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Biomedical subjects

T Strack

Publications and source records attributed to T Strack.

At least 19 recordsLinked to original sources
PubMed1999

Effectiveness of human ultralente versus NPH insulin in providing basal insulin replacement for an insulin lispro multiple daily injection regimen. A double-blind randomized prospective trial. The Canadian Lispro Study Group.

OBJECTIVE: To compare human ultralente (UL) insulin with human NPH insulin as basal insulin replacement in patients who use insulin lispro before meals. RESEARCH DESIGN AND METHODS: There were 178 patients with type 1 diabetes who were randomized to receive either human NPH or UL insulin once daily at bedtime in a 1-year double-blind clinical study. Eight-point blood glucose profiles were collected once monthly in the first 4 months, then every 2 months for the remainder of the study. Patients were also asked to perform premeal blood glucose measurements every day throughout the study. If before-supper blood glucose levels consistently exceeded 8 mmol/l despite optimal postprandial control with the lunch dose of insulin lispro, a second dose of basal insulin before breakfast was administered. RESULTS: For the group as a whole, insulin doses before meals and basal insulin doses were similar at baseline. At study's end, meal doses remained the same (30 +/- 1 U/day for UL., 29 +/- 1 U/day for NPH), while basal requirements were somewhat higher for the UL group than the NPH group: 30 +/- 1 U/day vs. 26 +/- 1 U/day, respectively (P < 0.05). The rates of severe hypoglycemia were similar for patients on NPH (0.05 +/- 0.03 per patient every 30 days) and for UL (0.07 +/- 0.04 per patient every 30 days) insulin. There was no significant difference for glycemic control between the NPH and UL groups overall (HbAlc at the end of the study: 7.6 +/- 0.1 vs. 7.7 +/- 0.1%, respectively), and by study's end a similar number of patients in the NPH and the UL groups needed to be switched to twice daily basal insulin (21 and 24%, respectively). Patients requiring twice-daily injections of basal insulin had a longer duration of diabetes (17.8 +/- 1.5 vs. 14.0 +/- 0.8 years, P < 0.05) and a highest baseline HbAlc (8.6 +/- 0.1 vs. 8.0 +/- 0.1%, P < 0.002) and were significantly older (38 +/- 2 vs. 34 +/- 1 years, P < 0.007). Patients who were switched to twice-daily NPH insulin had lower HbAlc levels at study's end compared with those switched to twice-daily UL insulin (7.7 +/- 0.2 vs. 8.2 +/- 0.3%), but this difference was not statistically significant. Distribution of hypoglycemia across the day was also similar in both groups. CONCLUSIONS: UL or NPH insulin, when used as the basal insulin for multiple injection regimens, results in similar glycemic control in patients using insulin lispro before meals. However, in patients who require a second injection of basal insulin, NPH insulin appears to provide lower prebreakfast and prelunch glucose levels compared with UL insulin.

Adult↗
PubMed1998

Counterregulatory hormone responses after long-term continuous subcutaneous insulin infusion with lispro insulin.

OBJECTIVE: To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia. RESEARCH DESIGN AND METHODS: Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 +/- 0.48; mean HbA1c 7.84 +/- 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period. RESULTS: HbA1c was significantly lower with LP versus HR (7.47 +/- 0.28% vs. 7.9 +/- 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 +/- 2.9 vs. 11.8 +/- 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period. CONCLUSIONS: The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.

Adult↗
PubMed1998

Effect of continuous subcutaneous insulin infusion with lispro on hepatic responsiveness to glucagon in type 1 diabetes.

