The sore throat: a clinical approach to tonsillopharyngitis

Acute sore throat is a common complaint encountered by medical practitioners and health care workers routinely. The disease is mostly caused by viral infections of the upper respiratory tract and is usually self limiting. Symptoms rarely exceed two weeks, irrespective of the cause. Group A beta-haemolytic streptococci accounts for the majority of bacterial instances of tonsillopharyngitis. Clinical examination is not always adequate to diagnose bacterial infections, resulting in the irrational and over-prescribing of antibiotics, especially in upper respiratory tract infections, contributing to communal antimicrobial bacterial resistance. A few scoring systems are available to assist physicians in deciding on the aetiology without resorting to unnecessary laboratory investigations. This article briefly reviews the scoring systems and antimicrobial management of streptococcal throat infections

Psychosocial Risk Factors for Child Welfare among Postpartum Mothers with a History of Childhood Maltreatment and Neglect.

Background: Childhood maltreatment (CM) can increase the risk of psychosocial risk factors in adulthood (e. g. intimate partner violence, financial problems, substance abuse or medical problems). The transition to parenthood presents those affected by CM with particular challenges, in addition to usual birth-related stressors. Methods: In this cross-sectional study a total of 240 women were interviewed in the puerperium with respect to CM experiences, using the German version of the Childhood Trauma Questionnaire (CTQ). Current psychosocial risk factors (e. g. financial concerns, maternal mental illness, single parent) were assessed using the Constance Index (KINDEX) for early childhood risk factors. Associations between CM experience and psychosocial risk factors were calculated using simple correlation. Results: The average age of participants was 33 years. On the CTQ 13.8 % of participants reported emotional abuse, 6.7 % physical abuse and 12.5 % sexual abuse, while 32.1 % reported emotional neglect and 7.5 % physical neglect during childhood. With rising severity of CM, more psychosocial risk factors (KINDEX) were present. Conclusions: This study shows a clear association between experiences of maltreatment during childhood and the presence of psychosocial stressors among women in the puerperium. Regular screening for a history of CM and parental psychosocial stressors should be conducted early, i.e. during pregnancy, to avoid negative consequences for the child.

Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment.

Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic-pituitary-adrenal axis--in particular, the glucocorticoid receptor (hGR) gene--stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.

LENS: A New Pulsed Neutron Source for Research and Education.

A new pulsed neutron source is under construction at the Indiana University Cyclotron Facility (IUCF). Neutrons are produced via (p,n) reactions by a low-energy proton beam incident on a thin beryllium target. The source is tightly coupled to a cold methane moderator held at a temperature of 20 K or below. The resulting time-averaged cold neutron flux is expected to be comparable to that of the Intense Pulsed Neutron Source (IPNS) facility at Argonne National Laboratory. The initial experimental suite will include instrumentation for small angle neutron scattering (SANS), moderator studies, radiography, and zero-field spin-echo SANS.

Measurement of Parity Violation in np Capture: the NPDGamma Experiment.

The NPDGamma experiment will measure the parity-violating directional gamma ray asymmetry A γ in the reaction [Formula: see text]. Ultimately, this will constitute the first measurement in the neutron-proton system that is sensitive enough to challenge modern theories of nuclear parity violation, providing a theoretically clean determination of the weak pion-nucleon coupling. A new beam-line at the Los Alamos Neutron Science Center (LANSCE) delivers pulsed cold neutrons to the apparatus, where they are polarized by transmission through a large volume polarized (3)He spin filter and captured in a liquid para-hydrogen target. The 2.2 MeV gamma rays from the capture reaction are detected in an array of CsI(Tl) scintillators read out by vacuum photodiodes operated in current mode. We will complete commissioning of the apparatus and carry out a first measurement at LANSCE in 2004-05, which would provide a statistics-limited result for A γ accurate to a standard uncertainty of ±5 × 10(-8) level or better, improving on existing measurements in the neutron-proton system by a factor of 4. Plans to move the experiment to a reactor facility, where the greater flux would enable us to make a measurement with a standard uncertainty of ±1 × 10(-8), are actively being pursued for the longer term.

Commissioning of the NPDGamma Detector Array: Counting Statistics in Current Mode Operation and Parity Violation in the Capture of Cold Neutrons on B 4 C and (27) Al.

