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We have developed and tested a fractionated, purified and deproteinized emulsion of a mycobacterial cell wall (MCW) and report on a controlled study of this compound in the treatment of the experimental R3327-H adenocarcinoma of the prostate. The intraperitoneal route of administration was found ineffective at the weekly dose of 500 micrograms. The intratumoral administration of 1000 micrograms of MCW exhibited significant antitumor activity. Tumors larger than 2.2 cm.3 in volume showed evidence of temporary regression, but no cures were recorded in these animals. Complete tumor regression was found in 50% of the rats with tumor volumes less than 2.2 cm.3 at the onset of treatment. The animals in this group not responding initially were treated with a second 3-week course of MCW which resulted in complete tumor regression in one-half of the animals, for a total cure rate, in the smaller tumor cohort, of 75%. Mycobacterial cell wall is an effective biological response modifier in the Dunning R3327-H adenocarcinoma of the prostate in Copenhagen rats. Additional studies to elucidate the effect of the compound in relation to dose and tumor volume are underway.

Estrogen acts through two molecularly distinct receptors termed estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which bind estradiol with similar affinities and mediate the effects of estrogen throughout the body. ERα plays a major role in reproductive physiology and behavior, and mediates classic estrogen signaling in such tissues as the uterus, mammary gland, and skeleton. ERβ, however, modulates estrogen signaling in the ovary, the immune system, prostate, gastrointestinal tract, and hypothalamus, and there is some evidence that ERβ can regulate ERα activity. Moreover, ERβ knockout studies and receptor distribution analyses in the CNS suggest that this receptor may play a role in the modulation of mood and cognition. In recent years several ERβ-specific compounds (selective estrogen receptor beta modulators; SERM-beta) have become available, and research suggests potential utility of these compounds in menopausal symptom relief, breast cancer prevention, diseases that have an inflammatory component, osteoporosis, cardiovascular disease, and inflammatory bowel disease, as well as modulation of mood, and anxiety. Here we demonstrate an antidepressant-like effect obtained using two SERM-beta compounds, SERM-beta1 and SERM-beta2. These compounds exhibit full agonist activity at ERβ in a cell based estrogen response element (ERE) transactivation assay. SERM-beta1 and 2 are non-proliferative with respect to breast as determined using the MCF-7 breast cancer cell-based assay and non-proliferative in the uterus as determined by assessing the effects of SERM-beta compounds on immature rat uterine weight and murine uterine weight. In vivo SERM-beta1 and 2 are brain penetrant and display dose dependent efficacy in the murine dorsal raphe assays for induction of tryptophan hydroxylase mRNA and progesterone receptor protein. These compounds show activity in the murine forced swim test and promote hippocampal neurogenesis acutely in rats. Taken together these data suggest that ERβ may play an important role in modulating mood and the ERβ specific compounds described herein will be useful tools for probing the utility of an ERβ agonist for treating neuroendocrine-related mood disturbance and menopausal symptoms.

This paper presents a case study of county spending in Wyoming during the 1970s and 1980s to test the applicability of several competing perspectives upon budget policy derived from higher level and more visible governments in the United States. Our findings about the consequences of Wyoming's boom and bust cycle during the 1970s and 1980s for county finances possess several implications for the competing theories of budget policy. Concerning how budgets are made, they confirm the growing consensus that models of “budgetary incrementalism” are inadequate, as well as providing some evidence consistent with the “garbage can” model of decision-making. However, they also suggest that “the baby should not be thrown out with the bath water,” since temporal consistency and incrementalism are evident in several areas. Turning to the factors affecting budget substance, resource base turned out to be the most important factor influencing Wyoming county budgets. Several instances of special social needs and politica...

Reflex sympathetic dystrophy (RSD) or complex regional pain syndrome type 1, is characterized by spontaneous pain or allodynia and hyperalgesia disproportionate to the inciting event, multiperipheral nerve involvement, edema, vasomotor or sudomotor change, and possible loss of function. It has been described in relation to various insults, including a number of infectious and inflammatory conditions. We report a case of a patient who developed RSD 1 week after an exacerbation of hidradenitis suppurativa, a rare chronic inflammatory disease of apocrine sweat glands. The patient responded well to a combination of range-of-motion exercises, thermal modalities, and oral steroids. Hidradenitis suppurativa should be considered when searching for an etiology of new onset RSD.

