Clinical experience with an integrated continuous glucose sensor/insulin pump platform: A feasibility study

The recent US Food and Drug Administration approval of an integrated real-time continuous glucose monitoring (CGM) system and insulin pump (Medtronic Mini-Med Paradigm REAL-Time System; Medtronic MiniMed, Inc., Northridge, Calif) is the most recent breakthrough paving the way toward the development of a closedloop insulin delivery system that could revolutionize diabetes care. An early prototype of the MiniMed Paradigm REAL-Time System—which provided both realtime CGM and insulin pump therapy but was not yet fully integrated—was tested in 20 volunteer subjects with type 1 diabetes who wore the device for up to 2 y. Subjects were instructed on the technical use of the device but were provided no additional support, aside from their usual diabetes care. Participation in the trial averaged 317 d (minimum, 88 d; maximum, 618 d). Five participants prematurely dropped out of the study (2 because of the inconvenience of carrying 2 devices). Data from all subjects were analyzed. Subjects reduced their A1C by a mean of 1.1% (standard deviation, 0.8). After 3 mo of device use, the number of participants who achieved A1C <7% increased by more than 3-fold. Individuals with baseline A1C ≥7% had a 67% likelihood of achieving an A1C <7% by the first follow-up assessment. This observational study of combined CGM and insulin pump therapy suggests that this innovative device can help people achieve improved glycemic control. Given that only about one third of individuals with diabetes are achieving glycemic control targets, more effective methods to help patients avoid the devastating consequences of uncontrolled diabetes are desperately needed.     

Association of CYP2D6 100 C > T and 2850 C > T polymorphisms with generalized tonic clonic seizures among Indians

Summary. Multiple avenues of research have provided evidence for the role of genetic and environmental factors in epilepsy. Previous studies indicated an association of debrisoquine hydroxylase (CYP2D6) with susceptibility to epilepsy. In this study, association of CYP2D6 100C > T and 2850C > T polymorphisms with generalized tonic clonic seizures (GTCS) among Indians has been analysed using case-control approach. A significant association of 2850C > T (P = 0.015) has been observed. Comparison between phenytoin toxic and others among patients showed no association of these polymorphisms with phenytoin toxicity. The first two authors contributed equally in this work     

Multicenter clinical trial results with the LifeSite hemodialysis access system

BACKGROUND: The LifeSite Hemodialysis Access System is a subcutaneous access device designed to maximize blood flow while minimizing access-related complications. The purpose of this study was to compare the efficacy and safety of the LifeSite System to a similar but transcutaneous access device, the Tesio-Cath Hemodialysis Catheter. METHODS: The study was conducted in two phases. A multi-center randomized prospective design was utilized for the first phase (Phase 1) where thirty-four patients were enrolled in the Tesio-Cath group and 36 patients into the LifeSite group where 0.2% sodium oxychlorosene was used as an antimicrobial solution for the LifeSite. A nonrandomized, but otherwise identical, second phase of the study followed where a 70% isopropyl alcohol solution was utilized as the antimicrobial solution for 34 additional LifeSite patients (Phase 2). RESULTS: Device function was evaluated in Phase 1 of the trial. Actual blood flow (determined by ultrasound dilution) was greater in the LifeSite versus the Tesio-Cath group (358.7 vs. 331.8 mL/min, P < 0.001 for machine-indicated blood flow of 400 mL/min). Infection comparisons were performed for all three groups encompassing Phase 1 and 2 of the trial; Tesio-Catheter, LifeSite System with oxychlorosene, and LifeSite System with 70% isopropyl alcohol. Device-related infections were defined as systemic bacteremia without another obvious site of origin and exit site infections requiring systemic antibiotics or device removal. This revealed infection rates per 1000 device use days of 1.3 for the LifeSite alcohol group, 3.3 for the Tesio-Cath group, and 3.4 per for the LifeSite oxychlorosene group. There was no statistically significant difference in device related infection rates between the Tesio-Cath and the LifeSite oxychlorosene groups. There were significant differences in infection rate between LifeSite alcohol group and the other two groups (P < 0.05). Device thrombosis was defined by the need for instillation of thrombolytic agents to maintain blood flow>300 mL/min. There was no difference in the need for thrombolytic infusions between the LifeSite oxychlorosene group and the Tesio-Cath group (P = 0.1496); however, the LifeSite alcohol group required significantly fewer thrombolytic infusions than the Tesio-Cath group (P = 0.0295) to maintain adequate blood flow. Device survival at 6 months after stratification by diabetic status and adjusting for age was significantly better in the LifeSite alcohol group (89.9%) than in the LifeSite oxychlorosene group (64.8%, P = 0.0286) and in the Tesio-Cath (69.1%, P = 0.0292) group. CONCLUSIONS: The LifeSite Hemodialysis Access System, when used with 70% isopropyl alcohol as an antimicrobial solution, provides superior performance with a lower infection rate and better device survival than a standard cuffed tunneled hemodialysis catheter.     

UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver

Oxazepam is a commonly used 1,4-benzodiazepine anxiolytic drug that is polymorphically metabolized in humans. However, the molecular basis for this phenomenon is currently unknown. We have previously shown that S-oxazepam glucuronide, the major oxazepam metabolite, is selectively formed by UDP-glucuronosyltransferase (UGT) 2B15, whereas the minor R-oxazepam glucuronide is produced by multiple UGTs other than UGT2B15. Phenotype-genotype studies were conducted using microsomes and DNA prepared from the same set of 54 human livers. Sequencing of the UGT2B15 gene revealed three nonsynonymous polymorphisms, D85Y, T352I, and K523T, with variant allele frequencies of 0.56, 0.02, and 0.40, respectively. D85Y genotype showed a significant effect (p = 0.012) on S-oxazepam glucuronidation with lower median activities in 85Y/Y livers (49 pmol/min/mg protein) compared with 85D/D livers (131 pmol/min/mg), whereas 85D/Y livers were intermediate in activity (65 pmol/min/mg). There was also a significant trend (p = 0.049) for higher S-oxazepam activities in the two 352T/I livers (135 and 210 pmol/min/mg) compared with the remaining 352T/T livers (median, 64 pmol/min/mg). Conversely, K523T genotype had no apparent effect on oxazepam glucuronidation (p > 0.05). Donor gender also significantly influenced S-oxazepam glucuronidation with higher median activities in male (65 pmol/min/mg) compared with female (39 pmol/min/ mg) livers (p = 0.042). R-Oxazepam glucuronidation was not affected by either genotype or gender (p > 0.05). In conclusion, gender and D85Y genotype are identified as major determinants of S-oxazepam glucuronidation by human liver and may explain in part polymorphic oxazepam glucuronidation by human subjects.     

Laparoscopic removal of a rudimentary uterine horn during pregnancy. A case report

BACKGROUND: A unicornuate uterus with a rudimentary horn is a müllerian anomaly associated with endometriosis and pregnancy complications, including miscarriage, ectopic pregnancy, uterine rupture, preterm labor and malpresentation. Therefore, the horn is removed if it is thought to contain functional endometrium. This is usually done by laparotomy in the nonpregnant state. CASE: A woman presented during pregnancy with symptoms, examination and ultrasonogram suspicious for an ectopic pregnancy. Intraoperative findings and final pathology, however, showed a rudimentary uterine horn, which was laparoscopically removed, and a concomitant intrauterine pregnancy. CONCLUSION: A rudimentary uterine horn may present during pregnancy and mimic an ectopic pregnancy. In this case, the horn was removed laparoscopically.     

Nontropical pyomyositis: analysis of eight patients in an urban center

Nontropical pyomyositis is rare and usually associated with immunodeficiency virus (HIV) infection. This study assessed manifestations and response to treatment of nontropical pyomyositis in an area with a high prevalence of HIV seropositivity. We undertook a chart review of eight consecutive patients treated for pyomyositis - primary infection of skeletal muscles - from 1988 through 1998. All patients complained of myalgia; four (50%) had fever and six (75%) had leukocytosis. Muscles involved were deltoid, quadriceps, gluteus, and psoas. Six (75%) patients had identifiable risk factors for pyomyositis: HIV seropositivity (two), history of intravenous drug abuse (one), chronic paraplegia and malnutrition (one), diabetes and chronic renal failure (one), and leukemia (one). One patient had had streptococcal pharyngitis previously but was otherwise healthy; another, a 2-year-old, had no evidence of underlying disease. Staphylococcus aureus was the most common organism isolated (50%). Four patients were treated with incision and drainage plus antibiotics; the remaining four patients were treated with intravenous antibiotics only; all recovered. Nontropical pyomyositis, which is often associated with HIV seropositivity or chronic illness, has a favorable outcome. Treatment can be effective even without surgical intervention.