Comprehensive analysis of urinary metabolites of N' -nitroso-nornicotine

A detailed study of the urinary metabolites of N'-nitrosonornicotinehas been perfomed, employing a simple high pressure liquid chromatographicmethod. The percentage excretion of the principal urinary metaboliteswas determined over a dose range of 3–300 mg/kg in theF-344 rat, as follows: 4-hydroxy-4-(3-pyridyl)butyric acid (37.1–53.3%,respectively, of the dose), N'-nitrosonornicotine-l-N-oxide(6.7–10.7%), norcotinine (3.2–5.1%), 4-oxo-4-(3-pyridyl)butyricacid (31.1–12.8%), N' -nitrosonornicotine (3.3–5.2%).In the strain A mouse and Syrian golden hamster, the urinarymetabolites were qualitatively similar to those observed inthe F-344 rat. The interrelationships of the various metabolitesof N'-nitrosonornicotine which have been observed in vitro andin vivo were established. The in vitro metabolites resultingfrom 2'-hydroxylation by liver microsomes, myosmine and 4-hydroxy-l-(3-pyridyl)-1-butanonewere converted, by the F-344 rat, primarily to 4-oxo-4-(3-pyridyl)butyricacid as a urinary metabolite. The in vitro metabolite resultingfrom 5'-hydroxylation by liver microsomes, 2-hydroxy-5-(3-pyridyl)tetrahydrofuran,gave 4-hydroxy-4-(3-pyridyl)butyric acid as its major urinarymetabolite, apparently via 5-(3-pyridyl)-tetrahydrofuran-2-one.N'-nitrosonornicotine-l-N-oxide, the remaining major in vitrometabolite, was excreted to a large extent unchanged in F-344rat urine. The urinary metabolites from 2'-hydroxylation and5'-hydroxylation of N'-nitrosonornicotine, 4-oxo-4-(3-pyridyl)butyricacid and 4-hydroxy-4-(3-pyridyl)butyric acid, respectively,were not formed from the in vivo metabolite norcotinine andwere not interconverted significantly by the F-344 rat. Thus,these metabolites appear to be reliable indicators for the twopossible in vivo -hydroxylations of N'-nitrosonornicotine.     

Traditional and modern medicine in Malaysia

Malaysia has a large variety of traditional medical systems that are a direct reflection of the wide ethnic diversity of its population. These can be grouped into four basic varieties, namely, traditional "native," traditional Chinese, traditional Indian and modern medicine, examples of which are described. In spite of the great inroads made by modern medicine, the traditional systems are firmly established. Patients move from one system to another or use several systems simultaneously. The integration of the traditional Malay birth attendant into the health team is described. The forces influencing the development, acceptance and integration of the medical systems is discussed.     

Total anomalous pulmonary venous connection to the left vertical vein. A plain-film sign useful in early diagnosis.

Total anomalous pulmonary venous connection to the left vertical vein often may be recognized on the plain postero-anterior chest radiograph by the characteristic supracardiac shadow. This "snowman sign" is useful in older patients but rarely is apparent in infancy. In such young patients the authors have discovered a density anterior to the trachea on the lateral chest radiograph. This finding is present prior to the appearance of the snowman sign and should prove useful in the early diagnosis of this anomaly, facilitating prompt, appropriate treatment. Five representative cases are tabulated and developmental and clinical aspects are reviewed.     

