Depressive symptoms post hip fracture in older adults are associated with phenotypic and functional alterations in T cells

Background

Ageing is accompanied by reduced immunity, termed immunesenescence. The immune system does not act in isolation and is sensitive to both psychological and physical stress. Hip fracture is a common physical stressor in older adults with a high incidence of new onset depression, which relates to poorer prognosis. We therefore set out to examine the possible synergistic effects of physical stress (hip fracture) and psychological stress (depressive symptoms) on the aged immune system.

Results

T cell phenotype and function was assessed in 101 hip fracture patients (81 female) 6 weeks after hip fracture and 43 healthy age-matched controls (26 female). 38 fracture patients had depressive symptoms at 6 weeks. T cell frequency (p?=?.01) and numbers (p?=?.003) were both lower in depressed hip fracture patients compared to healthy controls. The frequency of senescent CD28^-ve (p?=?.001), CD57^+ve (p?=?.001), KLRG1^+ve (p?=?.03) CD8 T cells, as well as senescent CD28^-ve CD4^+ve (p?=?.01) and CD57^+ve CD4^+ve (p?=?.003) T cells were higher in depressed hip fracture patients compared with healthy controls and the frequency of CD28^-ve CD8 T cells was also higher when compared to patients with hip fracture alone (p?=?.01). Additionally, activated CD69^+ve (p?=?.005) and HLADR^+ve (p?<?.001) CD8 T cells, were also higher in depressed hip fracture patients compared to healthy controls. On examining cytokine production by activated T cells, a significant increase in TNFα (p?=?.03) and IL6 (p?=?.04) production was observed in CD4 T cells from hip fracture patients with depressive symptoms compared to healthy controls.

Conclusions

As none of the patients in the study had a prior history of depression, our data suggest that the development of depressive symptoms in hip fracture patients is associated with altered T cell phenotype and increased pro-inflammatory function which is not seen in patients who do not develop depression after hip fracture. Treating depressive symptoms promptly in hip fracture patients may therefore improve immunity and outcomes in these patients.

     

Conduction of the cardiac impulse. 3. Characteristics of very slow conduction

The excitability of short segments (5–7 mm) of bundles of canine Purkinje fibers was depressed by exposure to 15–18 mM K⁺, to 15–18 mM K⁺ plus 5 x 10^-6 epinephrine or norepinephrine, to low K⁺, and to low Na⁺. The depressed segment was in the center chamber of a three-chamber bath; the ends of the bundle were exposed to normal Tyrode solution. Each method of depression resulted in slow and probably decremental conduction with an effective conduction velocity in the middle chamber of about 0.05 m/sec, or one-way block, or two-way block with summation of the graded responses in the depressed region. The action potential in the depressed segment (the slow response) differs from the normal action potential in its response to applied stimuli. A second active depolarization can be evoked by cathodal stimulation during much of the slow response. The response in the depressed segment is graded. The response of depressed fibers may depend on excitatory events similar to those responsible for the slow component of the cardiac action potential. It is suggested that the slow response can propagate, at least decrementally, in fibers in which the rapid, Na⁺-dependent upstroke is absent, and can cause reentrant excitation by so doing.     

Defective serotonin transport mechanism in platelets from endogenously depressed patients

The 5-HT uptake kinetics in platelets from ten depressed patients were studied with a highly reproducible method which detects specific changes in the platelet 5-HT transport. The six patients with endogenous depression had a disturbed 5-HT-uptake. A passive diffusion of 5-HT predominated over the active 5-HT-transport. This disturbance was not found in the four non-endogenously depressed patients or in the fifty normal controls. These findings suggest that platelets from endogenously depressed patients may have abnormal physical membrane characteristics.     

Social and psychological factors of the suicidal tendencies of Chinese medical students

Background

Over the past few decades, concern about suicide by college students has been on the rise worldwide, in general and in China particularly. The main objective of this study is to investigate the effects of social and psychological factors on the suicidal tendencies of Chinese medical students.

