Optimizing the Medication Distribution Process for Inpatient Units.

Pharmacy robots and automated dispensing cabinets are commonly used to distribute medications to inpatient units efficiently and safely. Decisions regarding the use of these technologies are often made without full knowledge regarding system effects. This paper determines a cost effective and safe way to distribute medications to patients across a hospital system by minimizing the distribution cost and missing dose rate. A mathematical model is formulated which captures key aspects of the pharmacy distribution process to determine a primary pathway to distribute each medication and dose type to each unit. The model focuses on three primary distribution pathways: cart fill via pharmacy robot, cart fill via pharmacy technician, and automated dispensing cabinets. The problem is solved using a complete year of data from the Geisinger Medical Center. The model results demonstrate the trade-off between pharmacy technician and nurse workload and missing dose rates that occur as hospitals move from a centralized pharmacy to automated dispensing cabinets. These results demonstrate the importance of evaluating the labor effort and missing dose rates when determining the best method to distribute medication.

Ras2 is important for growth and pathogenicity in Fusarium circinatum.

In this study, we investigated to possible role of Ras2 in Fusarium circinatum- a fungus that causes pine pitch canker disease on many different pine species and has a wide geographic distribution. This protein is encoded by the RAS2 gene and has been shown to control growth and pathogenicity in a number of fungi in a mitogen-activated protein kinase- and/or cyclic adenosyl monophosphate pathway-dependent manner. The aim was therefore to characterize the phenotypes of RAS2 gene knockout and complementation mutants of F. circinatum. These mutants were generated by transforming protoplasts of the fungus with suitable split-marker constructs. The mutant strains, together with the wild type strain, were used in growth studies as well as pathogenicity assays on Pinus patula seedlings. Results showed that the knockout mutant strain produced significantly smaller lesions compared to the complementation mutant and wild type strains. Growth studies also showed significantly smaller colonies and delayed conidial germination in the knockout mutant strain compared to the complement mutant and wild type strains. Interestingly, the knockout mutant strain produced more macroconidia than the wild type strain. Collectively, these results showed that Ras2 plays an important role in both growth and pathogenicity of F. circinatum. Future studies will seek to determine the pathway(s) through which Ras2 controls these traits in F. circinatum.

First divertor Thomson scattering measurements on MAST-U.

MAST-U is equipped with a Super-X divertor, which aims to reduce heat flux to the target and promote detachment. Measurements of plasma electron density and temperature in the Super-X chamber offer insight into the processes at work in this type of divertor. First data have been obtained from the MAST-U divertor Thomson scattering diagnostic designed to measure these quantities. Following a Raman scattering calibration in nitrogen, the diagnostic operated over a number of plasma pulses in the first physics campaign. Electron density and temperature measurements have been taken in attached and detached conditions as the strike leg moved through the field of view of the diagnostic. The system operated with a dedicated 30 Hz laser with timing synchronized to seven similar lasers installed in the core Thomson system. Electron densities in the range of 1 × 1018-5 × 1019 m-3 have been measured by the system throughout these regimes. Although the system was specified to measure from 1 to 40 eV, electron temperatures in the Super-X divertor in the first campaign were low, and measurement down to 0.5 eV has been critical, particularly close to the detachment front. This generation of polychromator has been designed with increased stray light rejection compared to those used in the core system. This has proved successful with very low levels of stray light observed.

Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery.

BACKGROUND: Major surgery is associated with postoperative insulin resistance which is attenuated by preoperative carbohydrate (CHO) treatment. The effect of this treatment on clinical outcome after major abdominal surgery has not been assessed in a double-blind randomized trial. METHODS: Patients undergoing elective colorectal surgery or liver resection were randomized to oral CHO or placebo drinks to be taken on the evening before surgery and 2 h before induction of anaesthesia. Primary outcomes were postoperative length of hospital stay and fatigue measured by visual analogue scale. RESULTS: Sixty-nine and 73 patients were evaluated in the CHO and placebo groups respectively. The groups were well matched with respect to surgical procedure, epidural analgesia, laparoscopic procedures, fasting period before induction and duration of surgery. Postoperative changes in fatigue score from baseline did not differ between the groups. Median (range) hospital stay was 7 (2-35) days in the CHO group and 8 (2-92) days in the placebo group (P = 0.344). For patients not receiving epidural blockade or laparoscopic surgery (20 CHO, 19 placebo), values were 7 (3-11) and 9 (2-48) days respectively (P = 0.054). CONCLUSION: Preoperative CHO treatment did not improve postoperative fatigue or length of hospital stay after major abdominal surgery. A benefit is not ruled out when epidural blockade or laparoscopic procedures are not used. REGISTRATION NUMBER: ACTRN012605000456651 (http://www.anzctr.org.au).

