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Biomedical subjects

M Davidian

Publications and source records attributed to M Davidian.

34 records · Page 2Linked to original sources
PubMed1995

Therapeutic effects of diethylcarbamazine and 3'-azido-3'-deoxythymidine on feline leukemia virus lymphoma formation.

Twenty-four specific pathogen-free kittens were infected with the Rickard strain of feline leukemia virus (FeLVR). The kittens were divided into four equal groups and were orally administered either a high dose of diethylcarbamazine (DECH, 12 mg kg-1), a low dose of diethylcarbamazine (DECL, 3 mg kg-1), 3'-azido-3'-deoxythymidine (AZT, 15 mg kg-1, b.i.d.), or a placebo (250 mg granular dextrose) daily for 10 weeks. Blood was collected at 2-week intervals for complete blood counts (CBC) and flow cytometric analysis (FACS) of peripheral blood lymphocytes (PBL). Plasma was assayed for antibodies to FeLV gp70 and for FeLV p27 antigen using ELISA assays. For FACS analysis, lymphocytes were incubated with monoclonal antibodies to feline Pan T, CD8+, CD4+, and B cell (Anti-Ig) antigens. In the placebo treated cats, FeLVR infection caused an early (2 weeks p.i.) and persistent decrease in leukocyte numbers attributable primarily to a decrease in neutrophil numbers and a secondary lesser decrease in B and CD4+ lymphocyte numbers. The DEC-treated groups showed a delayed but similar leukopenia by 4 weeks p.i. The lymphopenia in the DEC groups (primarily B cells and CD4+ cells) was reversed by 10 weeks p.i., but the neutropenia persisted. AZT treatment inhibited FeLVR-induced lymphopenia but did not prevent a reduction in neutrophil numbers. A marked p27 antigenemia that peaked at 4 weeks p.i. was noted in the placebo treated cats and in most cats (11/12) treated with either dose of DEC. However, AZT significantly inhibited the p27 antigenemia and all cats were negative for p27 antigen between 6 and 10 weeks of treatment. In general, placebo treated cats as well as DECH and DECL cats had low levels of antibody to gp70 throughout the study, suggesting FeLVR-induced immunosuppression. In contrast, significantly higher titers of anti-gp70 antibodies were seen in AZT-treated cats at 6 weeks p.i., and were maintained throughout treatment. Eighteen month survival rates provide efficacy data for AZT as well as both DEC treatment groups. While all placebo treated cats were euthanized by 52 weeks p.i. due to FeLV associated lymphomas with a mean survival time of 35.5 weeks p.i., median survival time of the AZT treated group was > or = 102 weeks p.i., while that of the DECH and DECL groups was 69.7 and 72 weeks p.i., respectively. Thus, DEC as well as AZT therapy delays the development of lymphomas associated with FeLV infection and significantly improves survival.

Animals↗
PubMed1994

Assays for recombinant proteins: a problem in non-linear calibration.

Quantification of protein levels in biological matrices such as serum or plasma frequently relies on the techniques of immunoassay or bioassay. The relevant statistical problem is that of non-linear calibration, where one estimates analyte concentration in an unknown sample from a calibration curve fit to known standard concentrations. This paper discusses a general framework for calibration curve fit to known standard concentrations. This paper discusses a general framework for calibration inference, that of the non-linear mixed effects model. Within this framework, we consider two issues in depth: accurate characterization of intra-assay variation, and the use of empirical Bayes methods in calibration. We show that proper characterization of intra-assay variability requires pooling of information across several assay runs. Simulation work indicates that use of empirical Bayes methods may afford considerable gain in efficiency; one must weigh this gain against practical considerations in the implementation of Bayesian techniques. We illustrate the methods discussed using a cell-based bioassay for the recombinant hormone relaxin.

Bayes Theorem↗
PubMed1993

Morphological and physiological changes in the urinary tract associated with ureteral dilation and ureteropyeloscopy: an experimental study.

