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Biomedical subjects

C Peters

Publications and source records attributed to C Peters.

At least 145 records · Page 8Linked to original sources
PubMed1996

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Adolescent↗
PubMed1996

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.

Bone Marrow Transplantation↗
PubMed1996

Hydrocele of the spermatic cord: embryology and ultrasonographic appearance.

Five cases of hydrocele of the spermatic cord are presented. All five patients had a firm inguinal mass, and ultrasonography, performed to exclude adenopathy, incarcerated hernia, and paratesticular tumor, showed an avascular cystic mass superior to and separate from the testicle. A testicular hydrocele did not coexist. This typical appearance should lead to a confident diagnosis of this benign but rare anomaly. Elective surgery may prevent the development of an acquired indirect hernia.

Diagnosis, Differential↗
PubMed1996

Ten-year experience with the artificial urinary sphincter in children.

PURPOSE: To assess the efficacy of the artificial urinary sphincter survival and continence were first evaluated 5 years ago. We now evaluated the effects of the artificial urinary sphincter more than a decade after implantation. MATERIALS AND METHODS: Before 1985 an artificial urinary sphincter was implanted in 22 male and 14 female consecutive patients 4 to 30 years old (median age 12). In addition, between 1985 and 1990, 18 other children underwent artificial urinary sphincter implantation. Results of both series were compared. RESULTS: Of the 25 sphincters in the original series that were functioning after 5 years 1 was removed and 2 patients were lost to followup, resulting in 22 functioning implants (61% of the patients). Mean survival time of the prostheses was 12.1 years and average followup for functioning sphincters was 13.7 years. There was no statistically significant difference in artificial urinary sphincter survival between the original group at 5 years and the second group treated after 1985. Of the patients in both groups with sphincters in place 32 of 39 (82%) were dry. Augmentation cystoplasty was performed in 9 of 18 patients (50%) in the second series (5 preoperatively and 4 postoperatively) compared to 10 of 36 (28%) in the original series at 5 years (3 preoperatively and 7 postoperatively). Renal failure developed in 6 patients from both series. CONCLUSIONS: The artificial urinary sphincter is a durable long-term solution for children with intractable incontinence. Long-term surveillance of the urinary tract is mandatory because of the potential for renal failure in patients who have bladder hypertonicity after placement of the device.

Adolescent↗
PubMed1996

Expression of PRL-1 nuclear PTPase is associated with proliferation in liver but with differentiation in intestine.

Mechanisms controlling the tyrosine phosphorylation of cellular proteins are important in the regulation of cellular processes including growth and differentiation. It has become clear that a number of protein tyrosine phosphatases (PTPases) that dephosphorylate tyrosyl residues may play a role in the growth response, both in growth-promoting and growth-inhibiting capacities. We identified PRL-1, a unique nuclear PTPase that is an immediate-early gene in liver regeneration and is positively associated with growth, including fetal and neoplastic hepatic growth and anchorage-independent growth after overexpression in fibroblasts. In this study, we show that PRL-1 nuclear protein levels in regenerating liver parallel those of its mRNA, although the peak occurs later, just before the onset of DNA synthesis. We further show that PRL-1 is significantly expressed in intestinal epithelia and that, in contrast to the expression pattern of PRL-1 in liver, its expression is associated with cellular differentiation in intestine. Specifically, PRL-1 is expressed in villus but not crypt enterocytes and in confluent differentiated but not undifferentiated proliferating Caco-2 colon carcinoma cells. The expression of PRL-1 in intestine shows inverse correlation with proliferating cell nuclear antigen expression, a marker for S-phase cells. These results suggest that PRL-1 may play different roles in these two digestive tissues. Such a dichotomy of roles has previously been described for some protein tyrosine kinases and might be due to the availability of alternate substrates in different tissues.

3T3 Cells↗
PubMed1996

Erythropoietin pharmacokinetics in premature infants: developmental, nonlinearity, and treatment effects.

