ABSTRACT
Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates. INTRODUCTION: Hip fractures rank amongst the top 10 causes of disability and current mortality of hip fractures is high. Objectives were to determine 1) prevalence of cognitive impairment, 2) whether Montreal Cognitive Assessment (MoCA) score was an independent risk factor associated with mortality, 3) MoCA cut-off that result in high risk of mortality. METHODS: This was a cohort study between July 2019 to June 2020. Inclusion criteria were 1) hip fracture, 2) > = 65 years old, and 3) low-energy trauma. Patients undergo assessment for cognitive impairment with MoCA. Prevalence was assessed, MoCA cut-off point, and accuracy of statistical model was evaluated. Logistic regression modelling was used to assess association between mortality and MoCA. RESULTS: There were 260 patients recruited. Two hundred twenty-five patients had MoCA score < 22 signifying cognitive impairment, and 202 patients had MoCA score of < 19. 46 hip fracture patients died at 1-year follow-up. 45 of these patients had MoCA score < 19, and 1 patient had a MoCA > 22. Results showed statistical significance and good model effect (at least 0.8) with MoCA cut-off points between < 15 and < 19 (p < 0.05). After controlling confounding factors, statistical significance still existed in MoCA cut-off point at < 15 (odds ratio (95% CI) = 11.71 (1.14, 120.71); p = 0.04). CONCLUSION: Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality in hip fracture patients. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality at 1-year after a hip fracture. AUC with MoCA score < 15 was 0.948. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates.
Subject(s)
Cognitive Dysfunction , Hip Fractures , Aged , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Cohort Studies , Hip Fractures/complications , Humans , Mental Status and Dementia Tests , Neuropsychological Tests , Risk FactorsABSTRACT
During the COVID-19 pandemic, WHO and CDC suggest people stay 1 m and 1.8 m away from others, respectively. Keeping social distance can avoid close contact and mitigate infection spread. Many researchers suspect that suggested distances are not enough because aerosols can spread up to 7-8 m away. Despite the debate on social distance, these social distances rely on unobstructed respiratory activities such as coughing and sneezing. Differently, in this work, we focused on the most common but less studied aerosol spread from an obstructed cough. The flow dynamics of a cough jet blocked by the backrest and gasper jet in a cabin environment was characterized by the particle image velocimetry (PIV) technique. It was proved that the backrest and the gasper jet can prevent the front passenger from droplet spray in public transportation where maintaining social distance was difficult. A model was developed to describe the cough jet trajectory due to the gasper jet, which matched well with PIV results. It was found that buoyancy and inside droplets almost do not affect the short-range cough jet trajectory. Infection control measures were suggested for public transportation, including using backrest/gasper jet, installing localized exhaust, and surface cleaning of the backrest.
ABSTRACT
The data presented in this data article comprises the critical parameters of dispersion stability such as the particle effective diameter, zeta potential, sedimentation velocity and stability factor for Cu/Al2O3 single particle nanofluid and hybrid nanofluid samples at various ultra-sonication times, that is, 0.5â¯h, 1.0â¯h, 2.0â¯h and 3.0â¯h. The data for effective diameter and zeta potential was generated using the particle size analyser and zeta potential analyser respectively. The measured data for effective diameter and zeta potential was processed to generate the data for sedimentation velocity and stability factor. The ultra-sonication time with maximum value of stability factor was used for sample preparation of Cu/Al2O3 single particle nanofluid and hybrid nanofluid in the related research article "On trade-off for dispersion stability and thermal transport of Cu-Al2O3 hybrid nanofluid for various mixing ratios" (Siddiqui et al., 2019) [1].
ABSTRACT
The occurrence of SARS in March 2003 has resulted in an increased interest, worldwide in emerging infectious diseases. The SARS experience provided us a lesson on the importance of promoting hygienic practices among individuals and different working sectors. In Hong Kong, a voluntary organization called the UNITE proposed a Hygiene Charter which aimed at taking hygiene to new levels. This action has been supported by individuals and different sectors including the Personal and Family, Management, Buildings, Catering, Education, Finance and Commercial, Industrial, Medical and Health, Public Transportation, Social Welfare, Sports and Culture and Tourism. As promotion and maintenance of environmental health requires input from different sectors, the signing of the Hygiene Charter provides an opportunity for individuals and the public to show their pledge and commitment to good hygiene practices. As a result, with environment improvement and good infectious disease control measures, prevention of epidemics of infectious diseases is deemed to be possible.
