An unusual case of extra bone formation

The patient, a 40-yr-old female with fibrodysplasia ossificansprogressiva, first presented in her teens with pain and stiffnessof     

Transmissible spongiform encephalopathies

Nosologically, transmissible spongiform encephalopathies (TSE or prion diseases) should be grouped with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, which are all caused by toxic gain of function of an aberrant form of a constitutively expressed protein. Failure to clear these proteins from the brain induces neuronal dysfunction. Transmissibility is the property that separates TSE from other neurodegenerative diseases, and this property seems to reside within the structure of the abnormal protein. The human phenotypic range of these encephalopathies includes Creutzfeldt-Jakob disease and its variant form, kuru, Gerstmann-Str?ussler-Scheinker syndrome, and fatal familial insomnia. Notwithstanding the generally low incidence of TSE and their limited infectiousness, major epidemics such as bovine spongiform encephalopathy and kuru arise in situations where intraspecies recycling of the abnormal protein is sustained. Moreover, evidence of chronic subclinical infection in animals offers insights into pathogenesis and prompts re-evaluation of the notion of species barriers and present infection control measures. Since case-to-case transmission is the only known mechanism underlying epidemics of TSE, potential reservoirs of infectivity in the tails of epidemics need continued vigilance.     

Chronic Pancreatitis and the Hepatobiliary System

Alcohol-induced chronic pancreatitis involving the head of pancreas may have profound effects on the hepatobiliary system. The natural history, complications, and management of the syndrome are presented, using selected cases to emphasize important features. Chronic pancreatitis can cause mechanical obstruction to both the distal common bile duct and the proximal pancreatic duct. In the common bile duct this will result in proximal dilatation above the stenosis with bile stasis. Possible sequelae are ascending cholangitis, cholecystitis, biliary calculi formation, and secondary biliary cirrhosis. The mechanical effects of stricture of the proximal pancreatic duct may exacerbate pancreatic dysfunction. The clinicopathological spectrum of chronic pancreatitis with biliary obstruction encompasses three clinical types–"transient,""recurrent." and "persistent." The widespread effects of the syndrome are evident from the involvement of pancreas, proximal pancreatic duct, papilla of Vater, liver, peripheral biliary tree, common bile duct, gallbladder, and reticuloendothelial system. Essential to management is surgery which should be considered when there is objective evidence of obstruction to the common bile duct. Choledochoduodenostomy is the preferred type of operation. If dilatation is mild and jaundice transient, conservative therapy with careful observation is advocated.     

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids

The Oxford Cholesterol Study is a randomized placebo-controlledtrial designed primarily to assess the effects of simvastatinon blood cholesterol levels and side-effects in preparationfor a large, long-term trial of the effects of cholesterol-loweringdrug therapy on mortality. At present there is only limitedevidence from randomized comparisons of the effects of HMG-CoAreductase inhibitors, such as simvastatin, on thrombogenic,as distinct from atherogenic, pathways in coronary heart disease.The present sub-study was carried out to assess the effectsof simvastatin on a range of haemostatic variables, as wellas on free fatty acids and on lipoprotein fractions not studiedin detail previously. At an average of about 2 years after starting study treatment,non-fasting blood samples were obtained from a sequential sampleof 162 participants who had been randomly allocated to receive40 mg (54 patients) or 20 mg (57 patients) daily simvastatinor matching placebo treatment (51 patients). Only patients whoreported taking their study treatment and who were not knownto be diabetic or to be taking some other lipid lowering treatmentwere to be included. The principal comparisons were to be ofthose allocated simvastatin (i.e. 20 and 40 mg doses combined)vs those allocated placebo. Among patients allocated simvastatin, marginally significantlower factor VII antigen levels (12·10%±6·08of standard; 2P<0·05) and non-significantly lowerfactor VII coagulant activity (8·24%±4·99of standard) and fibrinogen concentrations (0·10±0·08g.l^–1) were observed. In contrast, plasminogen activatorinhibitor activity was significantly higher (2·62±1·03IU; 2P<0·01) among patients allocated simvastatin.No significant differences were seen in the other haemostaticfactors studied (e.g. prothrombin fragment 1·2, factorXII and C$$$ inhibitor). Total free fatty acid concentrationwas marginally significantly reduced (2P=0·02) with simvastatin,but none of the reductions in individual free fatty acids wassignificant. Lipoprotein fractions were only measured amongpatients allocated 40 mg daily simvastatin or placebo. Comparedwith placebo, simvastatin produced significant decreases notonly in LDL cholesterol (1·74±0·15 mmol.1^–1;2P<0·0001) but also in VLDL cholesterol (0·28±0·08mmol.1^–1; 2P<0·001) and IDL cholesterol (0·17±0·03mmol.1^–1; 2P<0·0001). There were also lowertriglyceride levels associated with LDL (0·07±0·01mmol.1^–1; 2P<0·0001), IDL (0·03±0·01mmol.1^–1; 2P<0·01) and VLDL (0·27±0·14;2P=0·05). The effects of simvastatin on haemostatic variables appear tobe far less marked than its lipid effects. Given the associationsof haemostatic factors with coronary heart disease incidence,larger randomized comparisons of the HMG-CoA re1ductase inhibitors(and of the newer fibrates, which may produce greater effects)are needed to provide more reliable estimates of the extentto which they influence these variables.     