Findings

Of the 540 students surveyed, 48 had a suicidal tendency to some extent. The highest rate of suicide was observed for fourth-year students, followed by the fifth-year, first-year, third-year, and second-year students. Female students and students not satisfied with their major had a higher rate of suicidal tendency. However, mature coping strategies had a protective effect on suicide. The stepwise regression analysis shows that academic burden, grade, and introversion/extraversion are the most significant risk factors for the suicidal tendency of Chinese medical students.

Conclusion

Suicide is affected by demographic risk factors as well as psychological factors. Our results lend support to a multi-factorial approach to the understanding and prevention of suicide by college students.

     

Enhanced serum cortisol response to 5-hydroxytryptophan in depression and mania

The serum cortisol responses to D, L-5-hydroxytryptophan (5-HTP), 200 mg per oral, in unmedicated depressed and manic patients, were both significantly greater than that of normal controls. The cortisol response to 5-HTP in depressed patients was significantly correlated with ratings of specific symptoms of depression. It was also greater in non-psychotic than in psychotic depressed patients as well as in those manic or depressed patients who attempted suicide compared to those who had not. In view of evidence for decreased brain serotonergic activity in depression and perhaps mania, the results suggest at least some serotonin receptors may be supersensitive in some patients with affective disorders.     

Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital

Background

An important number of patients with suspected cardiac chest pain have non-obstructive coronary artery disease. Our purpose was to describe the clinical characteristics of patients with normal or near-normal coronary arteries in routine cardiological practice in a secondary care hospital.

Methods

In 2013, consecutive patients referred for invasive coronary angiography with suspected cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn, the Netherlands). Coronary arteries were defined as normal or near-normal if they showed no stenosis or only slight wall irregularities on visual assessment. Patients with a final non-cardiac diagnosis for the chest pain were excluded.

Results

A total of 558 patients were included. Of these, 151 (27%) showed normal or near-normal coronary arteries on visual assessment. This group of patients were significantly more often female (p < 0.001), younger (p < 0.001) and non-diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or near-normal coronary arteries at coronary angiography showed an elevated troponin.

Conclusion

In routine cardiological practice, around 1 out of 4 patients with suspected cardiac chest pain undergoing invasive angiography had normal or near-normal coronary arteries. We suggest that premenopausal women with suspected cardiac chest pain could be considered for non-invasive coronary imaging as a first step in clinical practice.

     

Castelli risk indexes 1 and 2 are higher in major depression but other characteristics of the metabolic syndrome are not specific to mood disorders

Aims

This study examined whether Castelli risk indexes 1 (total/high-density lipoprotein (HDL) cholesterol) and 2 (low density lipoprotein (LDL)/HDL cholesterol) and other shared metabolic disorders might underpin the pathophysiology of the metabolic syndrome, major depression or bipolar disorder.

Main methods

This cross-sectional study examined 92 major depressed, 49 bipolar depressed and 201 normal controls in whom the Castelli risk indexes 1 and 2 and key characteristics of the metabolic syndrome, i.e. waist/hip circumference, body mass index (BMI), systolic/diastolic blood pressure, total cholesterol, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides, insulin, glucose, hemoglobin A1c (HbA1c) and homocysteine were assessed.

Key findings

Castelli risk indexes 1 and 2 were significantly higher in major depressed patients than in bipolar disorder patients and controls. There were no significant differences in waist or hip circumference, total and LDL cholesterol, triglycerides, plasma glucose, insulin, homocysteine and HbA1c between depression and bipolar patients and controls. Bipolar patients had a significantly higher BMI than major depressed patients and normal controls.

Significance

Major depression is accompanied by increased Castelli risk indexes 1 and 2, which may be risk factors for cardiovascular disease. Other key characteristics of the metabolic syndrome, either metabolic biomarkers or central obesity, are not necessarily specific to major depression or bipolar disorder.     

Quantitation of T- and B-lymphocytes in peripheral blood of patients with solid tumours. I. Relation to other parameters of in vivo and in vitro immune competence.

