Keratoconus in monozygotic twins in New Zealand

We report on a case of keratoconus in identical twins who were brought up in Christchurch, New Zealand. Videokeratoscopy using an EyeSys^a (EyeSys Laboratories, Houston, Texas, USA) revealed not only marked differences in severity of keratoconus between the sisters, but also non-equivalent cone types. Both twin sisters reported an exacerbation of their keratoconus during pregnancy and during breast feeding. Various factors affecting the development and progression of keratoconus are discussed. (Clin Exp Optom 1995; 78: 4: 125–129)     

Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1.

N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4-nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4-cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response.     

Effect of inhaled fluticasone propionate on BAL TGF-beta(1) and bFGF concentrations in clinically stable lung transplant recipients.

BACKGROUND: Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations. RESULTS: In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations. CONCLUSIONS: Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.     

Polyamines found in gingival fluid enhance the secretory and oxidative function of human polymorphonuclear leukocytes in vitro

Many bacterial and host cells contain large amounts of polyamines that can be released at infection sites as a result of cell lysis. Consequently, the putrescine and spermidine content of gingival fluid from inflamed periodontal pockets (0.1 to 1 mM) is sharply elevated in comparison to peripheral blood. At these levels, polyamines potentiated fMet-Leu-Phe-induced Ca²⁺ signaling in polymorphonuclear leukocytes (PMNs) in vitro. Consistent with the essential role of Ca²⁺ signaling in PMN activation, secondary granule release and superoxide anion production by fMet-Leu-Phe-stimulated PMNs was enhanced in the presence of polyamines. Thus, polyamines may play a local role in modulating the antimicrobial activity of PMNs in periodontal disease.     

Comparison of the metabolism and disposition of [3-14C]coumarin in the rat and marmoset (Callithrix jacchus)

Male Sprague-Dawley rats and marmosets were given a single oral 25 mg/kg dose of [3-14C]coumarin and the excretion of radioactivity in the expired air, urine and faeces monitored up to 96 h. Excretion profiles were similar in both species with the bulk of the dose being excreted in the urine and faeces within 24 h. Chromatographic analysis of 0-48 h urine samples revealed similar metabolic profiles with only small amounts of unchanged coumarin and very little 7-hydroxycoumarin. Coumarin 7-hydroxylase activity was not detectable in hepatic microsomes from either species. These results demonstrate that the disposition of [3-14C]coumarin was similar in the rat and marmoset, a New World primate, and that both species, unlike man, are poor 7-hydroxylators of coumarin.     

Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and adriamycin infusions plus high-dose decadron

Thirty patients with Philadelphia chromosome-positive lymphoid (20 patients) or undifferentiated (ten patients) chronic myelogenous leukemia in blast crisis were treated with 0.4 mg of vincristine by continuous intravenous infusion (CIV) daily for 4 days; (doxorubicin) 12 mg/m2 of Adriamycin (Adria Laboratories, Columbus, OH) by continuous intravenous infusion daily for 4 days; and 40 mg of decadron daily on days 1 through 4, 9 through 12, and 17 through 20 (VAD). Course 2 was given starting on day 24 with the addition of cyclophosphamide 1 g/22. Overall nine patients achieved complete remission (30%) and three attained a partial remission (10%), for an overall response rate of 40%. Four patients expired during induction whereas 14 had resistant disease. Response rate was significantly higher for patients with lymphoid compared to undifferentiated morphology (55% versus 10%; P = 0.05). In lymphoid blast crisis, Calla-positive disease was associated with a higher response rate compared to Calla-negative disease (75% versus 25%; P = 0.08). Eleven patients developed infections, and seven had fever without documented infections. The median overall survival was 29 weeks. Median survival was 43 weeks for patients achieving complete remission and 20 weeks for those with resistant disease. Remission duration was 39 weeks. After primary and salvage therapy, nine patients are alive, six of them in continuous remission for 19+ to 112+ weeks. The authors conclude that VAD chemotherapy is an effective regimen with acceptable toxicity in patients with lymphoid blast crisis especially those with Calla-positive disease. Alternate induction regimens for undifferentiated disease and for maintenance therapy are currently being investigated.     

The effects of anticholinergics on the photopalpebral reflex, memory and mood

This study investigated central anticholinergic drug effects on: (1) the Randt Memory Test, a relatively new instrument which measures the acquisition and recall of verbal and pictorial information; (2) the averaged photopalpebral reflex (PPR), an electrophysiological parameter, the validity of which needs to be further investigated in pharmacological research and; (3) mood as measured by a 16-item visual analogue scale. Atropine (1 mg and 2 mg), pirenzepine (20 mg) and a placebo were administered intramuscularly in a double-blind cross-over trial in eight healthy volunteers. There were no inter-treatment differences on the Randt Memory Test. This finding is seemingly in contrast to those reported by some authors using other memory tests. In contrast to the reported effects of some benzodiazepines, the anticholinergics used in the present study did not prolong the latencies of the PPR, but reduced the amplitudes. Visual analogue scales indicated central effects for both pirenzepine and atropine. This implies pirenzepine's penetration of the blood-brain barrier and a physiological function for central muscarinic-1-receptors. The significant anticholinergic effects were exclusive to the "alertness" factor.     

The sensitivity of Drosophila larvae to continuous-wave ultrasound.

The threshold for killing of freshly hatched Drosophila larvae exposed to continuous-wave (CW) ultrasound shows a minimum at approximately 0.3 MHz. This suggests that the stiffness of the material surrounding the gas bodies in the organism is comparable to water. From this, it is apparent that the gas bodies in three-day-old larvae that we have used in earlier studies are far larger than resonance size at the frequencies (1-5 MHz) used. Yet, these larvae were killed by short exposures to low-temporal-average-intensity pulsed ultrasound with peak intensities of the order of 10 W/cm2. Hence, it appears that "large" bubbles cannot be ignored in considerations of the biological effects of pulsed ultrasound and lithotripsy.