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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 343 records · Page 19Linked to original sources
PubMed1995

Paclitaxel: a radiation sensitizer of human cervical cancer cells.

Paclitaxel is an exciting chemotherapeutic agent active in a variety of malignant tumors. This study was designed to explore the radiosensitizing potential of paclitaxel in human cervical cancer cell lines. The cell lines ME180, SiHa, and MS751 were evaluated. Experiments were performed in the proliferative phase of growth. Paclitaxel doses were treated at 0.01x, 0.02x, 0.03x, 0.04x, and 0.05x peak plasma concentration (PPC) in ME180 and 0.001x, 0.002x, 0.003x, 0.004x, and 0.005x PPC in SiHa and MS751. Radiation (RT) doses of cobalt-60 were 0, 2, 4, 6, 8, and 10 Gy. In the combination group RT was given 48 hr after paclitaxel treatment. To allow for median effect analyses, combination doses were kept at a fixed ratio: 0.01x/2 Gy, 0.02x/4 Gy, 0.03x/6 Gy, 0.04x/8 Gy, and 0.05x/10 Gy for ME180 and 0.001x/2 Gy, 0.002x/4 Gy, 0.003x/6 Gy, 0.004x/8 Gy, and 0.005x/10 Gy in MS-751 and SiHa. Adenosine triphosphate bioluminescence was performed on Day 7 after treatment and compared to untreated controls. Dose-response data were fit to the linear quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. The median effect principle was used to evaluate the nature of the interaction between the two therapeutic modalities. Paclitaxel increased radiation cytotoxicity in all three cell lines. Mean inactivation D values for RT versus combination were 6.70 (+/- 0.15) and 4.33 (+/- 0.43) (P = 0.004) in ME180, 6.08 (+/- 0.70) and 4.54 (+/- 0.093) (P = 0.033) in MS751, and 7.03 (+/- 0.46) and 5.97 (+/- 0.51) (P = 0.034) in SiHa. The interaction of paclitaxel and RT was found to be supraadditive in ME180 and SiHa and subadditive in MS751. We conclude that paclitaxel has modest radiation-sensitizing effects in cervical cancer cell lines and that further clinical trials should be considered.

Cell Survival↗
PubMed1995

Localization of foot and mouth disease virus RNA in tissue culture infected cells via in situ polymerase chain reaction.

Foot and mouth disease virus RNA was visualized in infected primary tissue culture cells by in situ PCR incorporating digoxigenin-labeled dUTP. The viral RNA polymerase gene was used as a target for amplification. Infected cells revealed cytoplasmic staining, predominantly perinuclear. The intensity of staining was in proportion to the degree of cytopathology observed and similar to the results obtained using immunoperoxidase staining. The in situ PCR technique for FMDV detection could be applied to formalin-fixed samples and be useful for the study of persistent infections.

Animals↗
PubMed1995

Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.

The beta 3-adrenergic receptor (AR) is widely distributed in peripheral tissues, but up to now it has not been detected in the central nervous system. By using the polymerase chain reaction (PCR) technique, we found the beta 3-AR mRNA to be present in all the regions of the human brain we investigated. The quantities found were very low compared to those of the beta 1-AR and beta 2-AR mRNAs, being hardly detectable in adult brain. In contrast, the brain of very young infants contained about 100 times more beta 3-AR mRNA than the adult brain, whereas the amounts of beta 1-AR and beta 2-AR transcripts were essentially the same. In addition, using PCR we have cloned a central beta 3-AR coding region from a human frontal cortex cDNA library and have found it to be identical to the corresponding peripheral sequence.

Aged↗
PubMed1995

Idiopathic dialysis ascites in the nineties: resolution after renal transplantation.

The incidence of idiopathic dialysis ascites seems to have decreased since the introduction of more effective techniques for control of fluid overload and uremia in chronic hemodialysis patients. Most of the patients reported so far had some predisposing factor, such as malnutrition or sustained fluid overload. We report a case of idiopathic dialysis ascites in a young well-nourished woman with an excellent control of fluid overload and in whom biocompatible dialyzer membranes and volumetric controlled ultrafiltration had been used since her onset of chronic dialysis. Extensive studies excluded the existence of an underlying cause for ascites. Ascitic fluid had the characteristics of an exudate, and a peritoneal biopsy specimen showed chronic nonspecific inflammatory changes. Massive ascites persisted for 6 months, requiring repeated paracentesis, until the performance of a successful renal transplantation. Coinciding with the recovery of renal function, a dramatic disappearance of ascites was observed.

