Inhibitory effects of chemically-different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Frog (Rana catesbeiam) corneas were mounted in an Ussing chamber, modified to facilitate dissection and to avoid edge damage to the epithelial tissue during mounting and measurements. When bathed in Conway solution of pH 7.4 the corneas displayed highly stable electrical properties, with a transepithelial potential difference (PD) of 16.6 ± 1.0 mV and a short-circuit current (SCC) of 10.3 ± 0.8 μA cm^-2. The DC resistance was 2.0 ± 0.15 k. cm² (mean ± SE, n= 45). An increase in the intracellular cyclic AMP level induced by prostaglandin E₂ and by 3-isobutyl-i-methylxanthine (IBMX) resulted in an increase in SCC. Ortho-vanadate, an inhibitor of Na⁺-K⁺-ATPase, reduced SCC. The acidic loop diuretics furosemide, bumetanide and the le vorotatory form of indacrinone (MK-196) reduced SCC byaboutso%at concentrations of 500,100 and 46 μM, respectively. The (–)form of MK-196 was four times more active than the (+)form. Dimethylation of the SO₂NH₂ group reduced the activity of bumetanide. The basic diuretics muzolimine (Bay G 2821) and MK-447, were found, similarly, to reduce SCC by about 50% at concentrations of 500 μM. In view of their ‘high ceiling’ type of saluretic effects in whole animals, these basic agents should therefore be classified as ‘loop’ diuretics. The effects of these structurally highly different ‘loop’ diuretics are similar in epithelia which secrete (cornea) and in those which absorb (the renal thick ascending limb of Henle's loop; TALH) chloride ions. This could indicate that they interact with the same ‘diuretic receptor’ and have a common mode of action in both types of epithelia. Moreover, their effects on chloride transport parallel their saluretic effects. Amphibian cornea should therefore be a convenient model tissue for studies of the modes of action and the structure-activity relationships of loop diuretics.     

Underlay tympanoplasty with the graft lateral to the malleus handle

In conventional underlay tympanoplasty the graft is placed medial to the malleus handle. The present study evaluates the results of a modification of this technique, in which the graft is placed lateral to the malleus handle, which has been dissected from the drum remnants. 39 ears with predominantly large or anterior pars tensa perforations were operated upon in this manner. After a median observation time of 20 months one ear was found to have a small reperforation. All ears had normal tympanomeatal angles, but 12 ears showed a small degree of laterofixation of the graft from the malleus handle. Analysis of the hearing showed good hearing improvement and no adverse effects attributable to the dissection of the ossicular chain. It is concluded that the technique is a good alternative to conventional underlay myringoplasty in ears with perforations involving the area anterior to the malleus handle.     

Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy

Abstract. To study the possible importance of variation at the apolipoprotein (apo) E gene locus for the clinical expression of heterozygous familial hypercholesterolaemia (FH), we determined apo E phenotype and serum lipoprotein pattern in 120 patients with FH. The allele frequency of the patients studies were: ε2 0.033, ε3 0.733, and ε4 0.233. There was no influence of apo E phenotype on the serum concentrations of total, VLDL, LDL or HDL cholesterol, triglycerides, or of apo AI, B or (a). Serum concentrations of apo E were significantly higher in patients with the apo E 3/3 phenotype compared to those with apo E 4/3 or 4/4, and the highest concentrations were found in patients carrying the ε2-allele. The cholesterol-lowering response to therapy with cholestyramine or pravastatin was not related to apo E phenotype. It is concluded that variation at the apo E gene locus is not of major importance for the expression of heterozygous FH.     

Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial

BACKGROUND: Oral anticoagulants, such as dabigatran etexilate, an oral, direct thrombin inhibitor, that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism (VTE) after total knee replacement surgery. METHODS: In this randomized, double-blind study, 2076 patients undergoing total knee replacement received dabigatran etexilate, 150 mg or 220 mg once-daily, starting with a half-dose 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery, for 6-10 days. Patients were followed-up for 3 months. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and mortality during treatment, and the primary safety outcome was the incidence of bleeding events. RESULTS: The primary efficacy outcome occurred in 37.7% (193 of 512) of the enoxaparin group versus 36.4% (183 of 503) of the dabigatran etexilate 220 mg group (absolute difference, -1.3%; 95% CI, -7.3 to 4.6) and 40.5% (213 of 526) of the 150 mg group (2.8%; 95% CI, -3.1 to 8.7). Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion. The incidence of major bleeding did not differ significantly between the three groups (1.3% versus 1.5% and 1.3% respectively). No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up. CONCLUSIONS: Dabigatran etexilate (220 mg or 150 mg) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery.     