OBJECTIVE: People with type 1 diabetes frequently develop a blunted counterregulatory hormone response to hypoglycemia coupled with a decreased hepatic response to glucagon, and consequently, they have an increased risk of severe hypoglycemia. We have evaluated the effect of insulin lispro (Humalog) versus regular human insulin (Humulin R) on the hepatic glucose production (HGP) response to glucagon in type 1 diabetic patients on intensive insulin therapy with continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: Ten subjects on CSII were treated for 3 months with lispro and 3 months with regular insulin in a double-blind randomized crossover study After 3 months of treatment with each insulin, hepatic sensitivity to glucagon was measured in each subject. The test consisted of a 4-h simultaneous infusion of somatostatin (450 microg/h) to suppress endogenous glucagon, regular insulin (0.15 mU x kg(-1) x min(-1)), glucose at a variable rate to maintain plasma glucose near 5 mmol/l, and D-[6,6-2H2]glucose to measure HGP During the last 2 h, glucagon was infused at 1.5 ng x kg(-1) x min(-1). Eight nondiabetic people served as control subjects. RESULTS: During the glucagon infusion period, free plasma insulin levels in the diabetic subjects were 71.7+/-1.6 vs. 74.8+/-0.5 pmol/l after lispro and regular insulin treatment, with plasma glucagon levels of 88.3+/-1.8 and 83.7+/-1.5 ng/l for insulin:glucagon ratios of 2.8 and 3.0. respectively (NS). However, plasma glucose increased to 9.2+/-1.1 mmo/l after lispro insulin compared with 7.1+/-0.9 mmol/l after regular insulin (P < 0.01), and the rise in HGP was 5.7 +/-2.8 micromol x kg(-1) x min(-1) after lispro insulin versus 3.1+/-2.9 micromol x kg(-1) x min(-1) after regular insulin treatment (P=0.02). In the control subjects, HGP increased by 10.7+/-4.2 micromol x kg(-1) x min(-1) under glucagon infusion. CONCLUSIONS: Insulin lispro treatment by CSII was associated with a heightened response in HGP to glucagon compared with regular human insulin. This suggests that insulin lispro increases the sensitivity of the liver to glucagon and could potentially decrease the risk of severe hypoglycemia.

Adult↗
PubMed1997

Insulin lispro in CSII: results of a double-blind crossover study.

Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection, resulting in higher insulin levels at an earlier point in time and a shorter duration of action. The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postprandial and overall control in 30 IDDM patients (age, 35.1 +/- 1.5 years; male-female ratio, 17:13; BMI, 24.8 +/- 0.5 kg/m2; HbA1c, 8.03 +/- 0.13% at baseline) treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) in a double-blind crossover clinical study. Patients were randomized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months. All meal boluses were given immediately before breakfast, lunch, and supper. An eight-point blood glucose profile was measured once weekly, and HbA1c levels were measured monthly. At the end of the 3-month treatment period, HbA1c levels were significantly lower with insulin lispro, compared with human regular insulin: 7.66 +/- 0.13 vs. 8.00 +/- 0.16% (P = 0.0041). While preprandial, bedtime, and 2:00 A.M. values for blood glucose were not significantly different, 1-h postprandial blood glucose was significantly improved after breakfast, lunch, and dinner with insulin lispro, compared with human regular insulin: 8.35 vs. 9.79 mmol/l (P = 0.006), 7.58 vs. 8.74 mmol/l (P = 0.049), and 7.85 vs. 9.01 mmol/l (P = 0.03). The incidence of hypoglycemia per 30 days (blood glucose levels, <3.0 mmol/l) was 8.4 +/- 1.3 before randomization, decreasing to 6.0 +/- 0.9 for insulin lispro and to 7.6 +/- 1.3 for regular insulin during the last month of the study. Two patients in each group reported insulin precipitation. We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia.

Adult↗
PubMed1996

Phase I trial of gemcitabine and cisplatin in advanced non-small cell lung cancer: a preliminary report.

A phase I trial was performed to investigate the tolerability and efficacy of the novel nucleoside analogue gemcitabine in combination with cisplatin in the treatment of advanced non-small cell lung cancer. Both cisplatin and gemcitabine were administered as 30 min infusions weekly x 3 with a week of rest. There was one dose escalation of cisplatin from 25 mg/m2 (dose level 1) to 30 mg/m2 (in subsequent dose levels 2-5), such that the mean dose intensity for the weekly x 3 q 4 week cycle was 22.5 mg/m2/week which is close to that achieved with 100 mg/m2 bolus monthly. Gemcitabine was initiated at 1000 mg/m2 (dose levels 1 and 2) then escalated by 250 mg/m2/week to 1750 mg/m2 (dose level 5). Of 32 chemotherapy-naive patients entered (22 males, 10 females; median age 61 years, range 29-74 years), 11 had localized tumours (2 stage IIIa, 9 IIIb) and 21 had stage IV tumours with haematogenous metastases and a poor prognosis. Twenty-one patients had adenocarcinoma, 4 squamous cell carcinoma, 6 large cell undifferentiated tumors, and one had mixed squamous and adenocarcinoma. Dose-limiting toxicity was not seen in more than one patient in cycle 1 at any dose level. Grade 4 granulocytopenia and thrombocytopenia occurred more frequently with repeated dosing, necessitating dose reductions except at the lowest dose level (cisplatin 25 mg/m2, gemcitabine 1000 mg/m2). Non-haematological toxicity was mild and rapidly reversible. Cisplatin administration led to a higher frequency of nausea and vomiting than that seen with gemcitabine alone, but this was easily controlled with antiemetics. In the 28 patients evaluable, to date responses have been seen at most dose levels, with an overall response rate 35.7%. This phase I trial is ongoing and further dose escalation is intended to determine the MTD of gemcitabine.