The NPDGamma γ-ray detector has been built to measure, with high accuracy, the size of the small parity-violating asymmetry in the angular distribution of gamma rays from the capture of polarized cold neutrons by protons. The high cold neutron flux at the Los Alamos Neutron Scattering Center (LANSCE) spallation neutron source and control of systematic errors require the use of current mode detection with vacuum photodiodes and low-noise solid-state preamplifiers. We show that the detector array operates at counting statistics and that the asymmetries due to B4C and (27)Al are zero to with- in 2 × 10(-6) and 7 × 10(-7), respectively. Boron and aluminum are used throughout the experiment. The results presented here are preliminary.

New Pulsed Cold Neutron Beam Line for Fundamental Nuclear Physics at LANSCE.

The NPDGamma collaboration has completed the construction of a pulsed cold neutron beam line on flight path12 at the Los Alamos Neutron Science Center (LANSCE). We describe the new beam line and characteristics of the beam. We report results of the moderator brightness and the guide performance measurements. FP12 has the highest pulsed cold neutron intensity for nuclear physics in the world.

Proposed Measurement of the Beta-Neutrino Correlation in Neutron Decay.

Currently, the beta-neutrino asymmetry has the largest uncertainty (4 %) of the neutron decay angular correlations. Without requiring polarimetry this decay parameter can be used to measure λ (ga/gv ), test Cabibbo-Kobayashi-Maskawa (CKM) unitarity limit scalar and tensor currents, and search for Charged Vector Current (CVC) violation. We propose to measure the beta-neutrino asymmetry coeffcient, a, using time-of-flight for the recoil protons. We hope to achieve a systematic uncertainty of σa / a ≈ 1.0 %. After tests at Indiana University's Low Energy Neutron Source (LENS), the apparatus will be moved to the National Institute of Standards and Technology (NIST) where the measurement can achieve a statistical uncertainty of 1 % to 2 % in about 200 beam days.

Separating different contributions to the shear force in near-field microscopy.

The shear force between a gold and a graphite sample and an approaching near-field optical probe using tuning fork detection is studied in detail. The adiabatic and dissipative contributions are clearly distinguished by monitoring the amplitude as well as the phase of the tip vibration when approaching the surfaces. Their relative strengths vary differently but characteristically with the distance. The interaction starts in case of graphite at a much larger distance. The adiabatic contribution is larger in the case of gold, whereas graphite shows mostly dissipative interaction. Measurements at various temperatures are performed using a gold sample, showing a dependence of the shear force on the temperature.

Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment.

BACKGROUND: In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal. AIMS: To characterise complete and incomplete responders. METHODS: Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years. RESULTS: In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only difference between the two groups before treatment was higher levels of alkaline phosphatase and gamma glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for gamma glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no differences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups. CONCLUSIONS: In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and gamma glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment.

Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy. METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry. RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed. CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.

Peri-hepatic lymphadenopathy in primary biliary cirrhosis reflects progression of the disease.

OBJECTIVE: We prospectively investigated the peri-hepatic lymph node volume in patients with primary biliary cirrhosis (PBC) and healthy controls to evaluate the correlation with histology, biochemical and immunological features. MATERIALS AND METHODS: The total peri-hepatic lymph node volume in the liver hilus was evaluated by high-resolution ultrasound in 67 consecutive patients with PBC and in 43 healthy controls. Stages I-IV of PBC were biochemically, immunologically and histologically proven in all patients. RESULTS: Adequate visualization of the liver hilus was achieved in 59/67 patients (88%) with PBC and in 39/43 healthy controls (91%). Lymph nodes in the liver hilus were sonographically detected in all 59 patients with PBC and in 26/39 healthy controls (67%) with adequate visualization of the liver hilus. The mean peri-hepatic lymph node volumes were: stage I (n = 9): 0.8 +/- 0.5 ml; stage II (n = 28): 2.4 +/- 1.5 ml; stage III (n = 21): 4.2 +/- 2.3 ml; stage IV (n = 9): 3.2 +/- 1.0 ml. The peri-hepatic lymph node volume did not significantly correlate with cholestasis, liver function tests or the immunological status. CONCLUSIONS: Enlarged lymph nodes in the liver hilus are sonographically detectable in almost all patients with PBC. The total peri-hepatic lymph node volume in patients with PBC reflects histological stage, i.e. larger lymph nodes are observed in more advanced disease.

The effect of bile salts and calcium on isolated rat liver mitochondria.

