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Background: The isolation of microsatellite markers remains laborious and expensive. For some taxa, such as Lepidoptera, development of microsatellite markers has been particularly difficult, as many markers appear to be located in repetitive DNA and have nearly identical flanking regions. We attempted to circumvent this problem by bioinformatic mining of microsatellite sequences from a de novo-sequenced transcriptome of a butterfly (Euphydryas editha)., Principal Findings: By searching the assembled sequence data for perfect microsatellite repeats we found 10 polymorphic loci. Although, like many expressed sequence tag-derived microsatellites, our markers show strong deviations from Hardy-Weinberg equilibrium in many populations, and, in some cases, a high incidence of null alleles, we show that they nonetheless provide measures of population differentiation consistent with those obtained by amplified fragment length polymorphism analysis. Estimates of pairwise population differentiation between 23 populations were concordant between microsatellite-derived data and AFLP analysis of the same samples (r = 0.71, p<0.00001, 425 individuals from 23 populations)., Significance: De novo transcriptional sequencing appears to be a rapid and cost-effective tool for developing microsatellite markers for difficult genomes.

The burden of constipation from the patient's perspective has been well described. The aim of this study was to evaluate the cost of managing constipation in patients taking opioids in a specialist palliative care inpatient unit. A retrospective review of the medical records of 58 patients (70 admissions) who died during a six-month period was undertaken to identify prescribing patterns for opioids and oral laxatives and tasks associated with managing constipation in these patients. A prospective time and motion study also was undertaken, whereby staff recorded the time and resources required to perform each task. These data were then applied to the actual frequency recorded in the retrospective review to calculate the direct cost of managing constipation in those 70 admissions during that six-month period. There was no discernable pattern in oral laxative prescribing. The mean cost of managing constipation was 29.81 pounds (48.74 USD) per admission, with staff time accounting for 85% of the cost. The most time-consuming activity was staff discussion about bowel management, which occurred at least once daily for doctors and twice for nurses and involved up to eight members of staff at a time. The cost of managing constipation is skewed in that it costs 30 pounds (49 USD) or less in 71% of admissions but exceeded 100 pounds (163 USD) in 5%. In the latter group, earlier and/or more effective intervention for constipation could lead to clinical and economic benefits., (Copyright (c) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

In this paper, an attempt is made to establish the direction of causality between a range of psychological factors and aircraft noise annoyance. For this purpose, a panel model was estimated within a structural equation modeling approach. Data were gathered from two surveys conducted in April 2006 and April 2008, respectively, among the same residents living within the 45 Level day-evening-night contour of Amsterdam Airport Schiphol, the largest airport in the Netherlands (n=250). A surprising result is that none of the paths from the psychological factors to aircraft noise annoyance were found to be significant. Yet 2 effects were significant the other way around: (1) from 'aircraft noise annoyance' to 'concern about the negative health effects of noise' and (2) from 'aircraft noise annoyance' to 'belief that noise can be prevented.' Hence aircraft noise annoyance measured at time 1 contained information that can effectively explain changes in these 2 variables at time 2, while controlling for their previous values. Secondary results show that (1) aircraft noise annoyance is very stable through time and (2) that changes in aircraft noise annoyance and the identified psychological factors are correlated.

Nicotine has been found in many studies to improve cognitive function. However, some studies have not found this effect and others have seen nicotine-induced impairments. Systemic administration bathes the brain with drugs. However, the brain is quite intricately organized with various regions playing very different roles in the bases of cognitive function. We have examined the role of nicotinic receptors in a variety of brain areas for memory. In the hippocampus and amygdala, local infusions of both alpha7 and alpha4beta2 antagonists methyllyaconitine (MLA) and dihydro-beta-erythroidine (DHbetaE) significantly impair memory. In the current studies we locally infused acute and chronic doses of MLA and DHbetaE into the mediodorsal thalamic nucleus and tested memory function on a 16-arm radial maze. The rats also received systemic nicotine to determine the impact of more generalized nicotine effects. Since nicotinic treatments are being developed for cognitive impairment of schizophrenia, interactions were studied with the antipsychotic drug clozapine. In the acute study, the 6.75 microg/side of DHbetaE improved working memory. Co-administration of MLA reversed the DHbetaE-induced improvement. Chronic DHbetaE infusions into the mediodorsal thalamic nucleus also improved working memory. Systemic nicotine reversed this effect. Clozapine had no significant interaction. Nicotinic alpha4beta2 receptors in the mediodorsal thalamic nucleus appear to play an opposite role with regard to working memory than those in the hippocampus and amygdala. Heterogeneity in response to nicotinic drugs given systemically may be due to anatomically distinct nicotinic systems in the brain and their unique roles in the neural bases of cognitive function.