Adult↗
PubMed1996

Phase I dose-escalation trial of gemcitabine and cisplatin for advanced non-small-cell lung cancer: usefulness of mathematic modeling to determine maximum-tolerable dose.

PURPOSE: This study was undertaken to determine the maximum-tolerated doses of gemcitabine and cisplatin, each given weekly for 3 weeks with a 1-week rest. PATIENTS AND METHODS: Patients less than 75 years of age were eligible if they had stage III/IV non-small-cell lung cancer (NSCLC), life expectancy > or = 12 weeks, hemoglobin level > or = 10 g/dL, granulocyte count > or = 2 x 10(9)/L, platelet count > or = 100 x 10(9)/L, hepatic enzymes < or = three times the upper limit of normal, and creatinine concentration < or = 130 mumoles/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week for 3 weeks. At dose level 2, cisplatin was increased to 30 mg/m2/wk for 3 weeks, and thereafter only gemcitabine was increased by 250 mg/m2/wk at each dose level to a maximum of 2,250 mg/m2/wk. RESULTS: There were 33 men and 17 women, with a median age of 62 years. Pathology included adenocarcinoma in 35 patients, squamous in eight, large cell in six, and mixed histology in one. Sixteen patients had stage III and 34 had stage IV tumors. The median nadir granulocyte and platelet counts decreased with each dose level, but cycle 1 dose-limiting toxicity (DLT) in > or = two patients was not encountered in cycle 1, even at the highest dose level. Cumulative marrow toxicity was seen at all levels, which resulted in frequent dose reductions or omissions. A mathematic model of all toxicities over time suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in < or = 33% of patients over four cycles. Of 47 assessable patients, 14 achieved a partial response (30%; confidence interval, 17% to 43%). The median duration was 16 weeks and the median survival time was 24 weeks (range, 3.5-64+). CONCLUSION: Weekly gemcitabine and cisplatin are active against NSCLC, and the recommended phase II doses are 30 and 1,500 mg/m2/wk for 3 weeks, respectively.

Adenocarcinoma↗
PubMed1996

Final results of the Canadian phase I dose escalation trial of gemcitabine and cisplatin for advanced non-small cell lung cancer.

When given at doses of > or = 1,250 mg2 weekly x 3 with a 1-week break, single-agent gemcitabine induces responses in more than 20% of previously untreated patients with non-small cell lung cancer (NSCLC). This study was undertaken to determine the maximum tolerated doses for a 4-week cycle of gemcitabine and cisplatin given in combination weekly x 3 with a 1-week rest. Patients younger than 75 years were eligible if they had stage III/IV NSCLC, life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 2 x 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes < or = 3 times the upper limit of normal, and serum creatinine < or = 130 mumol/L. The starting doses for gemcitabine and cisplatin were 1,000 mg/m2 and 25 mg/m2 per week x 3, respectively. At dose level 2 cisplatin was increased to 30 mg/m2/week x 3. Thereafter only the gemcitabine was increased, by 250 mg/m2/wk at each dose level, to a maximum of 2,250 mg/m2/wk at dose level 7. The median nadir granulocyte and platelet counts decreased with each dose level, but dose-limiting toxicity in two or more patients was not encountered in the first treatment cycle, even at dose level 7. Cumulative bone marrow toxicity was seen at all dose levels, and this resulted in frequent dose reductions or omissions. Dose delivery was well maintained over time only at dose level 1. Grade 3-4 nonhematologic toxicity was infrequent and rarely dose limiting. An assessment of all toxicities seen during the treatment cycles was undertaken using continual reassessment methodology. This model suggested that dose level 4 (cisplatin 30 mg/m2/wk and gemcitabine 1,500 mg/m2/wk) would be the maximum dose at which grade 4 toxicity would be expected in up to 33% of patients at any time over four treatment cycles. Of 47 patients evaluable for response, partial remission was seen in 14, with an overall response rate of 30% (confidence interval, 17% to 43%). The median duration of response was 16 weeks and the median survival time was 24 weeks (range, 3.5 to 64+ weeks). A phase II trial is planned in which dose level 4 will be evaluated in a larger cohort of patients with NSCLC.

