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Biomedical subjects

C Franco

Publications and source records attributed to C Franco.

At least 37 records · Page 2Linked to original sources

Postchemotherapy late recurrence of non metastatic gestational trophoblastic disease following a partiale mole. A case report.

The authors describe a case of a 35-year-old woman who showed elevation of betahCG 13 months after the complete regression of betahCG values following chemotherapy for an incomplete mole. This case outlines the necessity for careful monitoring of betahCG levels in low risk gestational trophoblastic diseases for a period of time longer than one year after achieving the first clinical remission.

Abortion, Spontaneous↗

Determination of clenbuterol residues in bovine hair by using diphasic dialysis and gas chromatography-mass spectrometry.

A method for the determination of clenbuterol (4-amino-3,5-dichloro-alpha[(tert.-butylamino)methyl]-benzyl alcohol hydrochloride) in hair of living cows has been developed. Hair samples were digested in an alkaline medium. The diphasic dialysis technique is a semi-permeable membrane technology developed for the direct extraction of relatively low-molecular-mass analytes such as clenbuterol. In this case, we used sodium citrate buffer to homogenize the digested hair, dichloromethane was used as the extraction solvent at 37 degrees C, and stirring was applied at 150 rpm for 4 h. The analysis was carried out using gas chromatography-mass spectrometry. The calibration curve for clenbuterol in hair was linear in the range from 12.5 to 400 ng g(-1). The detection limit of clenbuterol was 5 ng g(-1) and the quantification limit was 12.5 ng g(-1), in hair. A good inter-day reproducibility was obtained (R.S.D. = 7.08%). The repeatability and intra-day reproducibility (50 ng g(-1) of hair, n = 10) show R.S.D.s of 7.1 and 9.5%, respectively.

Animals↗

Determination of dexamethasone in bovine liver by chemiluminescence high-performance liquid chromatography.

A new method for the determination of dexamethasone (9alpha-fluoro-11beta,17alpha,21-trihydroxy-16alpha -methylpregna-1, 4-diene-3,20-dione) in bovine liver was developed. This new liquid-liquid extraction method comprises the addition of sodium hydroxide to the tissue sample followed by extraction with ethyl acetate. After centrifugation, the extract is evaporated to dryness and the residue dissolved in acetonitrile. The cleaning of the fat is performed with n-hexane, and the acetonitrile layer is evaporated. Analysis of the extracts is performed using high-performance liquid chromatography with chemiluminescence detection employing luminol as CL reagent. A series of recovery curves performed at spiking levels of 50, 30, 10, 5, and 2.5 ppb show that at least 80% of DEX can be recovered from liver and that the chemiluminescence detection yields satisfactory results with respect to sensitivity (LOD 0.2 ppb), reproducibility (CV% 10.7) and repeatability (CV% 6.2-8.9).

Animals↗

Mobilization of peripheral blood stem cells with docetaxel and cyclophosphamide (CY) in patients with metastatic breast cancer: a randomized trial of 3 vs 4 g/m2 of CY.

The purpose of this study was to develop a regimen of docetaxel, cyclophosphamide (CY) and filgrastim for mobilization of peripheral blood stem cells (PBSC) in patients with metastatic breast cancer (n = 66). A phase I trial of CY 2, 3 or 4 g/m2 with docetaxel 100 mg/m2, in consecutive cohorts of four patients each, did not reveal any dose-limiting toxicities and subsequent patients were randomized to receive 3 or 4 g/m2 of CY. The median yield of CD34+ cells from all patients was 11.06x10(6)/kg (range, 0.03-84.77) from a median of two aphereses (range, 1-7); 6.52x10(6) CD34+ cells/kg/apheresis (range, 0.01-52.07). Target CD34+ cell doses > or =2.5 and > or =5.0x10(6)/kg were achieved in 89% and 79%, respectively. There were no statistically significant differences in CD34+ cell yields or target CD34+ cell doses achieved following 3 or 4 g/m2 of CY. Patients with only one prior chemotherapy regimen yielded a median of 12.82x10(6) CD34+ cells/kg/apheresis compared to 5.85 for those receiving > or =2 regimens (P = 0.03). It was concluded that the combination of docetaxel, 100 mg/m2, CY 3 g/m2 without mesna could be administered with acceptable toxicity with collection of adequate quantities of PBSC from the majority of patients.