Adult↗
PubMed1995

Pharmacological evidence for the existence of different subtypes of muscarinic acetylcholine receptors for phosphoinositide hydrolysis in neonatal versus adult rat atria.

The negative inotropic effect of carbachol, as well as phosphoinositide hydrolysis, was measured in atria from neonatal and adult rats. Carbachol increased phosphoinositide hydrolysis and decreased dF/dt of both neonatal and adult atria; however, the neonatal atria showed hypereactivity to carbachol as compared with adult atria. Inhibition of phospholipase C reduced the supersensitivity to carbachol upon contractility in neonatal atria producing values similar to those of the adult atria, suggesting that muscarinic acetylcholine receptor (mAchR) stimulation is secondary to receptor-mediated hydrolysis of phosphoinositides. Pharmacological analysis with mAchR antagonists tends to support the idea that m1 and m2 subtypes are the most important mediators of the response to carbachol in neonatal atria. In adult atria, the effect of carbachol is coupled only to mAchR m2 subtypes.

Animals↗
PubMed1995

Disposal-related sharps injuries at a New York City Teaching Hospital.

OBJECTIVE: To characterize disposal-related sharps injuries. DESIGN: A three-part study including (a) descriptive analysis of disposal-related injuries in a 1-year period, (b) 4:1 matched case-control study of nurses injured while using sharps disposal containers, and (c) survey to solicit opinions of users of containers. SETTING: An 1,181-bed teaching hospital in New York City. PARTICIPANTS: For epidemiologic analyses, persons with self-reported injuries identified via New York State and Occupational Safety and Health Administration forms and control nurses without self-reported injuries. For survey, convenience sample of hospital nurses, laboratory workers, and maintenance workers. MAIN OUTCOME MEASURES: Circumstances of injuries determined by study questionnaires. Employee opinions obtained by questionnaires and discussions during small group sessions. RESULTS: Three hundred sixty-one persons reported sharps injuries, of whom 72 (20%) had disposal-related injuries. Persons with disposal-related injuries included four hospital visitors and one patient. Of 67 disposal-related injuries among employees, 25 (37%) directly involved use of a sharps disposal container. Significant risk factors for injury included container height greater than 4 ft above the floor, distance less than 5 ft from site of sharp object use to nearest container, and lack of attendance at universal precautions inservice classes. Survey groups involved 69 employees who identified a variety of preferred features for sharps disposal containers. CONCLUSIONS: Disposal of sharp objects is an important cause of sharps injuries. Ergonomic factors, worker education, and appropriate container design should be considered in injury prevention strategies. Relevant guidelines and regulations are lacking and are needed.

Case-Control Studies↗
PubMed1995

In vitro chemosensitivity of paclitaxel and other chemotherapeutic agents in malignant gestational trophoblastic neoplasms.

This is the first report on the ATP cell viability assay as a chemosensitivity test system for gestational trophoblastic neoplasms (GTN). We obtained chemosensitivity profiles in two established trophoblastic cell lines and four fresh tumors. Ten drugs were tested in vitro in the two cell lines JAR and JEG-3. The IC50 values of the 10 chemotherapeutic agents tested were very similar for both cell lines. The three most active drugs in these cell lines were VP-16, paclitaxel and vincristine. This is the first report on the activity of paclitaxel in trophoblastic cell lines. We furthermore evaluated this assay for chemosensitivity testing in four fresh malignant GTN tumors: one placental site trophoblastic tumor, one chorocarcinoma and two invasive moles. The placental site trophoblastic tumor specimen revealed to be rather chemoresistant in vitro whereas the other three tumors were chemosensitive. From our cell line data we conclude that the ATP cell viability assay is a practicable assay for chemosensitivity testing of GTN cell lines and gives repeatable results. However, the value of this assay for fresh GTN chemosensitivity testing needs to be defined.

Adenosine Triphosphate↗
PubMed1995

Quantitative neuropathology of a focal nerve injury causing hyperalgesia.

