Cluster analysis demonstrates co-existing sites of fragility fracture and associated comorbidities.

We undertook cluster analysis in 11,003 patients who had sustained ≥ 1 fragility fracture, to find associations between fracture sites and comorbidities. We identified three distinct groups of fracture sites and four clusters of fractures and comorbidities. Knowledge of factors associated with fracture sites will aid prophylaxis in at-risk patients. INTRODUCTION: Fragility fracture (FF) prevalence is increasing. Subsequent fractures lead to greater morbidity and mortality. Few data are available on the association between FF sites and comorbidities. OBJECTIVES: 1. Establish the most common sites of FF and clusters within patients. 2. Identify patterns of co-existing FF and associated comorbidities. METHODS: We retrospectively reviewed clinical records of patients undergoing bone mineral density estimation at a district hospital in North-West England, 2004-2016, identifying those who had sustained ≥ 1 FF. Demographics, FF site(s), comorbidities, and medications were recorded. Cluster analysis was performed on fracture sites alone, and sites and comorbidities, using Jaccard similarity coefficient. Results were plotted on a dendrogram and divided into clusters. RESULTS: Of 28,868 patients, 11,003 had sustained ≥ 1 FF, 84.6% female, with overall mean age 67.5 years and median T-score - 1.12 SD. FF of the forearm was more frequent (n = 5045), most commonly co-existing with tibia/fibula fractures. Three FF site clusters were identified: ankle and elbow; forearm, tibia/fibula, ribs and spine; and pelvis, femur and humerus. When including comorbidities, four clusters were identified: forearm, tibia/fibula, spine, associated with family history of FF, smoking, corticosteroids and bisphosphonates; pelvis associated with hyperparathyroidism, PMR, coeliac disease and HRT; femur and humerus associated with IBD and RA; and ribs associated with alcohol and hyperthyroidism. CONCLUSION: Cluster analysis demonstrated three fracture site clusters, and four subgroups of FF sites and comorbidities. Cluster analysis is a novel method to evaluate comorbidities associated with FF sites. Knowledge of factors associated with FF sites will aid prophylaxis in at-risk patients.

Predictors of fracture risk in patients with systemic lupus erythematosus.

Objectives Bone loss in systemic lupus erythematosus is multifactorial. Recent studies demonstrate corticosteroids, previous fractures and increasing age decrease bone mineral density. The effect of body mass index and fat mass are less well characterized. We sought to determine fracture risk factors in patients undergoing dual-energy X-ray absorptiometry scanning at a district hospital in 2004-2015. Methods Standard dual-energy X-ray absorptiometry parameters were recorded, plus rheumatoid arthritis diagnosis, smoking status, alcohol consumption, family history of fractures, history of secondary operation and corticosteroid use. Data were analyzed using Fisher's exact test for categorical data and logistic regression for continuous data. Results One hundred and fifty patients (141 women, nine men) with SLE were included; 52 (34.6%) had sustained at least one fracture. Fracture risk increased with increased age, body mass index, fat mass and average tissue thickness, and decreased lean mass (adjusted for steroid use), as well as with smoking and rheumatoid arthritis. Increased femoral and vertebral bone mineral density conversely decreased fracture risk. Conclusion Our study suggests increased age, body mass index, fat mass, smoking and/or rheumatoid arthritis increase fracture risk in SLE patients. To our knowledge, this is the first demonstration of a correlation between increased fat mass, adjusted for steroid use and fracture risk, in adults, potentially indicating a differential effect of fat on bone metabolism and lessening of lean body mass.

Changes in living arrangement, daily smoking, and risky drinking initiation among young Swiss men: a longitudinal cohort study.

