A clinical decision rule to enhance targeted bone mineral density testing in healthy mid-life women.

SUMMARY: The rates of bone mineral density testing for osteoporosis among healthy mid-life women are high, although their osteoporosis or fracture risk is low. To reduce unnecessary testing, we created and evaluated a tool to guide bone density testing based on the woman's age, weight, fracture history, and menopausal status. INTRODUCTION: This study aims to improve case finding of mid-life women with low bone mass on bone mineral density (BMD) assessment. METHODS: Among healthy women aged 40-60 years having their first BMD test, osteoporosis risk factors were assessed by questionnaire and BMD by dual-energy X-ray absorptiometry. The combination of risk factors that best discriminated women with/without low bone mass (T-score ≤ -2.0) was determined from the logistic regression model area under the curve (AUC) and internally validated using bootstrapping. Using the model odds ratios, a clinical prediction rule was created and its discriminative properties assessed and compared with that of the osteoporosis self-assessment tool (OST). Sensitivity analyses examined results for pre-/peri- and post-menopausal women, separately. RESULTS: Of 1,664 women referred for baseline BMD testing, 433 with conditions known to be associated with bone loss were excluded. Of 1,231 eligible women, 944 (77%) participated and 87 (9.2%) had low bone mass (35 pre-/peri- and 52 post-menopausal). Four risk factors for low bone mass were identified and incorporated into a clinical prediction rule. Selecting women for BMD testing with weight of ≤70 kg or any two of age >51, years' post-menopause of ≥1, and history of fragility fracture after age 40 was associated with 93% sensitivity to identify women with low bone mass, compared with 47% sensitivity for an OST score of ≤1 (AUC 0.75 versus OST AUC 0.69, p = 0.04). Results restricted to post-menopausal women were similar. CONCLUSIONS: Among healthy mid-life women receiving a baseline BMD test, few had low bone mass, supporting the need for guidance about testing. A prediction rule with four risk factors had improved sensitivity over the OST. Further validation is warranted.

The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty.

Stress and exploration of novel environments induce neural expression of immediate early gene transcription factors (IEG-TFs). However, as yet no IEG-TF has been shown to be required for the normal biological or behavioral responses to these stimuli. Here we show that mice deficient for the IEG-TF early growth response gene (Egr) 3, display accentuated behavioral responses to the mild stress of handling paralleled by increased release of the stress hormone corticosterone. Egr3-/- mice also display abnormal responses to novelty, including heightened reactivity to novel environments and failure to habituate to social cues or startling acoustic stimuli. In a Y-maze spontaneous alternation task, they perform fewer sequential arm entries than controls, suggesting defects in immediate memory. Because stress and novelty stimulate hippocampal long-term depression (LTD), and because abnormalities in habituation to novelty and Y-maze performance have been associated with LTD deficits, we examined this form of synaptic plasticity in Egr3-/- mice. We found that Egr3-/- mice fail to establish hippocampal LTD in response to low frequency stimulation and exhibit dysfunction of an ifenprodil-sensitive (NR1/NR2B) N-methyl-d-aspartate receptor subclass. Long term potentiation induction was not altered. The NR2B-dependent dysfunction does not result from transcriptional regulation of this subunit by Egr3, because NR2B mRNA levels did not differ in the hippocampi of Egr3-/- and control mice. These findings are the first demonstration of the requirement for an IEG-TF in mediating the response to stress and novelty, and in the establishment of LTD.

Ovarian metastasis of a malignant melanoma: A case report.

Malignant melanoma represents 3% of cancers at the woman. The metastatic gynecological localization are rare and ovary is an exceptional site. Prognosis of metastatic ovary malignant melanoma is pejorative (5% 5 years survival). We report a case observed in a 65-year-old patient, who developed 2 melanomas of the left leg and presented a right ovarian tumor during a supervision tomodensitometric 7 years after diagnostic initial. The immunohistochemical assays after annexectomy confirmed the diagnostic of ovarian metastasis. To evoke an ovarian metastasis localization of a malignant melanoma in front of the increasing incidence is a decisive for prognosis.

Combination therapy for advanced pancreatic cancer using Herceptin plus chemotherapy.

The HER2/neu oncogene is overexpressed in up to 70% of human pancreatic cancer specimens when compared to normal pancreatic tissue. This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptin. Herceptin has been successfully used in combination with other chemotherapeutic agents in breast cancer, a cancer in which only 30% of patients harbor elevated HER2/neu levels. In the present study, we investigated the therapeutic efficacy of Herceptin in combination with gemcitabine and docetaxel. Gemcitabine is currently the standard chemotherapeutic agent used to treat pancreatic cancer. In contrast, docetaxel, a taxane, is only just being investigated in pancreatic cancer. Tumor cell resistance to taxanes is at least in part mediated by the HER2/NEU oncogene. We have previously characterized HER2/NEU expression in human pancreatic cancer cell lines and studied the anti-tumor activity of Herceptin monotherapy in vitro and in vivo. In the present study, combination therapy resulted in a dramatic improvement of animals bearing human pancreatic cancer xenografts. Furthermore, metastasis and production of ascites was lower when a combination of these three agents was used. We conclude that, as with breast cancer, the anti-tumor activity of Herceptin may be improved by combination with taxanes or gemcitabine.

Antiarrhythmics. N-(aminoalkylene)trifluoroethoxybenzamides and N-(aminoalkylene)trifluoroethoxynaphthamides.

