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Biomedical subjects

J H Anderson

Publications and source records attributed to J H Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes.

OBJECTIVE: A precise time-action profile of insulin lispro (Humalog) at mealtime may reduce the incidence of severe hypoglycemia. Because it is a rare complication, we performed a cumulative meta-analysis to compare the frequency of severe hypoglycemia during insulin lispro and human regular insulin therapy in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: The analysis included eight large multi-center clinical trials, three with parallel and five with crossover designs. The studies included 2,576 type 1 diabetic patients in total, with 2,327 receiving insulin lispro and 2,339 receiving regular human insulin, representing > 1,400 patient-years of insulin therapy Severe hypoglycemia was defined as coma or requiring glucagon or intravenous glucose. The patients received either NPH or ultralente as their basal insulin and insulin lispro or regular human insulin before each meal. RESULTS: Seventy-two patients (3.1%) had a total of 102 severe hypoglycemic episodes during insulin lispro therapy compared with 102 patients (4.4%) with a total of 131 episodes during regular human insulin therapy (P=0.024). CONCLUSIONS: The results of this meta-analysis demonstrate that in type 1 diabetic patients, the frequency of severe hypoglycemia can be reduced by taking insulin lispro as compared with regular human insulin therapy.

Clinical Trials as Topic↗
PubMed1997

Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.

BACKGROUND: Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy. It has a fast absorption rate and short duration of action. The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been tested. OBJECTIVES: To compare insulin lispro and human regular insulin in the mealtime treatment of patients with NIDDM. METHODS: A 6-month, randomized, multinational (16 countries), multicenter (80 sites) clinical trial with an open-label, crossover design was performed in 722 patients with NIDDM. Insulin lispro was injected immediately before and human regular insulin 30 to 45 minutes before the meal. RESULTS: Throughout the study, the postprandial rise in serum glucose levels was significantly lower during insulin lispro than human regular insulin treatment. At end point the rise (mean +/- SEM) in serum glucose levels was 30% lower at 1 hour (2.6 +/- 0.1 mmol/L [46.8 +/- 1.8 mg/ dL] for lispro vs 3.7 +/- 0.1 mmol/L [66.6 +/- 1.8 mg/dL] for human regular insulin) and 53% lower 2 hours after the test meal (1.4 +/- 0.1 mmol/L [25.2 +/- 1.8 mg/dL] for lispro vs 3.0 +/- 0.1 mmol/L [54.0 +/- 1.8 mg/dL] for human regular insulin) with insulin lispro compared with human regular insulin therapy (P < .001 for both intervals). During insulin lispro therapy the rate of hypoglycemia overall (P = .01) and overnight (P < .001) was lower and the number of asymptomatic hypoglycemic episodes was smaller (P = .03) than during human regular insulin therapy. Associated with a similar 13% increase (P < .001) in the total daily insulin dose, the glycosylated hemoglobin level decreased (P < .001) equally in both treatment groups. Serum lipid and lipoprotein levels remained unchanged. There were no differences in the adverse events between the 2 treatment groups. CONCLUSIONS: Compared with human regular insulin therapy, mealtime therapy with insulin lispro reduced postprandial hyperglycemia and may decrease the rate of mild hypoglycemic episodes in patients with NIDDM.

Blood Glucose↗
PubMed1997

Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset.

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant cerebellar ataxia associated with small expansions of the trinucleotide repeat (CAG)n in the gene CACNL1A4 on chromosome 19p13, which encodes the alpha1 subunit of a P/Q-type voltage-gated calcium channel. We describe clinical, genetic, neuroimaging, neuropathological, and quantitative oculomotor studies in four kindreds with SCA6. We found strong genetic linkage of the disease to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles in two large ataxia kindreds. The expanded alleles were all of a single size (repeat number) within the two large kindreds, numbering 22 and 23 repeat units. It is noteworthy that the age of onset of ataxia ranged from 24 to 63 years among all affected individuals, despite the uniform repeat number. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of ocular motor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibulo-ocular reflex. These studies identify a distinct phenotype associated with this newly recognized form of dominant SCA.

Adult↗
PubMed1997

Failure of the Hong Kong criteria to predict the severity of acute pancreatitis.

