Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.     

Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report

OBJECTIVE: To describe a case of left vagal nerve stimulation (VNS) resulting in immediate cessation of status epilepticus (SE) with good neurological outcome. CASE DESCRIPTION: A 30-year-old man with medically intractable seizures including episodes of SE was successfully treated using left VNS. After requiring discontinuation of phenytoin, valproic acid, carbamazepine, and topiramate because of severe allergic reactions resembling Stevens-Johnson syndrome, the patient required pentobarbital coma along with phenobarbital, tiagabine, and levetiracetam for seizure frequency reduction. He underwent left vagal nerve stimulator placement after nearly 9 days of barbiturate-induced coma, with stimulation initiated in the operating room. On the following day, electroencephalography revealed resolution of previously observed periodic lateral epileptiform discharges and the patient was free of seizures. Prestimulation seizure frequency was recorded at 59 times a day, with some seizures enduring 45 minutes despite barbiturate coma. Poststimulation, the patient has been free of seizures for 19 days and is presently taking only levetiracetam and phenobarbital, from which he continues to be successfully weaned without seizures. He is awake, alert, and can recall events leading up to his seizures, with good long-term memory and residual left upper extremity and lower extremity weakness. CONCLUSION: This case illustrates the role of left vagal stimulation in the treatment of SE and otherwise medically intractable seizures caused by allergic reactions. To our knowledge, this is the first case in the world literature for adults reporting cessation of SE after VNS. Another case with a similar improvement has been reported in the pediatric population.     

Abnormal left ventricular relaxation and symptoms of heart failure

Objectives

The purpose of our study was to assess the echocardiographic and angiographic parameters in patients with symptomatic heart failure (HF) and mild diastolic dysfunction (grade I).

Background

It remains uncertain why some patients with mild diastolic dysfunction exhibit HF symptoms and others are asymptomatic.

Methods

The study enrolled 80 hospitalized patients with impaired left ventricular (LV) relaxation. Patients were divided into two groups; one group had chronic functional class II to III dyspnea and the other group had no symptoms of HF. After admission, echocardiography and coronary angiography were performed for all patients and LV systolic and diastolic parameters were compared between the two groups.

Results

More patients in the asymptomatic group were hypertensive (p-value: 0.012). However, coronary artery disease was more prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF) was significantly lower in symptomatic patients [median 54.33 %, 95 % confidence interval (53.76–54.87 %) in asymptomatic patients and median 49.43, 95 % confidence interval (47.23–50.91 %) in symptomatic patients, p-value <0.001]. Furthermore, the systolic LV internal dimension was significantly larger in this group (p-value: 0.037). The results of logistic regression identified that only the absolute level of the LVEF was the negative determinant of the occurrence of HF in patients with impaired LV relaxation.

Conclusion

Our study showed that LV systolic performance has an important role in occurrence of HF symptoms in patients with grade I diastolic dysfunction.

     

Pylephlebitis: a Review of 95 Cases

Journal of Gastrointestinal Surgery - Pylephlebitis, or suppurative thrombophlebitis of the portal mesenteric venous system occurring in the setting of abdominal inflammatory processes, is a rare...     

Differentiation of renal cell carcinoma subtypes by multislice computerized tomography

Purpose

We differentiated renal cell carcinoma subtypes using multislice computerized tomography (CT).

Materials and Methods

We reviewed the CT images of 87 patients with renal cell carcinoma. Three subtypes of renal cell carcinoma were noted, including clear cell in 37 cases, papillary in 26 and chromophobe in 24. Biphasic CT (unenhanced, corticomedullary and excretory phases) was done in all patients. We compared patient age and sex, tumor size, enhancement degree and pattern (homogeneous, heterogeneous and predominantly peripheral), the presence or absence of calcification or cystic degeneration (necrotic or hemorrhagic areas within the tumor) and tumor spreading patterns, including perinephric change, venous invasion and lymphadenopathy, in the 3 subtypes.

