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Biomedical subjects

A M Davidoff

Publications and source records attributed to A M Davidoff.

41 records · Page 3Linked to original sources

p53 alterations in all stages of breast cancer.

Overexpression of the nuclear phosphoprotein p53 is one of the most frequently detected abnormalities in human cancer and appears to be associated with mutation of the p53 gene. In this study of breast cancer, p53 overexpression was detected in two (15%) of 15 pure intraductal tumors, 73 (25%) of 291 primary invasive carcinomas, 13 (50%) of 26 lymph nodes containing metastatic breast cancer, and two of four established breast cancer cell lines. Sequence analysis of selected specimens confirmed that p53 overexpression was associated with mutation of the gene, while no mutations were detected in specimens without p53 overexpression. Thus, overexpression of p53 occurs in all stages of breast cancer and is consistently associated with the production of mutant proteins. Immunohistochemical analysis is a simple method which reliably predicts the presence of most p53 gene mutations in breast cancer specimens.

Base Sequence↗

Occult spinal dysraphism in patients with anal agenesis.

Recent reports have suggested an association between congenital anorectal anomalies and occult spinal dysraphism. Eighty-seven patients with anal agenesis have been treated at this institution over the last 14 years. Two of these patients had spinal cord anomalies recognized at birth (a myelomeningocele and a tethered spinal cord). Two additional patients presented with progressive neurologic deficits in early childhood and were each found to have a tethered spinal cord. To further assess the magnitude of this problem, we have used magnetic resonance imaging (MRI) of the spine to survey prospectively 23 infants with anal agenesis. Twenty-one former patients who were asymptomatic were recalled and also studied. Four of 44 patients (9%) were found to have significant occult spinal dysraphism; each child had undergone neurosurgical operation without morbidity. MRI found each child to have a tethered spinal cord, either as an isolated lesion (2) or in association with a syrinx (1) or lipomyelomeningocele (1). One of these patients had a neurologic deficit detected on careful preoperative evaluation. The other three, two of whom were less than 2 years old, had no detectable deficit. Neither the extent of the anorectal malformation, the absence of associated congenital anomalies, nor the demonstration of normal vertebral anatomy on plain radiographs of the spine precluded the presence of occult spinal dysraphism. Therefore, we recommend that all patients with anorectal anomalies undergo MRI imaging of their spines during initial evaluation to screen for occult spinal dysraphism. In addition, consideration should be given to recalling older patients for MRI evaluation.

Abnormalities, Multiple↗

Relation between p53 overexpression and established prognostic factors in breast cancer.

The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In breast carcinoma overexpression of p53 is associated with point mutations within highly conserved regions of the p53 gene. These altered genes encode stable p53 proteins that can be detected by standard immunohistochemical techniques unable to detect rapidly degraded wild-type protein. The level of p53 expression in 184 primary breast cancer specimens was assessed by immunohistochemical analysis and related to the following established prognostic factors for breast cancer: age, stage, metastatic involvement, concentration of estrogen and progesterone receptors, proliferative index, and HER-2/neu overexpression. Fifty (27%) of these primary breast cancer specimens had widespread overexpression of p53. Highly significant associations were found between p53 overexpression and late stage, metastatic spread, and low concentration of progesterone receptors. The presence of elevated levels of mutant p53 may itself be a prognostic factor in human breast cancer and activation of this oncogene may be important in the ability of a tumor to metastasize.

Breast Neoplasms↗

Pneumatosis intestinalis. Surgical management and clinical outcome.

Pneumatosis intestinalis (PI) occurs in a wide variety of patients, some of whom require urgent surgery, while others can be observed with resolution of symptoms and radiographic findings. During 1 year, 27 patients with PI were prospectively evaluated for clinical, laboratory, and radiographic features that would be useful in predicting the need for surgery, the pathologic findings, and patient outcome. Sixteen of the twenty-seven patients underwent laparotomy, with only one negative exploration. Of the 11 patients not explored, there were two deaths in moribund patients. Seven of nine patients with jejunostomy tubes, recent gastrointestinal anastomoses, inflammatory bowel disease, lactulose therapy, or chemotherapy who did not have clinical evidence of an acute surgical abdomen or metabolic acidosis survived without surgery (two deaths unrelated to the gastrointestinal tract). Patients presenting with bowel obstruction and PI required surgery in seven of nine cases, did not have necrotic bowel, and had 11% mortality. Eight patients with ischemic bowel had a 75% mortality rate, despite surgery. Patients with PI and clinical evidence of bowel obstruction or ischemia usually require urgent surgery, while asymptomatic patients without metabolic acidosis can be safely observed.

Female↗

Wilms tumor presenting with abdominal pain: a special subgroup of patients.

BACKGROUND: Although significant progress has been made in the management of children with Wilms tumor, two major controversies still exist: the extent of radiographic evaluation necessary before surgery and the role of preoperative chemotherapy. This study sought to determine whether patients with Wilms tumor who presented with abdominal pain defined a special subset of patients who might require a more extensive preoperative work-up and neoadjuvant chemotherapy. METHODS: From 1970 to 1995, 250 children were treated for Wilms tumor at a single pediatric institution. A retrospective chart review determined presenting signs and symptoms for each patient. RESULTS: Thirty-four (14%) patients (mean age 5.5 years) sought medical attention with a chief complaint of abdominal pain. The stage distribution for these patients tended to be higher and was significantly different (P <.001, chi(2)-analysis) from those presenting without pain. Four (14%) of 29 patients with tumor available for analysis were found to have anaplastic histology. CONCLUSION: These data suggest that patients with Wilms tumor who present with abdominal pain represent a special subgroup that tends to be older and has an increased incidence of tumor rupture, anaplasia, and higher stage. These patients may benefit from a more extensive preoperative evaluation and consideration of neoadjuvant chemotherapy.

Abdominal Pain↗