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Biomedical subjects

M Pepe

Publications and source records attributed to M Pepe.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nutritional effects of long-term gastrostomy feedings in children with cystic fibrosis.

OBJECTIVE: To analyze the long-term nutritional effects of supplemental gastrostomy feedings in undernourished patients with cystic fibrosis. DESIGN: Longitudinal, retrospective assessment of anthropometric measures before and for up to 4 years after gastrostomy. SUBJECTS/SETTING: All patients at a large cystic fibrosis care center who underwent gastrostomy between 1980 and 1993 when they were at least 1 year old and were followed up for a minimum of 1 year after gastrostomy. STATISTICAL ANALYSES PERFORMED: The Mann-Whitney U test was used to compare anthropometric values measured during 4 postgastrostomy time intervals with values measured during the year preceding gastrostomy. RESULTS: The 21 patients ranged in age from 1.1 to 20.8 years (median age = 7.4 years). They had mild to moderate malnutrition at the time of gastrostomy. Patients were followed up for a mean of 39 months after gastrostomy. Supplemental feedings were associated with significant improvements in weight and height percentiles for age, and in weight as a percentage of ideal weight. Improvement in weight occurred earlier than improvement in height. Among subjects followed up for at least 18 months after gastrostomy, median weight percentile for age increased from 2% for the year before gastrostomy to 12% for the period 6 to 18 months after gastrostomy (P < .001) and 19% for the period 30 to 48 months after gastrostomy (P = .002 compared with before gastrostomy). Other nutritional parameters followed similar, although less dramatic patterns. Gastrostomy feedings were well tolerated and associated with only minor complications. CONCLUSIONS: Long-term gastrostomy feedings appear to be a safe and effective means of improving nutrition in malnourished patients with cystic fibrosis. Clinical dietitians should function as care managers for patients with cystic fibrosis who are receiving supplemental gastrostomy feedings.

Adolescent↗
PubMed1999

Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone.

The role of androgenic hormones in human sexuality, in the mechanism of erection and in the pathogenesis of impotence is under debate. While the use of testosterone is common in the clinical therapy of male erectile dysfunction, hypogonadism is a rare cause of impotence. We evaluated serum testosterone levels in men with erectile dysfunction resulting either from organic or non-organic causes before and after non-hormonal impotence therapy. Eighty-three consecutive cases of impotence (70% organic, 30% non-organic, vascular aetiology being the most frequent) were subjected to hormonal screening before and after various psychological, medical (prostaglandin E1, yohimbine) or mechanical therapies (vascular surgery, penile prostheses, vacuum devices). Thirty age-matched healthy men served as a control group. Compared to controls, patients with impotence resulting from both organic and non-organic causes showed reduced serum levels of both total testosterone (11.1 +/- 2.4 vs. 17.7 +/- 5.5 nmol/L) and free testosterone (56.2 +/- 22.9 vs. 79.4 +/- 27.0 pmol/L) (both p < 0.001). Irrespective of the different aetiologies and of the various impotence therapies, a dramatic increase in serum total and free testosterone levels (15.6 +/- 4.2 nmol/L and 73.8 +/- 22.5 pmol/L, respectively) was observed in patients who achieved normal sexual activity 3 months after commencing therapy (p < 0.001). On the contrary, serum testosterone levels did not change in patients in whom therapies were ineffective. Since the pre-therapy low testosterone levels were independent of the aetiology of impotence, we hypothesize that this hormonal pattern is related to the loss of sexual activity, as demonstrated by its normalization with the resumption of coital activity after different therapies. The corollary is that sexual activity may feed itself throughout the increase in testosterone levels.

Adolescent↗
PubMed1997

Gender gap in cystic fibrosis mortality.

