Hypertension and Afro-descendant ethnicity: a bad interaction for lupus nephritis treated with cyclophosphamide?

Hypertension and ethnicity are important prognostic factors in evolution of lupus nephritis. A cohort of 75 patients with lupus nephritis treated with cyclophosphamide was conducted to investigate the evolution of creatinine levels between Caucasians and Afro-descendants. A multiple linear model was used to evaluate the combined effects of ethnicity and hypertension over delta creatinine controlling confounders. Sample characteristics were: 85% females; mean (+/-SD) age of 33.6 +/- 12.0 years; 77% Caucasians; 40% hypertensive at renal biopsy; 91% WHO class IV; mean basal creatinine: 1.5 +/- 1.3 mg/dL; mean final creatinine: 2.1 +/- 2.5 mg/dL; 40% anaemia; proteinuria: 5.4 +/- 4.8 g/day. Comparing Caucasians and Afro-descendants, it was found: 28.1% versus 72.2% for hypertension (P = 0.002); 31.6% versus 66.7% for anaemia (P = 0.018); 5.9 +/- 5.0 versus 3.8 +/- 4.0. g/day (P = 0.02) for proteinuria. Other comparisons including basal creatinine did not reach statistical significance. Comparing outcomes between Caucasians and Afro-descendants, it was found: 10.5% versus 22.2% for doubling of creatinine (P = 0.24); 0.41 +/- 2.03 versus 1.05 +/- 2.41 for delta creatinine ( P = 0.29); 8.8% versus 22.2% for haemodialysis (P = 0.21) and 3.5% versus 5.6% for death (P = 0.99). Analysing delta creatinine with multiple linear regression showed that hypertension had a significant overall effect (b = 0.80; SE = 0.32; P = 0.015), ethnicity alone was not significant (b = 0.35; SE = 0.29; P = 0.228); however, the effect of hypertension on delta creatinine was more intense among Afro-descendants than among Caucasians (interaction term b = - 0.83; SE = 0.37; P = 0.027). Afro-descendants lupus patients experience worst prognosis of renal function probably due to the effect of hypertension and not ethnicity per se.

Clinical relevance of low levels of preformed alloantibodies detected by flow cytometry in the first year post-kidney transplantation.

OBJECTIVE: To determine the prevalence of transplants performed with a false-negative cytotoxicity cross-match and to analyze the clinical relevance of alloantibodies (Ab) detected only by flow cytometry (flow). METHODS: We studied 66 patients undergoing kidney transplantation from a cadaveric donor. All patients had a simultaneous negative T+AHG+DTT and B+DTT. Pretransplant sera were retrospectively analyzed by flow cytometry according to an Emory University protocol: (1) T+ and B-: Ab anti-class I; (2) T- and B+: anti-class II; (3) T+B+: anti-class I + II. Chi-square, Fisher exact, Student t test, and Kaplan Meier analyses were employed with significance assigned at P < or = .05. RESULTS: The overall incidence of false-negative cytotoxicity was 33.3% (22/66), namely, 6.1% (n = 4) anti-class I; 9.1% (n = 6) anti-class II; and 18.2% (n = 12) anti-class I + II. Primary nonfunctioning grafts occurred in 6.8% (3/44) and 13.6% (3/22) negative and positive flow patients (two anti-class I + II and one class II; P = .39). The incidence of graft loss in the first year was respectively, 13.6% (6/44) and 18.2% (4/22; two anti-class II and two anti-class I + II; P = .72). Compared to flow-negative grafts, creatinine levels were significantly higher among flow-positive patients at 8 and 12 weeks. One-year graft survivals were 86.4% among negative versus 81.8% for the positive group (P = .67). CONCLUSIONS: We observed that 33% of kidney transplant recipients had low levels of alloantibodies detected only by flow. This single factor was associated with the worst graft function in the first trimester with a suggestion of a higher risk for non-functioning graft.

Cryoablation of benign breast tumors: evolution of technique and technology.

We report on improvements in cryoprobe design and techniques of cryoablation as a minimally invasive alternative to open surgery for the treatment of benign breast tumors. In the study, which was conducted in 12 centers, 124 lesions in 102 patients were monitored for a period of 12 months after cryoablation. Two different treatment techniques were used: Double HI FREEZE and Tailored Freeze. In patients treated with the Tailored Freeze technique significantly better results were recorded 12 months after the procedure: the median reduction in tumor volume was 91%, 73% of all tumors treated were nonpalpable, 84% of lesions less than 2.5 cm in maximum diameter were nonpalpable, and none of the 31 mammograms performed yielded abnormal findings. Patient satisfaction was good to excellent in 92% of the patients. The safety profile of this technique was excellent; all complications were minor. Evolution of cryoablation freezing techniques, coupled with improvements in cryoprobe design, has resulted in significant improvements in both safety and effectiveness.