T-type calcium channels are important in burst firing and expressed in brain regions implicated in schizophrenia. Therefore, we examined the effects of novel selective T-type calcium channel antagonists in preclinical assays predictive of antipsychotic-like activity. TTA-A2 blocked the psychostimulant effects of amphetamine and MK-801 and decreased conditioned avoidance responding. These effects appeared mechanism based, rather than compound specific, as two structurally dissimilar T-type antagonists also reduced amphetamine-induced psychomotor activity. Importantly, the ability to reduce amphetamine's effects was maintained following 20 days pre-treatment with TTA-A2. To explore the neural substrates mediating the observed behavioral effects, we examined the influence of TTA-A2 on amphetamine-induced c-fos expression as well as basal and stimulant-evoked dopamine and glutamate release in the nucleus accumbens. TTA-A2 decreased amphetamine-induced c-fos expression as well as MK-801-induced, but not basal, glutamate levels in the nucleus accumbens. Basal, amphetamine- and MK-801-induced dopamine efflux was altered. These findings suggest that T-type calcium channel antagonism could represent a novel mechanism for treating schizophrenia.

Despite the fact that the Reagan election was viewed as a power shift toward the West, the decade of the 1980s produced cruel disappointment. The region was generally left out of the economic recmery of the nation because of the bust in the agricultural and mineral industries. These state and local gmernments which sufferfrom high costs and low resources were particularly dependent on the national gmernment at the very time when the Reagan Administration was cutting federal aid and transferring power to the states. Unlike Nixon's New Federalism which helped the state and local governments of the West, Reagan's policies caused their relative position in federal aid flows to deteriorate. Although the Reagan revolution in cutting domestic programs was viewed as the embodiment of western rugged individualism, the region lost in terms of federal aid to small rural local governments.

Chronic infections in the urinary environment include medical device related infections, chronic cystitis, chronic prostatitis, and infected struvite stones. Many different uropathogens are associated with these infections, but their common feature is adhesion, followed by growth as microcolonies and biofilms. In acute infections, the disease runs its course before being cleared by antibiotics or host defence mechanisms present at the tissue surface (e.g. the mucous layer and the immune response) and within the urine itself (e.g. low iron levels and high osmolality due to urea) and micturition. Chronic urinary tract infections (UTI) arise when the natural host defences are defective or obstructed by the presence of a foreign object such as a catheter or calculus. In these cases, adherent pathogens are not cleared or eradicated. Rather they coat themselves with an extracellular polysaccharide matrix, and upon growth form encapsulated microcolonies and biofilms. This mode of growth enables the biofilm to be notoriously resistant to both the immune response of the host and to antibiotics. In order to accurately mimic the chronic human UTIs in animals, it is essential that the uropathogens are encouraged to grow in their natural state as biofilms. In this report, several models used to examine chronic biofilm-associated infections are described.

1. Pneumococcus polysaccharides Types I, II and III adsorbed on collodion particles, and Types I and III adsorbed on carbon (norit) are antigenic in mice. 2. Unadsorbed pneumococcus polysaccharide of Type I is antigenic in mice in proper dilution. One preparation of Type II polysaccharide was not antigenic, while another one immunized against Types I and II. Type III polysaccharide was only slightly antigenic against Type III but immunized against Type I. 3. The antigenicity of pneumococcus polysaccharide in optimal dosage is tentatively explained by an adsorption phenomenon taking place in the body in instances in which the polysaccharides had not been adsorbed before injection. 4. The aggressin-like action of large doses of pneumococcus polysaccharides Types I, II and III is further established.

