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Biomedical subjects

D Rodriguez

Publications and source records attributed to D Rodriguez.

At least 91 records · Page 5Linked to original sources

Italian population data on the loci LDLR, GYPA, HBGG, D7S8 and GC.

Allele and genotype frequencies for the five loci LDLR, GYPA, HBGG, D7S8 and GC were determined for 374 unrelated Italians using a multiplex PCR-amplification and typing commercial kit. The distribution of the genotype frequencies showed no deviations from Hardy-Weinberg expectations. The combined power of discrimination and chance of exclusion for all five loci were 0.999 and 0.702, respectively. A test for homogeneity was performed and no significant differences were observed among the Caucasian population samples.

Alleles↗

Patterns of recurrence following pelvic exenteration and external radiotherapy for locally advanced primary rectal adenocarcinoma.

BACKGROUND: Local recurrence remains the main site of failure after pelvic exenteration for locally advanced primary rectal adenocarcinoma. This is a report on the patterns of recurrence in a group of such patients treated with pelvic exenteration and radiotherapy. METHODS: Between 1980 and 1992, we treated 49 patients. Thirty-one received preoperative radiotherapy (pre-RT), 4,500 cGy. Six weeks later, we performed posterior pelvic exenteration (PPE) in 21 patients, and total pelvic exenteration (TPE) in 10. Nine patients received postoperative radiotherapy (post-RT), 5,000 cGy after a PPE. Nine patients had surgery only, PPE (n = 7) and TPE (n = 2). RESULTS: Surgical mortality occurred in 16% of those patients who received pre-RT. The median follow-up was 52 months. Recurrences occurred in 23% of those patients who received pre-RT (local, one; local/distant, one; distant, four); in 88% of those patients treated with surgery only (local/distant, four; distant, four); and in 11% of those treated with post-RT (distant, one). The 5-year survival for patients who received radiotherapy was 66 versus 44% for those treated with surgery only. CONCLUSION: Local control of locally advanced primary rectal adenocarcinoma requiring a pelvic exenteration is improved by the addition of radiotherapy. When recurrences do occur they are predominantly at extrapelvic sites.

Adenocarcinoma↗

Quantification of antigen specific CD8+ T cells using an ELISPOT assay.

An ELISPOT assay to detect and determine the number of antigen specific CD8+ T cells was standardized using cloned murine CD8+ T cells specific for the epitope SYVPSAEQI of a rodent malaria antigen. This assay is based on the detection of IFN-gamma secretion by single cells after their stimulation with antigen. The interferon secretion is visualized as spots revealed by using enzyme labeled anti-IFN-gamma monoclonal antibodies. Using known numbers of cloned murine CD8+ T cells it was determined that the assay detects 80-95% of these CD8+ T cells. The optimal culture conditions for the stimulation of the CD8+ T cells were determined and the antigen concentration, number of antigen presenting cells and supplement of growth factors required to perform the assay were defined. This ELISPOT assay can be performed with spleen cells from immunized mice, and provide the precise number of antigen specific CD8+ T cells present in mixed lymphocyte populations. This method is more sensitive than the chromium-51 release assay, and much simpler than the conventional precursor frequency analysis, providing the number of antigen specific CD8+ T cells in 36-48 h.

Amino Acid Sequence↗

Clinical, biochemical, and molecular analysis of a maternally inherited case of Leigh syndrome (MILS) associated with the mtDNA T8993G point mutation.

We report a new case of Leigh disease (subacute necrotizing encephalomyelopathy) in a girl with mitochondrial DNA (mtDNA) mutation in the ATPase6 gene at nucleotide position 8993. Sequence analysis of mtDNA revealed a T-to-G transversion at nucleotide position 8993 in the ATPase6 gene. Southern blot restriction analysis of patient muscle mtDNA showed only a mutant pattern for the mutation 8993. Molecular analysis of seven subjects from the family showed that except for the father they all carried the 8993 mtDNA mutation in all studied tissues, with high percentages in the two symptomatic children and even in one asymptomatic boy.

