High initial values of beta-subunits of human chorionic gonadotropin in ovum donation pregnancies indicate better implantation.

Fifty-five patients were treated by ovum donation, and a control group of 165 patients underwent IVF. The number of pregnancies obtained were 28 and 25, respectively. The initial beta-hCG values, as well as the PRs and implantation rates, in the ovum donation series were significantly higher than those of the IVF series. The clinical significance and potential application of these observations are discussed.     

Growth inhibition of prostate cancer xenografts by halofuginone

BACKGROUND: Halofuginone, an inhibitor of collagen type I synthesis, is an anti-angiogenic agent. Here we evaluated the efficacy of halofuginone to inhibit prostate cancer (PC) xenografts representing various phenotypes of the disease. METHODS: An androgen-dependent (CWR22), an androgen-independent (PC3), and a neuroendocrine (WISH-PC2) PC xenograft were used. Halofuginone was given orally or injected intraperitoneally. Tumor size, collagen alpha1(I) gene expression (in situ hybridization), collagen content (sirius red staining), angiogenesis (immunohistochemistry with factor VIII antibodies), and apoptosis/necrosis (DNA fragmentation) were evaluated. RESULTS: Halofuginone inhibited the growth of all subcutaneously implanted xenografts and of WISH-PC2 when transplanted orthotopically. The effect was dose-dependent (WISH-PC2) and accompanied by decrease in plasma PSA levels (CWR22). In all xenografts, halofuginone inhibited collagen alpha1(I) gene expression, reduced collagen content, and endothelial cell number resulting in an increase in apoptosis/necrosis. CONCLUSIONS: Oral administration of halofuginone slowed the progression of PC xenografts representing a broad range of phenotypes. Halofuginone may become a new modality for PC prevention.     

Structural determinants of A(3) adenosine receptor activation: nucleoside ligands at the agonist/antagonist boundary

Mutagenesis of the human A(3) adenosine receptor (AR) suggested that certain amino acid residues contributed differently to ligand binding and activation processes. Here we demonstrated that various adenosine modifications, including adenine substitution and ribose ring constraints, also contributed differentially to these processes. The ligand effects on cyclic AMP production in intact CHO cells expressing the A(3)AR and in receptor binding were compared. Notably, the simple 2-fluoro group alone or 2-chloro in combination with N(6)-substitution dramatically diminished the efficacy of adenosine derivatives, even converting agonist into antagonist. Other affinity-increasing substitutions, including N(6)-(3-iodobenzyl) 4 and the (Northern)-methanocarba 15, also reduced efficacy, except in combination with a flexible 5'-uronamide. 2-Cl-N(6)-(3-iodobenzyl) derivatives, both in the (N)-methanocarba (i.e., of the Northern conformation) and riboside series 18 and 5, respectively, were potent antagonists with little residual agonism. Ring-constrained 2',3'-epoxide derivatives in both riboside and (N)-methanocarba series 13 and 21, respectively, and a cyclized (spiral) 4',5'-uronamide derivative 14 were synthesized and found to be human A(3)AR antagonists. 14 bound potently at both human (26 nM) and rat (49 nM) A(3)ARs. A rhodopsin-based A(3)AR model, containing all domains except the C-terminal region, indicated separate structural requirements for receptor binding and activation for these adenosine analogues. Ligand docking, taking into account binding of selected derivatives at mutant A(3)ARs, featured interactions of TM3 (His95) with the adenine moiety and TMs 6 and 7 with the ribose 5'-region. The 5'-OH group of antagonist N(6)-(3-iodobenzyl)-2-chloroadenosine 5 formed a H-bond with N274 but not with S271. The 5'-substituent of nucleoside antagonists moved toward TM7 and away from TM6. The conserved Trp243 (6.48) side chain, involved in recognition of the classical (nonnucleoside) A(3)AR antagonists but not adenosine-derived ligands, displayed a characteristic movement exclusively upon docking of agonists. Thus, A(3)AR activation appeared to require flexibility at the 5'- and 3'-positions, which was diminished in (N)-methanocarba, spiro, and epoxide analogues, and was characteristic of ribose interactions at TM6 and TM7.     

