Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma.

Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Histologically, diffuse islet hyperplasia with increased number and size of islet cells is present and confirms the diagnosis. Differentiating NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy is the procedure of choice; however, recurrence of symptoms, although less debilitating, occurs commonly. Medical management with diazoxide, verapamil and octreotide can be used for persistent symptoms. Ultimately, near-total or total pancreatectomy may be necessary. We report a case of a 67-year-old male with hypoglycemia in whom preoperative workup, including computerized tomography abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH instead.

Erroneous HbA1c results in a patient with elevated HbC and HbF.

BACKGROUND: HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. METHODS: HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. RESULTS: HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. CONCLUSION: Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM.

Ultrafast excited state dynamics of the green fluorescent protein chromophore and its kindling fluorescent protein analogue.

Fluorescent proteins exhibit a very diverse range of photochemical behaviour, from efficient fluorescence through photochromism to photochemical reactivity. Remarkably this diverse behaviour arises from chromophores which have very similar structures. Here we describe measurements and modelling of the excited state dynamics in the chromophores of GFP (HBDI) and the kindling fluorescent protein, KFP (FHBMI). The methods are ultrafast fluorescence spectroscopy with sub 50 fs time resolution and the modelling is based on the Smoluchowski equation. The excited state decays of both chromophores are very fast, longer for their anions than for the neutral form and independent of wavelength. Detailed studies show the mean fluorescence wavelength to be independent of time. The excited state decay times are also observed to be a very weak function of solvent polarity and viscosity. These results are modelled utilising recently calculated potential energy surfaces for the ground and excited states as a function of the twist coordinates about the two bridging bonds of the chromophore. For FHBMI and the scarce data on the neutral HBDI the calculations are not successful suggesting the need for refinement of these potential energy surfaces. For HBDI in methanol the simulation is successful provided a strong dependence of the radiationless decay rate on the coordinate is assumed. Such dependence should be included in future calculations of excited state dynamics. When the simulations are extended to more viscous solvents they fail to reproduce the observed weak viscosity dependence. The implications of these results for the nature of the coordinate leading to radiationless decay in the chromophore and for the photodynamics of fluorescent proteins are discussed.

Ultrafast Studies of the Photophysics of Cis and Trans States of the Green Fluorescent Protein Chromophore.

Cis-trans photoisomerization is proposed as a key process in the photoswitching of some photoactivatable fluorescent proteins. Here we present ultrafast fluorescence measurements of the model GFP chromophore (HBDI) in the cis state and in a mixture of the cis and trans states. Our results demonstrate that the mean lifetimes of the cis and trans states are remarkably similar. Therefore, the specific isomer of the chromophore cannot be solely responsible for the different photophysics of the bright and dark states of photoactive proteins, which must therefore be due to differential interactions between the different isomers of the chromophore and the protein.

Can the clinical pulmonary infection score impact ICU antibiotic days?

BACKGROUND: The Clinical Pulmonary Infection Score (CPIS) has been used in the intensive care unit (ICU) as a decision tool for initiation of antibiotics in suspected pneumonia and also for discontinuing antibiotics if the CPIS score is 6 on day one receiving antibiotics empirically for pneumonia. METHODS: Over 11 months, we evaluated empiric antibiotics prospectively in two ICUs of a large tertiary university teaching hospital. A pneumonia committee (PC) reviewed all patients and defined pneumonia according to the guidelines of the U.S. Centers for Disease Control and Prevention (CDC). The CPIS was calculated for all patients at day one and day three of antibiotic therapy. The percentage of patients with a CPIS6 (823 antibiotic-days). In contrast, the PC determined 19 patients (23%) to have pneumonia by the CDC definition (731 antibiotic-days), with eight of these patients having a CPIS6. Pneumonia committee review resulted in fewer patients believed to have pneumonia and a greater percentage with a CPIS>6 (odds ratio [OR] 2.7; 95% confidence interval [CI] 0.86, 8.6; p=0.05). Restriction of antibiotics to patients with a CPIS>6 would have saved 1,460 antibiotic-days at day one and 1,053 days if treatment was delayed until day three. Clinical Pulmonary Infection Score ROC curves for the PC showed an area under the curve (AUC) of 0.82 (95% CI 0.72, 0.91), whereas the AUC for the ICU group was 0.85 (95% CI 0.79, 0.92). The sensitivity and specificity of a CPIS>6 for the PC were 79% and 75%, respectively, with correct prediction 76% of the time. The inter-observer reliability of the CPIS had a kappa value of 0.88. CONCLUSIONS: This prospective evaluation confirms that 50% of antibiotic-days in our ICU are used empirically for pneumonia when that infection is not likely to be present by either CDC or CPIS criteria. Although the CPIS has good reliability and acceptable sensitivity and specificity, PC review and CPIS