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Biomedical subjects

J Koval

Publications and source records attributed to J Koval.

At least 19 recordsLinked to original sources

Blunt external trauma to the trachea: report of two cases.

We present two cases of blunt external trauma to the trachea. The first was a 19-year-old man who had suffered rupture of the first tracheal ring as a consequence of attempting suicide by hanging from a cable. The second was an 11-year-old boy who fell from a bicycle and struck his neck against the handlebars. Fracture of the second tracheal ring was found at surgery. Both cases were treated by primary repair. A surgical exploration is essential in the case of subcutaneous emphysema, even if no respiratory distress is present and a radiological evaluation is negative. Follow up, according to the extent and type of injury, is recommended to prevent post traumatic stenosis of the trachea.

Adult↗

The influence of falling, fear of falling, and balance confidence on prosthetic mobility and social activity among individuals with a lower extremity amputation.

OBJECTIVE: To assess in amputee patients the relationship between having fallen in the past 12 months, fear of falling, and balance confidence on mobility capability, mobility performance, and social activity. DESIGN: Population-based survey and chart review. SETTING: Two university-affiliated outpatient amputee programs in southwestern Ontario. PARTICIPANTS: Community-living individuals (n = 435) with a unilateral lower limb amputation. INTERVENTIONS: Patient chart review and a survey questionnaire. MAIN OUTCOME MEASURES: Self-report assessment of prosthetic capability and performance and social activity participation was assessed with the Prosthetic Evaluation Questionnaire mobility subscale, the Houghton Scale, and the Frenchay Activities Index. RESULTS: Falling experiences in the past 12 months were not significantly associated with any outcomes. Fear of falling was important in univariate relationships in all 3 outcomes, but not when balance confidence was included in multivariable modeling. Balance confidence was statistically significant with each of the outcomes and remained significant with inclusion of the covariates. There was statistical interaction (balance confidence x automatism; balance confidence x medication count) in modeling mobility capability and in modeling mobility performance (balance confidence x pain + balance confidence x amputation level). The final models accounted for 70%, 60%, and 55% of the variation in mobility capability, mobility performance, and social activity, respectively. CONCLUSION: Balance confidence was the only factor associated with mobility capability and performance and social activity in the final adjusted models. Clinicians and researchers should consider this variable in the rehabilitation of amputee patients.

Accidental Falls↗

Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes.

Glucose phosphorylation, catalyzed by hexokinase, is the first committed step in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isoform that is present in muscle and is regulated by insulin and muscle contraction. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was performed to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed before and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mRNA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P <.05 for both). Exercise did not significantly increase HKI mRNA. When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no statistically significant differences were found. In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) significantly in both obese nondiabetic and type 2 diabetic patients. The present results indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients.

Adult↗

A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators.

BACKGROUND: Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS: We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

Adult↗

Regulation of hexokinase II expression in human skeletal muscle in vivo.

The phosphorylation of glucose to glucose-6-phosphate (G-6-P) is the first committed step in glucose uptake in skeletal muscle. This reaction is catalyzed by hexokinase (HK). Two HK isoforms, HKI and HKII, are expressed in human skeletal muscle, but only HKII is regulated by insulin. The present study was undertaken to determine the time course for the regulation of HK activity and expression by physiological plasma insulin concentrations in human skeletal muscle in vivo. A hyperinsulinemic-euglycemic glucose clamp and percutaneous muscle biopsy were performed in separate groups of healthy subjects after 60, 120, 180, and 360 minutes of euglycemic hyperinsulinemia. Muscle biopsies were subfractionated into soluble and particulate fractions to determine HKI and HKII activities. RNA was extracted from a separate portion of the muscle biopsy, and HKI and HKII mRNA content was determined using an RNase protection assay. Glycogen synthase (GS) activity and fractional velocity were also determined. HKII mRNA was increased 2-fold by 120 minutes and remained high versus the basal value for up to 360 minutes. HKI mRNA was unchanged throughout the study. HKII activity increased after 360 minutes of insulin infusion, and this increase was limited to the soluble fraction. In contrast, insulin induced a 1.5- to 2-fold increase in GS fractional velocity that was sustained for 360 minutes. The time course of the ability of hyperinsulinemia to increase HKII mRNA indicates that insulin is likely a physiological regulator of HKII expression in human skeletal muscle in vivo.

Adult↗

Regulation of MAP kinase pathway activity in vivo in human skeletal muscle.

