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Biomedical subjects

B A Brody

Publications and source records attributed to B A Brody.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intraoperative diagnostic techniques for stereotactic brain biopsy: cytology versus frozen-section histopathology.

Stereotactic brain biopsy has gained widespread acceptance as a primary diagnostic tool for the evaluation of intracranial lesions. Intraoperative evaluation of such specimens has included the use of both cytological and frozen section histologic techniques. The current study seeks to compare the diagnostic utility of frozen section histopathology and cytology in the intraoperative evaluation of stereotactic brain biopsies in HIV-seropositive patients. Seventy-five HIV-seropositive patients undergoing stereotactic brain biopsy for the evaluation of intracranial lesions were evaluated; intracranial diseases were predominantly infectious or hematologic malignancies. Comparison of frozen section and cytology as a means of intraoperative evaluation showed cytology to have a greater sensitivity (86 vs. 78%), positive (95 vs. 90%) and negative (50 vs. 39%) predictive values and a greater overall diagnostic efficiency (84 vs. 75%) than frozen section. Thus, cytology is a highly effective tool equaling and in some cases surpassing frozen section in terms of sensitivity, predictive value, and overall accuracy. Cytologic examination may often be used as the sole means of intraoperative diagnosis, obviating the need for the freezing and sectioning of fresh tissue and potentially reducing specimen turn around time as well. In other cases, cytology can be used in conjunction with other methodologies for arriving at both intraoperative and final diagnoses in these often difficult cases.

Biopsy↗
PubMed1994

Mutations within the transmembrane glycoprotein of Mason-Pfizer monkey virus: loss of SU-TM association and effects on infectivity.

We have previously reported that an 11-amino-acid deletion (D33) within the immunosuppressive peptide (ISP) region of the Mason-Pfizer monkey virus transmembrane (TM) glycoprotein, gp22, caused the loss of interaction between TM and the surface (SU) glycoprotein, gp70. This resulted in the secretion of large amounts of biologically active SU glycoprotein, and we postulated that the ISP might represent a point of contact between the two glycoproteins. To further define the amino acids that might be involved in this proposed region of interaction, we have made two neighboring 4-amino-acid deletions within the area defined by the D33 mutation and have carried out saturation mutagenesis on this 8-amino-acid region. We found that one of the smaller deletions (delta D), and two single point mutations (R68S and L72P), gave the same phenotype as the original D33 mutant. These results provide additional support for the hypothesis that this region of the TM glycoprotein is in contact with the SU glycoprotein and is important in maintaining the noncovalent interactions of the glycoproteins that function to hold the complex together.

Amino Acid Sequence↗
PubMed1994

Is cost a barrier to screening mammography for low-income women receiving Medicare benefits? A randomized trial.

BACKGROUND: In 1991, Medicare began covering screening mammograms subject to copayment and deductible. This study evaluated the effectiveness of Medicare in removing financial barriers to screening mammography among low-income older women. METHODS: In an inner-city public hospital's General Medicine Clinic, 119 consecutive, eligible, and consenting Medicare-enrolled women without known risk factors for breast cancer other than age, and no mammogram in the previous 2 years, were entered into a randomized controlled trial with follow-up after 2 months. The mean age was 71 years; 77% were black, 92% had an annual income below $10,000, and 52% had had a previous mammogram. All patients were counseled concerning indications for screening mammograms and Medicare coverage, and all were referred to a low-cost mammography facility. Sixty-one subjects were randomly assigned a voucher for a free screening mammogram at the referral facility. Obtaining a mammogram within 60 days of study entry was the main outcome measure. RESULTS: Of the women given vouchers, 27 (44%) obtained screening mammograms, compared with six (10%) of those without vouchers (P < .001). Adjustment by multiple logistic regression confirmed this association, yielding an adjusted odds ratio of 7.4 (95% confidence interval, 2.5 to 21.4). Knowledge concerning mammography and breast cancer increased significantly overall (and within randomization groups) between initial interview and follow-up; fear did not change. For women without the voucher, the main reason for not obtaining a mammogram was financial; the main reason for women with the voucher was transportation. CONCLUSION: In a low-income, inner-city population of older women, financial barriers to screening mammography persist despite Medicare coverage.

Aged↗
PubMed1994

Postassembly cleavage of a retroviral glycoprotein cytoplasmic domain removes a necessary incorporation signal and activates fusion activity.

Viral protease-mediated cleavage within the cytoplasmic domain of the transmembrane (TM) glycoprotein of the type D retrovirus, Mason-Pfizer monkey virus, removes approximately 16 amino acids from the carboxy terminus of the protein. To determine the functional significance of this cleavage in the virus life cycle, we introduced premature stop codons into the TM coding domain, resulting in the production of truncated glycoproteins. Progressive truncated of the cytoplasmic domain identified the carboxy-terminal third as being required for efficient incorporation of the glycoprotein complex into budding virions and profoundly increased the fusogenic capability of the TM glycoprotein. These results, together with the ability of matrix protein mutations to suppress TM cleavage, imply that this portion of the glycoprotein interacts specifically with the capsid proteins during budding, suppressing glycoprotein fusion function until virus maturation has occurred.

