Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy

Background

Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade.

Case-diagnosis/treatment

A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab.

Conclusions

Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.     

Beneficial effects of Etanercept on experimental necrotizing enterocolitis

Purpose

Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats.

Methods

Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations.

Results

The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde were higher in the placebo group compared to the Etanercept group.

Conclusion

Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1β.     

New parameters in identification of right ventricular myocardial infarction and proximal right coronary artery lesion

OBJECTIVE: The diagnosis of right ventricular myocardial infarction (RVMI) accompanied by acute inferior myocardial infarction (MI) is still a problem that we encounter. This study was designed to find out the usefulness both of peak myocardial systolic velocity (Sm) and of the myocardial performance index (MPI) of the right ventricle measured by pulsed-wave tissue Doppler imaging (TDI) in assessing right ventricular function. METHODS: Sixty patients who experienced a first acute inferior MI (mean [+/- SD] age, 57 +/- 9 years) were prospectively assessed. An ST-segment elevation of >or= 0.1 mV in V(4)-V(6)R lead derivations was defined as an RVMI. From the echocardiographic apical four-chamber view, the Sm, the peak early diastolic velocity, peak late diastolic velocity, the ejection time, the isovolumetric relaxation time, and the contraction time of the right ventricle were recorded at the level of the tricuspid annulus by using TDI. Then, the MPI was calculated. The patients were classified into the following three groups, according to the localization of the infarct-related artery (IRA) detected using coronary angiography: group I, proximal right coronary artery; group II, distal right coronary artery; and group III, circumflex coronary artery. RESULTS: RVMIs were detected in sixteen patients, and the IRA in 27 patients was the proximal right coronary artery. The right ventricular Sm was observed to be significantly low in patients with RVMIs and those in group I compared to those without RVMIs and those in groups II and III (10.9 +/- 1.3 vs 14.3 +/- 3.2 cm/s, respectively [p < 0.001]; 11.5 +/- 2.5 vs 15.1 +/- 3 cm/s, respectively; and 14.9 +/- 2.6 cm/s, respectively [p < 0.001]). In the diagnosis of RVMI, the values for sensitivity, specificity, negative predictive value, and positive predictive value of Sm < 12 cm/s were 81%, 82%, 92%, and 62% respectively, and in the diagnosis of the proximal right coronary artery as the IRA, those values were 63%, 88%, 74%, and 81%, respectively. The MPI was high in the same patient groups (0.83 +/- 0.12 vs 0.57 +/- 0.11 in those patients without RVMI, respectively, [p < 0.001]; 0.74 +/- 0.13 vs 0.56 +/- 0.15 in group II and 0.54 +/- 0.07 in group III, respectively [p < 0.001]). The sensitivity, specificity, negative predictive value, and positive predictive value of an MPI of > 0.70 in the diagnosis of RVMI were calculated as 94%, 80%, 97%, and 63%, respectively, and in the diagnosis of the proximal right coronary artery as the IRA, those values were 78%, 91%, 83%, and 88% respectively. CONCLUSIONS: An Sm <12 cm/s and an MPI > 0.70 obtained by TDI may define RVMI concomitant with acute inferior MI, and the IRA.     

Depression scores and associated factors in pregnant and non-pregnant women: a community-based study in Turkey

The aims of this study were to evaluate and compare the depression scores of pregnant and non-pregnant women, and to identify the factors associated with depression scores in the two groups. This community-based study was conducted in a primary health care center catchment area in Ankara (population: 17,838) in January 2003. At the beginning of the study, the trimesters of all pregnant women (n = 66) were determined and as a control group (n = 138), two non-pregnant women matched for age and parity characteristics living in the same area were selected for each pregnant woman. Each participant completed a questionnaire and the Beck Depression Inventory (BDI). One-way ANOVA, univariate correlation, and multiple linear regression analyses were used in statistical evaluation. Depression scores of pregnant and non-pregnant women, and women at different trimesters of pregnancy were similar. Using a cut-off score > or = 18 on the BDI, 26.5% of non-pregnant women, 27.3% of pregnant women, 25.0% of pregnant women in their first and second trimester, and 30.0% of third trimester pregnant women were found to be depressive. According to multiple linear regression analysis, age, age at marriage, and the number of people living in the home were associated with depression in both groups. Depression scores were similar in pregnant women and non-pregnant controls. There were different associations between depression score and the study groups' characteristics.     

