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Biomedical subjects

R Blanco

Publications and source records attributed to R Blanco.

At least 145 records · Page 8Linked to original sources

Ultrasonic mucosectomy of the gallbladder. A histological analysis.

The Cavitron Ultrasonic Surgical Aspirator (CUSA) may be used to remove mucosa of organs of the gastro-intestinal tract. A histological analysis was performed on gallbladders treated with a CUSA-mucosectomy to assess the extent and degree of mucosectomy and to evaluate parietal damage. The histological studies performed on three specimens of chronic cholecystitis revealed a complete mucosectomy except in areas where Rokitansky-Aschof sinuses were present. There was no evidence of parietal damage. The CUSA may be used to remove the mucosa of gallbladders without injury to other layers, and may have a potential application in procedures such as mucosal cholecystectomy.

Cholecystitis↗

Rapid and sustained hematopoietic reconstitution by peripheral blood stem cell infusion alone following high-dose chemotherapy.

We utilized mobilized peripheral blood stem cells (PBSC) as sole support for hematologic reconstitution following high-dose chemotherapy in 52 patients with advanced solid tumors and lymphoma. PBSC were collected by large scale leukapheresis after mobilization with chemotherapy. Each apheresis product was analysed for total nucleated cells, CFU-GM and CD34+ content. Disease-specific high-dose chemotherapy regimens were administered followed by thawed PBSC. Colony-stimulating factors were not administered. The median time to an absolute neutrophil count > 0.5 x 10(9)/l was 13 days (range 9-26 days) and median time to a sustained platelet count > 20 x 10(9)/l without transfusion support was 10 days (range 5-43 + days). There was no difference in time to recovery by dose-intensive regimen or underlying disease. The times to recover ANC and platelets both correlated significantly with increasing doses of PBSC as assayed by CD34+ cells and CFU-GM. All four patients with prolonged platelet recovery times received < 20 x 10(4) CFU-GM/kg, establishing this as a threshold value for PBSC infusion. There were no late transient or sustained graft failures. For 26 patients alive 1 year after infusion, the mean total leukocyte count is 6.3 x 10(9)/l, mean hematocrit 35.5% and mean platelet count 182 x 10(9)/l. Thirteen patients followed at least 24 months after PBSC infusion have essentially normal blood counts. Mobilized peripheral blood progenitors are an effective source of stem cells which afford rapid and complete hematopoietic engraftment after myelo-suppressive chemotherapy regimens. Engraftment appears sustained with no late failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Evidence of a major gene in cleft lip/palate susceptibility by means of segregational analysis in the Chilean population].

The most generally accepted model for cleft lip/palate not associated to specific syndromes has been the one that postulates multifactorial inheritance with a threshold. Recent studies using complex analytical techniques have suggested the existence of a major gene with decreased penetrance in its etiology. Some authors have postulated that only a fraction of all cases of non-syndromic CL (P) would be explained by a single major gene. Other cases may be due to different genes, to environmental agents or to the interaction between them. The present study tests the monogenic inheritance model for CL (P) using segregation analysis in a sample of 211 extended pedigrees collected through CL (P) affected probands. The hypotheses of an autosomic recessive gene was analyzed in 151 sibships (size 2 or more) using "Apert's" method, "maximum likelihood method", "singles method" and "sib's, method" (single incomplete ascertainment). Results obtained do not support the hypotheses of autosomal recessive inheritance. Instead, the hypothesis of an autosomal dominant mode of inheritance with low penetrance is not rejected when analyzing the proportion of normal and affected progeny in certain types of matings in a subsample of 30 extended pedigrees with two or more affected individuals.

Chile↗

[Cleft lip and palate in the Chilean population: association with BamH1 polymorphism of the transforming growth factor alpha (TGFA) gene].

