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Biomedical subjects

R Gonzalez

Publications and source records attributed to R Gonzalez.

At least 55 records · Page 3Linked to original sources
PubMed2001

Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma.

Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and beta2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 microg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.

Adult↗
PubMed2000

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.

BACKGROUND: Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. METHODS: We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. RESULTS: Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent. CONCLUSIONS: In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Blood Flow Velocity↗
PubMed2000

Fetal therapy for obstructive uropathy: past, present.future?

Antenatal treatment of obstructive uropathy, although widely performed, remains controversial. An overview of prenatal therapy for obstructive uropathy, the limitations of the early published experience, advances of recent years, and future directions for treatment are reviewed. The clinical approach and outcomes of the Fetal Treatment Program of Hutzel Hospital and Wayne State University are presented. Patient selection for antenatal treatment is based on the existence of a significant threat of neonatal death due to pulmonary hypoplasia, pending exclusion criteria such as anatomical structural anomalies and chromosomal defects. Ultrasonography, karyotyping, and sequential urinary electrolyte analysis are essential. Current treatment involves the placement under ultrasonic guidance of a Rodeck vesicoamniotic shunt. Recent technical advances include the use of amnioinfusion for fetal visualization, temporary fetal paralysis, routine antibiotics, and more-precise catheter placement. The establishment of standardized short- and long-term outcome measures and the documentation of fetal and maternal complications are in progress. Procedural refinement, development of fetoscopic techniques and equipment, identification of urinary markers to aid patient selection, and the collection of multicenter outcome data will assist the future management of prenatally detected obstructive uropathy.

Animals↗
PubMed2000

Newer strategies for effective evaluation of primary melanoma and treatment of stage III and IV disease.

Our objective in this article is to update dermatologists on the clinical management of malignant melanoma, including the role of sentinel node biopsy and options for the treatment of stage III and stage IV disease. The role of the dermatologist throughout the continuum of care is emphasized, and the essential partnership with medical oncology in recognizing promising new options for patients with advanced disease is examined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Pioglitazone attenuates basal and postprandial insulin concentrations and blood pressure in the spontaneously hypertensive rat.

Subjects with hypertension are hyperinsulinemic and resistant to insulin-stimulated glucose uptake. A similar paradigm is found in the spontaneously hypertensive rat (SHR). These findings suggest the possibility that insulin resistance and hyperinsulinemia may play an important role in blood pressure regulation. Pioglitazone, a thiazolidinedione derivative, sensitizes target tissues to insulin and decreases hyperglycemia and hyperinsulinemia in various insulin-resistant animals. The purpose of this study was to assess the influence of pioglitazone administration on pre- and postprandial glucose and insulin concentrations and determine whether changes in beta-cell secretion resulted in any change in blood pressure measurements. Twelve SHR were fed custom diets ad libitum, six with and six without pioglitazone (20 mg/kg chow). Fasting and postprandial glucose levels were unaltered by pioglitazone treatment. Fasting insulin concentrations were similar at week 1, but were significantly lower (P < .01) in the pioglitazone group at weeks 3 (1.89 +/- 0.3 v7.94 +/- 1.5 ng/mL) and 4 (4.5 +/- 1.4 v9.1 +/- 0.7 ng/mL), compared with the control group. Pioglitazone also significantly (P < .01) lowered postprandial insulin concentrations after an oral glucose challenge. Systolic, mean, and diastolic blood pressures were significantly lower (P < .01), 177 +/- 3 v190 +/- 4.7 mm Hg, 162 +/- 2.1 v175 +/- 5.9 mm Hg, and 156 +/-2.1 v168 +/- 6.2 mm Hg, respectively, in the animals receiving pioglitazone versus the control group. Heart rate, body weight, serum cholesterol, and triglyceride levels were comparable between the two groups. In conclusion, pioglitazone significantly decreased fasting and postprandial insulin concentrations and effectively lowered blood pressure in the SHR.

Animals↗
PubMed2000

Kinetics of c-phycocyanin reaction with hypochlorite.

Hydrochlorous acid bleaches c-phycocyanin visible absorbance with a second-order rate constant (pH 7.4) of 1.3x10(3) M(-1) s(-1). In excess of protein, ca. 0.16 bilin moieties are disrupted by each reacted HOCl molecule. This indicates that the main reaction takes place at the apoprotein level, with a total rate constant (in monomeric units concentration) of 2.5x10(4) M(-1) s(-1). This rate constant is too low to provide protection to other biomolecules under physiological conditions. The reported antiinflammatory properties of phycocyanin are not then related to the removal of HOCl. On the other hand, the rather slow reaction rate with HOCI could be beneficial to its role as antiinflammatory agent since it will allow the protein to maintain its integrity at the inflammation locus.