Correlation between gross anatomical topography, sectional sheet plastination, microscopic anatomy and endoanal sonography of the anal sphincter complex in human males.

This study elucidates the structure of the anal sphincter complex (ASC) and correlates the individual layers, namely the external anal sphincter (EAS), conjoint longitudinal muscle (CLM) and internal anal sphincter (IAS), with their ultrasonographic images. Eighteen male cadavers, with an average age of 72 years (range 62-82 years), were used in this study. Multiple methods were used including gross dissection, coronal and axial sheet plastination, different histological staining techniques and endoanal sonography. The EAS was a continuous layer but with different relations, an upper part (corresponding to the deep and superficial parts in the traditional description) and a lower (subcutaneous) part that was located distal to the IAS, and was the only muscle encircling the anal orifice below the IAS. The CLM was a fibro-fatty-muscular layer occupying the intersphincteric space and was continuous superiorly with the longitudinal muscle layer of the rectum. In its middle and lower parts it consisted of collagen and elastic fibres with fatty tissue filling the spaces between the fibrous septa. The IAS was a markedly thickened extension of the terminal circular smooth muscle layer of the rectum and it terminated proximal to the lower part of the EAS. On endoanal sonography, the EAS appeared as an irregular hyperechoic band; CLM was poorly represented by a thin irregular hyperechoic line and IAS was represented by a hypoechoic band. Data on the measurements of the thickness of the ASC layers are presented and vary between dissection and sonographic imaging. The layers of the ASC were precisely identified in situ, in sections, in isolated dissected specimens and the same structures were correlated with their sonographic appearance. The results of the measurements of ASC components in this study on male cadavers were variable, suggesting that these should be used with caution in diagnostic and management settings.

Prevalence and risk factors for medical events following exercise at Australian Greyhound race meetings.

AIM: A prospective, observational study to determine the prevalence of post-exercise conditions at Australian Greyhound race meetings and to assess association with race performance and other environmental, race- and dog-related factors was undertaken. METHODS: A total of 4020 starters were observed (2813 Greyhounds, 1009 trainers, 536 races, 52 race meets, 48 race dates and 11 race tracks) following a race. The presence of diaphragmatic flutter (DF), ataxia, seizure, collapse or sudden death was recorded. Risk factors were screened by univariable logistic regression prior to multivariable backward stepwise model building. RESULTS: In this study, 962 starters (n = 768 dogs) had DF (23.9%), 16 starters were ataxic (0.4%) and there were no observed cases of collapse, seizure or sudden death. Race track location, increasing race distance, race grade based on increasing 1st place prize value, lower (earlier) race number at the meeting, age, a previous observation of DF at the last start, females, colour (white) and better finishing position were all associated with an increased risk of a Greyhound being observed with DF. However, when logistic regression assessing the random effect of dog was performed, the presence of previous DF was not significant. In this cohort, DF was common following strenuous exercise in Greyhounds and on its own does not appear to result in reduced performance or distress to the animal. CONCLUSION: The incidence of ataxia was low and collapse, seizure and sudden death were not observed. However, even though uncommon, ataxia has welfare concerns for racing Greyhounds that warrants further investigation.

Single-shot frequency-resolved optical gating for retrieving the pulse shape of high energy picosecond pulses.

Accurate characterization of laser pulses used in experiments is a crucial step to the analysis of their results. In this paper, a novel single-shot frequency-resolved optical gating (FROG) device is described, one that incorporates a dispersive element which allows it to fully characterize pulses up to 25 ps in duration with a 65 fs per pixel temporal resolution. A newly developed phase retrieval routine based on memetic algorithms is implemented and shown to circumvent the stagnation problem that often occurs with traditional FROG analysis programs when they encounter a local minimum.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. SUMMARY: Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.

Oral water soluble contrast for the management of adhesive small bowel obstruction.