The authors conducted the largest study to date of survival in cystic fibrosis. The study cohort consisted of all patients with cystic fibrosis seen at Cystic Fibrosis Foundation-accredited care centers in the United States between 1988 and 1992 (n = 21,047), or approximately 85% of all US patients diagnosed with cystic fibrosis. Cox proportional hazards regression analysis was used to compare the age-specific mortality rates of males and females and to identify risk factors serving as potential explanatory variables for the gender-related difference in survival. Among the subjects 1-20 years of age, females were 60% more likely to die than males (relative risk = 1.6, 95% confidence interval 1.4-1.8). Outside this age range, male and female survival rates were not significantly different. The median survival for females was 25.3 years and for males was 28.4 years. Nutritional status, pulmonary function, and airway microbiology at a given age were strong predictors of mortality at subsequent ages. Nonetheless, differences between the genders in these parameters, as well as pancreatic insufficiency, age at diagnosis, mode of presentation, and race, could not account for the poorer survival among females. Even after adjustment for all these potential risk factors, females in the age range 1-20 years remained at greater risk for death (relative risk = 1.6, 95% confidence interval 1.2-2.1). The authors concluded that in 1- to 20-year-old individuals with cystic fibrosis, survival in females was poorer than in males. This "gender gap" was not explained by a wide variety of potential risk factors.

Adolescent↗
PubMed1997

A comparison of peak sputum tobramycin concentration in patients with cystic fibrosis using jet and ultrasonic nebulizer systems. Aerosolized Tobramycin Study Group.

STUDY OBJECTIVE: To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis (CF) using a jet nebulizer delivery system. DESIGN: A multicenter, open-label, randomized, crossover study. SETTING: Ten tertiary care, university-affiliated, teaching hospitals in the United States. PATIENTS AND CONTROL SUBJECTS: Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age, had a diagnosis of CF, and expectorated daily sputum. No control subjects enrolled. INTERVENTIONS: Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in random order. Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream (Medic-Aid; Sussex, UK), and the Pari LC (Pari Respiratory Equipment; Richmond, Va), with a DeVilbiss Pulmoaide compressor (DeVilbiss Health Care; Somerset, Pa), both administering 300 mg tobramycin in 5 mL of 1/4 normal saline solution (NS). Patients were also administered 600 mg tobramycin in 30 mL of 1/2 NS with the UltraNeb 99/100 (DeVilbiss). MEASUREMENTS: Sputum and serum tobramycin concentration and pulmonary function were monitored. An adequate peak sputum tobramycin concentration was defined as > 128 microg/g sputum at any of three time points (10, 60, or 120 min) after completion of treatments. RESULTS: The peak tobramycin concentrations in expectorated sputum were 687+/-663 microg/g (mean+/-SD) with the Pari LC and 489+/-402 microg/g with the Sidestream. Adequate peak sputum tobramycin concentration was achieved in 93% of the patients with the Sidestream, and in 87% of the patients with the Pari LC. Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100, 1,498+/-1,331 microg/g with 30% of patients having levels exceeding 2,000 microg/g. Serum tobramycin concentrations were < or = 4 microg/mL for all patients following administration with each nebulizer. CONCLUSIONS: Adequately high sputum tobramycin concentrations were documented in sputum in > 85% of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems, Sidestream and Pari LC. The single tobramycin administration delivered by these two systems is well-tolerated.

Adolescent↗
PubMed1997

In vitro effects of recombinant human granulocyte-macrophage colony-stimulating factor (RhGM-CSF) on polymorphonuclear cell (PMN) and monocyte (MO) functional capacities in ovarian cancer patients versus human volunteers.

Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100 IU, respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.

Aged↗
PubMed1997

Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.

We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).

Animals↗
PubMed1997

Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?

One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.

Adult↗
PubMed1996

Risk factors for invasive Haemophilus influenzae disease among children 2-16 years of age in the vaccine era, Switzerland 1991-1993. The Swiss H. Influenzae Study Group.