CONCLUSION: The results of the present study demonstrate that the HK criteria do not provide effective prediction of severity. BACKGROUND: Fan et al. (1) have reported previously that a blood urea (BU) > 7.4 mmol/L and/or glucose (BG) > 11 mmol/L at the time of admission to hospital detects a severe attack of acute pancreatitis with a sensitivity of 76% and specificity of 75%. However, a similar study conducted in the West of Scotland did not confirm these findings (sensitivity 33% and specificity 83%). The reason underlying this discrepancy in prediction is unclear, but it may be because of differences in the nature of acute pancreatitis between Asian and Western populations. AIMS: In this study we examined the predictive ability of the Hong Kong (HK) criteria in a patient population similar to that studied by Fan et al. PATIENTS AND METHODS: A consecutive series of 130 patients experienced 135 attacks of acute pancreatitis. One-hundred-and-four (77%) attacks were mild and 31 (23%) severe (including 12 [9.0%] deaths). Eighty-nine (66%) episodes had a biliary etiology. In 19 (14%) of these episodes, the gallstones had a primary ductal origin being associated with recurrent pyogenic cholangitis. RESULTS: Median admission BU concentrations were 5.2 mmol/L (range 3.6-32.1 mmol/L) for the mild group and 7.6 mmol/L (range 3.6-28.8 mmol/L) for the severe group. Corresponding values of BG were 7.1 mmol/L (range 2.1-17.9 mmol/L) and 8.4 mmol/L (range 3.6-28.8 mmol/L), respectively. Differences in admission BU concentrations between patients with mild and severe episodes were significant (p = 0.0001). However, differences in BG concentrations were not (p = 0.16). In the severe group, 14 patients had BU and four patients BG concentrations above the cut-off values. The HK criteria predicted severe acute pancreatitis with a sensitivity of 52% and specificity of 80%. These results compare with values of 79 and 56% for the Ranson criteria and 83 and 60% for the Glasgow score. The best prediction was provided by the APACHE II score 24 h post admission (sensitivity 79%, specificity 82%).

Acute Disease↗
PubMed1997

Wilms tumor and multicystic dysplastic kidney disease.

PURPOSE: There is ongoing controversy concerning the management of multicystic dysplastic kidney disease, particularly with regard to the potential for malignant transformation. Our report fuels the debate by adding the 2 youngest patients in whom malignancy was present from birth or developed subsequently. MATERIALS AND METHODS: Two well documented cases of malignancy associated with multicystic dysplastic kidney disease are presented in 2 female infants (5 and 3 months old). The 5-month-old female infant was followed for multicystic dysplastic kidney disease and had no evidence of tumor either antenatally or at birth. The 3-month-old presented with hypertension and interventricular septal defect. A renal tumor was present on initial ultrasound. RESULTS: Even though malignant degeneration is rare in multicystic dysplastic kidney disease, 9 cases have been reported in the literature so far. Of these cases 3 were Wilms tumor, 5 were renal cell carcinomas and 1 mesothelioma. CONCLUSIONS: Our 2 cases lend support to the surgical management of multicystic dysplastic kidney disease, particularly as nephrectomy can now be performed in a day surgery setting with minimal morbidity. Only the risks of coexisting malignancy and possible malignant degeneration transformation are specifically addressed in this article. Other complications of multicystic dysplastic kidney disease such as hypertension, infection, abdominal pain, hematuria and persistent dysplastic renal tissue despite ultrasonographic resolution of multicystic dysplastic kidney disease are additional risk factors to be considered. A recommendation for nephrectomy in all cases of multicystic dysplastic kidney disease cannot be based only on these 2 cases. Several other factors must be weighed before making that decision.

Female↗
PubMed1997

Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.

Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.

Adult↗
PubMed1997

Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. The Benelux-UK Insulin Lispro Study Group.

OBJECTIVE: Several studies have suggested that use of the short-acting insulin analog, insulin lispro, in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin. This effect might be more pronounced in well-controlled patients, since intensive treatment of IDDM increases the rate of severe hypoglycemic events. This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients. RESEARCH DESIGN AND METHODS: This was an open, randomized, 6-month crossover study of 199 IDDM patients. Glycemic control was evaluated by HbA1c, home blood glucose measurements, and rate and timing of hypoglycemic events. At the end of the study, patients completed an evaluation form regarding therapy-related quality of life. RESULTS: HbA1c remained constant at approximately 7.3% throughout the study. Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin (mean -0.8 +/- 1.7 vs. 1.1 +/- 1.6 mmol/l, P < 0.001), as was the within-day variability (M value 27.7 +/- 19.7 vs. 30.2 +/- 23.1, P = 0.007). The incidence of severe hypoglycemic events (58 vs. 36, P = 0.037) including coma (16 vs. 3, P = 0.004) was significantly lower with insulin lispro than with regular insulin. Patients felt that insulin lispro increased flexibility and freedom of lifestyle. CONCLUSIONS: In well-controlled IDDM patients, insulin lispro is associated with a lower risk of severe hypoglycemia and coma.

