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Biomedical subjects

A Garcia

Publications and source records attributed to A Garcia.

At least 19 recordsLinked to original sources
PubMed2001

Carbon-11 labelled cholecystokininB antagonists: radiosynthesis and evaluation in rats.

Three cholecystokinin type B (CCKB) receptor antagonists were labelled with 11C and evaluated ex vivo in rat biodistribution studies. The CCKB antagonists were YF 476 and two other compounds of the basic 3-ureido-1,4-benzodiazepine class. Following tail-vein administration of [11C]-YF 476 exceedingly low levels of radioactivity were found in all brain regions from 5 to 60 min post-injection. Similar results were obtained using the other two 11C-labelled CCKB antagonists. In light of the very poor brain penetration of these compounds, reports on the central nervous system activity of this class of CCKB antagonists should be viewed with caution.

Animals↗
PubMed2001

Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction.

PURPOSE: Although echocardiography is important for making the diagnosis of left ventricular dysfunction, its cost and lack of availability limit its use as a routine screening test. B-Natriuretic peptide levels accurately reflect ventricular pressure, and preliminary studies with a rapid assay have found that levels are sensitive and specific for diagnosing heart failure in patients with dyspnea. We hypothesized that B-natriuretic peptide levels obtained through the use of a rapid assay should correlate with echocardiographic abnormalities of ventricular function. SUBJECTS AND METHODS: We studied 400 patients who were referred for echocardiography at the San Diego Veteran's Healthcare System between June and August 2000 to evaluate ventricular function. B-natriuretic peptide levels were measured by a point-of-care immunoassay; cardiologists assessing left ventricular function were blinded to the assay results. Patients were grouped into those with normal ventricular function, systolic dysfunction only, diastolic dysfunction only, and both systolic and diastolic dysfunction. RESULTS: Mean (+/- SD) B-natriuretic peptide concentration was 416 +/- 413 pg/mL in the 253 patients diagnosed with abnormal left ventricular function, compared with 30 +/- 36 pg/mL in the 147 patients with normal left ventricular function. Patients with both systolic and diastolic dysfunction had the highest levels (675 +/- 423 pg/mL). The area under the receiver operating characteristic (ROC) curve for B-natriuretic peptide levels to detect any abnormal echocardiographic finding was 0.95 (91% confidence interval: 0.93 to 0.97). B-Natriuretic peptide levels were unable to differentiate systolic vs. diastolic dysfunction. In patients with symptoms of heart failure and normal systolic function, B-natriuretic peptide levels >57 pg/mL had a positive predictive value of 100% for diastolic abnormalities. CONCLUSIONS: A simple, rapid test for B-natriuretic peptide levels can reliably predict the presence or absence of left ventricular dysfunction on echocardiogram. For some patients, a normal level may preclude the need for echocardiography.

Aged↗
PubMed2001

Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis.

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression during experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv. Mice with experimental autoimmune encephalomyelitis showed a significant induction of metallothioneins-I+II in the spinal cord white matter, and to a lower extent in the brain. Interferon-gamma receptor knockout mice suffered from a more severe experimental autoimmune encephalomyelitis, and interestingly showed a higher metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast to the metallothioneins-I+II isoforms, metallothionein-III expression remained essentially unaltered during experimental autoimmune encephalomyelitis; interferon-gamma receptor knockout mice showed an altered metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv background. Metallothioneins-I+II proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of metallothioneins-I+II proteins. From these results we suggest that metallothioneins-I+II but not metallothionein-III may play an important role during experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory cytokine interferon-gamma is unlikely an important factor in this response.

Animals↗
PubMed2001

A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study.

OBJECTIVES: The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND: Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient's symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS: We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS: Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS: In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.

Adult↗
PubMed2001

An admonition when measuring the lipophilicity of radiotracers using counting techniques.

Log P measurements are a fundamental physico-chemical parameter and one of the cornerstones of structure activity relationships in medicinal chemistry. Despite the attractiveness of the method, the use of counting techniques to measure the log P of lipophilic radiotracers is fraught with pitfalls due to the amplifying effects of small quantities of radioactive impurities. For example, a radiotracer with a log P of 4 containing only 0.1% of a radioactive impurity with a log P of -1 will have an apparent log P of 3 if measured using conventional shake-flask partition techniques, counting the radioactivity in each phase. However, pre-washing the radiotracer-containing organic phase with aqueous phase can, in many cases, allay doubts about the validity of such measurements.

1-Octanol↗
PubMed2001

Appendicitis caused by caecal carcinoma--a case report.

Appendicitis can occur rarely in association with carcinoma of the caecum, particularly in elderly patients. The prognosis for caecal or proximal colonic neoplasm presenting as appendicitis is poor. This is in part due to the association being missed at the initial laparotomy. We report a case of acute appendicitis provoked by an adenocarcinoma of the caecum which obstructed the lumen of appendix in an 84 years old patient by which a simple ileocaecal resection was performed. The difficulties of identifying a small tumor at laparotomy and the implication for optimal treatment are emphasized. It is suggested that a more aggressive attitude should be taken in the pre and postoperative management of any patient over 50 years of age who presents with appendicitis.