This study reports the development of a simple Chinese Prognostic Scale (ChPS) for predicting survival in advanced cancer patients. Data relating to 1,019 advanced cancer patients referred to a palliative home care service were retrospectively analyzed. The records were divided into two sets using stratified random sampling: 80% as a "training set" for developing the scale and 20% as a "testing set" for validating it. Demographic data, symptoms/signs, Karnofsky Performance Status (KPS), quality of life (QOL), and survival time were statistically analyzed to create the scale. In the training set, a total of 10 prognostic factors were determined: weight loss, nausea, dysphagia, dyspnea, edema, cachexia, dehydration, gender, KPS, and QOL. The ChPS score was calculated for each case by summing the partial scores of prognostic factors, ranging from 0 (no altered variables) to 124 (maximal altered variables). The score for a cutoff point of three months' survival was 28 (95% confidence interval: 26.6, 28.9). When scores were more than 28, survival appeared to be usually less than three months. The accuracy rate was 69.4% in the training set and 65.4% in the testing set. In conclusion, it is possible with this prognostic scale to guide physicians in predicting more accurately the likely survival time of Chinese cancer patients, and to help policy makers in establishing appropriate referral for hospice care.

Activated oncogenic signaling is central to the development of nearly all forms of cancer, including the most common class of primary brain tumor, glioma. Research over the last two decades has revealed the particular importance of the Akt pathway, and its molecular antagonist PTEN (phosphatase and tensin homolog), in the process of gliomagenesis. Recent studies have also demonstrated that microRNAs (miRNAs) may be responsible for the modulation of cancer-implicated genes in tumors. Here we report the identification miR-26a as a direct regulator of PTEN expression. We also show that miR-26a is frequently amplified at the DNA level in human glioma, most often in association with monoallelic PTEN loss. Finally, we demonstrate that miR-26a-mediated PTEN repression in a murine glioma model both enhances de novo tumor formation and precludes loss of heterozygosity and the PTEN locus. Our results document a new epigenetic mechanism for PTEN regulation in glioma and further highlight dysregulation of Akt signaling as crucial to the development of these tumors.

Evidence-based medicine demands 'gold standard' randomized controlled trials (RCTs). If strict criteria of quality, validity, and size are met, observational studies give the same result. Given the dearth of RCTs in palliative care, our aim was to identify good observational studies using PubMed searches and e-mail letters to experts in palliative care. The prior intention was provide the most comprehensive description possible to date of observational studies in palliative care, rather than to perform any statistical analyses. Three hundred and forty abstracts of study reports were identified, of which 27% (91) included > or = 200 subjects and 8% (27) > or = 1000 subjects. In reports with > or = 200 subjects, 51% included only cancer patients, and 42% included heterogeneous 'palliative care' patients. Prospective and retrospective studies accounted for 38% and 32% of all reports with > or = 200 subjects. In reports with > or = 1000 subjects, 59% were retrospective and 19% prospective. Patients had some input in 26% of studies with > or = 200 subjects, and 15% with > or = 1000 subjects. Only 12 prospective reports had one specific intervention. We found that palliative care is deficient not only in RCTs, but also good quality observational studies. Those that exist are extremely heterogeneous in subject, design, outcome reporting, and intervention.