Amino Acid Sequence↗
PubMed1993

Assessing empirical research in bioethics.

Empirical research can aid ethical reflection in bioethics by identifying issues, by seeing how they are currently resolved, and by assessing the consequences of these current resolutions. This potential can be misused when the ethical issues in question are fundamentally non-consequentialist or when they are consequentialist but the empirical research fails to address the important consequences. An example of the former problem is some recent studies about bad consequences resulting from commercialized living kidney donor programs. These consequences could be avoided, but the crucial non-consequentialist ethical issues about exploitation and commercialization would still remain. Examples of the latter problem are provided by recent studies of the allocation of ICU beds and of physician deception, where important consequences were not adequately studied.

Empirical Research↗
PubMed1993

Methodological and conceptual issues in health care system comparisons: Canada, Norway, and the United States.

There is a growing interest in comparison of international health care data with the hope that such studies will enable individual systems to learn from other systems. Such comparisons, however, presuppose that there exist common criteria for evaluating health care systems. The main thesis of this paper is that these comparative studies are misleading because they employ inappropriate operationalizations of these criteria because the operationalizations are based upon mistaken global conceptualizations of the criteria in question. The essay provides a methodological critique of what has been done and sets a new agenda for future research.

Canada↗
PubMed1992

A viral protease-mediated cleavage of the transmembrane glycoprotein of Mason-Pfizer monkey virus can be suppressed by mutations within the matrix protein.

The envelope glycoprotein precursor of retroviruses undergoes proteolytic cleavage in the Golgi complex to yield the mature surface and transmembrane (TM) glycoproteins of the virus. We report here that the TM glycoprotein of Mason-Pfizer monkey virus undergoes a second proteolytic processing event during a late maturation step that can follow virus release and Gag polyprotein cleavage. Cleavage results in the conversion of the cell-associated TM glycoprotein (gp22) to a virus-associated gp20. Processing continues after virus release and yields virions that contain predominantly gp20. A mutation within the active site of the Mason-Pfizer monkey virus aspartyl protease was shown to block both TM glycoprotein cleavage and the processing of the Gag polyprotein precursor. The role of the viral protease in cleavage of the TM glycoprotein localizes the cleavage site to the cytoplasmic domain of this protein. Surprisingly, point mutations within the matrix (MA) coding region of the gag gene can affect the extent to which gp22 is processed to gp20 and in one case [p10(MA)-A79V] results in greater than 90% inhibition of gp22 cleavage. The data provide genetic evidence of a specific interaction between the capsid proteins and the cytoplasmic domain of the TM glycoprotein of a retrovirus. This interaction is required for cytoplasmic domain cleavage to occur and may play a critical role in virus assembly and viral infectivity.

Amino Acid Sequence↗
PubMed1992

Mutations within the env gene of Mason-Pfizer monkey virus: effects on protein transport and SU-TM association.

By deletion mutagenesis analyses, we have examined the contribution of the immunosuppressive peptide (ISP) region within the transmembrane (TM) protein of Mason-Pfizer monkey virus to viral maturation and infectivity. Deletion of the entire region (mutant D105) results in the production of an Env precursor that is transport defective and therefore unable to be processed to mature glycoproteins. This mutation results in the release of noninfectious virions devoid of surface glycoproteins. A second deletion that removes the most highly conserved 11 amino acids of the ISP (mutant D33) does not affect the production, transport, or processing of the Env precursor yet produces virions that are noninfectious. The mutation was shown to cause the loss of interaction between the surface (SU) and TM proteins and result in the efficient shedding of gp70 into the culture medium. The released gp70 protein was biologically active and could still bind with high specificity to susceptible target cells. Since the ISP domain may represent an area of contact between SU and TM, it could provide an additional explanation for the amino acid sequence homology observed within this region of a variety of retroviruses.

Amino Acid Sequence↗
PubMed1992

Protection of macaques against infection with simian type D retrovirus (SRV-1) by immunization with recombinant vaccinia virus expressing the envelope glycoproteins of either SRV-1 or Mason-Pfizer monkey virus (SRV-3).

Rhesus macaques were immunized with live vaccinia virus recombinants expressing the envelope glycoproteins (gp70 and gp22) of simian type D retrovirus (SRV), serotype 1 or 3. All of the animals immunized with either the SRV-1 env or the SRV-3 env vaccinia virus recombinant developed neutralizing antibodies against the homologous SRV. In addition, both groups developed cross-reactive antibodies and were protected against an intravenous live-virus challenge with SRV-1. The four control animals immunized with a vaccinia virus recombinant expressing the G protein of respiratory syncytial virus were not protected against the same SRV-1 challenge. Although SRV-1 and SRV-3 immune sera showed cross-neutralization, they failed to neutralize a separate, more distantly related serotype, SRV-2, in an in vitro assay. These findings are consistent with the known degree of serologic and genetic relatedness of these three SRV strains.

