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Biomedical subjects

A J Krush

Publications and source records attributed to A J Krush.

At least 37 records · Page 2Linked to original sources
PubMed1990

Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polyposis in Gardner's syndrome.

We studied prospectively the utility of congenital hypertrophy of the retinal pigment epithelium as a predictor of colonic polyposis in offspring of patients with familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome). After they underwent initial indirect ophthalmoscopy, we followed up 34 individuals at 50% genetic risk for familial adenomatous polyposis with extracolonic manifestations due to an affected parent. All 34 obtained their first colorectal endoscopic examination during a follow-up period of up to 4 years. The 16 individuals who did not have congenital hypertrophy of the retinal pigment epithelium (aged 13 to 40 years; mean, 25 years) remained polyp free, while 14 of 18 individuals with congenital hypertrophy of the retinal pigment epithelium (aged 9 to 30 years; mean, 18 years) were found to have colorectal adenomatous polyposis. Our findings indicate that the presence of multiple patches of congenital hypertrophy of the retinal pigment epithelium in children and young adults at risk for familial adenomatous polyposis with extracolonic manifestations is a clinically useful predictor of colorectal polyposis.

Adenomatous Polyposis Coli↗
PubMed1988

Hepatoblastoma and familial adenomatous polyposis.

Eleven children have been identified as having hepatoblastoma and a family history of adenomatous polyposis, and 14 additional instances of this association have been collected from the literature. Among the 11 survivors of hepatoblastoma in the combined series, adenomatous lesions have been sought in seven and detected in six patients at ages 7 to 25 years. Five of these patients also have congenital hypertrophy of the retinal pigment epithelium, a marker for carriers of the polyposis gene. These findings strengthen the association between hepatoblastoma and familial adenomatous polyposis and have led to the establishment of the Hepatoblastoma-Adenomatous Polyposis Registry.

Adenomatous Polyposis Coli↗
PubMed1988

Hepatoblastoma, pigmented ocular fundus lesions and jaw lesions in Gardner syndrome.

Hepatoblastoma is a rare neoplasm of infants and children only recently documented in association with hereditary adenomatous polyposis of the colon [Kingston et al., 1983]. We report four children with hepatoblastoma from four unrelated families with Gardner syndrome (GS). One child, now 19 years old, survived after a resection of a hepatoblastoma in infancy and recently was found to have GS. He has an associated odontoma and pigmented ocular fundus lesions, both of which have been shown to be clinical markers of GS. Many individuals in these four GS families, both affected and at risk, have osteomatous jaw lesions and pigmented ocular fundus lesions. A search for colonic polyps should be made in families of infants and children with hepatoblastoma. If the child survives, he or she should be monitored for the later appearance of colonic polyps. The finding of jaw lesions and/or pigmented ocular fundus lesions in relatives at risk are indications of the possible presence of the GS gene.

Eye Diseases↗
PubMed1988

Arachnodactyly and unusual dermatoglyphics: study of a case.

Clinical and dermatoglyphic findings are reported on a 3-yr old girl with multiple congenital anomalies and unusual dermatoglyphics. The anomalies, including contractural arachnodactyly, rhizomelia (a relative shortening of the proximal segment of the limbs), skin dimples, clinodactyly, disharmonic hand bone maturation, absent, hypoplastic and unusually positioned digital and metacarpophalangeal flexion creases, are not indicative of Marfan syndrome, but it is unclear what this syndrome constitutes. Among the child's most striking dermatoglyphic features, the fingertip patterns (mostly large whorls with extralimital triradii) extend proximally to the middle phalanx and are associated with unusually placed triradii. The furrows between the epidermal ridges are narrower on the volar aspects of the middle and distal phalanges than on the proximal phalanges and palms, resulting in a higher ridge density in the former areas. Dermatoglyphic comparisons between the proposita and her parents are provided. These dermatoglyphic aberrations may indicate the presence of a deleterious agent active during the period of the development of the ridge configurations and of the digital flexion creases.

Child, Preschool↗
PubMed1988

Pigmented ocular fundus lesions in the inherited gastrointestinal polyposis syndromes and in hereditary nonpolyposis colorectal cancer.