Adult↗
PubMed1993

[Selective blood sampling from the sinus petrosus inferior: a comparison of CRF and TRH stimulation].

In 10 patients with hypophyseal Cushing microadenomas, selective bilateral sampling from the inferior petrosal sinuses was performed and the effect of stimulation by iv TRH and CRF was compared. On the side of the microadenoma. ACTH concentration rose from 650 +/- 242 pg/ml to 2712 +/- 843 pg/ml following injection of CRF and 2025 +/- 242 pg/ml after TRH. Contralateral values were 165 +/- 79 pg/ml, 490 +/- 200 pg/ml and 165 +/- 72 pg/ml respectively. Prolactin concentration on the side of the adenoma was 98 +/- 49 ng/ml before stimulation, 236 +/- 62 ng/ml after CRF and 747 +/- 168 ng/ml after TRH. Contralateral concentration was 22 +/- 10 ng/ml, 64 +/- 19 ng/ml respectively. Sampling localised all adenomas correctly, whereas contrast-enhanced MRT diagnosed only four adenomas.

Adenoma↗
PubMed1990

[Computer-assisted diabetes therapy--a challenge for modern medicine].

By the use of computers in the therapy of diabetes new diagnostic and therapeutic possibilities are brought about. The computers open the possibility for a comprehensive data seizing, evaluation of the stored material and possibilities of various abilities for demonstration. Moreover, it becomes possible to regulate the therapy more subtly with the help of self-adapting programs and in its consequence to render it more effective than the own management of therapy is able to do it. This manifests itself significantly in badly or only moderately stabilised diabetics. In very well educated and trained diabetics even the superiority of the management of the computer becomes visible. Here this can no more be shown in the improvement of the stabilisation of diabetes which can no more be improved without risks for the patient. In these patients it is the reduction of the frequency of hyperglycaemia, by means of which can be shown that the stabilisation of diabetes in diabetics who were well stabilised already before can still be improved by the computer therapy. In addition to this the computer seems to cause further positive effects on the learning behaviour of the diabetics.

Blood Glucose↗
PubMed1989

[Osteoporosis: a case report].

A 56-year-old female patient was admitted to our hospital because she was suffering from severe osteoporosis. The patient had experienced repeated spontaneous fractures for 1.5 years such as serial rib fractures, fractures of the sternum and most recently fracture of the neck of the femur after a minimal trauma. Histology revealed a low-turnover-osteoporosis. Subsequent radiologic examination showed extreme osteoporosis of the skeleton with numerous compression fractures of the vertebral bodies as the most outstanding finding. The bone histology and the relatively short history of spontaneous fractures led us to investigate endogenous hypercortisolism as a possible cause although clinical signs were absent. An attenuated diurnal variation of cortisol levels and lack of suppressibility of cortisol was found. Furthermore, magnetic resonance tomography showed a microadenoma of the pituitary gland. Computerized tomography of the adrenals was normal. Transsphenoidal surgery confirmed the tentative diagnosis and histological examination revealed a bilateral adenoma of the pituitary gland.

Adenoma↗
PubMed1988

Compliance in microcomputer-assisted conventional insulin therapy: computer simulation study results.

