James H. Anderson

MECHANICAL DEVICES FOR ARTERIAL OCCLUSION

Two mechanical devices for the purpose of occluding vessels are presented.Cotton tails, small metallic segments with attached cotton threads, will effectively occlude small arteries of approximately 2 mm. in diameter.Wool coils, 5 cm. segments of the outer portion of steel guidewires with attached wool strands, obstructed major vessels just beyond the tip of the catheter.The use of these devices has been investigated in dogs and then applied clinically in the occlusion of renal arteries in patients with hypernephroma.

Reduction of Postprandial Hyperglycemia and Frequency of Hypoglycemia in IDDM Patients on Insulin-Analog Treatment

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.

Transcatheter occlusion of abdominal tumors.

Radiological and clinical experience with transcatheter intravascular occlusion of abdominal and pelvic tumors in 55 patients is presented. Major indications include control of hemorrhage, palliation of local tumor symptoms, and preoperative management of facilitate surgery. Methods of occlusion included embolization (clot, subcutaneous tissue, and Gelfoam), introduction of a stainless steel coil into larger vessels, and balloon catheters. Hemorrhage was controlled in 8 of 12 patients with bleeding gastrointestinal and pelvic tumors. Experience in 36 patients with hypernephroma is discussed. Initial observations are presented, including occlusion of the hepatic artery for dearterialization of primary and secondary neoplasms and of the splenic artery for hypersplenism.

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 multicenter 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.

A Modular Surgical Robotic System for Image Guided Percutaneous Procedures

This paper presents a robotic system for precise needle insertion under radiological guidance for surgical interventions and for delivery of therapy. It is extremely compact and is compatible with portable X-ray units and computer tomography scanners. The system presents a modular structure comprising a global positioning module, a miniature robotic module, and a radiolucent needle driver module. This system is the newest member of a growing family of modular surgical robots under development. The system may be operated stand-alone under joystick control making it readily adaptable to any operating room, or under full image guided computer control.

System for robotically assisted prostate biopsy and therapy with intraoperative CT guidance

RATIONALE AND OBJECTIVES The purpose of this study was to assess the work-in-progress prototype of an image-guided, robotic system for accurate and consistent placement of transperineal needles into the prostate with intraoperative image guidance inside the gantry of a computed tomographic (CT) scanner. MATERIALS AND METHODS The coach-mounted system consists of a seven-degrees-of-freedom, passive mounting arm: a remote-center-of-motion robot; and a motorized, radiolucent needle-insertion device to deliver 17-18-gauge implant and biopsy needles into the prostate with the transperineal route. The robot is registered to the image space with a stereotactic adapter. The surgeon plans and controls the intervention in the CT scanner room with a desktop computer that receives DICOM images from the CT scanner. The complete system fits in a carry-on suitcase, does not need calibration, and does not utilize vendor-specific features of the CT scanner. RESULTS In open air, the average accuracy was better than 1 mm at a 5-8-cm depth. In various phantoms, the average orientation error was 1.3 degrees, and the average distance between the needle tip and the target was 2 mm. CONCLUSION Results of preliminary experiments indicate that this robotic system may be suitable for transperineal needle placement into the prostate and shows potential in a variety of other percutaneous clinical applications.

Health-Related Quality-of-Life Results From Multinational Clinical Trials of Insulin Lispro: Assessing benefits of a new diabetes therapy

OBJECTIVE To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R). RESEARCH DESIGN AND METHODS We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses. RESULTS Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies. CONCLUSIONS Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility.

Biosynthetic human proinsulin. Review of chemistry, in vitro and in vivo receptor binding, animal and human pharmacology studies, and clinical trial experience.

Objective To describe the rationale for the preclinical and clinical developmental course of human proinsulin (HPI), the second product after human insulin for the treatment of diabetes mellitus to be manufactured by DNA technology. Research Design and Methods The relevant and available published and unpublished preclinical and clinical information generated on pork proinsulin and human proinsulin has been integrated to demonstrate how certain clinically attractive features of pork proinsulin (a soluble intermediate-acting and possibly hepatospecific insulin agonist) led to the development of HPI. Results Clinical pharmacology studies demonstrated that HPI was definitely, although marginally, hepatospecific. More striking was the finding that the intrasubject/patient coefficient of variation of response to HPI was significantly less than that observed with NPH insulin. However, the fact that unique efficacy in controlled multicenter studies was not demonstrated suggested that these pharmacological features were not translated into clinical benefit. In one multicenter new patient study there were six myocardial infarctions, including two deaths, in patients treated for ≥1 yr with HPI and none in the control group. Conclusions To obtain an independent review of the risks and benefits of HPI, in February 1988, Lilly convened a consultant group that examined all relevant information on HPI available. These experts shared our concerns about the safety of HPI in light of the failure to demonstrate unique efficacy. Accordingly, clinical trials with HPI were suspended in February 1988. Experience with HPI demonstrates the challenge associated with the development of new drugs in general and insulin agonists in particular.

Improved mealtime treatment of diabetes mellitus using an insulin analogue

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus (IDDM) and 295 patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were randomized to inject either regular human insulin 30 to 45 minutes before eating, or insulin lispro immediately before each meal, in addition to basal insulin. The postprandial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy. At end point the increment was significantly lower at 1 hour (35%) and at 2 hours (64%) after the meal in IDDM patients; in NIDDM patients, the increment was nonsignificantly lower at 1 hour (19%) and significantly lower at 2 hours (48%). IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin (HbA1c) levels in patients receiving regular human insulin (8.1% vs 8.3%). In NIDDM patients, HbA1c levels decreased equally in both treatment groups. Due to its fast absorption rate, insulin lispro improves postprandial control in diabetes. Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience.

“Mini” Gianturco Stainless Steel Coils for Transcatheter Vascular Occlusion

Small stainless steel coils have been developed for transcatheter vascular occlusion procedures. The coils can be passed through a 5-French polyethylene catheter, extending the clinical applications of coil occlusion procedures for small and/or tortuous vessels. Two cases describing the use of these coils are reported.