Preclinical models of sexual desire: conceptual and behavioral analyses

The epidemiology, etiology and proposed treatments for the sexual desire disorders are briefly reviewed before turning to an analysis of preclinical models. We suggest that the concept of sexual desire in the human is equivalent to sexual motivation as employed in the scientific literature. Many animal tests for sexual motivation have been described over the years. Most of them are based on the evaluation of the rate or speed of performing learned operant responses. These are not ideal measures for inferring the intensity of sexual motivation. We present a test for sexual incentive motivation, which has been used in male and female rats. No learning is involved, and the test is rather insensitive to variations in ambulatory activity and it does not employ rate measures. A procedure that recently has attracted much attention, paced-mating behavior in the female, does not seem to be as useful as could be expected. In fact, it does not appear to be superior to tests for sexual receptivity (lordosis). The lack of established, clinically efficient treatments for sexual desire disorders makes it difficult to evaluate if any model has predictive validity. However, the model proposed here may be isomorphic and homologous to the human condition.     

Familial aggregation of Hodgkin lymphoma and related tumors

BACKGROUND: The importance of genetic factors in the etiology of Hodgkin lymphoma (HL) has been suggested by family and population studies. However, the spectrum of malignancies associated with common genetic etiology and the effects of gender and age on familial risk have not been established. METHODS: Diagnoses of lymphoproliferative malignancies were compared in 15,799 first-degree relatives of 5047 patients with HL versus 32,117 first-degree relatives of 10,078 control probands from Sweden and in 7185 first-degree relatives of 2429 patients with HL versus 27,434 first-degree relatives of 8,495 control probands from Denmark using marginal survival models. RESULTS: The risk of HL in relatives of patients with HL was increased significantly in both populations, with relative risks of 3.47 (95% confidence interval [95% CI], 1.77-6.80) in Sweden and 2.55 (95% CI, 1.01-6.45) in Denmark and a pooled estimate of 3.11 (95%CI, 1.82-5.29). In Sweden, risks for relatives of patients also were increased significantly for chronic lymphocytic leukemia and non-Hodgkin lymphoma (in males). Relative risks were higher in males compared with females and in siblings of patients compared with parents and offspring of patients. Relatives of patients with earlier-onset disease were at higher risk for HL. CONCLUSIONS: HL has an important familial component, which is stronger in families of affected individuals age < 40 years, in males, and in siblings, and it is shared with some (but not other) lymphoproliferative malignancies. The cumulative lifetime risks are very small, however, for the development of HL de novo or in first-degree relatives of affected patients.     

Identification of neurite extension inducing peptides by means of soluble combinatorial peptide libraries

To identify hexapeptides capable of inducing neurite outgrowth, we used three groups of soluble combinatorial peptide libraries each consisting of 100 mixtures of hexapeptides (each mixture consisting of 10,000 individual peptides) with partially predetermined sequences (in two out of six amino acid positions). Using this approach a number of neuritogenic peptides were identified. Three selected peptides, QSGKKF, QSGPLA and QSGKQG, were found to induce neurite outgrowth from primary hippocampal neurons with potency comparable to that of growth factors. None of the peptides protected cerebellar granule neurons from cell death induced by withdrawal of potassium chloride. The approach described here suggests the feasibility to use combinatorial peptide libraries in order to identify compounds capable of modulating a specific functional response in the nervous system, without prior knowledge of a molecular target.     

Improvement in mental health over time in Northern Norway

BACKGROUND: There are very few prospective studies of mental distress in the general population. Two studies of general health in Finnmark county in northern Norway, performed 9 years apart, contained questions about depression and sleeping problems, which made it possible to study change in mental distress over time in the general population. METHODS: In a self-administered questionnaire, the subjects were asked about depression and sleeping problems, both generally and related to the dark period in winter, at two points in time: in 1987/88 and 1996/97. The persons participating in the two surveys were partly the same and partly new individuals. More than 12000 persons responded in 1987/88 and more than 7000 people in 1996/97. The cohort that answered questions about sleeping problems and depression at both time-points consisted of 3318 and 3682 persons, respectively. RESULTS: The prevalence of depression and sleeping problems, both generally and related to winter,decreased significantly in the course of the 9-year time-span. The decrease was also true for the cohort that answered at both time-points, except for sleeping problems related to winter, which were unchanged. The pattern of changes was identical for both genders and all age groups. CONCLUSIONS: Mental health in the general population seems to have improved during the period studied. The findings are also relevant for the discussion of the validity of the concept Seasonal Affective Disorder, and the presumed connection to light-deprivation.     

