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Biomedical subjects

A Garcia

Publications and source records attributed to A Garcia.

At least 91 records · Page 5Linked to original sources

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator.

BACKGROUND: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. METHODS: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum." A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. RESULTS: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. CONCLUSIONS: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions.

Abdominal Neoplasms↗

A Theileria parva type 1 protein phosphatase activity.

The protozoan parasite Theileria (spp. parva and annulata) infects bovine leukocytes and provokes a leukaemia-like disease in vivo. In this study, we have detected a type 1 serine/threonine phosphatase activity with phosphorylase a as a substrate, in protein extracts of parasites purified from infected B lymphocytes. In contrast to this type 1 activity, dose response experiments with okadaic acid (OA), a well characterised inhibitor of type 1 and 2A protein phosphatases, indicated that type 2A is the predominant activity detected in host B cells. Furthermore, consistent with polycation-specific activation of the type 2A phosphatase, protamine failed to activate the parasite-associated phosphorylase a phosphatase activity. Moreover, inhibition of phosphorylase a dephosphorylation by phospho-DARPP-32, a specific type 1 inhibitor, clearly demonstrated that a type 1 phosphatase is specifically associated with the parasite, while the type 2A is predominantly expressed in the host lymphocyte. Since an antibody against bovine catalytic protein phosphatase 1 (PP1) subunit only recognised the PP1 in B cells, but not in parasite extracts, we conclude that in parasites the PP1 activity is of parasitic origin. Intriguingly, since type 1 OA-sensitive phosphatase activity has been recently described in Plasmodium falciparum, we can conclude that these medically important parasites produce their one PP1.

Animals↗

Radiotracer synthesis from [(11)C]-iodomethane: a remarkably simple captive solvent method.

A new method of [(11)C]-methylation is described, which attains the goals of simplicity, high radiochemical yields, speed, versatility, and automation. A standard high performance liquid chromatography (HPLC) injection loop on a standard HPLC injection valve is loaded with a solution (80 microL) of precursor (0.3-1.0 mg) in dimethyl formamide (DMF) or dimethyl sulfoxide (DMSO) (+ base if required). At ambient temperature [(11)C]-iodomethane is passed through the loop for 3-4 min with >90% trapping of activity. After a further 1-5 min, the contents of the loop are quantitatively injected onto the HPLC column for purification. Radiochemical yields are equal to or superior to conventional solution methods in all cases, even though no heat is applied. [(11)C]-labeled radiotracers that have been prepared by this method for human or animal studies include Raclopride, N-methylspiperone, Ro 15-1788, FLB 457, RTI-32, Rolipram, SCH 23390, and SKF 82957. Since no vials, transfer lines, cooling, heating, or sealing valves are required, no transfer losses occur, yields are high, and cleanup is minimal, this "loop method" is ideal for most radiopharmaceuticals prepared from [(11)C]-iodomethane.

Antipsychotic Agents↗

Protein phosphatase 2A: a definite player in viral and parasitic regulation.

Cells use phosphorylation/dephosphorylation mechanisms to regulate the activity of several proteins required to transmit information from the cell surface to the nucleus. Recent studies have significantly increased our knowledge regarding the structure/function of one major regulator of cell phosphorylation: protein phosphatase 2A (PP2A). This review will discuss the role of PP2A in virology and parasitology.

Animals↗

Follow-up of Card Agglutination Trypanosomiasis Test (CATT) positive but apparently aparasitaemic individuals in Côte d'Ivoire: evidence for a complex and heterogeneous population.

The aetiological diagnosis of human African trypanosomiasis (HAT) is based on the detection of the parasite, but currently available parasitological tests have low sensitivity and are hampered by fluctuating parasitaemia. The identification of seropositive individuals on whom to focus parasitological examination is based on antibody detection by means of the Card Agglutination Trypanosomiasis Test (CATT/T.b.gambiense). A complicating phenomenon is the occurrence of serologically positive but parasitologically unconfirmed results (isolated CATT positivity). This work presents a two-year longitudinal serological, parasitological and molecular follow-up of CATT-positive individuals including repeated examinations of each individual, to study the evolution over time of seropositivity at both the population and the individual levels. At the population level, the rate of seropositivity decreased during the first months of the survey, and afterwards showed remarkable stability. At the individual level, the results reveal the extreme heterogeneity of this population, with subjects showing fluctuating results, others with a short transient CATT positivity, and subjects that maintain their seropositivity over time. The stability of seropositivity and the pattern of results obtained with both immunological and parasitological examinations support the view that individual factors, such as immune response to infection, might be involved in the isolated CATT positivity phenomenon.

