Should the guidelines for monitoring serum cholesterol levels in the elderly be re-evaluated?

Elevated circulating cholesterol can have profound effects on the health of an individual. Such excess cholesterol can promote coronary artery disease, production and accumulation of β-amyloid in the brain, and possibly Alzheimer’s disease (AD). In a clinical trial evaluating the benefit of a cholesterol-lowering drug in the treatment of AD, mean cholesterol levels at baseline among individuals participating in the trial were found to be relatively high. Based on this observation we suggest that cholesterol levels should be actively monitored in the elderly, as many individuals with AD are over 65 years of age and therefore excluded by currently accepted guidelines.     

Restoration of transforming growth factor Beta signaling by functional expression of smad4 induces anoikis

Smad proteins transduce signals carried by the transforming growth factor beta (TGF-beta) cytokine superfamily from receptor serine/threonine kinases at the cell surface to the nucleus, thereby affecting cell proliferation, differentiation, as well as pattern formation during early vertebrate development. Smad4/DPC4, located at chromosome 18q21, was identified as a candidate tumor suppressor gene that is inactivated in nearly half of all pancreatic carcinomas. For functional characterization of Smad4, a recombinant adenovirus encoding Smad4 (Ad-Smad4) was generated. When Smad4 was expressed in Smad4-null breast carcinoma cell line MDA-MB-468 using the recombinant adenovirus, TGF-beta signaling was restored as determined by TGF-beta-dependent activity of plasminogen activator inhibitor 1 promoter and p21 expression. Infection with Ad-Smad4 in the presence of TGF-beta1 also resulted in an altered cell morphology that coincided with enhanced beta1 integrin expression and reduced efficiency of colony formation in soft agar. In agreement with increased p21 expression, Smad4-expressing cells showed modest reduction in S phase. However, Smad4 expression did not lead to induction of apoptosis under normal culture conditions. Interestingly, when Smad4-expressing cells were detached and incubated in suspension, they underwent rapid apoptosis in a TGF-beta-dependent manner. Induction of apoptosis caused by loss of anchorage is known as anoikis. Anoikis is believed to prevent colonization elsewhere of detached cells. Additional characterization revealed an increase in the level of focal adhesion kinase 2 (or Pyk2) and activation of caspases 2, 3, 6, and 8 during anoikis because of Smad4 expression and restoration of TGF-beta signaling. Because resistance to anoikis in tumor cells is thought to contribute to metastasis, our data suggest a functional basis for the strong correlation between defects in Smad4 and development of malignancy.     

Dermatitis herpetiformis and neurological dysfunction

Dermatitis herpetiformis and coeliac disease are gluten sensitive diseases, which have common immunopathological and genetic mechanisms. Neuropsychiatric complications have been reported in up to 26% of patients with coeliac disease. This is probably an overestimate, because of the chance associations with some common neurological conditions such as epilepsy. The pathogenesis is speculative but it has been postulated that gluten is neurotoxic possibly via immune mechanisms. The frequency of neurological dysfunction in patients with dermatitis herpetiformis has not been characterised. Patients with dermatitis herpetiformis might be expected to be particularly susceptible to neuronal damage as some continue to consume gluten when their dermatological symptoms are controlled by dapsone. Thirty five patients were recruited with dermatitis herpetiformis from dermatology clinics at St Mary's Hospital, London and Queen's Medical Centre, Nottingham and investigated for evidence of neurological abnormality. All patients underwent a full neurological examination and were asked about their neurological and general medical history by means of a structured questionnaire. Serum samples were taken and screened for the presence of anti-neuronal antibodies (anti-Hu and Yo) as well as anti-gliadin (IgA and G) anti-endomysial (IgA), and anti-tissue transglutaminase (IgA) antibodies. Neurophysiological tests were carried out where appropriate. Only two patients were identified with unexplained neurological abnormalities (one essential tremor, and one chorea). Two other patients had a history of migraine. The patient with chorea also had borderline/equivocally positive anti-Hu antibodies by immunofluorescence assay. All other samples were negative for anti-neuronal antibodies. Fifteen patients were positive for anti-gliadin antibodies (IgA and/or IgG), four for anti-endomysial antibodies (monkey oesophagus or umbilical cord), and six for anti-tissue transglutaminase antibodies. The presence of these antibodies did not correlate with the presence of neurological abnormalities. No cases of "gluten ataxia" were identified. In conclusion, there was no convincing evidence for immune mediated neurological damage in this pilot study of dermatitis herpetiformis.     

Neurological complications of coeliac disease

A variety of neurological disorders have been reported in association with coeliac disease including epilepsy, ataxia, neuropathy, and myelopathy. The nature of this association is unclear and whether a specific neurological complication occurs in coeliac disease remains unproved. Malabsorption may lead to vitamin and trace element deficiencies. Therefore, patients who develop neurological dysfunction should be carefully screened for these. However, malabsorption does not satisfactorily explain the pathophysiology and clinical course of many of the associated neurological disorders. Other mechanisms proposed include altered autoimmunity, heredity, and gluten toxicity. This review attempts to summarise the literature and suggests directions for future research.     

Early observations of the effect of extracorporeal shockwave lithotripsy on blood pressure: a prospective randomized control clinical trial

OBJECTIVE: To determine, in a randomized controlled clinical trial, the effect of extracorporeal shock wave lithotripsy (ESWL) on blood pressure. PATIENTS AND METHODS: The trial included 228 patients with small (< 15 mm) asymptomatic calyceal stones who were randomised to undergo ESWL (113 patients) or to an untreated (observed) control group (115 patients). Blood pressure was recorded at randomization using a standardized protocol. Patients undergoing ESWL received a mean (SD) of 5281 (3462) shocks over a mean of 1.75 sessions on one of two lithotripters. Patients were then followed annually, assessing blood pressure and changes in medication. Data were analysed on an intention-to-treat basis. RESULTS: At randomization, 43% of patients in the control group and 53% in the ESWL group were hypertensive. Of the 228 randomized, 200 patients completed at least one annual follow-up, of whom 192 (93 in the control and 99 in the ESWL group) had their blood pressure recorded. The mean follow-up was 2.2 years; 35 (37%) patients in the control and 46 (46%) in the ESWL group were hypertensive (P = 0.19). Seven (7%) patients in the control group and 11 (11%) in the ESWL group were newly diagnosed to be hypertensive (P = 0.35). CONCLUSIONS: In this randomized controlled clinical trial there was no evidence that ESWL causes changes in blood pressure.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Laparoscopic cholecystectomy: Imaging of complications and normal postoperative CT appearance

Six patients underwent imaging studies to evaluate complications related to laparoscopic cholecystectomy. In addition, computed tomography (CT) of the abdomen and pelvis was performed on six patients 3–5 days after uncomplicated laparoscopic cholecystectomy in order to further clarify the normal postoperative CT appearance in these patients. Complications included ureteral laceration with periureteric hematoma and ureteroperitoneal fistula, hepatic artery pseudoaneurysm, hepatic laceration, retained common bile duct stone, bile leak, and biloma of the abdominal wall. At 3–5 days following uncomplicated laparoscopic cholecystectomy, typical CT findings include fluid density in the gallbladder fossa, a very small amount of pelvic fluid, and small densities within the subcutaneous fat at the expected sites of trocar insertion.