Detecting mental disorders in general hospitals by the SCL-8 scale

OBJECTIVE: The objective of this study is to validate the eight-item dichotomised version of the Symptoms Check List (SCL-8d) as a screening tool for psychiatric disorders. METHODS: The study population included 198 consecutive new neurological inpatients and outpatients and 294 consecutive internal medical inpatients, aged 18 or older. All patients received the SCL-8d questionnaire, and a stratified subsample was interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. We tested the external SCL-8d validity using the SCAN interview as gold standard. The test was performed based on weighted data to correct for the skewness introduced by stratification. RESULTS: The diagnostic performance of the SCL-8d was excellent in the internal medical setting but not quite as good in the neurological sample. It performed better among the older compared with the younger patients, whereas the scale was not affected by gender. In the combined sample at the cut point 0/1, the sensitivity (SE) of the SCL-8d was 0.73 (confidence interval [CI](95%): 0.60-0.82), the specificity (SP) 0.61 (CI(95%): 0.53-0.68) and the positive predictive value (PPV) 0.42 (CI(95%): 0.34-0.50), using any International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric disorder, excluding somatoform and substance abuse disorders, as gold standard. The risk of a patient having a mental disorder (except phobia, substance abuse or somatoform disorder) was less than 6% in case of a negative screening test. In patients with a current depressive disorder, 87.1% (27/31) were screening positive, and all except 1 (93.0%) of the 14 patients with a modest to severe depression scored 1 or higher on the SCL-8d. All 17 patients with an anxiety disorder, excluding phobias, were screening positive. CONCLUSION: The study suggests that the SCL-8d is a valid, brief screening tool for use in nonpsychiatric medical settings, especially to detect emotional psychiatric disorders (EPDs).     

Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity

Objective To study the distribution of the thiopurine methyltransferase (TPMT) genotype among azathioprine (Aza)-tolerant and -intolerant patients with various disorders, and to investigate a possible relationship with the Aza metabolite levels.Methods Forty-six Aza-tolerant and six Aza-intolerant patients had the TPMT genotype distribution determined using a polymerase chain reaction (PCR) assay and the forty-six Aza-tolerant patients had the Aza metabolite levels determined using a high-pressure liquid chromatography (HPLC) analysis.Results One non-functional TPMT mutant allele was demonstrated in 2 of the 46 Aza-tolerant patients (4.4%) and one or two non-functional mutant alleles in 2 of the 6 Aza-intolerant patients (33.3%). Of the 4 patients, with one or two non-functional mutant alleles 2 (50%) were intolerant to Aza compared with 4 of the 48 patients (8.3%) with no mutations detected. The time to hepatotoxicity did not differ significantly between the 2 patients with one or two non-functional mutant alleles and the remaining 3 patients (P=0.5). The TPMT genotype distribution differed slightly in the three different categories of disorders (P=0.05). The median E-6-TGN level among the 2 TPMT heterozygous patients was 275 pmol/8×10⁸ RBC (range 240–310), whereas the remaining 44 patients had a median E-6-TGN level of 110 pmol/8×10⁸ RBC (range 0–440) (P=0.07).Conclusion Although TPMT genotyping cannot be recommended on behalf of the present study, it is to be expected that half of the patients with one or two non-functional TPMT mutant alleles will develop Aza intolerance leading to withdrawal of therapy. Thus, clinicians may anticipate about 5% of the patients to develop intolerance to Aza therapy solely for that reason.     

Nutritional status of patients with advanced cancer: the value of using the subjective global assessment of nutritional status as a screening tool

In patients suffering from advanced neoplastic disease, malnutrition is a common complication affecting both the survival and quality of life. In order to monitor early dietary interventions, an assessment of patients' nutritional status is essential. We assessed the nutritional status of 46 patients using two different methods: 1) an objective method of nutritional assessment and 2) the subjective global assessment (SGA) technique. It was found that 28 patients were characterized as malnourished by means of the objective method and 30 patients according to the SGA. The correlation of the results of the assessments between the two methods was high and a validation test of the SGA gave a sensitivity of 96% and specificity of 83%. The most frequent symptoms affecting food intake were anorexia, early satiety, dry mouth, pain and nausea. The results show that the SGA represents an easy method for assessment of the nutritional status in such cancer patients and that it can therefore be used as a screening tool. The high incidence of malnutrition in this group of patients, and their rare use of nutrient supplements, both indicate the importance of early nutritional assessment, and nutritional intervention when appropriate.