Background: In contemporary medical research, randomised controlled trials are seen as the gold standard for establishing treatment effects where it is ethical and practical to conduct them. In palliative care such trials are often impractical, unethical, or extremely difficult, with multiple methodological problems. We review the utility of Cochrane reviews in informing palliative care practice., Methods: Published reviews in palliative care registered with the Cochrane Pain, Palliative and Supportive Care Group as of December 2007 were obtained from the Cochrane Database of Systematic Reviews, issue 1, 2008. We reviewed the quality and quantity of primary studies available for each review, assessed the quality of the review process, and judged the strength of the evidence presented. There was no prior intention to perform any statistical analyses., Results: 25 published systematic reviews were identified. Numbers of included trials ranged from none to 54. Within each review, included trials were heterogeneous with respect to patients, interventions, and outcomes, and the number of patients contributing to any single analysis was generally much lower than the total included in the review. A variety of tools were used to assess trial quality; seven reviews did not use this information to exclude low quality studies, weight analyses, or perform sensitivity analysis for effect of low quality. Authors indicated that there were frequently major problems with the primary studies, individually or in aggregate. Our judgment was that the reviewing process was generally good in these reviews, and that conclusions were limited by the number, size, quality and validity of the primary studies.We judged the evidence about 23 of the 25 interventions to be weak. Two reviews had stronger evidence, but with limitations due to methodological heterogeneity or definition of outcomes. No review provided strong evidence of no effect., Conclusion: Cochrane reviews in palliative care are well performed, but fail to provide good evidence for clinical practice because the primary studies are few in number, small, clinically heterogeneous, and of poor quality and external validity. They are useful in highlighting the weakness of the evidence base and problems in performing trials in palliative care.

Previous research has stressed the relevance of nonacoustical factors in the perception of aircraft noise. However, it is largely empirically driven and lacks a sound theoretical basis. In this paper, a theoretical model which explains noise annoyance based on the psychological stress theory is empirically tested. The model is estimated by applying structural equation modeling based on data from residents living in the vicinity of Amsterdam Airport Schiphol in The Netherlands. The model provides a good model fit and indicates that concern about the negative health effects of noise and pollution, perceived disturbance, and perceived control and coping capacity are the most important variables that explain noise annoyance. Furthermore, the model provides evidence for the existence of two reciprocal relationships between (1) perceived disturbance and noise annoyance and (2) perceived control and coping capacity and noise annoyance. Lastly, the model yielded two unexpected results. Firstly, the variables noise sensitivity and fear related to the noise source were unable to explain additional variance in the endogenous variables of the model and were therefore excluded from the model. And secondly, the size of the total effect of noise exposure on noise annoyance was relatively small. The paper concludes with some recommended directions for further research.

Purpose of Review: Chronic cough is common and distressing, especially against the background of life-threatening illness. It is a symptom that has received scant attention, often eclipsed by pain, breathlessness, nausea and vomiting., Recent Findings: This paper reviews the recent literature in cough research: its mechanism, assessment and management. There is so little research from supportive and palliative care that much of our knowledge is extrapolated from research elsewhere. Objective measurement of cough has been facilitated by advances in measuring devices, while subjective assessment tools including cough-specific quality of life questionnaires are now available. These are practical, simple to use and can be incorporated into daily practice. A few drugs have come in and out of favour but there has been no solid advance in therapeutic options in over a decade., Summary: The availability of simple assessment tools places the imperative on clinicians to be more systematic in assessment of cough and its interventions. The mainstay of oral therapy for symptom control remains dextromethorphan, codeine and morphine. The potential for research is huge: from basic scientific understanding to clinical trials of innovative therapies.

Background: Noisy breathing (death rattle) occurs in 23 to 92% of people who are dying. The cause of death rattle remains unproven but is presumed to be due to an accumulation of secretions in the airways. It is therefore managed physically (repositioning and clearing the upper airways of fluid with a mechanical sucker) or pharmacologically (with anticholinergic drugs)., Objectives: To describe and assess the evidence for the effectiveness of interventions used to treat death rattle in patients close to death., Search Strategy: Randomised controlled trials (RCTs), before and after studies and interrupted time series (ITS) studies in adults and children with death rattle were sought by MEDLINE (1966 to 2007), EMBASE (1980 to 2007), CINAHL (1980 to 2007), the Cochrane Pain, Palliative and Supportive Care Trials Register and the Cochrane Central Register of Controlled Trials. In addition, the reference lists of all relevant trials and reports were checked and investigators who are known to be researching this area were contacted for unpublished data or knowledge of the grey literature., Selection Criteria: RCTs, controlled before and after studies and ITS reporting the outcome of pharmacological and non-pharmacological interventions for treating death rattle., Data Collection and Analysis: Data was extracted by two independent review authors and trials were quality scored. There was insufficient data to carry out an analysis., Main Results: Thirty studies were identified, of which only one study met the inclusion criteria. This small study was a randomised placebo-controlled trial of the use of hyoscine hydrobromide in patients with death rattle. Hyoscine hydrobromide tended to reduce death rattle compared to placebo but this was not significant. A larger randomised study, comparing atropine, hyoscine butylbromide and scopolamine, is in progress., Authors' Conclusions: There is currently no evidence to show that any intervention, be it pharmacological or non-pharmacological, is superior to placebo in the treatment of death rattle. We acknowledge that in the face of heightened emotions when death is imminent, it is difficult for staff not to intervene. It is therefore likely that the current therapeutic options will continue to be used. However, patients need to be closely monitored for lack of therapeutic benefit and adverse effects while relatives need time, explanation and reassurance to relieve their fears and concerns. There is a need for more well-designed multi-centre studies with objective outcome measures and the ability to recruit sufficient numbers.