Premature ejaculation (PE) is a common sexual dysfunction. Treatment ranges from behavior modification to systemic and topical pharmacological treatments. Results to date have been generally inconsistent and of limited effectiveness. New avenues of therapy are needed.To investigate the effect of extracorporeal functional magnetic stimulation (FMS) as a noninvasive treatment for men with PE.The NeoControl System for FMS was used in the study. Baseline assessment included: history and physical, medications, hormonal assessment and intravaginal ejaculatory latency time (IVELT) by stopwatch determination. Treatment involved a first phase of five biweekly sessions (primary outcome). Men who reported an improvement in IVELT and desired to continue were given a second identical course (secondary outcome). Outcome measures included: IVELT and a global assessment questionnaire (GAQ). The responses incorporated both the patient's perception of response together with the more objective IVELT timing and were rated as: 1. Worse: no improvement in GAQ or mean IVELT for the total number of attempts; 2. Unchanged: improvement in IVELT but the patient reported no improvement; 3. Slightly improved: increase in IVELT100% and a reported mild improvement and 4. Better: IVELT increase ofor = 100% with GAQ indicating "moderate" to "marked" improvement.Two primary outcome measures were considered in both treatment phases, the IVELT and the GAQ.Fourteen men were treated. Their mean age was 43.7 years. Fifty-seven percent reported primary PE and 63% were circumcised. Hormone levels were normal in all. Baseline IVELT for the group was 60.6 seconds. All patients completed phase I. Of these, 50% reported no change in the GAQ although they recorded an increase in IVELT; 29% were categorized as slightly better and 14% as better. Eight men entered phase II. Of these, 3 (37.5%) were unchanged; 2 (25%) were slightly better and 3 (37.5%) were classified as better. The response in these last three has persisted for over 6 months post treatment. Both phases of the study showed a trend towards IVELT improvement, more evident at the end of phase II. However the differences did not reach statistical significance on either phase. Side effects were mild and non-treatment related.The use of FMS is claimed to alter the spinal centers without altering cerebral neurotransmitters. Although there were some remarkable responses, our results, are not better than the purported responses to behavioral or pharmacological methodologies. There was a clear trend in IVELT improvement; however, this didn't translate into an equivalent subjective estimation by most of the subjects. This outcome dissonance might be diminished by longer/more intense regimens of treatment. The pilot nature of the study does not permit to draw solid conclusions but stimulate the search for a new therapeutic option in PE.

Since the passage of the Nineteenth Amendment, women's representation in public offices has grown slowly, and women are still greatly underrepresented in most states and in the national government. Since 1975, the women's movement has provided impetus for the steady growth in the numbers of women in office. The number of women in Congress, 31, is the highest ever. Women constitute 18 percent of the state legislatures, 17 percent of state executives, 9 percent of county governing boards, and 14 percent of mayors and city councils. The proportion of women in America's Congress is about half the average for national legislative bodies throughout the world. Many theories have been developed to explain the under-representation of women in politics. Political culture, socialization, and role conflict have all had an impact on women's representation. Discrimination against women by political elites and voters has also existed. Finally, the political structure itself forms barriers to the election of women. Current trends, however, are favorable to the continued gradual increase in the number of women in public office.

One of the complications of thermal injury is the development of scars and contractures during the healing process. This scarring can be devastating, especially when it involves the mouth. The purpose of this report is to describe the construction of an alternative vertical mouth stretching orthosis for vertical microstomia. By using thermoplastic splinting material and a long thread screw, a vertical mouth-stretching orthosis can be custom-fit to any patient's mouth. The device can be fabricated for a pediatric or adult patient for the rehabilitation of a circumferential mouth burn, especially targeting the vertical diameter. When using this device, patients gave positive feedback for comfort and ease of use, with increased mouth mobility and range of motion. This vertical orthotic device provides an economical and comfortable alternative for vertical mouth diameter enlargement to the current five devices available in the literature.

Background Recently a novel tryptophan hydroxylase isoform (TPH2) was identified and shown to be highly expressed in the central nervous system (CNS). Hormonal effects on TPH2 mRNA expression in the rodent dorsal raphe nucleus (DRN) are unknown. Methods In situ hybridization histochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the effects of dexamethasone or estradiol on TPH2 mRNA levels in the DRN of C57/Bl6 mice. Results Dexamethasone reduced TPH2 mRNA levels in the DRN of both ovx female and intact male mice. Reduction of TPH2 mRNA in the DRN was blocked by co-administration of mifepristone. Estradiol had no detectable effect on TPH2 mRNA levels in the DRN. Conclusions TPH2 mRNA is regulated by glucocorticoids but not estradiol in the mouse DRN. Glucocorticoid-mediated reduction of TPH2 message may have relevance to the etiology of major depression, psychotic major depression in particular, where elevated glucocorticoids are one hallmark of the disease.

