The use of the Ki-67 marker in the pathological diagnosis of the epithelioid variant of renal angiomyolipoma

Objective:  Epithelioid angiomyolipoma (EAML) is a rare malignant variant of renal angiomyolipoma (AML). There were 34 cases of EAML reported in 25 studies (including this present study) over the past decade. About 68% were females and 32% males. The mean age was 40.1 years, 53% developed metastatic disease after nephrectomy, and eight patients had TSC. All cases are reported positive when stained with HMB-45 which also labels all classical AML. This study evaluates the use of Ki-67 (proliferation marker) in the pathological diagnosis of EAML and distinction from classical AML. Method:  Immunohistochemical reactions for Ki-67 were generated on multiple representative blocks of tissue obtained from two cases of HMB-45 positive EAML and four cases of classic AML and the percentage of positively staining cells estimated. Results:  Both cases of EAML were strongly positive for Ki-67 while all four classic AML were completely negative. Conclusion:  The Ki67 is a useful marker in which distinguishes the malignant epithelioid variant of AML from classic AML.     

Hyperphosphatemia in children receiving peritoneal dialysis—an educational program

Hyperphosphatemia has been associated with the development of secondary hyperparathyroidism, renal osteodystrophy, cardiovascular calcification and increased risk of death. Using a one group, pretest-posttest study design, we sought to evaluate changes in serum phosphorus, calcium, parathyroid hormone and subject knowledge in response to a 3-month educational intervention. Mean serum phosphorus levels did not differ significantly between the three evaluation periods: pretreatment (5.69 mg/dl), treatment (5.84 mg/dl) and posttreatment (6.17 mg/dl). Mean serum calcium, calcium-phosphorus product and PTH values also did not differ significantly between the treatment periods. We observed no difference between the subject test scores between the two testing periods. Calcium-phosphorus product, serum phosphorus and PTH values on average, despite the education program, remained outside the K/DOQI target guidelines 44, 56 and 81% of the time, respectively. The results of this study suggest that an aggressive 3-month patient education program targeting dietary phosphorus knowledge, phosphate binder name and dosing, and knowledge of medical consequences associated with non-compliance had no effect on the serum phosphorus, calcium, PTH or phosphate binder need.     

Resolution of hypophosphatemia is associated with recovery of hepatic function in children with fulminant hepatic failure

Fulminant hepatic failure (FHF) is a rare but often fatal disease in children. Clinical and laboratory predictors of liver regeneration and recovery, however, have not been well established. We hypothesized that hypophosphatemia may indicate recovery of liver synthetic function in children with FHF. We retrospectively reviewed the medical records of children with FHF who were admitted to UCLA and recovered hepatic function either spontaneously or by liver transplantation (LTx). Serum phosphate (Ph) and prothrombin time or international normalized ratio (INR) were compared over the patient's clinical course. Records of 39 children who spontaneously recovered experienced profound hypophosphatemia that resolved as liver synthetic function improved. Similar patterns were seen in the 84 children who recovered after LTx. We found that hypophosphatemia precedes the recovery of liver synthetic function in children with FHF who recovered with or without transplantation, and that Ph levels return to normal as liver synthetic function improves. These data suggest that hypophosphatemia may be a useful laboratory indicator of recovering liver function in children with FHF.     

Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population

BACKGROUND: Malignant hyperthermia (MH) is a life-threatening and frequently fatal disorder triggered by commonly used anesthetics. MH susceptibility is a genetically determined predisposition to the development of MH. Mutations in the ryanodine receptor type 1 (RYR1) gene are the major cause of MH susceptibility. The authors sought to develop a reliable genetic screening strategy based on efficient and relatively inexpensive mutation-detection procedures. METHODS: A cohort (n = 30) of North American MH patients and MH-susceptible individuals was studied. RNA and DNA extracted from muscle tissue or blood lymphocytes were used for analysis. The entire RYR1 coding region was amplified in 57 overlapping fragments and subjected to denaturing high-performance liquid chromatography analysis followed by direct nucleotide sequencing to characterize RYR1 alterations. RESULTS: Nine previously reported and nine unknown RYR1 mutations were identified in 21 of 30 studied patients (70%). Some of the new mutations were located outside of known mutational "hot spots," suggesting that RYR1 contains previously unknown mutation-prone areas requiring analysis. The North American MH/MH-susceptible population is characterized by a high RYR1 allelic heterogeneity. CONCLUSIONS: Denaturing high-performance liquid chromatography analysis of RNA samples extracted from the biopsied skeletal muscle followed by DNA sequencing is a highly efficient methodology for RYR1 mutation detection. This approach allows increasing the rate of mutation detection to 70% and identifying mutations in the entire RYR1 coding region.     

