The principle of regulation in biology--from bone to eating behavior.

Cell physiology and molecular biology typically follow a reductionistic approach in science. In the last decade, molecular principles and pathogenetic factors involved in the development of many diseases have been successfully discovered. Therefore, early biological concepts based on systemic and cybernetic thoughts have been largely overshadowed by these more recent molecular and pathogenetic factors. This review highlights discoveries on bone development and hypothalamic controlled feeding and eating behavior with a cybernetic and systemic perspective. Interestingly, ancient ideas on bone development and hypothalamic function are still reasonable considerations to embed new molecular discoveries into a systemic concept of principles organizing nature.     

Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6.

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.     

Oxcarbazepine reduces seizure frequency in a high proportion of patients with both newly diagnosed and refractory partial seizures in clinical practice.

The antiepileptic efficacy and tolerability of oxcarbazepine, used both as monotherapy and adjunctive therapy, were observed for 1 year in 202 adult patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy in clinical practice in Italy. At first observation, the seizure free rate was 72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom oxcarbazepine replaced another monotherapy and 10.3% in patients given oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the duration of treatment (p < 0.0001). In the 160 completers the seizure free rate was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients reported adverse effects, mainly sedation and sleepiness; 5% discontinued oxcarbazepine because of adverse events. OXC is an effective and well-tolerated antiepileptic agent for the long-term treatment of partial epilepsy in adults.     

Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction.

Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study.     

Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients.

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients. In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD. In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0-18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25-80) yrs. Beryllium-contaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard. In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.     

NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

A survey: conscious sedation with epidural and zygapophyseal injections: is it necessary?

BACKGROUND CONTEXT: Substantial variation exists regarding the use of sedation before interventional spine techniques. Patient preference should play an important role in decision making regarding the need for sedation. However, little is known about patients' anxiety levels before spinal injections and their perceptions about the necessity of sedation. PURPOSE: To determine patient perception for need for sedation before epidural steroid injections and zygapophyseal joint injections. STUDY DESIGN/SETTING: Survey of consecutive spinal injection patients in an outpatient spine center. PATIENT SAMPLE: 500 consecutive lumbar, thoracic, and cervical patients receiving spinal injections. OUTCOME MEASURES: A 12-item questionnaire assessing patients' perceived anxiety before to a spinal injection. METHODS: Subjects were given the questionnaire after their spinal injection. Percentages requesting sedation for a first and potential second procedure were assessed. Additionally, anxiety level and pain rating, location of injection, age, sex, and other medication use were analyzed to determine the effect on the request for sedation. RESULTS: 17% of patients questioned requested sedation before an injection, and 28% would request sedation if they were to have a second injection. CONCLUSIONS: Routine sedation before diagnostic and therapeutic injections is not necessary as the majority of patients would not request sedation before the procedure when given the option. However, in some patients sedation is indicated, and all patients would benefit from educational material on sedation before the injection.     

Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.