Mutans streptococci colonization associates with the occupation of caretaker,a practise‐based study

International Journal of Paediatric Dentistry 2010; 20: 144–150 Background. The early mutans streptococci (MS) bacteria colonization is connected to early childhood caries. The aim of this study is to examine associations between the MS‐colonization and background factors in young children, in order to enhance the oral health program in a low caries prevalence community. Subjects and Design. An age cohort of 512 children was screened for MS in the oral biofilm at the age of 18 months. The caretakers were, using a structured form, interviewed of demographical factors and habits connected to oral health: antibiotic treatments, child’s appetite, frequency of night feeding, use of sugary products or drinks, and maternal xylitol use. The associations were evaluated with logistic regression analysis. Results. Mutans streptococci colonization was significantly associated with both the occupation of the caretaker and the non‐Finnish background. Conclusion. The early MS‐colonization, in preschool children, strongly associates with the socioeconomic status of the family.     

Improved Angiographic Measurement Accuracy with a New Calibration System

During transcatheter interventions, correct distance measurements are mandatory for proper device selection. We present a new calibration procedure in which distance calibration is performed with a high contrast metallic rod placed in the esophagus as a scaling device. Distortion related to differences in Calibration and object planes as well as axial angles were analyzed and appropriate correction factors calculated. A cardiac phantom served to test the accuracy and precision of the new measuring system. The mean measurement error was < 1.7% (range 0.1%–4.9%), and the mean measurement variability 1% (range 0.3%–1.9%). The accuracy of angiographic measurements can be significantly improved using a calibration device in the esophagus in combination with appropiate mathematical corrections.     

Does early exposure to cat or dog protect against later allergy development?

BACKGROUND: It is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested. OBJECTIVES: To assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7-9 and 12-13 years of age. METHODS: The prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the G?teborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7-9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub-sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed. RESULTS: Children exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7-9 years of age and of asthma at 12-13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12-13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis. CONCLUSION: Pet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.     

IgG and IgM Antibody Responses to Pneumococcal Vaccination in Splenectomized Children and in Children Who Had Non-Operative Management of Splenic Rupture

ABSTRACT. The IgG and IgM type specific anticapsular pneumococcal antibody titres were studied with ELISA during one year following vaccination with a 14-valent pneumococcal polysaccharide vaccine in four different patient groups: 41 children splenectomized after a traumatic rupture, 16 splenectomized because of disease, 15 non-surgically managed after splenic rupture, and 19 healthy controls. Serum samples were obtained before vaccination and after 14, 60, 180, and 360 days. The IgG antibody responses were equally good in all of the patient groups, while the IgM antibody responses were less pronounced in the splenectomized. In the non-surgically managed patients, the IgM antibody titres after vaccination, as well as antibody responses per se, were significantly higher for all 12 pneumococcal types studied than in the patients who were splenectomized. Both the IgG and the IgM antibody titres were highest at 14 days after vaccination. However, while the IgG titres for most pneumococcal types remained elevated at 360 days, the IgM titres soon fell to prevaccination levels. The antibody response was less good for the types 3 and 6 A. The results indicate that the IgG antibody response to pneumococcal polysaccharide vaccination is unaffected in splenectomized individuals, but the IgM antibody response is decreased. In patients with a healed traumatically damaged spleen, both the IgG and IgM responses seem to be normal.     

Congenital Malformations in Diabetic Pregnancy: the Clinical Relevance of Experimental Animal Studies

ABSTRACT. The aim of this work was to present recent observations on the occurrence of malformations in the offspring of diabetic rats and to discuss these findings in the light of present clinical experience. Comparison of malformation rates between different substrains of Sprague-Dawley rats showed marked differences in the occurrence of diabetes-induced malformations. These findings suggest that congenital malformations in diabetic pregnancy may result from a teratological insult in genetically predisposed individuals. Recent clinical reports seem to link facial malformations to an increased incidence of sacral-caudal malformations in human diabetic pregnancy. The present rat model, which exp- both these aberratio—Ucro-pathia and sacral dysgenesic-may therefore be a useful tool in studies of the aetiological relationships between disturbed maternal metabolism and skeletal malformations in the offspring. Malformations in fetuses of diabetic animals seem to arise from teratogenic insult(s) early in pregnancy. Hyperglycemia and hyperketonemia may both singly, and in combination, be of teratological significance. Insulin itself does not appear to be directly teratogenic. Furthermore, there is evidence to suggest that disturbed levels of trace metals, primarily zinc, may be a significant factor in the production of congenital malformations. The increased rate of malformations in diabetic pregnancy, therefore, appears to be multifactorial in origin.