OBJECTIVES: The aim of this study was to assess the association between changes in living arrangement and the initiation of daily smoking and monthly risky single-occasion drinking (RSOD) in a cohort of young Swiss men. STUDY DESIGN: Longitudinal cohort study. METHODS: The sample consisted of 4662 young men drawn from the Cohort Study on Substance Use Risk Factors who lived with their family at baseline. Follow-up assessments occurred 15 months later. Multiple regression models were adjusted for individual and family factors (family model), as well as for individual and peer-related factors (peer model). RESULTS: Relative to those still living with their parents at follow-up (n = 3845), those who had moved out (n = 817) were considerably more likely to have taken up smoking or RSOD after adjusting for several individual, family, and peer-related variables: OR (daily smoking) = 1.67 (95% CI 1.15-2.41) (P = 0.007) and OR (monthly RSOD) = 1.42 (95% CI 1.08-1.88) (P = 0.012). The strongest family-related predictors of smoking initiation were family structure and the lack of parental regulation and the strongest peer-related factors alcohol/drug problems in peers. Meanwhile, the strongest peer-related predictors of RSOD initiation were peer pressure (misconduct), perceived social support from friends, and perceived social support from a significant other, whereas family factors were not associated with RSOD initiation. Further subanalyses were conducted to examine the impact of different living arrangement changes on substance use initiation and revealed that living with peers at follow-up was associated with the greatest risk. CONCLUSIONS: We identified a strong association between moving out of one's parents' home and daily smoking and monthly RSOD initiation in young Swiss men. Moving out to live with peers was an especially strong predictor of substance use initiation. Campaigns that aim to prevent heavy smoking and drinking should be intensified at the end of obligatory school.

Evaluation of the parallel coupling constitutive model for biomaterials using a fully coupled network-matrix model.

In this article we discuss the effective properties of composites containing a crosslinked athermal fiber network embedded in a continuum elastic matrix, which are representative for a broad range of biological materials. The goal is to evaluate the accuracy of the widely used biomechanics parallel coupling model in which the tissue response is defined as the additive superposition of the network and matrix contributions, and the interaction of the two components is neglected. To this end, explicit, fully coupled models are used to evaluate the linear and non-linear response of the composite. It is observed that in the small strain, linear regime the parallel model leads to errors when the ratio of the individual stiffnesses of the two components is in the range 0.1-10, and the error increases as the matrix approaches the incompressible limit. The data presented can be used to correct the parallel model to improve the accuracy of the overall stiffness prediction. In the non-linear large deformation regime linear superposition does not apply. The data shows that the matrix reduces the stiffening rate of the network, and the response is softer than that predicted by the parallel model. The correction proposed for the linear regime mitigates to a large extent the error in the non-linear regime as well, provided the matrix Poisson ratio is not close to 0.5. The special case in which the matrix is rendered auxetic is also evaluated and it is seen that the auxeticity of the matrix may compensate the stiffening introduced by the network, leading to a composite with linear elastic response over a broad range of strains.

Brain metastases: An update on the multi-disciplinary approach of clinical management.

IMPORTANCE: Brain metastasis (BM) is the most common malignant intracranial neoplasm in adults with over 100,000 new cases annually in the United States and outnumbering primary brain tumors 10:1. OBSERVATIONS: The incidence of BM in adult cancer patients ranges from 10-40%, and is increasing with improved surveillance, effective systemic therapy, and an aging population. The overall prognosis of cancer patients is largely dependent on the presence or absence of brain metastasis, and therefore, a timely and accurate diagnosis is crucial for improving long-term outcomes, especially in the current era of significantly improved systemic therapy for many common cancers. BM should be suspected in any cancer patient who develops new neurological deficits or behavioral abnormalities. Gadolinium enhanced MRI is the preferred imaging technique and BM must be distinguished from other pathologies. Large, symptomatic lesion(s) in patients with good functional status are best treated with surgery and stereotactic radiosurgery (SRS). Due to neurocognitive side effects and improved overall survival of cancer patients, whole brain radiotherapy (WBRT) is reserved as salvage therapy for patients with multiple lesions or as palliation. Newer approaches including multi-lesion stereotactic surgery, targeted therapy, and immunotherapy are also being investigated to improve outcomes while preserving quality of life. CONCLUSION: With the significant advancements in the systemic treatment for cancer patients, addressing BM effectively is critical for overall survival. In addition to patient's performance status, therapeutic approach should be based on the type of primary tumor and associated molecular profile as well as the size, number, and location of metastatic lesion(s).

Quality of life of parents of mentally-ill children: a systematic review and meta-analysis.

