OBJECTIVETo compare the efficacy and safety of Technosphere insulin (TI) and insulin aspart in patients with type 1 diabetes. RESEARCH DESIGN AND METHODSThis open-label noninferiority trial compared the change in HbA 1c from baseline to week 24 of prandial TI (n = 174) with that of subcutaneous aspart (n = 171), both with basal insulin, in patients with type 1 diabetes and HbA 1c 7.5-10.0% (56.8-86.0 mmol/mol). RESULTSMean change in HbA 1c in TI patients (-0.21% [-2.3 mmol/mol]) from baseline (7.94% [63.3 mmol/mol]) was noninferior to that in aspart patients (-0.40% [-4.4 mmol/mol]) from baseline (7.92% [63.1 mmol/mol]). The between-group difference was 0.19% (2.1 mmol/mol) (95% CI 0.02-0.36), satisfying the noninferiority margin of 0.4%. However, more aspart patients achieved HbA 1c <7.0% (53.0 mmol/mol) (30.7% vs. 18.3%). TI patients had a small weight loss (-0.4 kg) compared with a gain (+0.9 kg) for aspart patients (P = 0.0102). TI patients had a lower hypoglycemia event rate than aspart patients (9.8 vs. 14.0 events/patient-month, P < 0.0001). Cough (generally mild) was the most frequent adverse event (31.6% with TI, 2.3% with aspart), leading to discontinuation in 5.7% of patients. Treatment group difference for mean change from baseline in forced expiratory volume in 1 s was small (40 mL) and disappeared upon TI discontinuation. CONCLUSIONSIn patients with type 1 diabetes receiving basal insulin, HbA 1c reduction with TI was noninferior to that of aspart, with less hypoglycemia and less weight gain but increased incidence of cough.

No abstract

BACKGROUND AND PURPOSE:Extension of malignant melanoma along cranial nerves is a little-known complication of malignant melanoma of the head and neck. We describe the clinical and MR imaging findings of perineural spread of malignant melanoma to cranial nerves, emphasizing that this entity occurs more commonly with desmoplastic histology and may have a long latent period following primary diagnosis.METHODS: At two institutions, we identified and retrospectively reviewed eight cases of malignant melanoma of the head and neck that had MR imaging evidence of perineural spread of disease. All patients underwent confirmatory tissue sampling.RESULTS: Seven patients had melanomas of the facial skin or lip, and one patient had a primary sinonasal lesion. By histopathology, these melanomas included five desmoplastic, two mucosal, and one poorly differentiated melanotic spindle-cell tumor. All patients developed symptomatic cranial neuropathy an average of 4.9 years from the time of initial diagnosis. MR imaging demonstrated postgadolinium enhancement of at least one branch of the trigeminal nerve in all cases and of at least one other cranial nerve in five cases. Other findings included abnormal contrast enhancement and soft tissue thickening in the cavernous sinus, Meckel's cave, and/or the cisternal segment of the trigeminal nerve.CONCLUSION: Although perineural spread of disease occurs most commonly with squamous cell carcinoma and adenoid cystic carcinoma, malignant melanoma must also be included in this differential diagnosis, particularly if the patient's pathology is known to be desmoplastic. Similarly, any patient with malignant melanoma of the head and neck who undergoes MR imaging should receive an imaging assessment focused on the likely routes of perineural spread.

According to the Rosenblueth-Simeone model, the heart rate (HR) is proportional to the sympathovagal balance. The individual proportionality constant is the intrinsic heart rate, which can only be determined invasively. The normalized low-frequency heart rate variability power (LF) has been raised as a calibrated noninvasive alternative. To concrete this assumption, we studied the individual LF-HR relation during incremental head-up tilt (0, 10, 20, 30, 40, 45, 50, 55, 60, 65, 70, 75, and 80 degrees) in 21 young, healthy males. HR (means +/- SD) increased from 61.0 +/- 9.1 beats/min at 0 degree to 85.9 +/- 18.3 beats/min at 80 degrees. LF increased from 45.8 +/- 16.7 nu at 0 degrees to 79.8 +/- 13.8 nu at 80 degrees (nu meaning normalized units). Individual regressions of LF on HR yielded correlation coefficients of 0.80 +/- 0.13 (means +/- SD). The demonstrated linear relation between LF and HR confirms the potential significance of heart rate variability as a noninvasive means of assessing the sympathovagal balance.

In 14 ADPKD patients the total body clearance and the urinary clearance of inulin using the constant infusion method were compared with the "single-shot" technique. Triplicate measurements of both clearances by each infusion method were obtained in 12 out of 14 patients. A high correlation was found between the total body clearance and the urinary clearance for both the constant infusion method (r = 0.96) and the single injection technique (r = 0.96). The coefficient of variation for the total body clearance of inulin was significantly lower for the constant infusion method and the single injection technique (7.8% and 7.1%) than for the urinary clearance of inulin (11.3% vs. 9.7%, P < 0.05). A constant overestimation of the urinary clearance by the total body clearance was observed with both methods (constant infusion method 8.3 ml.min-1 x 1.73 m-2 and single injection technique 13.4 ml.min-1 x 1.73 m-2). No concentration-dependent clearance was present. Determination of plasma inulin, especially at low levels, showed substantial interference by glucose. We conclude that, taking into account a constant overestimate of urinary clearance by the total body clearance of inulin, the single injection total body clearance possesses the best reproducibility and shows a good agreement with the conventional urinary clearance, which can be calculated by: GFR = TBCLss-13.1 ml.min-1 x 1.73 m-2 (in the range of 28 to 124 ml.min-1 x 1.73 m-2).