Intact mitochondria were incubated with and without calcium in solutions of chenodeoxycholate, ursodeoxycholate, or their conjugates. Glutamate dehydrogenase, protein and phospholipid release were measured. Alterations in membrane and organelle structure were investigated by electron paramagnetic resonance spectroscopy. Chenodeoxycholate enhanced enzyme liberation, solubilized protein and phospholipid, and increased protein spin label mobility and the polarity of the hydrophobic membrane interior, whereas ursodeoxycholate and its conjugates did not damage mitochondria. Preincubation with ursodeoxycholate or its conjugate tauroursodeoxycholate for 20 min partially prevented damage by chenodeoxycholate. Extended preincubation even with 1 mM ursodeoxycholate could no longer prevent structural damage. Calcium (from 0.01 mM upward) augmented the damaging effect of chenodeoxycholate (0.15-0.5 mM). The combined action of 0.01 mM calcium and 0.15 mM chenodeoxycholate was reversed by ursodeoxycholate only, not by its conjugates tauroursodeoxycholate and glycoursodeoxycholate. In conclusion, ursodeoxycholate partially prevents chenodeoxycholate-induced glutamate dehydrogenase release from liver cell mitochondria by membrane stabilization. This holds for shorter times and at concentrations below 0.5 mM only, indicating that the different constitution of protein-rich mitochondrial membranes does not allow optimal stabilization such as has been seen in phospholipid- and cholesterol-rich hepatocyte cell membranes, investigated previously.

Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid probably is not able to cure primary biliary cirrhosis. Therefore in this study ursodeoxycholic acid was administered together with prednisolone, since monotherapy with glucocorticoids has been shown to have some positive effects. METHODS: Thirty patients with primary biliary cirrhosis (stages I-III) were entered into the study. Fifteen were treated with ursodeoxycholic acid 10 mg.kg-1.day-1 and placebo (group A), 15 with ursodeoxycholic acid and 10 mg prednisolone (group B) for 9 months. Apart from the usual laboratory examinations, liver biopsies were taken from 29 patients before and after therapy. RESULTS: Liver enzymes decreased significantly compared to the initial values in both groups (p < 0.001), but in group B cholestasis-indicating enzymes and the immunoglobulins G and A improved more rapidly. Between both groups the differences for AP, GGT, IgG, IgA and gamma-globulins were significant (p < 0.05), but only for short terms. In group B, liver histology improved significantly (p < 0.003), which correlated with the decrease of IgG. Ursodeoxycholic acid became the predominant bile acid in the serum. Toxic bile acids did not increase. Bone densitometry revealed a slight deterioration of preexisting osteoporosis in one patient. CONCLUSIONS: Although combination therapy with ursodeoxycholic acid and prednisolone was not superior to monotherapy with ursodeoxycholic acid with regard to liver function tests, it had a highly beneficial influence on liver histology. In our previous trials with monotherapy histology remained unchanged. An early decrease in IgG during combination therapy seems to be an indicator of an amelioration of liver histology.

Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late stages of primary biliary cirrhosis.

Twenty-two patients with primary biliary cirrhosis were treated with ursodeoxycholic acid, 10 mg/kg per day. Fourteen patients with stages I/II were treated for 4-12 years (mean 7.5), and eight patients with stages III/IV for 5-12 years (mean 6.5). Twelve of 13 patients with early stages became asymptomatic. Aminotransferases, cholestasis-indicating enzymes and IgM improved (p < 0.01) and remained low during the whole treatment period. Ursodeoxycholic acid was the predominant serum bile acid, and lithocholic acid did not increase in the serum but did increase in the stool. Of eight patients with stages III/IV, seven were symptomatic, and four became asymptomatic. In all eight patients, laboratory data improved. Of these eight patients three experienced haemorrhage from oesophageal varices, two had to be transplanted, and one of them died. In one patient splenic rupture occurred, and in three liver function tests deteriorated. Although the number of patients was small, this is the longest treatment period so far reported. Ursodeoxycholic acid had no side effects for up to 12 years, and in patients with early stages it seemed to have a beneficial effect on symptoms and the progression of the disease. However, even with up to 12 years of therapy, ursodeoxycholic acid did not cause antimitochondrial antibodies to disappear either in the early or in the late stages, it was unable to prevent rebound effects during therapy intermission even after more than 5 years of continuous therapy, there was no decisive influence on liver histology and it did not cure the disease. Finally, although ursodeoxycholic acid improved life quality and laboratory data in all patients with late stages of the disease, it did not prevent complications due to cirrhosis.