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Biomedical subjects

G Rodriguez

Publications and source records attributed to G Rodriguez.

At least 109 records · Page 6Linked to original sources

[Intra- and postoperative cerebral blood flow in patients with subarachnoid hemorrhage from a ruptured aneurysm].

The CBF of eight patients, who underwent surgery for ruptured aneurysm, was monitored using the termodiffusion technique (TDF). The device employed in this investigation allowed a continuous monitoring in "real time" of the cortical flow. The purpose of the study was to detect disorders of autoregulation, which were evaluated with the autoregulation index (AI). Autoregulation was correlated with the neurological preoperative grading, the postoperative changes of CBF (Xe133 clearance) and the outcome. The results of this preliminary study showed a correlation between these parameters and stressed the value of CBF monitoring during surgery.

Adult↗

Regulation of growth of normal ovarian epithelial cells and ovarian cancer cell lines by transforming growth factor-beta.

OBJECTIVE: The purpose of this study was to study the role of transforming growth factor-beta in regulation of proliferation of normal and malignant ovarian epithelial cells. STUDY DESIGN: We examined production of and responsiveness to transforming growth factor-beta in primary monolayer cultures of epithelial cells from five normal human ovaries and in five ovarian cancer cell lines. RESULTS: In normal ovarian epithelial cells, proliferation always was inhibited by transforming growth factor-beta (greater than 40%) (p less than 0.01). Among the cancer cell lines, proliferation of one was markedly inhibited (greater than 95%) (p less than 0.01), two were only modestly inhibited (15% to 20%) (p less than 0.05), and two were unaffected. In addition, we found that all of the normal ovarian epithelial cells and four of five ovarian cancer cell lines produce transforming growth factor-beta ribonucleic acid and protein. CONCLUSIONS: These data suggest that transforming growth factor-beta may act as an autocrine growth inhibitory factor for normal ovarian epithelium in vivo. Because most of the ovarian cancer cell lines are relatively resistant to the growth inhibitory effect of transforming growth factor-beta and because one cell line does not produce transforming growth factor-beta, it is possible that loss of the transforming growth factor-beta pathway may play a role in the development of some ovarian cancers.

Cell Division↗

Long-term anorectal function in imperforate anus treated by a posterior sagittal anorectoplasty: manometric investigation.

Thirty imperforate anus patients were investigated by anorectal manometry 5 to 10 years after a posterior sagittal anorectoplasty. Anal resting tone (ART) and anal squeezing pressure (ASP) were subnormal in most patients. Rectal volume (RV) and sensation to balloon distension were within the normal range. Rectoanal reflex inhibition was demonstrated in 9 of 30 patients. Soiling was more common in patients with a very low ART (less than 40 cm H2O) and a low ASP (less than 100 cm H2O). Constipation was more common in patients with a large RV (greater than 150 mL). Still, the correlation to clinical results was incomplete. As regards to the correlation to type of malformation the rectal atresia patients showed near normal results. The vestibular fistula patients were next in results showing rectoanal reflex inhibition in 5/6 patients. There was no difference in the results between bulbar and prostatic fistula patients.

Adolescent↗

Carcinoid tumor with skin metastasis.

An 80-year-old male patient presented with a 4-month history of nine extremely painful cutaneous nodules located on his forehead, neck, thorax, arms, and thighs. Biopsies of two nodules were performed. Routine histology, immunohistochemistry for chromogranin, as well as electron microscopy demonstrated that the nodules corresponded to cutaneous metastases of a carcinoid tumor, probably originated in the gastric antrum. The present description is, to the best of our knowledge, the first one to correlate the spontaneous and pressure-induced pain in the nodules with perineural invasion and neural sectioning by tumoral cells. S-100 protein and electron microscopy demonstrated numerous Langerhans cells among the tumoral cells.

Aged↗

A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days.

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A phase I clinical and pharmacokinetic trial of hepsulfam.

Hepsulfam (1,7-heptanediol-bis-sulfamate) is one of a series of bis-sulfamate acid esters that was synthesized in an attempt to improve the antitumor efficacy of busulfan. Hepsulfam has shown broad antineoplastic activity in preclinical studies. This Phase I trial evaluated hepsulfam given as a single i.v. dose every 21-35 days. Twenty-nine patients with refractory solid tumors participated in this study. Twenty-six of these patients had had either prior chemotherapy or radiation therapy. Fifty-two courses of treatment were given at doses ranging from 30 to 360 mg/m2/day. The dose limiting toxicity was prolonged thrombocytopenia and granulocytopenia. This toxicity was cumulative with Grade 3 or 4 thrombocytopenia occurring in 3 of 15, 4 of 9, and 2 of 2 patients in the first, second, and third courses of greater than or equal to 210 mg/m2, respectively. This toxicity was noted in patients with less than or equal to 1 prior chemotherapeutic regimen, as well as in patients with greater than 1 prior chemotherapeutic regimens. Nonhematological toxicities included Grade 1 or 2 nausea and vomiting and fatigue. There was no evidence of pulmonary toxicity. Plasma levels of hepsulfam were quantified by gas chromatography in 12 patients. The plasma and blood half-lives were 15.9 +/- 4.6 and 90 +/- 13 h, respectively. No objective tumor responses were seen. We conclude that the maximally tolerated dose when hepsulfam is given as a single dose every 35 days is 210 mg/m2, but that there is significant risk of cumulative hematological toxicity at this level.