Adenocarcinoma↗
PubMed2001

Long-term follow-up of contralateral lobe in patients hemithyroidectomized for solitary follicular adenoma.

OBJECTIVES: Since there are no available conclusive studies on the long-term evolution of remnant thyroid tissue after hemithyroidectomy in patients who undergo surgery for solitary follicular adenomas, we searched for such cases in our records to elucidate this issue. DESIGN: Search criteria were as follows: (i) presence of a single palpable thyroid nodule with the remainder of the gland normal on palpation; (ii) clinically euthyroid status at the time of surgery; (iii) histological diagnosis of nodule as follicular adenoma; (iv) a hemithyroidectomy operation, sparing the contralateral lobe; (v) normal macroscopic aspect of the contralateral lobe at the time of surgery; and (vi) at least 4 years of postoperative follow-up. PATIENTS: Only 47 female cases were found to meet above criteria, with a mean age of 45.9 years (range: 23-79) at the time of surgery and a mean follow-up of 7.2 years (range: 4-32). Besides evaluating the presence or absence of antithyroid antibodies and the extranodular histology of tissue removed during surgery, a preoperative TRH test also allowed patients to be classified into two groups: normal extranodular thyroid (NET) (n = 32) and abnormal extranodular thyroid (AET) (n = 15). RESULTS: Eleven of the 15 patients with AET had thyroid autoimmunity, with or without overt histological thyroiditis, and the remaining four had subclinical hypothyroidism with negative antithyroid antibody titres. In the entire study population, only 28 patients received treatment with L-T4 immediately after surgery, none of whom had any alterations in the contralateral lobe. However, six of the nineteen patients not treated with T4 (31.6%) developed overt abnormalities in the contralateral lobe, including the only three with AET who had not received L-T4 treatment. The remaining three were two patients with NET, who showed postoperative TSH hyper-responsiveness to TRH (peak TSH > 25 mU/l), and one who developed a new follicular adenoma 32 years later. To date, none of the patients with NET, who had a normal TRH test after surgery, have developed any kind of alterations in the contralateral lobe, even those who received no L-T4 prophylactic treatment. CONCLUSIONS: The findings of this study suggest that: (i) there is a higher risk of follicular adenomas developing in a gland affected by thyroid autoimmunity than in a previously normal gland; (ii) L-T4 therapy may prevent the formation of new nodules or the development of goitre in the contralateral lobe; and (iii) in the absence of prophylactic treatment after surgery, the contralateral lobe of subjects with thyroid autoimmunity and/or previous subclinical hypothyroidism develops morphological abnormalities.

Adenoma↗
PubMed2001

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis.

The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D.

Age of Onset↗
PubMed2001

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Cytoskeletal Proteins↗
PubMed2001

A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study.

OBJECTIVES: To determine if changes in B-type natriuretic peptide (BNP) levels can accurately reflect acute changes in pulmonary capillary wedge pressure during treatment of decompensated heart failure. BACKGROUND: Tailored therapy of decompensated congestive heart failure with hemodynamic monitoring is controversial. Other than the expense and complications of Swan-Ganz catheters, its use in titration of drug therapy has no conclusive end point. Because BNP reflects both elevated left ventricular pressure and neurohormonal modulation and has a short half-life, we hypothesized that levels of BNP would decline in association with falling wedge pressures. Final BNP levels would perhaps signify a new set point of neuromodulation. METHODS AND RESULTS: Twenty patients with decompensated New York Heart Association (NYHA) class III-IV congestive heart failure (CHF) undergoing tailored therapy were studied. BNP levels were drawn every 2 to 4 hours for the first 24 hours (active treatment phase) and then every 4 hours for the next 24 to 48 hours (stabilization period). Hemodynamic data was recorded simultaneously. In 15 patients whose wedge pressure responded to treatment in the first 24 hours, there was a significant drop in BNP levels (55%) versus nonresponders (8%). There was a significant correlation between percent change in wedge pressure from baseline per hour and the percent change of BNP from baseline per hour (r = 0.79, P <.05). When the wedge pressure was kept at a stable, low level during the stabilization phase, BNP levels continued to fall another 37% (937 +/- 140 pg/mL at 24 hours to 605 +/- 128 pg/mL). Patients who died (n = 4) had higher final BNP levels (1,078 +/- 123 pg/mL v 701 +/- 107 pg/mL). CONCLUSIONS: The data suggest that rapid testing of BNP may be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Although BNP levels will not obviate the need for invasive hemodynamic monitoring, it may be a useful adjunct in tailoring therapy to these patients.

Aged↗
PubMed2001

Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction.

BACKGROUND: Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction. METHODS: Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.

