Efficacy of immunosuppressive therapy in IgA nephropathy presenting with isolated hematuria

The role of immunosuppressive therapy in the management of IgA nephropathy (IgAN) remains controversial. No consensushas yet emerged on the specific treatment of IgAN and this ismostly related to the lack of complete understanding of themultifactorial pathogenesis of the disease. Choice of appropriatetherapeutic agents is further limited by the difficulty inidentifying patients who would most likely benefit from therapy.Immunosuppressive therapy has not been recommended in patientswith isolated hematuria and well preserved renal function becauseof their generally favourable prognosis and there are no clinicaltrials in this area. Considering that mild IgAN may be an earlystage of the disease and can be reversed by immunosuppressiveagents we have used prednisolone and azathioprine in patientswith isolated hematuria in a prospective, randomized, controlledstudy since 1988. In this prospective study we have evaluated theeffect of prednisolone with azathioprine on the clinical courseof IgAN and its impact on histologic parameters and preventionof progression in patients with isolated hematuria. We studied 43biopsy-proven IgAN patients (29 males and 14 females, agedbetween 13–63 years, mean age 28 ± 6) with isolated hematuria andwell-preserved renal function (C_cr 89.2 ± 10.2 ml/min). Thepatients were assigned to two groups: 21 patients receivedprednisolone (40 mg/day) and azathioprine (100 mg/day) orally forfour months (group A) and 22 patients received no specifictreatment for IgAN and served as a control group (group B). InGroup A prednisolone was reduced to 20 mg/day at the end of thesecond month, then slowly tapered over a two-month period andstopped. The median duration of follow-up was 60 months (range12–120 months). At the end of the therapy hematuria disappearedin 17 patients. In three patients who did not respond to therapy,microscopic hematuria persisted. Of the 22 patients of group B,three had episodes of gross hematuria and proteinuria >500mg/day. No significant changes in biochemical profile wereobserved in either group. Thirteen patients (eight from thetreated, five from the untreated group) underwent a repeat biopsyafter 12 ± 6 months (range 10–25). An improvement ofhistopathological features was noted in Group A, whiledeterioration was noted in Group B. We conclude that earlytreatment with prednisolone and azathioprine appears to bebeneficial in preventing the progression of immunologic renalinjury and in improving histopathological features in IgANpatients with isolated hematuria.     

Angiostatic effects of suramin analogs in vitro

Suramin analogs are polyanionic naphthylureas structurally related to suramin, an antitumor agent with a narrow therapeutic window. The angiostatic activities of suramin and 16 suramin analogs were investigated using an easily quantifiable in vitro angiogenesis system. In addition, the antiproliferative activities of the analogs were studied in four different human tumor cell lines and in porcine aortic endothelial cells. The suramin analogs encompassed two main structural variations, i.e. their molecular size, and the number and substitution pattern of the sulfonate groups. Some suramin analogs with a reduced number of sulfonate groups (NF062, NF289 and NF326) showed significant dose-dependent angiostatic and also antiproliferative activities. The disulfonate NF062 was superior to suramin in inhibiting HT29 and T47D tumor cells while demonstrating a similar angiostatic potential as suramin. Therefore, the sulfonate groups in the para position of the amino groups of the naphthyl residues of suramin seem to be of special importance. The very small disulfonates (NF108, NF109, NF499, NF500 and NF241) and the asymmetric compound NF520, one half of the suramin molecule, are inactive. Therefore, a minimal molecule size seems to be essential for the biological activity. Suramin is a rather rigid molecule. The highly flexible analogs (NF527, NF528 and NF529) are inactive. This indicates that the molecular rigidity is important for the biological activity.     

Factors affecting haemorrhagic transformation in middle cerebral artery infarctions.

OBJECTIVE: Haemorrhagic transformation (HT) affects treatment and prognosis in patients with acute ischaemic stroke. The factors affecting haemorrhagic transformation in infarcts due to occlusion of middle cerebral artery (MCA) stem or branch were investigated. MATERIALS AND METHODS: Of 412 patients who were followed in our clinic between January 2001 and December 2001 with acute ischaemic stroke, 86 patients with occlusion in MCA stem or branch were enrolled in this study. These patients were divided into 2 groups, those with HT (n = 35) and without HT (n = 51). Age, sex, systemic arterial hypertension, diabetes mellitus, blood glucose level in the acute period, renal and liver function tests, systolic and diastolic arterial blood pressure in the acute period, previous cerebrovascular disease, leukoaraiosis, modified Rankin Disability Score (mRDS) and stroke subtype were evaluated. RESULTS: High blood glucose level in the acute period and presence of leukoaraiosis on cranial computerized (CCT) tomography were detected as risk factors in development of HT. HT was seen more frequently in MCA stem infarction than branch infarction. mRDS were worse in the group with HT. In multivariate analysis, there were independent relationships between mean blood glucose level on admission, mRDS, presence of diabetes mellitus, and MCA stem infarction and development of haemorrhagic transformation in patients with MCA territorial infarction.     

