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Biomedical subjects

C Alvarez

Publications and source records attributed to C Alvarez.

At least 145 records · Page 8Linked to original sources

Transient uptake and storage of serotonin in developing thalamic neurons.

Serotonin (5-HT) has been shown to affect the development and patterning of the mouse barrelfield. We show that the dense transient 5-HT innervation of the somatosensory, visual, and auditory cortices originates in the thalamus rather than in the raphe: 5-HT is detected in thalamocortical fibers and most 5-HT cortical labeling disappears after thalamic lesions. Thalamic neurons do not synthesize 5-HT but take up exogenous 5-HT through 5-HT high affinity uptake sites located on thalamocortical axons and terminals. 3H-5-HT injected into the cortex is retrogradely transported to thalamic neurons. In situ hybridization shows a transient expression of the genes encoding the serotonin transporter and the vesicular monoamine transporter in thalamic sensory neurons. In these glutamatergic neurons, internalized 5-HT might thus be stored and used as a "borrowed transmitter" for extraneuronal signaling or could exert an intraneuronal control on thalamic maturation.

Age Factors↗

Hypnotic drug use in Spain: a cross-sectional study based on a network of community pharmacies. Spanish Group for the Study of Hypnotic Drug Utilization.

OBJECTIVE: To investigate how hypnotic drugs are used in Spain, specifically, (1) to characterize the user population in some simple demographic (e.g., sex, age) and clinical (e.g., type of insomnia, type of physician who prescribed the drug) variables; (2) to estimate the proportion of long-term users (> 3 mo); (3) to determine the frequency of different administration schedules; (4) to determine whether the kind of hypnotic drug prescribed according to the duration of its effect correlates with the type of sleep disorder or patient age; and (5) to compare the dosage used by the elderly with that used by adults. DESIGN: Cross-sectional pharmacy-based study. SETTING: A network of 318 community pharmacies throughout Spain. SUBJECTS: Patients (n = 5324) requesting a hypnotic drug for insomnia who agreed to take part in the study. MAIN OUTCOME MEASURES: Distribution of the use of hypnotic drugs by age, sex, type of insomnia, type of physician, specific hypnotic drug, daily dosage, treatment schedule, and duration of treatment. RESULTS: Women (67%) and the elderly (58%) constituted the largest subgroups in the sample. Difficulties in sleep onset and in sleep maintenance as single disorders were reported by 38% and 37% of users, respectively. Prescriptions were written by general practitioners in 80% of cases. Daily use was reported by 88% and long-term use (> 3 mo) by 72% of the users. Long-term treatment was two- to threefold more frequent in the elderly than in middle-aged subjects. Intermediate-action hypnotic drugs were used by 59% of subjects, short-action drug by 24%, and long-action drugs by 17%. The type of hypnotic drug prescribed was not related to the kind of sleep disorder or the age of patients. Specialists prescribed long-action hypnotic drugs more often than did general practitioners. No relevant differences were observed between dosages used by the elderly and those used by adults. In both groups the dosage taken by most patients, regardless of the drug, corresponded to the available strength. Substitution drugs for triazolam belonged to the intermediate-action class in 53% of the cases. CONCLUSIONS: Recommendations on hypnotic drug use are largely not followed in Spain. Most patients are taking hypnotic drugs daily, over long time periods, and without an adequate dosage titration according to age. Measures should be taken to correct this situation.

Administration, Oral↗

Comparison of serodiagnostic tests and ultrasonography for cystic hydatidosis in an epidemiological study of rural Uruguay.

Cystic hydatidosis (CH) caused by Echinococcus granulosus is an important zoonosis worldwide. Several serodiagnostic and ultrasound tests are currently used for screening asymptomatic CH. The sensitivity of the serodiagnostic tests has been demonstrated by several groups to be lower than ultrasonography (US). To explain the mechanism of the difference in sensitivity, a large-scale US survey combined with an IgG4-enzyme-linked immunosorbent assay test was conducted in Uruguay. Our results suggest that certain cyst images, e.g., multivesicular cysts, may be closely associated with a high antibody response regardless of the cyst size, whereas other hydatid lesions, e.g., solid images with/without rolled parasite membranes, have lower antibody responses with a close relationship to cyst size. Seropositivity of subjects who had been treated surgically for removal of hydatid cysts in the last 5 yr was closest to that of actual CH patients, albeit free from CH by US. These findings are important for the proper use of serodiagnostic tests and US for community-based epidemiological studies.