Subject(s)
Environmental Health , Health Promotion/methods , Hygiene , Severe Acute Respiratory Syndrome/transmission , Adult , Female , Hong Kong , Humans , Male , Severe Acute Respiratory Syndrome/prevention & controlABSTRACT
BACKGROUND AND PURPOSE: Fecal occult blood tests (FOBT) and flexible sigmoidoscopy have previously been recommended for colon cancer screening. More recently, studies have recommended colonoscopy due to the high rates of advanced neoplasm not detected by FOBT and sigmoidoscopy. Previous studies of the effectiveness of colonoscopic screening in Taiwan were limited to families of patients with colorectal cancer. This study compared colonoscopy, sigmoidoscopy and FOBT for colorectal cancer screening in asymptomatic adults. METHODS: Screening colonoscopies and FOBT were performed in asymptomatic adults enrolled in our health-screening program between January 1997 and December 2000. Advanced neoplasm was defined as the presence of a polyp larger than 1 cm, polyps with villous or severe dysplastic features, or cancer. The junction of the splenic flexure and descending colon was defined as the boundary of the proximal and distal colon, and it was presumed that the distal colon would be examined using sigmoidoscopy in all patients. Data on the prevalence of polyps, advanced neoplasm, and cancer among different age groups were obtained. The results of chemical and immunologic FOBT were compared. The anatomic distributions of advanced neoplasm and cancer were analyzed. RESULTS: A total of 7,411 colonoscopic examinations were included in the analysis. Advanced neoplasms were present in 93 examinations (1.3%), including 16 cancers (0.2%). Chemical FOBT detected 20.2% of advanced neoplasms and 37.5% of cancers. Immunologic FOBT detected 48.3% of advanced neoplasms and 87.5% of cancers. If sigmoidoscopy had been performed in place of colonoscopy, 26.9% of advanced neoplasms and 12.5% of cancers would not have been detected. CONCLUSIONS: Colonoscopy can detect neoplastic lesions undetectable by FOBT and sigmoidoscopy in asymptomatic subjects. These results suggest that colonoscopy should be the method of choice in colon cancer screening.
Subject(s)
Colonoscopy , Colorectal Neoplasms/diagnosis , Occult Blood , Sigmoidoscopy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening , Middle AgedABSTRACT
OBJECTIVE: To develop a three-dimensional pre-surgical planner and an intraoperative guidance system for high tibial osteotomy. The parameters that describe the placement and orientation of the osteotomy resection planes were to be transmitted to an accompanying guidance system that allowed the surgeon to reproducibly perform the planned procedure. MATERIALS AND METHODS: The planning system and guidance system were coded using OpenGL on UNIX workstations. In vitro tests were performed to compare the reproducibility of the computer-enhanced technique to that of the traditional technique, and an in vivo pilot study was initiated. RESULTS: In vitro, the computer-enhanced technique produced a significant reduction, by one half, in both the maximum error of correction and the standard deviation of the correction error. Preliminary in vivo results on six patients suggest that similar error diminution will occur during regular clinical application of the technique. CONCLUSIONS: Both studies showed that the computer system is simple to use. The work suggests that three-dimensional planning and performance of high tibial osteotomy is essential for accurate correction of the alignment of the lower limb.
Subject(s)
Osteotomy/methods , Patient Care Planning , Therapy, Computer-Assisted , Tibia/surgery , Computer Simulation , Computer Systems , Humans , Image Processing, Computer-Assisted , Intraoperative Care , Joint Diseases/surgery , Knee Joint , Models, Anatomic , Osteotomy/instrumentation , Pilot Projects , Reproducibility of Results , Therapy, Computer-Assisted/instrumentation , Tibia/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , User-Computer InterfaceABSTRACT
A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.