Presence of proliferating (MiB-1-positive) cells in cervical smears of women infected with HIV is associated with clinical outcome: a study of Brazilian women.

The hypothesis tested was that there is an association between the presence of proliferating (MiB-1-positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV-positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV- women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB-1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB-1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB-1-positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient.

The "rejection reaction" is not confined solely to the allograft.

The rejection process refers primarily to the destruction of foreign tissues by host immune mechanisms. This process affects host lymphoid tissue profoundly and alters the migration patterns of lymphocytes in recipients of organ allografts. It has been shown that specifically sensitized lymphocytes traffic both to and from the transplant. A considerable amount of knowledge has been gathered on the preferential migration pathways of lymphocytes through lymphoid and mucosa-associated lymphoid organs. The factors regulating lymphocyte migration through non-lymphoid tissue in normal conditions are not well known and even less well understood in the context of graft rejection. In this article we described for the first time migration in a recipient non-lymphoid organ (heart) and it's potentially harmful effects in causing parenchymal damage during renal allograft rejection in the rat model. These lesions were detected during the process of developing a model of chronic renal allograft rejection. The pathogenesis of these cardiac lesions is not fully understood but possible mechanisms include upregulation of homing receptors/adhesion molecules, breakdown of peripheral tolerance and involvement of cross-reacting anti-endothelial antibodies.

Pathogenesis of glomerular sclerosis in subtotally nephrectomized analbuminemic rats.

The Nagase analbuminemic rat (NAR), a mutant of the Sprague-Dawley (SD) strain, exhibits persistent hypercholesterolemia, thrombocytosis, and enhanced platelet aggregation, abnormalities possibly involved in the genesis of glomerular sclerosis (GS). Previous observations suggest that these rats never develop aging GS. We studied the development of GS in NAR after 5/6 nephrectomy (Nx). Fifteen days after Nx, marked glomerular hypertension was observed in NAR, compared with only mild elevations in SD rats. Glomerular hypertrophy was more marked in SD rats than in NAR. Enalapril normalized glomerular volume and partially reversed glomerular hypertension in NAR without altering platelet function or cholesterol levels. Glomerular endothelial injury and intraluminal fibrin deposition were seen only in NAR. Two months after Nx, severe GS and massive glomerular lipid deposition were seen in NAR, whereas only mild glomerular injury occurred in SD rats. Enalapril attenuated GS and prevented lipid deposition in NAR. Glomerular hypertension may be a key factor in the genesis of GS in this model in association with endothelial injury, intracapillary coagulation, and lipid accumulation.

[Granulomatous reaction associated with metastatic epidermoid carcinoma. The importance of the use of multiple methods in diagnostic pathology]. / Reação granulomatosa associada a metástase de carcinoma epidermóide. Importância da utilização de múltiplos métodos em patologia diagnóstica.

A case of epidermoid carcinoma with metastasis to a cervical lymph node is reported. Due to an intense granulomatous reaction and the similarity of the neoplastic cells with the epithelioid cells there was diagnostic difficulty when based only on histology and fine needle aspiration cytology. The utilization of electron microscopy and immunoperoxidase defined the diagnosis. Discussion is made about the importance of the utilization of multiples methods in surgical pathology and the pathogenesis of the granulomatous reaction associated with malignant neoplasms.

Childhood Degos disease with prominent neurological symptoms: report of a clinicopathological case.

Degos disease is a rare disorder, characterized by a vasculopathy of unknown origin that leads to typical skin lesions and involves other organ systems. It is frequently a lethal condition; death occurs as a consequence of intestinal perforation. In about 20% of cases, the central nervous system is involved and the neurological symptoms can be prominent. The incidence of the disease in children is very uncommon. We report the case of teenage girl who had Degos disease with prominent neurological involvement.

Memory facilitation by naloxone is due to release of dopaminergic and beta-adrenergic systems from tonic inhibition.

The post-training IP administration of naloxone (0.8 mg/kg) facilitates memory consolidation of the habituation of a rearing response to a tone in rats. Amphetamine (1.0 - 2.5 mg/kg or nicotine (0.2 - 0.5 mg/kg), and amphetamine (2.5 mg/kg) plus nicotine (0.5 mg/kg) have no effect. The higher doses of amphetamine or nicotine, however, when given together with a dose of naloxone which is ineffective alone (0.2 mg/kg), markedly enhance consolidation. Haloperidol (0.5 mg/kg), propranolol (0.5 mg/kg), and phenoxybenzamine (2.0 mg/kg) have no effect on their own; whereas tolazoline (2.0 mg/kg) impairs consolidation. The effect of naloxone (0.8 mg/kg) is antagonized by haloperidol and by propranolol, but not by phenoxybenzamine or tolazoline. The results suggest that naloxone causes memory facilitation through the release of central dopaminergic and beta-adrenergic mechanisms from a tonic inhibitory influence of endogenous opiate peptide systems.