BACKGROUND: Continued surveillance, and detailed investigation of direct and indirect effects of conjugated vaccines and risk factors for invasive H.influenzae serotype B (Hib) disease in the vaccine era are important. METHODS: 143 cases with invasive disease between 1991 and 1993 aged 2-16 years were selected retrospectively from a large incidence trend study. Controls (n = 336) were recruited from local vital registries and matched to cases for age, gender, and residence. Hib vaccination histories among study subjects and their siblings and other sociodemographic variables were obtained by questionnaires completed by the parents of these children. Adjusted odds ratio (OR) estimates were calculated by conditional logistic regression analysis. RESULTS: Most vaccinated subjects had received the Polysaccharide-Diphtheria Toxoid vaccine and estimated vaccine efficacy was high (95%; 95% confidence interval [CI] 60-99%). Also, the results suggested that protection afforded by vaccination against Hib extended to the family members of vaccinated children. School attendance was found to be protective against invasive Hib disease (OR:0.33; CI:1.2-14.4). Cases more often than controls reported suffering from asthma and allergies (OR:4.8; CI:1.2-19.4). CONCLUSIONS: Post-licensure vaccine efficacy is high among children > or = 2 years of age. The observed association between asthma and epiglottitis is novel and deserves further investigation.

Adolescent↗
PubMed1996

Invasive Haemophilus influenzae disease and epiglottitis among Swiss children from 1980 to 1993: evidence for herd immunity among older age groups. The Swiss Haemophilus Influenzae Study Group.

We analysed time trends in the incidence of invasive Haemophilus influenzae disease in Switzerland between 1980 and 1993 to investigate whether conjugated H. influenzae type b vaccines, licensed in Switzerland in May 1990, confer indirect protection to children in older, non-vaccinated age groups. Data were obtained from the records of 39 Swiss paediatric clinics for 2,857 children 0-16 years old with invasive H. influenzae disease. Incidence time trends were analysed by Poisson regression. The diseases incidence decreased by 80% among 0-4-year-old children (i.e. those eligible for vaccination) between 1990 and 1993. Among children aged 5-16 years, there also was an abrupt 50% fall in the incidence of H. influenzae meningitis after 1990. However, the incidence of epiglottitis in this age group had started to decline before conjugated vaccines became available, with no additional decline thereafter. While our results suggest some indirect protection conferred to older, non-vaccinated children through the administration of conjugated vaccines to younger children, they also argue that underlying time trends of invasive H. influenzae disease need not be considered when interpreting incidence rates in the vaccine era.

Adolescent↗
PubMed1996

Effects of Panax Ginseng C.A. Meyer saponins on male fertility.

Sixty-six patients have been treated with Panax Ginseng C.A. Meyer extract, of whom 30 oligoastenospermic sine causa (group A), 16 oligoastenospermic with idiopathic varicocele (group B). Twenty age-matched volunteers were used as controls (group C). Use of Panax Ginseng extract showed an increase in spermatozoa number/ml and progressive oscillating motility, an increase in plasma total and free testosterone, DHT, FSH and LH levels, but a decrease in mean PRL. It is suggested that ginsenosides may have an effect at different levels of the hypothalamus-pituitary-testis axis.

Adult↗
PubMed1995

Abnormalities of pulmonary function tests after marrow transplantation predict nonrelapse mortality.

To determine whether pulmonary function test (PFT) results after marrow transplantation were predictive of nonrelapse mortality, a review was made of prospective, nonrandomized PFT results for association with nonrelapse mortality by log-rank test and Cox proportional hazards modeling. The setting was a tertiary referral center. The patients were all marrow recipients who performed PFT between Days 60 and 120 after marrow transplantation between July 1, 1983 and December 31, 1990 (n = 906). At 3 mo after transplantation, the mean values for total lung capacity (TLC) and diffusing capacity decreased, and restrictive ventilatory defects (TLC < 80% of predicted) were noted in 34% of the cohort. Airflow rates (FEV1/FVC) were unchanged. A restrictive lung defect at 3 mo after transplant or a significant decline (> or = 15%) in TLC from baseline despite remaining within the normal range was associated with a twofold increased risk of nonrelapse mortality. Neither airflow obstruction nor impairment in diffusing capacity was associated with an increased risk. Abnormalities of the TLC at 3 mo after transplant were associated with death with respiratory failure, but not with an increased risk of chronic graft-versus-host disease (GVHD). There is an increase in the nonrelapse mortality rate associated with either the presence of a restrictive defect 3 mo after marrow transplantation or a significant decline in lung volume compared with baseline. This effect is most pronounced more than 1 yr after marrow transplant and appears to be a result of an increase in the rate of death with respiratory failure, not chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention.