The authors studied pigmented ocular fundus lesions in three different forms of hereditary gastrointestinal polyposis and in hereditary nonpolyposis colorectal cancer. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was present in at least one member of 23 families with Gardner's syndrome. By contrast, CHRPE was not found in three families with familial polyposis coli, four families with hereditary nonpolyposis colorectal cancer, and three families with Peutz-Jeghers syndrome. Pigmented ocular fundus lesions of the CHRPE-type appear to be specific to Gardner's syndrome among inherited diseases with gastrointestinal polyposis.

Adenomatous Polyposis Coli↗
PubMed1987

Increased risk of cancer in the Peutz-Jeghers syndrome.

The Peutz-Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz-Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent)--gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma in 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz-Jeghers syndrome had been diagnosed (interval between diagnoses, 25 +/- 20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P less than 0.0001). Our results suggest that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.

Adolescent↗
PubMed1987

Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome.

We examined 134 members of 16 families with Gardner's syndrome for pigmented ocular fundus lesions. Of 41 patients with documented Gardner's syndrome, 37 (90.2 percent) had such lesions. The lesions were bilateral in 32 of the patients (78.1 percent) and in 2 of 42 controls (4.8 percent). Twenty (46.5 percent) of 43 first-degree relatives at 50 percent risk for Gardner's syndrome had bilateral pigmented fundus lesions, indicating that they had probably inherited the abnormal gene. The presence of bilateral lesions, multiple lesions (more than four), or both appeared to be a specific (specificity, 0.952) and sensitive (sensitivity, 0.780) clinical marker for Gardner's syndrome. The lesions are probably congenital; they were observed in a three-month-old baby at risk. The multiplicity of the pigmented fundus lesions and their association with diffuse disturbances of the retinal pigment epithelium in the same eye suggest a widespread expression of the abnormal gene in the retinal pigment epithelial cells.

Female↗
PubMed1987

Counseling families with hereditary gastrointestinal polyposis syndromes.

Counseling for families with one of the hereditary polyposis and/or colon cancer syndromes can be offered by a number of different professional persons depending upon the emotional needs of the counselee. It is sometimes difficult to persuade at-risk persons in polyposis families to institute a medical surveillance plan with their physicians because of their reactions to knowledge (or lack of it) of the family diagnosis. Counseling may reveal both emotional and financial problems as deterrents to needed medical planning. Support organizations and explanatory literature are helpful in allaying fears and promoting compliance.

Adenomatous Polyposis Coli↗
PubMed1987

Occult radiopaque jaw lesions in familial adenomatous polyposis coli and hereditary nonpolyposis colorectal cancer.

The purposes of this study were to determine the association, in 10 pedigrees, between adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, and occult radiopaque jaw lesions, and to assess whether these radiodensities are predictors for adenomatous polyposis. In seven kindreds with adenomatous polyposis, all patients with polyps had jaw lesions; in one kindred, no jaw lesions were found. In one of two kindreds with hereditary nonpolyposis colorectal cancer, no affected individuals had jaw lesions. In the other, the 1 affected patient with dental radiographs had generalized jaw lesions. Twelve children less than 16 yr old at risk for adenomatous polyposis were observed. Seven children with jaw lesions developed polyps after a mean interval of 4 yr. Five children without jaw lesions were polyp-free during a 5-10-yr follow-up. Thus, occult jaw lesions are consistently found only in some families with adenomatous polyposis coli, providing support for heterogeneity in polyposis syndromes. Jaw lesions are good predictors for polyp development in kindreds with adenomatous polyposis coli and jaw lesions. Their role as markers in hereditary nonpolyposis colorectal cancer needs exploration.

Adenomatous Polyposis Coli↗
PubMed1984

The bingo model of survivorship. II: statistical aspects of the bingo model of multiplicity 1 with application to hereditary polyposis of the colon.

