Biomedical subjects
P Blanchet
Publications and source records attributed to P Blanchet.
Assessment of the functional role of accessory pudendal arteries in erection by transrectal color Doppler ultrasound.
PURPOSE: Anatomical studies have demonstrated accessory pudendal arteries originating from supralevator vessels in about two-thirds of men. Injury to accessory pudendal arteries derived from inferior vesical and obturator arteries has been reported to be responsible for vasculogenic impotence after nerve sparing radical prostatectomy. We performed transrectal and perineal color Doppler ultrasound in patients before radical pelvic surgery to identify accessory pudendal arteries and assess their functional role during erection. MATERIALS AND METHODS: A total of 12 patients with a mean age of 60 years were examined before radical prostatectomy (10) or cystoprostatectomy (2). Transrectal and perineal color Doppler flow imaging and spectral waveform analysis were performed. Peak systolic velocity, end diastolic velocity, resistive index and arterial diameter were measured before and during pharmacologically induced erection. Transrectal color Doppler ultrasound data were compared with intraoperative findings. RESULTS: Transrectal color Doppler ultrasound visualized accessory pudendal arteries derived from supralevator arteries in 9, and prostatic and seminal vesicle arteries in all patients. Perineal color Doppler ultrasound visualized internal pudendal arteries in all patients. After intracavernosal injection of papaverine accessory and internal pudendal arteries displayed similar significant hemodynamic changes. Diameter as well as peak systolic and end diastolic velocities increased, and resistive index decreased. Prostatic and seminal vesicle arteries showed no significant change. Presence and location of accessory pudendal arteries demonstrated by transrectal color Doppler ultrasound were confirmed by intraoperative findings. CONCLUSIONS: During pharmacologically induced erection hemodynamic changes in accessory and internal pudendal arteries are similar to those described in cavernous arteries, thus demonstrating the functional role of accessory pudendal arteries in penile erection. Color Doppler ultrasound appears to be reliable to examine internal and accessory pudendal arteries based on morphological and functional criteria.
Abnormal restriction pattern of PIP gene associated with human primary prostate cancers.
The PIP gene, localized in the 7q34 region that contains a number of fragile sites such as FRA 7H and FRA TI, codes for gp17/PIP, a protein secreted by breast apocrine tumors. We analyzed the integrity of this gene in 20 tumors of the urogenital tract. We found rearranged EcoRI fragments in 5 of 15 primary prostate carcinomas. No rearrangement was found in normal prostates derived from five patients undergoing prostatocystectomy during treatment of bladder cancers. By Southern blot hybridization with PIP gene exon-specific probes, the rearrangements were mapped at or near the 3' end of the gene. These abnormalities were found, not only in the neoplastic cells invading the prostatic tissues, but also in seminal vesicles without histologic tumoral features. These data suggest a critical role of the PIP gene or neighboring genes in prostate cancer.
Expression of FMR1, FXR1, and FXR2 genes in human prenatal tissues.
We analyzed the distribution of FMR1, FXR1, FXR2 mRNA, and FMRP in whole normal human embryos and in the brains of normal and fragile X fetuses. The distributions of mRNA for the 3 genes in normal whole embryos and in the brains of normal male and female carrier fetuses were similar, with large amounts of mRNA in the nervous system and in several non-nervous system tissues. No FMR1 (mRNA and protein) was detected and no evident neuropathologic abnormalities found in the brains of male carrier fetuses, suggesting that the FMR1 product (FMRP) may have no crucial function in early stages of nervous system development. FXR1 and FXR2 mRNA had the same distribution and similar intensity in the brains of normal and pathologic fetuses (female and male carriers). The coexpression in the same tissues of FMR1, FXR1, and FXR2, associated with the normal expression of FXR1 and FXR2 and the absence of obvious neuropathological abnormalities in pathological brains, supports the notion that the FXR1 and FXR2 proteins partially compensate for FMRP function. However, the absence of significant overexpression of FXR1 and FXR2 in pathological brains suggests that these genes do not compensate for the lack of FMR1 expression. Alternatively, FMR1, FXR1, and FXR2 proteins may not have compensatory functions, but instead may regulate functions by hetero or homo oligomerization, as suggested by other studies. Thus, a dominant negative effect of abnormal multimeric protein complexes lacking FMRP (e.g. by modification of FXR1 and FXR2 protein functions) may result in the fragile X syndrome phenotype.