The absolute number of T- and B-lymphocytes in the peripheral blood was measured in 22 patients with disseminated nonlymphoid solid malignant tumours. Patients with normal absolute lymphocyte counts had normal absolute numbers of T- and B-lymphocytes; patients with low counts had low numbers. The percentage of T- and B-lymphocytes was similar, in both groups of patients, to that of healthy control subjects. Patients with a normal absolute lymphocyte count had better in vitro lymphocyte responses to mitogenic agents than did patients with low absolute lymphocyte counts. Improvement of depressed in vitro lymphocyte responses to normal on culture of cells in AB plasma was most likely in patients with normal absolute lymphocyte counts. The absolute lymphocyte count by itself, then, provides useful information about the immune status of patients with solid malignant tumours.     

Is sleep apnea underdiagnosed in adult patients with osteogenesis imperfecta? –a single-center cross-sectional study

Background

Patients with Osteogenesis imperfecta (OI) suffer from increased bone fracture tendency generally caused by a mutation in genes coding for type I collagen. OI is also characterized by numerous co-morbidities, and recent data from questionnaire studies suggest that these may include increased risk for sleep apnea, a finding that lacks clinical evidence from cohort studies. In this cross-sectional study, 25 adults with OI underwent clinical otorhinolaryngology examination as well as overnight polysomnography to address the question. The participants were aged between 19 and 77?years, and ten of them had mild clinical OI phenotype, seven had a moderately severe phenotype, and eight had a severe phenotype.

Results

We found obstructive sleep apnea (apnea hypopnea index ≥5/h) in as many as 52% of the OI patients in the cohort. Unexpectedly, however, no correlation was present between sleep apnea and daytime sleepiness, experienced bodily pain, severity of OI, Mallampati score, or neck circumference.

Conclusions

Seeing that the usual predictors showed no association with occurrence of sleep apnea, we conclude that obstructive sleep apnea may easily be left as an undetected disorder in individuals with OI. Recurrent nocturnal hypoxia due to episodes of apneas can even affect bone metabolism, thereby further aggravating bone fragility in patients with OI.

     

Peripheral metabolic abnormalities of lipids and amino acids implicated in increased risk of suicidal behavior in major depressive disorder

Suicide is the most serious consequence of major depressive disorder (MDD), yet a vast majority of MDD patients never attempt nor commit suicide. This discrepancy suggests a predisposition to suicidal behavior independent of MDD. However, the molecular basis of this predisposition remains largely unknown, hampering development of specific and targeted treatment of MDD patients at risk for suicide. A proton nuclear magnetic resonance (¹H NMR)-based metabonomic approach was used to capture metabolic perturbations related to suicide predisposition in the context of MDD. ¹H NMR spectra of plasma sampled from drug-naïve depressed suicide attempters (n = 21), non-attempters (n = 35), and healthy controls (n = 35) were recorded and analyzed through a multivariate statistical approach. Multivariate statistical analysis demonstrated that the depressed suicide attempter group was significantly distinguishable from the depressed non-attempter group and controls group. Several key metabolites, including lipids (low-density lipoprotein, very low-density lipoprotein, cholesterol and unsaturated lipid), lipid metabolism-related molecules (glucose, pyruvate and lactate) and amino acids (alanine, glycine and taurine) responsible for discriminating depressed suicide attempters from the nonattempters and controls were identified. This study is the first to indicate that peripheral perturbations in lipid and amino acid metabolism may be implicated in the predisposition to suicide in MDD patients.     

Heat-stress response of broiler cockerels to manipulation of the gonadal steroids,testosterone and estradiol

• 1.1. Estradiol supplementation resulted in heat-stress mortality in both intact and caponized cockerels accompanied by depressed plasma c corticosterone.
• 2.2. Phenotype-selection for large comb and high plasma testosterone increased heat tolerance which was attributed to an increased plasma corticosterone.
• 3.3. The results suggested that the presence of testosterone had a positive influence on the heat tolerance of broiler cockerels.

     

Normalization of defective monocyte chemotaxis during chemotherapy in patients with small cell anaplastic carcinoma of the lung

Summary Monocyte chemotactic responsiveness (MCR) in 14 patients with small cell anaplastic bronchogenic carcinoma was depressed before treatment compared with the MCR in 28 normal controls (P=0.00004). MCR was subsequently monitored during combination chemotherapy and after 6 months the MCR had become normalized compared with pretreatment values (P=0.00006).In addition, chemotactic factor inhibitor (CFI) activity in plasma was measured before treatment and after 6 months. When incubated with plasma before treatment casein had 62% of normal activity and when incubated with plasma after chemotherapy, 81% of normal activity (P=0.0009). CFI activity decreased by greater amounts in patients in complete remission than in patients in partial remission or in non-responders (P=0.01). This study supports the concept that cancer patients have depressed monocyte function. Chemotherapy seems to enhance monocyte chemotaxis in vitro and to decrease CFI activity in plasma.     

