Biomedical subjects
Publications and source records attributed to J Slack.
A 64-year-old female with the cancer family syndrome suffered from multiple malignant melanomas and a malignant fibrous histiocytoma. She has shown unusually long survival which is a feature of these patients.
Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at-risk individuals.
The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0.006 with a lifetime penetrance of 0.63. These genes account for 81% of colorectal cancer in patients under 35, however, by 65 about 85% are phenocopies.
Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic.
The risk of breast cancer in first degree relatives of patients with breast cancer can be derived from family history and is dependent upon the age at diagnosis in the index patient. For the relatives of index patients older than 55, the relative risk is 1.57, if less than 55 the relative risk is 2.29, and 3.85 if less than 45 (95% confidence limits 0.83 to 2.68, 1.18 to 4.01, and 1.67 to 3.85, respectively). First degree relatives of patients with bilateral breast cancer have a 6.43-fold increase in risk (95% confidence limits 1.32 to 18.77). The genetic contribution to overall lifetime liability to breast cancer in the relatives declines rapidly with increasing age of onset of breast cancer in the index patient from 37% at 20 years to 8% by 45 years. This information can be used in clinical practice for counselling and the establishment of screening programmes.
Two female sibs aged 15 and 18 years with microcephaly, mental retardation and marfanoid habitus who developed focal segmental glomerulonephritis leading to renal failure are described. This combination of features appears to represent a unique syndrome distinct from previous reports of microcephaly in association with the nephrotic syndrome. The mode of inheritance is likely to be autosomal recessive.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Restriction fragment-length polymorphisms in the chromosome 5q21-22 region can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. Two families are presented in which DNA diagnosis for familial adenomatous polyposis was performed using linked restriction fragment-length polymorphisms. Screening guidelines are improved using data from the polyposis registers at St. Mark's Hospital (London) and Western Australia (Perth) on at-risk family members who subsequently developed familial adenomatous polyposis. In these registers, 103 of 137 relatives tested positive on initial screening; of the remaining 34, the average interval between initial negative screening and development of familial adenomatous polyposis was 7.5 years. All those who had inherited the familial adenomatous polyposis gene manifested the polyps by age 34 years. Combined with linkage marker data, the a priori 50% risk for relatives can now be reduced to less than 0.5% by age 30 years if there is an initial negative result on sigmoidoscopy and a negative diagnosis by linkage analysis. The screening management for those found by linkage to have inherited familial adenomatous polyposis remains unchanged from established recommendations; however, for individuals who most likely have not inherited familial adenomatous polyposis, the clinician can emphasize the positive aspects of screening management, including longer screening intervals.
Either a simple balanced salt solution (BSS) or a bicarbonate-buffered, glutathione-containing commercial irrigant (BSS Plus, Alcon Laboratories, Fort Worth, Texas, U.S.A.) may be used during the vitrectomy portion of a corneal transplant procedure. To simulate the conditions present in the anterior chamber during the first few hours after vitrectomy and grafting, we performed in vitro perfusions of stored human corneas using each irrigant and measured corneal thickness over a 3-hour period. Irrespective of the preservation medium used (McCarey Kaufman, Chondroin Sulfate or Dexsol, all from Chiron Ophthalmics, Irvine, California) or duration of storage (2 or 4 days), corneas irrigated with BSS Plus exhibited significantly (p less than .05) decreased thickness compared with their paired mates irrigated with BSS. In ultrastructural studies performed on postperfusion corneas, there was a tendency toward improved surface morphology in the in vitro BSS Plus-perfused tissue. This study shows that in vitro corneal thickness after preservation is significantly irrigant dependent, with BSS Plus providing the essential ingredients to promote the corneal endothelial pump function.
A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0.003 giving a lifetime penetrance of 0.83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non-significantly younger than isolated probands.