Brain↗

[Use of intravenous midazolam in status epilepticus in children].

BACKGROUND: Status epilepticus is usually treated by benzodiazepines such as diazepam or clonazepam in association with phenytoin and phenobarbital. Midazolam (MDZ) is a recently developed short-elimination half-life benzodiazepine. CASE REPORTS: Four children, aged 3 days to 4 years, were hospitalized in the pediatric intensive care unit for life-threatening illness and developed status epilepticus. They were given an i.v. bolus dose of 300 to 500 micrograms/kg of MDZ immediately followed by a continuous i.v. infusion at the dose of 100 to 300 micrograms/kg/h. All seizures stopped within 1 hour after the bolus dose administration. No acute adverse events of MDZ were noted. Withdrawal symptoms in one patient were controlled by progressive reduction of MDZ doses. Neurologic sequelae were noted in three children, secondary to their primitive illness. CONCLUSIONS: High doses of MDZ are effective for treating refractory status epilepticus; optimal dosage and duration of treatment remains to be determined.

Anti-Anxiety Agents↗

Sphincter-saving surgery with and without pre-operative radiation therapy as treatment for adenocarcinoma of the mid-rectum.

AIMS: To determine if pre-operative radiation therapy induces a local response in patients with complete tumour penetration into the rectal wall and allows for anal sphincter preservation, we compared the results from pathological specimens and local recurrences as measurable end-points in patients treated with pre-operative radiation therapy plus low anterior resection vs. those only treated with low anterior resection. METHODS: From January 1986 to December 1992, we treated 62 patients with mid-rectal adenocarcinoma (5-10 cm from the anal verge as determined by rigid proctosigmoidoscopy with the patient in the jackknife position). Pre-operative evaluation included: complete blood cell count, chemistry profile and the determination of carcinoembryonic antigen, chest X-ray, barium enema or colonoscopy and CT scan of the abdomen and pelvis. Only tumours potentially curative by resection in patients with performance status 0-2 (ECOG) were included. Twenty-one patients received pre-operative radiation therapy at a dose of 45 Gy delivered to the pelvis; 4-8 weeks later a low anterior resection was performed. Forty-one patients were treated with low anterior resection alone. Surgical specimens were classified according to the Astler-Coller modification of Dukes' classification. RESULTS: There were 36 males and 26 females, with a mean age of 56 years. The surgical specimens of those treated only with surgery were classified as: A, 5; B1, 4; B2, 15; C1, 2; and C2, 15. Postirradiated specimens: no residual tumour, 3; A, 4; B1, 4; B2, 7; C2, 3. One surgical death occurred in the group who underwent surgery alone. The median follow-up was 50 months in patients treated with surgery alone vs. 62 months in the combined approach group. Local recurrences occurred in 15/40 patients treated with surgery alone and in 2/21 of those treated with the combined approach (P = 0.043). Anal sphincter continence was classified as excellent by 24/40 patients treated with surgery only and by 18/21 patients treated with the combined approach. The 5-year survival period was 58% in the surgery only group and 82% in the group with combined treatment (P = 0.08). CONCLUSIONS: The use of pre-operative radiation therapy plus low anterior resection was associated with a lower rate of local recurrence and with a higher number of surgical specimens with no lymph node metastases. Thus, this combined treatment modality should be further evaluated as a possible treatment of mid-rectal cancers in good surgical candidates selected for sphincter-saving procedures.

Adenocarcinoma↗

Enhanced proteolytic processing of the human immunodeficiency virus type 1 envelope protein in murine Ltk(-) cells.

Proteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) precursor glycoprotein (gp160) to produce the mature gp120 and gp41 proteins is required for virus infection and virus-induced cell fusion. It has also been suggested that cleavage of gp120 at the immunodominant V3 loop region is required for virus-to-cell and cell-to-cell fusion. In this investigation we have studied the proteolytic processing of the HIV-1 Env in cells of various origins (human, monkey, and mouse) infected with a vaccinia virus recombinant expressing the entire gp160 protein (VV-env-1). We have observed that in murine Ltk(-) cells, in addition to the proteolytic cleavage of gp160 at the gp120/gp41 site, there is also extensive intracellular proteolytic processing of gp160 at the V3 loop and at a novel site located at the C terminus of gp41. Similar proteolytic processing of the Env precursor was observed after treatment of extracts of VV-env-1-infected monkey cells with thrombin, a trypsin-like protease that has been shown to cleave the gp120 at the V3 loop. Our findings suggest that murine Ltk(-) cells could be a good model system for structural studies of Env with different HIV isolates and in searches for proteinase inhibitors that could prevent HIV-1 infection of susceptible cells by blocking proteolysis of Env.

Animals↗

Relationship between procedures and health insurance for critically ill patients with Pneumocystis carinii pneumonia.

The objective of the present study was to assess the association between type of health insurance coverage and use of diagnostic tests and therapies among patients with AIDS-related Pneumocystis carinii pneumonia (PCP). Fifty-six private, public, and community hospitals in Chicago, Los Angeles, and Miami were selected for the study, and the charts of 890 patients with empirically treated or cytologically confirmed PCP, hospitalized during 1987 to 1990 were retrospectively reviewed. Patients were classified by insurance status: self-pay (n = 56), Medicaid (n = 254), or private insurance, including health maintenance organizations and Medicare (n = 580). Primary outcomes were the use and timing of bronchoscopy, the type and timing of PCP therapy, and in-hospital mortality. The results indicate that Medicaid patients were less likely than privately insured patients to undergo bronchoscopy (relative odds = 0.61; 95% CI = 0.40, 0.93; p = 0.02) or to have their diagnosis of PCP confirmed (relative odds = 0.51; 95% CI = 0.33, 0.77), after adjusting for patient, severity of illness, and hospital characteristics. Medicaid patients were approximately three-fourths more likely than privately insured patients (relative odds = 1.73; 95% CI = 1.01, 2.96; p = 0.04) to die in-hospital, after adjusting for patient, severity of illness, and hospital characteristics. However, with further adjustment for confirmation of PCP, Medicaid patients no longer had a significantly higher likelihood of dying in-hospital. We conclude that Medicaid patients are less likely to receive diagnostic bronchoscopy than privately insured or self-insured patients, more likely to be empirically treated for PCP, and more likely to die in-hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

United States Supreme Court rules against Medicare providers in cost reimbursement case. Shalala v. Guernsey Memorial Hospital.

In the long run, the impact of Guernsey will depend on the interpretation and application of the decision by HCFA, the Provider Reimbursement Review Board, and the courts. If HCFA interprets the decision as a signal that the Supreme Court is willing to grant federal agencies broad latitude to avoid the rulemaking requirements of the APA, providers may have fewer opportunities for formal input into payment policy issues under the Medicare program. The impact of the case may well go beyond cost-based reimbursement issues and affect all aspects of the Medicare program.

Accounting↗

Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity.

We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8+ T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8+ T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.

Amino Acid Sequence↗

Human core temperature minimum can be modified by ambient thermal transients.

By using slow linear thermal transients (+/- 0.025 degree C/min) of reduced amplitude (+/- 3 degrees C around thermoneutrality), we were able to advance the minimum of human internal temperature (Ti) during nocturnal sleep. During experimental night the minimum of esophageal (Tes) and rectal (Tre) temperature were respectively advanced by 1.6 h (P < 0.01) and 2.6 h (P < 0.001) in comparison to reference night spent at thermoneutrality. It must be emphasized that the provoked advance of nocturnal Ti minimum was not accompanied by any change in sleep latency, efficiency, SWS and REM sleep percentages. The result shows that appropriate ambient temperature transient changes could be used to modify the course of human Ti one of the major biological rhythms usually considered as resistant to sleep-wake rhythm manipulation.

Adult↗

Adaptation of signal transduction in brain.