AIMS: To examine the quality of life (QOL) of parents of children with a specific mental disorder (any age). METHODS: Relevant articles were searched using different databases. Articles were included that compared the QOL of parents with mentally-ill children to parents of healthy controls or norm values or provided the required data for this comparison. A meta-analysis was conducted to obtain an overall mean effect size estimate. Additional analyses were performed to assess publication bias and moderation. RESULTS: Twenty-six out of 10 548 articles met the pre-defined inclusion criteria. Most of these studies focused on attention-deficit/hyperactivity disorder or autism spectrum disorder, used clinical samples that mainly included males and young children and studied the QOL of mothers. The meta-analysis revealed that parents of mentally-ill children are experiencing a clinically relevant reduction in their QOL relative to parents of healthy children and norm values (g = -0.66). CONCLUSIONS: The compromised QOL of parents of mentally-ill children needs to be considered and addressed by health professionals who are in contact with them. The paper provides insights into existing research gaps and suggests improvements for subsequent work.

Bilateral exudative retinal detachment in a child with orbital pseudotumor.

We describe a 15-year-old girl who presented with bilateral exudative retinal detachment, a previously unreported complication, due to orbital pseudotumor. She initially responded to steroids, but subsequently became steroid dependent. Azathioprine was effective in controlling further relapses during follow-up of 22 months.

Postrenal Transplant Metastatic Colonic Neoplasm: Posttransplant Lymphoproliferative Disorder or Adenocarcinoma?

Transplant recipients are vulnerable to a horde of infections and neoplastic conditions due to immunosuppression. Posttransplant lymphoproliferative disorder (PTLD) is a condition unique to the transplant recipient occurring due to monoclonal lymphocytic proliferation. It may affect any organ system with reportedly highest incidence in the gastrointestinal tract. The incidence of adenocarcinoma of the colon, however, has not been shown to be uniformly higher in transplant recipients. We report here an unusual case of adenocarcinoma of the ascending colon presenting with liver, lymph node and skin metastasis in a transplant recipient, which simulated PTLD both clinically and radiologically. For any gastrointestinal lesion in transplant recipient, the possibility of carcinoma must be considered. However, a high index of suspicion for PTLD facilitates early diagnosis since the treatment of the two conditions is starkly different.

Adult attention-deficit/hyperactivity disorder and its association with substance use and substance use disorders in young men.

BACKGROUND: Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men. METHOD: The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)). RESULTS: Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant. CONCLUSIONS: Our findings suggest that adult ADHD is significantly associated with a propensity to experiment with licit and illicit substances, especially at earlier ages, to exhibit risky substance use patterns, and to subsequently develop SUDs. Preventive strategies that include early intervention and addressing co-morbidity with ASPD may be crucial to reducing substance use and the development of pathological substance use patterns in young men affected by ADHD and, thus, helping to prevent further illness burden later in life.

Importance of photoperiods in determining temporal pattern of annual testicular events in rose-ringed parakeet (Psittacula krameri).

Male rose-ringed parakeets (Psittacula krameri) were transferred to a long photoperiod (LP; LD 16:8) or a short photoperiod (SP; LD 8:16) for 45 or 90 days on four dates corresponding to the beginnings of different reproductive phases in an annual testicular cycle, and testicular responsiveness was evaluated by comparison with the testicular volume, weight, seminiferous tubular diameter, and germ cell profiles of birds in a natural photoperiod (NP). Exposure of birds to LP during the progressive phase (November) led to precocious maturation of testes after 45 days, but induced regression at 90 days. After showing retarded gametogenic functions at 45 days, parallel (November) SP birds exhibited an accelerated rate of germ cell formation at day 90. During the prebreeding phase (January), there were no remarkable differences in any features of testes among NP. LP, and SP birds at 45 days, but gonadal involution in LP parakeets and active spermatogenesis in SP birds occurred after 90 days. The testes did not show any response to LP or SP for 45 and 90 days when the birds were transferred to altered photoperiods during the breeding (March) and preparatory (June) phases, indicating that the parakeets were photorefractory for at least 6 months (March through September). The results also suggest that initiation and termination of seasonal gametogenic activity in parakeets are possibly functions of endogenous rhythmicity or extraphotoperiodic environmental factors. Duration of light may have certain influences on the attainment of annual peak in spermatogenesis, but in all probability the species has a low photoperiod threshold for induction of testicular growth.

Estrogen activity and novel tissue selectivity of delta8,9-dehydroestrone sulfate in postmenopausal women.

