Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.      

Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.     

Desflurane enhances reactivity during the use of the laryngeal mask airway

BACKGROUND: Desflurane and sevoflurane have markedly different pungencies. The tested hypothesis was that patients breathing equivalent concentrations of desflurane or sevoflurane through a laryngeal mask airway (LMA) would have similar responses. METHODS: After institutional review board approval and informed consent were obtained, 60 patients were enrolled and given intravenous midazolam (14 microg/kg) and fentanyl (1 microg/kg) 5 min before induction of anesthesia. The LMA was inserted at loss of consciousness after 2 mg/kg propofol. When spontaneous breathing returned, a randomly assigned volatile anesthetic was started at an inspired concentration of either 1.8% sevoflurane or 6% desflurane at a fresh gas flow of 6 l/min in air:oxygen (50:50). After 5 min, a controlled movement of the LMA took place. Three minutes later, the inspiratory anesthetic concentration was changed to either 3.6% sevoflurane or 12% desflurane for 3 min. A blinded observer recorded movements and airway events during the start of anesthetic, LMA movement, deepening of the anesthetic, and emergence before LMA removal. RESULTS: There were no differences at anesthetic start and LMA movement. Desflurane titration to 12% increased heart rate, increased mean arterial blood pressure, and initiated frequent coughing (53% vs. 0% sevoflurane) and body movements (47% vs. 0% sevoflurane). During emergence, there was a twofold greater incidence of coughing and a fivefold increase in breath holding in the desflurane group. CONCLUSIONS: When airway responses to sevoflurane and desflurane were compared in elective surgical patients breathing through an LMA, there were significantly more adverse responses with desflurane at 12% concentrations and during emergence.     

Endovascular therapy for critical limb ischemia

AbstractChronic critical limb ischemia (CLI) occurs when arterial perfusion is reduced below a threshold level that results in rest pain and/or tissue breakdown in the lower extremities. Importantly, it is associated with high cardiovascular morbidity and mortality. Without prompt revascularization, CLI may result in loss of a limb (i.e. amputation) and/or life. The goal of endovascular therapy is the re-establishment of pulsatile, straight-line flow to the distal extremity. Percutaneous transluminal angioplasty (PTA) has been shown to be effective and safe in the setting of CLI, with limb salvage rates that compare favorably with surgical procedures. Stents are indicated for failed PTA, while adjunctive therapies such as lasers, thermal angioplasty and atherectomy devices lack data demonstrating improved efficacy compared with conventional lower extremity interventions. In addition to successful revascularization, the institution of lifestyle changes, atherosclerotic risk factor modification, and pharmacologic therapies are indicated to reduce cardiovascular morbidity and mortality.