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Biomedical subjects

J Koziol

Publications and source records attributed to J Koziol.

At least 19 recordsLinked to original sources
PubMed2005

Autoimmune thrombocytopenia: flow cytometric determination of platelet-associated autoantibodies against platelet-specific receptors.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antibody-induced platelet destruction. Despite its clinical importance, the diagnosis of ITP is one of exclusion, thus, inevitably associated with potential difficulties. We here describe a feasible diagnostic method using the commonly available technique of flow cytometry. An antigen-specific assay for platelet-associated antibody was developed and tested in 62 adult patients with chronic ITP, 14 patients with thrombocytopenia of decreased production and 60 healthy controls. The method is based on flow cytometric (FCM) detection of autoantibodies reacting with specific platelet receptors immobilized on microbeads. The average fluorescence level in the ITP group calculated as a ratio to normal was 4.07 (range 0.8-31.0), in the non-ITP thrombocytopenic patients 0.9 (range 0.7-1.2), and in the healthy controls 1.0 (range 0.7-1.3). The average assay coefficient of variation was 0.218 [95% confidence interval (CI) 0.213, 0.221]. The difference between the ITP patients and both groups was highly significant (P < 0.001), using a stringent non-parametric analysis. A comparison of the FCM assay with the radioactive immunobead assay previously reported on the same cohort of patients showed significant correlation (R2 = 0.71, 95% CI 0.39, 0.53). The overall performance of the FCM assay in discriminating between ITP patients and normals was estimated by the receiver operating characteristic (ROC) plot, showing an area under the curve of 0.96 (maximal value 1.0), with standard error of 0.033. We conclude that the present FCM assay is clinically useful for routine diagnosis and follow-up of ITP.

Area Under Curve↗
PubMed2000

Induced genome instability as a potential screening test for cancer susceptibility?

The variety of mutations associated with carcinogenesis, along with variations in penetrance and environmental factors, complicate the genetic screening for cancer predisposition. It is proposed here that the detection of inherent genome instability as determined by increased mutagen susceptibility may enhance the identification of populations at risk for cancer. In support for this hypothesis, our analysis reveals a strong association between mutagen-induced chromosomal instability in peripheral blood lymphocytes and the propensity for cancers of oral cavity, pharynx, larynx, and lung. DNA instability in response to a variety of mutagens identifies patients with gastrointestinal, brain, endocrine, breast, skin, and hematologic tumors as well as individuals with cancer family syndromes. Induced genome instability therefore appears to be strongly linked to cancer predisposition, and prospective studies may yield a screening test utilizing a panel of mutagens to better identify populations at risk.

Chromosomes, Human↗
PubMed1996

[Evaluation of magnesium, zinc, copper and calcium levels in workers exposed to organic solvents, hydrogen cyanide and harmful physical factors].

UNLABELLED: The aim of the work was to assess te effect of chronic occupational exposure to organic solvents, hydrogen cyanide, and harmful physical factors (noise, vibration and electromagnetic fields) on intra- and extracellular concentration of magnesium, zinc, copper and calcium. The study converted 83 persons (25 males and 57 females), aged 20-58 years (median: 37.8 +/- 8.64), employed in the MERA PAFAL SA Factory of Measuring Equipment, Swidnica, for 0.42 +/- 34 years (median: 11.84 +/- 9.28). The subjects were divided into four groups: Group A-25 persons exposed to organic solvents; Group B-24 persons exposed to hydrogen cyanide; Group C-19 persons exposed to noise and vibration; and Group D-8 persons exposed to electromagnetic fields. Blood samples (10 ml) were collected from each person. Intra- and extracellular concentrations of magnesium, zinc, copper and calcium were estimated. CONCLUSIONS: exposure to 1) organic solvents induces depletion of calcium and zinc from the body and intracellular cumulation of magnesium; 2) to hydrogen cyanide induces depletion of intracellular zinc and intracellular cumulation of magnesium and zinc; 3) to noise and vibration induces depletion of calcium, zinc and copper and intracellular cumulation of magnesium; and 4) electromagnetic fields does not induce any significant changes in ionic concentrations.

