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Biomedical subjects

M K Miller

Publications and source records attributed to M K Miller.

65 records · Page 4Linked to original sources

Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti-inflammatory drugs.

The nonsteroidal anti-inflammatory drugs, indomethacin and ibuprofen, have been shown to increase survival in various animal models of Gram-negative or endotoxin shock. To evaluate the use of these drugs in group B streptococcal sepsis, a clinically similar disease state, a newborn suckling rat model (4 to 5 days old) designed to simulate early-onset group B streptococcal sepsis was used. Sepsis was induced by a subcutaneous injection of group B streptococcal organisms (type III). A mortality ranging from 30% to 90% was used for the study. Indomethacin (3 mg/kg) or ibuprofen (4 mg/kg) treatment was administered by an intraperitoneal injection either at the time of the bacterial injection or after bacteremia (four hours) had occurred. Indomethacin clearly improved survival rates, even when given after bacteremia. Ibuprofen also clearly increased survival when given at the same time as the bacterial injection. Ibuprofen was more effective than indomethacin in the high mortality model (lethal dose for 90% survival of group). These drugs alter mechanisms that may be important in the irreversibility of sepsis and they may become useful adjuvants to our present treatment of early onset group B streptococcal sepsis.

Animals↗

Hispanic subgroup differences in prenatal care.

Within SES categories in the United States, racial and ethnic minorities generally fare less well on a variety of health-related indicators than do majority groups. Important differences exist within subgroups, however, and at present, these differences are poorly understood. In this paper we address Hispanic subgroup (Cuban American, Mexican American. Puerto Rican, and Central/South American) differences in utilization of prenatal care. Data from the 1986 and 1987 national Linked Birth/Infant Death files are used to assess patterns of prenatal care utilization across subgroups. Using Kotelchuck's Adequacy of Prenatal Care Utilization Index, we find that when controlling for other factors, Cuban American and Puerto Rican women are more likely to obtain adequate care than are Hispanic women of Mexican or Central/South American origin. Other factors important in understanding utilization patterns include marital status, education level, birthplace, and region of the country. We conclude with a discussion of the relatively weak link between prenatal care and birth outcomes and identify important cultural factors that may be important in understanding why this relationship is not stronger.

Adolescent↗

Hydroxyurea therapy for pediatric patients with hemoglobin SC disease.

PURPOSE: Hydroxyurea (HU) has laboratory and clinical efficacy in hemoglobin SS (HbSS) disease, but its benefits in hemoglobin SC (HbSC) disease are unknown. A recent adult HbSC disease pilot trial with HU therapy documented a modest laboratory benefit. Our goal was to evaluate the laboratory and clinical responses of selected pediatric patients with severe HbSC disease to HU therapy. PATIENTS AND METHODS: As part of a retrospective case series, patients were selected from the Duke Pediatric Sickle Cell Program based on the frequency and severity of their vasoocclusive events or an episode of acute chest syndrome. Oral HU therapy was started as a single daily dose and increased to the maximally tolerated dose based on myelosuppression. Laboratory evaluation was performed at baseline and monthly thereafter. Once the maximum tolerated dose was reached, laboratory data were monitored bimonthly. RESULTS: We treated six severely affected pediatric HbSC patients with HU for a median of 27 months. Mean corpuscular volume increased significantly (+26 fL) without change in hemoglobin concentration (-0.1 g/dL); neutrophils decreased significantly. Percentage of fetal hemoglobin (+8.5%) and percentage of F cells (+35.7%) increased significantly. Two experienced only mild and reversible toxicity. CONCLUSION: The laboratory responses in our pediatric patients with HbSC disease were striking, with increases in percentage of fetal hemoglobin and percentage of F-cells approaching responses observed in adult and pediatric patients with HbSS disease. All patients improved clinically. Our findings demonstrate that HU therapy benefits pediatric patients with severe HbSC disease, although larger clinical trials of HU therapy in HbSC disease are warranted.

Acute Disease↗

The micronuclear gene encoding beta-telomere binding protein in Oxytricha nova.

The micronuclear version of the gene encoding beta-telomere binding protein (beta-TBP) in Oxytricha nova has been sequenced and compared to the macronuclear beta-TBP gene, previously described. The micronuclear gene contains three AT-rich internal eliminated sequences (IES) of 37, 40, and 43 bp and four macronuclear destined sequences (MDS). The IES interrupt the gene once near the 5' end of the coding region and twice in the 3' trailer downstream from the TGA stop codon. The sequences of the micronuclear and macronuclear genes are colinear. Thus, the micronuclear beta-TBP gene is not scrambled, which contrasts with the highly scrambled state among the 14 MDS in the micronuclear alpha-TBP gene.

Animals↗

The potential toxicity to neonates of multivitamin preparations used in parenteral nutrition.

This study compares two groups of infants weighing less than 1500 g at birth. In the propylene glycol (PG) group, 30 infants received MVI-Concentrate containing 300 mg of PG daily with their intravenous nutrition (ivn), and vitamin E, 50 mg/week by intramuscular injection. In the mannitol group, 30 infants received MVI-Pediatric (containing 245 mg mannitol), 65% of a vial/day. Serum and urine osmolality, serum PG, blood-urea-nitrogen, creatinine, sodium, and glucose were measured on days 0, 2, 5, 12, 19, 26, 33 and 40 of ivn. Weight, urine output, and fluid intake were measured daily. Vitamin E levels were measured on days 5, 26, and 33 of ivn. There were no significant differences between the groups in birth weight, gestational age, sex, age, or weight at start of ivn. Our results indicated that neither MVI-Concentrate nor MVI-Pediatric was associated with a clinically significant diuresis. MVI-Pediatric, 65% of a vial/day, may produce higher than desirable blood levels of vitamin E, and use of drugs containing PG can produce significant blood levels of PG, in very low birth weight infants.

Diuresis↗