Adolescent↗

Constitutive PI3-K activity is essential for proliferation, but not survival, of Theileria parva-transformed B cells.

Theileria is an intracellular parasite that causes lymphoproliferative disorders in cattle, and infection of leucocytes induces a transformed phenotype similar to tumour cells, but the mechanisms by which the parasite induces this phenotype are not understood. Here, we show that infected B lymphocytes display constitutive phosphoinositide 3-kinase (PI3-K) activity, which appears to be necessary for proliferation, but not survival. Importantly, we demonstrate that one mechanism by which PI3-K mediates the proliferation of infected B lymphocytes is through the induction of a granulocyte-monocyte colony-stimulating factor (GM-CSF)-dependent autocrine loop. PI3-K induction of GM-CSF appears to be at the transcriptional level and, consistently, we demonstrate that PI3-K is also involved in the constitutive induction of AP-1 and NF-kappaB, which characterizes Theileria-infected leucocytes. Taken together, our results highlight a novel strategy exploited by the intracellular parasite Theileria to induce continued proliferation of its host leucocyte.

Animals↗

Evaluation of 2LHERP in preventing recurrences of genital herpes. Institut International 3IDI.

The objective of the study was to evaluate the effectiveness of a homeopathic complex in terms of intensity of attacks and duration of remission between attacks of genital herpes. Fifty three patients aged 18 or over with a minimum of four attacks annually were followed in this open multicentre study in a primary care setting. The principal parameters analysed were: frequency of attacks; intensity of symptoms, during treatment and/or after stopping treatment; treatment tolerance. Eighty-two percent of patients treated for recurrent genital herpes benefited. In 41% of cases, there was no recurrence after the first treatment with follow-up of between 8 and 50 months. In 32% of patients, one or two relapses, in 9% of patients recurrences continued but with reduced frequency and intensity.

Adult↗

Loss of heterozygosity on chromosome 17q in epithelial ovarian tumors: association with carcinomas with serous differentiation.

Loss of heterozygosity (LOH) on chromosome 17q is frequent in epithelial ovarian tumors, but its clinicopathologic significance remains to be elucidated. DNA of 50 patients with epithelial ovarian tumors was extracted from blood and from fresh-frozen and paraffin-embedded tissue (14 benign, 7 borderline, and 29 malignant). Six microsatellite loci were amplified by PCR (D17S250, TRHA1, D17S800, D17S855, D17S579, D17S513). LOH was scored by the absence or reduction of the signal to less than 50% of one of the alleles in tumor DNA compared with normal DNA. LOH was identified on chromosome 17q in at least one locus in 12 tumors (24%), all of them carcinomas (12 of 29 tumors, 41.3%). It occurred more frequently among high-grade serous carcinomas (8 of 14 tumors, 57%) and mixed endometrioid-serous carcinomas (2 of 5, 40%). LOH was detected in all informative markers of 10 tumors, suggesting the complete loss of an entire chromosome 17 homologue. Patients with LOH-positive carcinomas were older than those with LOH-negative malignant tumors (mean ages 67 and 49). The results support the hypothesis that LOH on chromosome 17q may be associated with the development of ovarian cancers in elderly patients, particularly with high-grade serous or mixed endometrioid-serous carcinomas.

Adenocarcinoma, Clear Cell↗

Single-dose AmBisome (Liposomal amphotericin B) as prophylaxis for murine systemic candidiasis and histoplasmosis.

AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida albicans or Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died. All AmBisome-treated mice survived, although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the C. albicans experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the Fungizone group and significantly lower than those in the untreated control group (P < 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was increased. In conclusion, these results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C. albicans models.

Amphotericin B↗

Behavior of resting Aedes aegypti (Culicidae: Diptera) and its relation to ultra-low volume adulticide efficacy in Panama City, Panama.

The resting behavior of Aedes aegypti (L.) adults was investigated in 14 districts of Panama City, Panama, in relation to ground ultra-low volume (ULV) applications of malathion. Adults primarily rested inside the premises (75.1%) at a distance > 6 m from the street (86.4%). Both sexes rested mainly in bedrooms, living rooms, and bathrooms. The small ULV aerosol droplets (2-4 microns) penetrated all indoor resting sites of Ae. aegypti, but in low amounts. Because of the low amount of insecticide reaching the primary resting sites within the premises, limited control of the Ae. aegypti was obtained. This limited the potential effectiveness of ground vehicle ULV applied insecticide as a dengue epidemic control method.

Aedes↗

Milk production and composition in captive Iberian red deer (Cervus elaphus hispanicus): effect of birth date.