Adult↗

[Insular carcinoma of the thyroid].

We report 5 cases of insular carcinoma of the thyroid. Most patients were females (80%) with an age range of 28 to 75 years. Treatment consisted of total or near total thyroidectomy plus modified cervical lymph node dissection in cases with lymph node metastasis. This was followed by radioiodine therapy and external radiation therapy in patients with residual disease. None of the patients had distant metastasis. However, three patients with involvement of the perithyroid soft tissue died within 4 years of the diagnosis. The other two patients are alive without evidence of disease. This type of thyroid carcinoma has an aggresive clinical course with frequent extension to the adjacent soft tissue associated to poor outcomes.

Adult↗

[Hürthle cell carcinoma of the thyroid. A 41 years experience].

BACKGROUND: Hürthle cells can be found in non malignant thyroidal diseases such as Basedow Graves and Hashimoto diseases. When Hürthle cells comprise more the 75% of cellularity, they become a neoplasm. There are malignant variants of these neoplasms, constituted by follicular and papillary Hürthle cell carcinomas. AIM: To report a 41 years experience with Hürthle cell carcinomas of the thyroid. MATERIAL AND METHODS: A retrospective review of all patients operated for a thyroid carcinoma and selection of those patients with Hürthle cell carcinoma of the thyroid. RESULTS: Twenty two patients (21 female, mean age 48 years old) with Hürthle cell carcinoma of the thyroid were selected. Total or near total thyroidectomy was the treatment of choice in 20 and 19 received 131I. Metastatic involvement of cervical lymph nodes was found in five patients and they underwent modified cervical lymph node dissection. During follow up, only one patient died of the disease. We did not find higher incidences of local recurrences, distant metastases or mortality rates, compared to well differentiated thyroid carcinomas. CONCLUSIONS: Hürthle cell carcinomas of the thyroid and well differentiated thyroid carcinomas have similar biological behaviors. Their treatment should be similar, including total or near total thyroidectomy plus modified cervical node dissection when there is lymph node involvement. Radioactive iodine therapy and suppressive levothyroxin therapy should follow.

Adenocarcinoma↗

Dexamethasone-induced changes in FAD-glycerophosphate dehydrogenase mRNA, content and activity, and insulin release in human pancreatic islets.

Human pancreatic islets were cultured for 63 hr at 2.8 or 16.7 mM D-glucose in the absence or presence of dexamethasone. In the 1.0 to 10 microM range, dexamethasone caused a concentration-related decrease in the FAD (flavin adenine dinucleotide)-linked mitochondrial glycerophosphate dehydrogenase (mGDH) mRNA content of the islets, and decreased both the mGDH content of the islets and the catalytic activity of the enzyme in islet homogenates, these effects being often more marked in islets cultured at 16.7 mM, rather than 2.8 mM, D-glucose. Even after culture in the presence of no more than 10 nM dexamethasone, namely under conditions in which the mGDH mRNA content and activity were both virtually unaffected, the corticosteroid restored the capacity of the beta-cells to display an increase in insulin output in response to a rise in D-glucose concentration in islets first cultured at 2.8 mM D-glucose but suppressed the insulinotropic action of the hexose in islets first cultured at 16.7 mM D-glucose. Whilst revealing an untoward effect of high concentrations of dexamethasone upon mGDH mRNA, content and activity in human islets, these findings also document a dual effect of a low concentration of the corticosteroid (10 nM) upon the secretory responsiveness of human islets to D-glucose, independently of any significant change in mGDH gene expression. It is proposed that such a dual action may account, in part at least, for both the well known increase in insulin output found in hypercorticism and the more recently discovered unfavourable direct effect of corticosteroid hormones on the secretory activity of islet beta-cells.

Adult↗

Site-directed mutations of the FAD-linked glycerophosphate dehydrogenase gene impairs the mitochondrial anchoring of the enzyme in transfected COS-7 cells.