Dexamethasone suppression test in major and minor depressive disorders

The validity of the dexamethasone ofe suppression test was evaluated for the differential diagnosis of major and minor depressive disorders. Thirty-eight out-patients (14 major depressed, 14 minor depressed and 10 normal controls) were studied. The Research Diagnostic Criteria of Spitzer et al. (1978) were used to classify these patients. Six out of the 14 major depressed patients had an abnormally high plasma cortisol at 4 p.m. and at 11.00 p.m. after midnight 2 mg-dexamethasone. None of the 14 minor depressed patients and none of the 10 controls had an abnormal response to dexamethasone. Based on these results, the dexamethasone suppression test has a sensitivity of 43%, a specificity of 100% and a high predictive value.     

Clinical and endocrine characteristics in atypical and classical growth hormone insensitivity syndrome

OBJECTIVE: Classical growth hormone insensitivity syndrome (GHIS) comprises a dysmorphic phenotype, extreme short stature (height SDS < 3), normal GH and low IGF-I and IGFBP-3. Wide clinical variation is recognised with classical and atypical forms. We aimed to delineate features of the milder "atypical" GHIS phenotype, and to determine whether this correlates with milder auxological and biochemical features. METHODS: Fifty-nine patients from a European series of 82 patients with GHIS, with strict diagnostic criteria of GHIS, were studied and assigned to classical or atypical GHIS groups according to facial phenotype, i.e. "classical" required 2 of 3 recognized GHIS features (frontal bossing, mid-facial hypoplasia and depressed nasal bridge), "atypical" required 0 or 1 of these facial features. Classical and atypical GHIS groups were compared in terms of (1) phenotypic features, including high-pitched voice, sparse hair, blue sclera, hypoglycaemia, microphallus, (2) birth length, height SDS, and (3) basal IGF-I, IGF-II, IGFBP-1, IGFBP-3, GHBP and increase in IGF-I on IGF-I generation testing. RESULTS: Fifty patients [24 males, 26 females, aged 8.6 +/- 4.6 years (mean +/- SD)] had "classical GHIS", 9 patients (7 males, 2 females, aged 7.8 +/- 4.1 years) had "atypical GHIS", 7 with normal facies. Atypical GHIS patients had lesser height deficit (Ht SDS -4.0 +/- 1.4) compared to classical GHIS (-6.7 +/- 1.4), less reduction in IGFBP-3 SDS (atypical -5.5 +/- 3.3; classical -8.6 +/- 2.4), and more had normal GHBP (>10% binding). Other variables were also less frequent in atypical GHIS patients: high-pitched voice 11% (70% classical), sparse hair 11% (42% classical), blue sclera 0% (38% classical), hypoglycaemia 11% (42% classical), and microphallus 14% (1 of 7 males), compared to 79% of classical (19 of 24 males). CONCLUSIONS: Atypical GHIS patients, with relatively normal facial appearance, demonstrate less height defect and biochemical abnormalities compared to classical patients. GH insensitivity may be present in children with short stature and an otherwise normal appearance.     

The association between type D personality,and depression and anxiety ten years after PCI

Objective

There are indications that type D personality and depression are associated in patients treated with percutaneous coronary intervention (PCI). However, at present it is unclear whether this relationship holds in the long term. This study’s aim was to investigate the association between type D personality at 6 months post-PCI (baseline), and depression at 10-year follow-up. A secondary aim was to test the association between type D personality at baseline and anxiety at 10-year follow-up.

Methods

A cohort of surviving consecutive patients (N = 534) who underwent PCI between October 2001 and October 2002. Patients completed the type D personality scale (DS14) measuring type D personality at baseline, and the Hospital Anxiety and Depression Scale (HADS) measuring anxiety and depression at baseline and at 10 years post-PCI.