The gross and microscopic effects of four common modes of ureteral dilation and ureteroscopy were examined in 26 renoureteral units in 13 minipigs. Acutely, ureters subjected to mechanical (bougie, Teflon, or balloon) ureteral dilation and ureteropyeloscopy (UPS) demonstrated active mucosal bleeding with multiple sites of perforation, whereas ureters subjected to hydraulic dilation and UPS were significantly less traumatized. Two weeks after mechanical ureteral dilation and UPS, 3 of 6 ureters were obstructed radiographically, whereas all 7 hydraulically dilated ureters were unobstructed. By 6 weeks, all radiographic evidence of obstruction had resolved in the mechanically dilated group. While 5 of 6 mechanically dilated ureters showed extensive scarring with muscle loss 4 to 6 weeks after dilation, no scarring was seen in those ureters dilated hydraulically. Renal pelvic pressure (RPP) was measured continuously with a nephrostomy catheter in vivo during (bougie, Teflon, balloon and hydraulic) ureteral dilation and UPS. Renal pelvic pressure during rigid ureteroscopy approximated the resting pelvic pressure plus the irrigant height above the kidney or set pressure on a hydraulic pump, plus a "scope effect" which was characterized by a 20 to 25 mm. Hg increase in RPP produced by moving the endoscope in the ureter without flow. The effects on RPP of continuous bladder drainage with a uretheral catheter and renal pelvic decompression with an open-ended ureteral catheter passed into the renal pelvis through the ureteroscope working channel were also examined. The maximum RPP was evaluated in vitro in a separate group of 16 freshly harvested pig kidneys of similar weight examined immediately after sacrifice and was found to be 439 mm. Hg. We also studied the immediate and long-term effects of low (< 120 cm. H2O or 90 mm. Hg) versus high (> 200 cm. H2O or 150 mm. Hg) RPP on renal histology. Acutely, high pressure caused diffuse denudation and flattening of the caliceal urothelium, submucosal edema and congestion not seen in calyces subjected to low irrigant pressure. Four to six weeks later, there was a higher incidence of columnar metaplasia, subepithelial nests and pericalyceal vasculitis in calyces subjected to high pressure as compared with those subjected to low irrigant pressure. Acutely, renal tubules subjected to high irrigant pressure demonstrated marked vacuolization and degeneration, whereas tubules subjected to low pressure appeared normal. At 4 to 6 weeks, focal scarring was seen in 5 of 7 kidneys subjected to high irrigant pressure, whereas no scarring was noted in all 6 kidneys subjected to low irrigant pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Some general estimation methods for nonlinear mixed-effects models.

A nonlinear mixed-effects model suitable for characterizing repeated measurement data is described. The model allows dependence of random coefficients on covariate information and accommodates general specifications of a common intraindividual covariance structure, such as models for variance within individuals that depend on individual mean response and autocorrelation. Two classes of procedures for estimation in this model are described, which incorporate estimation of unknown parameters in the assumed intraindividual covariance structure. The procedures are straightforward to implement using standard statistical software. The techniques are illustrated by examples in growth analysis and assay development.

Calibration↗
PubMed1992

Smooth nonparametric maximum likelihood estimation for population pharmacokinetics, with application to quinidine.

The seminonparametric (SNP) method, popular in the econometrics literature, is proposed for use in population pharmacokinetic analysis. For data that can be described by the nonlinear mixed effects model, the method produces smooth nonparametric estimates of the entire random effects density and simultaneous estimates of fixed effects by maximum likelihood. A graphical model-building strategy based on the SNP method is described. The methods are illustrated by a population analysis of plasma levels in 136 patients undergoing oral quinidine therapy.

Absorption↗
PubMed1989

Electrocardiographic pseudo-myocardial infarct pattern in malignant cardiac disease.

A patient with disseminated diffuse histiocytic lymphoma had persistent electrocardiographic (ECG) signs of acute myocardial infarction without clinical, enzymatic, or hemodynamic evidence of myocardial necrosis. The ECG findings were felt to be secondary to myocardial tumor invasion by antemortem noninvasive testing. This was confirmed by postmortem examination. Based on this report and a literature review, the particular ECG findings noted (lateral leads) are felt to be highly predictive of direct tumor invasion in this setting.

Adult↗
PubMed1989

Gastrointestinal milk intolerance of infancy.

During a period of 30 months, cow's milk- or soy protein-induced colitis was diagnosed in 22 infants. All patients presented with hematochezia. Only three patients had substantial diarrhea. Colonoscopic evaluations demonstrated a characteristic mucosal appearance, manifested by aphthoid ulcerations with intervening, normal-appearing mucosa. Histologic findings included surface ulcerations and associated inflammation of the lamina propria and submucosa, marked by substantial eosinophilic infiltration. Both clinical symptoms and colonoscopic abnormalities rapidly resolved in all patients after the elimination of cow's milk and/or soy protein from the diet. These data indicate that hematochezia may be the predominant symptom of cow's milk protein and soy protein intolerance in many affected infants, and that colonoscopy is the most effective means of establishing a definitive diagnosis in this patient population.

Colitis↗
PubMed1988

Progesterone receptors in the human heart and great vessels.

Progesterone receptors (PgR) were identified in 31 of 50 specimens of human (men and women) thoracic ascending aorta, internal carotid, coronary artery, and left atrial appendage. This was accomplished with a peroxidase-antiperoxidase immunocytochemical assay employing a highly specific monoclonal antibody to primate PgR. In the aorta, specific staining was seen in the nuclei of smooth muscle cells and endothelium of intima, media, and adventitia. In the myocardium, staining was localized to the nuclei of the myocardial fibers. In internal carotid and coronary arteries, PgR was localized to endothelial nuclei of intima, and in vascular channels within the atherosclerotic plaques. PgR was also visible in the smooth muscle cell nuclei of uninvolved media and intima and at the plaque periphery. In contrast, receptor was not identified in vessels of the human uterus, breast, prostate, kidney, or gastrointestinal tract. These findings suggest that the heart and great vessels are target organs for steroid hormones.

Adult↗
PubMed1987

Life-threatening dysrhythmias in varicella myocarditis.