COS-7 cells were transfected with the green fluorescent protein (GFP) of Aequorea victoria, human mitochondrial FAD-linked glycerophosphate dehydrogenase (mGDH), a mGDHwt-EGFP construct, or two mutant mGDH-proteins fused with EGFP. The site of mutation was selected to affect cationic amino acids in the peptide signal sequence currently believed to play a key role in the subcellular distribution of mitochondrial proteins. All proteins were suitably expressed in the COS-7 cells. However, an increase in mGDH enzymatic activity above the control value in non-transfected COS-7 cell homogenates was only observed in cells transfected with mGDH, indicating that the catalytic activity of mGDH was masked in fused proteins. Confocal microscopy documented that, in the cells transfected with the mGDHwt-EGFP construct, the fusion protein was located exclusively in mitochondria, this contrasting with the nuclear labelling of cells expressing the green fluorescent protein alone. The mitochondrial anchoring of the mutated mGDH fused protein was altered, this alteration being most obvious in the mGDH313233-EGFP mutant. These findings raise the idea that a conformation change of the mGDH protein, as resulting from either an inherited or acquired alteration of its amino acid sequence, may affect its subcellular distribution and, hence, modify its immunogenic potential.

Amino Acid Sequence↗

Reduction of islet amylin expression and basal secretion by adenovirus-mediated delivery of amylin antisense cDNA.

Reduction of amylin content and secretion in rat islets was attempted by transduction with an adenovirus bearing a 0.2-kb fragment of rat amylin cDNA inserted in the antisense orientation (AdCMV-alpha amylin). Exposure of islets to AdCMV-alpha amylin at a multiplicity of infection (moi) of 200 (1.2 x 10(7) pfu/ml) reduced amylin mRNA levels by 37 +/- 5% (p < 0.005), whereas infection with an adenovirus expressing the reporter gene of beta-galactosidase (AdCMV-lacz) did not modify amylin expression. Transduction with the antisense construct was specifically associated with the decrease (30 +/- 6%; p < 0.001) in the amylin content. Insulin content was unaltered in AdCMV-alpha amylin islets compared to AdCMV-lacz-transduced or untransduced cells. Basal amylin secretion (2.8 mM glucose) was 36 +/- 3% (p < 0.005) lower in AdCMV-alpha amylin islets than in untransduced or AdCMV-lacz-transduced islets. In contrast, no difference in amylin secretion in response to high glucose concentrations (16.7 mM) was detected in AdCMV-alpha amylin-transduced islets. Thus, a reduction of amylin content and basal secretion in islet cells can be achieved by the adenovirus-mediated expression of antisense RNA.

Adenoviridae↗

Presence of the 918 mutation in the RET proto-oncogene in a Mexican patient with multiple endocrine neoplasia type 2B.

The dominantly inherited Multiple Endocrine Neoplasia cancer syndrome type 2B (MEN2B) is characterized by the presence of medullary thyroid carcinoma (MTC), phaechromocytoma (PHAEO), mucosal neuromas, ganglioneuromas of the intestinal tract, skeletal and ophthalmic abnormalities. MEN2B has been associated with a specific point mutation in the tyrosine kinase domain of the RET proto-oncogene (918RET mutation). We investigated a Mexican patient MEN2B for the presence of the 918RET mutation using the polymerase chain reaction followed by restriction endonuclease digestion. We have detected this mutation in DNA from the patient's MTC, PHAEO, and peripheral blood cells, but not in DNA from the patient's mother, suggesting that this mutation arose de novo. Our results are in agreement with the suggestion that the 918RET mutation is present in a vast majority of MEN2B cases around the world.

Adult↗

[Carpal tunnel syndrome: clinical and neurophysiological correlation: review of 100 cases].

INTRODUCTION: The diagnosis of carpal tunnel syndrome (CTS) continues to be neurophysiologically and clinically controversial. This study attempts to find the correlation between the subjective symptomatology and the neurophysiological affectation, establishing a diagnostic guide for the family doctor in order to recognize early CTS for referral to the specialist doctor. PATIENTS AND METHODS: After a sample of 100 cases with clinical suspicion of CTS, a clinical evaluation was made with the symptoms (paresthesias, pain, loss of strength), signs (Tinel, Phalen), and the neurophysiological evaluation with electroneurography (ENG) of the median and cubital nerve (sensory velocity (SV), motor distal latency (MDL)), and electromyography (EMG) of tenar eminence muscles. With this data an epidemiological study was made with correlation between the clinical and neurophysiological parameters. RESULTS: The patients with pain, loss of strength and Tinel's sign had significant alteration of the parameters of ENG and EMG. Tinel's sign had a sensitivity (SE) = 30.1% and a specificity (SP) = 73% for MDL, a SE = 32.5% and a SP = 88.2% for SV. Phalen's sign had a SE = 22.2% and a SP = 94.6% for MDL, a SE = 18.1% and a SP = 94.1% for SV. CONCLUSIONS: The guide to recognize clinically the patients which must be studied neurophysiologically that have a high probability to suffer CTS is: diagnosis for motor alteration, pain (SE = 79%), loss of strength (SP = 86%) and Phalen's sign (SP = 94.6%). Sensory alteration: paresthesias (SE = 97%), Tinel's sign (SP = 88.2%) and Phalen's sign (SP = 94.1%).