Animals↗

[Complete cytogenetic remission of chronic myeloid leukemia with low-dose interferon alfa-2b and monthly high-dose busulfan].

Two patients with chronic myelogenous leukaemia were treated according to an original regimen consisting of the association of alpha-2b interferon, three days a week, plus hydroxyurea during ten months, followed by interferon (same doses) and intermittent high doses of busulphan (50 mg, one dose per month, up to 6 doses). Both patients achieved minor cytogenetic remission in the first stage (50% and 80% of Ph'-positive metaphases, respectively). Upon concluding the second phase, one patient attained complete cytogenetic remission and the other showed major cytogenetic remission (3% Ph'-positive metaphases); complete remission was achieved in the second patient after 4 more doses of busulphan. Both patients remain in complete cytogenetic remission after 4 and 2 years, respectively, with three weekly doses of interferon as maintenance therapy. This protocol is quite different to others applied so far and might represent a good choice for patients unsuitable for bone marrow transplantation.

Adult↗

Pancreatic interstitial pH in human and feline chronic pancreatitis.

BACKGROUND & AIMS: Advanced chronic pancreatitis is associated with a reduction in pancreatic blood flow. To determine the physiological significance of this decrease, pancreatic interstitial pH was measured in a model of obstructive chronic pancreatitis in cats and in patients with chronic pancreatitis. METHODS: In cats, pancreatic interstitial pH and blood flow were measured serially under basal conditions and after secretory stimulation as chronic pancreatitis evolved. Basal pancreatic interstitial pH was also measured in patients undergoing an operation for chronic pancreatitis or periampullary cancer (controls). RESULTS: In normal cats, pancreatic interstitial pH was 7.41 +/- 0.01 and blood flow was 124 mL.min-1.(100 g pancreas-1). With the evolution of chronic pancreatitis, interstitial pH and blood flow progressively decreased to 7.21 +/- 0.04 (P < 0.007) and 75 +/- 11 (P < 0.007), respectively. From 1 to 2 weeks, secretory stimulation reduced pancreatic interstitial pH and blood flow further, but as secretory function was lost, this effect disappeared. In patients with chronic pancreatitis, the interstitial pH was lower (7.02 +/- 0.06) than in controls (7.25 +/- 0.04; P < 0.05). CONCLUSIONS: These observations are consistent with the hypothesis that, in chronic pancreatitis, acidic metabolites associated with pancreatic secretion accumulate within the pancreas, probably because of impaired blood flow.

Adult↗

Changes in insulin action and insulin secretion in the rat after dietary restriction early in life: influence of food restriction versus low-protein food restriction.

The effect of a limited period of undernutrition in young rats on insulin secretion and insulin action during adulthood has been studied. Four-week-old female rats were either food-restricted (35% restriction, 15% protein diet) or protein-calorie-restricted (35% restriction, 5% protein diet) for 4 weeks. Food-restricted rats gained weight at a lower rate than control rats. In the protein-calorie-restricted group, the alteration of weight gain was more severe. Basal plasma insulin was reduced only in protein-calorie-restricted rats. Glucose-stimulated insulin secretion (delta I) obtained in vivo after an intravenous glucose load was only moderately decreased in food-restricted group, whereas it was severely blunted in the protein-calorie-restricted group. In this last group, impairment of the insulin secretory response to glucose was related to an intrinsic impairment of beta-cell secretory capacity, since the insulin secretory response to glucose or arginine was decreased when tested in vitro (perfused pancreas). In food-restricted rats, basal plasma glucose level was kept normal, while a mild deterioration of glucose tolerance was detectable. This was related, of course, to the decrease of delta I as identified in vivo. However, data obtained under basal or euglycemic-hyperinsulinemic conditions provided direct evidence that insulin-mediated total glucose uptake (weight-related expression) was paradoxically enhanced. A similar conclusion was reached in protein-calorie-restricted rats; the increase of overall insulin-mediated glucose uptake was even more important. Such an adaptation, which was operating in both types of restriction, may help limit the deterioration of glucose tolerance in the face of impaired insulin release. In the basal postabsorptive state, the higher glucose utilization rate in both models originated from increased hepatic glucose production rates. During hyperinsulinemia, endogenous glucose production in food-restricted rats was normally blunted, but not in protein-calorie--restricted rats, thus indicating resistance of the hepatic glucose production pathway to insulin action in this group.