People move to another house for different reasons. It is sometimes presumed that a process of self-selection might take place on the basis of noise sensitivity, i.e., sensitive people would either leave high noise areas or not move into these areas in the first place. Thus, a "survivor population" would remain in the high noise areas. This research aims to investigate whether such a process can be observed in the Netherlands. The study does not show evidence of a process of self-selection based on noise sensitivity. Nevertheless, the results suggest that noise-sensitive people are less satisfied with their living environment and are more willing to move than those who are not noise sensitive. Due to the limited sample size, external validity is limited.

The management of 'death rattle' was reviewed by a task group on behalf of the Association for Palliative Medicine's Science Committee. Evidence was searched for the effectiveness of various anti-muscarinic drugs in drying oropharyngeal and bronchial secretions in dying patients. Clinical guidelines were constructed based on evidence from volunteer and clinical studies. Death rattle occurs in half of all dying patients and some response occurs in around 80% of treated patients. Clinical studies demonstrate that subcutaneous hyoscine hydrobromide 400 microg is more effective at improving symptoms at 30 min than glycopyrronium 200 microg by the same route. Volunteer studies demonstrate that intramuscular glycopyrronium 400 microg is as effective in drying secretions at 30 min as a dose of 200 microg given intravenously. Duration of response is shortest for hyoscine butylbromide (1 h) and longest for glycopyrronium (more than 6 h). There is insufficient evidence to support the use of one drug over another in a continuous infusion and prescribers should base decisions on different characteristics of each anti-muscarinic drug.

The results of a retrospective study of fall incidence during a 1-year period in a psychiatric hospital in Singapore are reported, involving 309 patients who fell one or more times during their stay. The profile of inpatients involved in falls was identified. Data were derived from standard incident forms completed whenever patients had a fall. A total of 348 falls were identified for the 1-year period. Results revealed higher fall rates in younger male epileptic patients; elderly female patients, age 70 and older with depression or dementia; individuals with concomitant medical conditions; and patients taking three types of medication. The majority of falls occurred when the activity level was high in the ward. Young epileptic patients and elderly depressed patients were prone to repeated falls. These results have the potential to assist in identifying patients at high risk and in designing and implementing strategies to prevent such incidents.

Ninety-two strains of lactic acid bacteria (LAB) were isolated from a Malaysian food ingredient, chili bo, stored for up to 25 days at 28 degreesC with no benzoic acid (product A) or with 7,000 mg of benzoic acid kg-1 (product B). The strains were divided into eight groups by traditional phenotypic tests. A total of 43 strains were selected for comparison of their sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) whole-cell protein patterns with a SDS-PAGE database of LAB. Isolates from product A were identified as Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus farciminis, Pediococcus acidilactici, Enterococcus faecalis, and Weissella confusa. Five strains belonging to clusters which could not be allocated to existing species by SDS-PAGE were further identified by 16S rRNA sequence comparison. One strain was distantly related to the Lactobacillus casei/Pediococcus group. Two strains were related to Weissella at the genus or species level. Two other strains did not belong to any previously described 16S rRNA group of LAB and occupied an intermediate position between the L. casei/Pediococcus group and the Weissella group and species of Carnobacterium. The latter two strains belong to the cluster of LAB that predominated in product B. The incidence of new species and subspecies of LAB in chili bo indicate the high probability of isolation of new LAB from certain Southeast Asian foods. None of the isolates exhibited bacteriocin activity against L. plantarum ATCC 14917 and LMG 17682.

