Biomedical subjects
Publications and source records attributed to J Griffin.
IVUS measurements of stent and reference lumen dimensions and cross-sectional areas are highly reproducible. Furthermore, paramedical personnel can be trained to perform these measurements accurately. Thus, IVUS measurements may become the gold standard for the acute, chronic, and serial assessment of stent implantation procedures.
Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured IFN-alpha levels in CSF and blood by ELISA in human immunodeficiency virus (HIV)-positive patients with (n = 21) and without (n = 23) dementia and HIV-negative controls (n = 48). IFN-alpha was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-alpha in the CSF was correlated with the clinical parameter of increasing Memorial Sloan Kettering scores; although these correlations were not statistically significant, they further suggest an association of increased CSF IFN-alpha with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-alpha-positive macrophages and astrocytes in frontal cortex and white matter and IFN-alpha mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-alpha is made by cells within the brain and suggesting that the significant increases of IFN-alpha protein found in the CSF of patients with HIV-associated dementia complex are derived from intrinsic brain cells such as macrophages and astrocytes. Increased local production of IFN-alpha during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.
Phagocytosis leads to the destruction of many bacteria and the proteolytic degradation of bacterial antigens within phagolysosomes to produce immunogenic peptides that bind to Class II major histocompatibility (MHC) molecules within vacuolar compartments. On the other hand, Class I MHC molecules bind cytosol-derived peptides, including peptides from bacteria that escape the vacuolar system and penetrate into the cytosol. A recently described pathway may also allow the presentation of peptides from intravacuolar organisms by Class I MHC molecules in some cases. T cell recognition of peptide-MHC complexes then provides the primary basis for specific immunity to protein antigens of bacteria. This article will review the subcellular compartments and mechanisms involved in generating immunogenic peptides, the subcellular localization of MHC molecules that bind these peptides, and bacterial parameters that affect antigen processing.
STUDY DESIGN: In a prospective, single-blinded study, the incidence of false-positive screening tests for sacroiliac joint dysfunction was investigated using the standing flexion, seated flexion, and Gillet tests in 101 asymptomatic subjects. OBJECTIVES: This study determined if these commonly used sacroiliac screening tests can be abnormal in an asymptomatic population. SUMMARY OF BACKGROUND DATA: The sacroiliac joint is a potential source of back and leg pain. One condition affecting this joint is termed sacroiliac joint dysfunction. Diagnosis of this is made primarily by physical examination using screening tests as preliminary diagnostic tools. These screening tests evaluate for asymmetry in sacroiliac motion due to a relative, unilateral hypomobility in one the sacroiliac joints. The specificity of these tests, however, has not been thoroughly evaluated in a well-selected asymptomatic population. METHODS: A single-blinded examiner performed the standing flexion, seated flexion, and Gillet tests on all subjects. An asymptomatic and a symptomatic group were studied. RESULTS: Overall, 20% of asymptomatic individuals had positive findings in one or more of these tests. The specific percentage of false positives are reported by test, age, sex, and side. CONCLUSION: This study suggests that asymmetry in sacroiliac motion due to relative hypomobility as determined by these tests can occur in asymptomatic joints. Obviously, one should not rely solely on these tests to diagnose symptomatic sacroiliac dysfunction.
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Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 x 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFN gamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 x 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 x 10(6) U/m2/day also could not complete a full course of rIFN gamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFN gamma plasma levels in patients who tolerated a complete infusion were < 40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFN gamma at doses as low as 2 x 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 x 10(6) U/m2/day.
To determine whether insurance status (payer class) affects the amount and type of pain medication prescribed, and whether patients in those groups without prescription drug coverage received lower-cost medications, a case-control study with retrospective chart review was initiated in a university-based hematology/oncology practice in northwest Louisiana. Charts of 710 active patients among all insurance groups (private insurance, Medicare, Medicaid, State Hospital System) were analyzed to determine insurance status, pain medication (amount and type), and diagnosis. The proportion of Medicaid patients receiving pain medications was significantly increased in relation to their representation in the practice when compared with Medicare patients, patients with private insurance, uninsured patients whose health care costs were provided by the State Hospital System, and the overall patient population. Medicaid patients, especially those with solid tumor malignancies, received the most expensive class of pain medications at a significantly higher rate than other patients. In the studied population of hematology and oncology patients, there is a significant difference in the amount and type of pain medications prescribed between patients with prescription drug coverage (Medicaid) and those without (all other groups including those covered by the statewide system). We propose that consideration be given to alternative methods of financing prescription medications for medically indigent patients.
