Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.     

Bilateral anterior uveitis and interstitial nephritis

Five patients had bilateral anterior uveitis associated with renal disease. Interstitial nephritis was histologically confirmed in three cases. Fatigue, anorexia, abdominal pain, weight loss, and anemia were common systemic complaints or findings. In each case, the uveitis was anterior, eventually bilateral, and associated with minimal visual impairment. Complications of the uveitis included increased intraocular pressure, synechiae, keratic precipitates, macular edema, and intraretinal hemorrhage as well as cells in the anterior vitreous humor and an exudate over the pars plana. Sj?gren's syndrome, systemic lupus erythematosus, sarcoid, and syphilis were excluded as diagnoses that could explain the association of renal and uveal disease.     

Ocular syphilis in patients with human immunodeficiency virus infection

We diagnosed ocular syphilis in three homosexual men infected with human immunodeficiency virus (HIV). Ocular inflammation included uveitis, optic neuritis, and retinitis. Dermatologic and central nervous system manifestations of secondary syphilis were also present. The history of homosexuality was difficult to obtain. Concomitant infection with HIV may alter the course of syphilis, obscure the diagnosis, and impair the response to therapy.     

Plasma concentrations of endogenous hormones during one regular treatment cycle with a low-dose oral contraceptive and during two cycles with deliberate omission of two tablets.

In this open, prospective, phase-I study we closely monitored levels of endogenous progesterone, 17beta-estradiol, luteinizing hormone (LH) and follicle stimulating hormone in six healthy women. We determined plasma concentrations every 1-3 days during one untreated baseline cycle and during the first treatment cycle with regular pill intake of an oral contraceptive containing 30 microg ethinylestradiol plus 75 microg gestodene. During the following two treatment cycles, two tablets were deliberately omitted (in cycle 2 on days 6/7 and in cycle 3 on days 11/12). All but possibly one volunteer ovulated in the untreated pre-cycle, as concluded from LH peaks followed by marked increases of progesterone. During the regular first treatment cycle and even after deliberate omission of two tables in treatment cycles 2 and 3, the progesterone and estradiol levels remained low, so that we concluded that no ovulation took place. However, two volunteers showed some sort of LH peak in the first regular treatment cycle and all women showed LH increases of > 40 microg/ml in at least one omission cycle. In ten out of 12 cycles, omissions of pill intake were followed by an episode of intermenstrual bleeding. In conclusion, we have shown that, after omission of two consecutive oral contraceptive tables, the endogenous hormone parameters did not provide evidence for ovulation. Although this provides confirmation of the robustness of this oral contraceptive towards non-compliance, the widely published practical recommendations should be followed.     

Thrombin Inhibits the Migration of Human Liver Myofibroblasts

Scarring of the cornea, the transparent tissue at the front of the eyeball, is an important cause of visual impairment. A major chemokine upregulated in tear fluid after corneal injury is platelet‐derived growth factor (PDGF), which induces the stromal cells of the cornea (keratocytes) to assume a fibroblastic phenotype. We have investigated the role of PDGF in matrix contraction by human corneal fibroblasts (HCF) using the standard three‐dimensional (3D) fibroblast‐populated collagen matrix model (FPCM).
When stimulated with PDGF, HCF in monolayer (2D) display circular ruffles (CR) on their dorsal surface. Using immunolabeling, we found that CR contain proteins of the Arp2/3 complex, which is required for the assembly of filamentous actin during protrusive activity. This PDGF‐mediated ruffling ability is altered by antibodies or blocking peptides that specifically interfere with the Arp2/3‐mediated pathway of actin polymerization, as well as by the myosin light chain kinase inhibitor, ML9. Preincubation with anti‐PDGF‐BB antibody or with the tyrosine kinase inhibitor, AG1295, also inhibits CR. While PDGF efficiently stimulates HCF‐mediated cell protrusive activity and macroscopic collagen gel contraction in the 3D model, this effect is directly inhibited by all the substances which inhibit CR in 2D, demonstrating a direct involvement of the PDGF‐mediated CR pathway in tissue contraction. Thus, 3D PDGF‐induced matrix contraction by HCF involves the same players as CR, a phenomenon observed in 2D cell cultures: PDGF‐BB receptor, receptor tyrosine kinase, the machinery for filamentous actin assembly (Arp 2/3 complex, Scar and Wasp proteins), and myosin. The functional role of circular ruffling or its equivalent in three‐dimensional fibroblast‐populated collagen matrices seems to be a rapid reorganization of the actin cytoskeleton in preparation for cell‐matrix interaction.     

The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients.

We evaluated the predictive value of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in 32 depressed outpatients completing a double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe), which failed to show any significant difference between SAMe and placebo. Treatment response was defined as the change in Hamilton Rating Scale for Depression (HRSD-24) score between baseline and the end of the six-week trial. Subjects with TSH response outside the normal range (7-25 uU/ml) had a significantly greater response than patients with a normal response. There was also a significant correlation between absolute deviations from the mean TSH response (16 uU/ml) and changes in HRSD-24 scores.