Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS.

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies.

BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization.     

Left main coronary artery stenosis no longer a risk factor for early and late death after coronary artery bypass surgery--an experience covering three decades.

OBJECTIVE: To analyse early and late mortality after coronary artery bypass grafting (CABG) in patients with and without left main coronary artery (LMCA) stenosis during the 30-year period 1970-1999. METHODS: A total of 1888 of 10,647 patients (18%) who underwent a first isolated CABG at the Karolinska Hospital in Stockholm, Sweden, during 1970-1999 had significant left main coronary artery stenosis. The Swedish National Cause of Death Register was used to determine mortality up to five years after the operation. RESULTS: The proportion of patients with LMCA stenosis of all CABG patients increased from 7% during the 1970s to 26% in 1999. During 1970-1984 early mortality was 5.8% in patients with LMCA stenosis compared with 1.5% in patients without LMCA stenosis (odds ratio (OR) 3.7 (95% confidence interval (CI) 1.8-7.6)). The corresponding rates during 1995-1999 were 2.0% versus 2.2% (OR 0.8 (95% CI 0.5-1.5)), respectively. The increased risk of early death in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. Five-year survival in males was 88% after operations performed during 1994-1999 compared with 82% after CABG performed during 1970-1984. Five-year mortality, exclusive of early deaths, during 1970-1984 was higher in patients with LMCA stenosis (12.8%) than in those without (8.4%) (relative risk 1.7 (95% CI 1.1-2.5)). An increased risk of late mortality in patients with LMCA stenosis was neutralised in males during 1985-1994 and in females during 1995-1999. CONCLUSIONS: During 1970-1999 there was a decrease of early and five-year mortality in patients with LMCA stenosis after CABG despite increase of patient age and risk factors. There were gender differences so that the risk of death in patients with compared with in those without LMCA stenosis was neutralised in males during 1985-1994 and in females during 1994-1999. The continuous decline of mortality during three decades most likely reflects improvement of the peri- and postoperative management of patients undergoing CABG during this period.     

Renal disease in a patient with hereditary complete deficiency of the fourth component of complement

Hereditary complete deficiency of the fourth component of complement (C4) is an extremely rare disorder with 17 cases reported so far. Twelve of these patients suffered from a systemic-lupus-erythematosus-like illness. The patient we here describe presented with severe Henoch-Sch?nlein purpura (HSP) at the age of 17. Immunofluorescence of a kidney biopsy showed granular deposits of IgG, IgA, IgM, C3 and fibrinogen in the mesangium and segmentally along the basement membrane. Six years later, the patient developed hypertension and nephrotic syndrome. Renal function deteriorated rapidly. He was on hemodialysis for 12 months and then received a cadaveric kidney graft. After 2 years of uncomplicated course, microhematuria and proteinuria developed. Immunofluorescence of a transplant biopsy was virtually identical to the pattern in the patient's own kidneys. We thus conclude that the patient had recurrence of his primary disease in the graft. Three and a half years after transplantation hemodialysis had to be restarted. This unique case supports the current view that deficiency of classical pathway components predisposes to the development of immune complex diseases and that the complement system is activated via the alternate pathway in HSP. Furthermore, we assume that complete C4 deficiency was the major cause for the recurrence and unfavorable outcome of HSP in the graft.     

Einmal- versus wiederverwendbare Instrumente in der laparoskopischen Cholezystektomie — Kostenkalkulation und Nutzwertbestimmung

Zusammenfassung Grundlagen: Seit Einführung der laparoskopischen Cholezystektomie wird diskutiert, ob bei diesem Eingriff Einmal- oder wiederverwendbare Instrumente eingesetzt werden sollten. Argumenten der Wirtschaftlichkeit wurden Aspekte der Sicherheit und Hygiene entgegengestzt. Eine Beurteilung des Ger?teeinsatzes unter Berücksichtigung der Kosten als auch des Nutzwertes der Instrumente ist bis heute nicht erfolgt. Methodik: Es wurde ein Kostenvergleich von 3 Varianten des Instrumenteneinsatzes durchgeführt (1. wiederverwendbare Instrumente, 2. Einmalger?te, 3. kombinierte Anwendung). Der Wirtschaftlichkeitsrechnung wurde eine Nutzwertbestimmung der einzelnen Instrumente durch die Operateure entgegengestellt. Ergebnisse: Durch den Einsatz von wiederverwendbaren Instrumenten ist eine betr?chtlichen Kostenreduktion (5888 ATS bei ausschlie?licher Anwendung von wiederverwendbaren Ger?ten. 3945 ATS bei kombiniertem Einsatz) zu erreichen. Der Nutzenvergleich zeigte beim Clipsetzer und dem Port für die erste Insertion Vorteile für die Einmalinstrumente. Schlu?folgerungen: Aufgrund der Ergebnisse von Kostenkalkulation und Nutzwertbestimmung stellt der kombinierte Einsatz von wiederverwendbaren und Einmalinstrumenten derzeit die beste Alternative dar.      

Hypoosmolare Hyponatri?mie als Leitsymptom bei Hypothyreose

Zusammenfassung Anamnese und Diagnostik: Ein 75-jähriger Patient wies neben unspezifischen anamnestischen Symptomen (Appetitverlust, Merkfähigkeitsstörung und Muskelschwäche) klinisch diskrete Beinödeme, abgeschwächte Muskeleigenreflexe und eine deutliche Gedächtnisstörung auf. Aufgrund einer euvolämischen, laborchemisch hypoosmolaren Hypoatriämie und eines Urinnatriums im Normbereich wurde als Arbeitsdiagnose von einem Syndrom der inadäquaten ADH-Sekretion (SIADH) ausgegangen. Während sich weder in der Anamnese noch in den folgenden Untersuchungen eine dem SIADH zugrunde liegende Pathologie eruieren ließ, ergab sich in den weiteren Laboruntersuchungen der Befund einer ausgeprägten Hypothyreose. Die Hyponatriämie bei Hypothyreose spiegelt eine Komponente der renalen Funktionsstörung bei Schilddrüsenhormonmangel wider. Therapie und Verlauf: Nach Flüssigkeitsrestriktion und Hormonsubstitution erreichte der Patient schnell normale Natriumwerte und zeigte eine deutliche Besserung seiner kognitiven Fähigkeiten. Schlussfolgerung: Als Schlussfolgerung aus dieser Kasuistik wird Zurückhaltung bei der Diagnose eines SIADH empfohlen, bevor nicht eine sorgfältige Untersuchung des Nebennieren- und Schilddrüsenhormonstatus erfolgt ist. Abstract Case History and Diagnosis: A 75-year-old male patient presented with a history of anorexia, muscle weakness, and increasing memory loss. He had mild pedal edema and decreased deep tendon reflexes. As the laboratory tests showed hypoosmolar hyponatremia and urinary sodium within the normal range, a syndrome of inappropriate ADH secretion (SIADH) was presumed. While neither the medical history nor any of the diagnostic procedures revealed any underlying pathology explaining the SIADH, laboratory tests showed significant hypothyroidism. Hypothyroid states are associated with significant changes in renal function, one of which is hypoosmolar hyponatremia. Treatment and Course: Treatment included fluid restriction and hormone substitution and resulted in a quick correction of the hyponatremia and a clear improvement of the patient's cognitive function. Conclusion: It is concluded that the diagnosis of SIADH should only be made after thorough investigation of the adrenal and thyroid hormone status.