BACKGROUND: Adhesions are the leading cause of small bowel obstruction. Gastrografin transit time may allow for the selection of appropriate patients for non-operative management. Some studies have shown when the contrast does not reach the colon after a designated time it indicates complete intestinal obstruction that is unlikely to resolve with conservative treatment. When the contrast does reach the large bowel, it indicates partial obstruction and patients are likely to respond to conservative treatment. Other studies have suggested that the administration of water-soluble contrast is therapeutic in resolving the obstruction. OBJECTIVES: To determine the reliability of water-soluble contrast media and serial abdominal radiographs in predicting the success of conservative treatment in patients admitted with adhesive small bowel obstruction.Furthermore, to determine the efficacy and safety of water-soluble contrast media in reducing the need for surgical intervention and reducing hospital stay in adhesive small bowel obstruction. SEARCH STRATEGY: The search was conducted using MESH terms: ''Intestinal obstruction'', ''water-soluble contrast'', "Adhesions" and "Gastrografin". The later combined with the Cochrane Collaboration highly sensitive search strategy for identifying randomised controlled trials and controlled clinical trials. SELECTION CRITERIA: 1. Prospective studies were included to evaluate the diagnostic potential of water-soluble contrast in adhesive small bowel obstruction.2. Randomised clinical trials were selected to evaluate the therapeutic role. DATA COLLECTION AND ANALYSIS: 1. Studies that addressed the diagnostic role of water-soluble contrast were critically appraised and data presented as sensitivities, specificities and positive and negative likelihood ratios. Results were pooled and summary ROC curve was constructed.2. A meta-analysis of the data from therapeutic studies was performed using the Mantel -Henszel test using both the fixed effect and random effect models. MAIN RESULTS: The appearance of water-soluble contrast in the colon on an abdominal X ray within 24 hours of its administration predicts resolution of an adhesive small bowel obstruction with a pooled sensitivity of 0.97, specificity of 0.96. The area under the curve of the summary ROC curve is 0.98. Six randomised studies dealing with the therapeutic role of gastrografin were included in the review, water-soluble contrast did not reduce the need for surgical intervention (OR 0.81, p = 0.3). Meta-analysis of four of the included studies showed that water-soluble contrast did reduce hospital stay compared with placebo (WMD= - 1.83) P<0.001. AUTHORS' CONCLUSIONS: Published literature strongly supports the use of water-soluble contrast as a predictive test for non-operative resolution of adhesive small bowel obstruction. Although Gastrografin does not cause resolution of small bowel obstruction there is strong evidence that it reduces hospital stay in those not requiring surgery.

Stapled versus handsewn methods for ileocolic anastomoses.

BACKGROUND: Ileocolic anastomoses are commonly performed for right-sided colon cancer and Crohn's disease. The anastomosis may be constructed using a linear cutter stapler or by suturing. Individual trials comparing stapled versus handsewn ileocolic anastomoses have found little difference in the complication rate but they have lacked adequate power to detect potential small difference. To our knowledge, this is the first systematic review specifically investigating ileocolic anastomosis. OBJECTIVES: To compare outcomes of ileocolic anastomoses performed using stapling and handsewn techniques. The hypothesis tested was that the stapling technique is associated with fewer complications. SEARCH STRATEGY: MEDLINE, EMBASE, Cochrane Colorectal Cancer Group specialised register SR-COLOCA, Cochrane Library were searched for randomised controlled trials comparing use of a linear cuter stapler with any type of suturing technique for ileocolic anastomoses in adults from 1970 to 2005. Abstracts presented to the following society meetings between 1970 and 2002 were handsearched: American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland, European Association of Coloproctology. SELECTION CRITERIA: Randomised controlled trials comparing use of linear cutter stapler (isoperistaltic side to side or functional end to end) with any type of suturing technique in adults. DATA COLLECTION AND ANALYSIS: Eligible studies were selected and their methodological quality assessed. Relevant results were extracted and missing data sought from the authors. RevMan 4.2 Analysis version 1.0.5 was used to perform meta-analysis when there were sufficient data. Sub-group analyses for cancer and inflammatory bowel disease as indication for ileocolic anastomoses were performed. MAIN RESULTS: After obtaining individual data from authors for studies that include other anastomoses, six trials (including one unpublished) with 955 ileocolic participants (357 stapled, 598 handsewn) were included. The three largest trials had adequate allocation concealment. Stapled anastomosis was associated with significantly fewer anastomotic leaks compared with handsewn (S=5/357, HS=36/598, OR 0.34 [0.14, 0.82] p=0.02). One study performed routine radiology to detect asymptomatic leaks. For the sub-group of 825 cancer patients in four studies, stapled anastomosis led to significant fewer anastomotic leaks (S=4/300, HS=35/525, OR 0.28 [0.10, 0.75] p=0.01). There were too few Crohn's disease patients to perform sub-group analysis. All other outcomes: stricture, anastomotic haemorrhage, anastomotic time, re-operation, mortality, intra-abdominal abscess, wound infection, length of stay, showed no significant difference. AUTHORS' CONCLUSIONS: Stapled functional end to end ileocolic anastomosis is associated with fewer leaks than handsewn anastomosis.

