Straight to flexible sigmoidoscopy: rationalization of 2-week wait referrals in suspected colorectal cancer.

AIM: The 2-week wait pathway was designed to decrease the time from presentation to primary care of patients with 'red flag' symptoms of suspected cancer for review by a specialist for the diagnosis or exclusion of cancer. In our tertiary referral centre we have found that 968 colonoscopies per year are required to satisfy the demand for the 2-week wait, leading to limited colonoscopy availability for other services. We sought to determine the yield of colorectal cancer found at colonoscopy referred via the 2-week wait and referenced to the original red flag symptoms. This was in order to select the most efficacious alternative primary investigation based upon presenting symptoms. METHOD: Electronic records were retrospectively analysed. All patients who went through the 2-week wait for suspicion of colorectal cancer in 2013 and were found to have colorectal cancer on colonoscopy were included. Patients not undergoing colonoscopy as the first investigation were excluded. The splenic flexure was deemed to be within the range of a flexible sigmoidoscope. RESULTS: In all, 2950 referrals were made. 968 colonoscopies were performed as the primary investigation of which 35 were found to have colorectal cancer. No patients referred with rectal bleeding and another symptom had a tumour more proximal to the range of flexible sigmoidoscopy. 80% of tumours proximal to the splenic flexure were suitable for CT diagnosis alone. CONCLUSION: Our data support the use of flexible sigmoidoscopy alone as an initial investigation for patients presenting with rectal bleeding with or without additional colorectal symptoms. Patients with anaemia (without bleeding) or change in bowel habit (without bleeding) may be investigated with CT colonography alone; colonoscopy may then be used selectively prior to surgery.

Stressful life events, personal losses, and perimenopause-related depression.

We compared the number and quality of life events reported by depressed perimenopausal women and a non-depressed comparison group. Additionally, we examined the effects of the presence of hot flushes on life event reports. All women were 44-55 years old, had irregular menses and elevated plasma gonadotropin levels. The Psychiatric Epidemiology Research Interview recorded both the frequency of occurrence and the desirability of life events experienced by the women during the six months prior to the interview. Depressed perimenopausal women (n=50) reported significantly more undesirable events [Student's t-test (unpaired) with Bonferroni correction, t(98)=3.9, p=0.001] but not more exit events (e.g., divorce, last child leaving home or death in family) (t(98)=0.9, p=NS) compared to the non-depressed women (n=50). There were no effects of hot flushes on these diagnostic differences. The "empty nest" syndrome does not appear to be relevant in the development of perimenopausal depression. Nevertheless, independent of the presence of hot flushes, perimenopausal depressed women are more likely to report both negative life events and diminished self esteem.

Basal plasma hormone levels in depressed perimenopausal women.

BACKGROUND: An association between abnormal changes in reproductive endocrine function during the perimenopause and the onset of depression in some women has been suggested but remains controversial. METHODS: We examined basal plasma hormone levels in two samples of women with well characterized, first onset depression (major or minor) during the perimenopause and matched comparison groups of asymptomatic women. Results were compared by analysis of variance. RESULTS: No significant diagnosis-related differences were observed in plasma hormone measures of the following: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), estrone (E1), total (T) or free testosterone (FT), or the E2/LH ratio. We did identify significantly lower morning plasma dehydroepiandrosterone (DHEA) and its sulphated metabolite DHEA-S (but not cortisol) levels in the depressed women compared to the non-depressed comparison group. Women with hot flushes (regardless of the presence of depression) were significantly older than women without flushes, had significantly higher plasma levels of FT, LH and FSH, and had significantly lower E2/LH ratios. CONCLUSIONS: Women with first onset depression during the perimenopause are not distinguished from controls on the basis of basal hormone measures of ovarian estrogens, testosterone, or gonadotropins. However, perimenopause-related changes in E2 may interact with low levels of DHEA in some women to increase their vulnerability to develop depression. In contrast to perimenopause-related vasomotor symptoms, depression during the perimenopause is not associated with a simple hormone deficiency state. The relatively low levels of E2 and E1 in the depressed women may have met statistical significance in a much larger and homogenous sample.

Estrogen replacement in perimenopause-related depression: a preliminary report.