Erythropoietin (EPO) pharmacokinetic studies were performed in premature infants (birth weight < 1.25 kg) and normal adults. Infants were divided into two subgroups on the basis of whether they received chronic treatment with recombinant human EPO (rhEPO; 500 IU.kg-1.wk-1 for 6 wk) beginning at 2-4 wk of life. Ten adults and seven rhEPO-treated infants underwent intravenous pharmacokinetic studies at escalating rhEPO doses: 10, 100, and 500 IU/kg. To test for pharmacokinetic developmental and treatment effects, an equal number of non-EPO- and EPO-treated infants were studied with 100 IU/kg on the last day of treatment. Compared with adults, very low birth weight infants demonstrated significantly greater plasma clearance and distribution volume and significantly shorter fractional elimination times (FET) and mean residence time (MRT) at all three rhEPO doses. Both infants and adults demonstrated nonlinear EPO elimination, i.e., increasing rhEPO dosing was associated with decreasing plasma clearance and increasing FET and MRT. In the absence of rhEPO treatment there were no pharmacokinetic differences between the two subgroups of infants studied 6 wk apart. In contrast, the rhEPO-treated infant subgroup demonstrated a significant increase in clearance and a decrease in FET and MRT following 6 wk of treatment. Enhancement of rhEPO efficacy in the prevention and treatment of anemia in premature infants may require higher doses administered in a progressively increasing fashion.

Adult↗
PubMed1996

Effect of chronic erythropoietin administration on plasma iron in newborn lambs.

Erythropoietin, the primary stimulator of erythropoiesis, represents an important potential therapy for the anemia of prematurity. Enhancement of the therapeutic benefit of recombinant human erythropoietin (rhEp) in very-low-birth-weight infants will require a better understanding of rhEp's pharmacodynamic effects including its interaction with iron in stimulating erythropoiesis. The purpose of this study was to determine the effects of chronic rhEp administration on plasma iron levels and hematopoiesis using a twin lamb model. Nine pairs of twin lambs in which one twin was randomized to receive rhEp, and the other saline, were studied during a 1-week baseline and a subsequent 4- to 5-week treatment period. The effects of therapy on plasma iron levels and erythropoiesis were measured by integrating the areas under the concentration-time curves (AUC) of the study variables. During the rhEp treatment period, significantly greater negative daily AUCs were observed in the rhEp-treated lambs for plasma iron concentration (p = 0.0008), while significantly greater positive daily AUCs were observed for hemoglobin concentration (p = 0.04) and reticulocyte count (p = 0.02). In the rhEp-treated group, pretreatment iron concentrations were directly associated with the magnitude of the iron response during treatment such that the greater the pretreatment iron, the greater the daily AUC below the plasma iron concentration-time plot (r = -0.66, p = 0.05). For the placebo-treated group, this association tended toward, but did not achieve, statistical significance (r = -0.52, p = n.s.). These observations suggest that treatment of rapidly growing newborn lambs with rhEp results in increased iron utilization due to increased erythropoiesis and depends on iron status at the initiation of rhEp treatment. Use of the term neonatal lamb model offers advantages over studies in human infants for more detailed or invasive examinations of the interaction of iron and rhEp treatment.

Animals↗
PubMed1996

Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients.

Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS-VI), is a lysosomal storage disorder characterized by the defective degradation of dermatan sulfate due to the deficiency of N-acetylgalactosamine-4-sulfatase (4S). The clinical severity of MPS-VI ranges in a continuum from mildly affected to severely affected patients. Mutations in MPS-VI patient samples were identified by chemical cleavage and direct DNA sequencing of PCR products derived from patient cDNA. Five amino acid substitutions were identified (T92M, R95Q, Y210C, H393P, and L498P), individually introduced into the wild-type 4S cDNA by site-directed in vitro mutagenesis, and transfected into Chinese hamster ovary cells. Three of the five mutations (R95Q, Y210C, and H393P) were observed in >1 of 25 unrelated MPS-VI patients; however, the mutations were not found in 20 control individuals. The residual 4S activity and protein (biochemical phenotype) were determined for each mutant in order to confirm their identity as mutations and to dissect the contribution of each mutant allele to the overall clinical phenotype of the patient. For each patient, the combined biochemical phenotypes of the two 4S mutant alleles demonstrated a good correspondence with the observed clinical phenotype (with the possible exception of a patient who was a compound heterozygote for T92M and L498P). This preliminary correspondence between genotype and the phenotype in MPS-VI may, with further refinement, contribute to the assessment of therapeutic approaches for MPS-VI patients.