Recent basic and clinical advances have consolidated the concept of tissue-selective estrogens, i.e. molecules that express different degrees of partial agonist, full agonist or antagonist activity in different tissues or cells. Delta8,9-Dehydroestrone sulfate (delta8,9-DHES) is a conjugated estrogen and a component of conjugated equine estrogens (CEE). It is metabolized in the human in at least a 1:1 ratio to its 17beta form, 17beta-delta8,9-DHES. To evaluate its activity in different clinical and biochemical parameters, a clinical research study was conducted with delta8,9-DHES and estrone sulfate as a comparator in postmenopausal women. Delta8,9-DHES was given orally at a daily dose of 0.125 mg for 12 weeks in a group of 10 women. Two additional groups of women received either estrone sulfate alone (1.25 mg/day) or the combination of delta8,9-DHES and estrone sulfate at the previously specified doses. A significant and consistent suppression of hot flushes (number, severity, and total score) was observed with delta8,9-DHES, reaching more than 95% suppression in all parameters of vasomotor symptoms. This level of activity was equal to that obtained with the much higher dose of estrone sulfate, and it was sustained for the duration of the treatment period (12 weeks). Measurements of a bone resorption marker, i.e. urinary excretion of N-telopeptide, demonstrated that delta8,9-DHES at 8 weeks produced a degree of suppression (40%) similar to that observed with the higher dose of estrone sulfate. Gonadotropin secretion (FSH and LH) was significantly suppressed in women receiving delta8,9-DHES, similar to that observed with estrone sulfate alone or with the combination of the two. Other parameters, such as total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol were not modified significantly, whereas serum globulins (sex hormone-binding globulin and corticosteroid-binding globulin) showed only marginal increases after delta8,9-DHES administration. Taken together with preclinical data, it is found that delta8,9-DHES is an active estrogen with a distinct pharmacological profile that results in significant clinical activity in vasomotor, neuroendocrine (gonadotropin and PRL) and bone preservation parameters, whereas displaying little or no efficacy, at the dose tested, on other peripheral parameters normally affected by estrogens. Collectively, this information supports the concept that delta8,9-DHES is an integral component of CEE, with distinct tissue selectivity contributing to the CEE's overall clinical activity, and places this estrogen as a distinct member of a novel class of centrally active molecules with unique peripheral tissue selectivity.

Effects of equine oestrogens on markers of vasoactive function in human coronary artery endothelial cells.

A large proportion of the beneficial effects that oestrogens demonstrate on the vasculature are believed to be mediated via direct effects on the vascular wall. In this study we compared a number of oestrogenic compounds isolated from pregnant mare's urine including 17beta-oestradiol and oestrone, in terms of their abilities to inhibit stimulated endothelin-1 release from normal human coronary artery endothelial cells (CAEC). We also examined their ability to stimulate expression of constitutive endothelial nitric oxide synthase (eNOS) and explored their effects on cellular angiotensin converting enzyme (ACE). All the oestrogens tested were able to inhibit serum-stimulated ET-1 release. Oestrone and 17alpha-dihydroequilenin failed to significantly affect cellular eNOS levels. 17Beta-oestradiol and oestrone significantly increased cellular ACE levels while 17beta,delta(8,9)-dehydroestradiol decreased cellular ACE. We discuss these observations in terms of their potential clinical relevance and use as a means of screening novel oestrogen-like compounds.

Pharmacokinetics and pharmacodynamics of long-acting propranolol 60-mg capsules: a comparative evaluation.

This double-blind, placebo-controlled, four-period cross-over study was undertaken to evaluate the sustained-release characteristics of long-acting propranolol hydrochloride (Inderal LA, Ayerst Laboratories, New York, NY) 60 mg qd, to compare the pharmacokinetic and pharmacodynamic properties of this formulation with conventional propranolol 20 mg tid, and to evaluate the proportionality of long-acting propranolol 60 mg (LA 60 mg) and long-acting propranolol 80 mg (LA 80 mg). Pharmacodynamic effects were evaluated in 34 healthy subjects by assessing heart rate, systolic blood pressure, and the product of heart rate and systolic blood pressure (double product) after exercise-induced tachycardia following both acute (day 1) and steady state (day 4) drug administration. The Cmax following administration of LA 60 mg was 9.5 and 11.4 ng/mL on days 1 and 4, respectively, compared with 18.8 and 20.0 ng/mL with 20 mg tid (P less than .0001). The tmax for LA 60 mg was significantly later (P less than .0001) than for conventional propranolol. Additionally, the apparent plasma half-life was significantly longer (P less than .0001) than with conventional propranolol. The LA 60-mg formulation was dose proportional to the LA 80-mg formulation. Pharmacodynamic evaluations showed no significant differences between LA 60 mg and 20 mg tid at any times tested with either acute or steady state dosing. This study demonstrates that LA 60 mg displays characteristics of a sustained-release formulation, is proportional with LA 80 mg, and produces pharmacodynamic effects that are similar to 20-mg tid dosing.