Primary hypoparathyroidism in dogs: a retrospective study of 17 cases.

OBJECTIVE: To evaluate the clinico-pathological findings, response to treatment and prevalence of complications in dogs with primary hypoparathyroidism. DESIGN: Retrospective study of 17 dogs presenting to the University of Melbourne Veterinary Clinical Centre and Murdoch University Veterinary Hospital over a 15 year period (1990 to 2004). Case records were evaluated for signalment, body weight, diet type, historical and clinical findings, serum total calcium, phosphate, albumin and parathyroid hormone concentrations, urinary fractional excretion ratios of calcium and phosphate, electrocardiogram (ECG) results, treatments administered, outcome and period of follow-up. RESULTS: The most common breeds identified were St Bernard (three dogs), Chihuahua (two dogs), German Shepherd (two dogs) and Jack Russell Terrier (two dogs). Three dogs were cross bred. Seizures, muscle tremors and fasciculations, stiff gait, tetany, muscle cramping, behavioural change and hyperventilation were the most common clinical signs. Vomiting, inappetence, diarrhoea, abdominal pain, hyperthermia, facial pruritus, ataxia, weakness, cataracts, and circling also occurred with less frequency. The mean duration of observed clinical signs preceding diagnosis was 33 days (median 13 days, range 1 to 173 days). All dogs had marked hypocalcaemia with normal or mildly increased serum albumin concentrations. Mean phosphate concentrations were significantly higher in inappetent dogs (P = 0.049). Mean serum calcium concentrations were significantly lower in dogs with cataracts compared to those without (P = 0.046). There were no other significant relationships between serum calcium or phosphate concentrations and the clinical presentation or outcome. No significant correlations were identified between the presence of a particular clinical sign and the duration of clinical signs. ECGs were obtained in four dogs and all exhibited QT interval prolongation due to a ST-segment prolongation. Sixteen of 17 dogs were treated successfully for hypocalcaemia and discharged from hospital. Acute management included parenteral calcium gluconate (10 dogs) and intravenous anticonvulsants (five dogs). Chronic therapy included oral vitamin D analogues and calcium supplementation. Treatment complications occurred in two dogs and included acute renal failure (one dog) and iatrogenic tissue necrosis following subcutaneous calcium administration (one dog). The mean follow-up period was 14.5 months (median 13 months, range 0 to 39 months). Twelve dogs were alive at the last follow up and two dogs were euthanased for unrelated reasons. The type of vitamin D analogue used was not associated with outcome. CONCLUSION: Primary hypoparathyroidism was an uncommon diagnosis in dogs. Saint Bernards, cross bred dogs, German Shepherd dogs and Terrier breeds were most commonly affected. Neurological signs were the most common presenting clinical signs, although alimentary signs may have been more common than previously reported. Dogs with primary hypoparathyroidism appeared to have a good prognosis following initiation of calcium supplementation and vitamin D therapy. Complications of treatment were uncommon and could be minimised with regular monitoring.

Reference limits for urinary fractional excretion of electrolytes in adult non-racing Greyhound dogs.

OBJECTIVE: To determine reference limits for urinary fractional excretion of electrolytes in Greyhound dogs. METHODS: Urinary fractional excretion was calculated using a spot clearance method preceded by a 16 to 20 hour fast in 48 Greyhound dogs. Raw data analysed using the bootstrap estimate was used to calculate the reference limits. RESULTS: The observed range for urinary fractional excretion in Greyhound dogs was 0.0 to 0.77% for sodium, 0.9 to 14.7% for potassium, 0 to 0.66% for chloride, 0.03 to 0.22% for calcium and 0.4 to 20.1% for phosphate. Expressed as percentages, the suggested reference limits for fractional excretion in Greyhound dogs are as follows: sodium < or = 0.72, potassium < or = 12.2, chloride < or = 0.55, calcium < or = 0.13 and phosphate < or = 16.5. CLINICAL SIGNIFICANCE: Veterinary practitioners may use these reference limits for urinary electrolyte fractional excretion when investigating renal tubular disease in Greyhound dogs.

Dose-associated pulmonary complication rates after fresh frozen plasma administration for warfarin reversal.

