Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.     

Pathophysiology of SPINK mutations in pancreatic development and disease.

The endogenous pancreatic trypsin inhibitor, SPINK, is believed to limit enzyme activity in the pancreas and reduce the risk of pancreatitis. Recently, mutations in the SPINK1 gene have been associated with development of both acute and chronic pancreatitis. In most patients with SPINK1 mutations, the genetic variants do not cause the disease independently, but may act in concert with other genetic or environmental factors. Recent studies, using mice in which the trypsin inhibitor gene has been deleted or overexpressed, provide novel insights into the role of SPINK in pancreatic development and pancreatitis.     

Aerobic exercise training fails to lower hypertriglyceridemia levels in persons with advanced HIV-1 infection.

The purpose of this study was to determine whether blood lipid and lipoprotein concentrations varied in 5 men with advanced HIV-1 infection after 12 months of aerobic exercise training. Prior to exercise, the mean baseline cholesterol and high-density lipoprotein cholesterol (HDL-C) serum concentration were each lower, and mean baseline triglyceride concentration was higher compared to a healthy population norm. Consistent exercise training for 12 months failed to significantly (p > .05) alter cholesterol or HDL-C. Triglyceride concentration was significantly (p < .05) elevated above baseline (63 mg/dL) regardless of exercise compliance. The results suggest that long-term exercise training cannot correct lipid profile abnormality, particularly hypertriglyceridemia, common to individuals with advanced HIV-1 infection.     

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Zinc deficiency and hyperprolactinaemia are not reversible causes of sexual dysfunction in uraemia

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.     

The syndrome of senile gait

Summary Infrared computed stroboscopic photometry was used to quantify the kinematic profiles of walking in 10 elderly patients with symmetrical neurological disturbances of gait and in 19 age-matched neurologically healthy people. Clinical examination of the patients revealed similar profiles of walking even though their diagnoses were vascular dementia (2), normal pressure hydrocephalus (2), Alzheimer dementia with possible normal pressure hydrocephalus (2), mixed Alzheimer and vascular dementia (1), peripheral neuropathy (1), Alzheimer dementia with parkinsonian features (1), and un determined (1). Quantitatively, the patients' gait kinematics deviated greatly from control values, but these deviations were statistically attributable to reductions in stride. We suggest that many gait disturbances in elderly people are similar, regardless of etiology, because the characteristics of these gait disturbances are heavily veiled by nonspecific stride-dependent changes that comprise the syndrome of senile gait.