Performance standards for toric soft contact lenses.

PURPOSE: To simplify the clinical assessment of toric soft contact lens (TSCL) on-eye behavior by establishing a set of standard clinical evaluation techniques. The likely performance range expected among the TSCL wearing population was determined for a series of lens designs and acceptable performance standards indicated for each variable. METHODS: Four prism-ballast, two peri-ballast and one dynamic stabilization TSCL designs were each worn by groups of 20 subjects in a nondispensing study. After 20 min of lens wear, lenses were assessed, in right eyes only, for subjective comfort (100-point scale), lens mislocation (degrees deviation from vertical) and rotational recovery after deliberate 30 degrees mislocation (degrees/10 blinks). The percentage of lenses orienting within +/-10 degrees of target orientation (zero rotation) and the variability of orientation (standard deviation of mislocation) were also calculated for each lens group. RESULTS: Based on partitioning of the data distributions for each variable, performance was designated as excellent, acceptable or poor. Corresponding performance cut-offs were determined at > or =90, 89 to 80, and <80 for subjective comfort, < or =+/-6 degrees , +/-7 degrees to 10 degrees , and >+/-10 degrees for mislocation, >10 degrees /10 blinks, 10 degrees to 6 degrees /10 blinks, and <6 degrees /10 blinks for rotational recovery. For groups of wearers the appropriate cut-offs were > or =90%, 89 to 70%, and <70% of lenses orienting within +/-10 degrees of target orientation and <+/-6 degrees , +/-6 degrees to 10 degrees , and >+/-10 degrees for variability of orientation. CONCLUSION: Techniques suitable for the evaluation of TSCL clinical performance have been described and guidelines for the assessment of such lenses established. In the process, we have identified potential performance differences that may relate to variations in TSCL design.     

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

Effects of electrical or chemical stimulation of the prefrontal cortex on arrhythmias induced in cats by electrical stimulation of the anteromedial hypothalamus

When the anteromedial hypothalamus is stimulated with a chronically implanted electrode in conscious cats, negative emotional behaviors such as restlessness and escape occur during stimulation and ventricular extrasystoles occur in rapid succession immediately after the end of stimulation. It has been shown in the lightly anesthetized cat that the activity of the sympathetic nervous system becomes predominant during stimulation of the anteromedial hypothalamus thereby causing the rises in blood pressure and heart rate. However, immediately after the cessation of the stimulation, this 'sympathetic dominant' state was observed to be switched to the 'parasympathetic dominant' state with falls in blood pressure and heart rate which was very frequently followed by the appearance of the ventricular extrasystoles (Poststimulus Arrhythmia: PSA). The purpose of this experiment was to examine how the electric and pharmacological stimulation of the prefrontal cortex modulate the rise in the blood pressure and heart rate and PSA caused by electric stimulation of the anteromedial hypothalamus. When the prefrontal cortex was electrically stimulated simultaneously with stimulation of the anteromedial hypothalamus in 24 lightly anesthetized cats, PSA was inhibited or facilitated or remained unchanged depending on the site of stimulation in the prefrontal cortex. When dopamine or noradrenaline was microinjected into the site of prefrontal cortex where PSA was inhibited, PSA was suppressed and this effect was blocked by microinjection of haloperidol or phenoxybenzamine, respectively. Dopamine was ineffective when injected in the site where PSA was facilitated; PSA was facilitated by microinjection of noradrenaline and this effect was inhibited by microinjection of propranolol. Although changes in blood pressure and heart rate were observed when the inhibition or facilitation of PSA was elicited by prefrontal injection of noradrenaline, no changes in cardiovascular parameters occurred when dopamine injection caused the inhibition of PSA. These results suggest (1) that activation of the dopamine receptor or alpha adrenoceptor in the prefrontal cortex is involved in the inhibition of PSA, and activation of beta adrenoceptor is concerned with facilitation of PSA and (2) that the mechanisms of dopamine receptor mediated inhibition of PSA appear to be different from those of inhibition of PSA by activation of the alpha adrenoceptor in the prefrontal cortex.     

Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics. Well-controlled multicenter trial

Antithrombin III (AT III) is known to be the most important inhibitor of serine protease in the coagulation system. In the presence of heparin, AT III is converted from its progressive activity state to an immediate activity state. In disseminated intravascular coagulation (DIC) in the field of obstetrics, the treatment has to be initiated very early. Heparin treatment, on the other hand, is critical since frequently postpartal or postoperative wound bleeding is present. We, therefore, established diagnostic criteria for the early diagnosis of DIC and investigated the clinical efficacy of a therapy with AT III in a well-controlled comparative study versus the injectable synthetic protease inhibitor FOY. The results of the trial showed that the AT III group (92%; n = 24) was significantly (p less than 0.001) superior in clinical efficacy to the FOY group (60%; n = 15). No side effects whatsoever were observed after treatment with AT III concentrate (Behring Institute). From these results, it could be concluded that a single therapy with AT III concentrate can sufficiently control the symptoms of DIC in the field of obstetrics without the risk of increased bleeding.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.