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Biomedical subjects

E Brown

Publications and source records attributed to E Brown.

At least 127 records · Page 7Linked to original sources

Organ transplantation criteria represent insurer dilemma.

In its simplest form, technology assessment, as used for coverage decision making, involves an analysis of published data regarding the safety and effectiveness of a technology, either on its own merits or in comparison with a competing technology. However, while the medical literature, and thus technology assessments, typically focus on a well-defined population, a positive coverage policy almost immediately creates pressure for broadening patient selection criteria. A variant on this phenomenon is the patient selection criteria for organ transplantation. These criteria are based not only on the scientific merits of the procedure but also on frequently ill-defined notions of the most appropriate allocation of a scarce resource, which in turn is determined by supply and demand at individual transplant centers. In these cases, the payer may defer to the patient selection criteria of the individual transplant center. However, the situation arises when a patient, rejected at one transplant center, "shops" and finds another center that has more favorable selection criteria. How, then, can the payer resolve these discrepancies and establish consistent policy guidelines? Should allocation of scarce donor organs be part of a technology assessment and coverage decision? The case of liver transplantation will be used here to illustrate the insurer's dilemma.

Eligibility Determination↗

The mandate for investigational cancer therapies.

The heated national health care reform debate of the summer of 1993 has now simmered down, but pieces of the debate are still percolating along at the state level. Within the past year, numerous states have introduced bills that would mandate insurance coverage for investigational cancer therapies--in particular high-dose chemotherapy and bone marrow transplant for breast cancer. The problem with these initiatives, well-intended though they may be, is that they threaten to spread unproven technologies at a rapid rate and at the same time miss the opportunity to collect data that would prove the safety and effectiveness of the methods. The author explores these issues and suggests how managed care companies can play a more aggressive role in parrying the threat.

Bone Marrow Transplantation↗

The medical device payment controversy rages on.

Who will pay for investigational research? This seemingly endless debate assumes different guises as different aspects of the health care industry come under scrutiny. The latest wrinkle in the debate involves reimbursement for devices that are not FDA approved. My September column discussed the issue of funding investigational cancer therapies, specifically high-dose therapy and bone marrow transplant, as treatments for various malignancies. That controversy was centered on the use of FDA-approved drugs in settings beyond the labeled indications. However, the issue with medical devices is different. It involves implantable devices that the FDA says have not proven to be safe and effective.

Device Approval↗

Effect of resuscitation solutions on the immune status of dogs in hemorrhagic shock.

The purpose of this study is to examine the effects of three different types of fluid resuscitation on the immune system of dogs in hemorrhagic shock. Using a modified Wigger shock model, 18 conditioned male dogs were bled to mean arterial blood pressure of 60 mm Hg for 90 minutes and placed into three groups based on the resuscitative method. Group I: Crystalloid Resuscitation; Group II: Autotransfusion; Group III: Banked Blood. Laboratory methods for immune status evaluation included total lymphocyte count, T4/T8 ratio, total serum immunoglobulins, and immunoglobulin electrophoresis. These values were obtained pre-hemorrhagic shock, just before resuscitation, and subsequently on days 1, 4, and 7. Humoral immunity, represented by total serum immunoglobulin levels (IgA, IgG, IgM), was higher in Groups II and III when compared with group I on all post-resuscitation days. IgA and IgM levels were higher in Group III compared with Groups I and II. IgG level was higher in Group II compared with Groups I and III. Cellular immunity was also affected by transfusion. Total lymphocyte count was increased in Group II on Day 1; however, the three groups were similar with respect to this variable on subsequent days. The absolute T4 helper cell level in Group II was similar to Groups I and III until Day 7, at which time the level became higher in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Polycystic disease of the parotid glands.

A 31-year-old woman had bilateral swelling of the parotid glands at 4 months of pregnancy. MR imaging showed marked enlargement of the parotid glands with increased signal on images with long repetition times. A diagnosis of polycystic disease of the parotid gland was made after biopsy and histologic examination. The radiographic and histologic features of this rare disease are discussed.

Adult↗

Prevalence of incidental intraspinal lipoma of the lumbosacral spine as determined by MRI.

