Telomerase activity and genetic alterations in primary breast carcinomas

It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that the ectopic expression of telomerase promotes tumorigenesis via a telomere length-independent mechanism. In this study, the relation between telomerase expression and the extent of chromosomal aberrations was investigated in 62 primary breast carcinomas. Telomerase activity was measured using a polymerase chain reaction-based telomeric repeat amplification protocol assay and 92% of the tumors were found to express telomerase with a relative activity ranging from 0 to 3839.6. Genetic alterations were determined by G-banding and comparative genomic hybridization analysis and 97% of the tumors exhibited chromosomal aberrations ranging from 0 to 44 (average: 10.98). In the overall series, the relationship between telomerase activity levels and genetic changes could be best described by a quadratic model, whereas in tumors with below-average genetic alteration numbers, a significant positive association was recorded between the two variables (coefficient=0.374, P=.017). The relationship between telomerase activity levels and the extent of genetic alteration may reflect the complex effect of telomerase activation upon tumor progression in breast carcinomas.     

Self-perpetuating effects of birth size on blood pressure levels in elderly people

It has been suggested that essential hypertension is determined by 2 separate mechanisms: a growth-promoting process in childhood and a self-perpetuating mechanism in adult life. We report a clinical study of 500 people taken from a cohort of 7086 men and women who were born in Helsinki from 1924 to 1933, and whose body size at birth was recorded. As expected, blood pressure levels were inversely related to birthweight and birth length. These associations, however, were confined to the 213 people who had previously been diagnosed as having hypertension. In them, a 1-kg increase in birthweight was associated with a 6.4-mm Hg (95% confidence interval, 1.0 to 11.9) decrease in systolic blood pressure recorded at the clinic, and with a 9.3-mm Hg (95% confidence interval, 2.1 to 16.5) decrease recorded by ambulatory measurement. We conclude that pathological processes initiated in utero become self-perpetuating in adult life and lead to hypertension. Among elderly people with established hypertension, these processes have a strong effect on blood pressure levels, because they are processes that do not respond well to treatment.     

Mobility provocation radiostereometry in anterior cervical spine fusions

This study aimed to evaluate the use of mobility-provocation radiostereometry (RSA) in anterior cervical spine fusions and compare the results to deformation studies on the same patients and plain flexion-extension radiographs. Mobility-provocation RSA was used to evaluate anterior cervical spine fusions in 45 patients. The motions recorded at 3 and 12 months postoperatively were compared to RSA measurements of deformation of the fusion over time and to plain flexion-extension radiographs in the same patients taken 3 months postoperatively. Studies of rotations from right to left revealed ten cases with significant motion at 3 months, and three at 12 months. With motion from flexion to extension, ten cases showed significant motion at 3 months and three at 12 months. In only three cases was the mobility-provocation RSA considered to add any information on the stability of the fusions compared to that obtained with the deformation studies. In 37 patients mobility-provocation radiography in flexion-extension using conventional technique was done to evaluate the accuracy. The mean difference between angular motions recorded on plain radiographs and rotations around the transverse axis in flexion to extension recorded with RSA was 1.6° (range 0.04°–8.04°, SD 2.1°). The corresponding 95% and 99% confidence limits for the difference between the two methods were 5.8° and 7.2°. The study showed that the use of mobility-provocation RSA did not add any information over that obtained by deformation RSA studies. Conventional radiography is too inaccurate to measure inducible displacement in this patient population.     

Management of cholangitis

Acute cholangitis remains a life-threatening complication of biliary obstruction, particularly in the elderly with comorbid disease or when there is a delay in diagnosis and treatment. The initial management consists of fluid resuscitation, correction of coagulopathy, and administration of broadspectrum antibiotics. The choice of antibiotics should cover both gram-negative and gram-positive organisms associated with cholangitis until the results of a blood culture are available. The timing and choice of biliary decompression varies depending on the response to antibiotic therapy, the presence of comorbid disease, and the underlying cause. Biliary sepsis resolves in most patients with conservative treatment, thus allowing time to perform more detailed noninterventional imaging (e.g., spiral computed tomography [CT], magnetic resonance cholangiopancreatography [MRCP]) to determine the underlying cause and level of biliary obstruction. Those with cholangitits who do not respond to conservative therapy will require urgent biliary decompression. In patients with choledocholithiasis, endoscopic drainage is now the treatment of choice or, if this fails, transhepatic biliary decompression is a useful alternative. Various endoscopic options are available for managing choledocholithiasis, ranging from endoscopic papillotomy (EP) and extraction of stones, to the placement of a biliary drainage system. In patients who respond to antibiotic therapy, EP with stone extraction is preferred, while in those with ongoing sepsis and multiple large stones, the placement of a stent with or without an EP is the safest option. Transhepatic biliary drainage is now reserved for failure of endoscopic drainage and for patients with suspected hilar cholangiocarcinoma or intrahepatic stones. Surgical biliary decompression is seldom required in the emergency setting, but still plays an important role in the definitive treatment of the underlying cause.     

