Low fibrosis progression of recurrent hepatitis C in apolipoprotein E epsilon4 carriers: relationship with the blood lipid profile.

BACKGROUND: The histological outcome of chronic hepatitis C is better among carriers of the apolipoprotein E (ApoE) epsilon4 allele, for reasons unknown. The orthotopic liver transplantation (OLT) setting allows to separate the role played by liver-derived ApoE (graft) from ApoE of different origin (recipient). Patients and METHODS: Forty-six OLT recipients with recurrent hepatitis C were studied. Grafts and recipients were genotyped for ApoE. In a follow-up extending up to 4 years, the serum triglycerides-to-cholesterol ratio (T/C ratio) was measured 1 year after OLT, whereas fibrosis progression was assessed yearly and expressed as fibrosis units/month (FU/mo). RESULTS: A T/C ratio < or =0.75 was observed in 13/15 cases in which both donor and recipient were epsilon4 carriers, 10/19 cases in which epsilon4 alleles were of exclusive recipient's origin and 5/12 cases in which epsilon4 alleles were of exclusive donor's origin or absent (P<0.02). One year after OLT, a fibrosis progression < or =0.100 FU/mo was associated with a low T/C ratio (24/34 vs. 4/12, P<0.05). An Ishak staging score >2 was reached later by male recipients who were epsilon4 carriers (P<0.002). CONCLUSIONS: Recipient's carriage of ApoE epsilon4 affects fibrosis progression of recurrent hepatitis C through gender-specific mechanisms, associated with a peculiar, ApoE-associated, lipid profile.     

Prevalence and characteristics of early-onset type 2 diabetes in Mexico

OBJECTIVE: To investigate the prevalence and characteristics of patients with type 2 diabetes diagnosed before the age of 40 years (early-onset disease) in a nationwide, population-based study. METHODS: Using a multistage sampling procedure, we enrolled a representative sample of Mexican urban adults aged 20 to 69 years. Weight, height, blood pressure, and plasma levels of glucose, insulin, and other metabolic parameters were measured in all subjects. RESULTS: We identified 993 subjects with type 2 diabetes, including 143 subjects aged 20 to 39 years (14% of those with diabetes). Subjects with early-onset diabetes had a greater prevalence of obesity and higher plasma insulin and lipid levels than did age-matched controls, and a greater prevalence of high-density lipoprotein cholesterol levels <35 mg/dL and severe hypertriglyceridemia than did older subjects with diabetes. Those (n = 32) with a normal body mass index (20 to 25 kg/m(2)) tended to have insulin deficiency as the main abnormality, whereas the "metabolic syndrome" characterized the remaining 111 subjects with early-onset diabetes. CONCLUSION: Most patients with early-onset type 2 diabetes in Mexico are obese or overweight, suggesting that obesity treatment and prevention programs may be effective in reducing the prevalence of this disease.     

Fetal HLA typing in beta thalassaemia: implications for haemopoietic stem-cell transplantation

Stem-cell transplantation can cure beta thalassaemia. We aimed to assess whether fetal HLA typing done early in the pregnancy of couples who were at risk of beta thalassaemia could provide an alternative to pregnancy termination if the prospect of a bone-marrow transplantation from a family member was available. In our clinic in Sardinia, we did fetal HLA typing for 49 couples at risk of having a baby with beta thalassaemia. Two affected children were born and successfully received a transplantation from a family donor. Five non-affected fetuses were HLA compatible with an affected sibling and their cord blood was harvested for a future transplantation.     

Glomerular hypertension and injury in desoxycorticosterone-salt rats on antihypertensive therapy

Uninephrectomized male Munich-Wistar rats received either weekly subcutaneous injections of vehicle and water for drinking; injections of desoxycorticosterone (DOC) and 1% saline (SALT) for drinking; or DOC and SALT with hydrochlorthiazide, hydralazine, reserpine and KCl added. All studies were performed six weeks after UNX. At that time, rats receiving DOC and SALT alone were hypertensive and had significantly more proteinuria and morphologic evidence of glomerular injury than rats given vehicle and tap water which were normotensive. Antihypertensive therapy normalized mean arterial pressure in DOC-SALT rats, but failed to prevent proteinuria, mesangial expansion or focal segmental glomerular lesions. Micropuncture studies revealed that glomerular capillary pressure was elevated in both untreated and treated DOC-SALT animals. We conclude that drugs which successfully reduce systemic blood pressure may fail to correct glomerular capillary hypertension in DOC-SALT rats. As persistence of intrarenal hypertension is associated with significant glomerular injury, normalization of glomerular capillary pressure rather than systemic arterial pressure is crucial to the prevention of glomerular injury in this model.     

The in vitro and in vivo effects of extracorporeal shock waves on malignant cells

Summary The in vitro cytotoxic effect of extracorporeal shock waves (ESW) on renal cell carcinoma (RCC) cells was compared to the effect on normal human embryonic kidney (NHEK) cells. In the in vitro studies cell samples were brought into the second focal point and exposed to different numbers of shock wave impulses. The four parameters of RCC tumor cell injury which were measured, i.e., cell viability, cell growth, cell attachment and electron microscopic evidence of damage, were augmented with increasing SW levels. At 2,000 shock waves (SW) a significant decrease in RCC viability, cell growth and cell attachment was seen compared to the NHEK cells. In the in vivo experiment a FANFT induced bladder tumor was transplanted into the right hind legs of C3H/He mice and the tumors were exposed to 1,400 SW. Preliminary data showed that 1,400 SW at day 12 post transplant significantly inhibited tumor growth. Combining 1,400 SW with cis-diamminedichloroplatinum (4 mg/kg) did not enhance the tumor inhibitory effect of each individually. Doxorubicin (5 mg/kg) and 1,400 SW produced a significant synergistic tumor inhibitory effect.Supported by The University Urological Research Foundation     

Lymphocyte subpopulations in anaphylactoid purpura.

The immunoglobulins, complement components C3 and C4, lymphocyte subpopulations, and K-cell activity were studied in 13 children with anaphylactoid purpura and in 12 children of the same ages who acted as controls. The children with anaphylactoid purpura had significantly lower T-cell counts, greater K-cell activity and IgM values, and lower C3 levels than the controls.