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Biomedical subjects

J H Anderson

Publications and source records attributed to J H Anderson.

At least 37 records · Page 2Linked to original sources

Impact of insulin lispro on HbA1c values in insulin pump users.

AIM: To compare the therapeutic efficacy of the short-acting insulin analogue insulin lispro (Humalog) with that of buffered regular human insulin (Velosulin) in patients on insulin pump therapy. PATIENTS AND METHODS: Sixty-two (45 women and 17 men) young patients with type 1 diabetes using insulin pump therapy were compared while using buffered regular human insulin for a mean +/- s.e.m. of 20.1+/-1.2 months or insulin lispro for a mean +/- s.e.m. of 19.7+/-0.5 months. The initial mean +/- s.e.m. age and duration of diabetes were 29.1+/-0.9 and 17.7+/-0.9 years, respectively. The mean HbA1c values, basal insulin dosages, premeal insulin dosages and number of low blood sugars were recorded during treatment with both insulins. RESULTS: Mean +/- s.e.m. HbA1c values were significantly lower (p < 0.001; paired Wilcoxon t-test) during insulin lispro treatment (7.4+/-0.1%) as compared to treatment with buffered regular human insulin (7.9+/-0.1%). Total units of insulin (mean +/- s.e.m.)/kg/day was significantly (p = 0.03) lower (0.61+/-0.02) during the insulin lispro treatment period as compared to the buffered regular human insulin treated period (0.65+/-0.03). Total mean +/- s.e.m. (U/kg/day) of basal insulin administered per day was higher when patients received insulin lispro treatment (0.44+/-0.02 vs. 0.42+/-0.01 for buffered regular human insulin treated period; p = 0.002). The premeal insulin boluses (mean +/- s.e.m.) for the two treatment groups were significantly different with less insulin required for the insulin lispro treatment period for all three meals (p < 0.001, t-test). The number of mild/moderate and severe hypoglycaemic episodes were similar in the two groups. CONCLUSION: We conclude that use of insulin lispro in pump therapy significantly lowers HbA1c values in comparison to therapy with buffered regular human insulin insulin without increasing hypoglycaemic episodes.

Adult↗

Feasibility of ablating normal renal parenchyma by interstitial photon radiation energy: study in a canine model.

BACKGROUND AND PURPOSE: A miniature photon radiosurgery system (PRS) has been described as an alternative to surgical resection and external-beam radiation for tumors and may now offer an alternative for ablation of renal lesions. We evaluated the feasibility of ablation by PRS in a normal parenchyma canine model. MATERIALS AND METHODS: Twelve mongrel dogs were used in this survival study. In the left and right kidneys of each animal, a peripheral lesion and central-hilar lesion, respectively, were induced with PRS. The probes were placed in the renal parenchyma, and local radiation of 15 Gy at a radius of 1.3 cm was delivered over 10 minutes. Serum electrolytes were measured serially. Computed tomography scans were obtained, and the animals were sacrificed for pathologic correlation. In a separate study, the liver received three additional treatments of 10 to 20 minutes of radiation. RESULTS: Eleven dogs survived this 6-month study and were sacrificed as scheduled. One animal expired after 2 weeks from radiation-induced fulminant hepatic failure with normal renal function. No other complications were observed. The average lesion size was 2.5 cm in diameter. Histologic analysis confirmed coagulative necrosis with sharp demarcation from the surrounding parenchyma. CONCLUSION: Preliminary studies demonstrate the feasibility of PRS ablation of the renal parenchyma. Further tumor model testing will be important to determine the ultimate efficacy of local photon radiation energy.

Animals↗

Similarity in the response of smooth pursuit and manual tracking to a change in the direction of target motion.

