in 14 women and 11 men with symptomatic ureteropelvic junction syndrome. RESULTS: The mean operating time was 200 minutes (range: 120-360 minutes) and mean blood loss was 60 ml. Surgical conversion was necessary in three cases due to the difficulty of dissection and in one case because of rupture of the ureter. Analgesic prescription was generally only necessary for the first 2 postoperative days. The mean hospital stay was six days (range: 2-16 days). Patients were able to return to work an average of 10 days after the operation. With a mean follow-up of 9 months (range: 6 to 18 months), all patients were asymptomatic except for one patient who reported pain at a trocar site. Follow-up urography at 3 months showed marked improvement in 18 patients (85.7%), moderate pyelocaliceal dilatation in 2 cases and one failure. CONCLUSION: Lumboscopic pyeloplasty is an alternative to endopyelotomy. It provides a comparable success rate to that of conventional surgery, while reducing the morbidity, length of hospital stay and convalescence. However, it requires mastery of intracorporeal suture techniques.

Adult↗
PubMed2000

Results of concomitant radio-chemotherapy for invasive bladder tumors.

INTRODUCTION: The aim of this study was to evaluate combined radiation and chemotherapy for invasive bladder tumors and to define possible biological prognostic factors. MATERIALS AND METHODS: Forty-five patients (mean age 75 years, range 68 to 86) were treated by deep bladder resection with combined radiation (5 courses of 10 Grays [Gys]) and chemotherapy (2 cycles of 100 mg of cisplatin over 7 weeks). Subsequent to the treatment, evaluations at 10 weeks, then 3 months, 6 months, and 12 months, and every year, included a clinical examination, Karnofsky evaluation, a cystoscopy with urinary cytology, and systematic deep bladder pathology biopsies after a computer tomography (CT) scan. In our series, DNA analysis and an immuno-histochemistry study of MiB1, p53, and MdR were also performed in the last 20 patients. RESULTS: At 6 months, progression of the disease was evaluated in 26% of cases; at 12 months, satisfactory local control was evaluated in 60% of cases. However, only 15 patients were in complete remission after a period of 2 years. Of these, only eight patients were in remission with more than 42 months follow-up. We observed aneuploid tumors in 30% of cases; these patients died after 6 months despite concomitant radio-chemotherapy. In our experience, the results of associated immuno-histochemistry markers was not really contributive. CONCLUSION: This therapeutic alternative may be useful in patients where a cystectomy cannot be performed. It not only permits bladder conservation, but also offers satisfactory, significant quality of life, even if survival rates remain uncertain.

Aged↗
PubMed1999

Adenocarcinoma on renal allograft as a complication at 5 years.

We report a new case of renal carcinoma in allograft kidney, 5 years after transplantation, which presented as a suspect allograft abscess in a complex history of recurrent urinary infection. Only surgical management with peroperative histological evaluation permitted us to confirm the diagnosis of malignancy.

Adenocarcinoma↗
PubMed1999

Shortcomings of diuresis scintigraphy in evaluating urinary obstruction: comparison with pressure flow studies.

BACKGROUND: In at least 15 % of dilated urinary tracts, diuresis renography fails to assess the presence or absence of urinary obstruction. OBJECTIVE: To determine the shortcomings of (99 m)Tc-DTPA frusemide diuresis renography by reference to pressure flow studies. MATERIALS AND METHODS: Thirty-four patients, aged 1 month to 20 years, with questionable obstruction were evaluated by diuresis renography and pressure flow studies (the Whitaker test) as the reference method during the same short period of time. Discrepancies were analysed. RESULTS: In patients with type I or IIIa renographic response, pressure flow studies never led to any change in management. Poor function, major dilatation and prior surgery were found to be risk factors of inaccurately obstructive pattern (type II) on renography (n = 6). In patients with type IIIb response, pressure flow studies could show low-grade (n = 3) or intermittent obstruction (n = 2). Intermittent obstruction was also demonstrated in two patients with type II response. CONCLUSION: In patients with risk factors, type II response was sometimes inaccurate, and urodynamic evaluation showed absence of obstruction and led to conservative management. Type IIIb response should be considered equivocal rather than partially obstructive, and pressure flow studies could be considered in such patients.

Adolescent↗
PubMed1999

Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors.

The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 index in superficial papillary bladder tumors and to correlate it with the S-phase fraction (SPF) measured by flow cytometry. Three hundred nineteen patients with newly diagnosed superficial (pTa, pT1) bladder tumors were included between September 1990 and April 1992. Patients with bladder carcinoma in situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, whereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-67 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The relation between Ki-67 expression and prognostic variables (stage, grade, tumor size, multifocality, age, and sex) was investigated by the chi-square test. Cox regression was used to describe the association between Ki-67 and tumor recurrence in 308 patients with follow-up while adjusting for potentially confounding prognostic variables. The frequency of high Ki-67 expression (> or =10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patients experienced tumor recurrence in a median follow-up of 68 months. Stage, grade, tumor size, and multifocality were all independent predictors of recurrence. Ki-67 index greater than 10% was found to be an independent predictor of tumor recurrence among patients with tumors larger than 3 cm in diameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation was observed between Ki-67 expression and the SPF (Spearman's correlation coefficient = 0.23, P = .004). In addition, aneuploid tumors had significantly higher expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Moreover, patients with DNA aneuploid bladder tumors were more likely to have more than 10% Ki-67-positive cells than those with diploid tumors. In patients with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those with tumors larger than 3 cm.

Aged↗