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Patients who had undergone curative resection for colorectal cancer were studied to compare the efficacy of faecal occult blood detection (Haemoccult test) with colonoscopy in the detection of metachronous tumours. Fifty nine patients were studied and both Haemoccult testing and colonoscopy were successfully completed in 54 patients. In 37 patients, both tests were negative. One patient with a positive Haemoccult test had no colonoscopic abnormality and remains alive and well two years later. There were, however, 16 patients with negative Haemoccult tests in whom an abnormality was found on colonoscopy. In four patients, one Dukes's A cancer and seven tubulovillous adenomas were found--all neoplastic lesions that would have been missed if surveillance had been by Haemoccult alone.
Studies from our laboratory have demonstrated that human CG (hCG), human LH, (hLH), and an hCG-like protein extracted from Xanthomonas maltophilia were able to induce Candida albicans transition from the blastospore to the germ tube stage. In the present study, we describe the characterization of an hCG-like material extracted from Candida albicans blastospores (CaCGLP), which is potent in inducing transition and presumably represents the endogenous transition-inducing substance. This material was extracted from Candida albicans blastospores with glacial acetic acid and purified by affinity chromatography using a polyclonal rabbit anti-hCG antibody. The product obtained is a 68-kilodalton single band protein, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Under reduced conditions a protein smear is seen. Amino acid analysis showed a predominance of glycine (22%), followed by serine (12%), and glutamate (12%). This protein reacted in the following hCG immunoassays: 1) a polyclonal rabbit anti-hCG equilibrium assay, 2) a carboxyl-tail hCG equilibrium assay, 3) two hCG equilibrium assays using monoclonal antibodies (CG no. 4 and CG no. 9), 4) a free alpha-subunit equilibrium assay using a monoclonal antibody, and 5) an ultrasensitive immunoradiometric assay for hCG which does not cross-react with hLH, nor the free beta-subunit of hCG. The CaCGLP showed no reaction in a specific hLH immunoradiometric assay. When CaCGLP was tested in the transition assay, in the presence of 4% rat serum, it was found that this protein was 100 times more potent than hCG in producing Candida albicans transition. We conclude that Candida albicans produces a protein that has certain tertiary structure similarities to hCG and that this material is able to induce germ tube formation. We postulate that CaCGLP has an autocrine/paracrine effect in Candida albicans as a transition factor to control its own pathogenicity.
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Munchausen's syndrome was first described by Asher in 1951. Then Ireland, et al, described eight criteria that characterized these patients. These characteristics include factitious illness of a dramatic nature, factitious evidence of disease, evidence of multiple medical procedures, pathologic lying, aggressive behavior, leaving the hospital against medical advice, multiple hospitalizations with traveling and absence of any obvious secondary gain. Another form of this disease is Munchausen's syndrome by proxy which describes parental behavior that creates the appearance of, or produces, physical illness in a child with harmful consequences to the child. In this report, we present a complex case of Munchausen's syndrome in a patient who has been traveling around the country, going from one hospital to another for several years. We ask physicians to be aware of the features of this patient, bearing in mind that this was her third hospitalization at the University of Wisconsin Hospital in Madison.
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A second-generation implantable pacemaker-cardioverter-defibrillator was evaluated in 200 patients with sustained ventricular tachycardia, ventricular fibrillation or prior cardiac arrest. The device permits demand ventricular pacing for bradyarrhythmias and for long QT interval or tachycardia suppression, uses programmable (3 to 30 J) energy shocks for conversion of ventricular tachycardia and ventricular fibrillation and is used with conventional pacing and defibrillation leads. Ventricular tachycardia/fibrillation recognition is based on the ventricular electrogram rate and requires reconfirmation before shock delivery. Two hundred patients (mean age 62 years, mean left ventricular ejection fraction 36%) were enrolled and followed up for 0 to 23 months (mean 12). Epicardial lead system implantation was performed with use of an anterolateral thoracotomy (38%), median sternotomy (26%) and subxiphoid (20%) or subcostal (16%) approach. Perioperative mortality rate was 5.5% (all nonarrhythmic deaths). Implant defibrillation threshold ranged from 3 to 30 J (mean 15), with initial programmed shock energy ranging from 3 to 30 J (mean 22). Ventricular tachycardia/fibrillation sensing threshold ranged from 0.7 to 1.8 mV (median 1) and the tachycardia detection interval from 288 to 416 ms (median 320). Reprogramming of implant variables was necessary for reliable electrographic sensing (54 patients), programmed shock therapy (61 patients) and tachycardia detection rate (63 patients). Device activation for potential shock delivery occurred in 111 patients (55.5%) with actual shock delivery after ventricular tachycardia/fibrillation reconfirmation in 66 patients (33%). During follow-up study, there was a 1% arrhythmia mortality rate, 6.5% cardiac mortality rate and 10.5% total mortality rate. This study demonstrates that the programmable implantable pacemaker-cardioverter-defibrillator is effective in preventing arrhythmic death, yet reduces patient exposure to repeated shock therapy. Reprogramming is usually necessary during follow-up for optimal function.