Results

The degree of enhancement was significantly different among the 3 subtypes in the corticomedullary and excretory phases (p <0.001). Cystic degeneration was more evident in the clear cell subtype than in the other subtypes regardless of tumor size (p <0.001). A hypervascular pattern (higher tumor enhancement after contrast material injection due to higher vascularity) was noted in 48.6% of clear cell subtype in comparison to 15.4% of papillary and 4.2% of chromophobe subtypes (p <0.001). The chromophobe subtype showed homogeneous enhancement in 75% of cases in comparison to 45% and 65% of clear cell and papillary subtypes (p >0.05). Calcification was evident in 21.6%, 23.1% and 25% of clear cell, papillary and chromophobe subtypes, respectively (p >0.05).

Conclusions

To differentiate the subtypes of renal cell carcinoma the degree of enhancement is the most valuable parameter. The presence or absence of cystic degeneration, vascularity and enhancement patterns can serve supplemental role in differentiating renal cell carcinoma subtypes.     

The Concept of Tubularized Incised Plate Hypospadias Repair for Different Types of Hypospadias

Purpose: Using the concept of tubularized incised plate (TIP) urethroplasty technique for proximal, distal, primary, secondary and complicated cases of hypospadias. Material and methods: From June 2002 to December 2003 TIP urethroplasty was performed in 15 patients between the age of 1–18-year-old with penosecrotal, mid shaft and subcoronal hypospadias. In 13 of them TIP urethroplasty used as the primary repair while in two of them as secondary repair. Results: No clinically important complications were observed in those boys who underwent primary reconstruction. One of them had meatal stenosis at the early postoperative period which was corrected by dilatation of the external meatus by feeding catheter at intervals up to 2 months postoperatively. Three boys had very narrow fistula which just allow leak of few drops of urine through urination. One boy with penoscrotal hypospadias who underwent two-stage repair had fistula. Conclusion: The concept of TIP urethroplasty is the procedure of choice for the treatment of proximal hypospadias and, it seems to be suitable for distal, secondary and even complicated hypospadias reconstruction. The advantages of this procedure include its simplicity, low complication rates and very good appearance of the glance with normal meatus.     

Gastrocystoplasty in patients with an areflexic low compliant bladder

AIM: This study was performed with the aim of evaluating gastrocystoplasty as a method of management of patients with an areflexic low compliant bladder. PATIENTS AND METHODS: We performed gastrocystoplasty in 30 patients (19 males and 11 females) with an areflexic low compliant bladder. The mean age of the patients was 23.4+/-11 years (range 4-32). The etiology of lower urinary tract dysfunction was myelodysplasia in 26 patients and spinal cord injury in 4. Twenty-three patients had normal renal function and 7 had impaired renal function (creatinine 2.0-5.0mg%). Additionally, 4 patients had an artificial urinary sphincter implanted and seven had an antireflux procedure performed. RESULTS: Renal function remained stable or improved in 29 patients. Postoperatively, there was a 225% increase from mean preoperative capacity and a 52% decrease from the preoperative end filling pressure. Nineteen patients voided spontaneously and 11 used clean intermittent catheterization to empty the bladder. Twenty-five patients were continent with augmentation alone, four with augmentation and artificial sphincter implantation while one remained incontinent, as sphincter implantation could not be performed due to the young age of the patient. Five patients (17%) had transient hematuria and dysuria after augmentation. There were no mortalities and complications included prolonged urinary leakage in one patient and mild gastric bleeding in another two. CONCLUSION: The use of the stomach for augmenting the areflexic low compliant bladder is clearly advantageous over other tissues as it increases bladder capacity and compliance with consequent achievement of continence and preservation of upper tracts. An artificial urinary sphincter can be safely implanted in the same session. Because of its inherent fibromuscular properties, the gastric patch contributes to the force of urination resulting in better bladder emptying. Patients with impaired renal function are protected from hyperchloremic metabolic acidosis.     