Adult↗

Determination of residues of the beta-agonist clenbuterol in liver of medicated farm animals by gas chromatography-mass spectrometry using diphasic dialysis as an extraction procedure.

A method has been developed for the rapid confirmation of clenbuterol in cow liver using gas chromatography coupled with detection by mass spectrometry of the trimethylsilyl derivatives of clenbuterol. The technique used for the extraction was diphasic dialysis. It was observed that the best suitable solution to homogenize the liver the barium hydroxide-barium chloride buffer, the optimal extraction solvent was tert.-butylmethyl ether at an extraction temperature of 37 degrees C, and stirring should be applied at 150 rpm for 4 h. This extraction method improves clenbuterol recovery up to values of 99.3%. With the use of the barium buffer, derivatization is performed more efficiently and the detection and quantification limits can be decreased to values close to 250 ppt and 500 ppt, respectively.

Adrenergic beta-Agonists↗

Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases.

To contribute to a better understanding of the prognostic differences between atypical and malignant meningiomas as defined by the World Health Organization (WHO) and the influence of the grade of initial surgical excision on postoperative course, 42 cases of atypical and 29 of malignant meningioma were studied, along with long-term follow up. The two groups were compared with respect to long-term survival, recurrence-free survival, and median time to recurrence. The prognostic significance of the Simpson grade of surgical resection and tumor location was also considered. Survival at 5 and 10 years was recorded in 95% and 79%, respectively, of patients with atypical meningioma and in 64.3% and 34.5% of patients with malignant meningioma (p = 0.001). Recurrence-free survival and median time to recurrence were also significantly longer in patients with atypical than in those with malignant meningiomas: 11.9 versus 2 years (p = 0.001) and 5 versus 2 years (p < 0.0041), respectively. Six (26%) of the 23 recurring atypical meningiomas became malignant. Simpson Grade I resection and location in the cerebral convexity, which were closely related, were found to be associated with a significantly better clinical course in the entire series (p < 0.0016). Patients with atypical meningiomas fared better than those with malignant meningiomas after incomplete surgical excision (Simpson Grades II-III), but the difference was not statistically significant. Multivariate analysis using the Cox model indicated that radical extirpation (Simpson Grade I vs. II-III) and histological findings (atypical meningioma vs. malignant meningioma) were significantly related to prolonged survival (p < 0.0003 and p < 0.0388, respectively). In conclusion, the current study shows that for most patients with atypical meningioma the prognosis was less severe than for those with malignant meningioma, but the risk of a downhill course resulting from malignancy after incomplete resection and recurrence was not negligible (26%). In addition, the WHO classification was found to be inadequate for a minority of the atypical meningioma cases, which currently have the same unfavorable course as cases of malignant meningioma. The results also indicate that objective Simpson Grade I extirpation of convexity meningiomas can be successful despite histological findings of malignancy.

Journal Article↗

Mutation in the calcium-binding domain of the mitochondrial glycerophosphate dehydrogenase gene in a family of diabetic subjects.

The Ca(2+)-sensitive and mitochondrial enzyme FAD-linked glycerophosphate dehydrogenase (m-GDH) represents an essential component of the pancreatic B-cell glucose-sensing device. This report deals with the first identified case of mutation in the calcium-binding domain of the m-GDH gene in a patient with type-2 diabetes and his glucose-intolerant half sister. Single strand conformation polymorphism analysis indeed revealed an abnormal mobility of the 32P-labelled polymerase chain reaction product in these two subjects. The corresponding base pair mutations and amino acid changes were documented. In the diabetic proband, the relative extent of the Ca(2+)-induced activation of m-GDH in CD3+ T-lymphocytes was lower than in his brother with a normal m-GDH gene sequence.

Base Sequence↗

Nucleotide sequence of cDNA fragments coding for the FAD-,glycerophosphate- and calcium-binding domains of human islet mitochondrial glycerophosphate dehydrogenase.