Safety of reassessment-and-release practice for mental health patients boarded in the emergency department

Objectives

Among emergency department (ED) mental health and substance abuse (MHSA) patients, we sought to compare mortality and healthcare utilization by ED discharge disposition and inpatient bed request status.

Delayed Periocular Hemorrhage After Upper Blepharoplasty

Periocular and orbital hemorrhage are rare complications of blepharoplasty, with a reported incidence of 0.055%. These complications are even less common more than 48?h after surgery. The authors report 2 cases of postoperative hemorrhage 5 and 8 days following uncomplicated upper blepharoplasty in which the initiating factor seems to have been uncontrolled hypertension. Details of the presentation, management and follow-up of each patient are described. These cases serve as an important reminder that patients must be appropriately counseled regarding the postoperative implications of their systemic conditions.     

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared the clinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.     

Active Extrusion of Heinz Bodies in Drug-Induced Haemolytic Anaemia

S ummary . A patient with repeated episodes of sulphonamide-induced haemolytic anaemia is reported. The haemolytic episodes were associated with a high percentage of Heinz bodies which had the unique feature of being actively extruded from the erythrocytes. Detailed morphological and biochemical studies are outlined, but the basis for the tendency to form Heinz bodies remains unclear. It is suggested that the phenomenon of active extrusion may provide an alternative route, independent of the reticuloendothelial system, for the removal of Heinz bodies. The close resemblance between the active expulsion of the Heinz bodies and the physiological denucleation of the maturing erythroblast is noted and a similar mechanism postulated.     

The influence of adrenergic, dopaminergic, cholinergic and serotoninergic drugs on plasma prolactin levels in ovariectomized, estrogen-treated rats.

Levels of plasma prolactin were estimated in ovariectomized, estrogen-treated rats following the systemic administration of several neural blocking and stimulating drugs. Phenoxybenzamine, an alpha-adrenergic blocker, at high doses, increased plasma prolactin. Phenotlamine, another alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, also increased prolactin but the responses were small and transient. Clonidine, an alpha-adrenergic stimulating drug, elevated prolactin levels whereas the beta-adrenergic stimulator isoproterenol had no effect. Dopaminergic blockade by pimozide increased levels of prolactin while stimulation of dopamine receptors by apomorphine decreased prolactin release. Atropine (a muscarinic chilinergic blocker), arecoline (a muscarinic stimulator) and nicotine (a nicotinic cholinergic stimulating drug) did not affect basal prolactin levels. Mecamylamine (a nicotinic blocker) produced a small transient elevation in plasma prolactin. Methiothepin, an alleged serotoninergic blocker, markedly increased prolactin secretion, as did serotonin. The data suggested the involvement of several neurotransmitters in the control of basal secretion of prolactin.