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Biomedical subjects

L Klassen

Publications and source records attributed to L Klassen.

10 recordsLinked to original sources
PubMed1999

Herpes zoster and multiple sclerosis.

BACKGROUND: Clinical experience suggests that young multiple sclerosis patients may have herpes zoster (HZ) earlier and more often than the general population. As there is evidence of a relationship between varicella zoster virus (VZV) and MS, a study of HZ and MS was undertaken. METHODS: Eight hundred and twenty-nine patient-members of the Manitoba Chapter of the Canadian Multiple Sclerosis Society were surveyed by mail. Six hundred and thirty-three (76%) responded. Questions included: age at diagnosis of MS, history of HZ (yes, no, probably), number of episodes of HZ and age at each occurrence, date of birth, and sex of respondent. The controls were consecutive patients with other neurological diseases (OND) attending local neurological or neurosurgical clinics, plus practice-based and population-based surveys of herpes zoster without reference to any other disease. The OND controls were assessed at the time of their outpatient visits. RESULTS: In the MS group with a positive/probable history of HZ, the HZ/MS rate was 106/633 (16.8%); in the practice-based survey the rate was 192/3534 (5.4%); and among the patients with OND it was 42/616 (6.8%). The HZ occurred at an earlier age in the MS group. The majority of male patients had HZ prior to the diagnosis of MS. The date of diagnosis is more likely to be a precise memory as opposed to the onset of symptoms. More than one attack of HZ was also more common in the MS group. CONCLUSIONS: This survey adds to the evidence that patients with MS have a unique relationship with the herpes zoster virus.

Adolescent↗
PubMed1998

Vagus nerve stimulation therapy: nurses role in a collaborative approach to a program.

Approximately 300,000 Canadians have epilepsy. Of those 30 percent fail to achieve satisfactory seizure control with current antiepileptic drug therapy (Vagus Nerve Stimulator Study Group, 1995). The development and availability of new therapeutic options cannot be overlooked for medically intractable patients. Chronic Vagus Nerve Stimulation (VNS) has demonstrated a 50 percent reduction in seizure frequency in 1/3 of patients with refractory partial onset seizures (Uthman, et al, 1993). Individuals undergoing this procedure require the attention of health care professionals from both the neurological and neurosurgical programs. This unique intervention demands that the patient's device be tested intra-operative, and programming begin during the immediate post-operative phase. Assessment of tolerance and side effects to vagus nerve stimulation therapy, as well as continued evaluation of the patients seizure control are necessary to direct staged programming of the device. This poster will demonstrate how the nurses from the neurology and neurosurgery clinics have been able to collaborate to ensure patients needs are met. Patient education is crucial to assisting the patient through this procedure, and key points will be identified. The implementation of coordinating the approach for programming the patient's device will be depicted. Future recommendations for long-term outcome measurement will be addressed.

Continuity of Patient Care↗
PubMed1995

Immunologic effects of levamisole in mice and humans: evidence for augmented antibody response without modulation of cellular cytotoxicity.

Selected immunomodulatory effects of levamisole were studied in patients with asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice treated with methyl-azoxymethanol acetate) for colon tumors. In the patient population studied, there was no augmentation of cellular cytotoxicity or alteration in lymphocyte subpopulations that participate in these functions. An increase in Fc receptor binding on circulating monocytes was apparent at the 4-week timepoint; however, a corresponding increase in antibody-dependent cellular cytotoxicity was observed in only one of the six patients studied. In most patients, cellular cytotoxicity diminished with time. No significant effects on cellular immunity or carcinogenesis were observed in our murine studies. However, treatment with levamisole did increase circulating immunoglobulin levels and IgM response in mice immunized with the T-dependent antigen keyhole limpet hemocyanin. This parameter was not tested in the human trial. Failure to demonstrate antitumor effects on cellular immunity by levamisole in both human and murine studies suggests that these effects, if they do exist, may involve immunological parameters that were not tested using our methods or that may not be apparent in patients with more advanced malignancy.

Adenocarcinoma↗
PubMed1991

Improved results of allogeneic bone marrow transplantation for advanced hematologic malignancy using busulfan, cyclophosphamide and etoposide as cytoreductive and immunosuppressive therapy.

Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02).

Adolescent↗
PubMed1990

Phase II trial of interferon gamma and monoclonal antibody 17-1A in pancreatic cancer: biologic and clinical effects.