Adolescent↗
PubMed1996

Alcohol risk assessment and intervention for family physicians. Project of the College of Family Physicians of Canada.

At-risk and problem drinkers (excluding those with severe dependency) are estimated to be 20% of the Canadian population. With minimal training family physicians can effectively manage patients with alcohol problems. The Alcohol Risk Assessment and Intervention Project of the College of Family Physicians of Canada has developed materials and training for family physicians to use in helping their patients reduce the risks of alcohol-related harm.

Alcoholism↗
PubMed1996

Effect of retinoic acid on wound healing of laser burns to porcine retinal pigment epithelium.

OBJECTIVE: To determine the effect of retinoic acid on wound healing of laser burns to explants of porcine retinal pigment epithelium (RPE). DESIGN: With the help of a mirrored attachment to a Coherent argon laser, laser burns (spot size 100 mu, power 500 mW, duration 0.2 seconds) were performed in 12 explants. The explants were then cultured in the presence (six explants) or absence (six explants) of 1 microM retinoic acid. Two explants in either group were recovered 4, 8 and 12 days after treatment for histologic study and scanning electron microscopy. OUTCOME MEASURE: Mean burn area remaining after culture. RESULTS: The area of wound remaining unhealed in the presence of retinoic acid was significantly larger than the area of wound remaining unhealed in the absence of retinoic acid at each time point. CONCLUSIONS: Retinoic acid inhibited wound healing of laser burns to porcine RPE. This effect may illustrate a role for retinoic acid in the pharmacotherapy of proliferative disorders.

Animals↗
PubMed1996

Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children: experience of eight European Countries. The EBMT Paediatric Diseases Working Party.

From September 1988 to December 1995 forty-four children (age < 17 years) with Ph1 Chronic Myelogenous Leukemia (CML) received unrelated donor marrow transplantation in 8 European Countries. Thirty-three evaluable children were typed by serological testing on HLA-A, B, and DR loci. Thirty of them were further DR subtyped by DNA techniques. Twenty-four pairs were 6 antigen matched. Seven were mismatched at 1 locus (2 pairs at A and B loci respectively and 3 at DR locus). Two out of 30 pairs evaluated by molecular biology had one antigen mismatched at DRB1 locus. Thirty-two (96%) out of 33 evaluable children reached a sustained granulocyte count higher than 0.5 x 10(9)/l at a median of 21 (range 14-88) days after transplantation. The remaining child failed to engraft. Two children developed secondary graft failure. A platelet count greater than 50 x 10(9)/l sustained for at least seven consecutive days without transfusion support was reached at a median of 25 (range: 20-144) days by 24 out of 33 evaluable children and 9 children never recovered to above 50 x 10(9)/l. Twenty-one out of 33 evaluable children developed grade I (n = 7), grade II (n = 8), grade III (n = 2) or grade IV (n = 4) acute GvHD (63%). Seven of the 30 evaluable children surviving more than 100 days developed chronic GvHD (20%) which was limited in 4 cases and extensive in 3. Relapse occurred in 3 of the 44 (7%) children at 2 to 24 months (median 14). Twenty-four month relapse rate was 14%. Seventeen out of 44 children (38%) died of transplant related mortality (TRM), 4 (9%) of secondary tumor, 4 (9%) of infections, 3 (7%) of organ failure, 1 (2%) of interstitial pneumonia, 5 (11%) of unknown causes. Actuarial TRM was 61% for children grafted before December 1991 and 33% for children grafted after January 1992 (p = .01). EFS was 49.7%; it was 65% for children receiving more than 3.5 x 10(9)/Kg MNC.

Adolescent↗