Subjects were asked to track, with their eyes or their hand, the movement of a target that maintained a constant speed and made a single, abrupt change in direction. The tracking speed and direction of motion after the step change in target direction were compared for the eyes and the hand. After removal of the saccades from the eye movement records, it was found that in both cases, there was a slow rotation from the initial direction to the new direction. For the eyes and the hand, it was found that this change in direction of movement occurred at a similar rate that was proportional to the magnitude of the abrupt change in target direction. This was further described by comparing the direction of pursuit tracking with the response of a second-order system to a step input. In addition, it was found that the speed of manual and pursuit tracking was modulated in a similar manner, with a reduction in tracking speed occurring before the change in tracking direction. This reduction in speed following the change in the direction of target motion was very similar for the hand and the eye, despite the large difference in the inertias of the two systems. Taken together, these data suggest that the neural mechanisms for smooth pursuit and manual tracking have common functional elements and that musculoskeletal dynamics do not appear to be a rate-limiting factor.

Analysis of Variance↗

Mental maze solving.

We sought to determine how a visual maze is mentally solved. Human subjects (N = 13) viewed mazes with orthogonal, unbranched paths; each subject solved 200-600 mazes in any specific experiment below. There were four to six openings at the perimeter of the maze, of which four were labeled: one was the entry point and the remainder were potential exits marked by Arabic numerals. Starting at the entry point, in some mazes the path exited, whereas in others it terminated within the maze. Subjects were required to type the number corresponding to the true exit (if the path exited) or type zero (if the path did not exit). In all cases, the only required hand movement was a key press, and thus the hand never physically traveled through the maze. Response times (RT) were recorded and analyzed using a multiple linear regression model. RT increased as a function of key parameters of the maze, namely the length of the main path, the number of turns in the path, the direct distance from entry to termination, and the presence of an exit. The dependence of RT on the number of turns was present even when the path length was fixed in a separate experiment (N = 10 subjects). In a different experiment, subjects solved large and small mazes (N = 3 subjects). The former was the same as the latter but was scaled up by 1.77 times. Thus both kinds of mazes contained the same number of squares but each square subtended 1.77 degrees of visual angle (DVA) in the large maze, as compared to 1 DVA in the small one. We found that the average RT was practically the same in both cases. A multiple regression analysis revealed that the processing coefficients related to maze distance (i.e., path length and direct distance) were reduced by approximately one-half when solving large mazes, as compared to solving small mazes. This means that the efficiency in processing distance-related information almost doubled for scaled-up mazes. In contrast, the processing coefficients for number of turns and exit status were practically the same in the two cases. Finally, the eye movements of three subjects were recorded during maze solution. They consisted of sequences of saccades and fixations. The number of fixations in a trial increased as a linear function of the path length and number of turns. With respect to the fixations themselves, eyes tended to fixate on the main path and to follow it along its course, such that fixations occurring later in time were positioned at progressively longer distances from the entry point. Furthermore, the time the eyes spent at each fixation point increased as a linear function of the length and number of turns in the path segment between the current and the upcoming fixation points. These findings suggest that the maze segment from the current fixation spot to the next is being processed during the fixation time (FT), and that a significant aspect of this processing relates to the length and turns in that segment. We interpreted these relations to mean that the maze was mentally traversed. We then estimated the distance and endpoint of the path mentally traversed within a specific FT; we also hypothesized that the next portion of the main path would be traversed during the ensuing FT, and so on for the whole path. A prediction of this hypothesis is that the upcoming saccade would land the eyes at or near the locus on the path where the mental traversing ended, so that "the eyes would pick up where the mental traversal left off." In this way, a portion of the path would be traversed during a fixation and successive such portions would be strung together closely along the main path to complete the processing of the whole path. We tested this prediction by analyzing the relations between the path distance of mental traverse and the distance along the path between the current and the next fixation spot. (ABSTRACT TRUNCATED)

Adult↗

Coordination of a step with a reach.