Aged↗

Effects of beta-adrenoreceptor antagonists on cerebral blood flow of cirrhotic patients with portal hypertension.

The current study evaluated the effect of two beta adrenergic-blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133-Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end-tidal pCO2(PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P less than .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferroni's correction) showed a significant increase in CBF after ATN as compared with both placebo (P less than .02) and PRP (P less than .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.

Adrenergic beta-Antagonists↗

Regional cerebral blood flow asymmetries in a group of 189 normal subjects at rest.

Regional cerebral blood flow (rCBF) asymmetries were studied in 189 subjects (96 males and 93 females) at rest with the 133Xenon inhalation method using a fixed detector system. rCBF asymmetries in the resting condition were very small, nevertheless a significant (p less than 0.001) effect for their topographical distribution was present, reflecting higher rCBF in the right fronto-temporal and left parieto-occipital regions. rCBF asymmetries were not correlated with age, and there were no significant differences between males and females. Asymmetries are therefore useful from a statistical point of view in detecting rCBF abnormalities in the resting condition: they are more stable than absolute values in normal subjects and no matching according to age or sex is required when statistical comparisons are performed.

Adolescent↗

Spinal cord stimulation and cerebral haemodynamics.

An increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglio et al. (1988) using the 133-Xenon wash-out technique. In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1-verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same. Finally, in two patients the effect of SCS on CO2 autoregulation was studied with TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF.

Blood Flow Velocity↗

CBF side-to-side asymmetries in stenosis-occlusion of internal carotid artery. Relevance of CT findings and collateral supply.

Cerebral blood flow (CBF) was studied at rest by 133-Xenon inhalation method in 15 normal subjects, in 10 patients with cerebral infarction and normal angiograms of major cerebral arteries and in 28 patients with unilateral stenosis-occlusion of the internal carotid artery (ICA), with or without cerebral infarction. All the normals and 20 patients with ICA stenosis-occlusion were tested again after cerebral vasodilatation induced by an intravenous bolus of acetazolamide. At rest the patients with cerebral infarction, irrespective of whether ICa stenosis-occlusion was present or not, showed abnormal side-to-side CBF asymmetry. After cerebral vasodilation variations in side-to-side asymmetry were shown to depend on the inefficiency of the collaterals and not on the degree of ICA obstruction or on the presence of cerebral infarction. These data indicate that at rest side-to-side CBF distribution is influenced more by the presence of an ischemic zone than by a ICA stenosis-occlusion and that under these circumstances the hemodynamic effect of the vascular stenosis cannot be assessed. After cerebral vasodilatation a subset of patients--irrespective of the degree of ICA obstruction and of whether or not cerebral infarction is present--with true cerebrovascular insufficiency can be isolated.

Acetazolamide↗

Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease.

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.

Adenocarcinoma↗

Brain functional imaging in senile psychopathology.

Quantified electroencephalogram (EEG) and regional cerebral blood flow (rCBF) measurements are reliable and currently employed techniques in the functional exploration of the aging brain; they can be routinely employed, since discomfort to the patient is minimal. Topographical analysis of EEG and rCBF results is performed in our laboratory by a fully automated mapping system, which also enables statistical comparisons in real time. The goal of our study is to ascertain if there are systematic modifications in the topographic distribution of rCBF and EEG parameters in normal aging, dementia, cerebrovascular disease and in conditions of increased risk for cerebral pathology (e.g. hypertension). Dementias and cerebrovascular pathologies present characteristic brain functional abnormalities, which can be detected by comparing the patient data to an age-matched normal population by the appropriate statistical tests; therefore, the accurate selection of healthy aged controls appears as a crucial issue in order to improve the sensitivity of statistics.

Adult↗

Changes in infratentorial blood flow following experimental cerebellar haemorrhage. A preliminary report.

The temporal progression of changes in blood flow within the hemispheric cerebellar cortex, following an experimental cerebellar ipsilateral haemorrhage, was investigated in rats by using the hydrogen clearance technique. Stereotactical injection of 50 microliters of fresh autologous blood into the paramedian white matter was found to produce an early drop of cerebellar blood flow, with subsequent rise toward higher values. An increase of the intracranial pressure only occurred at the time of injection of blood. Arterial blood gases, mean arterial blood pressure and blood glucose levels did not exhibit significant changes. Histochemical evaluations of glycogen phosphorylase showed a posthaemorrhagic pattern of enzyme depletion, consistent with the occurrence of an ischaemic damage in both the cerebellum and the brain stem.

Animals↗