Benzamides and naphthamides characterized by one or more 2,2,2-trifluoroethoxy ring substituents have been prepared and evaluated as antiarrhythmic agents in mice. Structure-action studies reveal that antiarrhythmic activity is highly dependent upon the number and position of 2,2,2-trifluoroethoxy groups. The most potent compounds are derived from 2,5-bis(2,2,2-trifluoroethoxy)benzamide, and, within this group, wide variation of the amide side chain is possible without adversely affecting the antiarrhythmic activity.

Problems in implementing the 1991 Treatment of Mental Patients Law in Israel.

The application of the new Treatment of Mental Patients Law, 1991, has been responsible for significant changes in the work of mental health workers, in particular those involved in the often complex process of civil commitment for examination/hospitalization. The experience of implementing this new law shows that some of the clauses related to this process contain controversial concepts. These concepts will be the focus of this paper.

Novel segment polarity gene interactions during embryonic head development in Drosophila.

In the trunk of the Drosophila embryo, the segment polarity genes are initially activated by the pair-rule genes, and later maintain each other's expression through a complex network of cross-regulatory interactions. These interactions, which are critical to cell fate specification, are similar in each of the trunk segments. To determine whether segment polarity gene expression is established differently outside the trunk, we studied the regulation of the genes hedgehog (hh), wingless (wg), and engrailed (en) in each of the segments of the developing head. We show that the cross-regulatory relationships among these genes, as well as their initial mode of activation, in the anterior head are significantly different from those in the trunk. In addition, each head segment exhibits a unique network of segment polarity gene interactions. We propose that these segment-specific interactions evolved to specify the high degree of structural diversity required for head morphogenesis.

Ectopic orthodenticle expression alters segment polarity gene expression but not head segment identity in the Drosophila embryo.

The cephalic gap genes specify anterior head development in the Drosophila embryo. However, the mechanisms of action of these genes remain poorly understood. Here, we focused on the cephalic gap gene orthodenticle (otd), which establishes a specific region of the anterior head. It has been proposed that otd acts in a combinatorial fashion with the cephalic gap genes empty spiracles (ems) and buttonhead (btd) to assign segmental identities in this region. To test this model, we used a heat-inducible transgene to generate pulses of ubiquitous otd expression during embryonic development. Ectopic otd expression caused significant defects in head formation, including the duplication of sensory structures derived from otd-dependent segments. However, these defects do not appear to result from the transformation of head segment identities predicted by the combinatorial model. Instead, they correlate with specific regulatory effects of otd on the expression of the segment polarity genes engrailed (en) and wingless (wg). Ectopic otd expression also caused the loss of head structures derived from the maxillary segment, which lies posterior to the otd domain. We show that this effect is associated with otd repression of the homeotic selector gene Deformed (Dfd).

The Cambridge Cognitive Examination (CAMCOG): validation of the Hebrew version in elderly demented patients.

BACKGROUND AND PURPOSE: The CAMCOG is the second most popular cognitive testing instrument in use by Israeli clinicians. The present study examines the reliability and validity of a Hebrew version of the CAMCOG in a group of dementia sufferers in a clinical setting. METHOD: Study participants included 36 dementia sufferers and 19 control non-demented, depressed elderly subjects, consecutive referrals to an outpatient psychogeriatric service and an 'open' ward of a psychiatric hospital. Operational clinical criteria for dementia and its subtypes and for the various forms of depression were used as the 'gold' standards. The CAMCOG was translated into Hebrew and then back to English. Seven items needed modifications for local usage. RESULTS: Interrater and test-retest scores calculated as exact agreement rates ranged from good to excellent for all items, although test-retest reliability scores were generally lower than interrater scores. Kappa statistics ranged from good to excellent for all but one item in the interrater scores and for two items in the test-retest scores. A strong convergent validity was found with the MMSE score (r=0.89, p<0.01). The 79/80 cutoff point provided moderate sensitivity (57.9%), excellent specificity (97.2%) and a strong predictive value (83.6%). CONCLUSION: The Hebrew version of the CAMCOG was found to be an appropriate instrument to discriminate between demented and non-demented depressed controls in a clinical setting. In light of the demographic, cultural and linguistic heterogeneity of the Israeli elderly population, further studies should examine the psychometric characteristics of the CAMCOG in a more varied sample and also using other cutoff points in order to establish if an increase in its discriminatory power is obtainable.

Examining the reliability and validity of the Hebrew version of the Mini Mental State Examination.

The Mini Mental State Examination is used worldwide for the screening and diagnosis of dementia. The aim of the present study was to examine the reliability and validity of the Hebrew version of the Mini Mental State Examination. The Hebrew version of the Mini Mental State Examination was administered to 36 demented and 19 non-demented elderly persons. Test-retest reliability scores were calculated as exact agreement rates, and ranged from good to excellent for all the items. Strong convergent validity, as measured by the correlation between the MMSE and the CAM-COG (r = 0.94), was found. Good predictive value was observed as over three-quarters of the participants were correctly classified as demented or non-demented. The Hebrew version of the MMSE was found to be a useful and valid instrument for the determination of dementia in the elderly population.

[Surgical treatment of rectal prolapse]. / Khirurgicheskoe lechenie vypadeniia priamoi kishki.

The experience with surgical treatment of rectal prolapse in 82 patients is presented. In stage I-II prolapse, the interventions on the external anal sphincter and prolapsing rectum are the operations of choice, and in stage III-IV-intraabdominal fixation of the rectum by the lavsan strip to the anterior longitudinal ligament of the vertebral column, the free ends of which are sutured to the lateral surfaces of the rectum. The incidence of recurrences of the disease was 2.9%.