Although natural reaching behavior can easily include forward body movement, most laboratory studies of reaching have constrained the body to be stationary. Recently, however, it has been shown that normal subjects exhibit a different pattern of errors when attempting to pinpoint remembered target locations, depending on whether or not the reach includes a step. In the study of Flanders et al., these errors appeared to be due to the strategy of eye/head/hand coordination which normally comes into play when the body is moving toward the target. Since the spatial positioning of the head was found to partially explain the errors in hand placement, the present study examined the movements of patients with bilateral vestibular deficits in order to further analyze the whole-body coordination. Somewhat surprisingly, the patients exhibited the same pattern of head movement and the same errors in hand placement as did the control subjects. Nevertheless, the patients' movements clearly exhibited evidence for an abnormal decomposition of elbow extension and trunk rotation. Furthermore the patients' (spatial) hand paths were significantly more curved than those of control subjects and, only in the patients, paths to remembered targets were significantly more curved than paths to visible targets. Thus for movements to remembered targets, the patients tended to move the hand to the same incorrect spatial positions as control subjects but spatiotemporal aspects of the arm and body movement differed. The results are consistent with the idea that vestibular patients are overly dependent upon visual cues, and support the hypothesis that this stepping and reaching behavior is largely dependent upon a visual reference signal.

Adult↗

Safety of insulin lispro: pooled data from clinical trials.

The safety of insulin lispro was compared with that of regular human insulin of recombinant DNA origin (Humulin R, Lilly), with special emphasis on the development and progression of the chronic complications of diabetes mellitus in relation to insulin therapy. Ten clinical trials of 3634 patients with type 1 and type 2 diabetes mellitus were analyzed. The primary focus was treatment-emergent adverse events, and the secondary focus was the development and progression of the chronic complications of diabetes. The evaluations were based on pertinent laboratory values, predetermined disease-specific COSTART (coding symbol and thesaurus for adverse event terminology) terms, physician evaluations of patients, and physical examinations. There were no clinically or statistically significant differences in the frequency of treatment-emergent adverse events or progression of retinopathy, neuropathy, or cardiovascular disease reported with each therapy. There was no difference between insulin lispro and Humulin R in the occurrence and progression of kidney disease as measured by changes in serum creatinine levels. Pooled data from clinical studies show that insulin lispro has a safety profile comparable to that of Humulin R.

Adolescent↗

Improved postprandial blood glucose control and reduced nocturnal hypoglycemia during treatment with two novel insulin lispro-protamine formulations, insulin lispro mix25 and insulin lispro mix50. Mix50 Study Group.

The objective of this 6-month, open-label, randomized, two-period crossover study was to compare glycemic control when patients were treated with (1) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation, neutral protamine lispro (NPL), and (2) 2 manufactured premixed human insulin formulations, human insulin 50/50 and human insulin 30/70. One hundred individuals, 37 with type 1 diabetes mellitus (12 females, 25 males; mean age, 39.4 years; mean body mass index [BMI], 24.8; mean duration of diabetes, 12.9 years) and 63 with type 2 diabetes mellitus (33 females, 30 males; mean age, 59.0 years; mean BMI, 28.4; mean duration of diabetes, 12.6 years), were treated with insulin lispro mixtures. Insulin lispro Mix50 (50% insulin lispro/50% NPL) and human insulin 50/50 (50% regular insulin/50% neutral protamine Hagedorn [NPH] insulin) were administered before breakfast; insulin lispro Mix25 (25% insulin lispro/75% NPL) and human insulin 30/70 (30% regular insulin/70% NPH) were administered before dinner. Blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG <3.0 mmol/L), insulin dose and timing of dose before meals, and hemoglobin A1c were measured. Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups. However, compared with human insulin mixtures, twice-daily administration of insulin lispro mixtures resulted in improved postprandial glycemic control, similar overall glycemic control, and less nocturnal hypoglycemia, as well as offering the convenience of dosing closer to meals.

Adult↗

Insulin lispro in the treatment of patients with type 2 diabetes mellitus after oral agent failure.