Bile Pigments↗
PubMed2000

Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients: follow-up study and prognostic significance.

BACKGROUND: Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma DNA and patient survival. PATIENTS AND METHODS: Thirty-five patients with SCLC were selected after histological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chosen for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for mutations of the TP53 gene in tumor and plasma DNA. RESULTS: In 25 patients (71%) at least one molecular change precisely matching that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and patients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant difference (P = 0.02) in survival compared with patients bearing only one of these molecular changes. In 15 cases it was possible to find a correlation either between tumor response and disappearance of abnormal plasma DNA, or tumor progression and persistence of plasma DNA alterations. CONCLUSIONS: Free plasma DNA with molecular alterations is present to a high degree in plasma DNA of SCLC patients and may have a role as a prognostic factor.

Adult↗
PubMed2000

gamma-ray irradiation induces B7.1 expression in myeloid leukaemic cells.

Expression of B7 molecules provides co-stimulatory signals to T lymphocytes, which prevent the induction of anergy. It has been previously reported that B7.1 gene transfer in a murine leukaemia model induced a potent antileukaemic immunity and that relative expression of B7.1 and B7.2 in human acute myeloid leukaemia (AML) had prognostic significance. As ex vivo engineering of leukaemic cells for immunotherapy protocols would require prior irradiation of these cells before reinjection to the patient, we investigated in murine and leukaemic cell lines and in 20 ex vivo primary cultured acute myeloid leukaemic cells the effect of gamma-irradiation on the expression of B7 molecules. We observed that gamma-irradiation enhanced B7.1 molecule expression in murine leukaemic cell lines and in B7.2 molecules in human HL60 and K562 cell lines. gamma-Irradiation induced B7.1 molecule expression in 90% AML samples but only 21% showed B7.2 molecule expression enhancement. B7.1 expression was increased both at the protein and RNA level in human AML cells but only at the protein level in the DA1-3b murine cell line. Oxidative stress increased B7.1 expression in the murine DA1-3b cell line but human cell lines and AML samples remained unaffected both by heat shock and oxidative stress, suggesting different pathways of B7.1 induction between mouse and human cells. Our data show that B7.1 expression can be induced by ex vivo irradiation of AML cells, indicating that these cells can express co-stimulatory molecules without gene transfer.

Animals↗
PubMed2000

Deletion of the unique gene encoding a typical histone H1 has no apparent phenotype in Aspergillus nidulans.

We have cloned the H1 histone gene (hhoA) of Aspergillus nidulans. This single-copy gene codes for a typical linker histone with one central globular domain. The open reading frame is interrupted by six introns. The position of the first intron is identical to that of introns found in some plant histones. An H1-GFP fusion shows exclusive nuclear localization, whereas chromosomal localization can be observed during condensation at mitosis. Surprisingly, the deletion of hhoA results in no obvious phenotype. The nucleosomal repeat length and susceptibility to micrococcal nuclease digestion of A. nidulans chromatin are unchanged in the deleted strain. The nucleosomal organization of a number of promoters, including in particular the strictly regulated niiA-niaD bidirectional promoter is not affected.

Amino Acid Sequence↗
PubMed2000

Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA).