Animals↗

Isolation and properties of white skeletal muscle alpha-actinin from sea-trout (Salmo trutta) and bass (Dicentrarchus labrax).

Fish alpha-actinin purified from sea-trout and bass white muscle by means of two different extraction procedures was used to investigate the eventual presence of different muscle isoforms in Z-disks. These fish alpha-actinins have the same apparent molecular weight (100 kDa) and the same isoelectric point (pI = 5.6), and also have a total antigenic identity towards anti-bass and anti-chicken alpha-actinin antibodies, suggesting a single molecular species. The role of fish alpha-actinin as an anchorage site for thin actin filaments and elastic titin filaments in Z-bands was studied. Despite conservation of the actin-binding site, fish alpha-actinin has a better actin-binding ability (kD = 0.3 microM) than chicken smooth muscle alpha-actinin (kD = 1.6 microM). Several other structural and functional characteristics of fish alpha-actinin were also studied: conservation of sequence and domain structure, the role of divalent ions (Ca2+, Mg2+) and the dielectric constant of the medium in alpha-actinin-actin interaction. Although the reason for fish white muscle alpha-actinin's close affinity to actin was not clearly established, our results suggested that the physicochemical environment of the Z-filaments in Z-disks might be crucial.

Actinin↗

A new large-scale process for taxol and related taxanes from Taxus brevifolia.

PURPOSE: In view of the demonstrated antitumor activity of taxol, ready availability of the drug is important. The current isolation methods starting from the bark of Taxus brevifolia involve multiple manipulations, leading to only taxol and in a yield of 0.01%. A new process consisting of a single reverse phase column is introduced here, and the present purpose is to determine its large scale applicability. METHODS: The chloroform extractable fraction of the bark of T. brevifolia is applied directly on to a C-18 bonded silica column in 25% acetonitrile/water, with elution using a step gradient: 30-50% acetonitrile/water. On standing, eight different taxanes, including taxol, crystallize out directly from different fractions. The crystals are filtered and purified further by recrystallization. Taxol and four other taxanes are purified this way. The other three require a short silica column. Taxol is freed from cephalomannine by selective ozonolysis. RESULTS: The large scale process gave taxol (0.04%), 10-deacetylbaccatin III (0.02%), 10-deacetyl taxol-7-xyloside (0.1%), 10-deacetyl taxol-C-7-xyloside (0.04%), 10-deacetyl cephalomannine-7-xyloside (0.006%), taxol-7-xyloside (0.008%), 10-deacetyl taxol (0.008%) and cephalomannine (0.004%). Processing of the needles of T. brevifolia gave brevifoliol (0.17%), and that of the wood, 10-deacetyl taxol-C-7-xyloside (0.01%) and 10-deacetyl taxol-C. CONCLUSIONS: The reverse phase column process is simpler (one column, direct crystallization), more efficient (eight taxanes obtained simultaneously) and also gives higher yields.

Antineoplastic Agents, Phytogenic↗

T cell-independent B cell response to self-monosialogangliosides: primary response monoclonal antibodies.

Purified GM1 and GM2 gangliosides incorporated into liposomes were injected subcutaneously in BALB/c mice every 3-4 days after pretreatment of the animals with low-dose cyclophosphamide. Serum samples were collected at different intervals and tests by ELISA for the presence of anti-ganglioside antibodies. Four doses (50 micrograms each) were sufficient to raise a measurable primary type of response to GM1, while nine doses were required to obtain measurable IgM antibody titers to GM2. Three monoclonal antibodies (MAbs) wer generated by fusing splenocytes with mouse myeloma cells. The specificity of MAbs was determined by ELISA and HPTLC-immunostaining using a panel of purified glycolipids. The MAb designated E1 showed a high degree of specificity because it reacted only with N-acetyl GM2. Monoclonal antibody A3 reacted predominantly with GM2 and GM1, but also reacted moderately with the GM3 ganglioside. The epitope recognized by this MAb is suggested to be the trisaccharide sequence GalNAc beta 1-4(NeuAc alpha 2-3)Gal. The third MAb (F6) reacted strongly with GM1 but a weak reactivity was also observed with GD1b as well as with asialo-GM1, indicating that the terminal tetrasaccharide Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal- structure is probably involved in antigenic recognition. Formalin-fixed and paraffin-embedded tissue sections were stained with the E1 and A3 MAbs, using the avidin-biotin complex (ABC) technique. Strong immunoreactivity for E1 appeared in the tumor cells of five primary lung carcinomas and in five malignant melanomas. No immunoreactivity was demonstrated in the parenchyma of a lung without malignancy, or in a metastasis from a colon carcinoma.