UNLABELLED: ESSENTIALS: Fresh frozen plasma (FFP) may be associated with a dose-based risk of pulmonary complications. Patients received FFP for warfarin reversal at a large academic hospital over a 3-year period. Almost 20% developed pulmonary complications, and the risk was highest after > 3 units of FFP. The risk of pulmonary complications remained significant in multivariable analysis. BACKGROUND: Fresh frozen plasma (FFP) is often administered to reverse warfarin anticoagulation. Administration has been associated with pulmonary complications, but it is unclear whether this risk is dose-related. Aims We sought to characterize the incidence and dose relationship of pulmonary complications, including transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI), after FFP administration for warfarin reversal. METHODS: We performed a structured retrospective review of patients who received FFP for warfarin reversal in the emergency department (ED) of an academic tertiary-care hospital over a 3-year period. Logistic regression was used to explore the relationship between FFP dose and risk of pulmonary events. RESULTS: Two hundred and fifty-one patients met the inclusion criteria. Overall, 49 patients (20%) developed pulmonary complications, including 30 (12%) with TACO, two (1%) with TRALI, and 17 (7%) with pulmonary edema not meeting the criteria for TACO. Pulmonary complications were significantly more frequent in those who received > 3 units of FFP (34.0% versus 15.6%, 95% confidence interval for risk difference 7.9%-8.9%). After stratification by subtype of complication, only the risk of TACO was statistically significant (28.3% versus 7.6%, 95% confidence interval for risk difference 8.2%-16.6%). In multivariable analysis controlling for age, sex, initial systolic blood pressure, and intravenous fluids given in the ED, > 3 units of FFP remained a significant risk factor for pulmonary complications (odds ratio 2.49, 95% confidence interval 1.21-5.13). CONCLUSIONS: Almost 20% of patients who received FFP for warfarin reversal developed pulmonary complications, primarily TACO, and this risk increased with > 3 units of FFP. Clinicians should be aware of and prepared to manage these complications.

Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients.

The expression of genes coding for regulatory enzymes involved in the uptake, synthesis and mobilisation of lipid was measured in adipose tissue of cancer patients. Total RNA was isolated from subcutaneous adipose tissue of control and cancer patients and the various mRNAs measured by Northern blot analysis. The total lipoprotein lipase enzymic activity and the relative levels of the mRNAs for lipoprotein lipase and for fatty acid synthase were not significantly different between cancer patients and control patients. However, there was a significant two-fold increase in the relative level of mRNA for hormone-sensitive lipase (HSL) in adipose tissue of cancer patients compared with control patients. The cancer patients also exhibited a two-fold elevation in serum triacylglycerol levels and serum free fatty acid levels. There was a significant correlation between the serum free fatty acid level and expression of HSL mRNA in the adipose tissue. The serum levels of insulin and tumour necrosis factor-alpha were not different between cancer and control patients. The results suggest that at least one of the mechanisms for depletion of lipid from adipose tissue in cancer patients operates at the level of increased expression of mRNA of the lipolytic regulatory enzyme, hormone-sensitive lipase.

Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression.

The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome.

Oral water soluble contrast for the management of adhesive small bowel obstruction.

