The effect of growth hormone supplementation on late nutritional independence in pediatric patients with short bowel syndrome

Purpose

The use of growth hormone (GH) supplementation for intestinal adaptation among adult patients with short bowel syndrome (SBS) has provided mixed results. This report examines the effect of GH supplementation on SBS in pediatric patients.

Methods

Two girls with SBS from neonatal gastrointestinal catastrophes received exogenous GH at 0.3 mg/kg per week subcutaneously and concurrent glutamine supplementation, beginning at 6 and 6½ years of age. Changes in growth (height and weight) and changes in enteral and parenteral energy requirements were evaluated.

Results

Treatment duration was 8 and 2.5 years, respectively. Patient weights increased from the 5th to the 41st percentile and from the 17th to the 23rd percentile, respectively. Height increased from the 1st to the 57th percentile in the former patient and increased from less than the 1st to the 17th percentile in the latter. Both patients are independent of parenteral nutrition and take enteral nutrition alone. Tolerance for enteral diets was significantly improved in each girl, with only 2 stools per day maintained in one patient.

Conclusions

The data show that late exogenous treatment with GH and glutamine supplementation improved growth parameters in pediatric patients with SBS. Growth hormone and glutamine supplementation may be beneficial in promoting late intestinal adaptation in pediatric patients with SBS. These data also suggest that these adjuncts may be useful in the early phases of intestinal adaptation.     

Testicular hypotrophy does not correlate with grade of adolescent varicocele

PURPOSE: Testicular hypotrophy is the most widely accepted indication for correcting adolescent varicocele. Previous studies in adolescents have shown a relationship between increasing grade of varicocele and the likelihood of testicular hypotrophy. As this relationship has significant clinical implications, we studied the correlation between grade and testicular volume disproportion in our adolescent varicocele population. MATERIALS AND METHODS: We reviewed the adolescent varicocele database at our institution. A total of 168 patients 8 to 21 years old were studied. We routinely calculated testis volumes using scrotal ultrasound. Testicular disproportion was calculated using the equation [(size of unaffected testis) - (size of affected testis)]/(size of unaffected testis) x 100%. Disproportion was categorized as less than 10%, 10% to 20% and more than 20%. Varicoceles were graded by an attending urologist with the patient standing, using the system of Dubin and Amelar. Analysis of variance and Pearson chi-square indicated no significant differences in volume differential between varicocele grades. RESULTS: Mean +/- SD volume differential was 18% +/- 15% for grade I, 25% +/- 20% for grade II and 19% +/- 14% for grade III. ANOVA revealed no significant difference in mean volume differential between the 3 varicocele grades (p = 0.10). When categorizing patients into 3 levels of volume differential (less than 10%, 10% to 20%, more than 20%) no significant correlation was observed between varicocele and volume differential (p = 0.48, chi-square test). CONCLUSIONS: Grade of varicocele does not correlate with presence or severity of testicular disproportion in adolescent boys with varicocele as measured by scrotal ultrasound.     

Truncated N-terminal mutants of SV40 large T antigen as minimal immortalizing agents for CNS cells

Immortalized central nervous system (CNS) cell lines are useful as in vitro models for innumerable purposes such as elucidating biochemical pathways, studies of effects of drugs, and ultimately, such cells may also be useful for neural transplantation. The SV40 large T (LT) oncoprotein, commonly used for immortalization, interacts with several cell cycle regulatory factors, including binding and inactivating p53 and retinoblastoma family cell-cycle regulators. In an attempt to define the minimal requirements of SV40 T antigen for immortalizing cells of CNS origin, we constructed T155c, encoding the N-terminal 155 amino acids of LT. The p53 binding region is known to reside in the C-terminal region of LT. An additional series of mutants was produced to further narrow the molecular targets for immortalization, and plasmid vectors were constructed for each. In a p53 temperature sensitive cell line model, T64-7B, expression of T155c and all constructs having mutations outside of the first 82 amino acids were capable of overriding cell-cycle block at the non-permissive growth temperature. Several cell lines were produced from fetal rat mesencephalic and cerebral cortical cultures using the T155c construct. The E107K construct contained a mutation in the Rb binding region, but was nonetheless capable of overcoming cell cycle block in T64-7B cell and immortalizing primary cultured cells. Cells immortalized with T155c were often highly dependent on the presence of bFGF for growth. Telomerase activity, telomere length, growth rates, and integrity of the p53 gene in cells immortalized with T155c did not change over 100 population doublings in culture, indicating that cells immortalized with T155c were generally stable during long periods of continuous culture.     

Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier

We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.     

A therapeutic HIV vaccine: how good is good enough?

The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources.     

Management of menstrual problems and contraception in adolescents with mental retardation: a medical, legal, and ethical review with new suggested guidelines

The controversial history of the reproductive rights of the mentally retarded has led to the formulation of laws in the past century designed to protect women from forced sterilization. Significantly, however, in their official ethical guidelines, The American College of Obstetricians and Gynecologists states that "sterilization should not be denied to individuals simply because they also may be vulnerable to coercion" (Int J Gynaecol Obstet 1999; 65:317). Recent advances in medical and surgical methods of contraception and control of menstrual abnormalities have led to a re-evaluation of the management of adolescents with special needs. Physicians, the courts, parents, and caretakers need to be aware of the latest medical and surgical options available, the current applicable laws in each state if such exist, and the ethical guidelines to determine what treatment option is in the best interests of the patient. This review examines the history of the sterilization of the mentally retarded, the latest surgical and pharmacologic treatments available, and the current legal environment and proposes an algorithm to facilitate the management of menstrual hygiene and contraception.     

IUD use and the risk of endometrial cancer

OBJECTIVE: Although the intrauterine device (IUD) is one of the most widely used forms of contraception throughout the world, its potential long-term effects on the uterus have not been thoroughly evaluated. This paper reports the long-term results of IUD use on the incidence of endometrial cancer. STUDY DESIGN: The data is part of a nationwide case-control, pilot study that was undertaken in order to evaluate the possible influence of ovulation induction drugs on the risk of endometrial cancer. The study included 128 living women 35-64 years old, with a histologically confirmed diagnosis of endometrial carcinoma. The controls were 255 women from the same dialing areas selected by random digit dialing. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. RESULTS: The following parameters were found to be independently associated with endometrial cancer controlling for age: nulliparity OR=2.7 (95% CI 1.1-6.5, P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI>/=27 OR=2.3 (95% CI 1.4-3.8, P=0.001).The use of oral contraceptives and IUD were found to be protective; OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61, P=0.001, 0.19-0.70, and 0.003, respectively). CONCLUSIONS: IUD use may have a protective effect on endometrial cancer risk. The protective effect of IUD may be either, through the intense inflammatory response that leads to other lisosomal and inflammatory actions, which may include cells responsible for early elimination of hyperplastic endometrial epithelial cells or, the more complete shedding of the endometrium associated with IUD use may decrease hyperplasia of the endometrium, a known risk factor for endometrial carcinoma.     

Towards a critical health psychology practice

The field of critical psychology is exerting an influence in the way various sub-disciplines within psychology operate. In this article we use a critical psychology framework to review the field of health psychology. Through the use of values, assumptions and practices we review progress in health psychology and offer recommendations for aligning contemporary practices with current thinking in critical psychology. We discuss typical expectations, critical formulations and critical practice for interventions with individuals, groups and communities along these dimensions.