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Biomedical subjects

A Lazenby

Publications and source records attributed to A Lazenby.

At least 19 recordsLinked to original sources
PubMed2001

Use of the 'real-ear to dial difference' to derive real-ear SPL from hearing level obtained with insert earphones.

The electroacoustic characteristics of a hearing instrument are normally selected for individuals using data obtained during audiological assessment. The precise inter-relationship between the electroacoustic and audiometric variables is most readily appreciated when they have been measured at the same reference point, such as the tympanic membrane. However, it is not always possible to obtain the real-ear sound pressure level (SPL) directly if this is below the noise floor of the probe-tube microphone system or if the subject is unco-operative. The real-ear SPL may be derived by adding the subject's real-ear to dial difference (REDD) acoustic transform to the audiometer dial setting. The aim of the present study was to confirm the validity of the Audioscan RM500 to measure the REDD with the ER-3A insert earphone. A probe-tube microphone was used to measure the real-ear SPL and REDD from the right ears of 16 adult subjects ranging in age from 22 to 41 years (mean age 27 years). Measurements were made from 0.25 kHz to 6 kHz at a dial setting of 70 dB with an ER-3A insert earphone and two earmould configurations: the EAR-LINK foam ear-tip and the subjects' customized skeleton earmoulds. Mean REDD varied as a function of frequency but was typically approximately 12 dB with a standard deviation (SD) of +/- 1.7 dB and +/- 2.7 dB for the foam ear-tip and customized earmould, respectively. The mean test-retest difference of the REDD varied with frequency but was typically 0.5 dB (SD 1 dB). Over the frequency range 0.5-4 kHz, the derived values were found to be within 5 dB of the measured values in 95% of subjects when using the EAR-LINK foam ear-tip and within 4 dB when using the skeleton earmould. The individually measured REDD transform can be used in clinical practice to derive a valid estimate of real-ear SPL when it has not been possible to measure this directly.

Acoustic Stimulation↗
PubMed2000

Colitis induced by enteric bacterial antigen-specific CD4+ T cells requires CD40-CD40 ligand interactions for a sustained increase in mucosal IL-12.

C3H/HeJBir is a mouse substrain that is highly susceptible to colitis. Their CD4+ T cells react to Ags of the commensal enteric bacteria, and the latter can mediate colitis when activated by these Ags and transferred to histocompatible scid recipients. In this study, multiple long-term C3H/HeJBir CD4+ T cell (Bir) lines reactive to commensal enteric bacterial Ags have been generated. All these were Ag specific, pauciclonal, and Th1 predominant; most induced colitis uniformly after transfer to scid recipients. Lesions were focal and marked by increased expression of IL-12p40 and IFN-gamma mRNA and protein. Pathogenic Bir T cell lines expressed CD40 ligand (CD40L) when cultured with Ag-pulsed APCs in vitro. Production of IL-12 was also increased in such cultures, an effect that was Ag- and T cell-dependent and required costimulation by CD40, but not by B7. The two Bir T cell lines that did not induce lesions after transfer failed to significantly express CD40L or increase IL-12 when cultured with Ag-pulsed APCs. Administration of anti-CD40L blocked disease expression induced by pathogenic T cells. We conclude that interactions in the colon mucosa between CD40L-expressing Bir Th1 cells with APCs endogenously loaded with commensal bacterial Ags are critical for sustained increases in local IL-12 production and progression to colitis.

Adoptive Transfer↗
PubMed2000

A prospective trial of telepathology for intraoperative consultation (frozen sections).

Telepathology is a maturing technology that, for a variety of reasons, has not been widely deployed. In addition, clinical validation is relatively modest compared with accepted telemedicine applications such as teleradiology. A prototype telepathology system (Tele-Path(sm)) featuring high-resolution images selected from a remote microscope site has been developed at the University of Alabama at Birmingham (UAB). To validate the diagnostic efficacy of the system, a prospective study was undertaken of parallel diagnoses by conventional microscopy and telepathology with a remotely operated microscope. Slides from 99 intraoperative consultations from 29 tissue/ organ sites in the University of Alabama Hospitals by 9 academic pathologists were used in the study. Each microscopic and telepathology diagnosis was compared with the final diagnosis rendered by a referee pathologist. Diagnoses were classified as correct, false positive, or false negative or classification error. Of the 99 frozen sections evaluated, 3 cases were deferred. Of the remaining 96 cases, 2 received incorrect diagnoses in both the microscopic and telepathology arms of the study. Three errors occurred only in the telepathology arm. There was 1 false-positive diagnosis, 1 false-negative diagnosis, and 1 classification error. Statistical analysis indicated no significant difference between telepathology and conventional microscopy. Qualitative data indicated that the pathologists were generally satisfied with the performance of the system. Telepathology using this system paradigm is sufficiently accurate for real time utilization in a complex surgical environment. Telepathology therefore may be an effective model to support the surgical services of hospitals lacking full-time pathology coverage, resulting in full-time access to anatomic pathology services.