This study assessed the safety profile and efficacy of a new combination therapy (insulin lispro plus sulfonylurea) in patients with type 2 diabetes mellitus experiencing secondary oral agent failure. A total of 423 patients were randomly assigned to 3 treatment groups: preprandial insulin lispro plus sulfonylurea (L + S), bedtime neutral protamine Hagedorn (NPH) insulin plus sulfonylurea (N + S), and preprandial insulin lispro plus bedtime NPH insulin (L + N). Mean decreases in glycosylated hemoglobin from baseline were 1.60%+/-1.27% for patients receiving L + S, 1.21%+/-1.21% for those receiving N + S, and 1.40%+/-1.46% for those receiving L + N (within treatment, P<0.001; for L + S vs. N + S, P = 0.003). Fasting blood glucose level was higher in patients receiving L + S (171+/-46.5 mg/dL) or L + N (166+/-52.5 mg/dL) than in those receiving N + S (144+/-48.2 mg/dL) (P<0.001, for both comparisons). Conversely, postprandial blood glucose level was lower in patients receiving L + S (165+/-41.6 mg/dL) or L + N (165+/-46.3 mg/dL) than in those receiving N + S (213+/-58.3 mg/dL) (P<0.001, for both comparisons). The overall rate of hypoglycemia (episodes per 30 days) was not statistically significant when the L + S, N + S, and L + N therapies were compared (0.99+/-1.74 vs. 0.87+/-2.31 vs. 1.16+/-2.38, respectively). The rate of nocturnal hypoglycemia was lowest in the L + S group (0.00+/-0.00 vs. 0.10+/-0.37 for the N + S group vs. 0.15+/-0.54 for the L + N group; P = 0.004). L + S, which has a safety profile equal to those of N + S and L + N, is an effective treatment for patients with type 2 diabetes who experience oral sulfonylurea agent failure. L + S offers an alternative to these established combination therapies in patients whose type 2 diabetes cannot be controlled with a sulfonylurea alone.

Adult↗

Brachytherapy optimal planning with application to intravascular radiation therapy.

We have been studying brachytherapy planning with the objective of minimizing the maximum deviation of the delivered dose from prescribed dose bounds for treatment volumes. A general framework for optimal treatment planning is presented and the minmax optimization is formulated as a linear program. Dose rate calculations are based on the dosimetry formulation of the American Association of Physicists in Medicine, Task Group 43. We apply the technique to optimal planning for intravascular brachytherapy of intimal hyperplasia using ultrasound data and 192Ir seeds. The planning includes determination of an optimal dwell-time sequence for a train of seeds that deliver radiation while stepping through the vessel lesion. The results illustrate the advantage of this strategy over the common approach of delivering radiation by positioning a single train of seeds along the whole lesion.

Algorithms↗

Colonic motility is abnormal before surgery for rectal prolapse.

BACKGROUND: Abdominal rectopexy remains the operation of choice for patients with rectal prolapse. Recurrence rates are low but the functional results are poor. Hindgut motility was measured before abdominal rectopexy to determine whether an underlying neuropathy might explain these poor results. METHODS: Seven women of mean(s.d.) age 56(10) years had a multilumen catheter inserted in the colon before abdominal rectopexy. Colonic intraluminal pressure was recorded for a mean(s.d.) of 19(3) h; the number of peaks over 5 and 50 mmHg, motility and high-amplitude propagated contractions (HAPCs) were measured before and after a meal and compared with the findings in five controls. RESULTS: Patients had high numbers of contractions greater than 5 mmHg and high motility before meals. Controls responded to meals by increasing motility, unlike patients. HAPCs were seen in one patient but in all controls. CONCLUSION: These data show that patients with rectal prolapse have a hindgut motility abnormality before abdominal rectopexy, similar to that observed in spinal cord injury. This may explain the poor functional results after surgery, offering a rationale for colonic resection.

Adult↗

Identification of patients likely to benefit from biofeedback for outlet obstruction constipation.

