Early Low-Grade Proteinuria: Causes, Short-Term Evolution and Long-Term Consequences in Renal Transplantation

Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1-3 months and 3-12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p<0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival.     

Body composition in the elderly: Total body water and anthropometry

Body composition measured with isotopic dilution was compared with anthropometric measurements. The study was carried out in 47 subjects from both sexes, 65 to 92 years old. Total body water (TBW), anthropometric measurements, and dynamometry were assessed. TBW was significatively higher in men than women and decreased with age. Dynamometry and fatfree mass were well correlated (r=0.73 in males and r=0.58 in females) and significantly different between sexes. A negative correlation was found for dynamometry with age, being significant for women. Linear regression equations to predict TBW from anthropometric measurements in males and females were obtained: Males: TBW(I)=19.349+0.617 weight(kg) — 0.931 mid-arm circumference(cm)+0.122 dynamometry (kg) Females: TBW(l)=−5.531+0.343 weight(kg)-0.213 triceps skinfold (mm)+ 0.148 dynamometry(kg) + 3.424 wrist diameter (cm). This simple model is proposed for use in epidemiological and field studies where other more sophisticated methods can not be applied.     

Temporal sequence of gene expression leading caudal prosencephalon to develop a midbrain/hindbrain phenotype.

Transplantation of prosomeres 1-2 into the cerebellar plate were used, by using chick/quail chimeras, to analyse the temporal sequence of the genetic cascade leading the graft to develop a midbrain/hindbrain phenotype. Our results show that (1) at Hamburger and Hamilton (HH) stage 13, Pax2 and En2 are already induced within the graft, before all other genes of the cascade, whereas misexpression of Fgf8 is also observed within the contiguous host cerebellar plate; (2) within the graft, Otx2 repression and Gbx2 induction (see Hidalgo-Sánchez et al. [1999] Development 126:3191-3203) are secondary events that affect, from stages HH14-15, the areas in contact with the host Gbx2/Fgf8-expressing cerebellar plate; (3) at these stages, the repressed Otx2 territory extends beyond the areas induced to express Gbx2, with the two territories not abutting before HH17-18; (4) Fgf8 expression becomes progressively induced within the Otx2-repressed/Gbx2-induced territory, starting at HH15-16. Our results support the hypothesis that the host-Gbx2/graft-Otx2 interface could trigger the genetic cascade induced within the graft and that the Gbx2-induced domain could play a key role during the establishment of the induced intragraft midbrain/hindbrain boundary.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

Factors affecting the cold transfer during cryotherapy

Cryotherapy of the cervix was made in 40 patients for chronic cervicitis, and the thickness of the ice zone around the probe was measured in function of treatment time, under standard cooling conditions. The pace of growth of the ice zone allowed the author to draw conclusions as to the conductivity of the studied tissue. It was established that in the study-group, the patient's age and their histories of abortions did not influence the cold transfer significantly. The difference between the average values of ice zone thickness measured in the groups of nulliparae and multiparae was, however, significant. Findings have shown that the spread of cold in the cervical tissue in nulliparous women is better than in multiparae and so a greater efficacy of cryotherapy can be expected in nulliparae.     

Locked intramedullary nailing for complex non-union of the tibia

Ten patients with complex non-union of the tibia were treated by locked intramedullary nailing. These patients had scarred skin as a result of initial severe open fractures, multiple debridement or fasciotomies with external fixators and skin grafts applied. Seven of the patients also had previous osteomyelitis or pin track infections. Fully pain-free walking was achieved in all patients and radiological union in nine patients without the need for a bone graft. Four patients developed infection after nailing, of which three resolved with treatment.     

The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and rat islets and HIT-T15 B cells

Summary In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p<0.01) lower and serum insulin levels were significantly (p<0.01) higher in treated diabetic animals (10.4±1.0 mmol/l and 12.8±1.1 U/ml respectively) compared to untreated diabetic controls (17.4±1.7 mmol/l and 8.0±0.7 U/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion.     

Comparison of chitin and Amberlite IRA-938 for alpha-galactosidase immobilization

Watermelon alpha-galactosidase (EC 3.2.1.22) was immobilized on a natural (chitin) and a synthetic anion-exchange (Amberlite IRA-938) support by covalent coupling methods. The procedure entails the activation of supports with 1,1'-carbonyldiimidazole (CDI), followed by immobilization of the enzyme on to these supports without and with a spacer arm; gamma-aminobutyric acid (GABA). Optimization of activation was performed by changing the CDI concentrations and coupling efficiencies. The comparison of two immobilization techniques for both chitin and Amberlite IRA-938 was made by comparing different enzyme concentrations against enzyme activity yield. Furthermore, the storage stability of the immobilized enzymes was also investigated and chitin immobilized alpha-galactosidase was found to be better. Although the activity yield of immobilized enzymes were the same for both supports, the short storage stability of immobilized enzyme on Amberlite IRA-938 is currently a drawback to its applications.     

In vivo activation of NK cells induces inhibition of lung colonization of H-2 positive and H-2 negative fibrosarcoma tumor clones

The role of different tilorone analogs in the abrogation of the metastatic spread of H-2 positive and H-2 negative tumor clones was studied. Pre-treatment of BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of an H-2 negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental metastasis assay. This effect was also evident when clones were treated with other tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2 negative chemically induced fibrosarcoma clones were also tested. The effect was not due to direct toxicity of the tilorone analog on tumor cells, but instead was dependent on NK cells; this was suggested by the finding that treatment of mice with anti-asialo GM₁ abrogated the effect of the tilorone analog (RMI 10,874DA compound). Interestingly, the inhibition of lung colonization after intravenous injection was again observed regardless of the H-2 phenotype of the tumor clones, and H-2⁺ and H-2^– clones were similarly inhibited.In vitro assays of NK sensitivity of tumor clones showed that lysis varied depending on the H-2 phenotype of tumor clones, indicating an absence of correlation betweenin vivo andin vitro results.