Cell culture models were used to study the effects of long-term ethanol exposure on neuronal cells. Effects on phospholipase C and phospholipase D mediated signal transduction were investigated by assaying receptor-binding, G protein function, activities of lipases, formation of second messengers and c-fos mRNA. The signal transduction cascades displayed abnormal activities from 2 to 7 days of exposure which differed from the acute effects. Phosphatidylethanol formed by phospholipase D is an abnormal lipid that may harmfully affect nerve cell function.

Acclimatization↗

Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy.

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.

Base Sequence↗

Promoting quality mental health care delivery with critical path care plans.

1. Mental Health providers are under increasing pressure to provide objective, individualized care that produces outcomes that may be measured against accepted clinical standards. 2. Clinicians may now track patient responses throughout a continuum of treatment in varying locations by using a customized critical path/treatment plan format. 3. Care delivery is documented by superimposing actual occurrences over desired ones on a critical pathway.

Continuity of Patient Care↗

A proposal for the establishment of the National Center for Phytogenetic Resource Conservation in the Venezuelan Republic.

The conservation of biodiversity, a valuable natural resource, is considered essential. In the face of continued threats to this resource the establishment of a National Center for Phytogenetic Resource Conservation in Venezuela is proposed. The proposed center would have the following main objectives: inventory of resources, establishment of a plant gene bank, basic ecological research, promotion of cultivation of useful but endangered species, promotion of national and international information-exchange, and protection of natural habitats. The organizational structure of the proposed center is outlined.

Conservation of Natural Resources↗

Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria.

Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.

Amino Acid Sequence↗

Hemodialysis changes the QRS amplitude in the electrocardiogram.

We studied eight patients to determine whether changes occur in the QRS amplitude when these patients are submitted to hemodialysis. The following variables were assessed before and after each (N = 28) hemodialysis session: (1) plasma sodium and potassium concentrations, (2) QRS amplitude, (3) the heart rate and its variability, (4) ventricular volumes, ventricular mass, ejection fraction and circumferential fiber shortening, (5) arterial pressure and end systolic stress, and (6) body weight. QRS amplitude was computed as the algebraic sum of the positive and negative waves of each QRS complex of the electrocardiogram. QRS amplitude changes were compared to body weight, ventricular volumes, ventricular mass, ejection fraction, circumferential fiber shortening, plasma potassium and sodium concentrations, arterial pressure, end systolic stress, heart rate, and R-R variability. After the hemodialysis sessions we found a significant increase (P = 0.0006) in QRS amplitude and a significant decrease in body weight (P = 0.0001), end diastolic volume (P = 0.043), plasma potassium concentration (P = 0.000001), end systolic stress (P = 0.025) and systolic arterial pressure (P = 0.023). Hemodialysis did not produce significant changes in the other variables. The statistical analyses performed did not show any significant influence of any of the measured variables on the QRS amplitude change. The QRS amplitude increases after hemodialysis but the cause of this increase is still unclear.

Arrhythmias, Cardiac↗

Recombinant vaccinia viruses expressing GP46/M-2 protect against Leishmania infection.

Leishmania is a genus of parasitic protozoa capable of causing a spectrum of human diseases. The GP46/M-2 membrane glycoprotein has been demonstrated in a murine model system to elicit a protective immune response against infection with Leishmania amazonensis; in highly susceptible BALB/c mice, immunization leads to significant protection against infection. In the present study, for induction of long-term immunological effects, two recombinant vaccinia viruses, derived from the wild type and attenuated variant 48-7 and expressing the GP46/M-2 protein, were constructed; to ensure safety, we used the attenuated vaccinia virus mutant (48-7) as a live vector. Susceptible BALB/c mice immunized with either GP46/M-2-recombinant vaccinia virus were significantly protected against infection with L. amazonensis; 45 to 76% of the animals were completely protected (sterile) against a challenge inoculum of 10(3) infective organisms. The protectively immunized animals demonstrated T- and B-cell-dependent immunological responses; both lymphokine responses as well as antibody responses and long-term memory are indicative of T-cell activation. This first report of the use of a recombinant vaccinia virus to induce protection against a Leishmania infection indicates that recombinant vaccinia viruses should be of value in the design of a safe and effective vaccine against this parasitic disease.

Animals↗