Concordance for cognitive impairment: a study of 50 community-dwelling elderly female-female twin pairs

The present study sought to determine concordance of cognitive impairment among elderly female twins. Cognitive testing was performed by telephone interview in a sample of 100 female-female twins older than 65 years. The participants were 32 monozygotic (MZ) and 18 dizygotic (DZ) female twin pairs, all between the ages of 65 and 86 years; their mean age was 70.2 +/- 4.6 years. All were recruited from the Institute of Psychiatry Volunteer Twin Register (IPVTR). We used the Telephone Interview for Cognitive Status (TICS) and analyzed the modified total score. Correlation's of age and zygosity were computed in relation to score on cognitive interview, and differences between MZ twin pairs (n = 32) and DZ pairs (n = 18) were analyzed using the general linear model procedure. Five subjects of the 64 MZ females (7.8%) and one DZ female (2.4%) were found to be cognitively impaired. In no case was the second twin affected. No differences in cognitive score were found between MZ and DZ twin pairs. In both groups a highly significant correlation was found between age and lower score: R(2) = -0.32, P =.009. We conclude that aging-related impairment in cognitive testing did not differ between MZ and DZ elderly female twins. Although the overall sample size was relatively small and error variance may have been introduced by imprecise measures of zygosity, the present findings are suggestive of gender differences in cognitive performance that need further evaluation.     

Cognitive impairment in probable multiple sclerosis

OBJECTIVES: To evaluate and characterise cognitive impairment in the very early stage of multiple sclerosis (MS), in which patients are still diagnosed as suffering from probable MS. METHODS: The Brief Repeatable Battery-Neuropsychological (BRB-N) that has been validated for MS patients was used. Abnormal performance was defined as one standard deviation below the mean reported for healthy age matched subjects. Neurological disability and brain magnetic resonance imaging (MRI) were performed for all patients. Correlation coefficients were calculated between disease burden variables and performance on the BRB-N. RESULTS: Sixty seven patients with probable MS were evaluated within a mean of one month of the onset of new neurological symptoms. Evidence for the presence of cognitive impairment was shown in 53.7% of patients. Verbal abilities and attention span were most frequently affected. Impairment was not correlated with neurological disability or MRI disease burden. CONCLUSION: Prevalent cognitive impairment already exists at onset of MS.     

Characterizing the elderly homeless: a 10-year study in Israel

Since 1980s there is a noticeable change in the homeless population in Western countries. Some researchers titled the change as the "new" homeless that are distinctly different than the "skid row" population described in the past. Among the "new" homeless there are increasing numbers of elderly subjects. The elderly homeless are a fragile and vulnerable group that suffers from high rates of physical and mental problems as well as increased mortality. The aim of the present study was to characterize the "new" elderly homeless. Over a 10-year period each homeless 65 years of age and older was assessed by a psychiatrist. The project was undertaken in Tel-Aviv, Israel, and was feasible due to close co-operation between the Municipal Welfare Department and mental health consultants. The Structured Clinical Interview for DSM-IV (SCID) was the main diagnostic tool. Ninety-eight subjects of 2567 homeless persons located and contacted were elderly (3.8%). Mean age for the elderly sub-group was 71.7+/-5.3 years and the great majority were male 94/98 (95.9%). In 44/98 (44.9%), a formal DSM-IV axis I psychiatric disorder was diagnosed, most common being dementia (15/44) and schizophrenia (15/44). A significant minority of 13/44 (29.5%) were diagnosed and treated prior to becoming homeless. Physical co-morbidity was found in nearly 2/3 subjects. Following intensive case-management by social workers, 35/44 (79.5%) subjects were successfully placed in permanent housing. The main conclusion is that the "new" elderly homeless are typically males suffering from frequent psychiatric morbidity and physical co-morbidity. Intensive case-management succeeded in achieving return to permanent housing in the majority of subjects.     