[Risk of flammable gas from aerosol sprays].
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CD44 is an independent prognostic factor in conventional renal cell carcinomas.
PURPOSE: CD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions. De novo expression of CD44 and its variant isoforms has been associated with aggressive behavior in various tumors. Since few data are available concerning the role of CD44 in the biological behavior of locally confined renal tumors, we analyzed the expression of CD44 in a large set of conventional renal cell carcinomas to determine its prognostic value in association with other clinicopathologic variables. MATERIALS AND METHODS: Ninety-one patients with locally confined conventional renal cell carcinomas were studied. CD44 standard form (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin-embedded tumor tissue by immunohistochemistry. The prognostic value of the usual clinicopathological variables and CD44 expression was tested using Kaplan-Meier plots by the log rank test and Cox multiple hazard regression analysis. RESULTS: No immunostaining was observed in normal renal tissue. Thirty-two of the 66 conventional renal cell carcinomas (48%) showed CD44H membranous staining of the tumor cells. Only 2 cancers displayed CD44v6 immunostaining. Among the different clinicopathological variables analyzed, tumor stage (p = 0.001), nuclear grade (p = 0.01), size (p = 0.02), vascular (p = 0.05) and perirenal adipose tissue invasion (p = 0.005), and CD44H expression (p = 0.01) were found to be significant prognostic parameters for survival using univariate analysis. Moreover, multivariate analysis indicated stage, nuclear grade and CD44 expression as independent prognostic factors both for overall and disease-free survival. CONCLUSION: CD44 can be considered as a useful prognostic parameter in conventional renal cell carcinoma and may be used in evaluation of the outcome of these tumors.
Complications of pancreas transplantation: radiological evaluation.
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Organ procurement by a transplant team outside of its original center: results of renal transplantation.
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Clonal analysis of renal sporadic angiomyolipomas.
Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.
Associative and limbic regions of monkey striatum express high levels of dopamine D3 receptors: effects of MPTP and dopamine agonist replacement therapies.
The role of the dopamine D3 receptor subtype in the central nervous system is still not well understood. It has a distinct and restricted distribution, mostly associated with limbic territories of the striatum (olfactory tubercle and the shell of nucleus accumbens) in rat brain. Dopaminergic denervation induced by a 6-hydroxydopamine lesion of the nigrostriatal system in rat down-regulates the expression of the D3 receptor. In the present study, we investigated the functional neuroanatomy of the dopamine D3 receptor subtype in the monkey (Macaca fascicularis) basal ganglia. We also studied the effect of administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and chronic D1-like (SKF 82958) or D2-like (cabergoline) agonist treatments on dopamine D3 receptor levels using receptor autoradiography. Our results clearly show that the distribution of D3 receptors in the monkey is more closely related to associative and limbic components of the striatum (caudate-putamen), as compared with its sensorimotor counterpart. Hence, D3 receptors may be more specifically involved in cognitive and motivational aspects of striatal functions, which are elaborated in prefrontal, temporal, parietal, cingulate and limbic cortices. Moreover, MPTP administration significantly decreased levels of D3 receptors and this effect was reversed or compensated by a chronic treatment with a D1-like, but not a D2-like, receptor agonist. The D3 receptor may represent an important target for adjunct or direct therapy designed to improve cognitive deficits observed in patients with Parkinson's disease, schizophrenia and other illnesses with frontal lobe cognitive disturbances.
Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association.
Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder.
Multiple congenital malformations associated with topical tretinoin.
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[Can the prostatic capsule be preserved during cystectomy for bladder tumors: a study of urethral and prostatic involvement in the cystectomy specimens].
OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective histological study was based on 260 specimens: radical cystectomies performed in 7 operative sites. The prostate and urethra were analysed in 3 planes (upper, middle and lower thirds). The apex was studied separately. Urethral invasion was identified by continuity of the tumour or by the presence of vesical CIS. RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to contiguous invasion (43/80). CIS is the second pathological association (44 urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency of urethral and prostatic involvement does not justify preservation of the prostate during cystectomy. A serial prospective study should define the precise criteria able to minimize the risk of conservative surgery.
[Pachydermoperiostosis with extramedullary hematopoiesis without myelofibrosis].
