Prospective, randomized, single-blind, sham treatment-controlled study of the safety and efficacy of an electromagnetic field device for the treatment of chronic low back pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of therapeutic electromagnetic fields (TEMF) on chronic low back pain. Secondary objectives included the investigation of the effects of TEMF on psychometric measures. SETTING: Pain Research center in an Urban Academic Rehabilitation Facility. DESIGN: Prospective, randomized, single-blind, placebo (sham) treatment-controlled design in which participants were evaluated over a 6-week period. A total of 40 subjects were randomly assigned: 20 subjects to 15 milliTESLA (mT) treatment using a prototype electromagnetic field device and 20 to sham treatment. INTERVENTIONS: After a 2-week baseline period, eligible individuals were randomized to one of the treatment groups (sham or 15 mT) for six 30-minute treatments over 2 weeks, then a 2-week follow-up period. OUTCOME MEASURES: The primary outcome measure was the self-report of pain severity using a 100 mm visual analog scale collected using a twice daily McGill Pain Questionnaire-Short Form. Several secondary measures were assessed. RESULTS: Both groups (15 mT and sham) improved over time (P < 0.05). Although groups were similar during the treatment period, treated subjects (TEMF of 15 mT) improved significantly over sham treatment during the 2-week follow-up period (20.5% reduction in pain; F(1,34) = 10.62, P = 0.003). There were no reported serious adverse events. CONCLUSIONS: This study demonstrates that TEMF may be an effective and safe modality for the treatment of chronic low back pain disorders. More studies are needed to test this hypothesis.

The analysis of factors influencing the success of diagnosing salpingemphraxis by x-ray hysterosalpingography.

OBJECTIVE: The factors influencing the diagnosing of salpingemphraxis by X-ray hysterosalpingography (HSG) are identified and summarized, to provide a reference for improving the precision of the diagnosis procedure. PATIENTS AND METHODS: In order to analyze the collected data, the methods of stratified sampling and retrospective analysis were adopted. Two county-level medical units, two medical units in prefecture-level cities and two provincial medical units in our province were chosen. Patients were selected from a group of women diagnosed with infertility and probable salpingemphraxis who were admitted to a hospital for further studies between February 2010 and January 2015. From those, 3 individual cases were selected in each month summing up to a total of 1,080 cases. Surgical processes and results were analyzed to identify the determining factors that lead to a precise diagnosis. RESULTS: The success rate of the surgical procedures had nothing to do with the trauma level of hospitals, instead it is positively correlated with the period of sampling (p < 0.05). The precision of surgeries correlates with the age group of the patients, the selection time bracket of samples, the types of contrast agents used, the location of the salpinx, whether anticholinergic agents are used before operations, the depth of catheter with double-cavity saccule, and the procedures for injecting contrast agents (p < 0.05). On the other hand, the precision of the surgeries has nothing to do with the level of hospitals, the types of X-ray machines used or the types of salpingemphraxis. Through multi-factor regression analysis, it can be seen that the selection time period of samples, the location of the salpinx, whether anticholinergic agents are used before operations, the depth of catheter with double-cavity saccule and the procedures for injecting contrast agents are independent risk factors that determine the precision of the procedure (p < 0.05). CONCLUSIONS: Clinical factors that seem to influence the precision of HSG are proposed based on analysis of a large sample in a small area using a stratified sampling method.

Gastric antisecretory agents. 2. Antisecretory activity of 9-[(aminoalkyl)thio]-9H-xanthenes and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines.

A series of 9-[(aminoalkyl)thio]-9H-xanthenes (3-6) and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines (7-10) possessing gastric antisecretory activity in the rat and dog is described Many of the compounds possessed good activity in the pylorus-ligated rat and several inhibited histamine-stimulated gastric acid secretion in the dog. The mechanism of acid secretion inhibition is not related to anticholinergic or histamine (H2) receptor antagonism.

Antiulcer agents. 3. Structure-activity-toxicity relationships of substituted imidazo[1,2-a]pyridines and a related imidazo[1,2-a]pyrazine.

Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

Fluorescence imaging of reactive oxygen metabolites generated in single macrophage cells (NR8383) upon phagocytosis of natural zeolite (erionite) fibers.

In this paper we address the phenomenon of reactive oxygen metabolite generation subsequent to phagocytosis of mineral fibers by macrophages. Natural erionite fibers were chosen because of their established toxicity. Macrophages (cell line NR8383) were loaded with the dye 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate and exposed to erionite particles by centrifuging cells and fibers together to effect adherence. Reactive oxygen metabolite generation was examined by monitoring the fluorescence of oxidized dye formed via the reaction with oxygen species produced during phagocytosis. Individual cells were repeatedly scanned for up to 2 hr to monitor the evolution of this fluorescence. It was found that erionite-exposed cells had a mean total fluorescence of three times that of controls during the first 35 min, declining to two times that of controls at 35-60 min and about the same level as that of controls at 60-80 min. Ultrastructural studies of similarly treated aliquots of cells showed marked variation in size and numbers of the phagocytized particles. This study demonstrates that intracellular oxidation can be monitored on a single cell basis over a period of time. Quantitative studies are in progress to establish the relationship between the phagocytized particulate load and the extent of fluorescence.