Results

At baseline, the prevalence of type D personality was 25?% (135/534). Type D personality patients were more often depressed (42?%) than non-type D personality patients (9?%). Response rate of anxiety and depression questionnaires at 10 years was 75?%. At 10-year follow-up, 31?% of type D personality patients were depressed versus 13?% of non-type D personality patients. After adjustments, baseline type D personality remained independently associated with depression at 10 years (OR = 3.69; 95?% CI [1.89–7.19]). Type D showed a similar association with anxiety at 10 years, albeit somewhat lower (OR = 2.72; 95?% CI [1.31–5.63]).

Conclusions

PCI patients with type D personality had a 3.69-fold increased risk for depression and a 2.72-fold increased risk for anxiety at 10 years of follow-up.

     

Laparoscopic ovarian transposition before pelvic radiation in rectal cancer patient: safety and feasibility

Background

Infertility due to pelvic radiation for advanced rectal cancer treatment is a major concern particularly in young patients. Pre-radiation laparoscopic ovarian transposition may offer preservation of ovarian function during the treatment however its use is limited.

Aim

The study investigates the safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian transposition and its effect on ovarian function in the treatment o locally advanced rectal cancer.

Methods

Charts review of all young female patients diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian transposition, then received preoperative radiotherapy at king Faisal Specialist Hospital and Research Centre between 2003?C2007.

Results

During the period studied three single patients age between 21?C27?years underwent pre-radiation laparoscopic ovarian transposition for advanced rectal cancer. All required pretreatment laparoscopic diversion stoma due to rectal stricture secondary to tumor that was performed at the same time. One patient died of metastatic disease during treatment. The ovarian hormonal levels (FSH and LH) were normal in two patients. One has had normal menstrual period and other had amenorrhoea after 4?months follow-up however her ovarian hormonal level were within normal limits.

Conclusions

Laparoscopic ovarian transposition before pelvic radiation in advanced rectal cancer treatment is an effective and feasible way of preservation of ovarian function in young patients at risk of radiotherapy induced ovarian failure. However, this procedure is still under used and it is advisable to discuss and propose it to suitable patients.     

Combined use of rapid d-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review

Objective To summarise the evidence supporting the use of rapid d-dimer testing combined with estimation of clinical probability to exclude the diagnosis of deep venous thrombosis among outpatients.Data sources Medline (June 1993 to December 2003), the Database of Abstracts and Reviews (DARE), and reference lists of studies in English.Selection of studies We selected 12 studies from among 84 reviewed. The selected studies included more than 5000 patients and used a rapid d-dimer assay and explicit criteria to classify cases as having low, intermediate, or high clinical probability of deep vein thrombosis of the lower extremity among consecutive outpatients.Review methods Diagnosis required objective confirmation, and untreated patients had to have at least three months of follow up. The outcome was objectively documented venous thromboembolism. Two authors independently abstracted data by using a data collection form.Results When the less sensitive SimpliRED d-dimer assay was used the three month incidence of venous thromboembolism was 0.5% (95% confidence interval 0.07% to 1.1%) among patients with a low clinical probability of deep vein thrombosis and normal d-dimer concentrations. When a highly sensitive d-dimer assay was used, the three month incidence of venous thromboembolism was 0.4% (0.04% to 1.1%) among outpatients with low or moderate clinical probability of deep vein thrombosis and a normal d-dimer concentration.Conclusions The combination of low clinical probability for deep vein thrombosis and a normal result from the SimpliRED d-dimer test safely excludes a diagnosis of acute venous thrombosis A normal result from a highly sensitive d-dimer test effectively rules out deep vein thrombosis among patients classified as having either low or moderate clinical probability of deep vein thrombosis.     

Use of speckle-tracking echocardiography–derived strain and systolic strain rate measurements to predict rejection in transplant hearts with preserved ejection fraction

Background

Noninvasive diagnosis of allograft rejection in heart transplant recipients is challenging. The utility of 2-dimensional speckle-tracking echocardiography (2D-STE) to predict severe rejection in heart transplant recipients with preserved left ventricular ejection fraction (LVEF) was evaluated.

