Cutaneous postural vasoconstriction is modified by exogenous but not endogenous female hormones in young women

Previously reported attenuation of skin postural vasoconstriction in women during the luteal menstrual cycle phase may be due to a progesterone-mediated decrease in myogenic or veno-arteriolar (VAR) mechanisms. Skin perfusion was measured in the shin and foot dorsum by Laser Doppler Fluxometry during leg dependency that increased vascular transmural pressure below (myogenic constriction only) and above (myogenic and VAR) the 25 mmHg threshold for activation of the VAR, and during venous distension to activate the VAR alone (cuff inflation to 50 mmHg). In six young women with normal menstrual cycles, vasoconstrictor responses to all interventions did not differ between days 7–13 (follicular) and 18–23 (luteal) of the normal menstrual cycle when progesterone levels were low and at their peak respectively. In eight women taking combined oral contraceptives (OC) and tested during pill consumption days, reductions in foot skin perfusion were smaller (P = 0.05) than in the luteal phase of the normal cycle for leg dependency below (−36.9 ± 5.2% OC vs. −52.5 ± 7.8% luteal, mean ± S.E.M.) and above (−43.7 ± 3.4% OC vs. −55.1 ± 4.8% luteal) the VAR threshold, and for venous distension (−53.1 ± 2.6% OC vs. 66.4 ± 5.5% luteal). In women with normal menstrual cycles, impaired postural vasoconstriction may be confined to those who experience pre-menstrual symptoms rather than a direct effect of endogenous hormones. Reduced vasoconstriction in the dependent foot during OC use is consistent with the known vasodilator action of exogenous hormones and its long-term effects     

Evaluation of non-invasive blood pressure measurement by the Finapres method at rest and during dynamic exercise in subjects with cardiovascular insufficiency

The accuracy and precision of the Finapres in recording rest and exercise blood pressure compared with the intra-arterial (aortic and brachial) and random-zero sphygmomanometer methods was assessed in 84 ischaemic patients in three different studies. Firstly, comparison at rest with the aortic intraarterial pressure in 50 ischaemic patients demonstrated that the Finapres systolic (136.5 ± 21.1 vs. 129.3 ± 19.0 mmHg;p < 0.001) and mean (92.4 ± 13.4 vs. 90.7 ± 11.4 mmHg;p < 0.001) arterial pressures were higher and diastolic pressures lower (70.4 ± 11.5 vs. 71.5 ± 9.8 mmHg;p < 0.001). The reproducibility of the Finapres and invasive method was similar for systolic (4.6% vs. 4.0%), diastolic (2.8% vs. 2.7%) and mean (3.3% vs. 3.0%) blood pressures. Second, in seven subjects studied twice at rest and during 4 min supine bicycle exercise, the exercise increase in blood pressure was greater on the Finapres compared with the brachial intra-arterial pressure (systolic +10.2 ± 6.3 vs. +3.6 ± 9.8 mmHg; diastolic +9.6 ± 11.1 vs. +0.2 ± 2.1 mmHg;p = 0.02 for each); however, at steady-state the peak/trough differences in pressure between the methods were similar. Thirdly, compared under rest conditions, to random zero sphygmomanometer (RZO), the Finapres systolic pressure was higher (6.8 ± 3.5 mmHg) and diastolic pressure lower (–6.0 ± 1.9 mmHg). During upright bicycle exercise, the difference between the Finapres and RZO in systolic blood pressure increased at each level of exercise (+14.3 ± 4.2, +17.9 ± 4.0 and +22.2 ± 4.1 mmHg respectively at each exercise stage:p < 0.01). For RZO, diastolic blood pressure fell as exercise workload increased whereas Finapres diastolic blood pressure increased on exercise (3.1 ± 2.6, 7.0 ± 2.1 and 8.1 ± 2.0 mmHg respectively:p < 0.01). Thus there were systematic differences between the values recorded by the Finapres and proximal blood pressure methods and limited agreement in the rest to exercise increments related to light exercise. Calibration of the Finapres values in terms of the other methods is limited by the variable relationship to these related changes in arterial distensibility.     

Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.     

Alveolar hydatid disease of the liver: computed tomography and transabdominal ultrasound with histopathological correlation.

The appearances of alveolar hydatid disease of the liver (AHDL) on computed tomography (CT) and ultrasound (US) were retrospectively compared with histopathological appearances in 67 patients with 100 separate lesions. The radiological features were correlated directly with the pathological specimens obtained from each patient. We conclude that the CT appearances are more specific, but that US has a role to play in mass screening in endemic areas, and intraoperatively.     

Evaluation of a Commercial PCR Kit for Diagnosis of Cytomegalovirus Infection of the Central Nervous System

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.     

Calcium entry blocker: Treatment in acute pain in cluster headache patients

15 chronic cluster headache patients in whom pain was induced by nitroglycerin received acute intravenous treatment with a calcium entry blocker. At the time of peak pain we noted a sudden decrease after the Verapamil injection. The mechanism by which the calcium entry blocker afforded relief is unlikely to have been vasodilatation in patients whose blood vessels had just been dilated by nitroglycerin. A more probable mechanism is blockade of the release of the pain-inducing neurotransmitters. The vasodilatation phase is not a primary factor in the onset of pain.

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Sommario Sono stati studiati 15 soggetti affetti da Cluster cronica inducendo loro la crisi dolorosa con Trinitrina, trattandoli poi con calcio antagonista (Verapamil) per via endovenosa. Al momento dell'apice del dolore, valutato dal paziente con un analogo visivo, la somministrazione di Verapamil endovena, determina una rapida estinzione del dolore. L'azione efficace del Ca-antagonista non può sicuramente essere rapportata alla vasodilatazione poiché la crisi dolorosa insorge già in una fase di vasodilatazione per l'azione della Trinitina. Il meccanismo d'azione più probabile è il blocco del release di neurotrasmettitori inducenti l'attacco doloroso. Si sottolinea che la vasodilatazione non è il fattore primario dell'induzione del dolore.

     

Pre- and postoperative evaluation of plasma creatine kinase in 142 children subjected to "uncomplicated" anesthesia in muscle biopsy

Pre- and postoperative serum CK activity is evaluated in 142 children submitted, "uneventfully", to diagnostic muscle biopsy under halothane (77 patients), ketamine (50 patients) or "local" (15 patients) anaesthesia. The purpose was to ascertain whether or not anaesthesia-induced-rhabdomyolysis (AR) was an asymptomatic (and unrecognized) complication of "uneventful" anaesthesia. The majority of patients with low preoperative CK values showed a slight increase of serum CK activity on the first postoperative day. On the contrary, a postoperative decrease was observed in the majority of patients with high preoperative values (namely in almost all ketamine patients and in 2/3 of halothane-patients). In no case postoperative increase reached a value suggesting the occurrence of AR even though a postoperative value of 16480 U/I was observed in a patient with Duchenne muscular dystrophy after halothane anaesthesia. Sudden interruption of motor activity induced by general anaesthesia seems to be the most important factor in reducing the release of CK from muscle. When preoperative release is low, any further postoperative reduction is not sufficient to balance the moderate increase of CK produced by the surgical procedure; the opposite should happen in patients presenting with high preoperative release. So far as anaesthetics are concerned, our data seem to suggest that ketamine has a higher "protective" role compared to halothane.