Aged↗
PubMed2001

Follow-up of Ascaris lumbricoides and Trichuris trichiura infections in children living in a community treated with ivermectin at 3-monthly intervals.

Ivermectin treatment was administered every 3 months over a 1-year period (April 1993-April 1994) to the whole eligible population of a village in South Cameroon where both Ascaris lumbricoides and Trichuris trichiura were hyper-endemic. A parasitological stool examination was performed before each treatment. Thirty children, aged 5-15 years, were not only found egg-positive for A. lumbricoides and/or T. trichiura before the first treatment but were also each treated and examined in each treatment round. Among these children, the intensity of infection with A. lumbricoides decreased significantly following the first treatment but thereafter remained steady. In contrast, the repeated ivermectin treatments had no significant impact on the intensity of the T. trichiura infections or on the prevalence of infection with T. trichiura or A. lumbricoides among the 30 children.

Adolescent↗
PubMed2001

Hormonal control of growth hormone secretion.

Growth hormone secretion by the somatotroph cells depends upon the interaction between hypothalamic regulatory peptides, target gland hormones and a variety of growth factors acting in a paracrine or autocrine fashion. This review will be focused on recent data regarding the mechanism by which growth hormone-releasing hormone (GHRH) influences somatotroph cell function and the physiological role played by Ghrelin and leptin in the regulation of growth hormone (GH) secretion. It is well established that binding of GHRH to its receptor leads to activation of protein kinase A (PKA). More recently, it was found that GHRH can also activate mitogen-activated protein (MAP) kinase both in pituitary cells and in a cell line overexpressing the GHRH receptor. Whether somatotroph adenomas, either with or without a GS-alpha mutation, have alterations in some of the components of the activation of the MAP kinase pathway remains to be known. The recent isolation of Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, can be considered a landmark in the GH field, which opens up the possibility of gaining greater insight into our understanding of the mechanisms involved in the regulation of GH secretion and somatic growth. Indeed, preliminary evidences indicate that this peptide exerts a marked stimulatory effect on plasma GH levels in both rats and humans. Finally, it is well known that GH secretion is markedly influenced by nutritional status. Leptin has emerged as an important adipose tissue-generated signal that is involved in the regulation of GH secretion, thus providing an integrated regulatory system of growth and metabolism. Although the effects of leptin on GH secretion in humans remain to be clarified, indirect evidences indicate that it may play an inhibitory role.

Ghrelin↗
PubMed2001

Opposing offspring sex ratio variations with increasing age and weight in mouflon mothers (Ovis musimon).

There are two main theories explaining offspring sex biases in polygynous mammals. Trivers and Willard (1973) argue that mothers with greater reproductive resources should invest in the sex with the greater variance in reproductive success, usually sons. In contrast, because daughters in many polygynous mammals stay with their mother and compete with her for food, Local Resource Competition theory (e.g. Clark, 1978; Silk, 1983) predicts that the mothers with the greatest reproductive resources should invest in daughters. We investigated the strategy of sex allocation of a captive, outdoor population of 139 mouflon mothers, Ovis musimon, kept in a game state. A complex picture emerged in which, despite weight and body condition being correlated with age in female mouflons, mothers lambed more daughters with increasing age but also, within a given age, gave birth to more sons with increasing weight. Results may be useful in game management aimed at increasing the recruitment or quality of males in managed populations.

Age Factors↗
PubMed2001

Calf growth in captive Iberian red deer (Cervus elaphus hispanicus): effects of birth date and hind milk production and composition.

This study examines effects of birth date, hind milk production and its composition, and weight of hind and calf at birth (HBW and CBW, respectively) on calf growth responses born to Iberian hinds (Cervus elaphus hispanicus) and lactating over 34 wk. Males showed daily gains greater than those of females (P = 0.04). Calf birth weight was strongly related to calf gain over a standard (15-wk) lactation (P < 0.01), but HBW did not influence growth or CBW (P > 0.10). After correcting for nutrient supply, birth date did not affect growth, but birth date x total protein yield (TPY), birth date x total fat yield (TFY), and birth date x total lactose yield (TLY) interactions influenced growth (P < 0.001), and early-born calves showed greater growth than those born late for wk 2 to 34 (P < 0.05). Calf birth weight showed the highest correlation with protein-to-fat ratio in milk (P < 0.001), a high correlation with milk protein content (P < 0.05), and a low negative correlation with fat (P < 0.10). Calf gains also showed the highest correlation with protein-to-fat ratio in milk (P < 0.05). Similarly, total milk yield (TMY), TPY, and TFY during lactation affected growth as single factors (P < 0.001). Calves showed not only an overall difference in daily gain between calves born early or late (P = 0.02), but also a greater speed of growth independently of CBW (percentage of weight gained per week, P < 0.001). Early-born calves were heavier at 12 and 18 mo (P < 0.05). Results suggest that selecting hinds of high milk production and nutrient supply and advancing calving date may increase growth of calves and their performance at adulthood.

Animal Husbandry↗