BACKGROUND: In three previous reports of primary hypertrophic osteoarthropathy, an associated extramedullary hematopoiesis was related to myelofibrosis. CASE REPORT: A 44-year-old male patient with primary hypertrophic osteoarthropathy diagnosed when he was 34-year-old was referred to our hospital with an abdominal mass fortuitously detected. DISCUSSION: The present case is unique for the patient developed an extramedullary hematopoïesis without associated myelofibrosis. It suggests the possible intervention of growth factors common to the skin fibroblasts and the blood progenitor cells in the pathogenesis of primary osteoarthropathy.
[Risk of complications during endovesical treatment with BCG for superficial tumor of the bladder].
OBJECTIVES: BCG therapy is the reference adjuvant treatment for multiple and voluminous or recurrent superficial bladder cancer and can cause specific complications. We assessed the frequency and therapeutic modalities involved associated with such complications in a personal retrospective series of patients. PATIENTS AND METHODS: BCG therapy was given to 148 patients who were followed for a mean 40 months. RESULTS: Forty-six percent of the patients developed a follicular reaction in the bladder wall: 14 developed complications requiring anti-tuberculosis treatment. The frequency of BCG therapy complications was higher in patients who had had tuberculosis previously (50%) than those who did not (13.8%). Complications were more frequent after early treatment. In the patients who developed BCGitis with fever, a 3-month regimen of rifampicin and isoniazine appeared to be sufficient. DISCUSSION: The frequency of BCG therapy complications (bladder anomalies excluded) was 7.8% with only 2.8% major complications. The development of a follicular reaction of the bladder wall does not appear to have any prognostic value. Special surveillance is needed in patients with a past history of tuberculosis. CONCLUSION: Adjuvant BCG therapy requires careful follow-up because of the risk of BCGitis which can be effectively treated with a 3-month double-antibiotic regimen.
Long-term results of combined kidney and liver transplantation at one center.
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Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein.
The kidney and several other thyroid hormone-responsive tissues contain a NADP-regulated thyroid hormone (TH)-binding protein (THBP), with an apparent molecular mass of 36 kDa on SDS-PAGE, responsible for most of the intracellular high-affinity T3 and T4 binding. THBP was purified to homogeneity from human kidney cytosol and used to generate proteolytic peptides. Microsequencing of four peptides revealed identity to amino acid sequences deduced from a human cDNA homolog to a cDNA encoding kangaroo mu-crystallin. This protein is a major structural kangaroo lens protein with no known function in other species. A full-sized cDNA (TH5.9) was isolated by 5'- and 3'-rapid amplification of cDNA ends using a human brain cDNA library and gene-specific PCR primers, confirming identity to the previously cloned human cDNA. The TH5.9 cDNA encodes a 314-residue protein (theoretical mol wt = 33,775) with significant homologies (40 to 60%) with two bacterial enzymes: lysine cyclodeaminase and ornithine cyclodeaminase. The TH5.9 cDNA was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein. Purified GST fusion protein, but not GST, bound T3 specifically with high affinity [dissociation constant (Kd) = 0.5 nM] in the presence of NADPH, and was labeled by UV-driven cross-linking of underivatized [(125)I]T3. T3 binding and photoaffinity labeling of GST fusion protein were activated by NADPH [activation constant (K[act]) = 10(-8) M], but not by NADH. The expressed protein displays the appropriate binding properties, indicating that TH5.9 cDNA encodes the NADP-regulated THBP characterized in human tissues.
Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson's disease.
The levodopa (LD) dose-antiparkinsonian response relationship becomes progressively steeper with advancing Parkinson's disease (PD). To establish the dose-response profile for the dyskinesiogenic effect of LD, we administered intravenous LD over a wide dose range to 25 patients with advanced PD. As expected in these patients with nonexistent therapeutic windows, the threshold doses (TD) for both motor effects were similar. Just around the TD, the relationship between LD dose and the magnitude of antiparkinsonian and dyskinesiogenic responses inclined steeply, reaching a plateau above 1.5 x TD. Response duration, however, continued to increase. The findings suggest that attempts to ameliorate dyskinesias in advanced PD patients by giving smaller, more frequent LD doses may be counter-productive due to shorter motor responses, more "off" time, and dose failures, while some may, in fact, benefit from higher LD doses to assure a full response and prolong its duration.