Background Distinct expression patterns of estrogen receptor (ER)-α and ER-β are displayed in the murine central nervous system. ER-β is the predominant form of the receptor expressed in the murine midbrain dorsal raphe nucleus (DRN). Tryptophan hydroxylase (TPH) is abundantly expressed in the serotonergic neurons of the DRN and is regulated by estrogen in both the monkey and the guinea pig. Methods In this study we used immunocytochemistry to show that ER-β and TPH are colocalized in the serotonergic cells of the murine DRN. We utilized the ER-α and ER-β gene deletion mouse models and in situ hybridization to demonstrate that ER-β is responsible for regulating TPH1 mRNA expression. Results Estrogen increased TPH1 mRNA expression in the DRN of wild type and ER-α knockout mice (α-ERKO) but not ER-β knockouts (β-ERKO). Conclusions These data indicate that ER-β is responsible for mediating estrogen regulated TPH1 expression in the murine DRN.

Objectives To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. Methods Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). Results Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. Conclusions This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.

The National Institutes of Health (NIH) chronic prostatitis symptom index was used to determine the prevalence of prostatitis-like symptoms among men (age 20 to 74 years) at risk in a community based study.The study was a cross-sectional postal survey of men age 20 to 74 years in Lennox and Addington counties, which included a large rural area, 1 major town and a suburban area with a stable population of men representative of Canadian demographics. The questionnaire collected information on 2 domains of chronic prostatitis identified in the NIH chronic prostatitis symptom index, including pain (location, severity and frequency), voiding function (irritative, obstructive), demographics, quality of life, general health and health seeking behavior. The self-reported pain score was used to identify prostatitis-like symptoms in the most discriminating domain. Based on analysis of the index final validation study comparing patients with prostatitis to normal controls and those with benign prostatic hyperplasia, the 2 questions most specific for prostatitis, including perineal and/or ejaculatory pain/discomfort, and a total pain score (0 to 21) 4 or greater were used to identify men with significant prostatitis-like symptoms.A total of 2,987 eligible men received the survey, and it was completed by 868 (29%). Of the men 84 (9.7%) were identified as having chronic prostatitis-like symptoms (mean NIH chronic prostatitis symptom index pain score 9.1 +/- 0.3). The average age of the prostatitis population was 50 years compared with 52 years for men without prostatitis-like symptoms. Prevalence was 11.5% in men younger than 50 years and 8.5% in men 50 years or older. Of the sampled population 57 (6.6%) men had prostatitis-like symptoms and an index pain score 8 or greater (moderate to severe). The index voiding score (0 to 10) was 4.1 +/- 0.5 in men younger than 50 years compared with 1.5 +/- 0.1 for normal controls, and 4.7 +/- 0.4 in those 50 years or older compared with 1.9 +/- 0.1 for normal controls. Of the prostatitis group 60% sought medical help for their symptoms.In our opinion this community based study using the new prostatitis symptom index confirms that chronic prostatitis-like symptoms are common.

To investigate the relative efficacy of heparin (H), pentosanpolysulfate (PPS) and hyaluronic acid (HA) in preventing the absorption of 14C labeled urea in protamine pretreated bladders compared with saline pretreated control bladders.Control Group - Rabbit bladders were pretreated with phosphate buffered saline (PBS) followed by instillation of 14C-urea. Radioactivity was determined in blood, bladder and fluid drained from the bladder. Protamine Group - Bladders were pretreated with of PBS followed by protamine sulfate. The bladders were then treated with 14C-urea and radioactivity determined as above. GAG Groups - Bladders were pretreated with saline and protamine as described above followed by instillation of: Group 3A - HA, Group 3B - H and Group 3C - PPS. The bladders were then treated with 14C-urea and radioactivity determined as described above.Protamine treated bladders demonstrated significantly more radioligand uptake in bladder tissue compared with control bladders. There was no significant difference in radioligand uptake in bladders treated with PPS and H compared with control. While not significantly different, there was considerably more radioligand concentration in the blood of rabbits with bladders treated with protamine and protamine-HA compared with those of control rabbits and those treated with protamine-PPS and protamine-H.Exogenous GAG's are effective in providing an epithelial permeability barrier in protamine pretreated bladders. There is a difference in the relative efficacy of the various GAG's in producing this effect.

Epilepsy is the UK's most common serious neurological condition affecting 1 in 131 adults in the UK. Around 75 people are newly diagnosed with the condition every day. Epilepsy can affect anyone, of any age at any time in their life. A diagnosis of epilepsy can have a devastating effect on the individual, his/her lifestyle and his/her family. Antiepileptic drugs (AEDs) are used to stop seizures happening—they do not cure epilepsy.