Adult↗
PubMed1995

Sleep electroencephalogram delta-frequency amplitude, night plasma levels of tumor necrosis factor alpha, and human immunodeficiency virus infection.

We tested the hypothesis that increases in tumor necrosis factor alpha (TNF-alpha) induced by human immunodeficiency virus (HIV) are associated with the increases in slow-wave sleep seen in early HIV infection and the decrease with sleep fragmentation seen in advanced HIV infection. Nocturnal sleep disturbances and associated fatigue contribute to the disability of HIV infection. TNF-alpha causes fatigue in clinical use and promotes slow-wave sleep in animal models. With slow progress toward a vaccine and weak effects from current therapies, efforts are directed toward extending productive life of HIV-infected individuals and shortening the duration of disability in terminal illness. We describe previously unrecognized nocturnal cyclic variations in plasma levels of TNF-alpha in all subjects. In 6 of 10 subjects (1 control subject, 3 HIV-seropositive patients with CD4+ cell number > 400 cells per microliters, and 2 HIV-positive patients with CD4+ cell number < 400 cells per microliters), these fluctuations in TNF-alpha were coupled to the known rhythm of electroencephalogram delta amplitude (square root of power) during sleep. This coupling was not present in 3 HIV-positive subjects with CD4+ cell number < 400 cells per microliters and 1 control subject. In 5 HIV subjects with abnormally low CD4+ cell counts ( < 400 cells per microliters), the number of days since seroconversion correlated significantly with low correlation between TNF-alpha and delta amplitude. We conclude that a previously unrecognized normal, physiological coupling exists between TNF-alpha and delta amplitude during sleep and that the lessened likelihood of this coupling in progressive HIV infection may be important in understanding fatigue-related symptoms and disabilities.

Adult↗
PubMed1995

2-Chlorodeoxyadenosine activity in patients with untreated, indolent non-Hodgkin's lymphoma.

Based on the encouraging results of the use of 2-chlorodeoxyadenosine ([2-CdA], cladribine) in patients with advanced, low-grade lymphomas resistant to conventional therapy and the acceptable toxicity profile encountered, we conducted a phase II trial of 2-CdA in patients with untreated indolent lymphomas. Twenty-eight patients with untreated low-grade lymphomas were given 2-CdA at 0.1 mg/kg/d as a 7-day continuous infusion every 28 to 35 days. A total of 89 courses, median of three courses per patient, of 2-CdA were administered. Seventeen men and 11 women with a median age of 58 years were treated. Fifteen patients had diffuse small lymphocytic (8 with plasmacytoid features), 10 had follicular small cleaved-cell, and there were single patients with monocytoid B-cell, mantle cell and mucosa-associated lymphoid tissue (MALT) lymphoma histologies. All 28 patients were evaluable for toxicity and 26 were evaluable for response. Nine (35%) patients (4 with diffuse small lymphocytic, 3 with follicular small cleaved-cell, 1 with mantle cell, and 1 with MALT lymphoma) achieved a complete response, and 14 (54%) patients (8 with diffuse small lymphocytic, 5 with follicular small cleaved-cell, and 1 with monocytoid B-cell lymphoma) achieved a partial response, for an overall response rate of 88%. The median response duration was 10 months (range, 3 to 44+). Myelosuppression was the principal toxicity. Actuarial survival at 60 months from initial diagnosis was 60% (95% confidence interval, 35% to 82%) and at 48 months from treatment onset was 62% (95% confidence interval, 39% to 83%). These results establish the major activity of 2-CdA in patients with untreated indolent lymphoma, especially those with the diffuse small lymphocytic subtype.

Actuarial Analysis↗
PubMed1995

Cytokine gene therapy with interleukin-2-transduced fibroblasts: effects of IL-2 dose on anti-tumor immunity.

