Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Colonic lavage prior to colonoscopy: comparable outcomes of two polyethylene-glycol preparations and a sodium-phosphate solution

OBJECTIVE: Comparison of three cleansing solutions for bowel preparation prior to colonoscopy. DESIGN: Prospective, randomized. METHOD: 140 outpatients referred for colonoscopy were randomized into three groups for cleansing with 4 litres PEG 4000, 4 litres PEG 3350 or with 90 ml sodium phosphate with an additional 2.5 litres of fluid. Between cleansing and colonoscopy, patients filled in a questionnaire concerning taste, abdominal cramps and tolerance to the procedure. Blinded to the type of cleansing the endoscopist scored the effects on the colon and rectosigmoid, and made the endoscopic diagnosis. RESULTS: All data were available for 127 of the 140 patients (50 men, 77 women), mean age 51 years (range 18-96). Comparison between the three groups showed no statistically significant difference in the opinion of the patients concerning taste, abdominal cramps and tolerance of lavage. The endoscopist's scoring of total colon cleansing showed a small reduction in colon cleanliness when using sodium phosphate compared to PEG 3350 (p = 0.03). No differences were found between the two PEG solutions. Combining both PEG solutions and comparing them with the sodium-phosphate solution showed fewer abdominal cramps (p = 0.07) with sodium phosphate and a cleaner colon with PEG (p = 0.07). Women complained slightly more of abdominal cramps and were slightly less tolerant of the procedure than men. Previous colonic surgery did not influence the results. Patients with diverticula were older, but no other effect of cleansing was found. CONCLUSION: The three preparations are comparable in their cleansing effect and tolerance by the patient.     

Hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography and endoanal magnetic resonance imaging in evaluating perianal fistulas: agreement and patient preference

OBJECTIVES: To determine agreement between hydrogen peroxide-enhanced three-dimensional endoanal ultrasonography (3D HPUS) and endoanal magnetic resonance imaging (MRI) in preoperative assessment of perianal fistulas, and to assess patient preference with regard to these techniques. METHODS: Forty patients (31 males, aged 21-70 years) with symptoms of a perianal fistula and a visible external opening underwent preoperative 3D HPUS and endoanal MRI. The results were assessed separately by experienced observers. Fistulas were described according to the following characteristics: classification of the primary fistula tract according to Parks, location of the internal opening, presence of secondary tracts and fluid collections. Patients were asked to score the amount of discomfort experienced during both procedures and express their preference for either method. RESULTS: The median time interval between 3D HPUS and endoanal MRI was 14 days (range, 0-91 days). The methods agreed in 88% (35/40, kappa = 0.45) for the primary fistula tract, in 90% (36/40, kappa = 0.83) for the location of the internal opening, in 78% (31/40, kappa = 0.62) for secondary tracts, and in 88% (35/40, kappa = 0.63) for fluid collections. Both methods were associated with similar discomfort, and there was no patient preference for one procedure over the other. CONCLUSIONS: 3D HPUS and endoanal MRI are equally adequate for the evaluation of perianal fistulas. Both methods are associated with similar discomfort and patients have no preference for either procedure.     

RENAL FUNCTION IN CHRONICALLY CATHETERIZED CONSCIOUS DIABETIC RATS USING CONSTANT AND SERVO-CONTROLLED INFUSION

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.     

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.     

Pineal germinoma: MR imaging

Magnetic resonance (MR) imaging characteristics of pineal germinomas are described in seven patients imaged with MR and computed tomography (CT). In patients with symptoms of an enlarging process in the quadrigeminal plate cistern, MR imaging was as sensitive as CT scanning in detecting the mass. MR imaging did not detect a normal-sized, calcified neoplastic gland. Germinoma, germinoma with embryonal cell carcinoma elements, and pineoblastoma demonstrated different MR signal characteristics. Although direct coronal and sagittal MR images were useful in defining the relationship of the tumor to the posterior third ventricle, Sylvian aqueduct, and vein of Galen, the ease, rapidity, and sensitivity of CT scanning suggest that CT should remain the modality of choice for initial evaluation and screening of the pineal region, especially in the younger pediatric population, in whom detection of calcification may provide the only clue of an abnormality.     

Vasodilator agents and supracollicular transection fail to inhibit cortical spreading depression in the cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.