Several genetic mutations in mice and rats that produce lifelong growth hormone (GH) deficiency result in overexpression of GH-releasing hormone (GHRH) mRNA in hypothalamic arcuate nucleus neurons. In order to examine the development of this condition, GHRH mRNA expression was quantified in Ames dwarf (df/df) and normal (DF/?) mice at 1 (day of birth), 3, 7, 14, 21 and 60 postnatal days (d) following in situ hybridization. Total mRNA was assessed using computer-assisted densitometry after X-ray film autoradiography, and mRNA expression per neuron was quantified by counts of grains per cell after emulsion autoradiography. Total GHRH mRNA was the same in dwarf and normal mice at 1, 3 and 7d. GHRH mRNA in dwarfs increased at 14d to 240% of that in DF/? (p < 0.005); the percentage overexpression in dwarf mice remained >/=200% through 60d, although total GHRH mRNA increased in both dwarfs and normals during this period. GHRH mRNA per neuron was the same in normal and dwarf mice at 1d, then increased in dwarfs to 190% of that in normals at 3d (p < 0.05), and rose to 300% of normal levels by 7d and beyond (p < 0. 005). There was no sexual dimorphism in expression by either measure in normal or dwarf mice. These results indicate that an increase in GHRH mRNA in Ames dwarf mice is first detectable at 3d, a period of approximately 7d after the failure to initiate GH production, which occurs normally at embryonic day 17.5. The onset of GHRH overexpression occurs earlier than the decline of either hypophysiotropic somatostatin or dopamine in Ames dwarf mice. This difference may be due to the stimulatory action of GHRH, as opposed to the inhibitory effects of factors examined previously.

Lifelong deficiency of growth hormone (GH) in spontaneous or transgenic dwarf mice has been shown to be accompanied by reduced hypophysiotropic somatostatin (somatotropin release-inhibiting hormone, SRIH) expression in hypothalamic anterior periventricular nucleus (PeN). However, the postnatal developmental pattern of SRIH expression in the absence of GH is unknown. Therefore, SRIH mRNA levels in GH-deficient Ames dwarf (df/df) mice and normal (DF/?) littermates were determined both in adults, to compare with other GH-deficient models, and at selected days of postnatal development, to determine the effects of GH deficiency on SRIH neuron development. DF/? and df/df mice of both sexes at postnatal ages 1, 3, 7, 14, 21 and 60 days (adult) were examined. In situ hybridization and image analysis were used to quantify the relative abundance of total SRIH mRNA in the PeN, and SRIH mRNA per cell was determined in PeN and medial basal hypothalamus (MBH). In adult df/df mice, total PeN SRIH mRNA was 45% (p < 0.05) of that in DF/? littermates, which is consistent with studies of other GH-deficient dwarf mice. In developing animals, SRIH expression in the PeN of DF/? mice began at 3 days of age and increased at subsequent ages to reach adult levels. In df/df mice, PeN SRIH mRNA levels at 60 days were significantly greater than at 1-21 days of age (p < 0.05). However, levels were not different over 1-21 days of age, and were consistently lower in df/df than DF/? mice. The difference in total PeN SRIH mRNA between df/df and DF/? mice was statistically significant at 7 days, and at each subsequent age. There were no differences between DF/? and df/df mice in the number of grains per cell in either PeN or MBH at any age. Thus, the reduced total hypophysiotropic SRIH mRNA in GH-deficient Ames dwarf mice appears developmentally shortly after initial detectability of SRIH in the PeN. Because SRIH mRNA per cell was the same for DF/? and df/df mice, the decreased total mRNA in dwarfs suggested reduced SRIH cell numbers in PeN, which was corroborated by immunocytochemical findings. The reduction of SRIH in df/df mice at 7 days of age suggests that GH production during embryonic or very early postnatal development is important to activation of PeN SRIH transcription.

