STREPTOCOCCAL ANTIBODY CROSS-REACTIVITY WITH HLA-DR4+VE B-LYMPHOCYTES. BASIS OF THE DR4 ASSOCIATED GENETIC PREDISPOSITION TO RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE?

B-lymphocytes obtained from patients with either rheumatic feveror rheumatic heart disease and from normal subjects were reactedwith serum obtained from rabbits immunized with streptococcalcell wall antigen. The presence of cytotoxicity was sought usingan inverted phase microscope after differential uptake of eosindye. The serum was found to be significantly more cytotoxicto HLA-DR4 containing cells of both patients and normals comparedwith DR4 negative cells (P<0. 0001). KEY WORDS: Streptococcal cell wall antigen, Antiserum, Cytotoxicity     

Determinants of pulmonary blood volume

Pulmonary blood volume was determined by the radiocardiographic technique in 49 patients coming to cardiac catheterization. Since this method has not been directly compared with the more commonly used double injection of dye. 25 comparisons were carried out in 13 patients of the series. Agreement was good over a range of 4.5-21.1 heart cycles since there was no statistically significant difference between transit time values measured by the two methods.The relation of pulmonary blood volume to other hemodynamic factors in these 49 patients, with and without cardiac or pulmonary disease, was evaluated by means of multiple regression analysis. The analysis carried out for mean transit time indicates that this parameter varies predominately with flow. Pulmonary blood volume, in this series of resting recumbent individuals, varies to a significant degree only with total blood volume and with pulmonary venous pressure. No parameters of vascular distensibility, such as pulmonary vascular resistance, were found to affect the volume of blood in the lungs.The fact that variations in pulmonary blood volume among the subjects could be described by a multiple regression equation linear with respect to total blood volume and pulmonary venous pressure indicates that these variations are the result of passive distention of components of the vascular bed.     

Potential predictors of information-seeking behavior by homosexual/bisexual (gay) men with a human immunodeficiency virus seropositive health status.

Seeking ways to improve their health, gay men with human immunodeficiency virus (HIV) infections living in San Francisco are developing information networks and patterns of self-care behavior. Drawing from a set of explanatory theories, this cross-sectional survey with retrospective elements examined patterns and potential predictors of information-seeking activity in a cohort or 162 HIV seropositive (HIV+) men, 60 of whom provided complete data sets. The study suggests that 1 year after becoming aware of an HIV+ health status, most patients have developed multifaceted information networks. The amount of tangible aid acquired from these networks and frequency of consultation is positively related to patterns of HIV self-care behaviors and "feeling calm" (p less than 0.01), suggesting that these variables may be important markers for the need of supportive-educative nursing care. Suggestions for nursing practice and research are also described.     

Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in mice

Studies were carried out in streptozotocin-treated diabetic mice to evaluate their behavioral responses to different noxious stimuli. In opposition to rats, streptozotocin-injected diabetic mice display a persistent hypoalgesia to non-noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive responses of diabetic mice to formalin injection were significantly reduced in both acute and inflammatory phases. However, no overt differences were detected between nondiabetic and diabetic mice in their sensitivity to noxious heat (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied to the hind paw. To evaluate whether neurotrophin treatment could normalize the sensory deficits, nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3 weeks. Neurotrophin-treated mice were also compared to mice that received insulin for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment only reversed behavioral responses to chemogenic stimuli during the acute phase of the formalin test. These results demonstrate that diabetic mice develop reduced sensitivity to mechanical and chemical stimuli. Furthermore, these studies show that dorsal root ganglion neurons in diabetic mice are responsive to treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their ability to affect distinct somatosensations.     

Contribution of the Vertebral Posterior Elements in Anterior–Posterior DXA Spine Scans in Young Subjects

Because DXA is a projection technique, anterior–posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6–25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L₃ vertebra and for a 10‐mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 ± 4.2% of the total BMC, with a significant difference between males (49.9 ± 4.0%) and females (52.8 ± 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity.     

Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression

Background and purpose:

Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca²⁺-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.

Experimental approach:

In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.

Key results:

Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.

Conclusions and implications:

Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca²⁺-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1.     

Overcoming the challenging cervix: techniques to access the uterine cavity

OBJECTIVE: To identify cervical stenosis and review medical, surgical, and radiological modalities to access the uterine cavity. MATERIALS AND METHODS: Computerized searches of Medline and PubMed from 1996 to 2005 were conducted using the key words "cervix," "cervical ripening," and "cervical stenosis." References from identified publications were manually searched and cross-referenced to identify additional relevant articles. We review relevant techniques on how to access the uterine cavity when cervical stenosis is encountered. RESULTS: Many gynecologic procedures require uncomplicated access through the cervix to access the uterine cavity, including hysteroscopy, dilation and curettage, sonohysterogram, hysterosalpingogram, endometrial biopsy, and embryo transfer for in vitro fertilization. These procedures can be quite complicated when a cervix is obstructed. Management techniques described include the medical use of misoprostol and laminaria, intraoperative ultrasound guidance, and operative creation of a new passage. Additionally, techniques for bypassing the obstructed cervix and preventing cervical stenosis have been described. CONCLUSIONS: Cervical stenosis can result in iatrogenic complications. Preoperative identification, cervical ripening agents, osmotic dilators, and the use of ultrasound guidance are useful in overcoming cervical stenosis. It is also key to identify those at risk for cervical stenosis and implement preventative techniques as needed.