The genetic epidemiology of ovarian cancer has been investigated by complex segregation analysis of 462 pedigrees ascertained through a normal consultant. The observed pattern of ovarian cancer is compatible with an autosomal dominant gene. The gene frequency of the abnormal allele is 0.0015-0.0026 with a lifetime penetrance of 0.74-0.79. The gene frequency accounts for a significant proportion of ovarian cancer in young women. By age 70 the majority of affected women are phenocopies. The results from this analysis should enable the risks of ovarian cancer to be more accurately estimated than by empiric methods for relatives of affected women, and can maximize the usefulness of screening programmes and future linkage studies.
A consecutive cohort of 71 women eligible for amniocentesis because they were over 38 years of age completed questionnaires during the first trimester of pregnancy. Sixty-one women underwent amniocentesis, an uptake rate of 86%. Uptake was associated with a less negative attitude towards termination of an affected baby and a higher perceived risk of the fetus being abnormal. It was not associated with actual age-related risks. There was no significant relation between actual risk and perceived risk. The results of this study suggests that it is important for doctors to understand the basis of women's decisions to have amniocentesis, and the difference between actual and perceived risk if they are to communicate effectively with women about the test and their options.
Patients with pain are not a new phenomena. For centuries, the incidence of pain has been well-documented. Responsibility for pain management has not been a universal priority for health care providers; however, pain management must be considered an integral part of the nursing role. The health care system must facilitate the improved management of patient's pain. A better understanding of the factors that underpin the effective management of a patient's pain is necessary. In this article, the theoretical foundation and conceptual model used in the expansion of this knowledge is presented. Further, the physiologic and pharmacologic principles related to this patient care issue are discussed. Appropriate consideration of the nurse's significant part in the management of pain is emphasized.
Primary human monocytes and the human monocytic cell line THP-1 were induced to express receptors for interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Treatment of primary monocytes with dexamethasone resulted in a 10-fold increase in receptor number over untreated cells, to approximately 2,000 receptors/cell. Treatment of THP-1 cells with phorbol ester followed by prostaglandin E2 and dexamethasone resulted in the expression of approximately 30,000 receptors/cell. Competitive binding assays on THP-1 cells showed that both IL-1 alpha and IL-1 beta bind to the same receptor. The monocyte IL-1R is significantly smaller (63 kDa) than the T cell IL-1R (80 kDa) and is immunologically distinct. However, induction of monocytes and monocytic cell lines leads to the appearance of an abundant mRNA of approximately 5,000 bases which hybridizes to a cDNA probe from the T cell-type IL-1R. Sequence data obtained from a cDNA clone of this mRNA indicate that the message is identical to the T cell IL-1R mRNA throughout the coding region. A smaller mRNA, also homologous to the T cell IL-1R mRNA, accumulated in induced THP-1 cells and has a shorter 3'-untranslated region than the larger. Data are presented which suggest that neither form of this message encodes the 63-kDa IL-1R, but rather that this protein is the product of a separate nonhomologous mRNA.
IL-1 and IL-4 are important mediators of B cell growth and differentiation. The cell-surface receptors for these cytokines have recently been cloned and recombinant soluble receptors have been produced that bind their respective ligand. The ability of soluble forms of the murine IL-1R (sIL-1R) and IL-4R (sIL-4R) to inhibit B cell functions in vitro was examined. Proliferation of B cells treated with anti-Ig plus IL-1 or IL-4 was inhibited by the appropriate soluble receptor. sIL-4R also inhibited IL-4-dependent B cell differentiation as measured by: induction of IgG1 and IgE secretion by LPS blasts, down-regulation of IgG3 secretion by LPS blasts, increased Ia expression, and increased Fc epsilon R (CD23) expression. The inhibitory effects of the soluble receptors were found to be highly specific in that sIL-4R had no effect on IL-1-induced B cell activity and sIL-1R had no effect on IL-4 activity, further demonstrating the existence of two independent pathways of B cell activation directed by IL-1 and IL-4.
Explore the source record for details and available documents.
Explore the source record for details and available documents.