This study describes milk production and milk composition of Iberian red deer (Cervus elaphus hispanicus) females (hinds) and the effect of calving date and BW change of hinds by milking over 34 wk. All hinds produced milk throughout the 34-wk study period, well over the standard lactation period. Total milk yield was 224.1 +/- 21.1 L, and daily production was 0.91 +/- 0.06 L. Milk yield decreased with lactation stage (P = 0.01) and the later a calf was born (P = 0.008), and it was greater in posterior quarters (P < 0.05). Milk yield was unaffected (P > 0.10) by side position or milking order of the udder. Milk production did not correlate with hind BW (P > 0.1). Hinds lost 4.4% BW during lactation (P < 0.001); losses increased the later a calf was born (P = 0.012). Iberian red deer milk had 11.5% fat, 7.6% protein, 5.9% lactose, and 26.7% DM. Stage of lactation affected fat (P < 0.001), protein (P = 0.002), DM (P < 0.001), and protein:fat ratio (P < 0.001), but not lactose (P > 0.1). These constituents became concentrated as lactation proceeded, and protein was substituted by fat. Calving date had a similar concentrating effect on fat (P < 0.001) and DM (P < 0.001), whereas it decreased lactose (P = 0.015) and protein (P = 0.002), thus producing a substitution of protein by fat (ratio of protein to fat, P < 0.001). Milking order of quarters or their position had no effect on milk composition (P > 0.10). Results suggest that milk production and milk energetic quality might increase by advancing calving date in red deer hinds.

Animals↗

Vitamin B12 deficiency and incontinence in older people.

OBJECTIVES: To investigate the relationship between urinary incontinence and Vitamin B12 deficiency in community-living older people using standard serum cobalamin levels as well as the metabolites methylmalonic acid (MMA) and total homocysteine (HCYS). DESIGN: A prospective cross-sectional study of community-living older people. PARTICIPANTS: Independent and cognitively normal adults (mean age=72 years, range=65-89 years) living in the community. One hundred and nineteen volunteers were recruited at group meetings, activity groups, and through the use of posters. MEASUREMENTS: Information on urinary continence was provided by the participant during a systematic medical history, and was defined as any amount of uncontrolled leakage of urine. Vitamin B12, methylmalonic acid and homocysteine levels were determined in all subjects. MAIN RESULTS: We found no significant differences between the continent and incontinent group in regard to their serum Vitamin B12 (OR=1.34, CI: 0.39-4.58, p=.424), methylmalonic acid levels (OR=0.71, CI: 0.24-2.10, p=.386), or total homocysteine levels (CI: 0.29-4.54, p=.535). CONCLUSIONS: In our study continence was not significantly affected by the B12 status of the subject; neither serum B12 levels or the metabolites MMA and HCYS (reflecting B12 function) were significantly different in the continent group versus the incontinent one.

Aged↗

Safety, immunogenicity and antibody persistence of an inactivated hepatitis A vaccine in 4 to 15 year old children.

Among 277 healthy Venezuelan children, aged between 4 and 15 years, who were screened for hepatitis A virus (HAV) antibodies, 118 seronegative children were enrolled in an open study. Each child received one dose of the Pasteur Mérieux Connaught inactivated hepatitis A vaccine (AVAXIM¿trade mark omitted¿, 160 antigen units), followed by a booster dose 24 weeks later. All seronegative subjects seroconverted 2 weeks after immunisation (antibody titres greater, similar20 mIU/ml), and antibody titres were still over greater, similar20 mIU/ml after 24 weeks, at the moment of the booster dose. The anti-HAV antibody geometric mean titre (GMT), as measured by a modified radio-immunoassay (HAVAB(R), Abbott Laboratories, North Chicago, IL, USA), was 73.7 mIU/ml, 2 weeks after the first dose. Four weeks after the booster, the GMT value reached 6999 mIU/ml, representing a 29.6-fold rise from pre-booster levels. One year after the booster dose, the GMT value was 1673 mIU/ml in the 92 subjects who provided blood samples at this time, all of whom were still seroconverted ( greater, similar20 mIU/ml). No serious adverse event related to the vaccination occurred during the study. No immediate systemic reaction occurred. Local reactions were reported by 9.3% of subjects who received the primary injection and 5.5% of those given the booster dose. The systemic reactions were mainly fever and myalgia reported over the 7 days following the injection by 3.4% of subjects after the first dose and 5.5% of subjects after the booster dose. A clinically significant elevation of serum transaminase from pre-immunisation levels was noted in one subject (AST level 2.2 times the upper normal limit) 2 weeks after the first injection, although this was not associated with any clinical signs of impaired liver function. This trial demonstrated that AVAXIM¿trade mark omitted¿ containing 160 antigen units is safe and highly immunogenic in healthy children aged between 4 and 15 years, and could be included in the childhood vaccination schedule to control infection in areas endemic for hepatitis A.