Subject(s)
Interferon-gamma/adverse effects , 2',5'-Oligoadenylate Synthetase/metabolism , Adrenocorticotropic Hormone/blood , Adult , Aged , Antibody-Dependent Cell Cytotoxicity/immunology , Bone Marrow Cells , Colony-Forming Units Assay , Cytotoxicity, Immunologic , Dose-Response Relationship, Drug , Drug Evaluation , Female , Humans , Hydrocortisone/blood , Interferon-gamma/administration & dosage , Interferon-gamma/pharmacology , Killer Cells, Natural/immunology , Male , Middle Aged , Monocytes/immunology , Neoplasms/blood , Neoplasms/immunology , Neoplasms/pathology , Recombinant ProteinsABSTRACT
Viable hypoxic cells have reduced radiosensitivity and could be a potential cause for treatment failure with radiotherapy. The process of reoxygenation, which may occur after radiation exposure, could increase the probability for control. However, incomplete or insufficient reoxygenation may still be a potential cause for local treatment failure. One mechanism that has been thought to be responsible for reoxygenation is an increase in vascular prominence after radiation. However, the effect is known to be heterogeneous. In this study, tumor microvascular hemodynamics and morphologies were studied using the R3230 Ac mammary adenocarcinoma transplanted in a dorsal flap window chamber of the Fischer-344 rat. Measurements were made before and after (at 24 and 72 hr) 5-Gy radiation exposure to assess microvascular changes and to explore possible explanations for the heterogeneity of the effect. There was considerable heterogeneity between tumors prior to radiation. Vascular densities ranged from 67 to 3000 vessels/mm3 and median vessel diameters from 22 to 85 microns. Pretreatment perfusion values varied by a factor of six. In irradiated tumors, conjoint increases in both vascular density and perfusion occurred in most tumors, although the degree of change was variable from one individual to the next. The degree of change in density was inversely related to median pretreatment diameter. Relative change in flow, as predicted by morphometric measurements, overestimated observed changes in flow measured hemodynamically. These results support that heterogeneity in tumor vascular effects from radiation are somewhat dependent on pretreatment morphology as well as relative change in morphology. Since changes in flow could not be completely explained by morphometric measurements, however, it is likely that radiation induced changes in pressure and/or viscosity contribute to the overall effect. Further work in this laboratory will investigate these hypotheses.
Subject(s)
Adenocarcinoma/radiotherapy , Mammary Neoplasms, Experimental/radiotherapy , Microcirculation/radiation effects , Adenocarcinoma/blood supply , Animals , Mammary Neoplasms, Experimental/blood supply , Microcirculation/pathology , Microcirculation/physiopathology , Neoplasm Transplantation , Rats , Rats, Inbred F344 , Regional Blood Flow/radiation effectsABSTRACT
The purpose of this study was to compare microvascular morphometric and hemodynamic characteristics of a tumor and granulating normal tissue to develop quantitative data that could be used to predict microvascular characteristics which would be most likely associated with hypoxia. The dorsal flap window chamber of the Fisher 344 rat was used to visualize the microvasculature of 10 granulating and 12 tumor (R3230 AC adenocarcinoma) tissues at 2 weeks following surgical implantation of the chamber. Morphometric measurements were made from photomontages and video techniques were used to assess red cell velocities in individual vessels. The percent vascular volume of both tissues was close to 20%, but significant differences were noted in other morphometric and hemodynamic measurements. Individual vessel dimensions (length and diameter) in tumors averaged twice as large as those in granulating tissues. Furthermore, red cell velocities were twice as high in tumors as in granulating tissues. In addition to these large differences in average values, there was significant heterogeneity in tumor microvascular morphometry, indicating spatial nonuniformity compared with the granulating tissue. Approximations of vessel spacing, indicated an average of 257 and 118 microns in tumors and granulating tissues, respectively. Vessel densities were four times greater in granulating tissues than in tumor tissues. These results indicated that intervessel distances were more likely to result in hypoxia in tumors, especially considering the wide variability in that tissue. Analysis of flow branching patterns showed that vascular shunts occurred frequently in vessels ranging from 10 to 90 microns in diameter. The results of this study indicate, in this tumor model, that conditions such as low vascular density, vascular shunts, excessive vascular length and/or low red cell velocity exist to a greater extent than the granulating tissue control. These conditions are likely to be conductive to the development of hypoxia.