The chronic constriction injury (CCI) model of neuropathy in the rat produces hyperalgesia and allodynia in the sciatic distribution of one hindlimb. We previously described the pathology of the affected nerves at the light microscopic and electron microscopic levels and in this report quantify the morphological changes of the nerves. This analysis gives new insights into the pathophysiology and pain-related mechanisms in this model of human neuropathy. We observed that total fascicular area increased up to fourfold due to an initial massive increase in edema and, later, endoneurial cells. Intact myelinated nerve fibers were reduced from 75% of fascicular area to 29.7% on day 1 and to a minimum of less than 0.5% on day 14 when edema had resolved. The few surviving myelinated fibers were in the small to medium size range. Fiber size histograms revealed an increase in fiber size early on, corresponding to fiber swelling, and the later loss of large as well as small myelinated fibers. Unmyelinated nerve fibers dropped from 19.36/1,000 microns 2 to 6.08/1,000 microns 2 on day 5, and increased from there on. Sprouts were first visible on light micrographs on day 7, occupying 6.8% of fascicular area, while regenerating fibers that were undergoing myelination reached 42.6% of fascicular area by day 42. Macrophage numbers were maximal on day 14 and were still increased on day 42. These data support the hypothesis that the pathogenesis of the extended hyperalgesia following chronic constrictive nerve injury is temporally linked with Wallerian-like degeneration and macrophage activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Gamma interferon is critical for resistance to Theiler's virus-induced demyelination.

Administration of neutralizing monoclonal antibody to gamma interferon increased Theiler's virus-induced demyelination and virus antigen persistence in the spinal cord in susceptible SJL/J mice and completely abrogated resistance such that all C57BL/10SNJ mice developed demyelination. These experiments support the hypothesis that gamma interferon is critically important for resistance to Theiler's virus-induced disease but is not required for myelin destruction.

Animals↗
PubMed1995

Optic neuritis: a population-based study in Olmsted County, Minnesota.

We reviewed the records of all patients with optic neuritis (ON) in Olmsted County, Minnesota, identified through the comprehensive records-linkage system at the Mayo Clinic, and identified 156 ON patients from 1935 to 1991 who had onset of the disease while residing in Olmsted County (incidence cases). Poisson regression analysis revealed that age, gender, and calendar year were associated with incidence. The annual age- and sex-adjusted incidence rate was 5.1 per 100,000 person-years from 1985 to 1991. On December 1, 1991, 128 patients with a documented history of ON resided in Olmsted County (prevalence cohort). The age- and sex-adjusted prevalence rate per 100,000 was 115. The average length of follow-up for the incidence cohort was 13.2 years. Life table analysis showed that 39% of the 95 patients with isolated ON in the incidence cohort had progressed to clinically definite multiple sclerosis (MS) by 10 years of follow-up, that 49% had by 20 years, 54% by 30 years, and 60% by 40 years. There was no difference in the risk of developing MS between men and women. The presence of venous sheathing (p = 0.044) and evidence for recurrent ON (p < 0.0001) were associated with an increased likelihood of developing MS. The estimated 25-year survival rate was 88.3% +/- 5.8% for the incidence cohort with isolated ON, compared with 83.9% for the general US population of similar age and sex.

Adolescent↗
PubMed1995

Multifocal inflammatory leukoencephalopathy associated with levamisole therapy.

Cerebral demyelinating disease developed in a patient during adjuvant therapy with levamisole for malignant melanoma. This patient had no evidence of previous neurologic disease. Levamisole was administered for 5 weeks (total dose, 1,500 mg). Over a period of 3 weeks, the patient became progressively confused and ataxic. MRI with gadolinium enhancement demonstrated prominent multifocal enhancing white matter lesions. CSF examination revealed an inflammatory profile. After discontinuation of treatment with levamisole and a short course of corticosteroid therapy, the patient's condition dramatically improved. MRI also indicated improvement. Observations in our patient suggest that the leukoencephalopathy that developed in previously reported patients who received 5-fluorouracil and levamisole may have been caused at least partly by levamisole.

Antineoplastic Agents↗
PubMed1995

Differences in the dynamics of parathyroid hormone secretion in hemodialysis patients with marked secondary hyperparathyroidism.