Periprocedural hemodynamic instability with carotid angioplasty and stenting

BACKGROUND: Carotid angioplasty and stenting is used for treatment of carotid stenosis. Stent deployment may induce HDI and thereby cause systemic or neurologic deficits. This study defines characteristics and predictors of HDI with CAS. METHODS: A total of 132 patients who had undergone CAS were evaluated for periprocedural and postprocedural HDI (hypertension, systolic blood pressure >160 mm Hg; hypotension, systolic blood pressure <90 mm Hg; or bradycardia, heart rate <60 beats per minute). RESULTS: Frequencies of HDI were 6.8% for hypertension, 32.6% for hypotension, and 15.9% for bradycardia. In addition, CAS of the right side (P < .01), carotid bulb lesions (P < .05), eccentric posterior carotid plaque (P < .0001), and general anesthesia (P < .05) were associated significantly with postprocedural HDI. Male sex (OR, 3.4; 95% CI, 1.8-67.2; P < .001), age of 80 years or older (OR, 0.4; 95%CI, 0.1-1.4; P = .011), and plaque ulceration (OR, 0.5; 95% CI, 0.1-9.5; P = .008) independently predicted postprocedural hypertension. Male sex (OR, 2.5; 95% CI, 1.3-24.9; P < .001), preprocedural major stroke (OR, 0.1; 95% CI, 0.01-0.8; P = .002), carotid bulb lesions (OR, 1.6; 95% CI, 1.1-25.9; P = .024), and contralateral carotid occlusion (OR, 0.6; 95% CI, 0.2-4.9; P = .040) all predicted postprocedural hypotension. Bradycardia was associated with diabetes mellitus (OR, 0.7; 95% CI, 0.3-2.4; P = .033), preprocedural TIA (OR, 1.7; 95% CI, 1.4-17.9; P = .020), and minor stroke (OR, 1.5; 95% CI, 1-10.9; P = .037). In 5 patients, HDI predisposed neurologic or systemic deterioration. CONCLUSIONS: Hemodynamic instability is common with CAS; hypotension and bradycardia are more frequent than hypertension. Some clinical, angiographic, and procedural variables can predict these HD changes.     

Evaluation of a synchronous twin-pulse technique for shock wave lithotripsy: a prospective randomized study of effectiveness and safety in comparison to standard single-pulse technique

OBJECTIVE

To asses the efficacy and safety of bidirectional synchronous twin‐pulse extracorporeal shock wave lithotripsy (ESWL) compared with standard ESWL.

PATIENTS AND METHODS

Between March 2003 and December 2006, 240 patients with a radio‐opaque single renal stone of ≤25 mm were randomized to treatment either by the Twinheads (TH) lithotripter (FMD, Lorton, Virginia, USA) or the Dornier Lithotripter S (DLS, Dornier MedTech Europe GmbH, Germering, Germany). Before and after ESWL, urinary N‐acetyl‐B‐glucosaminidase (NAG) levels were assessed and patients were evaluated with dynamic MRI. The efficacy and complications were compared, with success defined as no residual fragments.

RESULTS

For stones of >10 mm the rate for the failure of disintegration was 13.3% for the DLS vs 1.4% for the TH (P = 0.009). For stones of ≤10 mm the stone‐free rate was 74.4% for the TH vs 67.7% for the DLS (P = 0.6), while for stones of >10 mm it was 78.1% and 66.7%, respectively (P = 0.14). The median (range) number of sessions in both groups was 2 (1–5). After ESWL urinary NAG levels were increased significantly in both groups; in the TH group it declined below the level before ESWL after 2 days, while in the DLS group it remained high after 7 days. In the DLS group four patients developed subcapsular or parenchymal haematoma after ESWL, vs none in the TH group. There was loss of corticomedullary differentiation after ESWL in three patients in the DLS group and only one in the TH group. In the DLS group there was a statistically significantly decrease in bilateral renal perfusion after ESWL, but no changes in the TH group.

CONCLUSIONS

Synchronous twin‐pulse ESWL has clinical advantages over standard ESWL in terms of safety and efficacy.