Multifocal polyostotic aneurysmal bone cysts in a llama.

A 3.3-year-old 125-kg castrated male llama was evaluated because of acute non-weight-bearing lameness on the left hind limb. Physical examination revealed crepitus in the midportion of the femur. On radiographs, a comminuted middiaphyseal fracture was seen. There was also a region of bone lysis with cortical thinning and expansion in the distal metaphysis and epiphysis of the left femur. Multiple small circular lesions were observed in the proximal metaphysis of the left femur, and the proximal portion of the left tibia appeared irregular. The owner elected to pursue treatment, and the fracture was repaired with 2 compression plates. Multiple bone biopsy specimens were obtained and submitted for bacterial culture and histologic examination. Cultures yielded neither bacteria nor fungi. Histologic examination revealed fibrous connective tissue, normal appearing cortical bone, and an absence of medullary structures. The llama was maintained in a hind-limb sling for 14 days after surgery, at which time follow-up radiography revealed a comminuted fracture of the proximal portion of the femur. The llama was euthanatized, and multifocal polyostotic aneurysmal bone cysts were found in the proximal and distal metaphyses of the left femur and tibia. Cysts were lined by fibroblasts or endothelial-like cells.

Migration and the phases of population redistribution.

PIP: This paper describes a framework for major historical settlement patterns, the major stages of population redistribution that accompany such migration, and the other forms of migration that occur within a given settlement pattern. Using a top-down approach has the advantage of tying together a number of diverse types and patterns of migration from differing historical periods and geographic areas. This broad macro level framework is one in which the level of social and economic interaction increases with economic development. With increasing economic development comes the need for greater interaction through the exchange of goods and the establishment of commercial and administrative functions for society. Explanation of the changing trends in population redistribution requires a detailed look at the phases of population redistribution: 1) initial urbanization, 2) frontier expansion, 3) traditional urbanization, 4) overurbanization, 5) suburbanization, and 6) metropolitan and nonmetropolitan turnaround. Less massive migration movements occur within a given settlement pattern as adjustments are made in the population distribution to reflect the relative economic fortunes of competing subunits of the society. In addition, migration may occur with little or no population redistribution because the net migration cancels out a differential in natural increase between subunits, or because the gross in-migration and out-migration cancel out and produce close to zero net migration. Lastly, research on the current migration turnaround from metropolitan to nonmetropolitan areas, emphasizing the change in social interactions from face to face contact to a society in which a large portion of interactions can be performed at a distance, is suggested.^ieng

The Canada-United States joint immigration study: issues in data comparability.

PIP: The Canada-US immigration project is an attempt to assess carefully the flows, trends, and characteristics of immigrants between the 2 countries. The primary focus for data is the census information derived from the 1980 US and 1981 Canadian censuses. Some observations of the comparison follow. 1) US-born immigrants tend to migrate later. 2) Immigrants have an older age structure than the total population. 3) The sex ratio pattern is similar with older migrants having lower ratios. 4) Immigration of elderly/retired is not a common pattern. 5) Changes in regional destinations is a basic feature of immigration flows. The destination of US immigrants shifted over time from northern states to southern states. Destinations of Canadian immigrants shifted over time from Quebec and prairie provinces to Ontario and British Columbia. 6) A higher proportion of US immigrants ever married and were widowed; higher proportions of Canadian immigrants divorced, and lower proportions separated. These aspects reflect age structure. 7) US immigrants' fertility is similar to the US population in general; Canadian immigrants' fertility is similar to the Canadian population in general. 8) US immigrants born in Canada have a considerably higher attainment. 9) Males aged 16-64 among US immigrants born in Canada have a consistently higher labor force participation rate. 10) Professional specialty occupations increase in importance in the 1975-1980 period in both countries. 11) Incomes of recent immigrants who were full-time, year-round workers from Canada or the US were well above the incomes of the native populations of either country. Comparability had to be examined in light of the variations built into the 2 censuses. Some of these issues are: 1) differences in sampling and collection methods, 2) differences in under/over-enumeration, 3) misreporting of country of birth, 4) differences in questions used, 5) different editing and imputation procedures applied, 6) variations in residence rules, and 7) the exclusion or inclusion of certain groups in the national census counts.^ieng

Comparative demographic effects of Canadian-U.S. immigration flows.

