Reformulation and drop size of apraclonidine hydrochloride.

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.     

Clinical follow-up of 193-nm ArF excimer laser photokeratectomy.

The excimer laser has been undergoing rapid development for clinical use since the early 1980s. The authors report 2-year follow-up results from studies in 31 eyes (15 women and 14 men) to evaluate the excimer laser in performing photokeratectomy. Patients were divided into two groups: 27 eyes (group 1) underwent phototherapeutic keratectomy, and 4 eyes (group 2) underwent photorefractive keratectomy. Visual function improved in 21 of 27 eyes in group 1 and in 2 of 4 eyes in group 2. Complications were minimal and manageable. The authors describe a procedure to minimize induced hyperopia in phototherapeutic keratectomy patients, and, although not statistically significant, less induced hyperopia was noted in these patients. Photokeratectomy may be an alternative to penetrating or lamellar keratoplasty and more invasive refractive procedures, but the long-term effects must be carefully observed.     

5-HT1B Receptor Polymorphism and Clinical Response to Sumatriptan

The 5-HT₁ receptor agonist, sumatriptan, is highly effective in the treatment of migraine. Some patients, however, do not respond or experience recurrence of the headache. In addition, some patients report chest symptoms after sumatriptan. We investigated whether these different responses could be attributed to genetic diversity of the 5-HT_1B receptor, which most likely mediates the therapeutic action and the coronary side effects of sumatriptan. Allele frequencies of two polymorphisms in the 5-HT_1B receptor gene ( G861C and T-261G ) were investigated in migraine patients with consistently good response to sumatriptan (n=14), with no response (n=12), with recurrence of the headache (n=12), with chest symptoms (n=13), and in patients without chest symptoms (n=27). Allele frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not differ between patient groups, indicating that genetic diversity of the 5-HT_1B receptor does not seem to be involved in the different clinical responses to sumatriptan.     

Comparison of serum hepatitis C virus RNA and core antigen concentrations and determination of whether levels are associated with liver histology or affected by specimen storage time

An enzyme immunoassay has recently been developed for the hepatitis C virus (HCV) core antigen. To evaluate the possible association between core antigen and HCV RNA levels with regards to the change in liver histology over time as well as study the effect of duration of storage on viral load results, sequential sera were analyzed from 45 patients with chronic HCV infection who had undergone two or more liver biopsies. A relatively strong association was found between the core antigen and HCV RNA concentrations (r(s) = 0.8), with a core antigen level of 1 pg/ml corresponding to approximately 1,000 IU/ml. All 42 sera with detectable HCV RNA at the time of the second biopsy had core antigen concentrations above 1 pg/ml, and the three sera without detectable HCV RNA had concentrations below 1 pg/ml. No association was found between HCV RNA or core antigen levels and the stage of fibrosis in biopsy samples, progression of fibrosis, necro-inflammatory grade, steatosis, genotype, alanine aminotransferase level, or alcohol consumption. A significant association was demonstrated between the storage time of the samples and both the HCV RNA and core antigen concentrations. The median log HCV RNA concentrations (international units/milliliter) were 3.92 for the sera obtained at the time of the first biopsy (median storage time, 13.0 years) and 4.41 for the sera obtained at the time of the second biopsy (median storage time, 6.6 years) compared to 5.96, the median for 102 different routine clinical patient samples.     

High levels of Lp(a) lipoprotein in a family ith cases of severe pre-eclampsia

We report a family with two cases of severe pre-eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre-eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre-eclampsia that is genetically determined.     

Changes in the withdrawal bleeding pattern and endometrial histology during 17β-estradiol —dydrogesterone therapy in postmenopausal women: a 2 year prospective study

Objective: To describe changes in the withdrawal bleeding pattern and endometrial histology during a sequential 17β-estradiol —dydrogesterone regimen in postmenopausal women. Design: Open-label, non-comparative, prospective study. Setting: Gynecological outpatient department of a university hospital. Patients: Twenty-seven healthy nonhysterectomized postmenopausal women. Interventions: Continuous micronized 17β-estradiol supplementation, 2 mg daily, and cyclic administration of dydrogesterone, 10 mg daily for the first half of each 28 day treatment cycle. Main Outcome Measures: Changes in the characteristics of the withdrawal bleeding pattern and the endometrial biopsy histology during 2 years of treatment. Results: The initial withdrawal bleeding was comparable to normal menstruation with respect to amount and duration. During the 2 years of treatment the bleeding showed a significant tendency to become shorter with less blood loss. This was mainly the result of the decrease (P < 0.001) in the number of days per cycle with bleeding grade II (normal menstruation). None of the women developed endometrial hyperplasia, and in almost all women the given hormone replacement therapy regimen induced secretory or atrophic changes of the endometrium. Conclusions: This sequential 17β-estradiol —dydrogesterone regimen can be regarded as safe with respect to the prevention of endometrial disease and appeared to foster patient compliance.     

Increased Expression of Fas Ligand on Mycobacterium tuberculosis Infected Macrophages: A Potential Novel Mechanism of Immune Evasion by Mycobacterium tuberculosis?

We have studied the location and mechanism of apoptosis within the granulomas in the lungs at various stages of slowly progressive primary murine Mycobacterium tuberculosis infection. Parallel sections were analyzed for detection of mycobacterial antigens, Fas, and Fas ligand (FasL) by immunohistochemistry, and for apoptotic cells by terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. The frequency of apoptosis was high in the macrophage aggregates as compared to the lymphocyte aggregates and at the interface between them. Five to seven percent of the vacuolated macrophages in the granulomas expressed FasL intensely. These cells contained large amounts of mycobacterial antigens. These findings suggest that M. tuberculosis infection can induce increased expression of FasL in a population of infected macrophages. As a consequence the infected macrophages will be protected from the attack of cytotoxic T cells and activation of bactericidal mechanisms by Th1 type lymphocytes. This constitutes a novel evasion mechanism for M. tuberculosis possibly explaining the chronic course of infection.     

Interaction of Adenosine 5‘-Triphosphate (ATP) with Histamine Release Induced by Compound 48/80

The histamine releasing action of compound 48/80 disappeared after pretreatment of rat mast cells with ATP in the absence of divalent cations. The inhibitory action was evident already with 2 μM of ATP, provided the cells were preincubated with ATP for short periods of time prior to the addition of 48/80. When mast cells were exposed to 48/80 combined with ATP more than 10 μM of ATP was needed to induce inhibition of histamine release. This inhibitory effect was found to be specific for ATP compared with various organic phosphorous compounds tested and was not mimicked by EDTA. With concentrations of ATP less than 10 μM the sensitivity to the action of 48/80 was spontaneously restored after prolonged preincubation of the cells with ATP. The experimental findings suggest that ATP, in the absence of divalent cations, induced configurational changes of the plasma membrane of the mast cells so that 48/80 could no longer exert its degranulating and histamine releasing action.