BACKGROUND: Biofeedback for outlet obstruction constipation has a varying success rate. The aim of this study was to identify which patients are likely to respond to biofeedback. METHODS: Thirty patients with severe outlet obstruction constipation were treated by a specialist nurse using three or four sessions of visual and auditory feedback of anal sphincter pressures. All patients were assessed by evacuating proctography, whole-gut transit studies and anorectal physiology before treatment. RESULTS: Two patients did not complete the course of biofeedback. Nine patients improved. Before treatment these patients had predominantly normal anorectal physiology and were all able to open the anorectal angle at evacuating proctography. Nineteen patients did not improve, of whom only three had no measured abnormality other than inability to empty the rectum. Ten of these patients had abnormal anorectal physiology which may have been due to previous vaginal delivery. CONCLUSION: Biofeedback for outlet obstruction constipation is more likely to be successful in patients without evidence of severe pelvic floor damage.

Adolescent↗

Long-term efficacy of humalog in subjects with Type 1 diabetes mellitus.

AIMS: To evaluate the long-term effectiveness of Humalog insulin in lowering post meal glucose excursions. METHODS: Twenty young subjects with Type 1 diabetes mellitus (DM) who had received insulin-lispro (Humalog) for a least 1 year (mean +/- SD 1.8+/-1.6 years) were studied on two occasions, 3-14 days apart. They consumed a similar breakfast consisting of 450-600 kCal having fasted overnight. The same amount of human soluble Humulin Regular or Humalog insulin was given 10 min before the meal in a randomized, double-blind fashion. RESULTS: Postprandial glucose excursions at 30, 60, and 120 min were significantly lower (P<0.001, ANCOVA) when subjects received Humalog as compared to human soluble insulin. Serum-free insulin levels were significantly higher (P<0.001, ANOVA) at 30 and 60 min when subjects received Humalog as compared with human soluble insulin. Humalog antibody levels after up to 5.4 years of receiving Humalog insulin were not elevated beyond the values at 1 year. CONCLUSIONS: We conclude that Humalog insulin is effective in lowering postprandial glucose excursions even after up to 5.4 years of treatment.

Adult↗

Intra-arterial 5-fluorouracil and intravenous folinic acid in the treatment of liver metastases from colorectal cancer.

OBJECTIVE: To compare two regimens of intra-arterial chemotherapy for the treatment of hepatic metastases from colorectal cancer. DESIGN: Open study. SETTING: Teaching hospital, UK SUBJECT: 57 patients with unresectable metastases confined to the liver, and an indwelling catheter in the hepatic artery. INTERVENTIONS: The first 33 patients had a 24-hour intra-arterial infusion of 5-fluorouracil (5-FU) 1500 mg/m2, together with folinic acid 200 mg/m2 intravenously for the first and last two hours of the 5-FU infusion. This was repeated at weekly intervals for six weeks followed by a two-week gap before the next cycle. The remaining 24 patients had a two-weekly regimen in which folinic acid 200 mg/m2 was infused intravenously over 2 hours followed by an intra-arterial loading dose of 5-FU 400 mg/m2 over 15 minutes; 5-FU 1600 mg/m2 was then given by intra-arterial infusion over 22 hours. This was repeated on day 2 and then at two-weekly intervals. MAIN OUTCOME MEASURES: Response rate and toxicity. RESULTS: Median follow-up was 21 months, and estimated median survival 19 months. 29 patients (51%) have responded, 5 completely. There are no significant differences between the groups. Sites of progression were liver alone 26 (53%), lung alone 9 (18%), liver and lung 3 (6%), and the remainder in local or regional nodes (n = 7) or bone (n = 4). Six patients experienced WHO grade 3 or 4 toxicity. CONCLUSION: The two regimens have high response rates and cause little systemic toxicity. Intra-arterial chemotherapy for hepatic metastases from colorectal cancer is currently being compared with conventional systemic chemotherapy in a randomised controlled trial.

Adult↗

Oculomotor tracking in two dimensions.