Methods

Adult heart transplant patients with preserved LVEF (>?55%) and severe rejection by biopsy (Rejection Grade?≥?2R) or no rejection between 1997 and 2011 at the Mayo Clinic in Rochester, Minnesota were evaluated. Transthoracic echocardiography was performed within 1?month of the biopsy. LV global longitudinal and circumferential strain and strain rates (GLS, GLSR, GCS, and GCSR) were analyzed retrospectively.

Results

Of 65 patients included, 25 had severe rejection and 40 were normal transplant controls without rejection. Both groups had more men than women (64 and 75%, respectively). Baseline clinical variables were similar between the groups. Both groups had normal LVEF (64.3% vs 64.5%; P?=?.87). All non-strain echocardiographic variables were similar between the 2 groups. Strain analysis showed significantly increased early diastolic longitudinal strain rate (P?=?.02) and decreased GCS (P?<?.001) and GCSR (P?=?.02) for the rejection group compared with the control group. The area under the receiver operating characteristic curve for GCS was 0.77. With a GCS cutoff of ??17.60%, the sensitivity and specificity of GCS to detect severe acute rejection were 81.8 and 68.4%, respectively.

Conclusions

2D-STE may be useful in detecting severe transplant rejection in heart transplant patients with normal LVEF.

     

Rational/antiemotional behaviors in interpersonal relationships and the functional prognosis of patients with rheumatoid arthritis: a Japanese multicenter,longitudinal study

Background

The repression of negative emotions is a personality factor that received considerable attention in the 1950-60s as being relevant to the onset and course of rheumatoid arthritis (RA). Despite subsequent, repeated criticisms of the cross-sectional nature of the earlier studies, even to date few prospective studies have been reported on this issue. This multicenter study prospectively examined if “rational and antiemotional” behavior (antiemotionality), characterized by an extreme tendency to suppress emotional behaviors and to rationalize negative experiences in conflicting interpersonal situations, is associated with the functional prognosis of patients with RA.

Methods

532 patients with RA who regularly visited one of eight hospitals/clinics in Japan in 2000 were recruited for study. All completed a self-administered baseline questionnaire about lifestyle and psychosocial factors including antiemotionality. Two years after, 460 (mean age, 56.1 years; 54 men and 406 women) of 471 patients who continued to visit the clinics agreed to take the follow-up questionnaire. The functional status of the patients was evaluated by rheumatologists based on the ACR classification system.

Results

A multiple logistic regression model that included baseline demographic, disease activity/severity-related, therapeutic, and socioeconomic factors as covariates found a tendency toward higher antiemotionality to be related to poorer functional status at follow-up. This relationship was not explained by lifestyle factors.

Conclusions

Antiemotionality may be a prognostic factor for the functional status of patients with RA. This finding sheds light on a seemingly forgotten issue in the care of patients with RA.

     

Orthogonal P-wave morphology is affected by intra-atrial pressures

Background

It has previously been shown that the morphology of the P-wave neither depends on atrial size in healthy subjects with physiologically enlarged atria nor on the physiological anatomical variation in transverse orientation of the left atrium. The present study aimed to investigate if different pressures in the left and right atrium are associated with different P-wave morphologies.

Methods

38 patients with isolated, increased left atrial pressure, 51 patients with isolated, increased right atrial pressure and 76 patients with biatrially increased pressure were studied. All had undergone right heart catheterization and had 12-lead electrocardiographic recordings, which were transformed into vectorcardiograms for detailed P-wave morphology analysis.

Results

Normal P-wave morphology (type 1) was more common in patients with isolated increased pressure in the right atrium while abnormal P-wave morphology (type 2) was more common in the groups with increased left atrial pressure (P = 0.032). Moreover, patients with increased left atrial pressure, either isolated or in conjunction with increased right atrial pressure, had significantly more often a P-wave morphology with a positive deflection in the sagittal plane (P = 0.004).

Conclusion

Isolated elevated right atrial pressure was associated with normal P-wave morphology while left-sided atrial pressure elevation, either isolated or in combination with right atrial pressure elevation, was associated with abnormal P-wave morphology.