Attitudes Toward Sexuality Among Nursing Home Residents

There is a paucity of data regarding sexuality among nursing home residents. The aim of the present study was to evaluate sexual attitudes in a group of independent residents in a large urban nursing home. Ten items covering different aspects of sexual attitude were scored by two board certified psychiatrists following a semistructured interview. The study was undertaken at a large 1,200-bed nursing home providing services to both healthy independent elderly as well as geriatric patients. Subjects were 31 volunteers: 15 men and 16 women (mean age: 82.4 and 74.1 years, respectively), who consented to participate. Participants were cognitively intact and living independently at the nursing home. Exclusion criteria were: a) current major psychiatric morbidity, b) drug or alcohol abuse, c) Geriatric Depression Scale (short version) score 5, and d) Clinical Dementia Rating >0. A hierarchy of basic functions was constructed wherein each function was graded on a 5-point Likert-like scale reflecting its endorsed importance. The majority (23/31) felt that sexuality should be openly discussed with the elderly by health professionals. Twenty-one of 31 expressed willingness to receive medical consultation and treatment for sexual dysfunction as needed and 20/31 expressed a similar attitude if their partner so needed. The hierarchy of needs was rated by the participants (men and women, respectively) as follows: Mood (4.4; 4.3), Memory (4.2; 4.2), Sleep (3.8; 3.9), Sex (3.5; 2.8), and Appetite (2.8; 2.6). Sex is graded as moderately important among nursing home residents, more so in males. The majority of residents expressed positive attitudes towards open discussion of sexual matters and willingness to accept therapeutic interventions when needed.     

Screening for early cognitive impairment in multiple sclerosis patients using the clock drawing test

The clock drawing test (CDT) is a complex task assessing integrative functions, abstract thinking and visuospatial organization. In the present study we evaluated the CDT as a possible screening instrument for early cognitive impairment in multiple sclerosis (MS) patients. In total, 107 MS patients completed the CDT as well as a battery assessing five cognitive domains. There were 73 female and 34 male participants (mean age 45.4+/-11.6 years, range 19-69). The majority (76/107) were diagnosed with a relapsing-remitting disease course. Mean expanded disability status scale (EDSS) score was 4.3+/-2.4 (range 0-8). The CDT was scored on a 1-6 point scale with "1" being a perfect score and "6" reflecting severe disorganization. Mean CDT score was 2.6+/-1.4. In 53% of patients the CDT was normal while in 11.2% dementia was apparent. The CDT score did not correlate with the total EDSS. Significant correlations were obtained with the mental functional system score of the EDSS (r = 0.78; p = 0.0001), visual learning and recall, sustained attention and concentration. Our findings demonstrate the sensitivity of the CDT to several cognitive domains. The absence of correlation with total EDSS score coupled with significant correlation with the mental functional system suggests that the CDT may be useful for screening MS patients.     

Suicide in Israel: 1985-1997

OBJECTIVE: To examine trends in suicide rates in Israel over a 13-year period. METHOD: All cases of autopsy-confirmed suicide in Israel from 1985 to 1997 were retrospectively reviewed. RESULTS: An overall annual increase in suicide rates, with rates in men 3 times higher than those in women, was observed. Suicide rates were highest in the second and third decades of life. Unlike Western countries where gunshot wounds are the most common method of suicide for men and poisoning is most common for women, asphyxiation by hanging was the most common method used by men in Israel, followed by firearm wounds and jumping from heights. In women, however, jumping from heights was the most common method, followed by hanging and poisoning. CONCLUSION: Increasing rates of suicide may be associated with waves of immigration to Israel, increased substance abuse and depression and the political and social climate. Further study to examine the precipitating factors is warranted.