Protective effects of N-acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners

OBJECTIVE: Long-term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N-acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks. METHODOLOGY: Seventy-two male Wistar albino rats were used and divided into two groups: one group inhaled only thinners (TI), while the other inhaled TI plus NAC. Rats in the TI and TI + NAC groups were divided into four subgroups (each consisting of eight rats) according to the duration of exposure to TI: 2, 4, 6 and 8 weeks. A control group (n = 7) of rats inhaled neither TI nor NAC. Malondialdehyde (MDA) and GSH levels, and superoxide dismutase (SOD) activities were determined in the lung tissues. Histopathological findings were evaluated as acute and chronic changes in the alveoli and interstitium in the TI and TI + NAC groups and compared with those in the control group. RESULTS: While tissue MDA levels in the groups inhaling TI for 4, 6 and 8 weeks were significantly higher than those in the control groups (P < 0.01, P < 0.01, P < 0.0001, respectively), GSH levels were significantly lower (P < 0.05, P < 0.01, P < 0.01, respectively). Tissue SOD activities in the groups inhaling TI for 6 and 8 weeks were significantly lower than those in the control group (P < 0.05, P < 0.01, respectively). In the TI group, MDA levels were significantly increased (P < 0.01) with increasing duration of inhalation (from the second week through to the eighth week), while GSH levels and SOD activities were significantly decreased (P < 0.01, P < 0.01). Tissue MDA levels were significantly lower in the TI + NAC groups across all inhalation periods, when compared with the TI groups (P < 0.01, P < 0.0001, P < 0.0001, P < 0.0001, respectively). Tissue GSH levels in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.01, P < 0.01, P < 0.0001). Tissue SOD activities in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.0001, P < 0.05, P < 0.0001). Pathological examinations with light microscopy did not show any beneficial effect of NAC application in terms of deferring or alleviating the negative effects of TI. CONCLUSIONS: Thinners are agents that cause imbalance between oxidants and antioxidants produced by aerobic cellular systems. This imbalance between oxidant and antioxidant systems is decreased by the effect of NAC. However, ultrastructural studies may be needed to substantiate this evidence morphologically, as light microscopy was inconclusive.     

A case with diffuse uterine leiomyomatosis and review of the literature

Leiomyomas and diffuse uterine leiomyomatosis are smooth muscle tumors of the uterus. Diffuse uterine leiomyomatosis is a benign and extremely rare condition in which the uterus is symmetrically enlarged as a result of the almost complete replacement of the myometrium by innumerable poorly defined, confluent nodules. The etiology of these neoplasms is not completely understood. Initial symptoms of the diffuse uterine leiomyomatosis usually are abdominal pain and abnormal uterine bleeding. Similar to uterine leiomyomas, patients with leiomyomatosis present with menorrhagia, dysmenorrhea, abdominal pain, infertility, and pelvic pressure. Hormonal treatment usually fails to control the symptoms, anemia, or tumor growth after treatment is stopped. As a result, despite patients being in the third or fourth decades of life, hysterectomy has been the only permanent treatment option offered to patients for treatment of the symptoms related to uterine fibroids in diffuse leiomyomatosis. A case of a patient with a huge uterine mass (2,650 g in weight) who underwent hysterectomy due to diffuse uterine leiomyomatosis is presented together with a review of the literature.     

Carcinoma of the fourth part of the duodenum: Report of a case

Primary carcinoma of the duodenum is rare, accounting for only 0.35% of all gastrointestinal carcinomas, and carcinoma of the fourth part of the duodenum constitutes approximately 10% of duodenal carcinomas. Since the predominant symptoms of tumors in this part of duodenum are related to upper intestinal obstruction, the diagnosis is usually made late. We report the case of a 66-year-old man who presented with anemia, weight loss, and upper intestinal obstruction, and was found to have advanced primary carcinoma of the fourth part of the duodenum by upper gastrointestinal series and computed tomography (CT). A review of the literature indicates that survival, which is related to nodal status, the grade of the tumor, and surgical results, seems to be longer in patients with carcinoma in this part of the duodenum compared to those with carcinomas in other parts of the duodenum. Moreover, segmentary resection has been reported to achieve a favorable outcome.