Intralesional injection of 2% zinc sulfate solution in the treatment of acute old world cutaneous leishmaniasis: a randomized, double-blind, controlled clinical trial

Several in vitro and in vivo studies have shown inhibitory effects of zinc sulfate (ZnSO4) on Leishmania parasites. The objective of this study was to compare the efficacy of intralesional injections of 2% ZnSO4 solution with meglumine antimonate (Glucantime) in the treatment of acute Old World cutaneous leishmaniasis (CL). Seventy-two patients with CL lesions less than 8 weeks were recruited in a randomized, double-blind, clinical trial in an area endemic for Leishmania major after giving written informed consent. They were treated with 6 weekly intralesional injections of either drug. Among 36 patients with 53 lesions treated with ZnSO4 and 36 patients with 53 lesions treated with Glucantime, 13 patients with 19 lesions and 22 patients with 31 lesions completed the trial, respectively. Inadequacy of treatment was the main reason for drop-out in 12 (33.3%) and 2 (5.5%) patients in ZnSO4 and Glucantime groups, respectively (P < .05). Complete re-epithelialization was observed in 2 (10.5%) and 19 (61.3%) lesions 1 week after the end of treatment in the ZnSO4 and Glucantime groups, respectively (P < .05). In conclusion a 6-week course of weekly intralesional injections of 2% ZnSO4 solution was less effective than Glucantime in the treatment of acute Old World CL.     

Carotid endarterectomy in octogenarians: Does increased age indicate “high risk?”

OBJECTIVE: Carotid endarterectomy (CEA) is proven to be the most effective treatment for symptomatic carotid artery stenosis of 50% or greater and asymptomatic carotid stenosis of 60% or greater. Although the prevalence of carotid artery disease increases with age, most prospective and randomized trials have excluded patients older than 80 years, implying that they are either at higher procedural risk or have decreased life expectancy. Since advanced age (>/=80 years) has been viewed as a "high-risk" indicator for CEA, age >/=80 years has been used as an indication for alternative treatment. The study was conducted to determine if age >/=80 years is related to increased morbidity, mortality, and length of stay in patients undergoing CEA. METHODS: In the 12-year period from 1993 to 2004, 2217 CEAs were performed in 1961 patients. Three hundred sixty procedures were performed in 334 patients >/=80 years. Demographics, presentation, risk factors, operative outcome, and survival were analyzed. Contemporary literature was reviewed and the results summarized. RESULTS: In patients aged >/=80 years, compared with their younger cohort, there was no difference in stroke (1.1% vs 0.8%, P = .333) but there was a higher operative mortality (1.9% vs 0.8%, P = .053). The combined stroke/death rate was higher in octogenarians (3.1% vs 1.5%, P = .041). This difference was due to the greater stroke/death rate in symptomatic octogenarians vs asymptomatic octogenarians (6.0% vs 0.9%, P = .007). The average postoperative length of stay was 3.2 +/- 4.8 days for octogenarians compared with 2.4 +/- 3.5 days for their younger counterparts ( P < .001). Thirty-seven percent of the octogenarians were discharged on the first postoperative day vs 51% ( P < .001), whereas 13% remained hospitalized beyond 5 days vs 8% ( P = .003). Although Kaplan-Meier survival curves show a higher mortality in octogenarians, survival after CEA approaches that of the overall population. A summary of the contemporary literature of CEA in 2204 patients >/=80 shows an operative stroke rate of 2.23% and death rate of 1.28%, with a combined stroke/death rate of 3.51%. CONCLUSION: CEA is a safe and effective procedure in the octogenarian. The combined stroke/death rate is increased in patients aged >/=80, indicating increased risk, predominantly in symptomatic patients. Although CEA risk in octogenarians is higher compared with a younger cohort, outcomes remain within acceptable national guidelines and within outcome measures known to confer benefit compared with best medical care. Therefore, the term "high risk" should not be arbitrarily applied to patients reaching the 80-year threshold. This is confirmed by the contemporary literature.     