Diagnostic Errors↗
PubMed1998

CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease.

C3H/HeJBir mice are a new substrain that spontaneously develop colitis early in life. This study was done to determine the T cell reactivity of C3H/HeJBir mice to candidate antigens that might be involved in their disease. C3H/HeJBir CD4+ T cells were strongly reactive to antigens of the enteric bacterial flora, but not to epithelial or food antigens. The stimulatory material in the enteric bacteria was trypsin sensitive and restricted by class II major histocompatibility complex molecules, but did not have the properties of a superantigen. The precursor frequency of interleuken (IL)-2-producing, bacterial-reactive CD4+ T cells in colitic mice was 1 out of 2,000 compared to 1 out of 20,000-25,000 in noncolitic control mice. These T cells produced predominately IL-2 and interferon gamma, consistent with a T helper type 1 cell response and were present at 3-4 wk, the age of onset of the colitis. Adoptive transfer of bacterial-antigen-activated CD4+ T cells from colitic C3H/HeJBir but not from control C3H/HeJ mice into C3H/HeSnJ scid/scid recipients induced colitis. These data represent a direct demonstration that T cells reactive with conventional antigens of the enteric bacterial flora can mediate chronic inflammatory bowel disease.

Adoptive Transfer↗
PubMed1998

Cytomegalovirus colitis in acquired immunodeficiency syndrome: a clinical and endoscopic study.

BACKGROUND: Cytomegalovirus colitis is an important complication of the acquired immunodeficiency syndrome (AIDS), although the clinical and colonoscopic manifestations of this disease have not been systematically characterized. METHODS: Patients with AIDS and cytomegalovirus colitis were prospectively identified at two medical centers. The diagnosis of cytomegalovirus disease was based on established endoscopic and histologic criteria. At the time of sigmoidoscopic and/or colonoscopic examination, clinical features were recorded; the location, size, and appearance of all endoscopic abnormalities were documented; and multiple biopsies of any lesions were performed. RESULTS: Fifty-six patients were studied. The majority of the patients were homosexual men with severe immunodeficiency (median CD4 lymphocyte count 15/mm3, range 1 to 294/mm3). Chronic diarrhea and abdominal pain were the most frequent clinical manifestations, seen in 45 (80%) and 28 (50%) patients, respectively. Five patients (9%) presented with lower gastrointestinal hemorrhage, three of whom had no antecedent history of diarrhea. The colonoscopic abnormalities could be categorized into three main groups: colitis associated with ulcer (39%), ulceration alone (38%), or colitis alone (20%). Subepithelial hemorrhage was a prominent endoscopic manifestation of disease. Of the 31 patients undergoing colonoscopy to the cecum, in four (13%) endoscopic evidence of disease was limited to the colon proximal to the splenic flexure. CONCLUSIONS: Cytomegalovirus colitis in AIDS appears to have variable but stereotypical clinical and colonoscopic manifestations. Distal colitis associated with ulceration is the most common colonoscopic pattern.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A recombinant Listeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour cell challenge and causes regression of established tumours.

Listeria monocytogenes is an intracellular organism that has the unusual ability to live in the cytoplasm of the cell. It is thus a good vector for targeting protein antigens to the cellular arm of the immune response. Here we use a model system, consisting of colon and renal carcinomas that express the influenza virus nucleoprotein and a recombinant L. monocytogenes that secrets this antigen, to test the potential of this organism as a cancer immunotherapeutic agent. We show that this recombinant organism can not only protect mice against lethal challenge with tumour cells that express the antigen, but can also cause regression of established macroscopic tumours in an antigen-specific T-cell-dependent manner.

Animals↗
PubMed1995

Enterotoxigenic Bacteroides fragilis.

Enterotoxigenic Bacteroides fragilis (ETBF) has been recently associated with watery diarrheal disease in livestock and young children. These strains of B. fragilis secrete an extracellular heat-labile protein toxin with a mess of approximately 20 kD. This toxin has been shown to have two major biological activities: stimulation of secretion in ligated intestinal segments in lambs and calves and alteration of the morphology of intestinal epithelial cell lines in vitro. In vivo the pathology of animal intestine exposed to an ETBF strain is disruption of the colonic epithelium with rounded, swollen surface epithelial cells. Similarly, in vitro intestinal epithelial cells derived from human colonic carcinomas become rounded and detach from neighboring cells after treatment with the ETBF toxin. These results suggest that the ETBF toxin is a secretory cytoskeleton-altering toxin. However, the contribution of the ETBF toxin to the pathogenesis of ETBF-associated diarrheal disease remains to be determined.