Insulin and exercise potently stimulate glucose metabolism and gene transcription in vivo in skeletal muscle. A single bout of exercise increases the rate of insulin-stimulated glucose uptake and metabolism in skeletal muscle in the postexercise period. The nature of the intracellular signaling mechanisms that control responses to exercise is not known. In mammalian tissues, numerous reports have established the existence of the mitogen-activated protein (MAP) kinase signaling pathway that is activated by a variety of growth factors and hormones. This study was undertaken to determine how a single bout of exercise and physiological hyperinsulinemia activate the MAP kinase pathway. The euglycemic-hyperinsulinemic clamp and cycle ergometer exercise techniques combined with percutaneous muscle biopsies were used to answer this question. In healthy subjects, within 30 min, insulin significantly increased MAP kinase [isoforms p42(MAPK) and p44(MAPK) (ERK1 and ERK2)] phosphorylation (141 +/- 2%, P < 0.05) and activity (177 +/- 5%, P < 0.05), and the activity of its upstream activator MEK1 (161 +/- 16%, P < 0.05). Insulin also increased the activity of the MAP kinase downstream substrate, the p90 ribosomal S6 kinase 2 (RSK2) almost twofold (198 +/- 45%, P < 0.05). In contrast, a single 30-min bout of moderate-intensity exercise had no effect on the MAP kinase pathway activation from MEK to RSK2 in muscle of healthy subjects. However, 60 min of exercise did increase extracellular signal-related kinase activity. Therefore, despite similar effects on glucose metabolism after 30 min, insulin and exercise regulate the MAP kinase pathway differently. Insulin more rapidly activates the MAP kinase pathway.

Adult↗

Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma.

PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Acid Phosphatase↗

Effects of insulin on subcellular localization of hexokinase II in human skeletal muscle in vivo.

The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is the first committed step in glucose uptake into skeletal muscle. Two isoforms of hexokinase, HKI and HKII, are expressed in human skeletal muscle, but only HKII expression is regulated by insulin. HKII messenger RNA, protein, and activity are increased after 4 h of insulin infusion; however, glucose uptake is stimulated much more rapidly, occurring within minutes. Studies in rat muscle suggest that changes in the subcellular distribution of HKII may be an important regulatory factor for glucose uptake. The present studies were undertaken to determine if insulin causes an acute redistribution of HKII activity in human skeletal muscle in vivo. Muscle biopsies (vastus lateralis muscle) were performed before and at the end of 30 min insulin infusion, performed using the euglycemic clamp technique. Muscle biopsies were subfractionated into soluble and particulate fractions to determine if insulin acutely changes the subcellular distribution of HKII. Insulin decreased HKII activity in the soluble fraction from 2.20 +/- 0.31 to 1.40 +/- 0.18 pmoles/(min[chempt]micrograms) and increased HKII activity in the particulate fraction from 3.02 +/- 0.46 to 3.45 +/- 0.46 pmoles/(min[chempt]micrograms) (P < 0.01 for both). These changes in HKII activity were correlated with changes in HKII protein, as determined by immunoblot analysis (r = 0.53, P = 0.05). Insulin had no effect on the subcellular distribution of HKII activity, which was primarily restricted to the soluble fraction. These studies are consistent with the conclusion that, in vivo in human skeletal muscle, insulin changes the subcellular distribution of HKII within 30 min.

Adult↗

Insulin-induced hexokinase II expression is reduced in obesity and NIDDM.

NIDDM and obesity are characterized by decreased insulin-stimulated glucose uptake in muscle. It has been suggested that impaired glucose phosphorylation to glucose-6-phosphate, catalyzed in muscle by hexokinase (HK)II, may contribute to this insulin resistance. Insulin is known to increase HKII mRNA, protein, and activity in lean nondiabetic individuals. The purpose of this study was to determine whether defects in insulin-stimulated HKII expression and activity could contribute to the insulin resistance of obesity and NIDDM. Fifteen lean nondiabetic control subjects, 17 obese nondiabetic subjects, and 14 obese NIDDM patients were studied. Percutaneous muscle biopsies of the vastus lateralis were performed in conjunction with leg balance and local indirect calorimetry measurements before and at the end of a 3-h euglycemic-hyperinsulinemic clamp (40 or 240 mU x min(-1) x m[-2]). Leg glucose uptake in response to the 40-mU insulin infusion was higher in the lean control subjects (2.53 +/- 0.35 micromol x min(-1) per x 100 ml leg vol) than in obese (1.46 +/- 0.50) or NIDDM (0.53 +/- 0.25, P < 0.05) patients. In response to 240 mU insulin, leg glucose uptake was similar in all of the groups. In response to 40 mU insulin, HKII mRNA in lean control subjects was increased 1.48 +/- 0.18-fold (P < 0.05) but failed to increase significantly in the obese (1.12 +/- 0.24) or NIDDM (1.14 +/- 0.18) groups. In response to 240 mU insulin, HKII mRNA was increased in all groups (control subjects 1.48 +/- 0.18, P < 0.05 vs. basal, obese 1.30 +/- 0.16, P < 0.05, and NIDDM 1.25 +/- 0.14, P < 0.05). Under basal conditions, HKI and HKII activities did not differ significantly between groups. Neither the 40 mU nor the 240 mU insulin infusion affected HK activity. Total HKII activity was reduced in the obese subjects (4.33 +/- 0.08 pmol x min(-1) x g(-1) muscle protein) relative to the lean control subjects (5.00 +/- 0.08, P < 0.05). There was a further reduction in the diabetic patients (3.10 +/- 0.10, P < 0.01 vs. the control subjects, P < 0.01 vs. the obese subjects). Resistance to insulin's metabolic effects extends to its ability to induce HKII expression in obesity and NIDDM.