STUDY DESIGN: The prevalence and appearance on MRI of lipomas of the filum terminale was studied in a random population referred to MRI for evaluation of the lumbosacral spine. The MRI scans of 100 patients selected at random were retrospectively reviewed. OBJECTIVES: The study sought to determine the frequency and MRI appearance of incidental filum lipomas in a random population. SUMMARY OF BACKGROUND DATA: Postmortem studies have reported a 4%-6% incidence of occult fibrolipomas of the filum terminale in what were thought to be otherwise normal spinal cords. The improved resolution of MRI imaging allows the detection of small amounts of fat associated with the filum terminale that heretofore had not been demonstrated on radiologic imaging examinations. METHODS: The lumbosacral spine unenhanced MRI scans of 100 patients not previously operated upon were selected at random and were retrospectively reviewed by two of the authors (EB and JCM). RESULTS: Of the 100 MRI examinations reviewed, four patients were found to have small lipomas of the filum terminale. No spinal dysraphism or cord tethering were present in these four patients. Their clinical symptoms were related to disc herniation in two patients, spinal stenosis in one, and discitis in one. The lipomatous tissue was hyperintense to cerebrospinal fluid (CSF) on T1-weighted images and hypointense to CSF on T2-weighted images. CONCLUSIONS: Incidental lipomas of the filum terminale were present in 4% of 100 lumbosacral spine MRI examinations in a random population.

Adult↗

Electrolyte and acid-base disorders associated with AIDS: an etiologic review.

In summary, patients with HIV infection may develop a bewildering variety of electrolyte and acid-base disturbances. Hyponatremia from many causes is common and associated with an increased mortality. Potassium disorders are frequent, with hyperkalemia, even to life-threatening levels, more common than hypokalemia. Disturbances in calcium and uric acid homeostasis are less frequent. Acid-base disorders also complicate the clinical course of AIDS and, as with the electrolyte perturbations, may result from HIV infection itself, the illnesses associated with AIDS, or medications.

Acid-Base Imbalance↗

Coexistence of glucocorticoid receptor and pharmacokinetic abnormalities: factors that contribute to a poor response to treatment with glucocorticoids in children with asthma.

Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy.

Adolescent↗

The effect of drains in laparoscopic cholecystectomy.

A prospective controlled randomized study was performed on 100 patients undergoing elective laparoscopic cholecystectomy to evaluate the benefit of routine drainage in simple uncomplicated procedures. The 100 patients were randomized into two groups. Group 1 patients (n = 50) had a drain placed through the epigastric trocar site. The drain was removed before their discharge unless bile or blood was present. Group 2 patients (n = 50) did not have a drain placed. Eleven patients in group 2 (no drain) (22%) were discharged on the same day of surgery (within 8 h), and the remaining 89 patients in both groups were discharged the day after surgery (within 23 h). There were no wound infections or postoperative fever in either group. There were minor but not statistically significant differences between the two groups in postoperative severity and duration of abdominal pain, shoulder pain, and nausea. Furthermore, the two groups were similar in respect to postoperative recovery time and return to work.

Activities of Daily Living↗

On the respiratory flow in the cuttlefish sepia officinalis.

The respiratory flow of water over the gills of the cuttlefish Sepia officinalis at rest is produced by the alternate activity of the radial muscles of the mantle and the musculature of the collar flaps; mantle circular muscle fibres are not involved. Inspiration takes place as the radial fibres contract, thinning the mantle and expanding the mantle cavity. The rise in mantle cavity pressure (up to 0.15 kPa), expelling water via the siphon during expiration, is brought about by inward movement of the collar flaps and (probably) mainly by elastic recoil of the mantle connective tissue network 'wound up' by radial fibre contraction during inspiration. Sepia also shows a second respiratory pattern, in which mantle cavity pressures during expiration are greater (up to 0.25 kPa). Here, the mantle circular fibres are involved, as they are during the large pressure transients (up to 10 kPa) seen during escape jetting. Active contraction of the muscles of the collar flaps is seen in all three patterns of expulsion of water from the mantle cavity, electrical activity increasing with increasing mantle cavity pressures. Respiratory expiration in the resting squid Loligo vulgaris is probably driven as in Sepia, whereas in the resting octopus Eledone cirrhosa, the mantle circular musculature is active during expiration. The significance of these observations is discussed.

Journal Article↗

Chondrosarcoma of the skull base.

Chondrosarcomas are relatively rare tumors of the skull base. This article surveys the clinical and pathologic features of these lesions. In recent years there have been remarkable advances in both the imaging and treatment of these lesions. Both CT scanning and MR imaging are usually necessary for the complete evaluation of these tumors because of the involvement of both soft tissue and bony structures at the skull base. New surgical techniques and the use of high-energy proton beam irradiation have improved the prognosis for patients with these lesions.

Adult↗

Interleukin-2 activation of human bone marrow in long-term cultures: an effective strategy for purging and generation of anti-tumor cytotoxic effectors.

