Ionized magnesium levels and the ratio of ionized calcium to magnesium in asthma patients before and after treatment with magnesium.

OBJECTIVE: Prior studies have been equivocal about the efficacy of magnesium therapy in acute asthma exacerbations. We hypothesize that pretreatment ionized magnesium (Mg(2+)) levels and/or the ratio of ionized calcium to ionized magnesium (Ca(2+)/Mg(2+)) may have been confounding variables in these previous studies. Here, we report on the incidence of abnormal divalent ion levels in our asthma population. MATERIAL AND METHODS: The study was designed as a randomized, double-blind, placebo-controlled trial of intravenous magnesium. Inclusion criteria were: age >18 years, percentage predicted forced expiratory volume (FEV(1)) <75 % after an initial beta-agonist. African-American patients (AA) at an urban university hospital were randomized to 2 g IV Mg or placebo. Mg(2+) and Ca(2+)/Mg(2+) levels were measured pre- and post-infusion. Data were reported as means+/-SD. Student's t-test and Fisher's exact test were used where appropriate (alpha = 0.05, two tailed). RESULTS: Fifty-five AA patients (mean age of 42.7 years+/-15.6 years, range 18-75 years) were studied. A significantly (p<0.05) lower level of Mg(2+) was found in asthma (AS) patients compared with that in the AA group, by 0.03 mmol/L (95 % CI, 0.007-0.053 mmol/L). The AS group had a mean increase in Ca(2+)/Mg(2+) ratios over the AA group, of 0.27 (95 % CI, 0.16-0.38); 100 % of patients with abnormal divalent ion levels were corrected with IV magnesium. CONCLUSIONS: We identified a subgroup of asthmatic patients with significant abnormalities in their divalent ion concentrations, which was corrected with IV magnesium.

Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.

PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole cell potassium currents that were blocked by glibenclamide (10 microM.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of heart disease in Latin America. T. cruzi-induced microvascular compromise, in turn, is thought to play a major role in chagasic heart disease. Previous in vitro studies have implicated endothelin-1 (ET-1) as a potentially important vasomodulator present in increased levels in the supernatant of T. cruzi infected cultured human umbilical vein endothelial cells (HUVEC). Thus, the goal of the present investigation was to further evaluate the potentially important contribution of ET-1 to T. cruzi-induced alterations in vascular tone in vitro. Bioassay studies once again documented that exposure of isolated rat aortic rings to infected HUVEC supernatants elicited contractile responses whose steady-state magnitude was significantly greater than contractile responses elicited by exposure of aortic rings to uninfected HUVEC supernatants. Furthermore, the increased aortic contractility was significantly attenuated by the presence of the ET(A) subtype selective antagonists BMS-182,874 or BQ-123. Additionally, incubation of HUVEC with either verapamil or phosphoramidon prior to infection was also associated with reduced aortic contractility, upon exposure to the supernatant. Phosphoramidon, but not verapamil, produced a significant decrease in the measured ET-1 levels in the HUVEC supernatant. Consistent with the bioassay results, preincubation of Fura-2-loaded cultured rat aortic vascular smooth muscle cells with verapamil resulted in a near complete ablation of ET-1-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-1-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.

Further evidence for the selective disruption of intercellular communication by heptanol.

The lack of selective gap junctional uncoupling agents has hampered evaluation of the contribution of intercellular communication to pharmacomechanical coupling and vascular contractility. Thus we further explored the utility and selectivity of heptanol as a gap junctional uncoupling agent in isolated rat aortic rings. Fifty-two aortic rings were obtained from 15 rats and were precontracted to approximately 75% of maximum with phenylephrine (PE). When contraction achieved steady state (approximately 5 min), a single concentration of heptanol (200 microM) was added to each aortic ring at 1- to 3-min intervals for up to 42 min post-PE addition. At early time points (5-10 min after PE), heptanol elicited an approximately 50% loss of tension (i.e., relaxation). At subsequent time points post-PE, a gradual and time-dependent decrease in the magnitude of the heptanol-induced relaxation was observed until, after approximately 40 min, addition of heptanol was associated with little, if any, detectable relaxation. Linear regression analysis of the magnitude of the heptanol-induced relaxation vs. the square root of the elapsed time interval (from addition of PE) revealed a highly significant negative correlation (P < 0.001, R = 0.81). Studies conducted on KCl-precontracted aortic rings revealed no detectable heptanol-induced relaxation after development of the steady-state KCl-induced contraction. These data extend our previous observations to further document the potential utility of heptanol as a "relatively selective" uncoupling agent.

