Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.     

Effects of Repeated Deep Brain Stimulation on Depressive- and Anxiety-Like Behavior in Rats: Comparing Entopeduncular and Subthalamic Nuclei

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) has been routinely used for the treatment of some movement disorders. However, DBS may be associated with adverse psychiatric effects, such as depression, anxiety and impulsivity.ObjectiveTo compare DBS applied to the entopeduncular nucleus (EPN; the rodent homolog of the GPi) and STN in terms of their effects on depressive- and anxiety-like behavior in rats.MethodsDBS was applied for 21 days (4 h a day) to either the STN or EPN. Rats then underwent behavioral testing on learned helplessness and elevated plus maze tasks before being sacrificed for brain analyses of zif268, BDNF and trkB mRNA as well as BDNF protein levels.ResultsRepeated DBS of the STN, but not of the EPN, led to impaired performance in the learned helplessness task, suggesting that STN-DBS induces or potentiates depressive-like behavior. There was no effect of DBS on elevated plus maze or on open field behavior. Repeated STN-DBS, but not EPN-DBS, led to decreased levels of BDNF and trkB mRNA in hippocampus. Acute stimulation of the STN or EPN resulted in similar changes in zif268 levels in several brain areas, except for the raphe where decreases were seen only after STB-DBS.ConclusionsTogether these results indicate that the effects of STN- and EPN-DBS differ in behavioral and neurochemical respects. Results further suggest that the EPN may be a preferable target for clinical DBS when psychiatric side effects are considered insofar as it may be associated with a lower incidence of depressive-like behavior than the STN.     

The validation of personal health questionnaire amongst people of Pakistani family origin living in the United Kingdom

BACKGROUND: The Personal Health Questionnaire (PHQ) was developed to screen for depressive disorder in an English speaking population. Its validity in Urdu speaking people of Pakistani family origin living in UK is yet to be established. METHODS: The PHQ was used to screen for depression in a two phase primary care based study of depressive disorder in people of Pakistani family origin residing in Manchester, UK. A proportion of high scorers (PHQ> or =7) and a random selection of low scorers (PHQ 0-6) were interviewed with the Psychiatric Assessment Schedule (PAS) to confirm caseness (ID> or =5). A receiver operator characteristic curve (ROC) analysis was carried out to confirm the optimum threshold value. RESULTS: The PHQ was used to screen 218 subjects with cut off of PHQ> or =7. 46 high scorers and 31 low scorers were interviewed in second stage using PAS. At this threshold PHQ has a sensitivity of 70.4% and specificity of 89.3%. CONCLUSIONS: Findings of this study confirm high sensitivity and specificity of PHQ amongst people of Pakistani family origin. It can be used as a screening instrument to detect depression in Urdu speaking population in UK.     

A cross-sectional study of antenatal depression and associated factors in Malawi

Depression, and disabling levels of mixed depressive, anxious and somatic symptoms, termed common mental disorder, occurring in the perinatal period are an important health problem in low- and middle-income countries. In this cross-sectional study, pregnant women were recruited from a district hospital antenatal clinic in Malawi. Symptoms of depression and anxiety, and non-specific somatic symptoms commonly associated with distress, were measured using validated local versions of the Self Reporting Questionnaire (SRQ). In a sub-sample, Diagnostic Statistical Manual (DSM)-IV diagnoses of major and minor depressive disorders were made using the Structured Clinical Interview for DSM-IV. Maternal socio-demographic and health variables were measured, and associations with SRQ score and depression diagnosis were determined. Of 599 eligible women, 583 were included in the analysis. The adjusted weighted prevalence of current major depressive episode and current major or minor depressive episode were 10.7 % (95 % CI 6.9–14.5 %) and 21.1 % (95 % CI 15.5–26.6 %), respectively. On multivariate analysis, SRQ score was significantly associated with lower perceived social support, experience of intimate partner violence, having had a complication in a previous delivery, higher maternal mid-upper arm circumference and more years of schooling. Major depressive episode was associated with lower perceived social support and experience of intimate partner violence. This study demonstrates that antenatal depression/CMD is common in Malawi and is associated with factors that may be amenable to psychosocial interventions.     

Determinants of consultation rate in patients with anxiety and depressive disorders in primary care

BACKGROUND: Although it is recognized that anxiety and depression are associated with frequent attendance in primary care, not all patients with these disorders attend frequently. The factors associated with general practice consultation in the important group of patients with anxiety and depressive disorders are not clear. OBJECTIVES: Our aim was to determine prospectively the factors which predict consultation rate in a cohort of patients with anxiety and depressive disorders in primary care. METHODS: A total of 148 adult patients with a depressive, anxiety or panic disorder (DSM-III criteria) were studied prospectively for 6 months to determine the factors which predicted consultation rate during this time. Measures at baseline included: the Psychiatric Assessment Schedule, Hamilton Depression Rating Scale, Life Events and Difficulties Schedule, Clinical Anxiety Scale, details of substance misuse and demographic data. The principal outcome measure was the number of consultations recorded in the GP records over the following 6 months. The variables associated with consultation rate were assessed by multiple regression analysis, with number of consultations as the dependent variable. RESULTS: The median consultation rate during the 6 months of the study was five (range: 1-22). Thirty per cent of the sample consulted seven or more times during the 6 months and 10% consulted 12 or more times. The regression analysis demonstrated that the following variables contributed to the best model: prior consultation rate, past psychiatric history, ongoing social difficulties, current level of alcohol consumption, total psychiatric symptom score and total anxiety score. These variables together accounted for 41% of the variance in consultation rate. CONCLUSION: The detection and rigorous treatment of psychiatric disorder, the provision of social support and interventions for alcohol dependence may help to reduce the frequency of consultation of anxious and depressed patients in primary care. Future research to identify additional variables which explain the major part of the variance in consultation rate may pave the way for novel treatment approaches to the phenomenon of frequent attendance.     

Mechanical properties and innervation of the smooth muscle layers of the urethra of greyhounds

OBJECTIVE: To investigate the properties of the smooth muscle layers in the urethral wall of male and female greyhounds, and to consider their roles in continence and micturition. MATERIALS AND METHODS: The distribution and innervation of the smooth muscle layers of the prostate capsule and membranous urethra of male greyhounds were assessed. Strips of smooth muscle from these regions were used to determine the neuropharmacological properties by assessing the excitatory and inhibitory responses to nerve stimulation, and the effects of blocking agents. These were compared with strips from the proximal urethra and from the female urethra. RESULTS: The smooth muscle of the membranous urethra comprised 9% of the wall and received its innervation exclusively in branches from the pelvic plexus. The cholinergic innervation in the male produced 80% of the total contractile response in the longitudinal membranous urethra, 50% in the prostate capsule and 13% in the circular muscle of the proximal urethra. In the female all areas had poor contractile responses. Inhibitory fibres produced relaxation in all parts of male and female urethrae with the major effect caused by nitric oxide. Adrenergic nerves contributed to both residual excitation (alpha receptors) and inhibition (beta receptors). CONCLUSIONS: The longitudinal smooth muscle of the male membranous urethra probably shortens the urethra during micturition, through the activity of cholinergic nerves, whereas the circular smooth muscle of the proximal urethra, under adrenergic control, may be contracted during continence and ejaculation. In the female, the smooth muscle plays a minor role.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.