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.

Anemia, Aplastic↗
PubMed1993

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model.

PURPOSE: We explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. RESULTS: We found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation (p = .18). One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation (p > .20). With granulocyte colony stimulating factor administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with granulocyte colony stimulating factor after 400 cGy single dose total body irradiation, a study of granulocyte colony stimulating factor after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with granulocyte colony stimulating factor administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. CONCLUSION: Within the limitations of the experimental design, we conclude that single-dose and fractionated total body irradiation have comparable marrow toxicity in dogs.

Animals↗
PubMed1993

FK-506 and methotrexate prevent graft-versus-host disease in dogs given 9.2 Gy total body irradiation and marrow grafts from unrelated dog leukocyte antigen-nonidentical donors.

FK-506 was evaluated either alone or combined with methotrexate (MTX) for prevention of graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and dog leukocyte antigen-nonidentical unrelated marrow grafts. Studies with marrow autografts showed gut toxicity and weight loss to be major side effects of FK-506. There was no hematopoietic toxicity with FK-506. In an initial allograft study, 5 dogs were given FK-506 intramuscularly at 0.3 mg/kg/day from days 0 to 8 and then orally at 0.5 mg/kg/day. All 5 died, 3 with intussusception most likely due to FK-506 toxicity, 1 with graft failure, and 1 with GVHD. Subsequently, the FK-506 dose was reduced and these drug schedules were used: FK-506 days 0-8 at 0.15 mg/kg/day i.m. and then orally at 0.5 mg/kg/day until day 90, with or without MTX intravenously at 0.4 mg/kg days 1, 3, 6, and 11. Twenty allografts were done, 10 with FK-506 alone, and 10 with MTX/FK-506. Results were compared with those in concurrent and historical controls given either no immunosuppression (n = 64), MTX (n = 114), CsA (n = 15), or MTX/CsA (n = 17). Five of 20 current dogs died with intussusception, too early to be evaluated for GVHD. The 10 dogs given FK-506 alone survived significantly better than those not given immunosuppression but not differently from those given short-term MTX or CsA alone. Three died from toxicity, 2 with graft failure, and 4 with GVHD. Only 1 dog became a long-term survivor, and this dog inadvertently received a single dose of MTX on day 7. Two of 10 dogs given MTX/FK-506 died from toxicity, 1 died with graft failure, 2 died with GVHD, and 5 became long-term survivors, a result that is significantly better than seen with either drug alone and similar to that seen with MTX/CsA. Four of the 5 survivors had no clinical GVHD. FK-506 blood levels were 15-35 ng/ml between days 8 and 15, when gut toxicity was most severe. Thereafter, levels were approximately 5 ng/ml. In conclusion, FK-506 prolonged survival of recipients of dog leukocyte antigen-nonidentical unrelated marrow grafts. When FK-506 was combined with MTX, graft-host tolerance was induced in 50% of dogs, even though FK-506 was stopped on day 90.

Animals↗
PubMed1993

Splenectomy does not enhance engraftment of DLA-nonidentical marrow transplants.

Previous studies in mice and monkeys suggested that either splenic irradiation of splenectomy led to enhanced allogeneic marrow engraftment. These findings suggested that a population of radiation-resistant host cells involved in mediating marrow graft rejection are sequestered in the spleen. In this current study, the effect of splenectomy in dogs receiving 9.2 Gy total body irradiation (TBI) and unrelated dog leukocyte antigen (DLA)-nonidentical donor marrow grafts was studied. We found that splenectomy did not significantly change the incidence of graft failure as compared to that observed in previously and concurrently transplanted nonsplenectomized recipients.

Animals↗