Biomedical subjects
Publications and source records attributed to B Kaufman.
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BACKGROUND AND METHODS. Genetic analysis of tumor tissue has provided considerable insight into mechanisms of malignant transformation and progression. Neuroblastomas have been studied by cytogenetics, flow cytometry, and molecular genetic techniques, and these studies have identified several specific abnormalities that allow subclassification of these tumors into genetic/clinical subtypes. RESULTS AND DISCUSSION. Four genetic abnormalities have been identified that are characteristic of certain neuroblastomas. These include: (1) loss of heterozygosity (LOH) for the short arm of chromosome 1, including band 1p36; (2) amplification of the N-myc protooncogene; (3) hyperdiploidy, or near triploidy; and (4) defects in expression or function of the nerve growth factor receptor (NGFR). Abnormalities of the NGFR are found in virtually all neuroblastoma cell lines, and some primary tumors. The latter have not been studied extensively. Hyperdiploidy is associated with lower stages of disease and with a favorable outcome in infants. LOH for chromomors. The latter have not been studied extensively. Hyperdiploidy is associated with lower stages of disease and with a favorable outcome in infants. LOH for chromosome 1, band p36, and N-myc amplification are more common in patients older than 1 year of age with advanced stages of disease. The latter two genetic abnormalities may be related, and LOH for 1p36 may precede the development of amplification. When these abnormalities are combined with assessment of DNA content, three distinct genetic subsets of neuroblastomas can be identified. The first is characterized by a hyperdiploid or near-triploid modal karyotype, with few if any cytogenetic rearrangements. These patients generally are younger than 1 year of age with localized disease and a good prognosis. The second has a near-diploid karyotype, with no consistent abnormality identified currently. These patients generally are older with more advanced stages of disease that progress slowly and are often fatal. The third group has a near-diploid or tetraploid karyotype, with deletions or LOH for 1p36, amplification of N-myc, or both. These patients generally are older with advanced stages of disease that rapidly are progressive. Thus, genetic analysis of neuroblastoma cells provides information that has prognostic significance and can direct a more appropriate choice of treatment.
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The effectiveness of immigrants as agents of gene flow was investigated in a laboratory model, using mutant marker strains of the flour beetle, Tribolium castaneum (Herbst). We show that immigrants had an advantage over residents. The proportion of hybrid offspring (PHO), resulting from immigrant mating with residents, was higher than expected from their frequency in the parental population. This advantage was observed regardless of immigrant sex and immigrant strain. The advantage seems to result from immigrant mating advantage (although not a rare-male phenomenon) and not from better survival of hybrid offspring. However, hybrid offspring seem to be more resistant to sporozoan infection, resulting in higher PHO in sporozoan-infected cultures.
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This report concerns a patient with ophthalmoplegia, ataxia and hyporeflexia (Fisher's syndrome) with a lesion in the midbrain tegmentum demonstrated by computerized-tomography (CT) scanning. Spontaneous recovery was almost complete 1 month after the onset. Based upon its strategic location, it is suggested that the lesion can explain the findings in the patient. The CT finding, if confirmed, will necessitate a reconsideration of our current pathogenetic views about Landry-Guillain-Barré syndrome in general and Fisher's syndrome in particular.
Computerized tomography as a diagnostic procedure is characterized by its high sensitivity but limited specificity. This lack of specificity may result in an erroneous diagnosis and, possibly, in ill-advised therapy unless clinical and objective data are carefully considered in interpreting the study. The most common pitfalls encountered are the phenomena of contrast enhancement of infarcts and mass effect associated with infarcts. Many different pathological processes can have similar enhancement patterns. The evolution of high density, acute hemorrhage to isodense areas in the chronic hematoma can become a serious diagnostic problem unless an appropriate history is available. The authors discuss 30 cases in which misinterpretation of CT scans resulted in erroneous diagnoses. Seventeen of these patients underwent operation.
To the accepted classification of three types of normal pressure, nontraumatic cerebrospinal fluid (CSF) fistulas, we would add "acquired." This type of CSF fistula tends to occur from the middle cranial fossa because of the enlargement of "pitholes" that are normally present in its anterior medial aspect. The enlargement of these bony defects is due to normal intracranial pressure variations that, not uncommonly, create meningoceles and meningoencephaloceles. A portion of the floor of this area is aerated in up to 10% of the normal population by the lateral recess of the sphenoid sinus, the pterygoid recess. Thus, this area has the potential to act as a pathway between the middle fossa and the paranasal sinuses, allowing cerebrospinal fluid to pass into the sinuses. Isotope and computerized tomographic studies are helpful in the localization of such a CSF leak. Tomography of the base of the skull, however, is essential for the ideal definition of possible routes of fistulization. If there is any question of the presence of a middle fossa fistula, these studies can show whether the floor of this area is pneumatized and whether there are any defects in the floor. The treatment of such a fistula should include generalized reinforcement of the floor of the anterior middle fossa by a middle fossa approach. If any doubt exists as to the site of leakage (anterior or middle fossa), the minimal surgical procedure should include exploration of both areas via a frontotemporal craniotomy.
An unusual case of a vermian hematoma from the rupture of an angioma in a four-year-old child is presented. The lesion was treated successfully with complete recovery.
Pituitary function has been studied sequentially after transsphenoidal removal of pituitary microadenomas in two men with Cushing's disease. Patient 1 gradually regained normal glucocorticoid levels with normal diurnal variation, metyrapone responsiveness, and low dose dexamethasone suppressibility (17-hydroxycorticosteroid, 6.5-0.9 mg/24 h). GH levels rose from 1 to 35 ng/ml during insulin hypoglycemia and from 2.3 to 27 ng/ml during arginine infusion. PRL secretion rose normally in response to thorazine, and gonadotropin and TSH levels remained normal. Patient 2 regained significant metyrapone responsiveness by 9 months postoperatively (11-deoxycortisol rose to 11.7 micrograms/dl), had a normal spontaneous nocturnal rise in PRL secretion, and normal levels of testosterone and thyroid hormones. The return to normal of cortisol-ACTH dynamics and GH responsiveness in Patient 1 and the normal nocturnal surge in PRL secretion in Patient 2 imply that in these patients the etiology of Cushing's disease was not related to hypothalamic dysfunction.
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Five cases of spontaneous cerebrospinal fluid (CSF) fistulas originating from the middle fossa are described, including one patient with an "empty" sella. It is suggested that acquired meningocele and meningoencephalocele progress to become CSF fistulas. The normal anatomical and physiological factors which give rise to acquired bone/dural/arachnoid dehiscences are discussed and illustrated.
Subtraction radiography permits the use of 7-10 times less contrast material than is required without subtraction techniques. The first-order, second-order, and composite mask techniques are described and evaluated. While the second-order technique gives more complete cancellation of common structures, the more commonly used first-order technique was found to be adequate for most clinical uses. The smallest change in contrast which can be detected using subtraction radiography is limited by inherent background film noise in the original radiographs and not by statistical fluctuations in the x-ray quanta.
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Syncope precipitated by sneezing in an adult male associated with an Arnold-Chiari type I malformation and basilar invagination presents a clinical problem in the differential diagnosis and pathological anatomy of Valsalva-related syncope. An abnormally acute clivoaxial angle, small foramen magnum, and type I Arnold-Chiari malformation appear to be a combination of features intolerant of Valsalva-induced changes in cerebral volume, brain-stem position, CSF fluid dynamics, or blood vessel relationships. Proposed mechanisms of pressure transmission to the area of intracranial pathology are discussed.