Hemodialysis patients with predialysis intact parathyroid hormone (PTH) levels of more than 500 pg/mL are generally considered to have marked secondary hyperparathyroidism. Because the serum calcium level in these patients varies from low to high, it is not clear whether every hemodialysis patient with a PTH level > 500 pg/mL is part of a uniform group. The dynamics of PTH secretion in 21 hemodialysis patients with predialysis (basal) intact PTH levels > 500 pg/mL (range, 506 to 1978 pg/mL) has been evaluated. The basal/maximal PTH ratio, an indicator of the degree of relative PTH stimulation in the baseline state, was inversely correlated with the maximal PTH (r = -0.71), the basal serum calcium (r = -0.70), and the difference between the serum calcium at basal and maximal PTH (r = 0.81); the latter is the decrement in serum calcium from baseline necessary to maximally stimulate PTH. Because the basal PTH level appeared to be disproportionately influenced by hypocalcemia, the 21 patients were separated into two groups on the basis of the basal serum calcium (Group I < 9 mg/dL and Group II > 9 mg/dL). Basal PTH was not different between the two groups, even though maximally stimulated PTH (1,219 +/- 204 versus 2,739 +/- 412 pg/mL; P < 0.01) as induced by hypocalcemia and maximally suppressed PTH (217 +/- 37 versus 528 +/- 104; P = 0.05) as induced by hypercalcemia were less in Group I with the low basal calcium; moreover, the ratio of basal/maximal PTH was higher (73 +/- 6 versus 47 +/- 5%; P < 0.01) in Group I with the low basal calcium. These results suggest that the reason for a basal PTH > 500 pg/mL may be different among hemodialysis patients. In hypocalcemic patients, the low serum calcium appeared to be a major impetus for the high basal PTH level. In conclusion, (1) the maximally stimulated PTH appears to provide a better means of separating patients with marked secondary hyperparathyroidism than the basal PTH and (2) hemodialysis patients with basal PTH levels > 500 pg/mL may not be a uniform group.

Adult↗
PubMed1995

H-2 Dd transgene suppresses Theiler's virus-induced demyelination in susceptible strains of mice.

Theiler's murine encephalomyelitis virus is a picornavirus which induces chronic immune-mediated central nervous system demyelination and virus persistence in susceptible strains of mice. Using murine strains with congeneic recombinant haplotypes, the H-2D region within the class I major histocompatibility complex has been shown to be important in determining susceptibility/resistance to chronic Theiler's murine encephalomyelitis virus infection. We examined the role of H-2D in demyelinating disease with the use of transgenic D8 mice (H-2Dd, resistant haplotype) crossed to susceptible B10.Q (H-2q) and B10.S (H-2s) mice. Expression of the H-2Dd transgene dramatically suppressed demyelination and reduced the number of virus-antigen positive cells in the spinal cord 45 days following infection. More complete protection was observed in transgenic B10.Q (D8+) mice than in transgenic B10.S (D8+) mice. These experiments support the hypothesis that the immunologic basis of resistance by H-2D is determined by effective antigen presentation which prevents virus persistence and subsequent demyelination.

Animals↗
PubMed1995

Bovine somatotropin dose titration in lactating dairy ewes. 1. Milk yield and milk composition.

Seventy-four lactating dairy ewes were injected with recombinant bST (sometribove) in a sustained-release formulation. Ewes received 0, 80, 160, or 240 mg of bST every 14 d from wk 3 to 8 of lactation (part 1) and 0, 80, or 160 mg of bST every 14 d from wk 11 to 23 of lactation (part 2). Sometribove increased milk yield over that of the controls for all treatment groups. The increase was largest for the group that was administered 160 mg of bST: milk yield was 34.1 and 53.2% and 6% FCM was 36.9 and 51.8% for parts 1 and 2 of the study, respectively. Sometribove increased milk fat during part 1 of the study, but decreased milk fat during part 2. Protein contents of milk were decreased throughout the study. For all group, bST increased the yield of milk constituents over that of the controls. When milking frequency was reduced from twice to once daily, the difference in milk yield between control ewes and those treated with bST was maintained. Neither mastitis incidence nor milk SCC were affected by bST treatment. Recombinant bST is efficacious in increasing both actual milk yield and 6% FCM over the dose range of 80 to 240 mg/14 d without adverse effects for lactating ewes.

Animals↗