Acute studies of GH removal by hypophysectomy or GH replacement in adult rats have shown that GH has a positive influence on its hypothalamic inhibitory hormone somatostatin (SRIH). The present study was undertaken to assess the effect of lifelong exposure to elevated GH on the development and differentiation of SRIH-producing hypothalamic neurons, including comparison of differing GH levels and heterologous species of GH. Expression of somatostatin peptide and mRNA was evaluated using respective immunocytochemistry and in situ hybridization in brains of transgenic mice bearing constructs of either human (hGH) or bovine (bGH) linked to metallothionein (MT) promoter or bGH linked to phosphoenolpyruvate carboxykinase (PEPCK) promoter. Nontransgenic littermates served as controls. All transgenic constructs resulted in high levels of circulating heterologous GH and significantly elevated body weights. Both bGH levels and body weights were higher in PEPCK-bGH than in MT-bGH mice; mean weights were not different between MT-bGH and MT-hGH mice. Numbers of SRIH-immunoreactive neurons in the hypophysiotropic periventricular nucleus (PeN) of transgenic mice showed a two-fold increase (P < 0.01) relative to control animals; the number of SRIH-positive cells in the medial basal hypothalamus (MBH) was comparable for transgenic and control mice. Total SRIH mRNA in situ hybridization intensity also showed a two-fold increase (P < 0.05) in the PeN of all transgenic mice compared with controls, and was not elevated in the MBH. The higher levels of GH produced in PEPCK-bGH transgenic mice led to greater weight gain, but not to greater SRIH expression than in other GH-transgenic mice, suggesting that the increased SRIH cell number and mRNA in the PeN of MT-GH-transgenic mice may represent a plateau of maximal feedback stimulation. The results indicate that lifelong elevated heterologous GH in mice stimulates hypothalamic SRIH expression markedly. It is not known whether this mechanism is direct or indirect via a mediator of GH such as IGF, but the heterologous GH appears to be specific to these hypophysiotropic neurons.

Two hundred and ninety-nine patients admitted to the Bradbury Hospice, Hong Kong, during the period from 1 June 1992 to 31 May 1993 were studied. While a majority of the patients held realistic expectations of the hospice service, a small percentage expected cure, prolongation of life or even euthanasia. Physical symptoms were the main concern in a vast majority of patients, the commonest being pain. Only 1.7% regarded psycho-social problems as their main distress. Morphine was widely used for pain control, although 68% of patients required co-analgesics or palliative radiotherapy as well. Morphine was also the mainstay of treatment for dyspnoea. It might be worthwhile for hospices to be equipped with oxygen, as approximately 71% of our patients with dyspnoea as their main distress benefited from oxygen therapy. Many patients expressed fear of death; more worried about suffering. While 17.7% were assessed to be in the stage of acceptance on admission, 14.7% expressed self-pity when their search for meaning failed. Although many patients were atheists, a majority of patients with religious beliefs found that they could get support from their faith. A significant number of patients believed in Shumei. Increased knowledge of this religion would be helpful in taking care of these patients.

The effects of the muscarinic antagonist scopolamine on lordosis, solicitation, pacing, approach, attractivity, and activity were evaluated in ovariectomized rats brought into sexual receptivity with estrogen and progesterone. Systemic (1 mg/rat) or intraventricular (10 micrograms bilaterally) administration of scopolamine significantly reduced the incidence of lordosis and solicitation behaviors and disrupted typical pacing of sexual contacts with a stimulus male. In addition, females avoided contact with a stimulus male, but not a stimulus female, following intraventricular infusion of scopolamine. The levels of general activity and frequencies of sexual contacts were similar in females treated intraventricularly with scopolamine and vehicle solutions. Consequently, scopolamine disrupted various components of sexual behavior, including lordosis, solicitation, pacing, and approach, without altering female attractivity or general activity.

Daily late afternoon injections of melatonin (25 micrograms/day s.c.) were found to reduce the number of cells expressing estrogen receptor immunoreactivity in the medial preoptic area of ovariectomized inbred (LSH/SsLak) golden hamsters. Employing immunocytochemical analysis with the H222 monoclonal antibody to the human estrogen receptor, we examined the effects of melatonin on estrogen receptor expression in the hypothalamus, particularly the medial preoptic area, of ovariectomized virgin female hamsters. Analysis of the results showed that melatonin administration induced a 50-70% decrease in numbers of estrogen receptor-immunoreactive neurons in the medial preoptic area of ovariectomized female hamsters. Furthermore, an overall qualitative decrease in the intensity of estrogen receptor immunoreactivity was observed. In intact regularly cycling female hamsters used to monitor the efficacy of melatonin treatment, there were significant reductions in the serum levels of FSH, LH, and prolactin as measured by radioimmunoassay and in uterine and pituitary weights after 8 wk of melatonin treatment. These results suggest that melatonin may exert its anti-reproductive effects in hamsters by modulating estrogen receptor levels in medial preoptic area neurons, thus influencing steroid feedback mechanisms.