OBJECTIVES: We examined the efficacy of estrogen in the treatment of depression in perimenopausal women with and without hot flushes. STUDY DESIGN: Women with perimenopause-related depression were randomized in a double-blind parallel design to receive either 17beta-estradiol or placebo for 3 weeks. Subsequently, women receiving estradiol during the first 3 weeks continued receiving estradiol for an additional 3 weeks, whereas women who had received placebo crossed over to estradiol for 3 weeks. Outcome measures included standardized mood rating scales and a visual analog scale self-report instrument. RESULTS: Of 34 female subjects, 16 received estradiol first and 18 received placebo first. After 3 weeks of estradiol, standardized mood rating scale scores and visual analog scale symptom scores (eg, sadness, anhedonia, and social isolation) were significantly decreased compared with baseline scores (P <.01) and were significantly lower than scores in women receiving placebo (P <.01), who showed no significant improvement. Neither the presence of hot flushes nor the duration of treatment (3 weeks vs 6 weeks) influenced outcome. A full or partial therapeutic response was seen in 80% of subjects receiving estradiol and 22% of those receiving placebo. CONCLUSION: In this preliminary study estradiol replacement effectively treats perimenopausal depression independent of its salutary effects on vasomotor symptoms.

Concentration and extinction coefficient determination for oligonucleotides and analogs using a general phosphate analysis.

A general phosphate analysis (GPA) is developed which assays the concentration of nucleic acid oligomers and their analogs based on stoichiometric phosphorus in the sequence. The method involves complete digestion of the oligomer sample to orthophosphate using acid at high temperature and subsequent colorimetric analysis by phosphomolybdate complex formation. GPA is applied to oligomers having phosphodiester, methylphosphonate, and phosphorothioate backbone linkages. Given the absorption spectra of oligomers having these backbones, extinction coefficients are obtained and compared to other quantitative and predictive methods. In addition to sequences having the usual nucleoside residues found in naturally occurring nucleic acids, oligomers having base analog residues can be readily quantified by GPA.

Reduction in lung injury after combined surfactant and high-frequency ventilation.

Previous studies demonstrated that high-frequency oscillatory ventilation (HFOV) begun at birth limits the development of alveolar proteinaceous edema in premature monkeys at risk for hyaline membrane disease (HMD). We hypothesized that exogenous surfactant combined with HFOV would lead to even further reductions in edema. Twenty Macaca nemestrina monkeys were delivered at 134 d gestation (term = 168 d) and treated with either HFOV or conventional mechanical ventilation (CMV) from the first breath; modified bovine surfactant (Survanta [beractant]) was introduced into the trachea over the first few minutes of life. These animals were compared with 20 animals treated with either CMV or HFOV but without surfactant. At 6 h the lung was rapidly frozen in situ during inflation for determination of the volume fraction of alveolar edema. The combined use of surfactant and HFOV from the first breath reduced alveolar proteinaceous edema (3 +/- 1%; mean +/- SEM) from that seen with CMV alone (27 +/- 3%, p < 0.0001), CMV after surfactant (21 +/- 3%, p < 0.0001), and HFOV alone (13 +/- 3%, p < 0.015). We conclude that the use of surfactant with HFOV after premature birth is superior to either surfactant or HFOV alone in reducing lung injury during the first few hours of life. We speculate that this reduction in lung injury may reduce the incidence or severity of bronchopulmonary dysplasia.

Acute changes in vasoactive lipid mediators in experimental hyaline membrane disease.

Endothelial release of the arachidonate derivative PGI2 may be increased in response to cyclic lung stretching. We therefore sought to determine if the stable metabolite of PGI2, 6-keto-PGF1 alpha, would be found in increased quantities in primates ventilated with conventional mechanical ventilation (CMV) compared to treatment with high frequency oscillatory ventilation (HFOV). We also sought to determine if other membrane-derived vasoactive substances such as LTC4, PAF and TXB2 would be elevated in plasma and lung tissue of animals developing hyaline membrane disease (HMD) and if the levels would correlate with the severity of the respiratory distress. Twenty prematurely delivered monkeys were treated with either CMV or HFOV from the first breath after Cesarean delivery until sacrifice at 6 h of age. We found a significant increase from birth to 5 min and from 5 min to 5 h in 6-keto-PGF1 alpha, and a significant increase from 5 min to 5 h in TXB2. We found a significant decline from cord blood to 5 min of LTC4, without further change by 5 h. PAF was present in all plasma samples but showed no upward or downward trend. There was no difference in the 5-h plasma level or in the lung homogenate level of any of the lipid mediators between the two types of assisted ventilation. There was no correlation between any lipid mediator level and severity of the HMD, as measured by gas exchange, radiographic or histologic criteria, when assessed by each ventilator group alone or with both groups combined. We conclude that the immediate postnatal increases in TXB2 and PGI2 and decrease in LTC4 are not altered substantially by use of HFOV.

Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery.

The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients.

Exposure of hospital operating room personnel to potentially harmful environmental agents.

Epidemiologic studies of risk to reproductive health arising from the operating room environment have been inconclusive and lack quantitative exposure information. This study was undertaken to quantify exposure of operating room (OR) personnel to anesthetic agents, x-radiation, methyl methacrylate, and ethylene oxide and to determine how exposure varies with different operating room factors. Exposures of anesthetists and nurses to these agents were determined in selected operating rooms over three consecutive days. Each subject was asked to wear an x-radiation dosimeter for 1 month. Exposure to anesthetic agents was found to be influenced by the age of the OR facility, type of surgical service, number of procedures carried out during the day, type of anesthetic circuitry, and method of anesthesia delivery. Anesthetists were found to have significantly greater exposures than OR nurses. Exposure of OR personnel to ethylene oxide, methyl methacrylate, and x-radiation were well within existing standards. Exposure of anesthetists and nurses to anesthetic agents, at times, was in excess of Ontario exposure guidelines, despite improvements in the control of anesthetic pollution.

Effect of high-frequency ventilation on the development of alveolar edema in premature monkeys at risk for hyaline membrane disease.

High-frequency oscillatory ventilation (HFOV) permits adequate gas exchange but avoids the large phasic pressure-volume excursions of conventional mechanical ventilation (CMV); such avoidance may reduce the lung injury associated with hyaline membrane disease (HMD). We hypothesized that premature monkeys ventilated from birth with HFOV would have reduced lung injury compared to those assigned to CMV. Macaca nemestrina were delivered at 134 days (80% of term gestation) and ventilated from the first breath with either HFOV (n = 10) or CMV (n = 10). The mean airway pressure (Paw) was kept at 15 cm H2O pressure in HFOV animals; in CMV animals Paw was increased from 8 cm H2O at 2 h to 13 cm H2O at 6 h to prevent hypoxemia. At the conclusion of the 6-h experiment the HFOV animals had better oxygenation (p less than 0.05) and less evidence of HMD by chest radiograph (p less than 0.05). At 6 h of age a piece of the right middle lung lobe was removed, divided, and placed in fixatives for light and transmission electron microscopy. The lungs were subsequently inflated to 30 cm H2O pressure, and the right lower lobe was rapidly frozen in situ for morphometric studies. The proportion of peripheral lung tissue occupied by clear alveoli was greater in HFOV animals (66.3 +/- 14.8%) than in those assigned to CMV (44.2 +/- 16.9%, p less than 0.01); less alveolar debris and fluid was present in the HFOV animals (12.7 +/- 9.9%) compared with CMV animals (27.1 +/- 12.5%, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen synthesis during lung development and during hyaline membrane disease in the nonhuman primate.

To assess maturational changes in collagen synthesis, lung tissue was obtained from healthy Macaca nemestrina monkeys at different ages, ranging from 68% of term gestation to adulthood. We hypothesized that infants delivered prematurely have a greater rate of collagen synthesis than do older animals because of their greater rate of lung growth during gestation. Secondly, we hypothesized that lung repair in infants with hyaline membrane disease (HMD) is associated with an additional increase in lung collagen synthesis rate. Therefore, lung tissue was obtained during the first week of life from monkeys delivered at 82% of term gestation, a stage at which half of them developed HMD. The rate of total protein synthesis in lung samples was determined by measuring the incorporation of [3H]proline; the rate of collagen synthesis was determined by measuring the conversion of proline into hydroxyproline. Premature monkeys had a higher rate of collagen synthesis (9.9 +/- 2.7 nmol/mg DNA/h) than did term infants (5.3 +/- 1.1) or older animals (2.1 +/- 0.4, p less than 0.05). There was no additional increase in rate of collagen synthesis in animals with HMD from 3 h (14.3 +/- 6.9) to 7 days of age (15.1 +/- 6.1); control premature animals also had no significant change during the first week of life (10.9 +/- 3.0 at 3 h; 11.6 +/- 4.6 at 7 days). The early stage of recovery from HMD in premature monkeys does not appear to be associated with an increase in collagen production beyond the already increased synthesis rate associated with lung growth.

Postnatal changes in lung phospholipids and alveolar macrophages in term newborn monkeys.