Some Mendelian disorders (Huntington chorea, hereditary polyposis coli) are not manifest at birth but show a distribution in the age of onset. Patients at risk fall into three groups. In type I, they are affected when first examined. In type II, they are not affected at one visit, but are at a later visit. Those of type III (who comprise an indistinguishable mixture of those who have, and those who have not, inherited the gene) are never found to be affected. This paper posits a model that the age of onset is logistic. (It is a degenerate bingo model in which competing causes of death may be ignored.) The statistical properties of maximum likelihood estimation (MLE) are explored by Monte Carlo simulation of this logistic function with known arbitrary parameters. Two schemes are used: point-prevalence (or synchronic) data of types I and III, and piecewise longitudinal (diachronic) data; this allows all three types to be included. Samples of various sizes between 25 and 100 are used. While estimates of the parameters are positively biased (especially with small samples), the estimate of the mean appears to be consistent, almost unbiased, and fairly precise, though somewhat larger than the estimates from the lower bound (a fact that calls for some caution in interpreting actual data). The MLE was applied to 109 patients with the Gardner syndrome (GS); measures of variability found by applying MLE to four random subsets of 25 each were compared against the asymptotic estimates. The analysis was also applied to 36 persons with familial polyposis coli (FPC). The mean age of onset in GS and FPC was similar, and since they are rather earlier than is currently believed, it is recommended that regular supervision be started at not later than 10 years of age.

Adolescent↗
PubMed1983

Multiclonal origin of polyps in Gardner syndrome.

Electrophoretic analysis of glucose-6-phosphate dehydrogenase was performed on polyp tissue from three black female patients with Gardner syndrome and who are heterozygous for the A and B forms of this enzyme. Polyp tissues from the three patients displayed the AB phenotype. This finding suggests a multiclonal origin of polyps in Gardner syndrome. Studies of tumors originating from such polyps may provide information about the sequence of cellular events leading to malignant transformation.

Clone Cells↗
PubMed1983

CEA and genetics. Gardner's syndrome.

During an eight-year period, serial plasma determinations were made on members of a Gardner's syndrome family in order to see if 1. levels rise when polyps first appear, and when cancer occurs; and 2. levels fall after colectomy with ileoproctostomy, ileostomy, or rectal mucosal replacement surgery. CEA analyses were carried out in the laboratory of Norman Zamcheck, M.D., using the Roche method. Small increases in CEA titer accompanied the appearance of polyps and small decreases accompanied their removal. Further serial studies are needed to determine whether changes in CEA titer can be indicators of polyp and/or cancer occurrence.

Adult↗
PubMed1983

Clinical and dermatologic aspects of the hereditary intestinal polyposes.

Distinctive cutaneous lesions frequently accompany and occasionally precede the intestinal lesions in Gardner's syndrome, Peutz-Jeghers syndrome, and Muir's syndrome. Awareness of the dermatologic manifestations of these entities may facilitate early diagnosis in these potentially life-threatening hereditary disorders.

Adenoma↗
PubMed1982

Cancer in families of former medical students followed to midlife: prevalence in relatives of subjects with and without major cancer.

In an ongoing longitudinal study of former medical students, now physicians in midlife, the prevalence of cancer among relatives of 46 probands affected by cancer has been compared with that of two control groups of cancer-free probands. Overall, the prevalence of cancer among relatives of the three groups of probands was similar. However, male probands with cancer appeared to have a greater prevalence of cancer among their relatives than did male cancer-free probands, while the corresponding comparisons for the smaller groups of female probands showed the opposite tendency. Among the relatives of cancer probands of either sex, there was evidence of familial clustering of cancer. Where two relatives in a proband's family had the same type of cancer, the two relatives were usually on the same side (paternal or maternal) of the family. Ages at onset of cancer and types of cancer in relatives of the cancer and cancer-free probands did not reveal any significant differences.

Adult↗
PubMed1981

Social work role in research studies of families having hereditary cancer and pre-cancer diagnoses.

The social worker's role in genetic counseling, both as member of a clinical team and investigator in research including family studies, is demonstrated through description of research studies of families having hereditary cancer and pre-cancer diagnoses. Studies involve persons affected with a genetic disorder, those who are unaffected, healthy persons, all of whom may be asked to undergo uncomfortable and sometimes painful tests in order to increase scientific knowledge about a specific genetic disorder. Social work skill and knowledge, casework, interviewing techniques, understanding of the psychodynamics involved in persons with genetic disorders, ability to establish relationships with people, enabling patients to cope with their problems and interdisciplinary competence are all cared for in these projects. Additional qualifications can be acquired through courses in basic genetics and "on the job" training. The pursuit of scientific inquiry within the context of human values is shown as challenge and opportunity.

Attitude to Health↗