Ultrasound biomicroscopy in plateau iris syndrome.

Ultrasound biomicroscopy is a new technique that uses high-frequency ultrasound (50 to 100 MHz) to produce images of the entire anterior segment at high resolution (20 to 50 microns). The iridocorneal angle, iris, ciliary body, and posterior chamber can be imaged in detail and the dimensions and anatomic relationships of these structures determined. Plateau iris syndrome is a condition in which the angle remains appositionally closed or occludable after iridectomy for angle-closure glaucoma. How the iris remains in a position that allows it to occlude the angle has been uncertain. We performed ultrasound biomicroscopy eye examinations on eight patients with clinically diagnosed plateau iris syndrome. In all the patients, ciliary processes were situated anteriorly compared to the position in normal subjects and in patients with angle closure caused by pupillary block. The ciliary processes provide structural support beneath the peripheral iris, preventing the iris root from falling away from the trabecular meshwork after iridectomy.     

Preclinical pharmacokinetic, antitumor and toxicity studies with CL-994 (N-acetyldinaline)

CI-994, a substituted benzamide derivative, is a compound that showed solid tumor selectivity for a variety of solid tumor models compared to L1210 leukemia. Due to its lack of aqueous solubility, it requires oral administration. Female B6D2F₁ mice were treated with CI-994 once daily by oral administration of 50 mg/kg for 14 days. Following treatment mice were evaluated for pharmacodynamic effects as well as the pharmacokinetic behavior of CI-994 and the de-acetylated derivative dinaline. Mice samples (plasma, urine, feces) were analyzed using solid phase extraction, reverse phase HPLC and ultraviolet detection. The plasma distribution and elimination half-lives for CI-994 were 51 minutes and 9.4 hours, respectively, on D-1; 31 minutes and 3.4 hours, respectively on D-14. The apparent plasma distribution and elimination half-lives for dinaline were 27 minutes and 2.4 hours, respectively, on D-1; 40 minutes and 7.3 hours, respectively on D-14. The CI-994 AUC on D-1 and D-14 were 2879 and 2407 µ × minutes, respectively; while the dinaline AUC on D-1 and D-14 were 87 and 92 µg/ml × minutes, respectively. Urinary excretion for CI-994 and dinaline was higher on D-14, while the fecal excretion was the same on both days. The Colon #38 tumor growth in treated mice was reduced to 22% of that observed in the controls by D-19. The levels of all blood cells were reduced in the treated mice when compared to controls and the total WBC was the most affected (median 38%). Recovery to pretreatment levels occurred quickly following treatment cessation. Phase I evaluation of chronic oral administration of CI-994 is currently ongoing.     

Favorable responses to acute and chronic exercise in McArdle patients.

OBJECTIVE: This study reports acute exercise responses in a large (N = 46) series of patients with McArdle disease and responses to exercise training in a smaller (n = 9) set of patients. DESIGN: Patients were studied during both incremental and steady-state cycle ergometer exercise, using cardiopulmonary testing, and the patients were compared with age- and gender-matched controls. SETTING: The study was performed in a university setting (clinical exercise physiology laboratory). PARTICIPANTS: The 46 patients showed common features of McArdle disease. They were definitively diagnosed by histochemistry, biochemistry, and/or molecular genetic analysis. The 46 controls were healthy, sedentary individuals. INTERVENTION: Nine patients were studied before and after an 8-month supervised aerobic exercise training program (including five weekly sessions of walking and/or cycling exercise with a duration no greater than 60 minutes). MAIN OUTCOME MEASUREMENTS: The main indicators of exercise capacity that we measured were peak power output, peak oxygen uptake (VO2peak), and ventilatory threshold (VT). RESULTS: Exercise capacity (peak power output, 35% control; VO2peak, 44% control; VT, 66% control) was markedly depressed in the patients. The patients who trained improved peak power output (25%), VO2peak (44%), and VT (27%), with no evidence of negative outcomes from training. Although not achieving normal values, the response to training put the patients into the lower limit of normal controls. CONCLUSIONS: Under carefully controlled conditions, patients with McArdle disease may perform acute exercise safely, and they may respond favorably to training. This may offer an additional therapeutic option to help normalize the lifestyles of these patients.     

History of liver surgery

Although battle surgeons had débrided small bits of liver protruding through wounds since ancient times, formal entry into the peritoneal cavity to staunch hemorrhage due to trauma or to remove tumors or drain cysts had to await the advent of general anesthesia and antisepsis. After a burst of pioneering activity from 1880 to 1910, little progress was made until after World War II. In the last 40 years, remarkable advances have been made in the techniques of liver resection, our understanding of liver diseases requiring operation, and our ability to support patients through major resections. Liver transplantation epitomizes the challenges that can now be accepted, and its success augurs well for an increase in liver operations in the future.     

Membranolytic activities of quartz standards

The membranolytic activity of ten quartz specimens, determined quantitatively as the percentage of erythrocytes lysed as a function of mineral concentration, varied by up to 100 times depending on particle size, method of size reduction, thermal treatment, dispersal in the experimental system, and quartz variety. Five specimens that are currently used as standard fibrogenic dusts in pneumoconiosis research laboratories were obtained as fine powders. Two other specimens obtained as large single crystals and three additional ones obtained as massive crystalline specimens required pulverization before testing. The specimens were studied as size-heterogeneous powders, and after fractionation into narrow size bands. The membranolytic activity of the size fractions increased by an average of 30 times as the Stokes' diameter of the particles decreased from 20 to 1 μm. The five specimens that were reduced to powders in a carborundum mortar and pestle lost activity after hydration in the water-fractionation process. When these inactive quartz specimens were heated to 400–500°C for 6 hr, their activities were restored. The active and inactive quartz specimens were indistinguishable by electron microscopy, powder X-ray diffraction and optical microscopy. The physico-chemical properties of quartz are variable and therefore the mineral's biological potential varies considerably.     