In order to better understand the postnatal sequence of surfactant secretion and establishment of the alveolar macrophage (AM) population in newborn primates, healthy Macaca nemestrina monkeys were sacrificed during fetal life at term gestation (n = 5), or at 2 days (n = 5) or 3-4 weeks (n = 5) after term vaginal delivery. Excised lung tissue and left lung lavage were analyzed for phospholipid (PL) content, surface active material (SAM) extract, PL components, surface activity, pressure-volume characteristics, and AM number. Compared to term fetal animals, 2 day old term newborn monkeys were found to have a several-fold increase in lavage PL and SAM, and this was associated with greater maximal lung volume and drier lungs, but not improved deflation stability. During the subsequent 3-4 weeks of life, a 42% reduction in lung tissue stores of PL and SAM, and an 87% reduction in lavage PL and SAM were noted. Despite these major changes in quantity, there were relatively minor changes in the composition of the PL synthesized and released. The reduced quantity of SAM in the 3-4 week old animals led to a small decline in deflation stability. The several-fold increase in lavage PL and SAM during the first 2 days of life was accompanied by a 33-fold increase in AM; there was an additional 4-fold increase in AM number by 3-4 weeks of age. The abundance of lavage surfactant at 2 days of age may play a role in the influx of AM.

Surfactant quantity and composition during recovery from hyaline membrane disease.

The appearance of phosphatidylglycerol in the tracheal wash of infants with hyaline membrane disease (HMD) has been reported to be associated with clinical signs of recovery. We analyzed lung tissue and bronchoalveolar lavage surfactant in an animal model of HMD to determine whether phosphatidylglycerol or some other component is necessary for recovery. The amount and composition of phospholipid (PL) was determined in the premature Macaca nemestrina monkey (140 days' gestation) during an acute stage of HMD, and in two stages of recovery. These changes were compared to observations made in healthy premature controls (140 days), gestational age-matched fetuses (140 days), and fetuses of 150 days' gestation (term = 168 days). The amount of PL and its surfactant composition in lung homogenates of the right lower lobe and in lavage of the excised left lung was determined. Compared to 140-day fetuses, the healthy controls had a several-fold increase in lavage PL and disaturated phosphatidylcholine (DSPC) during the first few days of life (p less than 0.05). Prior to recovery, animals with HMD had no such increase in lavage PL or DSPC and demonstrated poor deflation stability. Recovery was associated with increased tissue and lavage PL (p less than 0.05) and increased fractions of phosphatidylinositol and DSPC (p less than 0.05), but not phosphatidylglycerol. The tissue compositional changes observed during recovery reflected maturational changes observed in the fetal animals studied at 10 days' greater gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in lung volume and deflation stability in hyaline membrane disease.

Total lung capacity (TLC), inspiratory capacity, functional residual capacity, and deflation stability of prematurely delivered Macaca nemestrina primates were measured serially during development of, and recovery from, hyaline membrane disease (HMD) to relate changes in lung volumes to changes in deflation stability. Gestational age-matched primates that did not develop HMD served as controls. TLC, measured by N2 washout, fell at 2-12 h of age (P less than 0.0001) in animals with HMD and remained lower than controls for at least 48 h (P less than 0.005). However, deflation stability, defined as the fraction of TLC remaining upon deflation to 10 cm H2O, improved from 2 to 12 h of age (P less than 0.001). Postmortem studies confirm the measurements of TLC and deflation stability and provide evidence that interstitial thickening and obstruction of air spaces with debris may be partially responsible for the observed changes in TLC in primates that develop HMD. It has been assumed that TLC is reduced in HMD because of atelectasis from elevated alveolar surface tension, but the sequential measurements in these animals suggest that other mechanisms also contribute.

Bronchopulmonary dysplasia and pulmonary insufficiency of prematurity. Lack of correlation of outcome with gas exchange abnormalities at 1 month of age.

A review of all infants admitted to the two intensive care nurseries in Seattle from July 1, 1980, through Dec 31, 1981, was performed to evaluate the outcome of infants still requiring supplemental oxygen and/or mechanical ventilation at 1 month of age. Sixty-three infants were identified. Fifty-six infants survived to at least 2 years of age, including 11 of 13 in the subgroup of infants requiring 40% or more oxygen at 1 month of age. Eight (14%) of the 56 survivors have required prolonged rehospitalization for pneumonia or other respiratory illnesses in the first two years following birth. We conclude that the degree of gas exchange impairment assessed at 1 month of age does not predict ultimate outcome from neonatal chronic lung disease.