Long and short-term outcomes in patients requiring continuous renal replacement therapy post cardiopulmonary bypass.

OBJECTIVE: The development of acute renal failure following cardiac surgery is a rare but devastating complication with high morbidity and mortality. This study aimed to assess the incidence of acute renal failure necessitating continuous renal replacement therapy (CRRT) in patients who required cardiopulmonary bypass, to determine the factors associated with mortality and to evaluate long-term outcome. METHODS: Patients who underwent cardiac surgery between October 1997 and 2003 and treated with CRRT were included (n=98). Six patients were then excluded (already in established renal failure pre-operatively) and one patient lost to follow-up. A retrospective analysis was carried out. RESULTS: Overall CRRT was used in 2.9% (92/3172). The mean (SD) age of patients was 68 (10) years. Their mean pre-operative creatinine level and duration of cardiopulmonary bypass were 154 (87)micromol/l and 160 (84)min, respectively. Mean duration from surgery to establishment of CRRT was 50 (42)h. Mean creatinine level prior to hospital discharge was 168 (93)micromol/l. Thirty-day mortality was 42%. Significant risk factors for death were complex procedures (odds ratio=9.9), gastro-intestinal complications (OR=7.2), cross-clamp time over 88min (OR=5.9), re-exploration (OR=4.0) and patients age over 75 years (OR=3.3). Actuarial 1 and 5-year survivals (95% CI) were 53 (43, 63) % and 52 (42, 62) %, respectively. Only 2 (2.2%) patients required long term renal support. CONCLUSIONS: Acute renal failure necessitating the use of CRRT is a rare but serious complication post cardiopulmonary bypass. In the long-term, surviving patients are not likely to require further renal support.     

Impact of malpractice caps on use and outcomes of radical cystectomy for bladder cancer: data from the surveillance, epidemiology, and end results program

PURPOSE: The impact of malpractice awards on insurance premiums and health care delivery generates much concern. To our knowledge no data exist regarding the impact of caps, or upper limits, on awards for noneconomic damages (also termed pain and suffering) on health care delivery patterns or outcomes. We investigated the effect of caps on the use of and outcomes following aggressive surgical treatment (radical cystectomy) in patients with bladder cancer. MATERIALS AND METHODS: We performed a retrospective cohort study of patients with bladder cancer who underwent radical cystectomy, identified from the Surveillance, Epidemiology, and End Results (SEER) Program database. Cystectomy rates and post-cystectomy disease specific survival were compared between SEER regions with and without a cap, while controlling for other variables. RESULTS: A significantly greater proportion of patients with stages III and IV bladder cancer underwent cystectomy in SEER regions with a cap. Cap status was a significant predictor of survival from bladder cancer. CONCLUSIONS: Radical cystectomy for bladder cancer is performed more often even for advanced bladder cancer in geographic regions with a cap with a positive impact on survival. The institution of caps may have beneficial effects on patterns of health care beyond that of merely decreasing insurance premium costs.     

Angiotension-converting enzyme gene I/D polymorphism in patients with angina and normal coronary arteriograms

A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).     

Refractory coeliac disease: remission with infliximab and immunomodulators

Coeliac disease is a T-cell-mediated enteropathy induced by gluten. A minority of patients who fail to respond to a gluten-free diet may require intervention with immunomodulating drugs. We report a case of refractory coeliac disease where remission was induced by the anti-tumour necrosis factor-alpha antibody infliximab and was maintained with prednisolone and azathioprine.