Sympathetic thyroidal vasoconstriction is not blocked by a neuropeptide Y antagonist or antiserum.

Sympathetic nerve fibers to thyroid blood vessels contain both norepinephrine (NE) and neuropeptide Y (NPY). To assess the involvement of endogenous NPY in the sympathetic neural control of thyroid blood flow, appropriate doses of a selective NPY antagonist, alpha-trinositol, and an NPY antiserum (NPY-AS) were used during cervical sympathetic trunk stimulation in anesthetized rats. During all experiments, thyroid blood flow was continuously monitored by laser Doppler blood flowmetry. Neither alpha-trinositol nor NPY-AS blocked the thyroidal vasoconstriction evoked by either the first or second stimulation of the cervical sympathetic trunks. Our results suggest that NPY is not involved either directly or indirectly during acute sympathetic vasoconstriction in the rat thyroid gland.

Rabies epizootics among raccoons vary along a North-South gradient in the Eastern United States.

The characteristics of rabies epizootics among raccoons were investigated in 11 eastern states along a North-South gradient from New York to North Carolina. Epizootics were defined as discrete intervals of time of at least 5 months in duration, when reported cases of raccoon rabies from an individual county exceeded the median value of raccoon rabies cases reported by that county over the entire period rabies was present among raccoons in the county. Over the approximately 20-year study period, 35,000 cases of raccoon rabies were reported, and epizootics were detected from 251 (64.4%) of 390 counties. The median annual incidence was 0.14 epizootics per year. During the first defined epizootic in a county, the median total number of raccoons reported rabid was 47, with a median monthly incidence of rabies in raccoons of 3.1. The median lag time from the first report of a rabid raccoon in a county to the beginning of the first epizootic was 4 months. Significant differences in the annual incidence of epizootics and monthly incidence of rabid raccoons during epizootics were observed among different states. Although human population density and per capita health spending within counties were positively associated with increasing magnitude of epizootics, a significant difference in the characteristics of rabies epizootics in northern and southern states was apparent. We hypothesize that environmental conditions and perhaps human influence resulted in rabies epizootics in southern states that were smaller, less-frequent, and lacking in well-defined temporal structure compared with those in northern states.

Biologic effects of delta-8-estrone sulfate in postmenopausal women.

OBJECTIVE: To determine in postmenopausal women the biological effects of delta-8-estrone sulfate, a novel estrogen component of Premarin (Wyeth-Ayerst, Philadelphia, PA). METHODS: An open-label, nonrandomized study of six healthy postmenopausal women was conducted. Each subject took 0.125 mg of delta-8-estrone sulfate daily for 8 weeks. Blood samples were collected at day 0 (baseline) and once a week for 8 weeks. Urine was collected on day 0 and at weeks 2, 3, 5, 6, 7, and 8. Serum gonadotropins (follicle-stimulating hormone/luteinizing hormone), plasma binding proteins (corticosteroid-binding globulin/sex hormone-binding globulin), a marker for bone turnover (urinary n-telopeptide), and markers for cardiovascular effects (cholesterol, low-density lipoprotein, high-density lipoprotein(c), low-density lipoprotein oxidation, and rate of diene formation) were measured. RESULTS: Follicle-stimulating hormone levels decreased from 84.0 +/- 8.5 to 67.0 +/- 8.5 mlU/mL (P = .02), whereas luteinizing hormone levels did not change. Corticosteroid-binding globulin levels increased from 3.30 +/- 0.16 to 4.10 +/- 0.16 mg/dL (P = .02), and no change in sex hormone-binding globulin was noted. The n-telopeptide levels decreased an average of 31% from 40.7 +/- 4.9 to 28 +/- 7.0 nmol/L bone collagen equivalents/mmol/L creatinine (P = .03). Plasma diene concentration and diene production rate decreased by 34% and 40%, respectively; these changes were not significantly different from baseline values. In contrast, a significant (P = .03) 68% increase in the lag time for low-density lipoprotein(c) oxidation (38.5 +/- 5.5 minutes versus 64.8 +/- 8.5 minutes) was observed. No significant change occurred in total cholesterol, high-density lipoprotein(c), and low-density lipoprotein(c). CONCLUSION: Small doses (0.125 mg) of delta-8-estrone sulfate have profound estrogenic effects in postmenopausal women. The changes observed in n-telopeptide levels and the lag-time delay in oxidation of low-density lipoprotein(c) indicate that this estrogen contributes toward the overall beneficial effects on bone and cardiovascular system associated with Premarin therapy.