AIM OF THE STUDY: An observational study with valaciclovir was conducted to assess clinical outcome in herpes zoster, especially pain and associated neurological signs and symptoms in relation to a series of demographic and disease characteristics discernible at presentation. The safety and acceptability of valaciclovir for treatment of zoster was assessed in a wide variety of primary care and clinic referral settings. METHODS: In total, 1897 immunocompetent adults with clinically diagnosed, localized acute herpes zoster were enrolled in this international, open-label study of valaciclovir. All subjects received treatment with oral valaciclovir (1000 mg three times daily) for 7 days from entry to the study and were asked to record the presence of zoster-associated pain and abnormal sensations throughout treatment and 6 months' follow-up. They were seen frequently in clinic to verify subjective assessments and for evaluation of rash healing. Safety and tolerability were assessed by adverse event monitoring. RESULTS: Overall, 1191 subjects (63%) were aged > or = 50 years, and 203 (11%) had ophthalmic zoster. Cessation of zoster-associated pain was significantly faster in the younger age group; median times to loss of zoster-associated pain were 23 days and 9 days in the > or = 50 and < 50 years age groups, respectively. Similarly, abnormal sensations resolved significantly more rapidly in the younger subjects; the median duration of abnormal sensations was 31 days in the > or = 50 year olds and 16 days in those aged < 50 years. In cases of ophthalmic zoster, the rate of pain resolution was not different from those with zoster in other dermatomes (median duration of pain 18 vs. 16 days). However, abnormal sensations persisted significantly longer in subjects with ophthalmic zoster than in those with zoster at other sites (47 vs. 22 days). In addition to advancing age, subjects suffering moderate to severe prodromal pain or acute pain during the rash phase were at significantly greater risk of zoster-associated pain and abnormal sensations persisting for longer. Subjects with concomitant neurological disorders were also more likely to develop prolonged abnormal sensations. Valaciclovir treatment was well tolerated, and adverse events were rare and generally mild. CONCLUSION: This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.

Acyclovir↗
PubMed2000

Procedural experience and comfort level in internal medicine trainees.

BACKGROUND: The American Board of Internal Medicine (ABIM) has recommended a specific number of procedures be done as a minimum standard for ensuring competence in various medical procedures. These minimum standards were determined by consensus of an expert panel and may not reflect actual procedural comfort or competence. OBJECTIVE: To estimate the minimum number of selected procedures at which a majority of internal medicine trainees become comfortable performing that procedure. DESIGN: Cross-sectional, self-administered survey. SETTING: A military-based, a community-based, and 2 university-based programs. PARTICIPANTS: Two hundred thirty-two internal medicine residents. MEASUREMENTS: Survey questions included number of specific procedures performed, comfort level with performing specific procedures, and whether respondents desired further training in specific procedures. The comfort threshold for a given procedure was defined as the number of procedures at which two thirds or more of the respondents reported being comfortable or very comfortable performing that procedure. RESULTS: For three of seven procedures selected, residents were comfortable performing the procedure at or below the number recommended by the ABIM as a minimum requirement. However, residents needed more procedures than recommended by the ABIM to feel comfortable with central venous line placement, knee joint aspiration, lumbar puncture, and thoracentesis. Using multivariate logistic regression analysis, variables independently associated with greater comfort performing selected procedures included increased number performed, more years of training, male gender, career goals, and for skin biopsy, training in the community-based program. Except for skin biopsy, comfort level was independent of training site. A significant number of advanced-year house officers in some programs had little experience in performing selected common ambulatory procedures. CONCLUSION: Minimum standards for certifying internal medicine residents may need to be reexamined in light of house officer comfort level performing selected procedures.

Adult↗
PubMed2000

Mutational status of K-ras and TP53 genes in primary sarcomas of the heart.

We investigated three patients with cardiac angiosarcomas and two with cardiac rhabdomyosarcomas, all for mutations at exons 5, 6, 7 and 8 of the p53 gene and at exon 1 of K-ras. No point mutations were observed in the p53 gene in any of the five cases; however, at exon 1 of K-ras, three patients (60%) presented the same mutation at the first base of codon 13 (G to A transition). Interestingly, this mutation was detected in both rhabdomyosarcoma and angiosarcoma histologic sarcoma types.

Adult↗
PubMed2000

A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.

The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.

Abdominal Neoplasms↗
PubMed1999

Transduction of bone marrow cells by the AdZ.F(pK7) modified adenovirus demonstrates preferential gene transfer in myeloma cells.

Adenoviral vectors can efficiently infect myeloma cell lines, but transduction of fresh myeloma cells performed at low multiplicity of infections (MOIs) showed only partial efficacy. The modified adenoviral vector AdZ.F(pK7), through binding of polylysines to heparan sulfate-containing receptors, could increase virus adsorption and gene transfer efficiency in myeloma cells, which express heparan sulfate-containing receptors. Thus, we investigated the ability of AdZ.F(pK7) vector to achieve efficient gene transfer in primary cultured fresh myeloma cells. Transduction of 16 primary cultured myeloma samples showed that gene transfer was much more efficient with AdZ.F(pK7) than with control AdZ.F. Both addition of soluble heparin and cell treatment with heparinase I dramatically inhibited gene transfer in myeloma cells by AdZ.F(pK7) but had no effect with AdZ.F, while addition of recombinant fiber protein inhibited AdZ.F but not AdZ.F(pK7), confirming that AdZ.F(pK7) gene transfer in myeloma cells is mediated by the targeting of heparan sulfates. AdZ.F(pK7) transduction of bone marrow cells showed that myeloma cells and hematopoietic progenitor AC133-, CD34-, and CD33-positive cells were efficiently transduced at an MOI of 100, but that only myeloma cells were significantly transduced at an MOI of 12. Thus, AdZ.F(pK7) vector seems to be well suited for immunological approaches of gene therapy or bone marrow-purging applications in multiple myeloma.