A comparison of self-report and clinical diagnostic interviews for depression: diagnostic interview schedule and schedules for clinical assessment in neuropsychiatry in the Baltimore epidemiologic catchment area follow-up

BACKGROUND: The field of psychiatric epidemiology continues to employ self-report instruments, but the low degree of agreement between diagnoses achieved using these instruments vs. that achieved by psychiatrists in the clinical modality threatens the credibility of the results. METHODS: In the Baltimore Epidemiologic Catchment Area follow-up, 349 individuals who had a Diagnostic Interview Schedule (DIS) interview were blindly examined by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Comparisons were made at the level of diagnosis, syndrome, and DSM-IV symptom group. Indexes of agreement were computed and characteristics of discrepant cases were identified. RESULTS: Agreement on diagnosis of major depressive disorder was only fair (kappa = 0.20), with the DIS missing many cases judged to meet criteria for diagnosis using the SCAN (29% sensitivity). A major source of discrepancy was respondents with false-negative diagnoses who repeatedly failed to report DIS symptoms attributed to life crises or medical conditions. Older age, male sex, and lower impairment were associated with underdetection by the DIS, using logistic regression analysis. In spite of the diagnostic discrepancy, there was substantial correlation in numbers of symptom groups in the 2 modalities (r = 0.49). Agreement was highest (about 55% sensitivity and 90% specificity) when both the SCAN and DIS thresholds were set at the level of depression syndrome instead of diagnosis. CONCLUSIONS: Weak agreement at the level of diagnosis continues to threaten the credibility of estimates of prevalence of specific disorders. A bias toward underreporting, as well as stronger agreement at the level of the depression syndrome and on ordinal measures of depressive symptoms, suggests that associations with risk factors are conservative.     

Mitochondrial DNA sequence diversity in bipolar affective disorder

OBJECTIVE: Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder. METHOD: The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups).RESULTS: The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded.CONCLUSIONS: The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.     

Intracellular processing and toxicity of the truncated androgen receptor: nuclear congophilia-associated cell death

The pathogenesis of the selective motor neuron death in spinal bulbar muscular atrophy (SBMA) is not fully understood. Similar to observations with other mutant polyglutamine (poly Q) expanded proteins, truncated androgen receptor (AR) with expanded poly Q tract cause intracellular aggregates; however, the precise relationship between aggregates and disease pathogenesis is unresolved. In order to have a better understanding of the cellular processing and toxicity of the mutant AR, we focused on a short N-terminal portion of AR containing normal or expanded poly Q repeats, and have carried out biochemical, immunocytochemical, cytochemical and ultrastructural studies of BHK cells at different intervals after transfection. In cells expressing mutant truncated AR, using an anti-AR N-terminal antibody, we observed no immune staining in the nucleus and identified immune negative aggregates surrounded by immunopositive material in the cytoplasm. Congo red staining identified a component of aggregates with a beta-pleated secondary structure in both cytosol and nucleus, while electron microscopy revealed a fibrillary-granular material as the ultrastructural correlate. In addition, acid phosphatase staining and ubiquitin immunocytochemistry demonstrated that in transfected cells, both lysosomal and nonlysosomal degradation systems are actively involved in handling the mutant truncated AR. The temporal relationship of nuclear congophilia to a subsequent massive cell death suggests that entry of proteolytic cleavage products into the nucleus, perhaps the expanded poly Q stretch itself, may play an important role in cell toxicity.     

Effects of support group intervention in postnatally distressed women. A controlled study in Taiwan

Objective: The symptoms of depression experienced by women during the postnatal period may have profound effects on the lifelong health of both the mother and the child. In this randomized controlled study, we systematically evaluated the effects of weekly supportive group meetings for women with postnatal distress. Methods: Sixty postnatally distressed women were randomly assigned to support (n=30) and control (n=30) groups. Women assigned to the support group participated in four supportive group sessions that comprised discussions concerning transition to motherhood, postnatal stress management, communication skills, and life planning. Results: Subjects who attended the support sessions had significantly decreased scores on the Beck Depression Inventory (BDI) and the Perceived Stress Scale (PSS), and significantly increased scores on the Interpersonal Support Evaluation List (ISEL) as evaluated at the end of the fourth weekly session. In contrast, no significant changes were observed in the control group during this period. Conclusion: This is the first controlled study to provide evidence that participation in support groups for postnatally distressed women provides quantifiable psychosocial benefits.