Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.     

Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees

Several psychophysiological abnormalities associated with schizophrenia have been proposed as genetic trait markers of vulnerability to the disorder. Smooth pursuit eye tracking dysfunction and abnormal long latency event-related potentials are the most promising candidates. Both are independent of the effects of psychotropic medication or mental state at the time of testing, and twin studies demonstrate that each has a high level of heritability. Having recorded smooth pursuit eye tracking and event-related potentials in 20 high-density schizophrenic families, we find abnormalities in one or both measures in most of the families studied. The abnormalities, when present, occur in the family members with schizophrenia and other forms of functional psychosis, and they have a bimodal distribution with approximately half the nonschizophrenic relatives also showing eye tracking dysfunction and/or abnormal event-related potentials. Some of these relatives had psychiatric symptoms; others were normal. Our results suggest that psychophysiological examination can help to clarify the boundaries of schizophrenia spectrum disorder. By helping to decide the phenotypic status of nonschizophrenic family members, this should increase the power of DNA linkage studies.     

Long-latency auditory event-related potentials in schizophrenia and in bipolar and unipolar affective disorder.

Long-latency auditory event-related potentials were examined in 96 subjects with schizophrenia, 99 with bipolar affective disorder and 48 with major depressive (unipolar) disorder, and compared with 32 in-patient and 213 normal controls. The latency of the P3 component was significantly greater in the schizophrenic and bipolar subjects compared to other groups. The difference was stable with respect to clinical state at the time of testing and was not due to age differences or the effect of psychotropic medications. The results support the clinical distinction between bipolar and unipolar affective disorders, but also show that P3 change is not specific to schizophrenia and found in bipolar but not unipolar affective disorder.     

Common bile duct calculi: updated experience with dissolution with methyl tertiary butyl ether

The authors describe their experience with methyl tertiary butyl ether (MTBE) in a larger series of patients than previously reported in order to acquaint physicians with both its effectiveness for dissolution of common bile duct calculi and the limitations of its use. Ten patients with 13 biliary calculi underwent percutaneous stone dissolution treatment with the experimental cholesterol solvent, MTBE. Three stones completely dissolved within 30 minutes, seven were reduced in size, and three were visibly unaffected. All stones not completely dissolved were easily extracted by means of a stone basket except for one in a patient taken to surgery. Although MTBE perfusion is an effective technique for management of biliary calculi, practitioners should be aware that its use is quite time consuming and its odor difficult to control.     

Eye-tracking dysfunction in the affective psychoses and schizophrenia.

Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.     

Acute intermittent porphyria and mental illness – a family study

All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway. This gene has been mapped to the long arm of chromosome 11, a region of the genome that has recently attracted considerable attention as a possible location for genes implicated in major mental disorder. This study was designed to show whether major mental illness co-segregated with acute intermittent porphyria in families where the two conditions are found. The study also investigated the relation between clinical mental symptoms and biochemical parameters of acute intermittent porphyria. The case records of 344 consecutive patients admitted to the Porphyrias Research Group in the Western Infirmary in Glasgow between 1950 and 1988 with acute intermittent porphyria were examined for evidence of psychiatric contact. Of 16 individuals identified, 12 were available for the study. Forty relatives of these 12 probands, including 9 who were asymptomatic carriers of AIP, were interviewed for lifetime history of mental illness and current symptoms. Comparisons were made between 4 groups of patients based on urinary porphyrin levels and erythrocyte enzyme activity; 1) manifest acute intermittent porphyria, 2) latent acute intermittent porphyria, 3) normal relatives and 4) total acute intermittent porphyria (latent and manifest combined). No association was found between AIP and schizophrenia or manic-depressive illness. Only one patient with schizophrenia was found in the sample of 344 case notes, and in 2 families bipolar illness was found but did not segregate with acute intermittent porphyria. The commonest psychiatric diagnosis in patients was generalized anxiety. In the total AIP group (latent and manifest), compared with normals, the rating scale measures of anxiety were significantly correlated with the level of porphyrin metabolites in the urine at the time of rating. This was true even in subjects with latent AIP, who were not at the time of testing aware that they were asymptomatic carriers of the illness. AIP should be considered in the differential diagnosis of generalized anxiety disorder.