Factors related to the appearance of alveolar macrophages in the developing lung.

The numbers of alveolar macrophages (AM) are known to be low in utero and to increase rapidly after birth. This study analyzed factors related to the appearance of AM in the lungs of term and preterm monkeys (Macaca nemestrina). We found that the numbers of AM were greater at birth in term than in preterm monkeys (p less than 0.01) and that they increased with postnatal age in term animals (r = 0.86) and in preterm animals without hyaline membrane disease (HMD) (r = 0.79). In contrast, the numbers of AM did not increase with postnatal age in preterm animals with HMD (r = 0.17). By multivariant analysis, AM numbers correlated most strongly with a combination of 2 variables: lavage fluid phospholipid and absence of HMD (r = 0.996). Preparations of alveolar surface-active material from newborn monkeys and to a lesser degree from adult monkeys were found to stimulate migration and polarization of monkey AM and blood monocytes in vitro. The migration-stimulating factor(s) in alveolar surface-active material had an apparent molecular weight greater than 10,000 and appeared not to be a lipoxygenase product of arachidonic acid metabolism. These data indicate a correlation between factors regulating lung pressure-volume stability and AM numbers and are consistent with a potential role for components of alveolar surface-active material in regulating the perinatal increase in AM.

Left ventricular function before and after reaching the anaerobic threshold.

Simultaneous pulmonary gas exchange analysis and exercise radionuclide angiography were performed in 24 normal patients (14 supine and ten upright). Left ventricular (LV) volumes and ejection fraction (EF) were measured at rest, anaerobic threshold (point of nonlinear increase in ventilation relative to oxygen uptake), and peak exercise. The anaerobic threshold occurred at a similar heart rate for supine vs upright exercise, 78 percent and 77 percent of peak heart rate, respectively. The anaerobic threshold occurred at a similar workload for supine vs upright exercise, 60 percent and 56 percent of peak workload, respectively. The anaerobic threshold also occurred at a similar oxygen uptake for supine vs upright exercise, 69 percent vs 69 percent of peak oxygen uptake, respectively. For both exercise modes, mean LVEF increased (p less than 0.01) by a similar amount (.06 vs .07) from rest to anaerobic threshold, but there was no further increase from anaerobic threshold to peak exercise. The mechanism of the increase was a reduction in end-systolic volume with little or no change in end-diastolic volume. This increase was not seen in patients with rest LVEF in the high normal range (greater than 0.68). Therefore, for both supine and upright exercise, the major augmentation in LVEF occurs at earlier stages of exercise, prior to the anaerobic threshold. After the anaerobic threshold, the LVEF response may be highly variable, and a uniform increase is not necessarily expected even in normal subjects.

Value and limitations of radionuclide angiography in determining the cause of reduced left ventricular ejection fraction: comparison of idiopathic dilated cardiomyopathy and coronary artery disease.

The radionuclide angiograms of 59 patients with a left ventricular (LV) ejection fraction (EF) less than 0.40, 23 with idiopathic dilated cardiomyopathy (IDC) and 36 with coronary artery disease (CAD) were analyzed to assess the usefulness of radionuclide angiography in distinguishing these conditions. Mean right ventricular EF was lower in the IDC group than in the CAD group, 0.31 vs 0.45 (p less than 0.01). LV wall motion was scored from 3 (normal) to -1 (dyskinesia). The incidence of akinesia was similar in IDC and CAD groups, 70% and 83%, respectively. Dyskinesia was more common in the CAD group (42% vs 17%), but the difference was not statistically significant. Segmental wall motion analysis showed similar patterns of wall motion in both groups, with contraction best preserved in the anterobasal, posterobasal and superolateral segments. Patients in the CAD group had worse apical motion (p less than 0.01) and better wall motion in the anterobasal (p less than 0.05) and superolateral walls (p less than 0.01), compared with patients in the IDC group. To assess symmetry of contraction, a maximum difference score was derived for each patient. Symmetry (a score less than 1) was present in 5 IDC and no CAD patients, whereas asymmetry (a score of 2 or more) was present in 27 CAD and 7 IDC patients (p less than 0.01). Wall motion became more symmetric in both groups when LVEF was less than 0.20. Logistic regression analysis revealed that the maximum difference score was the best predictor of the diagnosis, but only because of better separation at the extremes of maximum difference score values.(ABSTRACT TRUNCATED AT 250 WORDS)