Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

Impact of Sarcopenia on Outcomes Following Intra-arterial Therapy of Hepatic Malignancies

Background

Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT).

Methods

Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors.

Results

Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm²/m²) was greater than women (413 mm²/m²). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR?=?1.84) and Child's score (HR?=?2.15) (all P?<?0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR?=?1.84; P?=?0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients.

Conclusions

Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.     

Surgical management of corrosive-induced gastric injury in children: 10 years' experience

Aim

The purpose of this study was to report surgical management and outcome of corrosive-induced gastric injuries in children at our institute over the last decade.

Gene expression profile in obesity and type 2 diabetes mellitus

Obesity is an important component of metabolic syndrome X and predisposes to the development of type 2 diabetes mellitus. The incidence of obesity, type 2 diabetes mellitus and metabolic syndrome X is increasing, and the cause(s) for this increasing incidence is not clear. Although genetics could play an important role in the higher prevalence of these diseases, it is not clear how genetic factors interact with environmental and dietary factors to increase their incidence. We performed gene expression profile in subjects with obesity and type 2 diabetes mellitus with and without family history of these diseases. It was noted that genes involved in carbohydrate, lipid and amino acid metabolism pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways, ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligand-receptor interaction, nervous system pathways, neurodegenerative disorders pathways are upregulated in obesity compared to healthy subjects. In contrast genes involved in cell adhesion molecules, cytokine-cytokine receptor interaction, insulin signaling and immune system pathways are downregulated in obese. Genes involved in signal transduction, regulation of actin cytoskeleton, antigen processing and presentation, complement and coagulation cascades, axon guidance and neurodegenerative disorders pathways are upregulated in subjects with type 2 diabetes with family history of diabetes compared to those who are diabetic but with no family history. Genes involved in oxidative phosphorylation, immune, nervous system, and metabolic disorders pathways are upregulated in those with diabetes with family history of diabetes compared to those with diabetes but with no family history. In contrast, genes involved in lipid and amino acid pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling and PPAR signaling pathways are downregulated in subjects with diabetes with family history of diabetes. It was noted that genes involved in inflammatory pathway are differentially expressed both in obesity and type 2 diabetes. These results suggest that genes concerned with carbohydrate, lipid and amino acid metabolic pathways, neuronal function and inflammation play a significant role in the pathobiology of obesity and type 2 diabetes.     

Intraocular concentrations of clindamycin obtained by sequential parabulbar injections

PURPOSE: To measure the intraocular concentration of Clindamycin that can be maintained by sequential injection through a retained parabulbar catheter. MATERIALS AND METHODS: The peak intraocular concentration and half-life of Clindamycin after parabulbar injection was determined in a rabbit model. In a second experiment a parabulbar catheter was inserted and the maximum concentration that could be maintained by sequential injection through the catheter at intervals of 6 hours was determined. In a third experiment both eyes of the rabbit were catheterized and one infused with Clindamycin. The eyes were enucleated and studied by light and electron microscopy for changes induced by Clindamycin and the catheter. RESULTS: The concentration of Clindamycin after a single parabulbar injection of 10 mg/kg peaked in the retina and choroid at 2 hours and was 336 micrograms/g. The serum level at 2 hours was 2.2 micrograms/ml. The half-life in choroid and retina was 1 hour. Sequential administration at 6 hour intervals maintained a minimum concentration of 87 micrograms/ml. The vitreous concentration was maintained at 2 micrograms/ml. CONCLUSION: The level of Clindamycin in the retina and choroid obtained by sequential injections of 10 mg/kg exceeds the minimum lethal dose for organisms susceptible to the drug. The low serum concentration suggests that sequential doses of Clindamycin by the parabulbar route might be an effective therapy for toxoplasmic retinochoroiditis and would diminish the risk of colitis or other deleterious systemic side effects.     

Muscle weakness and cocontraction in upper limb hemiparesis: relationship to motor impairment and physical disability

The purpose of this article is to describe the relationship between poststroke upper limb muscle weakness and cocontraction, and clinical measures of upper limb motor impairment and physical disability. Electrormyographic (EMG) activity of the paretic and nonparetic wrist flexors and extensors of 26 chronic stroke survivors were recorded during isometric wrist flexion and extension. The root mean square (RMS) of the EMG signal was used as a measure of strength of contraction. A ratio of RMS of antagonist and agonist muscles was used as a measure of cocontraction. Upper limb motor impairment and physical disability were assessed with the Fugl-Meyer motor assessment (FMA) and the arm motor ability test (AMAT), respectively. The strength of muscle contraction was significantly stronger in the nonparetic limb (P < 0.001). The degree of cocontraction was significantly greater in the paretic limb (P < 0.001). The strength of muscle contraction in the paretic limb correlated significantly with FMA (r = 0.62 to 0.87, P < or = 0.001) and AMAT (r = 0.66 to 0.80, P < or = 0.001) scores. Similarly, the degree of cocontraction correlated significantly with FMA (r = -0. 70 to -0.64, P < or = 0.001) and AMAT (r = -0. 72 to -0.62, P < or = 0.001) scores. Muscle weakness and degree of cocontraction correlate significantly with motor impairment and physical disability in upper limb hemiplegia. This relationship may provide insights toward development of specific interventions. However, additional studies are needed to demonstrate a cause and effect relationship.     

Trauma-associated growth of suspected dormant micrometastasis

Background  

Cancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release.     

Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution

PURPOSE: Unresectable cholangiocarcinoma carries a dismal prognosis, with median survival times ranging from 6 to 12 months from the time of diagnosis. Palliative therapies have been disappointing and have not been shown to significantly prolong survival. Conversely, transcatheter arterial chemoembolization (TACE) has been effective in prolonging the lives of patients with hepatocellular carcinoma but has not been used against cholangiocarcinoma. Therefore, the purpose of the present study was to assess the safety and efficacy (ie, survival) of TACE in patients with unresectable intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Seventeen patients with unresectable cholangiocarcinoma were treated with one or more cycles of TACE between 1995 and 2004 at our institution. Follow-up imaging was performed on all patients 4-6 weeks after each TACE procedure to determine tumor response and need for further treatment. Survival was calculated with use of the Kaplan-Meier survival curve. RESULTS: The median survival for 17 patients treated with TACE was 23 months. Two patients with previously unresectable disease underwent successful resection after TACE. The procedure was well tolerated by 82% of the patients, who experienced no side effects or mild side effects that quickly resolved with conservative therapy alone. Two patients had minor complications (12%), which were managed successfully, and one had a major complication that resulted in a fatal outcome. This patient had a rapidly declining course from the time of diagnosis and died shortly after TACE. CONCLUSIONS: The results suggest that TACE was effective at prolonging survival of patients with unresectable cholangiocarcinoma. Therefore, for these patients, TACE may be an appropriate palliative therapy.