Aorta-common femoral artery bypass is the standard operation for relief of aortoiliac occlusive disease. When extensive superficial femoral artery disease coexists, the profunda femoris, even in its distal portion, may be used as the outflow vessel. To test this assumption we compared cumulative patency, limb salvage, and the need for distal bypass of 134 aorta-profunda femoris and 151 aorta-common femoral artery bypasses performed consecutively for aortoiliac occlusive disease over a 12-year period. We also analyzed results of proximal (n = 103) and distal (n = 31) aortoprofunda bypasses. Angiographic and noninvasive studies showed greater disease in limbs undergoing aorta-profunda femoris bypass. However, no difference was observed in cumulative patency (91% +/- 6% vs 96% +/- 3%) or limb salvage (90% +/- 6% vs 94% +/- 3%) at 5 years. Seventeen distal bypasses in the group undergoing profunda femoris bypass and 20 distal bypasses in the group undergoing common femoral artery bypass were required to maintain limb salvage. Proximal and distal aorta-profunda femoris bypasses showed no difference in cumulative patency (91% +/- 9% vs 95% +/- 6%) or limb salvage (94% in each group) at 3 years. Standard aorta-common femoral artery and aorta-profunda femoris bypass provide cumulative patency and limb salvage exceeding 90% at 5 years; concomitant or subsequent distal bypass was required in 12% or limbs undergoing aorta-profunda femoris bypasses. Both proximal and distal profunda femoris arteries provide a durable outflow tract when aortoiliac and femoropopliteal occlusive disease are combined.

The cholinergic agonist, carbachol, induces phase-dependent shifts in the timing of the circadian rhythm of locomotor activity (CRLA). The effects of carbachol injections into the lateral ventricles of hamsters were compared between circadian times that produce phase delays vs. phase advances in the CRLA. The shape of the dose-response curves and the ED50 for carbachol injections were similar for the two injection times. The second experiment demonstrated the dose-dependence of phase advances produced by carbachol injections into the area of the suprachiasmatic nucleus. These results indicate that carbachol exerts similar dose-dependent actions for both phases advances and phase delays.

Treatment with the short-acting benzodiazepine, triazolam, has been found to induce changes in both behavioral and endocrine circadian rhythms in hamsters. The objective of this study was to determine if these effects of triazolam could be generalized to other short-acting benzodiazepines. Therefore, the effects of midazolam on the biological clock of the hamster were examined in detail. A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light. Midazolam injections produced maximal phase advances at circadian time (CT) 6 and 9 and maximal phase delays at CT 15 and 21. Doses of 2.5 mg or larger produced phase shifts that were significantly different from those produced by the vehicle controls. In addition, the phase-shifting effects of midazolam were completely blocked by administration of the benzodiazepine receptor antagonist, RO 15-1788, indicating that the phase-shifting actions of midazolam are mediated via benzodiazepine receptors. These results indicate that the previously reported effects of triazolam on the circadian clock can be generalized to other short-acting benzodiazepines.

Ventral spinal roots at all spinal levels in humans contain many unmyelinated axons, as do all spinal roots of the cat which have been examined. Rats, however, have fewer unmyelinated fibers in cervical and certain lumbar ventral roots. To determine if unmyelinated fibers are distributed uniformly in ventral roots of the cat, cervical and lumbar ventral roots were examined by light and electron microscopy, and axons were counted. Lesions were made to determine the origin of unmyelinated fibers in ventral root L6. From 5 to 15% of the axons in cervical ventral roots are unmyelinated. This distribution of unmyelinated fibers in the cat is similar to the distribution in humans, although the cervical ventral roots of the cat contain relatively fewer unmyelinated fibers than the cervical ventral roots of humans. Approximately 24% of the axons in ventral root L6 are unmyelinated. More than 90% of these axons degenerate proximal to, but not distal to, a ventral rhizotomy and ipsilateral to a dorsal root ganglionectomy. Thus, most unmyelinated axons in ventral root L6 appear to rise from dorsal root ganglion cells. Much variation in the number and percent of unmyelinated axons in ventral roots at the same spinal level exists between individual cats and between opposite sides of the same cat.