The neuropeptides, VIP and NPY, that are present in the thyroid nerves are not released into the thyroid vein.

In the present study, we tested the hypothesis that the neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), which are present in the thyroid nerves, act as physiological neurotransmitters involved in the regulation of thyroid hormone secretion and thyroid blood flow. Specifically, we examined whether these neuropeptides can be released into thyroid blood vessels by electrical stimulation of the major thyroid nerves or whether their expression is altered by changes in iodine intake. Sprague-Dawley rats were used in this study. The cervical sympathetic trunk or the superior laryngeal nerve was stimulated by bipolar electrodes in anesthetized rats. During nerve stimulation, blood samples were withdrawn from the thyroid vein. Thyroid blood flow was monitored by laser Doppler blood flowmetry. Sympathetic stimulation caused a marked decrease in thyroid blood flow, which was associated with a significant increase in release of norepinephrine. However, these effects were not accompanied by any change in NPY release into the thyroid vein. Stimulation of the superior laryngeal nerve was not associated with changes in thyroid blood flow or VIP release into the thyroid vein. In a separate experiment, rats were fed a diet containing low-, high-, or normal iodine concentrations. Triiodothyronine (T3) and thyroxine (T4) levels in thyroid venous plasma were significantly reduced in rats fed a low-iodine diet but not in a separate group of rats fed a high iodine diet. However, these treatments had no effect on VIP or NPY concentrations in thyroid venous plasma or in thyroid ganglia. Thus, our results indicate that VIP and NPY, which are present in the thyroid nerves, may not be directly involved in the regulation of thyroid function.

Recent insights into the varying activity of estrogens.

Recent advances have added substantially to our understanding of the biology of estrogens. Estrogens are no longer considered to differ only in potency. Two estrogens can have similar effects in one tissue and very different effects in another. Additionally, an estrogen can have different effects in different tissues. It is now recognized that there are at least two estrogen receptors, ER-alpha and ER-beta, and that it is quite likely that estrogens also work through non-genomic mechanisms. The development of new methods of chromatographic separation has aided substantially in our ability to characterize the composition of Premarin, including the identification of estradiene, the fourth-most abundant estrogen in Premarin. Recent studies have contributed to our understanding of the unique profile of Delta(8,9) dehydroestrone sulfate, another of the Premarin estrogens. It was found that Delta(8,9) dehydroestrone sulfate is an active estrogen with a distinct pharmacological profile that results in significant clinical activity in vasomotor, neuroendocrine and bone preservation parameters. However, it displayed little or no efficacy, at the dose studied, on other peripheral parameters normally affected by classical estrogens. Increasing knowledge of the unique profiles of the Premarin components, as well as their complex interaction, will help to increase our understanding of the clinical profile of Premarin.

When does metoclopramide facilitate transpyloric intubation?

Postpyloric feeding probably reduces the incidence of tracheobronchial aspiration and improves feeding tolerance. However, duodenal intubation is often unsuccessful in critically ill patients due to gastric atony. Metoclopramide improves gastric emptying. In a pilot study, 12 adult patients were administered 10 to 20 mg of intravenous metoclopramide after weighted nasal feeding tubes had failed to spontaneously pass distal to the pylorus. In no patient did metoclopramide induce transpyloric passage of the tube. A randomized prospective study involving 10 adult patients was conducted to examine the effect of preinsertion intravenous metoclopramide on transpyloric intubation. All patients had failed to achieve spontaneous duodenal intubation. Five patients received 20 mg of metoclopramide 10 min prior to nasal insertion of a weighed feeding tube. Five control patients received no premedication. Four metoclopramide patients achieved duodenal intubation immediately. In none of the control patients did transpyloric intubation occur (p = 0.048). Metoclopramide, administered after nasogastric intubation, is ineffective in promoting transpyloric advancement of feeding tubes. There is a significant increase in transpyloric intubation when metoclopramide is administered prior to tube insertion.