Subject(s)
Adenocarcinoma/blood supply , Mammary Neoplasms, Experimental/blood supply , Microcirculation/pathology , Animals , Blood Flow Velocity , Capillaries/pathology , Granulation Tissue/blood supply , Microcirculation/physiopathology , Rats , Rats, Inbred F344ABSTRACT
Review of clinical hyperthermia (HT) trial results shows that there previously has not been a robust model relating efficacy of HT treatments to characteristics of the temperature distribution. Lack of a model has been an impediment in Phase II trials; these trials must include defining the prescription for HT treatment, optimizing the schedule of HT treatments, and defining quality assurance procedures. We propose a model that is based upon noting that the majority of a tumor volume is contained in the outermost "shell" of a solid tumor, across which shell the radial temperature distribution is assumed to be linear. Any linear distribution can be defined by coordinates of a point and a slope, and we choose the temperature at the radiographically defined edge of a tumor and the slope (dT/dr) across the outer shell as these determinants of the linear radial temperature distribution. A discriminant analysis of success or failure of treatment can then be based upon these two descriptors (Tedge, dT/dr). We have tested this model using data from patients with soft tissue sarcoma (Stage IIB or greater) that have entered an ongoing prospective trial of conventional preoperative radiotherapy (5000 cGy/25 Fx/5 wk) together with HT, the latter randomized to be given once or twice weekly during the 5 week course. Wide local excision of the primary tumor is done 1 month after completion of radiotherapy, and the extent of histologic change in the resected specimen is scored. Our model has an 86% predictive value for lack of complete or nearly complete necrosis in the resected specimen according to whether the time-averaged Tedge and slope during each HT treatment satisfy the equation Tedge + 1.2 (slope in degree C/cm) less than or equal to 40.6 degrees C in all but one treatment at most. Conversely, in 85% of cases with complete or nearly complete tumor necrosis, temperature distributions satisfied Tedge + 1.2 (slope in degree C/cm) greater than 40.6 degrees C during at least one HT treatment. Requiring greater than or equal to one third of treatments of a patient to satisfy the preceeding discriminant equation resulted in 80% of patients being correctly classified as a responder or nonresponder, with only one false positive prediction (patient incorrectly classified as a responder). The model can reveal systematic changes in the edge temperature distribution during the treatment course that are consistent with tumor perfusion changes inferred and measured by independent means.(ABSTRACT TRUNCATED AT 400 WORDS)
Subject(s)
Body Temperature , Hyperthermia, Induced , Neoplasms/therapy , Clinical Trials as Topic , Combined Modality Therapy , Humans , Models, Biological , Neoplasms/radiotherapy , Prognosis , Random Allocation , Sarcoma/radiotherapy , Sarcoma/therapy , Soft Tissue Neoplasms/radiotherapy , Soft Tissue Neoplasms/therapyABSTRACT
Interferon causes profound biological changes when given to patients with cancer and many of these could not be predicted from in vitro or animal model systems. We documented significant changes in hormonal levels for a group of 18 patients who were participants in a Phase I gamma-interferon trial. Adrenocorticotropic hormone, cortisol, and growth hormone were all significantly elevated 2 h after treatment with gamma-interferon, with cortisol and adrenocorticotropic hormone returning to base line by 24 h. A placebo group failed to show this change, suggesting a specific interferon effect. Possible mechanisms for these findings and implications for the use of interferons are discussed.