In recent studies we have demonstrated that the model that better explains the genetic etiology of non syndromic cleft lip/palate (CL/P) in the Chilean population is one that postulates the existence of a major dominant autosomic locus with low penetrance, without discarding the possible influence of polygenes. Similar conclusions have been communicated by others authors in different populations. Thus, investigations have been initiated to seek possible associations between candidate genes and restriction length polymorphisms (RFLP's), specifically between Transforming Growth Factor Alpha (TGFA) gene RFLP's and CL/P, in caucasian populations. Results thus far obtained have been inconclusive. Therefore, the aim of this work was to study this association in the Chilean population, that is ethnically different. The gene and phenotype frequencies of the TGFA gene BamH1 polymorphism in CL/P probands (n = 21) and controls (n = 16) were determined. No significant differences were detected in the frequencies of the A1 and A2 alleles of the TGFA gene between probands and controls. These results do not support an association between the cleft palate phenotype and TGFA RFLP.

Autoradiography↗

Long-term abrogation of autoimmune diabetes in nonobese diabetic mice by immunotherapy with anti-lymphocyte serum.

We investigated the therapeutic effect of anti-lymphocyte serum (ALS) on clinically overt diabetes by using a nonobese diabetic (NOD) mouse model of type I diabetes mellitus. ALS given within 14 days of disease onset gradually reversed hyperglycemia with a 76% cumulative incidence of remission. Combined use of anti-CD4 and anti-CD8 monoclonal antibodies, but not anti-CD4 or anti-CD8 antibody alone, was also effective with overall 64% remission. Diabetic NOD mice that failed to respond to ALS treatment accepted subsequent islet isografts for a prolonged period (mostly greater than 100 days), whereas islet isografts in diabetic NOD mice previously treated with normal rabbit serum were all destroyed as acutely as isografts in untreated diabetic NOD mice. These results suggest that persistence of diabetes was due to irreversible beta-cell destruction and that ALS has indeed abrogated autoimmunity. In addition, ALS treatment at the time of islet isografting achieved significant prolongation of graft survival with 8 of 13 mice maintaining euglycemia for greater than 100 days. Although ALS prolonged islet allograft survival in diabetic NOD mice, the degree of prolongation was much less for allografts than for isografts, suggesting that ALS is capable of suppressing autoimmunity more effectively than allograft responses.

Animals↗

Peripheral blood stem cell mobilization by chemotherapy with and without recombinant human granulocyte colony-stimulating factor.

Chemotherapy can serve as a stimulus for mobilizing hematopoietic progenitor cells to the peripheral blood for harvest via leukapheresis. Mobilized peripheral blood stem cells (PBSC) support rapid hematologic reconstitution after bone marrow aplasia induced by intensive myelosuppressive treatments. Our purpose was to develop effective mobilization regimens allowing collection of large quantities of PBSC. We administered high-dose cyclophosphamide (HDC, 4 gm/m2) or cyclophosphamide (4 gm/m2) plus etoposide (600 mg/m2) (HDCE) in a nonrandomized, sequential fashion to 94 patients with breast cancer, lymphoma, and other malignancies with collection of PBSC via leukapheresis during white blood cell (WBC) recovery from nadir counts. Each apheresis product was analyzed for total nucleated cell number, granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Twenty-four additional patients with comparable pretreatment characteristics received HDCE plus recombinant human granulocyte colony-stimulating factor (HDCE+G) after chemotherapy through the end of apheresis. Patients receiving HDC were matched for age, sex, and disease but were more heavily pretreated. HDCE was superior to HDC in mean daily CFU-GM and CD34+ yield (p < 0.05), even when groups were adjusted for performance status and amount of prior therapy. HDCE+G led to 3.7 times more CFU-GM and 4.7 times more CD34+ cells than HDCE. Target PBSC yield, defined as > 20 x 10(4) CFU-GM/kg and >4 x 10(8) cells/kg, was achieved by 92% of HDCE+G patients after a median of three aphereses, 56% of HDCE patients after five aphereses, and 16% of HDC patients after six apheresis (p < 0.0001). Prior chemotherapy inversely correlated with the quantity of PBSC harvested regardless of regimen utilized. Our results demonstrate effective chemotherapy regimens for harvesting hematopoietic progenitors in a diverse patient population. HDCE+G produced the highest number of progenitors, suggesting that increasing dose intensity and adding rhG-CSF enhances mobilization. Correlation between cumulative CD34+ and CFU-GM allows real-time flow cytometric analysis of the number of aphereses required to harvest target numbers of PBSC.

