MsFLASH participants' priorities for alleviating menopausal symptoms.

OBJECTIVE: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). METHODS: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. RESULTS: The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. CONCLUSIONS: Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.

p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome.

Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27(SJ), present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27(SJ) associates with C/EBPbeta, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27(SJ) with C/EBPbeta and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27(SJ) forces its entry into the nucleus and diminishes the capacity of p27(SJ) to suppress Tat activity, but does not alter its ability to suppress C/EBPbeta activation of the LTR. Results from binding assays showed the inhibitory effect of p27(SJ) on C/EBPbeta interaction with DNA. Finally, our results demonstrate that expression of p27(SJ) decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27(SJ) protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.

Molecular characterization of human zyxin.

Zyxin is a component of adhesion plaques that has been suggested to perform regulatory functions at these specialized regions of the plasma membrane. Here we describe the isolation and characterization of cDNAs encoding human and mouse zyxin. Both the human and mouse zyxin proteins display a collection of proline-rich sequences as well as three copies of the LIM domain, a zinc finger domain found in many signaling molecules. The human zyxin protein is closely related in sequence to proteins implicated in benign tumorigenesis and steroid receptor binding. Antibodies raised against human zyxin recognize an 84-kDa protein by Western immunoblot analysis. The protein is localized at focal contacts in adherent erythroleukemia cells. By Northern analysis, we show that zyxin is widely expressed in human tissues. The zyxin gene maps to human chromosome 7q32-q36.

Current therapy for Crigler-Najjar syndrome type 1: report of a world registry.

This study represents a multicenter survey on the management of patients with Crigler-Najjar syndrome (CNS) type 1. The aim of the survey was to find guiding principles for physicians in the care of these patients. Fifty-seven patients were included. At the time of inclusion, 21 patients had received a liver transplant (37%). The average age at transplantation was 9.1 +/- 6.9 years (range, 1-23 years); the age of the patients who had not been transplanted at the time of inclusion was 6.9 +/- 6.0 years (range, 0-23 years). Brain damage had developed in 15 patients (26%). Five patients died, and 10 are alive with some degree of mental or physical handicap. In 2 patients, ages 22 and 23 years, early signs of bilirubin encephalopathy could be reversed, in 1 by prompt medical intervention followed by liver transplantation and in the other by prompt liver transplantation. Seven patients underwent transplantation with some degree of brain damage at the time of the surgery; 1 of these died after retransplantation, 2 improved neurologically, and 4 remained neurologically impaired. The age of 8 patients with and 13 without brain damage at or before transplantation was 14.3 +/- 5.9 and 5.9 +/- 5.4 years (P < .01), respectively. Therapy of CNS type 1 consists of phototherapy (12 h/d), followed by liver transplantation. Phototherapy, although initially very effective, is socially inconvenient and becomes less efficient in the older age group, thus also decreasing compliance. Currently, liver transplantation is the only effective therapy. This survey shows that, in a significant number of patients, liver transplantation is performed after some form of brain damage has already occurred. From this, one must conclude that liver transplantation should be performed at a young age, particularly in situations in which reliable administration of phototherapy cannot be guaranteed.

Orthotopic liver transplantation for Crigler-Najjar type I disease in six children.

Hyperbilirubinemia in Crigler-Najjar disease type I (CN) can be partially controlled by daily phototherapy, but these children remain at permanent risk of developing brain damage due to kernicterus. Because liver transplantation is the only available curative treatment for liver-based inborn errors of metabolism, orthotopic liver transplantation (OLT) was performed in six patients with CN. Mean age at surgery was 52.5 months (range 27 to 100). Despite a mean daily phototherapy of 12.4 +/- 0.8 hr, mean bilirubin of the 6 patients was 388 microM/L (range 175 to 703) before OLT; one of them was also being treated with tin-protoporphyrin. All 6 had elevated AST/ALT, ranging from 1.4 to 6 times upper normal values. Complications occurred in three patients after OLT, including miliary tuberculosis in one, graft rejection and retransplantation in one, and hepatic artery thrombosis in one. All patients survive with normal serum bilirubin level (follow up 6 to 116 months). Four have normal enzymes on post-OLT follow-up (30 to 95 months), follow a normal education program, and have a normal social life. One recently transplanted patient has progressively normalizing liver function tests 6 months after OLT. One patient transplanted at 8 y.o. (now 116 months post-OLT) has moderate neurological delay due to pretransplant kernicterus, and posttransplant chronic persistent hepatitis. Our series shows that OLT cures hyperbilirubinemia in CN patients, with an excellent survival prospect. The procedure should be decided upon before neurological sequelae occur, since these persist after transplantation.

[Acute renal failure with high-dose combination therapy with penicillin G and amoxicillin]. / Akutes Nierenversagen unter hochdosierter Kombinationstherapie mit Penicillin G and Amoxicillin.

A 3 year old girl was admitted with suspected bacterial meningitis. The patient's history concerning renal and cerebral function and known allergies had been uneventful until that time. 36 h after initiation of a high dose antibiotic therapy with Penicillin G (0.5 Mega IE/kg/day) and Amoxicillin (400 mg/kg/day) macrohematuria and consecutive anuria was observed. Prerenal cardiocirculatory failure, a Schwartz-Bartter-reaction as well as coagulatory failure could be ruled out. There were no symptoms of hypersensitivity. Sonographic examinations of the kidneys and the urinary tract as well as urinanalysis suggested an acute tubular obstruction and papillary necrosis caused by amoxicillin. After changing the antibiotic regimen to chloramphenicol and induction of diuresis by furosemide and dopamine renal failure could be resolved within 39 h. The patient recovered completely. High dose therapy with amoxicillin (greater than 300 mg/kg/day) includes the risk of tubular obstruction due to cristalluria. Solubility of ampicillin in aqueous fluids (6.5 mg/ml at pH 7) should be supported by sufficient diuresis and urine alkalization.

Hyperthermia in cancer therapy.

Tumor hyperthermia is a rediscovered technique of oncotherapy which has confirmed value in many studies on cell cultures, rodent and mammalian tumors as well as first investigations on patients with tumors. The biological basis for using heat in the treatment of cancer is well established. Various direct and indirect mechanisms are significant for the effect of hyperthermia on tumor tissue. Whereas there are already extensive studies on the direct effects of hyperthermia on DNA, RNA, and protein synthesis, energy metabolism, and the membrane properties of tumor cells, the indirect effects have only been investigated more closely in recent years. These are likewise important for the damage to the tumor tissue and are mediated above all via alterations in the microcirculation and the environment. The recently gained increasing significance of this new technique in combination with other treatment modalities is well documented. Technical problems of heat application must be overcome, especially in deeper tumors and problems of thermometry must be solved in order to be able to apply tumor hyperthermia not only to selected advanced or recurrent tumors, but in order to use it as the fourth pillar of tumor therapy besides surgery, radiotherapy and chemotherapy. This article considers the biological basis and important aspects of hyperthermia therapy in combination with radiotherapy and chemotherapy.

Impact of various thermal doses on the oxygenation and blood flow in malignant tumors upon localized hyperthermia.

Upon localized hyperthermia at modest thermal doses an increase in tumor blood flow can be observed in many tumors which is paralleled by an improvement of the oxygenation status of the tissue. At intermediate or high thermal doses a pronounced restriction of the tumor circulation becomes obvious leading to a deterioration of the tumor oxygenation. As a consequence, a further enhancement of the thermal response of tumors relative to normal tissues has to be expected at intermediate or high thermal doses.