Adult↗
PubMed1997

A robotic system for percutaneous renal access.

PURPOSE: Percutaneous renal access can be challenging, particularly when the collecting system is not distended. Precise entry into a selected calyx facilitates subsequent percutaneous manipulations, but this skill requires extensive experience. In an attempt to improve accuracy while decreasing technical challenges, we developed a robotic system that automates the task of fluoroscopic image-guided percutaneous needle placement. MATERIALS AND METHODS: The prototype system consisted of a three degree-of-freedom robot with a needle injector end-effector. Imaging was provided by a biplanar fluoroscope. After correction of image distortion and fluoroscope calibration, robot to image-space registration was completed. To validate the system's ability to insert a needle into a calyx, ex vivo porcine kidneys suspended in agarose gel and distended with iodinated contrast solution were used as a model. In situ renal access tests with three 20 kg. pigs were performed. Access was confirmed by passing a flexible wire or aspirating iodinated contrast from the collecting system. RESULTS: The diameter of target calyces ranged from 3 to 7 mm. The in vitro accuracy of final needle tip positioning was 0.43 mm. In the ex vivo model, successful "one stick" access occurred on 10 of 12 attempts (83%). In situ access on the first attempt was successful for 6 of 12 target calyces (50%). Needle or tissue deflection accounted for each failure. CONCLUSION: The feasibility of a robotic system to assist in the percutaneous access of small and delicate renal calyces has been demonstrated. Additional work in reducing procedural steps and correcting for tissue deflection during needle passage is necessary to improve accuracy and to allow for clinical application.

Animals↗
PubMed1996

Pre-meal insulin analogue insulin lispro vs Humulin R insulin treatment in young subjects with type 1 diabetes.

The present prospective one-year randomized study was conducted to compare soluble human insulin, with a new rapid-acting human insulin analogue, lispro, with respect to postprandial glucose excursions, frequency of hypoglycaemic episodes, glucose control, and long-term safety in 39 subjects (20 females, 19 males) with Type 1 diabetes. The duration of diabetes, gender distribution, and age were similar in the two groups. The total number of hypoglycaemic episodes was significantly less (p < 0.04, Wilcoxon rank sum test) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period. The 2-h postprandial glucose excursion at 1 year was also significantly less (p < 0.05, ANOVA) in the group treated with insulin lispro. The reductions in the total number of hypoglycaemic episodes and in the postprandial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes. However, the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue.

Amino Acid Sequence↗
PubMed1996

Response to regional chemotherapy in patients with variant hepatic arterial anatomy.

Regional chemotherapy for colorectal liver metastases is conventionally delivered by a catheter inserted into the gastroduodenal artery. However, up to 40 per cent of patients have 'unconventional' hepatic arterial anatomy. The response rate to regional chemotherapy was examined in 28 patients with normal and in 17 with variant hepatic arterial anatomy. There was no significant difference in response rates between the two groups.

Antimetabolites, Antineoplastic↗
PubMed1996

Predicted and actual BCNU concentrations in normal rabbit brain during intraarterial and intravenous infusions.

Normal New Zealand White rabbits were used to compare theoretical brain concentrations (based upon pharmacokinetic modeling) with actual experimental concentrations of BCNU following intraarterial (IA) or intravenous (IV) infusions. IA infusion therapy for brain tumor patients has been promising based upon theoretical predictions but of limited effectiveness clinically. Experimentally-measured rabbit carotid artery flow rates (63.9 +/- 3.4 ml/min) [mean +/- 1 sem] and BCNU systemic clearances (197 +/- 10.2 ml/min) predicted a theoretical IA advantage of 4.1 +/- 0.2. Ipsilateral brain concentrations of BCNU during and after IA infusions (20 mg/min/m2 over 15 minutes) were: 16.2 +/- 2.9, 19.0 +/- 3.9, 20.3 +/- 2.8, 4.8 +/- 2.5, 2.1 +/- 1.5, and 1.7 +/- 1.6 micrograms/gm brain at 5, 10, 15, 25, 35, and 45 minutes after infusion start. Mean concentrations at same time points in contralateral hemisphere (IA infusions) were: 7.1 +/- 1.8, 9.0 +/- 1.8, 10.3 +/- 0.7, 4.2 +/- 1.4, 2.2 +/- 1.2, 2.0 +/- 1.5 micrograms/gm brain. Concentrations in either hemisphere during IV infusions were similar to contralateral hemisphere during IA infusions. Comparison of ipsilateral: contralateral hemisphere ratios during and after IA infusions were: 3.2 +/- 0.4, 2.6 +/- 0.3, 2.2 +/- 0.3, 1.1 +/- 0.3, 1.0 +/- 0.4, and 0.9 +/- 0.3 at the same time points. Although these data show higher drug concentrations with IA infusions, actual values were considerably less than predicted by theoretical modeling. This discrepancy between theoretical and experimental results emphasizes need for further study of causes and remedies so that IA therapy can achieve better drug concentrations with less toxicity.