We evaluated the effects of different doses of interleukin-2 (IL-2)-transduced fibroblasts in the treatment of colorectal carcinoma in the CT-26 murine tumor model. Immunization with a mixture of irradiated tumor cells and IL-2-transduced fibroblasts (100 units of IL-2/24 hr) induced significantly greater protection against a live tumor challenge compared to irradiated tumor cells alone (22/35, 65% vs. 10/30, 33%, p < 0.02). Protective effects were observed with doses of IL-2-transduced fibroblasts secreting from 5 to 100 units of IL-2/24 hr. Parallel experiments in nude mice produced no protection, indicating that the effects of immunization were mediated by a T-cell-dependent mechanism. In animals with established tumors, complete tumor remissions were observed following immunization with a mixture of irradiated tumor cells and IL-2-transduced fibroblasts secreting 100 units of IL-2/24 hr, but not after immunization with irradiated tumor cells alone (7/16 vs. 0/11 complete remissions, p < 0.02). Fibroblasts secreting higher doses of IL-2 were ineffective in generating systemic immunity, but were required to prevent tumor implantation. A statistically significant difference in the prevention of tumor implantation was observed between groups inoculated with a mixture of live tumor cells and IL-2-transduced fibroblasts (1,750 units of IL-2/24 hr) compared to control fibroblasts (6/8 vs. 0/12, p < 0.001). Similar results were observed in nude mice, suggesting that the implantation rejection response is mediated in part by cells other than thymus-derived T cells. Our data support the utility of IL-2-transduced fibroblasts and indicate that the level of IL-2 expression is an important variable in activating different effector components of antitumor immune responses in IL-2 gene therapy.

Adenocarcinoma↗
PubMed1995

Interleukin-2 gene therapy in a patient with glioblastoma.

A patient with glioblastoma multiforme (GBM) who had failed conventional therapy was treated with IL-2 gene therapy. The patient received 10 subcutaneous immunizations with autologous tumor cells and fibroblasts genetically modified to secrete IL-2 by retroviral gene transfer. An antitumor immune response mediated in part by CD8+ cytotoxic T cells was demonstrated with the patient's peripheral blood mononuclear cells. A magnetic resonance imaging (MRI) scan performed 4 weeks after the highest treatment dose revealed marked tumor necrosis. These results support the evaluation of this form of IL-2 gene therapy in additional patients with glioblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Interleukin-6 and interstitial cystitis.

We analyzed the presence of the cytokine interleukin-6 in urine samples from interstitial cystitis patients. Interleukin-6 was significantly elevated in patients with interstitial cystitis (169.29 +/- 90.81 pg./ml. versus 34.8 +/- 6.35 pg./ml. in controls). Representative urine samples were analyzed with specific antibody to interleukin-6 and greater than 80% of the biological activity was neutralized. These cytokine measurements were then compared with clinical parameters and interleukin-6 levels correlated positively with the pain scores. Studies on the potential cellular origin of interleukin-6 showed increased levels in spontaneously voided urine but not in ureteral urine, which was collected during cystoscopy, suggesting that interleukin-6 is the product of activated cells in the bladder. This finding is supported by in situ hybridization analyses, which showed that interleukin-6 messenger ribonucleic acid expressing cells are located in the interstitium and epithelial layer, and within blood vessels. The implications of these findings for interstitial cystitis pathogenesis are discussed.

Base Sequence↗
PubMed1994

Activation of urinary kallikrein in patients with interstitial cystitis.

A potential pathophysiological role for the urinary kallikrein-kinin system is suggested by the prominent symptoms of bladder pain and urinary frequency in interstitial cystitis. Kallikrein activity in the urine of 84 patients with interstitial cystitis and 33 normal volunteers was determined by cleavage of the synthetic substrate Val-Leu-Arg-pNA. Interstitial cystitis patients had significantly higher levels of kallikrein activity than did the normal volunteers. Kallikrein activity was correlated with symptoms of bladder pain and voiding frequency. The percentage of total urinary kallikrein in the active form correlated with active kallikrein levels and was also increased in interstitial cystitis patients, particularly those with higher levels of pain. Patients who underwent hydrodistention and subsequently experienced relief from the bladder symptoms had a decrease in urinary kallikrein levels, whereas patients who failed to improve following hydrodistention did not.

