Effects of severity of chronic obstructive pulmonary disease on thyroid function

To investigate thyroid function in chronic obstructive pulmonary disease (COPD), 46 consecutive patients (35 men) with stable, mild-to-severe disease, having a mean (SD) age of 67 +/- 7 years were studied. All subjects underwent pulmonary function tests (PFTs), arterial blood gas determination, and measurement of serum total thyroxine (TT4), total triiodothyronine (TT3), resin T3 uptake (RT3U), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) levels. The free thyroxine and free triiodothyronine indexes (FT4I = RT3U/30TT4 and FT3I = RT3U/30TT3, respectively) along with the TT3/TT4 ratio were calculated; the latter was used as a marker of peripheral conversion of thyroxine into triiodothyronine. Interleukin (IL)-6 was also measured to evaluate its potential associations with thyroidal hormone levels. On the basis of forced expiratory volume in 1 second (FEV1), patients were divided in 2 groups: group 1, (FEV1 > or = 50% of predicted, n = 26), with mild-to-moderate COPD and group 2 (FEV1 < 50% of predicted, n = 20) having severe disease. All subjects had normal serum thyroid hormone levels; for the entire COPD population, mean values were 7.80 +/- 1.60 microg/dL for TT4, 1.12 +/- 0.20 ng/mL for TT3, 29.0 +/- 1.88 for RT3U, 7.54 +/- 1.34 for FT4I, 1.07 +/- 0.16 for FT3I, 18.71 +/- 5.89 ng/dL for rT3, and 1.15 +/- 0.6 microU/mL for TSH. Mean TT3/TT4 ratio was 0.14 +/- 0.03. In group 1, TT3, TT4, and TT3/TT4 ratio did not correlate with age, FEV1, PaO2, or inhaled corticosteroids. Similarly, in group 2, TT3 and TT4 were unrelated to the above-mentioned variables; however, there was a strong positive correlation between TT3/TT4 ratio and PaO2 (r =.61, P =.004). IL-6 was within normal limits in all subjects, and it did not correlate with any thyroid hormone either in group 1 or in group 2. It is concluded that in stable COPD, severity of disease through hypoxemia is important in determining the peripheral metabolism of thyroid hormones. Whether this constitutes an adaptation is not known.     

Arrhythmic risk stratification in ischemic,non-ischemic and hypertrophic cardiomyopathy: A two-step multifactorial,electrophysiology study inclusive approach

Annual arrhythmic sudden cardiac death ranges from 0.6% to 4% in ischemic cardiomyopathy (ICM), 1% to 2% in non-ischemic cardiomyopathy (NICM), and 1% in hypertrophic cardiomyopathy (HCM). Towards a more effective arrhythmic risk stratification (ARS) we hereby present a two-step ARS with the usage of seven non-invasive risk factors: Late potentials presence (≥ 2/3 positive criteria), premature ventricular contractions (≥ 30/h), non-sustained ventricular tachycardia (≥ 1episode/24 h), abnormal heart rate turbulence (onset ≥ 0% and slope ≤ 2.5 ms) and reduced deceleration capacity (≤ 4.5 ms), abnormal T wave alternans (≥ 65μV), decreased heart rate variability (SDNN < 70ms), and prolonged QT_c interval (> 440 ms in males and > 450 ms in females) which reflect the arrhythmogenic mechanisms for the selection of the intermediate arrhythmic risk patients in the first step. In the second step, these intermediate-risk patients undergo a programmed ventricular stimulation (PVS) for the detection of inducible, truly high-risk ICM and NICM patients, who will benefit from an implantable cardioverter defibrillator. For HCM patients, we also suggest the incorporation of the PVS either for the low HCM Risk-score patients or for the patients with one traditional risk factor in order to improve the inadequate sensitivity of the former and the low specificity of the latter.     

Nicotinamide (niacin) supplement increases lipid metabolism and ROS‐induced energy disruption in triple‐negative breast cancer: potential for drug repositioning as an anti‐tumor agent

Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM‐induced metabolic regulation and the therapeutic efficacy of NAM in triple‐negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β‐oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next‐generation anti‐metabolic agent for TNBC treatment.     

Endovascular Repair of an Abdominal Aortic Aneurysm in a Patient with Horseshoe Kidney: Report of a Case

A horseshoe kidney poses special problems during treatment of an abdominal aortic aneurysm (AAA), and there is much controversy about the most suitable method of repair. We report the case of a 65-year-old man with a horseshoe kidney, in whom an AAA was treated with a unibody bifurcated endograft. During the procedure, the two anomalous renal arteries were sacrificed. Although there was transient elevation of the creatinine levels, the patient was discharged with normal renal function and no endoleak from the accessory renal arteries. Thus, when two normal and two accessory renal arteries arise from the non-aneurysmatic proximal aortic neck, providing that preoperative kidney function is normal, it seems that the treatment can be safely carried out using an endovascular technique and excluding the accessory renal arteries. This case supports the feasibility of endovascular surgery for the treatment of AAA in the presence of a horseshoe kidney.     