Compliance in diabetes self-management is a complex issue. It involves the interdependent daily actions of self-measurement of blood glucose and adherence to a prescribed schedule of daily activities. This impacts strongly on lifestyle because it necessitates precise meal timing as well as control of size and carbohydrate content. We sought to identify how strongly relaxing the lifestyle constraints per se would impact the ability to achieve improved metabolic control. To isolate these effects from those that result from poor measurement compliance, we used a computer simulator called OMNI et al. Furthermore, to standardize the "clinical" therapy, a second microprocessor device called an "Insulin Dosage Computer" was used to adjust insulin doses based on the usual clinical practice of four times a day precibal blood glucose measurements. Ten type 1 diabetic patients were stimulated and each followed for 120 simulated days. In each such subject, the simulation was repeated three times to include three different levels of lifestyle compliance ranging from excellent to poor. In all three protocols, starting from a level of poor control of diabetes, mean blood glucose values were significantly improved without significant differences after 120 days of computer-simulated treatment. Only the standard deviations, expressing the fluctuations of blood glucose and hence its stability, increased with decreasing lifestyle compliance. This computer simulation predicts that consistent self-monitoring of four blood glucose values per day is the cornerstone of diabetic self-control and that the use of these data according to a standardized therapeutic algorithm for insulin adjustment may successfully stabilize even patients with poor lifestyle compliance. Clinical studies must follow.

Blood Glucose↗
PubMed1987

Selective in situ pancreatic perfusion via chronic in vivo celiac artery catheterization.

A new technique to catheterize the celiac artery has been developed. This has opened the possibility for direct in vivo, in situ study of pancreatic endocrine cell function in a conscious experimental animal. The catheter is small, soft and placed without arterial ligation so that celiac artery, hepatic, splenic, and pancreatic blood flows were essentially not compromised. Arterial vessel integrity, absence of inflammation, and thrombosis as well as catheter patency were achieved for periods exceeding eight months. Metabolically and hormonally, the presence of the catheter had no effect on the fasting status. However, we found somewhat lower glucose levels and higher insulin levels in the response to oral glucose challenges after catheterization, but these differences were statistically not significant. Glucose loads of 50 mg/kg (0.75 g) administered directly to the pancreas via the celiac artery produced peak insulin levels similar to peripheral glucose loads some tenfold larger. We suggest that this technique may be useful to selectively study the first-pass pancreatic response to a variety of hormones, drugs or metabolic substrates.

Administration, Oral↗
PubMed1986

[Selective blood sampling from the inferior petrosal sinus using digital subtraction angiography].

Simultaneous bilateral venous sampling of blood from the inferior petrosal sinuses helps in the differentiation between peripheral and central ACTH hypersecretion. One can also locate the site of a hormonally active hypophyseal micro-adenoma that cannot be demonstrated by other methods. The authors have experience with fifteen patients and discuss the indications, technique and problems as well as the advantages of using digital subtraction angiography.

Adenoma↗
PubMed1985

Computer assisted conventional insulin therapy.

Considerable interest has recently been focused on the computer as a new method to improve outpatient treatment of insulin dependent diabetics. Different ways of programming procedures have been proposed to simulate an experienced physician's capability to adjust insulin dosage in a mathematical form. We report here the results of a controlled study with a program for conventional insulin therapy in in- and outpatient treatment. Eleven inpatient type-I-diabetics could be well controlled after 8 days, and 6 outpatient treated type-I-diabetics improved all relevant metabolic parameters after 30 days compared to a control period of the same duration. So, computer assisted therapy promises to be a worthful aid in the treatment of diabetes.

Blood Glucose↗
PubMed1984

Development of individual insulin infusion profiles for open loop infusion systems.

A computer controlled syringe-type insulin infusion pump storing up to 254 different infusion rates, eight different meal programs and two different basal rates automatically changeable during 24 h in EPROM was used for insulin infusion applying a wavy step profile. This profile approaching the physiological postprandial insulin secretion of the B-cell was calculated by an algorithm following the biphasic insulin secretion model proposed by E. Cerasi . The computer program for the open loop infusion device simulated the feed-back structure of a closed loop insulin secretion control by an algorithm based upon a theoretical postprandial blood sugar profile. Fifteen unstable juvenile onset insulin requiring diabetics could be well controlled after two to three days of an intravenous open loop insulin infusion program. The programs consisted of two constant basal rates and superimposed wavy step profile programs activated at the beginning of each meal. The preabsorptive bolus or cephalic phase was an additional tool both for improved postprandial blood sugar control and further reduction of insulin consumption. The programmable insulin infusion device proved as a valuable tool for the study of a sophisticated insulin infusion profile suitable as well for open loop as for closed loop insulin infusion systems.

Adult↗