Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension

BACKGROUND: Endothelial dysfunction with a loss of endothelium-dependent vasodilation has been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. METHODS AND RESULTS: Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise (Ex). Change in luminal area after acute administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest = 100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n = 30; hypertensive subjects, n = 18) and group 2 of 31 patients with (normotensive subjects, n = 15; hypertensive subjects, n = 16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P < .01) and group 2 (110 mm Hg versus 98 mm Hg, P < .025). In group 1, exercise-induced vasomotor response was significantly different between normotensive and hypertensive patients in normal (+20% versus +1%, P < .003) and stenotic vessels (-5% versus -20%, P < .025). However, in group 2 there was coronary vasodilation in normotensive and hypertensive patients for both normal (delta Ex +23% versus +21%, P = NS) and stenotic vessel segments (+24% versus +26%, P = NS). CONCLUSIONS: Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.     

Metallic or absorbable fracture fixation devices. A cost minimization analysis

Absorbable polyester pins and screws for the internal fixation of small fragment fractures have been commercially available for several years. The main advantage of these devices is that no implant removal procedures are required, which could result in financial savings. The current cost analysis, which included costs of medical care plus costs of lost time from work, was based on 994 fracture patients treated with absorbable internal fixation devices and 1173 patients operated on using conventional metallic devices. The fracture types studied were uni- and trimalleolar fractures of the ankle, fractures of the olecranon, and metacarpal fractures. When the costs for an implant removal procedure after metallic fixation were included, the average cost saved per patient by using absorbable implants varied from $410 in fractures of the olecranon to $903 in unimalleolar fractures. However, hardware removals often are optional. According to the results of this cost analysis, the break even point is attained at a removal rate of 19% for metacarpal fractures, 21% for unimalleolar fractures, 46% for fractures of the olecranon, and 54% for trimalleolar fractures. Only at a higher removal rate would the use of absorbable devices, with their current prices, be a financially more favorable alternative than the use of metallic ones.     

Plastic remodeling of the synaptic apparatus of skeletal muscles under physiological and pathological conditions

The synaptic apparatus of skeletal muscles undergoes continuous remodelling, by adapting to the functioning level of the peripheral neuromuscular apparatus under normal conditions, compensating and restoring its impaired function in pathology. This reorganization has specific features depending on the factors that influence it, such as increased function, decreased or no function, neuronal and nerve damage, synaptic toxin intoxication, autoantibody action, disturbances of trophic influences, etc. Damage to any link of the neuromuscular apparatus due to the above factors is likely to be an essential condition for remodelling.     

Ocular levels of azithromycin

OBJECTIVE: To assess azithromycin levels in human serum, aqueous humor, tear fluid, and conjunctival tissue specimens after administration of a single 1-g oral dose of azithromycin. METHODS: Sixty patients undergoing cataract surgery were included in this analysis. Serum, aqueous, and tear specimens were collected 3, 6, and 12 hours and 1, 2, 3, and 4 days after azithromycin administration. Conjunctival tissue biopsy specimens were collected 1, 2, 3, 4, 6, 8, 10, 12, and 14 days after azithromycin administration. All specimens were subjected to analysis by high-performance liquid chromatography-mass spectrometry. RESULTS: Azithromycin concentration ranges during the specified sampling times were as follows: serum, 21 to 974 ng/mL; tear, 82 to 2892 ng/mL; aqueous, 10 to 69 ng/mL; and conjunctival, 0.7 to 32 micrograms/g. Levels above the 90% minimal inhibitory concentration (MIC90) for Chlamydia trachomatis were detected after 4 days in all tear samples and after 14 days in all conjunctival tissue specimens following oral azithromycin administration. CONCLUSION: We demonstrated prolonged high levels of azithromycin in drug-targeted ocular tissue. Prolonged high concentrations of azithromycin in conjunctival tissue make this drug suitable for treatment of conjunctivitis caused by chlamydiae and other susceptible organisms.     

In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats]

BACKGROUND: General anaesthesia affects lung volume and pulmonary gas exchange. What role is played by mechanical stimulation by the endotracheal tube? METHODS: We investigated the effects of intubation on arterial oxygenation and lung volume in rats. RESULTS: Endotracheal intubation caused an increase in PA-aO2 and volume of trapped gas in the lung. This was accompanied by a reduction in neuropeptides and calcitonin gene-related peptide (CGRP) in trachea, bronchi and lung, and in vasoactive intestinal peptide (VIP) in the trachea. The increase in PA-aO2 and volume of trapped gas due to intubation was not altered in the animals given capsaicin, in which neuropeptide levels were reduced. CONCLUSIONS: These data suggest that the decrease in CGRP and VIP content in the airway tissues may be one of the consequences, but not the cause, of impaired gas exchange by endotracheal intubation. The increase in volume of trapped gas in the lung is apparently not mediated by activation of capsaicin-sensitive sensory nerves.     