Adolescent↗

Monitoring follicular development in cattle by real-time ultrasonography: a review.

The application of real-time ultrasonography to monitoring ovarian function in mammals has advanced the understanding of follicular dynamics and its regulation. Follicular development is a wave-like sequence of organised events. The waves consist of the synchronous growth of small (4 to 5 mm) antral follicles, followed by the selection and growth of one dominant follicle which achieves the largest diameter and suppresses the growth of the subordinate follicles. In the absence of luteal regression, the dominant follicle eventually regresses (becomes atretic) and a new follicular wave begins. The dominant follicle regulates the growth of the subordinate follicles, because the appearance of the next wave is accelerated if the dominant follicle is ablated, and delayed if the lifespan of the dominant follicle is prolonged. During bovine oestrous cycles, two or three successive waves emerge, on average, on the day of ovulation (day 0) and day 10 for two-wave cycles, and on days 0, 9 and 16 for three-wave cycles. During the oestrous cycle there are thus two or three successive dominant follicles, and the last of these ovulates. Ovarian folliculogenesis is a complex process involving interactions between pituitary gonadotrophins, ovarian steroids and non-steroidal factors. Subtle changes in the hormonal milieu regulate folliculogenesis and the emergence of a follicular wave is preceded by a small increase in the concentration of plasma follicle-stimulating hormone. The mechanisms that promote the selection of a dominant follicle have not been elucidated, but considerable progress has been made in understanding follicular development and its regulation. Most treatments designed to control the development of follicular waves have been based on the physical or hormonal removal of the suppressive effect of the dominant follicle, and the consequent controlled induction of the emergence of a new follicular wave. The studies reviewed here describe current methods for regulating the bovine ovarian cycle, interesting models for future studies, and information that may be used for improving reproductive efficiency.

Animals↗

Expression of HLA G in human tumors is not a frequent event.

Expression of HLA G may be a way for tumor cells to escape immuno-surveillance. HLA G is selectively expressed by extravillous trophoblast in the human placenta, a tissue that does not express HLA A or B molecules. It is tempting to propose that tumor cells resemble this unique HLA class I phenotype as they frequently lose classical HLA A, B and C class I expression. Such peculiar HLA class I distribution would in theory allow tumor cells to escape from T- and NK-cell cytotoxicity. To determine whether HLA G is expressed on tumor cells, we studied HLA G mRNA levels using RT-PCR and HLA G cell-surface expression by immunohistological techniques in a panel of 50 human solid tumor tissues, 31 tumor cell lines of different origin, 4 autologous mucosa samples and 3 peripheral white cell samples. We found mRNA transcripts of different HLA G isoforms in most of the samples studied. However, we did not detect cell-surface expression of HLA G using 3 specific monoclonal antibodies (MAbs; 87G, 01G and G223). HLA G was detected only in the U937 myelomonocytic cell line after stimulation with IFN-gamma. We favor the hypothesis that HLA G plays a minor role, if any, in providing an inhibitory signal to NK cells to escape immunosurveillance. We cannot, however, exclude the possibility that some other HLA G isoforms may be expressed in some tumors.

Antibodies, Monoclonal↗

PCR analysis in the pathological diagnosis of Whipple's disease: emphasis on extraintestinal involvement or atypical morphological features.

PCR analysis of species-specific bacterial 16S rRNA gene of Tropheryma whippelii was performed in biopsies from 10 cases of Whipple's disease (WD). In seven patients showing the typical clinical picture of WD, PCR was performed on the diagnostic intestinal biopsy. In the remaining three cases (an autopsy case of disseminated WD and two patients showing lymphadenopathy as the initial clinical presentation), PCR was done on lymph node specimens. In one of the lymph node biopsies, an unusual sarcoidlike granulomatous reaction had led to the diagnosis of sarcoidosis. The specific bacterial DNA was detected in all cases, both in intestinal biopsies and in lymph node specimens. Follow-up biopsies after antibiotic therapy were evaluated in two patients. The two follow-up biopsies were negative, although in both of them scattered nests of PAS-positive macrophages remained. The results of this study suggest that PCR analysis of species-specific sequences of the 16S rRNA of Tropheryma whippelii is a very useful tool for the pathological diagnosis of WD. It confirms the diagnosis of WD in intestinal biopsies as well as in extraintestinal sites, even when the morphological appearance is not typical. It is also the most precise technique for monitoring therapeutic effects.

Actinobacteria↗