Our previous studies have shown that IL-2 activated bone marrow cells develop potent tumoricidal activity in vitro and in vivo. With the dual aim of in vitro purging and generation of effectors which could mediate graft-versus-leukemia effects in vivo, IL-2 activation of human bone marrow in long-term cultures (LTC) was tested. Marked cytotoxicity was seen against A375 (melanoma), K562 (CML) and Daudi (lymphoma) cell lines in IL-2 (1000 U/ml) stimulated cultures. Hematopoietic progenitor cell number in these cultures was assessed by day 14 clonogenic assays. In 1-week-old IL-2 stimulated cultures a higher number of clonogenic cells was seen than control LTCs without IL-2. However, thereafter accelerated decrease in the number of clonogenic cells was seen in IL-2 cultures. In vitro purging efficacy was tested by elimination of A375 and K562 cells mixed with normal marrow at 1:10 and 1:100 ratios and co-cultured for 10 days. In IL-2 stimulated cultures, A375 cells capable of proliferation were not detectable at both mixing ratios. K562 elimination was complete only at 1:100 ratio. After 10 days in culture, no Ph1-positive metaphases were seen in IL-2 stimulated BM cultures of 4 patients with CML. These results indicate that IL-2 activation of BM in 1-2 week cultures can lead to generation of marked anti-tumor cytotoxicity and effective in vitro purging in a variety of tumor types.

Bone Marrow↗

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Contract Services↗

The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase as inferred from a database of in vivo substrates and from the in vitro glycosylation of proteins and peptides.

The acceptor substrate specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) was inferred from the amino acid sequences surrounding 196 O-glycosylation sites extracted from the National Biomedical Research Foundation Protein Database. When analyzed according to the cumulative enzyme specificity model (Poorman, R.A., Tomasselli, A.G., Heinrikson, R.L., and Kézdy, F.J. (1991) J. Biol. Chem. 266, 14554-14561) these data were found to be consistent with an enzymatic active site which interacts with an 8-amino-acid long segment of the substrate, spanning 3 amino acid residues preceding and 4 amino acid residues following the reactive serine or threonine. The model postulates independent interactions of the 8 amino acid moieties with their respective binding sites, designated as subsites P3 through P0 and P1' to P4'. High selectivity is expressed at all subsites toward serine, threonine, and proline. The inferred specificity was confirmed by in vitro bovine colostrum GalNAc-transferase-catalyzed glycosylation of unglycosylated proteins containing predicted sites for O-glycosylation and synthetic peptides designed to be GalNAc acceptors. In synthetic peptides the bovine colostrum GalNAc-transferase glycosylates threonine about 35 times faster than serine. Our results suggest that the specificity of the enzyme is not dependent on any particular secondary structure of the substrate but, rather, it is determined by the amino acids in the acceptor peptide segment as well as by the accessibility of this segment. It also appears likely that bovine colostrum GalNAc-transferase is able to catalyze in vivo the glycosylation of both threonine and serine residues.

Amino Acid Sequence↗

Factors that predict antiphospholipid immunoreactivity in young people with transient focal neurological events.

OBJECTIVE: To determine if clinical or radiological features in young people with transient focal neurological events may be used to predict the presence of antiphospholipid antibodies (aPL). DESIGN: A combined retrospective and prospective study of young people with transient focal neurological events. Likelihood ratios and confidence intervals were calculated for the proportions; logistic regression analysis was performed to determine features predictive of aPL immunoreactivity. SETTING: A referral hospital and adjacent outpatient clinic. PATIENTS: Sixty-eight patients with one or more transient focal neurological events were screened for aPL. Forty-seven patients were obtained retrospectively from medical record review of every outpatient personally seen by two of us (G.E.T. and S.R.L.) during a 4.5-year period. Twenty-one patients were prospectively added prior to retrospective analysis. Patients older than 50 years or those with multiple sclerosis or epilepsy were excluded. Five patients fulfilling study criteria were excluded because aPL assay results were unavailable. MAIN OUTCOME MEASURES: Transient neurological symptoms, stroke risk factors, occurrence of cerebral or ocular infarct or death, headache history, and serological and radiological studies were systematically obtained. RESULTS: There were 29 aPL-positive patients compared with 39 aPL-negative ones. Features that distinguished the aPL-positive group included more common monocular visual symptoms (38% vs 15%, P = .03), hemisensory symptoms (76% vs 41%, P = .004), and systemic lupus erythematosus (14% vs 0%, P = .03) and less common binocular visual symptoms (28% vs 51%, P = .05), accompanying headache (66% vs 87%, P = .03), and personal (48% vs 74%, P = .03) and family (29% vs 61%, P = .01) history of migraine. No differences were noted between the groups for age, gender, stroke risk factor profile, and radiological features. In a logistic regression analysis, the estimated odds ratio for aPL positivity in patients with monocular visual disturbance, hemisensory symptoms, and no family history of migraine were 5.3, 7.5, and 3.0, respectively, when controlling for the other variables. CONCLUSIONS: Several clinical features of transient focal neurological events in aPL-positive patients distinguish these individuals from their aPL-negative cohort. Amaurosis fugax, unilateral paresthesias, and no family history of migraine may predict aPL positivity in young persons with transient focal neurological deficits.

Adolescent↗