On the putative mechanistic basis for intraoperative propofol-induced penile erections.

Propofol is an hypnotic drug used in anesthesia which was noted to induce marked vasodilation in vivo and in vitro, and to elicit intraoperative penile erections. The goal of this study was to assess the putative mechanistic basis for this later observation by confirming its action in vivo in a rat model of penile erection, as well as by studying its effects in vitro on cultured human corporal smooth muscle cells and isolated corporal tissue strips. In vivo experiments were conducted on Fisher 344 rats anesthetized with sodium pentobarbital or propofol. Intracavernosal pressure was recorded during current stimulation of cavernous nerves. A significant increase in the intracavernous pressure response was recorded at all levels neurostimulation, ranging from 1-10 mA. In vitro experiments were conducted utilizing digital imaging microscopy to assess the effects of propofol (3-12 micrograms/mL) on ET-1-induced (50 nM) intracellular Ca2+ transients [Ca2+]i in Fura-2-loaded cultured human corporal smooth muscle cells (passage 3-4) as well as to evaluate the effects of propofol on phenylephrine (PE)-induced contractile responses on isolated corporal tissue strips. With respect to the former, resting cytosolic calcium levels were not altered during preincubation with propofol alone at clinically effective concentrations (12 micrograms/mL). However, propofol produced a concentration-dependent decrease in the peak amplitude of the transient ET-1-induced (50 nM) [Ca2+]i response (P < 0.001). Preincubation of the cells with calcium free/EGTA (1 mM) buffer produced a reduction in the peak amplitude of the ET-1-induced [Ca2+]i transient (55.5 +/- 6% (n = 10 cells, P < 0.01)) which was indistinguishable from that produced by 8 micrograms/mL of propofol (53.4 +/- 5.6% (n = 12 cells, P < 0.01)). However, propofol had no effect on the histamine-induced [Ca2+]i response. Lastly, preincubation of isolated human corporal tissue strips with propofol (100-200 microM; 30 min) caused a significant diminution in the peak amplitude of the PE-induced contractile response. Taken together, these data indicate that the mechanistic basis for intraoperative penile erections observed with propofol may be related, at least in part, to altered transmembrane calcium flux through voltage-dependent calcium channels, and thus, decreased corporal smooth muscle tone.

Efficacy of a sonic toothbrush on inflammation and probing depth in adult periodontitis.

This single-blind, 8-week study compared the efficacy of a sonic toothbrush and a manual brush in 40 patients with adult periodontitis. Qualitative clinical indices and quantitative laboratory methods were used to monitor the periodontal status of 3 pockets 5 to 7 mm deep in each subject. Patients were randomly assigned either a sonic or manual toothbrush. The two groups were comparable with respect to age, gender, and anatomical location of the test sites. Data were collected from all sites at baseline and at 2, 4, and 8 weeks. Over the 8-week period, both groups showed significant improvements in the clinical indices used. Descriptive statistics indicated the sonic brush group had greater improvement than the manual group in the clinical parameters (gingival index, bleeding index, probing depth, and clinical attachment level). Gingival crevicular fluid (GCF) flow was significantly lower in the sonic brush group (P = 0.018). Considerable variation was present in the levels detected for both inflammatory cytokines tested, however, concentration of interleukin-1 beta was significantly lower in the GCF of sonic group patients (P = 0.05), while concentration of interleukin-6 was significantly reduced in both groups (P < or = 0.05) (t tests). Under these conditions, there is some evidence to suggest that the sonic toothbrush is more beneficial in resolving inflammation in patients with moderate periodontal disease.

