Biomedical subjects
Publications and source records attributed to M G Carr.
Peptides based upon the non-prime side residues of the NS4A-4B cleavage site of hepatitis C virus (HCV) NS3-4A proteinase containing an alpha-ketoamide moiety in place of the scissile amide bond are potent inhibitors of this enzyme.
BACKGROUND: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2-3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4-5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. PATIENTS: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. MATERIALS AND METHODS: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. RESULTS: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2-3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4-5 years of age indicating a defect in the onset of meiosis. CONCLUSION: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2-3 months of age and fail to establish adequate meiosis which normally occurs at 4-5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.
Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.
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Foreign bodies of the esophagus are a common problem in children, with the majority of these foreign bodies being coins. Because there are various methods for managing esophageal coins, we retrospectively reviewed our experience of the past 4 years to establish a safe and cost-effective protocol for their management. From January 1987 to December 1990, 57 children were managed for esophageal coins in our institution. Nineteen children were managed endoscopically under general anesthesia, with a mean patient cost of $1,982 (excluding the surgeon and anesthesiologist charge). Thirty-eight children were managed with Foley balloon extraction or esophageal bougienage in the emergency department with a mean patient cost of $149 (excluding surgeon charge). Both methods were 100% effective, and there were no complications in either group. Rigid criteria were used in selecting patients for balloon extraction and bougienage. These were: (1) duration less than 24 hours; (2) no respiratory distress; and (3) no history of esophageal disease or surgery. Using these criteria, 16 of the 19 patients managed endoscopically could have safely and effectively been managed in the emergency department with a net savings of $1,833 per patient. We conclude that Foley balloon extraction and bougienage of esophageal coins in selected children is both safe and cost-effective. A protocol for managing children with esophageal coins is presented, and the techniques of Foley balloon extraction and esophageal bougienage are reviewed.
Necrotizing enterocolitis (NEC), a disease associated with prematurity, carries a significant morbidity and mortality. This study was designed to evaluate our progress in dealing with NEC both medically and surgically in a single large neonatal intensive care unit (NICU). We also sought to confirm the relation of birth weight and particular indications for operation to outcome. Over 6 1/2 years, there were 7,807 admissions to a large NICU. Though there has been a steady increase in total admissions, especially of infants weighing less than 1,000 gm, survival has improved significantly in all groups (mean 89.1%). NEC occurred in 358 infants (4.6%), and 115 (32%) required surgical intervention. Infants weighing between 751 and 1,000 gm had the highest incidence of NEC. There has been a significant decrease in the mortality of both medically and surgically treated infants with NEC; in both cases, this decrease is weight-dependent. We found that using erythema and edema of the abdominal wall and a fixed-loop roentgenographic pattern as early indicators of necrotic bowel significantly improves survival in surgically treated infants.
Tracheostomy in infants and children is associated with a high rate of accidental decannulation in the early postoperative period. Eighty-eight patients underwent tracheostomy from 1980 to 1985, and 22 were sutured in place. Accidental decannulation occurred in 31.8% of the nonsutured and 4.5% of the sutured tracheostomies. We advocate suturing tracheostomy tubes in place in infants and children and describe a simple suture technique for this purpose.