The cDNA fragments coding for the FAD-, glycerophosphate- and calcium-binding domains of mitochondrial glycerophosphate dehydrogenase (mGDH) were synthetized using RNA extracted from freshly isolated pancreatic islets of a normal subject and two-non-insulin-dependent diabetic patients. Single strand conformation polymorphism analysis of the PCR products yielded the same mobility as control cDNA probes. Likewise, the nucleotide sequence and corresponding amino acid sequence were identical to the normal gene bank sequence. These findings argue against the presence, in pancreatic islets, of an mGDH isoform distinct from that previously characterized in extrapancreatic organs.

Aged↗

Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases.

To contribute to a better understanding of the prognostic differences between atypical and malignant meningiomas as defined by the World Health Organization (WHO) and the influence of the grade of initial surgical excision on postoperative course, 42 cases of atypical and 29 of malignant meningioma were studied, along with long-term follow up. The two groups were compared with respect to long-term survival, recurrence-free survival, and median time to recurrence. The prognostic significance of the Simpson grade of surgical resection and tumor location was also considered. Survival at 5 and 10 years was recorded in 95% and 79%, respectively, of patients with atypical meningioma and in 64.3% and 34.5% of patients with malignant meningioma (p = 0.001). Recurrence-free survival and median time to recurrence were also significantly longer in patients with atypical than in those with malignant meningiomas: 11.9 versus 2 years (p = 0.001) and 5 versus 2 years (p < 0.0041), respectively. Six (26%) of the 23 recurring atypical meningiomas became malignant. Simpson Grade I resection and location in the cerebral convexity, which were closely related, were found to be associated with a significantly better clinical course in the entire series (p < or = 0.0016). Patients with atypical meningiomas fared better than those with malignant meningiomas after incomplete surgical excision (Simpson Grades II-III), but the difference was not statistically significant. Multivariate analysis using the Cox model indicated that radical extirpation (Simpson Grade I vs. II-III) and histological findings (atypical meningioma vs. malignant meningioma) were significantly related to prolonged survival (p < 0.0003 and p < 0.0388, respectively). In conclusion, the current study shows that for most patients with atypical meningioma the prognosis was less severe than for those with malignant meningioma, but the risk of a downhill course resulting from malignancy after incomplete resection and recurrence was not negligible (26%). In addition, the WHO classification was found to be inadequate for a minority of the atypical meningioma cases, which currently have the same unfavorable course as cases of malignant meningioma. The results also indicate that objective Simpson Grade I extirpation of convexity meningiomas can be successful despite histological findings of malignancy.

Female↗

Clinical algorithm for treatment of Plasmodium falciparum malaria in children.

BACKGROUND: Identification of children who need antimalarial treatment is difficult in settings where confirmatory laboratory testing is not available, as in much of sub-Saharan Africa. The current national policy in Malawi is to treat all children with fever, usually defined as the mother's report of fever in the child, for presumed malaria. To assess this policy and to find out whether a better clinical case definition could be devised, we studied acutely ill children presenting to two hospital outpatient departments in Malawi. METHODS: The parent or guardian of each enrolled child (n = 1124) was asked a standard series of questions about the symptoms and duration of the child's illness. Each child was examined, axillary and rectal temperatures and blood haemoglobin concentrations were measured, and a giemsastained thick smear was examined for malaria parasites. Logistic regression procedures were used to identify clinical predictors of parasitaemia. FINDINGS: High temperature (37.7 degrees C or above), nailbed pallor, enlarged spleen, and being seen at one of the clinics rather than the other were associated with an increased risk of malaria parasitaemia in univariate analyses. A revised malaria case definition of rectal temperature of 37.7 degrees C or higher, splenomegaly, or nailbed pallor was 85% sensitive in identifying parasitaemic children and 41% specific; the corresponding sensitivity and specificity for the nationally recommended definition that equates mother's history of fever with malaria were 93% and 21%. The revised case definition had 89% sensitivity in identifying parasitaemic children with haemoglobin concentration below 80 g/L and 89% sensitivity in identifying children with parasite density greater than 10,000/microL, characteristics that indicate a clear need for antimalarial treatment. INTERPRETATION: These results suggest that better clinical definitions are feasible, that splenomegaly and pallor are helpful in identifying children with malaria, and that much overtreatment of children without parasitaemia could be avoided.

Algorithms↗