Cutaneous horn of penis

Cutaneous horns of the penis are hyperkeratotic lesions of the skin which arise secondary to chronic irritation. Treatment is local excision with removal of a broad base. Examination of the base is important to rule out carcinoma as the underlying cause of the lesion. A case report is presented and the literature reviewed.     

Planum temporale asymmetry and ear advantage in dichotic listening in Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD).

The planum temporale is clearly involved in language processing, for it serves as the auditory association cortex. Research has consistently demonstrated that 60 to 70% of the population has leftward asymmetry of the planum temporale. Research has also suggested that dyslexic individuals tend to have either rightward asymmetry or symmetrical plana. Moreover, many studies have found a relationship between the presence of dyslexia and/or language impairment and deficits in the normal right ear advantage found in dichotic listening paradigms. In this context, this study examined the relationship between planum temporale asymmetry and ear preference in dichotic listening performance in children with Developmental Dyslexia and Attention-Deficit/Hyperactivity Disorder (ADHD). Subjects included 19 children with dyslexia (10 of whom had a comorbid diagnosis of ADHD), 23 children with ADHD, and 12 diagnosed normal control children. Dichotic listening data were not collected for 8 of the 12 normal control children and for 3 of the 23 ADHD children. Results revealed no significant difference between ADHD and dyslexic subjects in regard to ear advantage on the free recall dichotic listening task. In addition, although the directed dichotic listening tasks were not related to degree of planum asymmetry, as predicted, results indicated that subjects who consistently displayed an atypical left ear advantage tended to have larger right bank lengths than those who consistently displayed a typical right ear advantage. These findings support the notion that some individuals with dyslexia or language deficits tend to have a larger right planum temporale and that performance on dichotic listening tasks may reflect this relatively unusual pattern.     

Paradoxical Platelet Behaviour in Diabetic Ketoacidosis

Thrombotic events may occur in patients who present with severe uncontrolled diabetes or with diabetic coma. As a possible explanation for this, platelet function was investigated at presentation with diabetic ketoacidosis and during treatment in 10 patients. Concentrations of the platelet-specific proteins, platelet factor 4 (PF4) and betathromboglobulin (betaTG) were elevated and fell towards normal with treatment. Despite evidence of increased aggregation in vivo, platelets from subjects with ketoacidosis were insensitive to adenosine 5′-diphosphate (ADP), sensitivity increasing with correction of ketoacidosis. Platelets from ketoacidotic diabetics were initially insensitive to the anti-aggregatory action of prostacyclin (PGI₂) and became normal with treatment. Initial blood glucose concentrations correlated with log₁₀ ADP concentrations (r = 0.72, p < 0.01) and with log₁₀ PGI₂ ID₅₀ (the PGI₂ concentration required to half-inhibit ADP-induced aggregation) (r = 0.66, p < 0.025). Glucose concentrations throughout the 2-week study period correlated with all log₁₀ ADP concentrations (r = 0.32, p < 0.005) and all log₁₀ PGI₂ ID₅₀ concentrations (r = 0.51, p < 0.001). The decrease in ADP sensitivity in ketoacidosis, paradoxical in view of the evidence of increased in vivo platelet aggregation, may result from an acquired platelet storage pool deficiency.     

Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis.

BRL34915 (0.1-10 microM) suppressed the spontaneous tone of guinea-pig isolated trachealis in a concentration-dependent manner. BRL34915 was not antagonized by propranolol (1 microM). In trachea where spontaneous tone was suppressed by indomethacin (2.8 microM) but subsequently restored to the same level with acetylcholine or histamine, the relaxant potency of BRL34915 was reduced. In Krebs solution containing K+ (120 mM), isolated trachealis muscle developed near-maximal tension. The relaxant effects of BRL34915 were virtually abolished in this medium. Concentration-effect curves for KCl, acetylcholine and histamine were constructed in tissues treated with indomethacin (2.8 microM). BRL34915 (10 microM) depressed the foot of the concentration-effect curve for KCl and caused minor rightward shifts in the concentration-effect curves of acetylcholine and histamine. Four K+-channel inhibitors were tested. Apamin (0.1 microM) did not modify the action of BRL34915. Tetraethylammonium (8 mM) had little effect but procaine (5 mM) and 4-aminopyridine (5 mM) each significantly inhibited the relaxant action of BRL34915. Intracellular electrophysiological recording showed that BRL34915 (0.1 microM) caused very minor relaxation and little, if any, electrical change. Higher concentrations (1-10 microM) evoked relaxation, suppression of spontaneous electrical slow waves and marked hyperpolarization of the trachealis cells. In the presence of TEA (8 mM) or procaine (5 mM) the hyperpolarization induced by BRL34915 was significantly reduced. In trachealis skinned of its plasma membranes, tension development induced by Ca2+ (20 microM) was unaffected either by BRL34915 (10 microM) or by nicorandil (1 mM). In studies of the efflux of 86Rb+ from muscle-rich strips of trachea, BRL34915 (1 and 10 microM) increased the efflux rate constant. It is concluded that BRL34915 evokes relaxation of the trachealis by a mechanism that involves neither beta-adrenoceptor activation nor direct reduction of the sensitivity of the intracellular contractile machinery to cytosolic free Ca2+. The action of BRL34915 may depend on the opening of K+ channels in the plasma membrane which are permeable to 86Rb+. The opening of these channels, or the effects of their opening, may be reduced by K+-channel inhibitors such as 4-aminopyridine, procaine and TEA but not by apamin.