Graft versus graft and graft versus host reactions after HLA-identical bone marrow transplantation in a patient with severe combined immunodeficiency with transplacentally acquired lymphoid chimerism

We describe a patient with severe combined immunodeficiency and transplacental transfer of maternal T cells who received an unfractionated HLA-identical sibling bone marrow transplant without prior conditioning. He presented prior to transplantation with a dermatitis later diagnosed as mild graft versus host disease. He had a normal absolute lymphocyte count, but proliferative responses to mitogens were very low. Antigens of the noninherited maternal HLA haplotype were detected on his blood lymphocytes. After transplantation, he developed a severe reaction including fever, cutaneous erythema and hepatosplenomegaly. Lymphocytes carrying the noninherited maternal HLA haplotype disappeared from his circulation, and his unprimed mononuclear cells became spontaneously cytotoxic to maternal lymphoblasts. He subsequently developed a lymphocytosis of 69,000/mm³, diarrhea, elevated transaminases and a worsening rash, necessitating treatment with immunosuppressive agents. Full T-cell engraftment and evidence of B-cell function later ensued and spontaneously cytotoxic lymphocytes against maternal cells disappeared by 47 days post-transplantation. We postulate that the patient's constellation of signs and symptoms after transplantation represented a combination of severe graft versus graft and mild graft versus host reactions.     

Eosinophil chemotaxis and anterior uveitis from topical dimaprit and nordimaprit

Topical application of the H2-histamine receptor agonist, dimaprit (S-[4-N,N-dimethylaminopropyl]isothiourea), produced eosinophil chemotaxis into the anterior segment of rabbit eyes only when an H2-antagonist was co-administered. Nordimaprit (S-[4-N,N-dimethylaminoethyl]isothiourea), a structural homologue of dimaprit that lacked activity at histamine receptors, produced eosinophil chemotaxis whether or not an H2-antagonist was co-administered. Onset of eosinophil chemotaxis began after 2 or more days of treatment, and was accompanied by corneal edema, opacification, and ocular inflammation. There was no concurrent eosinophilia in the peripheral blood or in the conjunctiva. The response occurred in pigmented and albino rabbit eyes, and was facilitated by prior co-administration of proparacaine eye drops. Another dimaprit homologue without activity at histamine receptors, homodimaprit (S-[4-N,N-dimethylaminobutyl]isothiourea), did not produce eosinophil chemotaxis when applied topically, nor did the H2-agonists impromidine, histamine, or 4-methylhistamine, whether co-administered with an H2-antagonist or not. It was concluded that dimaprit and nordimaprit produced a selective eosinophil chemotaxis unrelated to H1- and H2-histamine receptor activity. However, the H2-agonist activity of dimaprit appeared to inhibit this response unless neutralized by an H2-antagonist. Topical application of dimaprit with an H2-antagonist or nordimaprit alone may allow large numbers of non-degranulated eosinophils, free of other cell types, to be harvested from the aqueous humor.     

Amino acid levels in elderly nursing home residents

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment.     

A short-term follow-up comparison of two trans-obturator tape procedures

The objective of the study was to compare the clinical outcomes at the short-term follow-ups of two novel transobturator mid-urethral sling procedures – the transobturator tape (TOT) procedure and the tension-free vaginal tape (TVT)-obturator procedure. The study cohort consisted two groups of 40 women with urodynamically proven stress urinary incontinence (SUI). The patients in one group underwent the TOT procedure, performed according to Delorme (Prog Urol 11:1306–1313, 2001); those in the second group underwent the TVT-obturator operation, performed according to de Leval (Eur Urol 44:724–730, 2003). Intra-operative diagnostic cystoscopy was not performed with either the TVT-obturator or the TOT procedures. The average follow-up was 12 months. The two patient groups were similar in terms of demographic and therapeutic criteria, except for patient age, which was significantly younger in the TVT-obturator group. Previously reported TVT-related operative complications, such as bladder penetration, intra-operative bleeding, field infection and post-operative pelvic floor relaxation, were not observed in patients of either group. Bowel and urethral injuries were also not recorded. The therapeutic failure rates were 10% for the TOT procedure and 5% for the TVT-obturator procedure. Urinary frequency and urgency post-operatively were reported in 25% of the TOT patients and 19% of the TVT-obturator patients, pelvic or vaginal pain affected 10% of the TOT and 5% of the TVT-obturator patients, while post-operative voiding difficulty was experienced by 12.5% of the TOT and 7.5% of the TVT-obturator patients. None of the above-mentioned differences between the two patient groups were of statistical significance. The TVT-obturator and TOT procedures, both minimally invasive, novel, mid-urethral sling procedures, seem to be safe, easy-to-perform and effective in treating female SUI. The patients of both study groups suffered less intra- and post-operative surgical complications than previously been reported in connection with the TVT operation. The TVT-obturator patients had fewer therapeutic failures, less post-operative urinary frequency and urgency, less pelvic pain and less voiding difficulty. All of these findings, however, had no statistical significance; consequently, long-term comparative data collection will be required before solid conclusions can be drawn on the superiority of either of these two operative techniques.     

Psychoeducational findings among children treated for phenylketonuria

Early treated phenylketonuric children who maintained a phe-restricted diet through age 10 were compared with those who discontinued the diet after age 6 on standardized tests of intelligence, school achievement, language, and perceptual skills. Mean IQ, reading, and spelling test scores improved between ages 6 and 10 for the on-diet children in comparison to those who were off diet. Mean scores on arithmetic, language, and perceptual skills, however, declined at a uniform rate for both groups. Children with PKU scored significantly lower than did their non-PKU siblings on tests of visual perception and visual-motor skills. We conclude that children with PKU should be maintained on a phe-restricted diet.     

Financial risk, hospital cost, complications and comorbidities (CCc) in non-CC stratified urology diagnostic related groups

The federal Medicare Diagnosis Related Group payment mechanism is undergoing constant change. Significant interest has been generated at the health policy level regarding reimbursement for patients with complications and comorbidities. The purpose of this study was to analyze hospital resource consumption for patients in the seventeen urology non-complicating condition (CC) stratified Diagnostic Related Groups (DRGs), currently 45 percent of urology DRGs. We analyzed 185 Medicare patients in these non-CC stratified urology DRGs and found that patients with more CCs per patient had higher total hospital costs per patient, financial risk under DRGs, a greater percentage of outliers, and a higher mortality, than patients in these same DRGs with fewer CCs per patient. These findings suggest that the current DRG system is inequitable to some patients and certain hospitals vis-a-vis non-CC stratified urology DRGs. The Health Care Financing Administration has not significantly changed the complicating condition urology DRG classification, as of its recent May, 1988 legislation. Financial disincentives to treat these patients may affect both their access and quality of care in the future.     

Cardia: study design, recruitment, and some characteristics of the examined subjects

In 1984, a prospective cohort study, Coronary Artery Risk Development in Young Adults (CARDIA) was initiated to investigate life-style and other factors that influence, favorably and unfavorably, the evolution of coronary heart disease risk factors during young adulthood. After a year of planning and protocol development, 5,116 black and white women and men, age 18-30 years, were recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of major risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors. This report presents the recruitment and examination methods as well as the mean levels of blood pressure, total plasma cholesterol, height, weight and body mass index, and the prevalence of cigarette smoking by age, sex, race and educational level. Compared to recent national samples, smoking is less prevalent in CARDIA participants, and weight tends to be greater. Cholesterol levels are representative and somewhat lower blood pressures in CARDIA are probably, at least in part, due to differences in measurement methods. Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.