BACKGROUND: Adhesions are the leading cause of small bowel obstruction. Most adhesive small bowel obstructions resolve following conservative treatment but there is no consensus as to when conservative treatment should be considered unsuccessful and the patient should undergo surgery. Studies have shown that failure of an oral water-soluble contrast to reach the colon after a designated time indicates complete intestinal obstruction that is unlikely to resolve with conservative treatment. Other studies have suggested that the administration of water-soluble contrast is therapeutic in resolving the obstruction. OBJECTIVES: The aims of this review are:1. To determine the reliability of water-soluble contrast media and serial abdominal radiographs in predicting the success of conservative treatment in patients admitted with adhesive small bowel obstruction.2. To determine the efficacy and safety of water-soluble contrast media in reducing the need for surgical intervention and reducing hospital stay in adhesive small bowel obstruction. SEARCH STRATEGY: The search was conducted using MeSH terms: ''Intestinal obstruction'', ''water-soluble contrast'', "Adhesions" and "Gastrografin", and combined with the Cochrane Collaboration highly sensitive search strategy for identifying randomised controlled trials and controlled clinical trials. SELECTION CRITERIA: 1. Prospective studies (to evaluate the diagnostic potential of water-soluble contrast in adhesive small bowel obstruction);2. Randomised clinical trials (to evaluate the therapeutic role). DATA COLLECTION AND ANALYSIS: 1. Studies addressing the diagnostic role of water-soluble contrast were critically appraised and data presented as sensitivities, specificities and positive and negative likelihood ratios. Results were pooled and summary receiver operating characteristic (ROC) curve was constructed. 2. A meta-analysis of the data from therapeutic studies was performed using the Mantel -Haenszel test using both the fixed effect and random effects model. MAIN RESULTS: The appearance of water-soluble contrast in the caecum on an abdominal radiograph within 24 hours of its administration predicts resolution of an adhesive small bowel obstruction with a pooled sensitivity of 0.96, specificity of 0.96. The area under the curve of the summary ROC was 0.98. Four randomised studies dealing with the therapeutic role of Gastrografin were included in the review, water-soluble contrast did not reduce the need for surgical intervention (odds ratio 1.29, P = 0.36). Meta-analysis of two studies showed that water-soluble contrast reduced hospital stay compared with placebo (weighted mean difference = - 2.58) P = 0.004. AUTHORS' CONCLUSIONS: Published literature strongly supports the use of water-soluble contrast as a predictive test for non-operative resolution of adhesive small bowel obstruction. Although Gastrografin does not cause resolution of small bowel obstruction, it does appear to reduce hospital stay.

Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects.

The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2,500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM; 19:00 to 21:00 h), or (3) dim (< 10 lux) red evening light (RED). In PMDD subjects, during the luteal phase compared to the follicular menstrual cycle phase, melatonin onset time was delayed, duration was compressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was decreased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the authors' previous observation that nocturnal melatonin concentrations are decreased in women with PMDD and suggest specific effects of light therapy on melatonin circadian rhythms that are associated with mood changes in patient versus control groups. The differential changes in onset and offset times during the menstrual cycle, and in response to AM and PM bright light compared with RED light, support a two-oscillator (complex) model of melatonin regulation in humans.

Blunted phase-shift responses to morning bright light in premenstrual dysphoric disorder.

Patients with premenstrual dysphoric disorder (PMDD) respond therapeutically to sleep deprivation and light therapy. They have blunted circadian rhythms of melatonin. The authors sought to test the hypothesis that these disturbances are a reflection of a disturbance in the underlying circadian pacemaker or, alternatively, that they reflect a disturbance in the input pathways to the clock. To test these hypotheses, after a 2-month diagnostic evaluation, 8 patients who met DSM-IV criteria for PMDD and 5 normal control (NC) subjects underwent two studies to determine whether PMDD subjects showed (1) altered melatonin sensitivity to light suppression (Study 1) and (2) altered phase-shift responses to morning light as a measure of the functional capacity of the underlying pacemaker (Study 2). In both studies, measurements were made during asymptomatic follicular and symptomatic luteal menstrual cycle phases in PMDD patients. The results of Study 1 showed no significant effect of group or menstrual cycle phase on the amount or percentage of suppression of melatonin by light. The results of Study 2 showed that with respect to the variable of offset time, PMDD subjects, when symptomatic, showed a reduced and directionally altered melatonin phase-shift response to a morning bright light stimulus; in 4 of 5 NC subjects, melatonin offset was advanced by bright morning light, whereas in PMDD subjects, it was delayed (3 subjects) or not shifted (5 subjects) (group effect, p = .045). Study 2 also revealed that area under the curve also changed differentially in PMDD versus NC subjects. In summary, the primary findings from this pilot study suggest that in PMDD there is a maladaptive (directionally altered and blunted) response to light in the symptomatic luteal phase. Because the suppressive effects of light were similar in PMDD and NC subjects, the previously observed low melatonin levels in this disorder do not likely represent a disturbance in pineal reactivity to suprachiasmatic nucleus efferents. Instead, the findings support a possible disturbance in PMDD in the clock itself or its coupling mechanisms.

Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects.

The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the temperature acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not associated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

Menstrual cycle effects on catecholamine and cardiovascular responses to acute stress in black but not white normotensive women.

This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately six weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women has higher systolic (P=.01) and diastolic (P=.01) pressures compared with white women. Black women showed greater diastolic pressure (P <.01) and plasma epinephrine (P <.05) responses to stress during the follicular compared with the luteal phase of the menstrual cycle; white women showed no significant changes in these variables. The findings extend the literature on race differences in responsivity to stress and indicate that in contrast to white women, reproductive hormones do influence cardiovascular and catecholamine responsivity to stress in black women.