The fragile X syndrome.

An amplification of a highly unstable DNA element has been identified at the fragile X locus in Xq27.3. This sequence appears to be both the source of the primary mutation causing the fragile X syndrome, apparently having its causative effect through the methylation of the FMR-1 HTF island and the region of cytogenetic fragility. The direct analysis of the genotype of carrier and affected individuals can be used as a direct diagnosis tool which will improve both the accuracy and speed of diagnosis. The identification of hereditary unstable DNA in a disease with such a wide level of non-penetrance and variable phenotype may give clues as to the basis of non-penetrance in other human genetic disorders.     

What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography?

OBJECTIVES: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. METHODS: Follow-up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (> or =12). RESULTS: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients.     

Use of a Strecker oesophageal stent in the treatment of benign oesophageal stricture

The use of self-expanding prostheses in the management of malignant oesophageal strictures has become well established. The majority of benign peptic oesophageal strictures can be successfully managed using endoscopic or fluoroscopically guided balloon oesophageal dilatation combined with long-term drug therapy, particularly using proton pumper inhibitors. Although endoscopic oesophageal dilatation can be performed on an outpatient basis, it requires repeated hospital visits. There is a small risk of oesophageal perforation whilst cardio-respiratory complications may be encountered during the use of intravenous sedation in an elderly population. The use of a self-expanding Strecker stent in a 98 year old woman with a benign oesophageal stricture is described.     

Direct evidence for hydroxyl radical-induced damage to nucleic acids by chromium(VI)-derived species: implications for chromium carcinogenesis

Reduction of Cr(VI) by NADH and NADPH has been shown to yieldCr(V) species, which have been detected by electron paramagneticresonance (EPR) spectroscopy. The fine structure on the EPRsignal of the Cr(V) species is consistent with the presenceof two NAD(P)H ligands in a square-pyramidal arrangement witha single oxygen (oxo) group at the apex. Neither this speciesnor the initial Cr(VI) complex damage DNA components as evidencedby the lack of effect of these compounds on the optical andEPR signals of the Cr(VI) and Cr(V) species respectively. Additionof hydrogen peroxide to the Cr(V) species is shown to resultin the formation of a further transient EPR signal, the parametersof which are consistent with an assignment to a Cr(V)-peroxidecomplex. Inclusion of the spin trap 5,5-dimethyl-l-pyrroline-N-oxidein this system demonstrates that hydroxyl radicals are alsogenerated, possibly via the decomposition of the peroxide complex.Inclusion of DNA components in this system together with thespin trap 2-methyl-2-nitrosopropane results in the detectionof base- and sugar-derived radicals; the characteristic EPRsignals of these species have allowed both the identificationof these species and their mechanism of formation to be determined.The signals from the former species are consistent with radicaladdition to the base, whereas the sugar-derived species arebelieved to be formed via hydrogen atom abstraction. In eachcase, this behaviour is consistent with hydroxyl radicals beingthe damaging species in systems where Cr(V) is generated inthe presence of hydrogen peroxide. These results therefore suggestthat it may be the hydroxyl radical that is the ultimate carcinogenicspecies in cells and systems exposed to Cr(VI).     

Severe rheumatic mitral stenosis with pericardial effusion causing left ventricular tamponade.

A woman of 38 was admitted for urgent surgery of severe mitral stenosis causing pulmonary oedema. Echocardiography showed a pericardial effusion with apparent distortion and collapse of the left ventricle. Urgent drainage of the effusion before mitral valve surgery led to an improvement in cardiac output with no detectable change in right heart pressures.     

Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.     

Noncompression unicortical miniplate osteosynthesis of mandibular fractures.

The use of transoral noncompression unicortical miniplates in treating 42 consecutive patients with 64 displaced mandibular fractures (excluding subcondylar) was reviewed. Titanium miniplates (Wurzburg) were used for fixation. The principles set forth by Champy and colleagues, with two plates for body and symphyseal fracture fixation and one plate superiorly along the oblique ridge for angle fractures, were performed. Intermaxillary fixation was not used postoperatively. Results compared favorably with other forms of treatment with no evidence of postoperative malocclusion, with an overall complication rate of 3%. The advantage of no external incision, avoidance of intermaxillary fixation, and normal postoperative incisal opening and occlusion make this technique our treatment of choice.