Computer use and carpal tunnel syndrome: a 1-year follow-up study

Context  Computer use is increasingly common among many working populations, and concern exists about possible adverse effects of computer use, such as carpal tunnel syndrome (CTS). Objectives  To estimate the prevalence and incidence of possible CTS and to evaluate the contribution of use of mouse devices and keyboards to the risk of possible CTS. Design and Setting  A 1-year follow-up study with questionnaires conducted in 2000 and 2001 at 3500 workplaces in Denmark, followed on each of the 2 occasions by a clinical interview on symptom distribution and frequency. Participants  The questionnaire was sent to 9480 members of a trade union, with an initial response rate of 73% (n = 6943), and 82% (n = 5658) at follow-up. Main Outcome Measures  At baseline, there were 3 outcome measures: tingling/numbness in the right hand once a week or more as reported in the questionnaire; tingling, numbness, and pain in the median nerve in the right hand confirmed by clinical interview; and tingling, numbness, and pain in the median nerve in the right hand at night confirmed by clinical interview. At 1 year of follow-up the main outcome of interest was onset of symptoms among participants who had no or minor symptoms at baseline. Results  The overall self-reported prevalence of tingling/numbness in the right hand at baseline was 10.9%. The interview confirmed that prevalence of tingling/numbness in the median nerve was 4.8%, of which about one third, corresponding to a prevalence of 1.4%, experienced symptoms at night. Onset of new symptoms in the 1-year follow-up was 5.5%. In the cross-sectional comparisons and in the follow-up analyses, there was an association between use of a mouse device for more than 20 h/wk and risk of possible CTS but no statistically significant association with keyboard use. Conclusions  The occurrence of possible CTS in the right hand was low. The study emphasizes that computer use does not pose a severe occupational hazard for developing symptoms of CTS.      

Impact of birth weight and genetic liability on psychopathology in children of bipolar parents

OBJECTIVE: To test different models for ways in which birth weight and familial loading influence the risk for psychopathology in bipolar offspring. METHOD: DSM-IV diagnoses of 140 bipolar offspring (12-21 years of age) were assessed with the K-SADS-PL. Parents were interviewed using the Family History-Research Diagnostic Criteria to determine familial loading of mood and substance use disorders. Parents reported the birth weight of their offspring. Age- and sex-adjusted hazard ratios were calculated. RESULTS: Low birth weight was associated with mood and non-mood disorders in bipolar offspring (hazard ratio = 0.6, confidence interval = 0.4-0.8), even after controlling for familial loading of unipolar disorder, bipolar disorder, or substance use disorder. There were no significant interactions between birth weight and familial loading of unipolar disorder, familial loading of bipolar disorder, and familial loading of substance use disorder. CONCLUSIONS: Birth weight is associated with mood as well as non-mood disorders. This association is independent from the association of familial loading of mood and substance use disorder with mood- and non-mood disorders in bipolar offspring.     

SK channels and the varieties of slow after-hyperpolarizations in neurons

Action potentials and associated Ca2+ influx can be followed by slow after-hyperpolarizations (sAHPs) caused by a voltage-insensitive, Ca2+-dependent K+ current. Slow AHPs are a widespread phenomenon in mammalian (including human) neurons and are present in both peripheral and central nervous systems. Although, the molecular identity of ion channels responsible for common membrane potential mechanisms has been largely determined, the nature of the channels that underlie the sAHPs in neurons, both in the brain and in the periphery, remains unresolved. This short review discusses why there is no clear molecular candidate for sAHPs.     

The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1beta-induced neurodegeneration

The neurotoxic effect of the pro-inflammatory cytokine interleukin (IL)-1beta was studied in monolayer cultures, obtained using roller-drum incubation of hippocampal slices from neonatal Sprague Dawley rats. Following exposure to recombinant rat IL-1beta for four days, a concentration dependent loss was observed in the number of NMDAR1 receptor subunit immunoreactive pyramidal neurons in the cultures, reaching significance at 10 ng/ml rIL-1beta. Also incubation with recombinant mouse IL-1beta caused a loss of pyramidal neurons, with a significant effect at a concentration of 30 pg/ml. The vitamin E analog trolox (30 microM) was found to exert a protective effect against the rIL-1beta induced neuronal degeneration. A neuroprotective action against rIL-1beta was also found after co-incubation with the NMDA antagonist dizocilpine (MK-801; 30 microM), while no protection was found with the GABAA mimetic clomethiazole. Hence, the pro-inflammatory cytokine IL-1beta is neurotoxic to hippocampal pyramidal neurons when studied in an in vitro system with advanced phenotypic characteristics. The neuroprotective effects exerted by trolox and MK-801 suggest that free radicals and NMDA receptor-mediated processes are involved in IL-1beta -induced neurodegeneration.     

Do depressive episodes lead to accumulation of vulnerability in the elderly?

The vulnerability-accumulation (or scarring) hypothesis postulates that the experience of depression induces a lasting increase in vulnerability, and through this raises the risk of recurrence. We examined the validity of the vulnerability-accumulation model for depressive episodes in later life. The sample comprised 26 elderly persons who had remitted from a depressive episode and 96 control respondents who were all selected from the participants of a large community survey among persons aged 57 years or more. Several psychosocial vulnerability indicators were assessed premorbidly, during the depressive episode and after remission. High levels of psychological distress, low life satisfaction, chronic somatic diseases, high neuroticism, and low scores on extraversion, mastery, and self-efficacy appeared to be predictors of depression in this sample. During the depressive episode, psychological distress was higher and life satisfaction, physical, role, and social functioning, as well as feelings of self-efficacy lower than before the episode. Physical and role functioning, cognitive function, and self-efficacy were lower after remission compared to premorbid levels, but (other) personality indices had not changed after remission compared to premorbid levels. Furthermore, we failed to find differences between first and recurrent episodes. Support for the vulnerability-accumulation model was limited at the most. Although psychosocial scarring may occur in the elderly, our findings tentatively suggest that this accumulation does not manifest itself in major vulnerability indicators such as neuroticism.