Subject(s)
Hormones/blood , Interferon-gamma/pharmacology , Adrenocorticotropic Hormone/blood , Drug Evaluation , Growth Hormone/blood , Humans , Hydrocortisone/blood , Thyrotropin/bloodABSTRACT
The temporal effects of 5.0 Gy of radiation on healing subcutaneous microvasculature were studied using a window chamber in the dorsal flap of the Fischer-344 rat. Microvascular function was assessed by morphometric and dynamic flow measurements which were made prior to and at 24 and 72 h after exposure. A comparison was made between chamber preps that were 3 and 14 days postsurgery. The hypothesis of the study was that the older preparation would be more refractory to damage by radiation. Both unirradiated preparations showed an increase in capillary numbers over the period of observation, while irradiated preps had a reduction, especially in vessels less than 50 microns in diameter. Red cells velocities increased by 20-100% in those vessels which survived the radiation exposure, indicating that tissue oxygen tensions might be preserved in spite of a loss of vasculature. These results explain the need for both morphologic and dynamic flow measurements when assessing the effect of therapeutic intervention on microcirculatory function. Further studies are underway to identify a fully mature capillary bed in this model, since it is apparent that capillary growth is continuing in the 14-day preparation.
Subject(s)
Skin Window Technique , Skin/blood supply , Wound Healing/radiation effects , Animals , Microcirculation/injuries , Microcirculation/physiology , Rats , Time FactorsABSTRACT
The outcome of patients with stage I malignant melanoma has been well assessed in terms of prognostic factors and their effect on survival; however, little is known of the recurrence patterns of cutaneous melanoma or the survival of these patients subsequent to recurrence. A retrospective, computer-aided chart review identified 4185 patients with melanoma who had stage I disease clinically. During a follow-up period of one to 14 years, 35.9% suffered a recurrence. Melanoma of the trunk (37.8%) and head and neck area (46.1%) had an increased incidence of recurrent metastases compared with melanoma of the extremities (29.8%). Local regional metastases accounted for 62.5%, 77.3%, and 85.6% of the recurrences in the head and neck, trunk, and extremity primary sites, respectively, with 65% of the relapses occurring within the first three years. Actuarial five-year survival rates of patients who had recurrent disease were significantly decreased compared with those of patients who had no evidence of metastases during their clinical course. A multivariate analysis was performed to estimate the survival of patients after recurrence. One may use this mathematical model to predict the outcome of individual patients after recurrence and provide a more rationally based prognosis for them and their families.
Subject(s)
Melanoma/therapy , Neoplasm Recurrence, Local/therapy , Skin Neoplasms/therapy , Adult , Aged , Combined Modality Therapy , Female , Humans , Male , Melanoma/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Skin Neoplasms/pathologyABSTRACT
Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.
Subject(s)
Polycythemia Vera/diagnosis , Thrombocythemia, Essential/diagnosis , Thrombocytosis/diagnosis , Adult , Aged , Aged, 80 and over , Algorithms , Diagnosis, Differential , Erythrocyte Indices , Female , Humans , Male , Middle Aged , Polycythemia Vera/blood , Polycythemia Vera/complications , Prognosis , Regression Analysis , Thrombocythemia, Essential/blood , Thrombocythemia, Essential/complicationsABSTRACT
A pilot study was undertaken to test whether alpha interferon (alpha-IFN) maintenance could continue to stabilize cancer measurements after induction therapy. Twenty-one patients who achieved stable disease at the end of their induction treatment were randomized to receive weekly maintenance with human lymphoblastoid interferon (HLBI) (3 MU/m2, i.m.) or to be followed and not given interferon. There were 12 patients in the maintenance groups and 9 in the control observation group. There was no time difference in disease progression between the two arms. This article considers the relevance of the stable disease category in trials of interferon.
Subject(s)
Interferon Type I/therapeutic use , Neoplasms/therapy , Adult , Aged , Breast Neoplasms/therapy , Colonic Neoplasms/therapy , Drug Evaluation , Female , Humans , Kidney Neoplasms/therapy , Male , Middle Aged , Random AllocationABSTRACT
The prognostic significance of disease features recorded at the time of diagnosis was examined among 813 patients with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia (CGL) collected from six European and American series. The survival pattern for this population was typical of "good-risk" patients, and median survival was 47 mo. There were multiple interrelationships among different disease features, which led to highly significant correlations with survival for some that had no primary prognostic significance, such as hematocrit. Multivariable regression analysis indicated that spleen size and the percentage of circulating blasts were the most important prognostic indicators. These features, and age, behaved as continuous variables with progressively unfavorable import at higher values. The platelet count did not influence survival significantly at values below 700 X 10(9)/liter but was increasingly unfavorable above this level. Basophils plus eosinophils over 15%, more than 5% marrow blasts, and karyotypic abnormalities in addition to the Ph1 were also significant unfavorable signs. The Cox model, generated with four variables representing percent blasts, spleen size, platelet count, and age, provided a useful representation of risk status in this population, with good fit between predicted and observed survival over more than a twofold survival range. A hazard function derived from half of the patient population successfully segregated the remainder into three groups with significantly different survival patterns. We conclude that it should be possible to identify a lower risk group of patients with a 2-yr survival of 90%, subsequent risk averaging somewhat less than 20%/yr and median survival of 5 yr, an intermediate group, and a high-risk group with a 2-yr survival of 65%, followed by a death rate of about 35%/yr and median survival of 2.5 yr.
