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Biomedical subjects

D M Martin

Publications and source records attributed to D M Martin.

95 records · Page 6Linked to original sources

Carboxyhemoglobin concentration as an index of bilirubin production in neonates with birth weights less than 1,500 grams: a randomized double-blind comparison of supplemental oral vitamin E and placebo.

A randomized double-blind study of the efficacy of oral vitamin E supplementation as a prophylactic treatment for hyperbilirubinemia was undertaken in preterm infants weighing less than 1,500 g. Hemoglobin (Hb) levels, blood carboxyhemoglobin saturation (HbCOc), end-tidal carbon monoxide concentration (ETCO), and serum total bilirubin levels were determined in each subject on the first and third days of the study. We found no differences between the vitamin E-treated and placebo-treated groups with respect to Hb, HbCOc, ETCO, or serum bilirubin levels on day 1 or 3. In addition, we reanalyzed our data to compare those infants who had low vitamin E levels at birth with those who had vitamin E levels greater than 0.4 mg/dl on day 1. We still observed no differences in Hb, HbCOc, ETCO, or serum bilirubin levels on day 1 or 3. The results of our study suggest that supplemental oral vitamin E therapy has no major effect on bilirubin production during the first 3 days of life in premature infants weighing less than 1,500 g at birth.

Administration, Oral↗

Nortriptyline plasma levels and clinical response in patients with familial pure unipolar depression and blunted TRH tests.

We studied the efficacy of nortriptyline (NT) when given in doses which produce tricyclic antidepressant (TCA) levels within the proposed therapeutic "window" in a select patient group to assess the "window" hypothesis in a group of patients that was biologically homogeneous with respect to the TRH test and clinically homogeneous with respect to RDC, DSM III, and Winokur criteria. Pharmacokinetic and dose differences were controlled for by administering a NT dose-prediction test, giving the indicated dose, allowing levels to reach steady state and changing the dose, if necessary, to maintain NT levels within the range of 90-130 ng/ml. Using this protocol nine of ten patients responded to NT. This rate of response for a severely depressed patient group is comparable to response data for ECT and recent European data using regular NT levels to change doses of NT and assess appropriate NT trial duration.

Adult↗

Thyroid stimulating hormone and growth hormone responses to thyrotropin releasing hormone in anorexia nervosa.

Ten female patients who satisfied objective criteria for the diagnosis of anorexia nervosa were given 500 microgram of thyrotropin releasing hormone. Thyroid stimulating hormone and growth hormone responses were measured in duplicate by radioimmunoassay. These patients had a low normal delta thyroid stimulating hormone but a delayed peak response. In addition, these patients had pathological growth hormone release in response to thytotropin releasing hormone infusion. Both delayed peak thyroid stimulating hormone and growth hormone response to thyrotropin releasing hormone have been reported for patients with hypothalamic disorders.

Adolescent↗

Immunologic monitoring with Orthoclone OKT3 therapy.

Muromonab-CD3 monoclonal antibody (Orthoclone OKT3) was used 146 times in 123 transplant recipients to treat or prevent rejection. Reversal and prevention of rejection were evaluated 1 week and 1 year after OKT3 therapy. Eighty-one percent (73 of 90) of the rejection episodes in kidney transplant patients were reversed with 67% of these grafts functioning at 1 year. Eighteen of 20 (90%) rejection episodes in liver transplant recipients were reversed, as were 11 of 13 (85%) heart transplant rejection episodes. Only one of five pancreas transplant episodes were reversed. OKT3 was used prophylactically in 18 transplant recipients (13 kidney, four heart, one liver). Immunologic monitoring (lymphocyte subsets, serum OKT3 levels, and antimurine antibodies) was performed during and after OKT3 therapy. Antimurine antibody formation rate was 28% (26 of 94 patients monitored). OKT3 therapy resulted in a rapid depletion of CD3+ cells from the peripheral circulation (less than 20/mm3) and trough serum OKT3 levels of greater than 800 ng/ml by the third day of therapy in all transplant types. Twenty-three patients (14 kidney, five liver, three heart, and one pancreas) were retreated with OKT3; reversal of rejection occurred in 87% of patients (13 of 15) with no antimurine antibodies and in 83% of patients (five of six) with a low antibody titer but did not occur in the two patients with a high antibody titer. Retreatment of patients with no anti-OKT3 antibody resulted in a depletion of CD3+ cells from the peripheral blood, but it took longer than in patients treated with OKT3 for the first time. Similarly, serum OKT3 levels increased slower in retreated patients compared with first treatment. In retreatment patients with a low titer antimurine antibody, often it was necessary to increase the dose of OKT3 to achieve adequate serum OKT3 levels and to deplete CD3+ cells. Antimurine antibody developed de novo in four of the 15 antibody negative patients (27%) who were retreated. Overall, OKT3 was an effective agent in reversing and preventing rejection in solid organ transplantation with few severe side effects and a low mortality. Retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low titer antibodies does not preclude successful retreatment with OKT3. Alternate antirejection therapy, however, should be used in patients with high titer antimurine responses.

Antibodies, Anti-Idiotypic↗

Cytolytic T-cell clones define HLA-A2-restricted human cutaneous melanoma peptide epitopes: correlation with T-cell receptor usage.

PURPOSE: We studied the T-cell receptor alpha chain and beta chain variable region usage in HLA-A2-restricted and melanoma-specific T lymphocytes and correlated such T-cell receptor usage with HLA-A2-presented peptide-specific T-cell recognition. MATERIALS AND METHODS: Tumor-infiltrating lymphocytes were isolated from a metastatic melanoma lesion and cloned by limiting dilution. Clonal and oligoclonal tumor-infiltrating lymphocytes were analyzed for major histocompatibility complex class I--presented melanoma peptide recognition by using acid-eluted and high-performance liquid chromatography--fractionated melanoma peptides presented by HLA-A2 as targets. The T-cell receptor variable regions of the alpha and beta chains of each individual T-cell clone or oligoclonal T-cell population were analyzed by mRNA extraction and reverse transcribed cDNA by polymerase chain reaction using a panel of T-cell receptor alpha and beta variable region specific primers. RESULTS: We demonstrated that individual T-cell clones are capable of recognizing peptides within multiple high-performance liquid chromatography fractions containing melanoma epitopes, and that individual high-performance liquid chromatography fractions containing melanoma epitopes can be recognized by T-cell clones exhibiting limited usage of the T-cell receptor alpha and beta variable region chains. DISCUSSION: These results confirm the heterogeneity of T-cell-defined melanoma antigens in a single individual and suggest the possibility of developing novel antimelanoma therapeutic reagents using either peptides (as immunogens) or the T-cell receptors themselves (as gene therapy when introduced into lymphoid effectors).

Antigens, Neoplasm↗