Unstimulated basophils in atopic and nonatopic subjects express intracellular interleukin-4: detection by flow cytometry

BACKGROUND: IgE-stimulated cultured basophils from atopic subjects are capable of secreting interleukin-4 (IL-4). We describe a flow-cytometric technique which identified intracellular IL-4 in unstimulated basophils unseparated from peripheral blood mononuclear cells (PBMC) in both atopic (AT) and nonatopic (NC) volunteers. METHODS: Freshly isolated PBMC were fixed in 4% paraformaldehyde (PFA). Surface staining with 22E7, a noncompetitive anti-FcepsilonRI-alpha antibody, allowed identification of basophils. Permeabilization by 0.1% saponin allowed staining of intracellular cytokines with specific monoclonal antibodies (mAbs). Two series of experiments utilizing different protocols and anticytokine mAbs were performed. The first protocol required a two-stage fluorochrome staining technique. The availability of fluorochrome-conjugated mAbs allowed a simpler, one-stage labelling procedure for the second protocol. RESULTS: With the first protocol, IL-4 (but not IFN-gamma), immunoreactivity was detectable in a majority (median 77%) of peripheral blood basophils from both AT and NC subjects (n=8). Basophil IL-4 immunoreactivity was again evident in experiment 2 but did not differ significantly between AT and NC subjects--either evaluated as percentage of IL-4+ basophils (AT median=66%, NC median=38.4%, P=0.41) or IL-4-specific mean fluorescence (AT median=0.85, NC median=0.3, P=0.07). CONCLUSIONS: This simple technique allowed the study of intracellular cytokine expression in unstimulated blood basophils. It demonstrated constitutive basophil expression of IL-4 (but not IFN-gamma) in all subjects, with no significant increases in atopics.     

Laparoscopic ultrasonography for abdominal tumor staging

In recent years, laparoscopic ultrasonography has been introduced as an adjunct to diagnostic laparoscopy for staging of tumors of the upper gastrointestinal tract, liver, biliary tree, and pancreas. It has proved feasible to visualize most anatomic structures in the upper abdomen consistently and in detail with laparoscopic ultrasonography. Recent publications indicate that laparoscopic ultrasonography may be useful for detecting small liver metastases, lymph node metastases, small primary tumors of the pancreas and bile ducts, and for the assessment of the local extension of tumors of the pancreas and stomach. The ongoing improvements in US technology and the results of larger studies will in the near future determine the precise place of this new imaging modality for staging of abdominal tumors.     

Microbial O2- and H2O2-electrode sensors for alcohol assays based on the use of permeabilized mutant yeast cells as the sensitive bioelements

Two types of alcohol-specific microbial/electrochemical biosensors have been developed using specially constructed mutant cells of the methylotrophic yeast Hansenula polymorpha. The cells were immobilized in a calcium alginate gel, and placed between two membranes on the surface of oxygen or hydrogen peroxide-electrodes. The O2 electrode based biosensor contained mutant cells with strongly elevated alcohol oxidase activity. The peroxide electrode based biosensor consisted of catalase-defective mutant cells which produce hydrogen peroxide in the presence of alcohol. Both types of mutant cells were used in permeabilized form in order to release some components of the cellular respiration system, thus increasing the selectivity of the cellular respiration response to alcohol (cell/O2-biosensor) Permeabilization also increased sensitivity of the signal and shortened the response time (cell/H2O2-biosensor). Cell/O2 biosensors were linear up to 1.2 mM for ethanol and 0.35 mM for methanol, cell/H2O2 biosensors were linear up to 4.0 mM for ethanol, and 1.2 mM for methanol. Results were reproducible, sample pretreatment was not required, and the sensors exhibited good operational and storage stability. The use of sucrose, dulcitol or inositol during the preparation of the sensors resulted in increased stability of cells during their liophilization and storage in the dried state. Both biosensors had similar selectivity towards alcohols in the order of methanol (100%), ethanol (21%), and formaldehyde (12%). No signal was observed with glucose or glycerol as substrates.