In contrast to the conventional pulmonary adenocarcinomas (CPAs), bronchioloalveolar carcinoma (BAC) grows predominantly by spreading along the existing alveolar septal framework. Within the BAC category, three subtypes have been identified: mucinous, nonmucinous, and sclerosing BAC. Of these, mucinous and sclerosing BACs have worse prognoses compared with nonmucinous BAC. However, the manifestation of aggressive behavior is different between the mucinous and sclerosing types of BACs. Multifocality is often produced by aerogenous spread, especially in the case of mucinous BACs. To study the differences between the BAC subtypes and the conventional pulmonary adenocarcinomas, we employed a battery of immunohistochemical stains marking the extracellular matrix architecture (laminin, collagen IV, fibronectin, and collagen III), a degradative enzyme against a basement membrane component (anti-type IV collagenase) and cellular receptors for laminin and collagen IV (alpha 2 integrin) on 16 BACs (5 mucinous, 5 nonmucinous, and 6 sclerosing) and 30 CPAs. The mucinous and nonmucinous BACs demonstrated neoplastic epithelial cells growing along a continuous basement membrane. A similar growth pattern with intact basement membrane was noted in the periphery of sclerosing BACs. However, in contrast to mucinous and nonmucinous BACs, all cases of sclerosing BACs showed disruption or complete absence of basement membrane components (laminin and collagen IV) around the embedded glands located centrally in the sclerotic fibrous stroma, as was seen in the basement membrane analysis of conventional adenocarcinomas. Furthermore, increased type IV collagenase activity was seen in the small centrally located embedded glands in comparison to the peripheral glands. These architectural alterations of basement membrane disruption and phenotypic expression of degradative activity may be a reflection of the invasive behavior of the sclerosing BACs and their tendency to produce lymph node metastasis. Although the mucinous BACs did not show evidence of basement membrane disruption, there was a marked increase in their levels of type IV collagenase expression along with consistently low levels of alpha 2 integrin receptor (laminin and collagen IV receptor) expression. These findings may be related to the ability of the mucinous BACs to detach from the underlying basement membrane and spread aerogenously, and is to be contrasted with the stromal infiltration and desmoplasia of sclerosing BACs and CPAs.
PURPOSE: A phase II trial that uses liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in patients with relapsed osteosarcoma is underway. To determine if in vivo cytokine induction plays a role in the mechanism of action of L-MTP-PE, we investigated the circulating cytokine levels of 16 patients who were undergoing therapy. PATIENTS AND METHODS: Patients had histologically proven osteosarcoma and pulmonary metastases that developed either during adjuvant chemotherapy or that were present at diagnosis and persisted despite chemotherapy. Patients were rendered disease-free by surgery. The major goal of the study was to improve the disease-free interval in this high-risk group. L-MTP-PE 2 mg/m2 was infused during a 1-hour period twice a week for 12 weeks, then once a week for 12 weeks. Serial blood samples were collected after L-MTP-PE administration and were assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha] interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-6, interferon-gamma [IFN-gamma], neopterin, C-reactive protein). RESULTS: After the infusion of L-MTP-PE, there was rapid induction of circulating TNF alpha and IL-6. TNF alpha levels peaked 1 to 2 hours after infusion in 10 of 16 patients, whereas peak IL-6 levels were detected at 2 to 3 hours in all patients. Induction of circulating TNF alpha and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL-1 alpha nor IL-1 beta was detected in the plasma. Neopterin levels increased at 24 hours postinfusion, which indicated macrophage activation, and were not related to the induction of circulating IFN-gamma. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNF alpha and IL-6, elevations in C-reactive protein and neopterin could be detected throughout the treatment course. CONCLUSION: It is concluded that L-MTP-PE has specific biologic effects in patients with osteosarcoma that may be important to the drug's immunostimulatory capacity and its effectiveness as an antitumor agent.