"A joint study by Statistics Canada and the U.S. Bureau of the Census examines special tabulations of U.S. residents born in Canada from the 1980 census of the United States and compares them with matching tabulations of Canadian residents born in the United States from the 1981 census of Canada. As might be expected, the two populations are remarkably similar and the preponderance of the migration flow is from Canada to the United States. The comparative social and economic characteristics of the two migrant stocks show the effects of increasing legal restrictions on migration between the two countries in the last two decades. The characteristics of the migrant flows have changed from large, unregulated population movements responding to economic motivations similar to internal migration flows to a much smaller, highly controlled movement more typical of long-distance international migration flows." This is a revised version of a paper originally presented at the 1987 Annual Meeting of the Population Association of America.

Cisapride for gastroesophageal reflux disease: a placebo-controlled, double-blind study.

OBJECTIVES: To evaluate the safety and efficacy of cisapride in patients with gastroesophageal reflux disease. METHODS: Patients (N = 177) were randomized to double-blind treatment with cisapride (10 or 20 mg q.i.d.) or placebo for 12 wk. Efficacy was determined by pre- and poststudy endoscopies, symptom assessments by patient and physician, and Maalox consumption. Safety evaluations included vital signs, electrocardiograms, clinical laboratory tests, and reports of adverse events. RESULTS: Cisapride 10 mg significantly reduced daytime and nighttime heartburn at 4 wk compared with placebo. Cisapride 20 mg reduced both daytime and nighttime heartburn at 4, 8, and 12 wk, compared with placebo, and was also significantly superior to the 10-mg dose at 12 wk. The percent of patients with endoscopic healing was significantly higher with cisapride 20 mg than with placebo [healing: 51 vs 36% (p < or = 0.044)]. Maalox usage declined significantly with cisapride 20 mg compared with placebo. No clinically significant changes in safety variables occurred with cisapride. The most frequently reported adverse events in the cisapride group were diarrhea, headache, and sinusitis. CONCLUSIONS: Cisapride 10 and 20 mg q.i.d. were safe and well tolerated in a population of patients with mild-to-moderate gastroesophageal reflux disease. Both symptoms and endoscopic grade improved after 12 wk of treatment with cisapride 20 mg q.i.d.

A survey of Census Bureau population projection methods.

"Population projections methods of the U.S. Census Bureau draw upon several different traditions of forecasting: demographic accounting, judgmental, time series, deterministic, and explanatory. This paper reviews each of the forecasting traditions in population projections, describes the U.S. Census Bureau's current methods for national and state population projections, and proposes new hybrid approaches such as demographic-time series methods for national fertility projections and economic-demographic methods for state migration projections. Throughout the article, possible parallels with forecasting in other disciplines are noted."

Urinary excretion and tissue accumulation of gentamicin and paraaminohippurate in postischemic rat kidneys.

Unilateral renal ischemia was induced in rats by clamping the left renal artery for 20, 60, and 120 min, respectively. One hour after the arterial clamp was removed, renal handling of gentamicin and paraaminohippurate (PAH) was studied over the next 2 hours; the kidneys were removed at the end of the experiments for determination of gentamicin and PAH content. The ischemic damage was evidenced by morphologic and functional changes. The glomerular filtration was decreased in proportion to the severity of ischemic injury. The excretion of gentamicin was highly correlated with GFR in normal and postischemic kidneys. In the cortex, ischemic injury resulted in reduced concentrations of gentamicin but markedly augmented those of PAH. The finding is consistent with the hypothesis that gentamicin is reabsorbed by the epithelial cells through the luminal membrane, whereas PAH enters via the peritubular membrane. In contrast, medullary concentrations of both compounds were similar, with suppression of uptake seen only after 120 min of ischemia. Conclusion. Ischemic damage impairs urinary elimination of gentamicin and the ability of renal parenchyma to retain the drug. Difference in uptake between gentamicin and PAH were unmasked in the postischemic kidneys.

Effects of hydration on gentamicin excretion and renal accumulation in furosemide-treated rats.

The effect of furosemide on gentamicin excretion and tissue accumulation was studied with clearance techniques in anesthetized rats, at two different infusion rates of saline or Ringer solution. Gentamicin ( approximately 20 mg/kg) was administered by constant intravenous infusion over a period of 3 h. With the low fluid infusion rate, furosemide (25 mg/kg intravenously) caused severe reduction in glomerular filtration rate and diminished urinary output of gentamicin. Serum and renal tissue levels of the antibiotic were significantly elevated. High fluid infusion prevented the decline of the glomerular filtration rate, with near normalization of all measurements. A fluid deficit incurred by furosemide was noted at both the low and high infusion rates. Complete correction of this fluid deficit by continuous adjustment of the infusion rate fully restored normal renal handling of gentamicin. These results suggest that furosemide had no direct effect on renal excretion of gentamicin. In comparison, renal handling of gentamicin in rats did not respond to changes in the rate of fluid infusion in the absence of furosemide therapy. It appears that gentamicin excretion and gentamicin accumulation in the renal cortex in furosemide-treated rats, in contrast with those in untreated rats, are influenced significantly by the rate of fluid infusion. Fluid administration sufficient to maintain the glomerular filtration rate was found to be necessary for appropriate gentamicin elimination, with consequent reduction in serum and renal tissue levels of the drug.