Sex differences and differences related to genotype have been observed in the nervous system. These observations provide the opportunity to relate differences in neural structure to functional differences. The spinal nucleus of the bulbocavernosus (SNB) was examined in castrated and gonadally intact male house mice from the following 3 genotypes: C57B1/6J, DBA/2J, and the B6D2F1 (F1) hybrid (resulting from a cross between a C57B1/6J female and a DBA/2J male). The number and size of SNB neurons were determined from thionin-stained thick sections from spinal cords of these mice. The gonadally intact DBA males had significantly fewer SNB motoneurons than either the C57 or F1 males, but no strain differences were observed for the size of SNB cells. Castration of adults significantly reduced SNB neuronal number, but not somatic area, in the C57s (the maternal strain) and reduced somatic area, but not neuronal number, in the DBAs (the paternal strain). Both characteristics of the SNB were reduced by castration in the F1 hybrid. Thus, the size and number of SNB neurons appear to be inherited independently and the influence of gonadal hormones on these traits varies with genotype.

The effects of light on the circadian system may involve the neurotransmitter acetylcholine (ACh). The purpose of the present study was to determine whether carbachol, a cholinergic agonist, mimics the phase-shifting effects of light on the circadian rhythm of locomotor activity (CRLA) in the Djungarian hamster. Phase response curves (PRCs) were measured for blind animals injected intracerebroventricularly with either vehicle or carbachol at different circadian times. Carbachol produced significant phase delays in the CRLA when administered at circadian time (CT) 12-16 and small, but significant phase advances when given at CT 8. No consistent phase shifts were observed in response to carbachol injections at other circadian times. Phase shifts produced by carbachol injections at CT 8 and 12 were similar for both sighted and blind animals. Light pulses to sighted hamsters produced phase advances at CT 20 and phase delays at CT 12. Both the carbachol PRC and the PRC for light pulses in the Djungarian hamster have phase delay regions in the early subjective night. However, these two PRCs have different phase advance regions. These results indicate that carbachol mimics some of the effects of light on the circadian system in the Djungarian hamster and support the hypothesis that cholinergic mechanisms may play a role in mediating some of the phase-shifting effects of light on the circadian clock of mammals.

The reduction of masculine sexual behavior following castration varies widely among genotypes. In contrast to the loss of sexual behavior by castrated males of other strains, males of the B6D2F1 genotype retain the ejaculatory reflex for many weeks after castration. The present study examined this retention phenomenon. Masculine sexual behaviors were measured before and after castration or sham operation in male C57BL/6J, DBA/2J, and B6D2F1 mice. Castrated C57BL/6J and DBA/2J males showed a rapid decline in copulatory behavior. In contrast, 30% of the B6D2F1 males continued to ejaculate 25 weeks after castration. Regardless of whether or not sexual behaviors were retained, levels of plasma testosterone and hypothalamic nuclear estrogen receptors were reduced by castration. These results suggest that the intra- and inter-strain differences in the retention of sexual behavior following castration are not due to differences in levels of steroid hormones. Further, some B6D2F1 males retain the ability to copulate in the absence of gonadal hormone levels required for the maintenance of sexual behavior in other genotypes.

Retention of masculine copulatory behaviors following castration varies among B6D2F1 male mice. In the present study, we examined the effect of test environment and the amount of behavioral testing after castration, on retention of copulatory responses in castrated B6D2F1 male mice. Results showed that weekly behavioral testing after castration was not necessary for the retention of ejaculatory reflexes. However, the test environment had a major effect. Following castration, 26% of the males completely stopped showing ejaculatory responses when tested in the test arenas. When these males were tested in their home cages, 75% achieved at least one ejaculatory response in four home cage tests. Castrated males that continued to copulate in the test arena situation also achieved ejaculatory reflexes in their home cages. These results indicate that for some B6D2F1 males, the retention of sexual behaviors after castration is influenced by environmental factors.

In contrast to the facilitative effects reported for other rodents, testosterone treatment at the time of castration previously was reported to inhibit masculine sexual behavior in male B6D2F1 mice. Males of this genotype vary in their behavioral response to castration. Some castrates retain sexual behaviors for many weeks after surgery, whereas others do not. In the present study, we sought to determine the effects of exogenous steroid hormone treatment on castrated B6D2F1 mice that had ceased to show copulatory behavior. Testosterone propionate and estradiol benzoate restored copulatory behavior to precastration levels in B6D2F1 males that did not retain sexual behaviors after castration.