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     

Nonoperative treatment ofacromioclavicular joint injuries

Nonoperative treatment is generally the choice for Type I and II acromioclavicular (AC) joint injuries. The situation issomewhat more controversial when Type III AC dislocations are considered, particularly with respect to athletes and heavy laborers. A number of recent studies have supported conservative treatment in these groups. There is general consensus as to the need for surgical intervention for Type IV, V, and VI AC injuries. Integral to any form of management, nonoperative or operative, is a rehabilitation program that addresses range of motion, strength, and neuromuscular control. We describe our program, which is divided into four phases: (1) Pain control and immediate protected range of motion and isometric exercises; (2) strengthening exercises using isotonic contractions and proprioceptive neuromuscular facilitation (PNF) exercises; (3) Unrestricted functional participation with the goal of increasing strength, power, endurance, and neuromuscular control; and (4) return to activity with sport specific functional drills. An athlete is ready to return to competitive sports once the following criteria are met: full range of motion (ROM), no pain or tenderness, satisfactory clinical exam, and demonstration of adequate strength on isokinetic testing. The unique considerations in a throwing athlete with an AC injury are also addressed. The primary goal of the nonoperative treatment protocol is to return the athlete to full activities as quickly and as safely as possible.     

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.     

A new syndrome with features of the Smith-Lemli-Opitz and Meckel-Gruber syndromes in a sibship with cerebellar defects

The Smith-Lemli-Opitz syndrome (SLOS) and the Meckel syndrome (MS) have been regarded as separate autosomal recessive entities. Recently, overlap of these two syndromes has been discussed. A sibship containing a probable new syndrome with features reminiscent of the SLOS and the MS is presented. The literature is reviewed with regard to the frequency of various malformations in these syndromes. Clinical manifestations and cerebellar abnormalities in these sibs are similar to those described in the Joubert syndrome (JS). These three cases may represent a new syndrome with features in common with SLOS, MS, and JS resulting from the same mutant gene, which exhibits considerable pleiotropy.     

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.     

Development of a molecular-beacon assay to detect the G1896A precore mutation in hepatitis B virus-infected individuals

The 1896 precore (PC) mutation is the most frequent cause of hepatitis B virus e-antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Detection of the 1896 PC mutation has application in studies monitoring antiviral therapy and the natural history of the disease. Identification of this mutation is usually performed by direct sequencing, which is both costly and laborious. The aim of this study was to develop a rapid, high-throughput assay to detect the 1896 PC mutation using real-time PCR and molecular-beacon technology. The assay was initially standardized on oligonucleotide targets and plasmids containing the wild-type (WT) and PC mutation and then tested on plasma samples from children with HBV DNA of >10(6) copies/ml. Nine individuals were HBeAg negative and suspected to harbor HBeAg mutations, while 12 children were HBeAg positive and selected as controls. Ninety percent (19 of 21) of plasma samples tested with molecular beacons were in complete agreement with sequencing results. The remaining 10% (2 of 21) of samples were identified as heterogeneous mixtures of WT and mutant virus by molecular beacons, though sequencing found only a homogeneous mutant in both cases. Overall, the 1896 PC mutation was detected by this assay in 55.5% of the children with HBeAg-negative infection. In summary, this assay is a rapid, sensitive, and specific technique that effectively discriminates WT from 1896 PC mutant HBV and may be useful in clinical and epidemiological studies.