Animals↗

Generation of a murine monoclonal antibody specific for N-glycolylneuraminic acid-containing gangliosides that also recognizes sulfated glycolipids.

The P3 murine monoclonal antibody (MAb) was generated by immunizing BALB/c mice with NeuGcGM3 included into liposomes. The specificity of this MAb was defined by an enzyme-linked immunosorbent assay and immunostaining on thin-layer chromatograms. P3 MAb binds to NeuGc-containing gangliosides and was shown also to react with sulfated glycolipids. A preliminary immunohistochemical study showed that the P3 MAb was able to recognize antigens expressed in human breast tumors.

Animals↗

Morphometric characterization of normal and abnormal human zygotes.

Human zygotes (n = 278) from 96 in-vitro fertilization gonadotrophin-stimulated cycles were photographed in their pronuclear stage (16-18 h post-insemination). Normal morphological fertilization (two pronuclei) was observed in 215 zygotes, 17 showed only one pronucleus, 40 showed three pronuclei and six showed four. Area, perimeter and maximum and minimum diameters of each zygote and pronucleus were measured using an IBAS 2000 (Kontron) image analyser. When the four groups were compared, whole zygotes did not show any morphometric difference. However, pronuclei from these groups showed that a high number of pronuclei was directly related to small pronuclei. Differences in pronuclear size and a linear increase in the nucleus/cytoplasm relationship were found which varied with the number of pronuclei.

Cell Nucleus↗

Catastrophic osteolysis in total knee replacement. A report of 17 cases.

One hundred eighty-five total knee revisions were done by the 2 senior authors from 1988 to 1994. Of these, 17 patients were identified as having severe osteolysis. The average age was 62.7 years, and the average weight was 90.8 g. All patients had osteoarthritis. Preoperative aspiration was negative in all patients. Eight patients had a metal-backed patella, 8 had a cementless implant, 4 had a cemented implant, and 5 had a hybrid implant. The average time interval from the index surgery to radiographic evidence of lysis was 56 months. Radiographic review showed gross polyethylene wear in 10 patients, loose tibial implants in 8, fractured baseplates in 2, and evidence of a metallic synovitis in 2. Retrieved polyethylene liners had a average thickness of 7 mm, and none were conforming. Osteolytic defects were defined and classified according to Engh's criteria. The histology showed a foreign body reaction with intracellular refractile polyethylene particles. Four cases had metallic debris. The exposure at the time of revision required a rectus snip in 4, V-Y-quadricepsplasty in 2, and tibial tubercle osteotomy in 1. Posterior stabilized implants were used in 65% and a constrained implant in 30%. Lytic defects were reconstructed with cement only in 47% of knees, allograft in 30%, and metallic wedges in 35%. Based on this report, the authors conclude that younger, overweight patients seem to be at higher risk of implant failure and that osteolysis is not restricted to cementless implants. Furthermore, because review of the radiographs leads to a constant underestimation of the lytic defect, the surgeon must be prepared to deal with complex revisions.

Aged↗

Histologic changes after stenting of the pancreatic duct.

The placement of stents has been proposed as a possible modality to treat pancreatic diseases. Ductal changes observed on endoscopic retrograde cholangiopancreatography during stenting are believed to be reversible when the stents are removed. We describe a patient with normal anatomy on baseline pancreatograms who underwent endoscopic sphincterotomy, followed by stent placement for 9 months. Symptoms progressed, leading to a pancreaticoduodenectomy. Histologic evaluation of the head of the pancreas revealed more extensive inflammatory changes in the duct and parenchyma drained by the stent. This suggests that stent-induced changes noted on pancreatography correspond to parenchymal changes that may be severe and irreversible.

Cholangiopancreatography, Endoscopic Retrograde↗

Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct.