Confucian societies have a well-deserved reputation for possessing patriarchal cultures which confine women to subordinate roles and almost entirely exclude them from the public sphere. In Taiwan, however, women have done quite well by international standards in winning legislative elections. This paper applies "countersocialization" theory to explain women's growing role in Taiwan's electoral politics. It finds that the careers of women politicians in Taiwan are strongly conditioned by their exposure to countersocialization, primarily in terms of their adult family environments. These findings are quite consistent with the arguments based on socialization theory that women's entrance into public life depends upon an individual psychological reorientation in which "political women" reject traditional cultural norms that limit them to subservient and privatized roles. Such a reorientation can be stimulated by a variety offactors to which an individual woman might be exposed-a mother's role model proving that women can have broader horizons, social and generational change legitimating more active roles, and (most importantly in our data) an adult family and spouse encouraging and supporting her "empowerment" in public affairs.

By analyzing roll call voting behavior and the socioeconomic characteristics of representatives to the 1970 Illinois Constitutional Convention, this study seeks to assess: (1) the roll call cohesiveness of Chicago Democrats and other voting groups in the assembly; (2) the social, economic, and ethnic composition of major voting blocs; and (3) the kinds of issues which may tend to factionalize machine delegates. Factor analysis shows that the Chicago Democratic group was by far the most unified voting set at the Con-Con. However, given the heterogeneous elements which comprised the machine bloc, there were various roll calls—basically revolving around divergent ethnic and religious interests -which promoted substantial disunity in the ranks of the Chicago organization.

While differences between men and women in political behavior have declined, women remain underrepresented in public office in America. Studies indicate that even women in elite positions in political parties have less ambition for elective office than their male counterparts. This article examines the countersocialization theory to see whether politically ambitious women undergo significantly different experiences from non-ambitious women and from ambitious men or whether factors leading to political ambition are the same for both men and women. Men and women state convention delegates in 1984 were asked questions regarding their desire for future elective public offices and their past political experiences. There was a significant difference in the level of political ambition of male and female delegates. However, the causes of political ambition appear to be diffuse, and factors leading to political ambition are similar for both men and women.

A force platform has been used to obtain records of the forces exerted on the ground by running quail. These records, with cinematograph film taken simultaneously, have been used to determine the fluctuations of kinetic and potential energy occurring during a step. This gives a first estimate of the energy required for running. Graphs of force against length changes during a step have been calculated for the major leg muscles, making certain assumptions. These graphs provide a second estimate of the energy required for running, and also show the stresses and strains which probably occur in the muscles. The bending moments required to break the major limb bones have been determined, and compared with the bending moments calculated to occur in running. A mathematical discussion provides estimates of the energy cost of a range of techniques of running.

This paper examines three alternative explanations for the relationship between gender and participation that focus upon: (1) childhood socialization, (2) adult role socialization and (3) structural factors of socioeconomic status. The data analysis of the Verba-Nie study of political participation in America finds some support for all three models, suggesting that the linkages between gender and participation are influences by a complex set of factors. Evidently, the adult role socializaiton and structural perspectives provide a more sophisticated elaboration of childhood socialization theory by specifying conditions that modify the strength of socialization into traditional female roles.

1. The mouse protection test used for the standardization of anti-pneumococcic serum Type I and II is very unreliable. 2. The specific polysaccharide precipitation test can be used to establish the comparative value of a test serum to a standardized serum. 3. The polysaccharide used for such tests does not have to be of the highest purity.

Tillett and Francis1,2 showed that patients suffering with pneumonia who were injected intracutaneously with small amounts of pneumococcus polysaccharide of the homologous and heterologous types, showed after some time antibodies not only against the infecting type of organism but against the other types. In explanation they suggested that probably the injections of the heterologous polysaccharides produced antibodies.Finland and Sutliff3 confirmed these findings and in addition4 showed in humans with histories free of recent infection antibody production following the intracutaneous injection of protein-free type specific polysaccharides of either Type I, II, or III Pneumo-cocei.The present study deals with antibody response following intracutaneous injection of a type specific polysaccharide of Pneumococ-cus Type I prepared according to the method of Heidelberger, Sia and Kendall.5 Using the same dose as that used by Tillett and Francis1 in their work on cutaneous reaction to pneumococcus polysaccharide...

This book argues that the capacity of a country to develop, and the levels of economic and social development achieved, depend more on the institutional parameters within which the development policies are implemented than on the policies themselves. It contends that forces of globalisation influence individual countries' economic and social institutions.