Animals↗
PubMed1992

MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review.

Findings on cranial magnetic resonance (MR) images were correlated with known histopathologic findings in 42 patients with tuberous sclerosis (TS), 17 of whom received gadopentetate dimeglumine, to extend the range of signs on MR images. Four neuroradiologists recorded the number, sites, configurations, and relative signal intensities of intracranial abnormalities. White matter lesions, found in 39 patients (93%), showed four distinct patterns: (a) straight or curvilinear bands extending radially from the ventricle through the cerebral mantle toward the cortex, (b) wedge-shaped lesions, (c) nonspecific conglomerate foci, and (d) cerebellar radial bands. It is concluded that cortical tubers, white matter lesions, subependymal nodules, and sub-ependymal giant cell astrocytomas (SGCAs) may be enhanced after administration of gadopenetetate dimeglumine. Enhancement of a TS lesion does not indicate neoplastic transformation into SGCA. Imaging surveillance every 12 months appears indicated during the peak ages (8-18 years) of occurrence of SGCA. The appearance of white matter lesions supports the theory that the cerebral lesions of TS may be caused by disordered migration of dysgenetic cells.

Adolescent↗
PubMed1992

The efficacy of image-guided stereotactic brain biopsy in neurologically symptomatic acquired immunodeficiency syndrome patients.

A prospective series of 50 neurologically symptomatic human immunodeficiency infected patients with intracranial lesions who underwent image-guided stereotactic brain biopsy is presented. Patients were diagnosed with primary central nervous system lymphoma (14 patients), progressive multifocal leukoencephalopathy (14 patients), toxoplasmosis (13 patients), human immunodeficiency virus encephalitis (3 patients), infarction (2 patients), and 1 patient each with metastatic adenocarcinoma, metastatic melanoma, cryptococcoma, and atypical mycobacterial infection. Two of the patients with toxoplasmosis had a second intracranial abnormality. Two biopsies resulted in either descriptive diagnosis only or were nondiagnostic; the definitive diagnostic efficacy of image-guided stereotactic biopsy was thus 96%. No deaths were incurred as a result of biopsy. Four intraoperative or postoperative hemorrhages occurred; in only 1 patient was there a residual neurological deficit related to the surgery. Image-guided stereotactic biopsy may thus be considered both safe and effective in this patient population.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Use of the Natural Death Act in pediatric patients.

OBJECTIVE: To review the use of Natural Death Act declarations (living will procedures) in pediatric patients. The implementation of such declarations for children is now possible in six states, including Texas, by specific statutory provisions. DESIGN: Retrospective study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Records of patients who had a Texas Natural Death Act declaration, either discussed and signed or discussed only, were studied. Patients who had another vehicle of limiting care (e.g., a do-not-resuscitate order) were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Reviewed characteristics included age, primary diagnosis, and concurrent complications. Also examined were who raised the issue of limiting care (parent or physician), the initial reaction of the other party, what support was withdrawn, what support was added, the final outcome (including the time from implementing limited care to death), and the description of witnesses. Discussions were held with parents of 17 patients, and 13 Natural Death Act declarations were actually implemented. In all but three instances, the patient died within 4 hrs from the time support was withdrawn. The main supports that were withdrawn were ventilators and catecholamines. In half of the cases, morphine sulfate was added for anticipated pain relief and sedation. All decisions were reached by close consultation between the family and the physicians, with the physicians raising the issue in 11 of the 17 cases and the family raising the issue in six cases. In 15 of the 17 patients, consultation with the Bioethics Committee was not necessary. The majority of difficulties involved resolving issues that beset patients with HIV infections, and finding appropriate witnesses as prescribed by the statute. CONCLUSIONS: We conclude that the Natural Death Act works well in situations involving dying children and their parents.

Adolescent↗
PubMed1991

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Birth Weight↗
PubMed1991

Spinal cord compression from a thoracic paraganglioma: case report.

A 34-year-old man with a 4-month history of midthoracic back pain sought treatment for a recent onset of lower extremity paresthesia and stiffness. A myelogram and computed tomographic myelogram disclosed an extradural block at the level of the 8th thoracic vertebral body with involvement of the pedicles, lamina, and spinous process. A posterior decompression of the spinal cord with subtotal resection of a highly vascular tumor was performed. The tumor was identified as a paraganglioma. In a second stage, the remainder of the tumor was embolized preoperatively, and gross total excision and sequential stabilization of the spine with a Luque rectangle and sublaminar wires were performed. The patient has been symptom free and without signs of a recurrence in the spine for over 13 months. A large abdominal paraganglioma was recently resected from its probable origin from the adventitia of the abdominal aorta.

Abdominal Neoplasms↗
PubMed1991

Physicians and rationing.

Current cost-containment pressures seem to be leading American health care into a world of rationing. Many people have urged that we resist rationing on the grounds that it would compromise the integrity of the patient-physician relation. I shall argue that rationing is in fact both inevitable and appropriate, but the world of rationing is one in which the role of the moral physician involves complex balancing of moral obligations.

Cost Control↗