Acidosis, alkalosis, and aqueous humor dynamics in rabbits

Systemic acidosis induced by intravenous administration of hydrochloric acid lowered intraocular pressure in unanesthetized rabbits. Aqueous humor flow was reduced by approximately 50%, as measured by the iodide method and as calculated from tonographic data. Outflow facility, episcleral venous pressure, plasma osmolality, blood pressure, pulse, and body temperature were not altered by systemic acidosis. Systemic alkalosis induced by intravenously administered sodium bicarbonate was associated with an increased intraocular pressure. Aqueous humor flow following systemic alkalosis was increased by approximately 100%, as measured by the iodide method and as calculated from tonographic data. Alkalosis was not associated with alterations in outflow facility, episcleral venous pressure, plasma osmality, blood pressure, pulse, or rectal temperature.     

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.     

Costs and effects of microsurgery versus radiosurgery in treating acoustic neuroma

This study analyses costs and effects of treating acoustic neuroma patients by using microsurgery compared to radiosurgery. Radiosurgery is the stereotactic application of radiotherapy and an innovative medical technology. Cost and effect estimates of conventional treatment were based on a retrospective study in the Netherlands. Similar data for a comparable group of patients in Sweden were collected for radiosurgery, as this treatment option is currently not available in the Netherlands. Fifty-three acoustic neuroma patients who had been operated on the University Hospital Rotterdam between November 1990 and February 1995 were included. This group was compared with 92 acoustic neuroma patients treated with radiosurgery (Gamma Knife. Stockholm, Sweden) in the same period. Data on health care use were collected from patient files. To obtain data on production losses and quality of life, a questionnaire was sent by mail in February 1995. This booklet consisted of the Health and Labour-questionnaire (HLQ), the Short Form-36 (SF36) and the EuroQol. The response rate was 92%. Direct costs for microsurgery amounted to Dfl. 20.072,- and for radiosurgery to Dfl. 14.272,-. Indirect costs were respectively Dfl. 16.400,- and Dfl. 1.020,-. General health rating was better for radiosurgery than for microsurgery. On the whole, differences in clinical outcomes between the two patient groups were small. Assuming a reasonable occupancy rate of the expensive radiosurgery equipment, we demonstrated that for the short term treating patients with acoustic neuroma with an extra-meatal tumour diameter of less than 3 centimeters, radiosurgery is more cost-effective than microsurgery.     

Role of a new Rho family member in cell migration and axon guidance in C. elegans

Rho family GTPases are thought to regulate actin-dependent processes, but their functions in vivo are still poorly understood. We have investigated the function of a new, widely expressed Rho family member in C. elegans by analyzing mutations in the endogenous gene. Activated and null alleles all inhibit cell migration, demonstrating that this protein is required for cell migration in vivo. Only a small subset of the migrations inhibited by activating mutations are inhibited by null mutations, suggesting that considerable functional redundancy exists within this system. Our findings support this conclusion and show that mig-2 functions redundantly with another pathway to regulate nuclear migration. Surprisingly, activated alleles also cause misguided axon growth, suggesting that Rho family GTPases may couple guidance cues to process outgrowth.     

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.