Adult↗
PubMed1991

The use of CT scanning to triage patients requiring admission following minimal head injury.

Recent data have suggested that patients with both a normal cranial CT scan and normal neurologic examination following minimal head injury (MHI) have no risk of neurologic deterioration. This study prospectively examined the safety of discharging patients from the emergency department (ED) after MHI whether or not there was a responsible observer at home. MHI was defined as a history of loss of consciousness (LOC), a Glasgow Coma Scale (GCS) score of 14 or 15, and no focal neurologic findings. In a 4-month period 111 patients with MHI were evaluated. Fifteen (14%) patients had a CT scan which revealed an intracerebral injury; 96 patients had a normal CT scan; five patients with normal CT scans were admitted because of persistent lethargy; and one patient was admitted after his CT that demonstrated an old infarct; the remaining 90 patients were discharged. There were 71 men and 19 women with a mean age of 29 years. The mechanism of injury was assault in 55, MVA in 30, and falls in five. The initial GCS in was 15 in 79 and 14 in 11. Fifty-eight per cent of patients were intoxicated. Fifty-seven (63%) patients were successfully contacted by telephone; none had developed any neurologic symptoms. Thirty-one patients who could not be followed up gave fictitious phone numbers. These data suggest that CT can reliably triage patients who can be discharged from the ED following MHI, even in the absence of a responsible observer. Hospital admission can be avoided in more than 80% of patients sustaining MHI, better utilizing scarce hospital resources.

Adolescent↗
PubMed1989

Durability of the viable aortic allograft.

Of 581 aortic allografts implanted since 1967, 421 were analyzed for structural deterioration. This series is unique in that it includes patients from the early allograft experience. All allografts were cleanly procured, antibiotic sterilized, and either stored at 4 degrees C for up to 8 weeks or frozen to liquid nitrogen temperatures with cryopreservation to preserve the viable cusp fibroblasts. There were 25 frozen mounted aortic valves with a median time to valve failure of 12.1 years, which was not significantly different from the 12.5-year period for 114 fresh free-sewn aortic valves. The median time to valve failure was 6.6 years for 90 fresh-mounted aortic valves and 8.6 years for 192 fresh-mounted mitral valves (p = 0.05). The difference between all mounted and unmounted grafts was significant (p = 0.0001). In all groups, viable fibroblasts were present in specimens explanted up to 5 years after the operation. All specimens returned after more than 10 years were almost totally acellular. Evidence of increased collagen, suggesting that the fibroblasts survive implantation and then gradually die, was present in all specimens. This series suggests that durability of the unmounted viable allograft for aortic valve replacement is greater than for other types of tissue valves. Pre-mounted allografts for aortic or mitral valve replacement have a median survival of 8 years and are not more durable than other tissue valves.

Aortic Valve↗
PubMed1988

Age-related macular degeneration and its management.

Age-related macular degeneration is a major cause of vision loss in older individuals. The clinical picture and pathogenesis of age-related macular degeneration is reviewed. Present treatment modalities for subretinal vascularization in exudative-type macular degeneration and their limitations are discussed. The role of low-vision aids in providing magnification for reading vision is described. The role of intraocular lens implantation is discussed, as well as the newly developed intraocular lens which, with the addition of a plus-lens, functions as a Galilean telescope to provide magnification for near vision.

Aged↗
PubMed1988

Experiences with an artificial sphincter to establish anal continence in dogs.