Aggressive surgical resection for hilar cholangiocarcinoma: is it justified? Audit of a single center's experience

BACKGROUND: The current study presents our experience with resectional surgery for patients with hilar cholangiocarcinoma (HC). METHODS: Medical records of 73 HC patients who were referred to our department between 1988 and 2006 were reviewed. Resectability rate, surgical mortality, and factors contributing to survival were investigated. RESULTS: Resectional surgery was performed in 59 patients (80.8%), 51 of whom (86.4%) underwent major hepatic resection. Negative margins were obtained in 35 of 51 patients (68.6%) and were associated with right-sided hepatectomy (80% vs 20%, P = .049). In-hospital mortality and morbidity were 6.8% and 25.4%, respectively. One-, 3- and 5-year survival rates after liver resection were 86%, 48.9%, and 34.9%, respectively. Histologic differentiation, left-sided hepatectomy, and inferior vena cava resection independently predicted survival. Patients undergoing R1 hepatectomy had significantly improved 5-year survival rates compared with patients who were unresectable (P <.01). CONCLUSIONS: Major hepatic resections with concomitant vascular resection and reconstruction, when needed, are justified for patients with Bismuth type III and IV hilar cholangiocarcinoma with negative nodes. Reluctance to incorporate segments V and/or VIII into a left lobectomy often results in tumor-positive margins and unfavorable prognosis. Resections for hilar lesions less than stage IVB, even when resulting in microscopically positive margins, confer prolonged survival compared with untreated patients. The results are further improved for patients with well-differentiated HC.     

Penicillinase-producing Neisseria gonorrhoeae isolated in Surabaya

Although penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) were discovered in 1976 in neighbouring countries, not until 1980 were such strains isolated and identified in Indonesia. In that year PPNG were detected in three male patients with gonococcal urethritis in Surabaya. The minimum inhibitory concentration of penicillin G for all three strains was 12 . 5 microgram/ml.     

Intraocular pressure changes during high-altitude acclimatization

Background To evaluate the relationship between hypobaric hypoxia acclimatization and intraocular pressure (IOP) during ascent, acclimatization, and descent between 2286 m and 5050 m. Methods The following acclimatization-indicative physiological parameters were compared daily with IOP changes in eight healthy climbers of the 2003 Greek Karakorum expedition in altitude stages between 500 m and 5050 m: hemoglobin oxygen saturation (PO₂), resting heart rate, blood pressure, retinal findings, and the Lake Louise score for acclimatization grading. Results IOP decreased significantly in the ascent phase (0.58 mmHg/100 m) and recovered (0.71 mmHg/100 m) during acclimatization and descent. A direct proportional correlation between decreases in PO₂ and IOP was evaluated. Arterial blood pulse and pressure increased during acclimatization, while IOP decreased. No retinal hemorrhages were observed in well-acclimatized and incompletely acclimatized climbers. Conclusions Every new active exposure to hypobaric hypoxia in the ascent phase induced a decrease in the IOP parallel to the PO₂ decrease and to the level of acclimatization. The results from our study suggest that IOP changes are related to hypoxia-induced respiratory alkalosis and acclimatization stage, which could be used as a simple mobile screening test for acclimatization level to reveal acute mountain sickness and its severe consequences.     

Effects of detraining on muscle strength and mass after high or moderate intensity of resistance training in older adults

This study examined the effects of a 12 weeks detraining period on muscle strength and mass in older adults who had previously participated in a 12 weeks resistance training programme of high [80% of one repetition maximum (1‐RM)] or moderate (60% of 1‐RM) intensity. Twenty older adults (60–74 years), separated into a high (HI; n = 10; age: 65 ± 5 years) and a moderate (MI; n = 10; age: 66 ± 4 years) intensity resistance training group, were measured in the 1‐RM knee extension and flexion strength, and the midthigh cross sectional areas (CSAs) of quadriceps, hamstrings and total thigh before and after a 12 weeks training period as well as after a 12 weeks detraining period. Maximum knee extension and flexion strength and the CSAs of all muscles decreased significantly (P<0·05) with detraining but remained higher (P<0·05) than pretraining levels for both groups. The HI group had a greater decrement (P<0·05) in maximum strength and the CSA of total thigh compared to the MI group but strength levels and the CSA following detraining were higher (P<0·05) for the HI group. The above data suggest that after a short detraining period of 12 weeks, muscle strength and hypertrophy levels of older adults decrease but remain greater than pretraining irrespective of training intensity. Greater declines in muscle strength are observed following HI training but still muscular strength and muscle mass are retained at a higher level than with MI probably due to the higher gains achieved during the training period.     

Atracurium and vecuronium: interaction with three orally administered calcium antagonists in animal experiments

Interactions between calcium antagonists (CA) and muscle relaxants have been reported however due to the extremely high dosages of CA used in these studies, the clinical relevance of the observed interactions has been questioned. In order to simulate clinical practice--which entails long-term oral treatment and significant reductions in systolic blood pressure--CA were administered to rats orally (by gavage) for 8 days at a dosage that induced a systolic blood pressure decrease of not more than 25 +/- 5 mmHg. Ten groups of six male Sprague-Dawley rats each, body weight (BW) 313 +/- 23 g, were subjected to oral administration of three different CA: nitrendipine (1 mg/kg BW), nisoldipine (1 mg/kg BW), and diltiazem (100 mg/kg BW) or their solvents (control) three times daily by gavage for a period of 8 days. One hour after the last dose of drug or solvent, the rats were anesthetized (pentobarbital 60 mg/kg BW) and mechanically ventilated via tracheostomy. Monitoring included rectal temperature, carotid artery pressure, central venous pressure, heart rate, blood gases, and end-tidal CO2. Evoked train-of-four (T4) twitch tension of the right tibialis anterior muscle was recorded continuously. After equilibration of vital signs and muscle twitch tension, vecuronium (150 micrograms/kg BW) or atracurium (500 micrograms/kg BW) was injected into the internal jugular vein four times at 5-min intervals after twitch tension had totally recovered and T4 fade had disappeared. Twitch depression, duration 90, and onset time of neuromuscular block in CA-pretreated animals were compared to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)