Animals↗
PubMed1995

Graft-versus-host-like colitis associated with malignant thymoma.

A case of a patient with a malignant thymoma who developed an unusual form of colitis is reported. The patient was a previously healthy 20-year-old man who was referred to the Johns Hopkins Medical Institution for biopsy and resection of a mediastinal mass, which proved to be a malignant thymoma. During this hospitalization and subsequently, the patient developed severe chronic diarrhea, the etiology of which remained uncertain after routine work-up, including cultures. Colonoscopic biopsies revealed only minimal inflammation but numerous, prominent apoptotic lesions within crypt epithelium, suggestive of an autoimmune or graft-versus-host-like colitis. The patient, who was immunocompetent and human immunodeficiency virus (HIV) negative, had no known risk factors for graft-versus-host-disease (e.g., no blood transfusions, no transplantation history before diarrheal episodes). Stool cultures for pathogenic bacteria and viruses were negative. The diarrhea and histologic findings eventually improved with steroid therapy yet returned on recurrence of the thymoma. This unusual form of colitis has not been previously reported to be associated with thymoma and is interesting in light of the role the thymus plays in immune regulation.

Adult↗
PubMed1994

In vivo priming of two distinct antitumor effector populations: the role of MHC class I expression.

Downregulation of major histocompatibility complex (MHC) class I expression is an important mechanism by which tumors evade classical T cell-dependent immune responses. Therefore, a system was designed to evaluate parameters for active immunization against MHC class I- tumors. Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine. This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells. A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells. This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene. Finally, class I MHC expression on the vaccinating cells inhibited the response generated against a MHC class I- tumor challenge. These results demonstrate that the host is capable of being immunized against a tumor that has lost MHC class I expression and reveal conditions under which distinct effector cells play a role in the systemic antitumor immune response.

Animals↗
PubMed1993

Controlled release, biodegradable cytokine depots: a new approach in cancer vaccine design.

Experimental studies using murine tumor models have demonstrated that potent systemic immunity can be generated using tumor vaccines engineered by gene transfer to secrete certain cytokines. The underlying physiological principle behind these strategies involves the sustained release of high doses of cytokine at the site of the tumor. In some cases, this paracrine approach appears to enhance tumor antigen presentation and avoids systemic cytokine toxicity. The widespread clinical use of autologous cytokine gene transduced tumor vaccines may be limited by the technical difficulty and labor intensity of individualized gene transfer. We have therefore explored an alternate approach to generating sustained release of cytokines local to the tumor cells. High doses of granulocyte-macrophage colony-stimulating factor encapsulated in cell-sized gelatin-chondroitin sulfate microspheres were mixed with irradiated tumor cells prior to s.c. injection. This vaccination scheme resulted in systemic anti-tumor immune responses comparable to granulocyte-macrophage colony-stimulating factor gene transduced tumor vaccines.

Animals↗
PubMed1993

Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.

To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

Animals↗
PubMed1989

AIDS in infancy: diagnostic, therapeutic, and ethical problems.

Congenital AIDS is on the rise and will pose multiple problems to society and to health care workers in particular, as more infants develop the disorder. Differentiation of AIDS from infantile grief reactions is of critical importance, as infants at risk for AIDS lose their mothers who have AIDS. Team approaches are optimal and should include psychiatric perspectives. Issues of diagnosis, maladaptive psychological reactions and ethical dilemmas are discussed and illustrated in a case history.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Collagenous colitis, enteropathic arthritis, and autoimmune diseases: results of a patient survey.

We surveyed all patients with collagenous colitis seen at Johns Hopkins over a 4-year period, using a standardized, previously validated telephone questionnaire. Of 29 patients, 2(7%), including the index case, had monoarticular reactive arthritis. Five additional patients (17%) had a coexisting autoimmune illness. Collagenous colitis should be added to the list of causes of enteropathic arthritis. In addition, collagenous colitis should be considered in the differential diagnosis of diarrhea occurring in patients with known autoimmune diseases.

Aged↗
PubMedDate not supplied

Carcinoid tumor of the hepatic duct presenting as a Klatskin tumor in an adolescent and review of world literature.

This is a case presentation of a 14-year-old boy with the radiological diagnosis of cholangiocarcinoma occluding the hepatic duct bifurcation. His only symptom at presentation was jaundice and further workup confirmed a mass at the porta hepatis. Surgical treatment resulted in a resection of the hepatic bifurcation tumor with a final pathological diagnosis of a carcinoid tumor of the hepatic duct bifurcation. To our knowledge, this is only the second case presented of a resected carcinoid tumor in adolescence. In this communiqué we present the above case and review of the world literature of biliary neuroendocrine tumors.

Adolescent↗