Adolescent↗

[Cleft lip and cleft palate: cephalometric characteristics of affected individuals, their relatives and a control population].

Eight cephalometric parameters were determined in individuals affected with cleft lip and cleft palate, their parents and siblings and a sample of normal individuals. No differences were found in males in any group. In contrast, affected females had lower measurements than their female relatives, and these lower latter in turn had measurements than control females. Although differences between groups were significant enough overlap existed and therefore genetic counseling based on these measurements would be uncertain.

Adolescent↗

[Familial association of epilepsy and cleft palate: an expression of predisposed common genetic factors or a teratogenic effect of the epilepsy genotype?].

The familial association of epilepsy and cleft lip with or without cleft palate (CL (P)) is analyzed assuming both entities share common genetic predisposing factors. The genealogical data stemming from 169 CL (P) probands and 168 epileptic probands yielded information on the prevalence rates of cleft and epileptic relatives. The working hypothesis assumes that the relatives of epileptic and cleft probands should have a greater liability to CL (P) and epilepsy, respectively. The results obtained do not support the hypothesis of an etiologic association given that a greater joint prevalence of epileptic and cleft relatives is only observed when the proband is epileptic and not with a cleft proband. This situation seems to reflect a teratogenic effect of the epileptic genotype which expresses itself in those individuals which simultaneously present a greater liability to cleft.

Cleft Lip↗

[Paternity study in Chilean families using DNA fingerprints and erythrocyte blood markers].

In the last decade, the electromorphic phenotype corresponding to extremely polymorphic zones of DNA, that include variable number of tandem repeat loci (VNTR) of oligonucleotide sequences, have been added to classical markers to elucidate the problems of parenthood identification and ascription in human beings. Using VNTR of several loci, a band profile practically unique for each individual is obtained (DNA-fingerprints). Since the pattern of VNTR electrophoretic bands is inherited from parents in a proportion of 50% from each one, this system is extremely useful for paternity ascription or exclusion. Nine nuclear families were studied, randomly selected from a group of 170 families that were analyzed using 5 erythrocyte genetic markers and with VNTRs detected using the multi locus probe (CAC)5, aiming to explore the concordance of both methods. Results were similar for both methods; however for VNTR, there is no information available on population frequency of polymorphisms.

Blood Group Antigens↗

Adsorption-desorption isotherm hysteresis of beta-lactoglobulin A with a weakly hydrophobic surface.

Adsorption-desorption isotherms of bovine beta-lactoglobulin A (beta-lact A) on a weakly hydrophobic stationary phase (C1-ether) were measured by frontal analysis. The adsorption isotherms obtained at different pH were found to be dramatically different in shape, column capacity and desorption reversibility. At pH 4.5, an S-shaped adsorption isotherm was observed whereas at pH 6.0 a Langmuir isotherm was found. In addition, the desorption isotherm at pH 6.0 was found to overlap with the adsorption isotherm, and the adsorption-desorption process of beta-lact A under this condition could be characterized by a fully reversible Langmuir model. The desorption isotherm at pH 4.5, however, did not retrace the adsorption isotherm, resulting in hysteresis loops. A higher aggregate (tetramer) of beta-lact A is shown to be in an equilibrium with the beta-lact A protomer (dimer) at pH 4.5 whereas the dimer alone is predominant at pH 6.0. It is further shown that changes in the absorption coefficient between the adsorption and the desorption cycles for the tetramer at pH 4.5 can account for the hysteresis. The results demonstrate that pH can be a sensitive parameter in protein adsorption isotherm behavior and ultimately the behavior of species in preparative-scale chromatography.

Adsorption↗

Pathophysiology of prolonged penile erection associated with trazodone use.

Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence.

Adolescent↗

Bone marrow regeneration after hormonal therapy in patients with bone metastases from prostate carcinoma.

Two patients with prostate carcinoma and bone metastases were treated with hormonal therapy. Radioimmune imaging of bone marrow performed with 99mTc-labeled antigranulocyte antibody BW 250/183 before treatment demonstrated absence of granulopoietic bone marrow in extensive regions of the central and proximal peripheral skeleton, indicating diffuse bone marrow invasion. Bone marrow scans performed after treatment demonstrated presence of granulopoietic bone marrow in these regions, indicating bone marrow regeneration. This finding was consistent with favorable response to treatment.