Thirty patients with advanced measurable pancreatic adenocarcinoma were entered onto a phase II trial with recombinant interferon gamma (Biogen, Cambridge, MA; 10(6) U/m2 daily for 4 days) and monoclonal antibody (Mab) 17-1A (Centocor, Malvern, PA; 150 mg in autologous leukocytes on days 2, 3, and 4 following interferon infusion). The effect of a single interferon gamma treatment on natural and antibody-dependent cellular cytotoxicity (ADCC), Fc receptor occupancy by antibody, and human leukocyte antigen-DR (HLA-DR) expression on monocytes and lymphocytes was also studied. Toxicity was modest and generally limited to grade I to II fever, nausea and vomiting, and hepatotoxicity. Five patients were considered to be nonassessable for response. Of the 25 assessable patients, one objective response (complete remission for a duration of 4 months) was observed. Stable disease for 2 months or greater was noted in nine patients. The median survival for the group was 5 months. Analysis of cytotoxicity data obtained prior to treatment showed reduced natural cytotoxic activity in these patients compared with normal volunteers. A significant improvement in natural cytotoxic activity to normal levels occurred within 24 hours following the interferon gamma infusion. This was also associated with augmented antibody-dependent cellular cytotoxicity. Although HLA-DR expression was not increased on either monocytes or lymphocytes, an increased capacity of both lymphocytes and monocytes to bind Mab 17-1A was observed. In all in vitro assays of ADCC, the presence of antibody excess was associated with improved cytolytic activity. In spite of the favorable modulation of cytolytic activity and improved ability of effector cells to bind Mab, we failed to demonstrated adequate clinical efficacy in the treatment of patients with pancreatic adenocarcinoma using this dose and schedule of interferon gamma and Mab 17-1A. Future trials will focus on alternate schedules of Mab 17-1A with the hope of improving tumor antigen saturation and circulating levels of infused antibody.

Adenocarcinoma↗
PubMed1986

Interleukin-2-induced chemotaxis of human T-lymphocytes.

Interleukin-2 (IL-2), a growth factor for T-lymphocytes, has been postulated to cause the accumulation of T-lymphocytes at sites of inflammation by inducing proliferation of these cells. We hypothesized that IL-2 might also serve to attract T-lymphocytes to inflammatory sites. To test this hypothesis, human T-lymphocytes were purified from the peripheral blood of normal volunteers by rosetting with neuraminidase-treated sheep red blood cells and tested for chemotactic activity by using a blind-well chamber technique. Purified IL-2 caused a greater than 20-fold attraction of T-lymphocytes compared with medium alone (P less than 0.001). This attraction was shown to be chemotactic rather than chemokinetic by checkerboard analysis. The T-lymphocyte chemotaxis could be completely inhibited by adsorption of the IL-2 with an IL-2-dependent cell line, and could be neutralized by monoclonal anti-IL-2 antibody. Further specificity of IL-2-directed chemotaxis was demonstrated by using species-specific IL-2. Mouse IL-2 was ineffective at promoting human T-lymphocyte chemotaxis. These data suggest that IL-2 may be responsible for the localized accumulation of T-lymphocytes both by causing attraction of these cells and by modulating their proliferation.

Animals↗
PubMed1985

Studies in metachromatic leukodystrophy: XV. Purification of normal and mutant arylsulfatase A from human liver.

In this report we describe a method to purify both normal and abnormal (inactive) arylsulfatase A. The abnormal enzyme protein was isolated both from cases of late infantile and early juvenile forms of metachromatic leukodystrophy. Conventional protein isolation methods reported earlier were followed by size exclusion high-performance liquid chromatography in the final purification stages. Both the mutant enzyme and the normal enzyme had the same HPLC elution behavior. They thus appeared to self-associate in a similar pH-dependent fashion. Both could be followed by their reaction to a rabbit antibody to normal human arylsulfatase A. The amount of homogenous protein obtained from about 500 grams of liver was 300-400 micrograms.

Cerebroside-Sulfatase↗
PubMed1981

Human suppressor cells: evidence of functionally distinct subsets.

Human suppressor cells (SC) differing in both kinetic characteristics and degree of specificity were induced in vitro either by Concanavalin A (CON A) (10 microgram/ml) or by repeated stimulation with allogeneic cells. CON A SC caused a characteristic early peak in blastogenesis (Day 2) when cocultured with fresh autologous cells in the presence of either CON A or augmented response fell rapidly to values 50--90% below positive controls by the usual optimal day for the particular stimulus. Treatment with 5-bromodeoxyuridine and light during rapid proliferation ablated the early responses but increased the later responses (i.e., reduced the suppression). The cells mediating both the early rise and late suppression were found to belong to a subset of T cells that lost their ability to form SRBC rosettes (theophylline sensitive) in the presence of the phosphodiesterase inhibitor, theophylline, and were inactivated by mitomycin C. In contrast, SC induced by repeated allogenic stimulation were suppressive in MLC but not CON A cultures, did not initiate early blastogenesis in the presence of naive cells and were partially mitomycin resistant. The mitomycin resistant SC induced by allogeneic stimulation are found in the theophylline resistant T-cell subset. These data are consistent with a model of human SC differentiation in which at least two subsets may be present: (1) a mitomycin sensitive, nonspecific cell that participates in an obligatory early autologous recognition event (induction?) and (2) a later occurring, more mitomycin resistant effector cell that appears to acquire specificity for the response that it affects.

Bromodeoxyuridine↗