Animals↗
PubMed1996

High-intensity focused ultrasound ablation of rabbit kidney tumors.

High-intensity focused ultrasound (HIFU) is a noninvasive surgical technique in which ultrasound energy is delivered transcutaneously to a discrete area within the body. This energy can result in a well-defined zone of cellular death within the targeted tissue. We used HIFU in an effort to ablate rabbit VX-2 kidney tumors. A tumor cell suspension was injected into a renal segmental artery (Phase 1, nine rabbits) or directly into the lower pole parenchyma (Phase 2, nine rabbits). After a 2-week incubation period, open direct contact (Phase 1) or transcutaneous ablation (Phase 2) was performed. In Phase 1, after sonablation, there was pathologic evidence of tissue destruction in nine animals, and seven had both gross and histologic evidence of tumor ablation. There was sharp demarcation between viable and ablated tissue. In Phase 2, pathologic evidence of kidney ablation was seen in seven of nine animals. However, only two rabbits showed the well-demarcated effects of ablation in the tumor. High-intensity focused ultrasound can be effective at causing cell death in renal tumors and surrounding renal tissue. However, with the present ultrasound technology, imaging of renal lesions in the rabbit model is not adequate to consistently localize and completely ablate tumor.

Animals↗
PubMed1996

Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin.

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.

Adult↗
PubMed1995

Determination of nitrosourea compounds in brain tissue by gas chromatography and electron capture detection.

A relatively simple, high-sensitivity gas chromatographic assay is described for nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small biopsy samples of brain and other tissues. After extraction with ethyl acetate, secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic anhydride. Compounds are separated and quantitated by gas chromatography using a capillary column with temperature programming and an electron capture detector. Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a correlation coefficient of 0.929, and an extraction efficiency from whole brain of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay has been facile and sensitive in over 1000 brain biopsy specimens after intravenous and intraarterial infusions of BCNU.

Animals↗
PubMed1995

Effect of contrast concentration on abdominal enhancement in the rabbit: spiral computed tomography evaluation.

RATIONALE AND OBJECTIVES: We examined the effect of varying the concentration of a nonionic iodinated contrast agent on hepatic and abdominal vascular enhancement using spiral computed tomography (CT) scanning. METHODS: Spiral CT scans of 10 New Zealand male rabbits were obtained after intravenous injection of 240 mg I/ml iohexol and 350 mg I/ml iohexol injected at a rate of 2 ml/sec. Each animal was studied at both concentrations using four different contrast volumes: 2.3, 1.7, 1.1, and 0.57 ml/kg. Enhancement values of the aorta, hepatic veins, inferior vena cava, and hepatic parenchyma were measured using a region-of-interest cursor. RESULTS: At all contrast doses, equal volumes of contrast iohexol-350 resulted in statistically higher hepatic (p < or = .003, paired Student's t test) as well as vascular (p < .04) enhancement compared with iohexol-240. The slopes and intercepts of the enhancement curves for iohexol-350 and iohexol-240 were not statistically different (p >> .05) when enhancement was plotted as a function of total grams of iodine administered. CONCLUSION: With spiral CT scanning, appropriate contrast doses and relative costs per dose of iohexol should be considered on the basis of total iodine load administered rather than total volume administered.

Animals↗
PubMed1995

Case study: fluoxetine in the multimodal treatment of a preschool child with selective mutism.

Selective mutism is a rare disorder with poor treatment outcome. The current study describes the successful treatment of selective mutism in a preschool-age girl, using a comprehensive multifaceted therapeutic approach. The components of this intervention reflect a conceptualization of selective mutism that emphasizes anxiety as a core feature but also focuses on associated factors such as oppositional behaviors.

Anxiety Disorders↗