Adult↗

Reported activities of daily living: agreement between elderly subjects with and without dementia and their caregivers.

OBJECTIVES: to determine how accurately information on disability provided by a caregiver (proxy respondent) reflected the opinion of subjects themselves, and if this agreement varied by severity of dementia or relationship of the caregiver to the subject. SETTING AND PARTICIPANTS: the study was based on data from the Canadian Study of Health and Aging, a multicentre study of dementia and health of Canadians age 65 and over. Eight hundred study subjects and their caregivers were independently interviewed regarding the subjects' activities of daily living (ADL). MEASUREMENTS: the percentage of subjects who were independent for individual ADL items and the agreement in these reports between subjects and caregivers were investigated using three-level kappa statistics. RESULTS: index subjects with caregivers other than spouses or offspring required more assistance with ADL. The reported percentage of independence decreased with increasing severity of dementia. There was more agreement between self- and proxy-reported level of independence for physical ADL than for instrumental ADL items. Agreement decreased with increasing severity of dementia. Few statistically significant differences were noted between level of agreement and caregiver relationship. CONCLUSION: satisfactory levels of agreement on ADL between cognitively normal subjects and their caregivers indicate that proxy respondents are a reasonable source of information on ADL when data collection from the subjects themselves is not feasible. Since agreement decreases as the severity of dementia increases, caregiver reports may be preferred for elderly patients even with mild dementia in order to facilitate longitudinal assessment of ADL ratings as the dementia progresses.

Activities of Daily Living↗

How do we teach anatomy?

Two approaches to anatomy teaching have been studied and compared. We have concentrated on the teaching time spent for all parts of anatomy and we have compared external recommendations with the teaching time actually given to the subject at our Faculty of Medicine. In addition to that, various opinions on informational and educational aims in medical anatomy teaching are presented. The comparison mentioned above can be used to select the most useful way in which anatomy may be taught, in the light of current curricular emphases and pressures, and in the context of sound educational principles.

Anatomy↗

103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.

PURPOSE: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the last follow-up were censored at that time. Patients whose PSA plateaued at a value greater than 1.0 were scored as failures at the time the PSA first plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%. In Cox proportional hazard multivariate analysis, the strongest predictor of failure was elevated acid phosphatase (p = 0.04), followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6). Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2 urinary symptoms. One patient, who had both a transurethral incision of the prostate (TUIP) and a transurethral resection of the prostate (TURP), developed low-volume urinary incontinence. The actuarial potency rate at 3 years after implantation was 77% for 46 patients who were sexually potent prior to implant. CONCLUSION: Biochemical freedom from failure rates following combined EBRT and 103Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable.

Aged↗

Factors associated with increased frequency of HIV-related oral candidiasis.

HIV-related oral candidiasis was investigated in 71 HIV-seropositive patients who received interviews, oral examinations and hematologic investigation. Diagnosis of candidiasis was based on clinical signs and examination of PAS-stained smears. The frequency of candidiasis was 24/71 (34%). The clinical presentations were pseudomembranous 8 (11%), erythematous 14 (20%), angular cheilitis 3 (4%). Twenty-six patients (37%) had candidiasis or were receiving antifungal treatment for recurrent pseudomembranous type. Twelve of 13 (92%) patients with AIDS and 14/58 (24%) without AIDS were affected. Bivariate analyses showed significant associations with AIDS, the use of zidovudine, low T4-count, xerostomia; marital status (sometime married), restricted performance status and age of greater than 35 yr. Multivariate logistic regression analysis showed that the presence of xerostomia was an independent and statistically significant predictor of HIV-related oral candidiasis. T4-count and restricted performance status were the second and third most important predictors.

Acquired Immunodeficiency Syndrome↗

[Personal experience with the difference limen in interrupted tones in differentiating between sensorineural and supracochlear hearing disorders].

The authors assessed the differences of the limen of interrupted sounds (sounds which last 500 ms, between which there are intervals of 200 ms) in healthy subjects and in patients with sensory neural and supracochlear hearing disorders. Essentially the results are consistent with those of Schorn and Fastl (2) and they suggest that patients with supracochlear hearing disorders are able to differentiate only much greater differences in intensity (more than 4 dB) between sounds, as compared with patients with sensory neural hearing disorders.

Audiometry↗