Results from studies of oculomotor tracking in one dimension have indicated that saccades are driven primarily by errors in position, whereas smooth pursuit movements are driven primarily by errors in velocity. To test whether this result generalizes to two-dimensional tracking, we asked subjects to track a target that moved initially in a straight line then changed direction. We found that the general premise does indeed hold true; however, the study of oculomotor tracking in two dimensions provides additional insight. The first saccade was directed slightly in advance of target location at saccade onset. Thus its direction was related primarily to angular positional error. The direction of the smooth pursuit movement after the saccade was related linearly to the direction of target motion with an average slope of 0.8. Furthermore the magnitude and direction of smooth pursuit velocity did not change abruptly; consequently the direction of smooth pursuit appeared to rotate smoothly over time.

Humans↗

Enhanced uptake of [11C]TPMP in canine brain tumor: a PET study.

UNLABELLED: In vitro studies have demonstrated the membrane potential-dependent enhanced uptake of phosphonium salts, including [3H]triphenylmethylphosphonium (TPMP), into mitochondria of carcinoma and glioma-derived tumor cells, suggesting the potential use of phosphonium salts as tracers for tumor imaging. This study characterizes the in vivo uptake of [11C]TPMP in canine brain glioma using PET. METHODS: Dynamic paired PET studies of [11C]TPMP followed by [68Ga]ethylenediaminetetraacetic acid (EDTA) were performed 4 d before and 9 d after tumor cell inoculation. Graphical analysis was used to evaluate [11C]TPMP retention in tumor tissue. Distribution of tracer uptake was compared with tumor histological sections. RESULTS: [11C]TPMP exhibited enhanced uptake and prolonged retention in tumor cells. Patlak plot was linear over the 20- to 95-min postinjection period (r = 0.97 +/- 0.1). [68Ga]EDTA exhibited a gradual washout from the tumor tissue. The tumor-to-normal brain uptake ratio at 55 to 95 min postinjection was 47.5 for [11C]TPMP and 8.1 for [68Ga]EDTA. Qualitative comparison with histological sections indicated that [11C]TPMP enhanced uptake was restricted to the tumor area. CONCLUSION: The enhanced uptake and prolonged retention in tumor suggest [11C]TPMP as a promising means for imaging of gliomas in dogs. The need for studies in humans is indicated.

Animals↗

A vascular catheterization simulator for training and treatment planning.

We have developed a working prototype of an augmented reality based vascular catheterization simulator. The simulator is called daVinci, and provides the interventional radiologists with a "hands on, user friendly, image based environment to augment training, enhance pretreatment planning and design interventional products and devices. daVinci is based on computational modeling of human anatomical images and provides the user with capabilities for realtime simulated navigation of catheters in both 2-D and 3-D modeled vessels. In addition, multiplaner CT, MRI and anatomical data sets are incorporated into the simulator to enhance the understanding of anatomical relationships associated with vascular catheterization procedures. The current prototype is designed for peripheral vascular applications. Additional systems are currently being considered for both interventional neuroradiology and cardiology.

Angiography↗

Effects of a short-acting insulin analog (Insulin Lispro) versus regular insulin on lipid metabolism in insulin-dependent diabetes mellitus.

Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the physiological postprandial insulin profile. The aim of this study was to compare the effects of intensive insulin therapy on lipid metabolism using preprandial IL and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM) subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did not change after both treatments. In IDDM patients, total cholesterol and triglyceride levels appeared lower after RI than after IL. The low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P < .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities were observed at baseline, the protein content was lower (P < .05) after IL (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05). LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both treatments and did not normalize. IDDM and control subjects showed similar LDL subfraction distribution at baseline and after both treatments. Two-hour postprandial VLDL composition alterations, although improved after RI, completely normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) activities were similar to the control group and did not change after both treatments. Hepatic lipase (HL) activity was lower in diabetic patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after both treatments. In conclusion, in IDDM patients, IL (injected immediately before the meal) may offer small different effects on lipoprotein metabolism versus RI (injected 30 minutes before the meal) that, taken together, do not seem relevant.

Adult↗