Adenoviridae↗
PubMed1999

Long-term outcome in children after antenatal intervention for obstructive uropathies.

BACKGROUND: Antenatal intervention has been done for fetal obstructive uropathy for over a decade, yet little is known about long-term outcomes. To assess the long-term implications of fetal intervention, we reviewed the outcomes of children who underwent vesicoamniotic shunt placement. METHODS: We reviewed the clinical outcomes of 14 children who underwent vesicoamniotic shunt placement at our institution and who survived beyond 2 years of age. FINDINGS: In 1987-96, 34 patients underwent vesicoamniotic shunt placement. 13 died and 21 survived, of whom 17 are now more than 2 years old. Three survivors were lost to follow-up. Mean age at follow-up was 54.3 months (range 25-114). Final diagnoses included prune belly syndrome (seven cases), posterior urethral valves (four), urethral atresia (one), vesicoureteral reflux (one), and megacystis (one). Height was below the 25th percentile in 12 (86%) with seven (50%) below the 5th percentile. Five (36%) had renal failure and had successful transplantation, three (21%) have renal insufficiency, and six (43%) have normal renal function. Seven (50%) are acceptably continent, five (36%) have not yet begun toilet-training, and two (14%) are incontinent. Three of four children with valves needed bladder augmentation. INTERPRETATION: Antenatal intervention may help those fetuses with the most severe forms of obstructive uropathy, usually associated with a fatal neonatal course. Intervention achieves outcomes similar to less severe cases that are usually diagnosed postnatally.

Catheters, Indwelling↗
PubMed1999

Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations.

Using different molecular techniques, DNA has been detected in the plasma of cancer patients with various types of tumors. We undertook the present study to investigate the presence of plasma DNA, before mastectomy, in patients with breast cancer at diagnosis and to analyze the clinicopathological spectrum of this subgroup of patients with respect to patients without DNA with tumor characteristics. We studied 62 patients with breast cancer, who were selected sequentially after mastectomy and diagnosis of breast carcinomas. Genomic DNA extracted from tumor and normal tissues, normal blood cells, and plasma was used for molecular studies. Alterations in polymorphic markers selected because they had been found to show a high rate of alterations in breast cancer in previous studies (D17S855, D17S654, D16S421, TH2, D10S197, and D9S161), as well as mutations in the p53 gene and aberrant methylation at the first exon of p16INK4a, were used to identify and characterize tumor and plasma DNA. Thirteen clinicopathological parameters were analyzed in each patient. We identified 56 cases (90%) with at least one molecular event in tumor DNA, and 41 cases (66%) with a similar alteration in plasma DNA. Comparison of the clinicopathological parameters between patients with and without plasma DNA revealed significant differences in the axillary involvement, rate of invasive ductal carcinoma, high proliferative index, and the parameter comprised of lymph node metastases, histological grade II, and peritumoral vessel involvement. A high proportion of breast cancer patients exhibited plasma DNA at diagnosis similar to tumor DNA, and its presence correlated significantly with pathological parameters associated with a poor prognosis.

Breast↗
PubMed1999

Abnormal frequencies of alleles in polymorphic markers of the 17q21 region is associated with breast cancer.

This study was carried out to evaluate the frequencies of alleles of four polymorphic markers in the 17q21 region in breast cancer patients, and their relation to seven pathological parameters. One hundred and sixty-four patients with breast cancer and 102 controls were analyzed. D17S856, D17S855, D17S1323 and D17S1327 polymorphic markers were studied, and used to investigate loss of heterozygosity in this region. The frequencies of alleles at marker D17S856 differed significantly in breast cancer patients and controls, and were related to histologic features considered to indicate a poor prognosis. When present, the pathophenotype of tumors associated with LOH in the 17q21 region is modified.

Alleles↗