Subject(s)
Leukemia, Myeloid/mortality , Adolescent , Adult , Age Factors , Aged , Cell Transformation, Neoplastic/pathology , Child , Child, Preschool , Europe , Female , Hematocrit , Humans , Leukemia, Myeloid/blood , Leukemia, Myeloid/classification , Leukocyte Count , Male , Middle Aged , Models, Biological , Platelet Count , Prognosis , Regression Analysis , Risk , Splenomegaly/mortality , United StatesABSTRACT
An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broad-scale evaluation of the immune response as a function of interferon dosage. Dose-limiting toxicity was generally due to constitutional symptoms which are remarkably similar to those produced by influenza, although transient peripheral and central neurotoxicity (including deterioration in cognitive and behavioral functions) is observed at higher doses. It is difficult to establish "clean" dose-response effects except for fever and bone marrow suppression, neither of which is a major dose limitation. Enhancement of the immune system was limited to natural killer cells which had a complex dose-response relationship, whereby low interferon concentrations were less stimulatory (than were high doses) following a single dose but gave more sustained stimulation over a 5-week course of 3 times per week i.m. administration. The effects on various measures of monocyte function and of nonspecific immunity (hypersensitivity, immunoglobulins, complement) were negative. We suspect that in practice it may be difficult to exploit the narrow dosage window of immunostimulation, but it is important to note that the nontoxic lower doses were more stimulatory than were the very high doses which are being used in numerous clinical trials.
Subject(s)
Interferon Type I/therapeutic use , Neoplasms/therapy , Adult , Aged , B-Lymphocytes/immunology , Burkitt Lymphoma/immunology , Cell Line , Drug Evaluation , Erythropoiesis/drug effects , Female , Granulocytes/drug effects , Hematopoietic Stem Cells/drug effects , Humans , Interferon Type I/blood , Interferon Type I/toxicity , Killer Cells, Natural/immunology , Kinetics , Lymphocytes/immunology , Male , Middle AgedABSTRACT
The in vivo and in vitro effects of partially purified human lymphoblastoid alpha-interferon (alpha-IFN) on natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood were tested in 17 cancer patients. The study tested single doses of alpha-IFN (part A), and repeated, incremental doses (15 over 5 weeks; part B). The initial response to alpha-IFN was a decline of NK and ADCC activity, reaching a nadir at 12 h. The decline was found to be partly related to nonadherent suppressor cells. The NK activity generally returned to or exceeded baseline within 24-48 h and stayed elevated for a week or more after a single injection. Interestingly, the decline in NK activity was not unique to the first injection, but was found even in chronic treatment 12 h after alpha-IFN injection. Dose-response studies showed that maximum stimulation was achieved by the end of the first week, when it was greater for patients receiving higher doses of alpha-IFN. However, patients who received repeated injections at lower doses were able to sustain this stimulation, whereas those who received higher doses were not. Very low doses (0.5 mU/m2) appeared to be maximally efficient. IFN administration to the same group of cancer patients seemed to have similar effects on ADCC against tumor cells. Furthermore, our study has shown that cells responsive in vitro to alpha-IFN (drawn prior to treatment) showed an increase in NK activity similar to that after in vivo administration of alpha-IFN, indicating a simple predictor of patients' responsiveness to IFN treatment. Taken together, these findings indicate that in vivo administration of alpha-IFN results in a dose-dependent augmentation of NK and ADCC activity in cancer patients.