[Multi-profile analysis of survival rate and cause of death in patients with non-Hodgkin's lymphoma]. / Mnogoprofil'nyi analiz vyzhivaemosti i prichin smerti bol'nykh nekhodzhkinskimi limfomami.

A relationship has been established between the survival rate of 378 patients who had died of non-Hodgkin's lymphoma (NHL) and their sex, age, ABO- and Rh-factors of the blood, primary focus of the tumor lesion, morphological variant, diagnostic period duration, and the treatment intensity. A higher incidence rate and a higher mean survival were recorded in 222 males, as compared to 156 females. Favourable and unfavourable for survival age interval has been distinguished for NHL disease. Patients with Rh+ showed a higher survival rate, although the incidence rate among Rh+ and Rh- subjects was similar. Prognostically favourable and unfavourable sites of the primary tumor and morphological variants of NHL were specified. The time spent for detailed verification of the diagnosis has been justified, and the presence of a direct proportional relationship between the intensity of the treatment and the mean survival of patients with varying forms of NHL has been proved.

Assessment of serum antibody patterns and analysis of subgingival microflora of members of a family with a high prevalence of early-onset periodontitis.

In a study of members of a large family with a high prevalence of early-onset periodontitis, we sampled the subgingival microflora and characterized 40 isolates from each sample. We surveyed serum samples by enzyme-linked immunosorbent assay for antibodies reacting with any of a panel of 21 periodontal bacteria. The mother and 7 of her 13 children had early-onset periodontitis. Bacteroides gingivalis was not detected in the subgingival flora of any affected or unaffected family member, and Actinobacillus actinomycetemcomitans was isolated from only one affected child. Capnocytophaga ochracea was isolated from five of seven affected children and from none of their normal siblings. We found no significant differences among the floras from family members who had rapidly progressive, juvenile, and prepubertal forms of periodontitis. Elevated levels of serum antibody reacting with one or more of the bacteria tested were found in all family members with disease, but in only one periodontally normal family member. Both children with prepubertal periodontitis had antibodies reacting with C. sputigena, a species not found in their subgingival floras, but with none of the other bacteria tested. All remaining affected family members had antibodies to one or more serotypes of A. actinomycetemcomitans, and four had antibodies reacting with additional bacteria, including C. sputigena, Eikenella corrodens, Fusobacterium nucleatum, and Haemophilus aphrophilus. Sera from patients contained antibodies specific for putative periodontal pathogens not found in their pocket flora, and conversely, putative periodontal pathogens for which no serum antibodies were found frequently comprised a large proportion (10% or more) of the pocket flora. In no case were both the bacterium and its antibody found. These observations are suggestive of sequential infection in the early-onset forms of periodontitis and of induction of protective immunity against reinfection by the same microorganism.

Clinical studies of one family manifesting rapidly progressive, juvenile and prepubertal periodontitis.

We report clinical, radiographic and historical data on a large family with an unusually high prevalence of periodontitis. The proband, a 20-year-old black male, had the classic features of juvenile periodontitis (JP). His father was periodontally normal, while his mother had lost all her teeth at age 27 because of rapidly progressive periodontitis (RP). In addition to the 13 living children the couple had had 2 miscarriages. Of the children, one had RP, five had JP and two had prepubertal periodontitis (PP). Both maternal grandparents of the proband had become edentulous at an early age, presumably because of early-onset periodontitis. Four of 10 siblings of the proband's mother had early-onset periodontitis. In contrast, the paternal grandparents did not have early-onset periodontitis nor was periodontitis unusually prevalent in the siblings of the proband's father. The pedigree for this family is consistent with, but does not prove, an X-linked dominant pattern of genetic transmission. The natural history of early-onset periodontitis and the relationship among PP, JP and RP are not understood. The fact that the mother of the proband had RP and she had offspring with RP, JP and PP indicates a close relationship among these diseases and argues in favor of a common underlying mechanism. JP was not preceded by PP in the proband nor his affected 21-year-old brother, but one sister had PP, and at age 15 manifested JP. In her case, the alveolar bone around the deciduous molars had been destroyed, but it regenerated as the permanent premolars erupted.(ABSTRACT TRUNCATED AT 250 WORDS)