Chronic pancreatitis is characterized by persistent and severe pain, which can be relieved by decompression of the main pancreatic duct (MPD). Both ductal and interstitial pressures have been shown to be increased in chronic pancreatitis in patients. A study was carried out of pancreatic interstitial pressure and pancreatic blood flow in normal cats and those in which chronic obstructive pancreatitis had been induced 5 weeks earlier to determine the effect of decompression of the MPD. In the normal pancreas, median(interquartile range (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did not change the interstitial pressure significantly, but was associated with a 40 per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100 g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per min per 100 g, significantly lower than in the normal pancreas. Furthermore, secretory stimulation was associated with a significant increase in median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After decompression of the MPD in cats with chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in interstitial pressure seen in the animals with obstruction. In contrast, ductal decompression improved the median(i.q.r.) basal pancreatic blood flow to 45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g. Decompression thus restored the normal pattern of secretory hyperaemia. Within the confines of this model, these observations demonstrate that chronic obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct drainage.

Animals↗

Neurochemical development of the hippocampal region in the fetal rhesus monkey. II. Immunocytochemistry of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex by the end of gestation.

Material for the study came from one 126 day-old rhesus monkey fetus and two 3 day-old neonates. The immunocytochemical detection of somatostatin, neurotensin (NT), parvalbumin, calbindin D-28K, DARPP-32 as well as tyrosine hydroxylase (TH), dopamine-beta-hydroxylase and serotonin (5-HT), was carried out on serial cryostat sections of the entorhinal cortex. The authors reported in a previous paper the precocious differentiation of the entorhinal cortex in rhesus monkey fetuses and featured the conspicuous expression of calbindin D-28K, somatostatin, neurotensin, and the monoaminergic innervation during the first half of gestation. The present study shows distinct temporal profiles of neurochemical development during the second half of gestation: the dense neuropeptidergic innervation remained a constant feature; the three aminergic systems gradually increased in density; parvalbumin, unlike calbindin D-28K, was primarily expressed during the last quarter of gestation. Three other prominent features of the last quarter of gestation are illustrated: the refinement of the modular neurochemical organization of the lamina principalis externa, the delayed chemoanatomical development of the rhinal sulcus area, and the establishment of a distinct rostrocaudal pattern of neurochemical distribution. In correspondence with the cluster-like organization of the lamina principalis externa, the authors observed in the olfactory, rostral, and intermediate fields of the neonate monkey entorhinal cortex, a particular subset of pyramidal-shaped neurons: located in layer III, they were characterized by fasciculated apical dendrites ascending between the cellular islands of the discontinuous layer II and the coexpression of calbindin D-28K and DARPP-32. Besides, most of the other chemical systems displayed a distinct, area-specific, patchy distribution, except for the homogeneously distributed noradrenergic innervation. In the olfactory and rostral fields, TH positive dopaminergic fibers accumulated on the neuronal islands of layers II-III, and parvalbumin labeled fibers on those of layer III, whereas patches of 5-HT and NT-like reactive terminals were segregated between the cellular islands, overlapping the DARPP-32/calbindin D-28 K labeled dendritic bundles. At the opposite, in the intermediate field, 5-HT positive terminals overlapped the cellular islands of layer II and thin fascicles of dopaminergic fibers ran in the inter island spaces. The somatostatin-LIR innervation was apparently too dense to reveal a patchy distribution that existed at earlier developmental stages. In the caudal field, the patchy pattern was replaced by a predominant bilaminar type of distribution of NT, 5-HT, and TH-like positive afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Emphysematous cholecystitis after ERCP.

Emphysematous cholecystitis is a rare variant of acute cholecystitis, most frequently seen in elderly, debilitated, or diabetic patients. This report documents the development of fulminant sepsis due to acalculous cholecystitis after endoscopic retrograde cholangiopancreatogram (ERCP) in an otherwise healthy patient with suspected malignant obstructive jaundice. Three other cases of acute cholecystitis have been reported in the literature after ERCP. Although not proven to prevent infectious complications during ERCP, strong consideration should be given to prophylactic antibiotics in patients with suspected malignant obstruction and/or coexistent medical illness, eg, diabetes. When attempts at decompression of the obstructed biliary system by endoscopy fail, decompression by percutaneous or surgical routes should be considered in a timely fashion.

Acute Disease↗