Influence of prednisolone on ethanol-induced gastric injury in the rat.

The purpose of the present study was to investigate the effect of prednisolone on gastric injury induced by ethanol in the rat. Gastric damage was produced by oral administration of 1 ml of absolute ethanol to rats previously fasted for 24 hr and deprived of water for 19 hr. The severity of the ethanol-induced gastric damage varied considerably within the vehicle-treated group of rats which served as controls. Prednisolone, administered orally as a single dose 15 min before alcohol challenge, significantly decreased the number of rats which developed severe lesions. Prednisolone was effective in increasing the resistance of the gastric mucosa to ethanol when given from 1 to 60 min before alcohol. The steroid proved ineffective when 90 min elapsed between prednisolone and ethanol administration, or when the steroid was given at the same time (0 min) as alcohol. The dose-response curve for prednisolone plateaued at high doses. Our results suggest that a prostaglandin-mediated endogenous cytoprotective potential exists in the rat gastric mucosa. Prednisolone may enhance the degree of mucosal protection afforded by this mechanism.

Effect of corticosteroids on indomethacin-induced intestinal ulceration in the rat.

A single dose of indomethacin induces a severe gastrointestinal syndrome in the rat, characterized by intestinal ulceration, perforation, and death. The mechanism by which indomethacin induces this syndrome is unclear, although it has been suggested that a loss of mucosal integrity leads to inflammation and necrosis of the intestinal wall. The purpose of the present investigation was to study the effect of corticosteroids on indomethacin-induced ulceration. Prednisolone administered orally, even as a single dose (10 mg/rat), significantly reduced the severity of ulceration following indomethacin. This protective effect was most pronounced when prednisolone was administered 1 hr postindomethacin and decreased as the period between indomethacin and prednisolone administration increased. Of the steroids studied, the rank order of efficacy in reducing the severity of indomethacin-induced ulceration was paramethasone acetate > betamethasone > prednisolone. Hydrocrotisone was not significantly effective at the doses ultilized. Our results suggest that corticosteroids exert a cytoprotective effect on intestinal mucosa similar to that produced by prostaglandins.

Effects of prostaglandin and kinin synthesis inhibitors on renal responses to furosemide in normal and low-sodium rats.

The role of renal prostaglandin (PG) and kallikrein-kinin systems in the renal effects of furosemide was assessed indirectly by using known inhibitors of synthetic pathways in conscious rats supplemented with physiological saline (2.0% body wt.). In normal rats oral pretreatment of indomethacin or meclofenamic acid (cyclooxygenase inhibitors) each at 10 mg/kg failed to alter the diuretic and natriuretic responses to furosemide (10 and 30/kg, p.o.). In contrast, the natriuretic and diuretic actions of furosemide in sodium-deficient rats were greatly inhibited by indomethacin and by meclofenamic acid independent of changes in endogenous creatinine excretion. Aprotinin (2..0 x 10(5) KIU/kg, s. c.), an inhibitor of kallikrein formation, did not impair the natriuretic and diuretic responses to furosemide in either normal or low-sodium rats. Additionally aprotonin did not influence the antagonistic effects of indomethacin against furosemide in low-sodium rats. These results suggest that the renal PG system but not the kallikreinkinin system is necessary for furosemide to produce optimal diuretic and natriuretic effects during sodium restriction.

In vitro interaction of zeolite fibers with individual cells (macrophages NR8383): measurement of intracellular oxidative burst.

Inhalation of fibrous minerals such as asbestos and erionite can cause various lung diseases, including cancer. The mechanism by which these fibers induce disease is an area of active research. Interaction of fibers with lung macrophages leads to release of many substances. Among these, reactive oxygen metabolites (which include hydrogen peroxide, superoxide, and possibly hydroxyl radicals) are proposed to cause cellular damage. In this paper, we report a method for observing intracellular hydrogen peroxide release as rat lung-derived macrophages (NR-8383) phagocytize erionite fibers. This is possible by observing the fluorescence of 2',7'-dichlorofluorescein-the intracellular, oxidized form of 5 (and 6)-carboxy-2', 7'-dichlorodihydrofluorescin formed in the presence of newly released hydrogen peroxide. We are able to image the fluorescence within a single cell, thereby allowing us to get information on the spatial distribution of the metabolites.