Aged↗

Composition of the parotid saliva in Chilean children with Down's syndrome.

Parotid gland saliva was collected from three groups of Chilean human subjects: Down syndrome, non-Down mentally retarded, and normal individuals. Their salivary flows, pH and electrolyte concentrations were determined. Variables were subjected to ANOVA statistical tests that showed no differences between Down and control groups in salivary flow, pH, chloride, sodium and bicarbonate concentrations. The potassium concentration in the saliva from Down syndrome patients was significantly lower than that of control individuals. Student's t-tests showed significant differences between Down syndrome individuals and controls for potassium and sodium. These last differences may be indicative of a characteristic trait of the trisomic state or of the syndrome itself.

Adolescent↗

Intrinsic fluorescence studies of the kinetic mechanism of unfolding of alpha-lactalbumin on weakly hydrophobic chromatographic surfaces.

The kinetic mechanism of unfolding of calcium depleted bovine alpha-lactalbumin adsorbed on two weakly hydrophobic chromatographic surfaces, methyl- and ethyl-polyether phases bonded to porous silica, with a solution phase of 3 M ammonium sulfate at pH 6.3, has been determined using intrinsic fluorescence and liquid chromatography (LC). The adsorbent has been packed into quartz flow cells which are used for both fluorescence measurements and as a microcolumn for LC. The LC measurements revealed two peaks for alpha-lactalbumin on both phases, the first being folded and the second unfolded. The rate of unfolding was measured to be 1.75.10(-3) min-1 on the Cl-ether and 7.42.10(-3) min-1 on the C2-ether phase. Fluorescence studies revealed a slow change in emission maximum from ca. 330 nm to 350 nm and a 4-fold increase in intensity for the protein adsorbed on the two supports. Variation of fluorescence intensity at a given wavelength revealed biphasic kinetics in which the rate law on the surface was deduced as F in equilibrium X----U, where F is the folded form, U an unfolded form and X an intermediate. The normalized emission spectra of the three species were calculated and it was found that there was approximately a 20-nm-red shift in the position of the maximum from F to U. The emission maximum for X was close to U on both columns; however, the normalized intensity for X was between F and U. Activation enthalpies and entropies were determined from the temperature dependence of the microscopic rate constants. The formation of the intermediate on the C1-ether phase was entropy driven whereas on the C2-ether phase it was enthalpy driven. Finally, the solution refolding rates of U desorbed from the two supports were found to be identical. The differences observed in the surface kinetics of unfolding on the two supports are related to the hydrophobic differences of the adsorbents.

Adsorption↗

Dysfunctional penile cholinergic nerves in diabetic impotent men.

Impotence in the diabetic man may be secondary to a neuropathic condition of the autonomic penile nerves. The relationship between autonomic neuropathy and impotence in diabetes was studied in human corporeal tissue obtained during implantation of a penile prosthesis in 19 impotent diabetic and 15 nondiabetic patients. The functional status of penile cholinergic nerves was assessed by determining their ability to accumulate tritiated choline (34), and synthesize (34) and release (19) tritiated-acetylcholine after incubation of corporeal tissue with tritiated-choline (34). Tritiated-choline accumulation, and tritiated-acetylcholine synthesis and release were significantly reduced in the corporeal tissue from diabetic patients compared to that from nondiabetic patients (p less than 0.05). The impairment in acetylcholine synthesis worsened with the duration of diabetes (p less than 0.025). No differences in the parameters measured were found between insulin-dependent (11) and noninsulin-dependent (8) diabetic patients. The ability of the cholinergic nerves to synthesize acetylcholine could not be predicted clinically with sensory vibration perception threshold testing. It is concluded that there is a functional penile neuropathic condition of the cholinergic nerves in the corpus cavernosum of diabetic impotent patients that may be responsible for the erectile dysfunction.

Acetylcholine↗

Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer.

Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.

Antibodies, Monoclonal↗