Varicella myocarditis is an unusual complication of a common childhood disease. Two patients with life-threatening dysrhythmias and circulatory failure are reported. One patient required permanent pacemaker implantation for acquired complete heart block, not previously described with varicella infection. Previously reported cases of varicella myocarditis are reviewed.

Arrhythmias, Cardiac↗
PubMed1983

Multimodality treatment of adenocarcinoma of the vagina Stage IV: potential for cure.

A 26-year-old nulligravida presented with a Stage IV adenocarcinoma of the vagina with a frozen pelvis and positive lymph nodes in the right external iliac and inguinal regions. Following transposition of the ovaries laterally, a successful treatment program of cyclic radiotherapy and 5-fluorouracil was undertaken. Patient is now alive 3 years posttherapy with a functional vagina, return of menses, and without evidence of tumor. She experienced a small-bowel stricture 5 months posttherapy which required small-bowel resection. This case suggests that an integrated multimodality program is feasible and that 5-fluorouracil may be synergistic with radiation.

Adenocarcinoma, Mucinous↗
PubMed1982

Gastrointestinal metastases from malignant tumors of the lung.

Autopsy data of 423 cases of primary tumor of the lung over a 36-year period were evaluated for the presence of gastrointestinal tract metastases. Fifty-eight cases (14%) were found and were analyzed for histologic nature of tumor, anatomic location, symptomatology and complications. The most common histologic type of lung tumor causing gastrointestinal tract metastasis was squamous cell (19 cases, 33%), followed by large cell (17 cases, 29%), and oat cell (11 cases, 19%). The esophagus was the most common site of involvement (33 cases). Fourteen of the 33 cases were involved by direct extension of the tumor. The middle third of the esophagus had metastases more commonly (16/33, 49%) than the other two sites. Most patients with gastrointestinal metastases had no symptoms. In those patients with symptoms, dysphagia was most common when the tumor involved the proximal gastrointestinal tract (esophagus, stomach), whereas, pain was most commonly seen with involvement of the distal gastrointestinal tract (small bowel, large bowel). Six of 20 patients (30%) with small bowel involvement experienced perforation and peritonitis as complications of metastatic involvement and two patients with large bowel metastasis had obstruction; a third had dehiscence of a previous anastomotic site. Gastrointestinal tract metastases from primary carcinoma of the lung are more common than previously thought and may be associated with serious clinical complications.

Adult↗
PubMed1979

Glucagonoma, chronic recurrent peptic ulcer disease, and enhanced amylase-creatinine clearance ratio. Report of a case with review of the literature.

A 53-year-old white woman developed diabetes mellitus, migratory erythema, and anemia, clinical features suggesting the presence of a "glucagonoma." Ten years earlier, after laparotomy and pancreatic biopsy, she had been told that she had an inoperable pancreatic carcinoma. Review of that biopsy together with current hormonal assay now confirms the diagnosis of glucagonoma. The recurrent peptic ulcer in this patient despite high levels of glucagon, a gastric inhibitory agent, is noted but not explained. An enhanced amylase-creatinine clearance ratio supports the notion that glucagon increases the clearances of amylase.

Adenoma, Islet Cell↗
PubMedDate not supplied

Intestinal duplication in a patient with neurofibromatosis: aid of ultrasound and CT scan in diagnosis.

A 5-year-old boy with neurofibromatosis is described, whose symptoms of abdominal pain and vomiting were due to an intestinal duplication. Intestinal duplication has not been previously reported as a cause of gastrointestinal symptoms in neurofibromatosis. The utilization of ultrasound and computerized tomography scan as useful modalities for the diagnosis of duplication of the bowel is described.

Child, Preschool↗
PubMedDate not supplied

Reduced cardiac selenium content in the acquired immunodeficiency syndrome.

Selenium deficiency has been implicated in the pathogenesis of a dilated congestive cardiomyopathy in areas of China (Keshan disease) and in several patients on long-term total parenteral nutrition. Recently a clinically and pathologically similar cardiomyopathy has been described in AIDS. Since blood selenium levels are low in AIDS, we assayed cardiac selenium status by a spectrofluorometric method in eight AIDS patients at autopsy compared to nine age-matched, non-AIDS autopsy controls with histologically normal hearts. We found (mean +/- SD) a cardiac selenium level of 0.327 +/- 0.082 microgram/g dry weight in AIDS vs 0.534 +/- 0.184 microgram/g dry weight in controls (p less than 0.01; Student's t test). There were no significant differences between the groups for heart weight, serum CPK, or other laboratory parameters. No specific chest x-ray or electrocardiographic abnormalities were present. Histologically, all AIDS hearts were abnormal; mostly with mild degrees of muscle hypertrophy or fibrosis. Foci of myocytolysis and myocyte necrosis and fibrous replacement of myocytes and monocytic infiltration were present in two AIDS cases. We conclude that heart tissue in AIDS demonstrates a significant selenium deficit. These data provide a potential link between selenium deficiency and cardiomyopathy in AIDS.

Acquired Immunodeficiency Syndrome↗