An implantable device for establishing urinary continence has been developed and has received FDA approval (AS 800, American Medical Systems, Inc.). The authors have applied this device to the control of anal continence in dogs. Fifteen mongrel dogs underwent either anal sphincter disruption (7) or abdominal-perineal resection (8). Such animals have bowel movements almost hourly. In each case, the device was implanted at the time of surgery. In dogs with working cuffs and disabled or absent sphincters, continence was maintained in seven out of 15 animals for periods of 4-8 hours. After cuff activation, intraluminal cuff pressures of 50-70 cm of water achieved continence for a period of 8 hours. In animals sacrificed from 1 to 12 months after implantation, the device was found to be well tolerated by the body with minimal fibrosis of the mucosa or muscularis of the bowel. Complications observed in the same four out of 15 animals during the study period were infection, device extrusion, and device malfunction. Infection resolved with local wound care and antibiotics (3/4) and the device was successfully replaced in two out of four instances of extrusion. With cuffs of proper size and pressure, this appliance may be effective in the control of human anal incontinence via the establishment of continent perineal colostomies following an abdominal-perineal resection.

Animals↗
PubMed1985

Analysis of incomplete multivariate data from repeated measurement experiments.

This paper analyses two sets of data that consist of repeated measurements with missing data. The missing observations always occur at the end of the series of repeated measurements. The score test for multivariate normal data is used to compare treatment groups; if the original data are not multivariate normal they are replaced by expected normal scores.

Animals↗
PubMed1983

Response of human myeloid leukemia cells to various sources of colony-stimulating activity and phytohemagglutinin-conditioned medium.

The response of human myeloid leukemia cells to various sources of colony-stimulating activity (CSA) and media conditioned by phytohemagglutinin-stimulated mononuclear cells (PHA-LCM) was investigated in liquid and colony culture. PHA-LCM, placenta-conditioned medium, GCT cell line-conditioned medium, leukocyte-conditioned medium, and partially purified CSA for human and murine cells were tested for ability to support growth of granulocyte-macrophage colonies from adherent cell-depleted human bone marrow. This activity was correlated with ability to support leukemia colony growth in methylcellulose, and [3H]thymidine incorporation in liquid culture by normal bone marrow cells, leukemia cells, and the KG-1 myeloid leukemia cell line. For normal cells, growth and liquid culture responses were highly correlated for various sources of CSA (r = 0.92), and addition of data using PHA-LCM changed results only slightly (r = 0.89). [3H]thymidine incorporation by leukemia cells from patients without a prior history of a myeloproliferative disorder was also highly correlated with normal CSA (r = 0.97) for sources other than PHA-LCM. Responses of leukemia blasts and KG-1 cells in liquid culture to PHA-LCM appeared in excess of its CSA for normal cells. Colony growth by leukemia cells was not clearly correlated with either liquid culture activity for leukemia cells or CSA for normal cells. PHA-LCM was also not statistically superior to placenta-conditioned medium as stimulus for leukemia colony growth, but was superior to placenta-conditioned medium for some patients. Differentiation in culture did not appear to depend on CSA source. We conclude that normal myeloid cells respond to CSA in a highly correlated fashion in both colony and liquid cultures. The majority of myeloid leukemia cells respond to either PHA-LCM or CSA, but the ability of PHA-LCM to support leukemia cell growth is greater than its CSA content. The possibility exists that overlapping populations responsive to CSA and to PHA-LCM are present simultaneously in patients with myeloid leukemia.

Bone Marrow↗
PubMed1983

Phase I-II study of 120-hour infused 5-FU and split-course radiation therapy in localized non-small cell lung cancer.

Thirty patients with locally advanced nonresectable non-small cell bronchogenic carcinoma were studied for tolerance and response to 120-hour continuously infused 5-FU (IFU) combined with chest x-ray therapy. The IFU was escalated in patient groups from 20 to 35 mg/kg/24 hours. Radiation was also escalated in patient subsets from 200 to 400 rads/fraction using a split-course technique to a total dose of 5000 rads. Tolerance was exceeded by IFU doses of 35 mg/kg/day. The complete response rate was ten of 28 patients (36%); a complete response was associated with a significantly prolonged survival. Radiosensitization of lung cancer by IFU appears clinically feasible in man.

Aged↗