Acute Thrombosis of Inferior Vena Cava in a Pregnant Woman Presenting with Sciatica:A Case Report

A 20-year-old pregnant woman was admitted to our department with symptoms of deep venous thrombosis in the left lower extremity and excessive lumbar pain. Low-molecular-weight heparin was administered. She recovered with this treatement, however, severe lumbar pain continued. A lumbar magnetic resonance imageg showed dilated epidural veins compressing the roots and acute thrombosis of the inferior vena cava extending to renal veins. During the same period she had acute deep venous thrombosis in her right leg. An urgent venous thrombectomy was performed. Sciatica and deep venous thrombosis resolved after the operation. Low-molecular-weight heparin was administered until the end of her pregnancy.     

Postnatal management of infants with antenatally detected hydronephrosis

With the increasing use of antenatal sonography, fetal hydronephrosis has been reported more frequently. Because of the lack of consensus regarding treatment of these infants, the postnatal approach toward fetal renal pelvis enlargement remains controversial. The aim of this prospective study is to demonstrate the postnatal investigation, treatment, and outcome of infants with prenatally diagnosed hydronephrosis. Infants whose antenatal ultrasound scan showed a fetal renal pelvis of 5 mm or greater were investigated postnatally using ultrasound (US) and voiding cystourethrography. When indicated, isotope studies and intravenous urograms were also performed. We followed prospectively neonates with antenatally diagnosed hydronephrosis and recommended management guidelines on the basis of our findings. In 156 neonates (193 kidney units) that were found to have hydronephrosis, the average gestational age at which the diagnosis was made was 32.94±5.10 weeks. The mean duration of postnatal follow-up was 26.3±13.56 months (range 3–60 months). The mean APPD of the fetal renal pelvis was 10.35±3.24 mm (5–9 mm in 84 kidneys, 10–14 mm in 96 kidneys and 15 mm in 13 kidneys). Of the 193 kidney units, 145 units were found to be pathological. The most common detected underlying abnormalities were ureteropelvic junction obstruction (in 91 kidneys; 62.7%) and vesicoureteral reflux (in 24 kidneys; 16.6%). Postnatally, 23 (45%) of 51 patients whose first US was normal were diagnosed postnatally as having urinary tract abnormality. There was a negative correlation between APPD and the rate of spontaneous resolution and positive correlation between APPD and the rate of surgery (P<0.01). In conclusion, because it is not possible to determine an upper limit of normal for the antenatal renal pelvis, any baby with AH should not be considered clinically insignificant. Infants with antenatal renal pelvis measurements 5 mm should be investigated postnatally. A normal postnatal ultrasound scan does not preclude the presence of urinary tract abnormality.     

Leishmanization: use of an old method for evaluation of candidate vaccines against leishmaniasis

To establish the safety and reproducibility of live challenge with Leishmania major, a single frozen stabilate was used in two open, single-arm leishmanization (LZ) trials. A total of 42 inoculations in 28 male adult volunteers were followed until complete healing. Lesions induced by LZ are as diverse as natural infection, but much milder. Total protection was seen in 100% (11/11) of recovered volunteers. LZ used as live challenge to test vaccine candidates reduces the required sample size, is cost effective for surrogate markers studies and will induce protection in the participants who are not protected by candidate vaccines.     

Detection of Mature Collagen in Human Dental Enamel

Mature dental enamel is the most mineralized of all mammalian tissues and considered to be free of collagen. Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are two nonreducible cross-links of mature collagen. Hydroxyproline (Hyp) is an amino acid that is believed to be indicative of the presence of collagen. We set out to assess the concentrations of Hyp, HP, and LP in dental enamel and dentin (control) to clarify whether there was minor collagen content in dental enamel. We studied 17.53 g of enamel and 22.12 g of dentin gained from 120 extracted human teeth. Enamel and dentin (control) were separated with a diamond dental drill under microscopic control by wasting a margin of enamel (Ca. 2 mm) at the dentin-enamel border. Collagen alpha-chains were analyzed by Sodium dodecylsulfate-polyacrylamide gel (SDS-PAGE) after decalcification and collagen extraction. Concentrations of HP and LP where measured by using high-performance liquid chromatography (HPLC). Hyp was analyzed by a spectrophotometric method. The pooled probe of enamel contained 0.23 mug/g of Hyp. This concentration was 49 times lower than that in dentin. Concentrations of HP and LP in enamel were 0.07 nmol/g and 0.02 nmol/g, respectively being 605.57 (HP) and 251.50 (LP) times lower in enamel as compared to dentin. Collagen type I was found in enamel; collagen types I and V were found in dentin samples. In reports of many studies and textbooks, collagen is considered to be completely absorbed in the course of the mineralization and maturation of dental enamel. We show that this is not the case. However, the concentration of collagen in enamel was considerably lower as compared to that in dentin.