Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

Headaches that kill: a retrospective study of incidence, etiology and clinical features in cases of sudden death.

OBJECTIVE: The study objective was to analyze cases of sudden death that presented to the National Deptartment of Clinical Neurosciences, Ireland, over a 10-year period (1997-2006) where headache was the presenting symptom. BACKGROUND: Headache is a common yet challenging presentation in clinical neurology. In the vast majority of cases, the cause is trivial and reversible-however, in a few patients it may be indicative of a more sinister intracranial process. Recognizing associated "red flag" features and identifying possible life-threatening causes are crucial in ensuring prompt and appropriate intervention. DESIGN/METHODS: A retrospective study/database of all autopsy cases presenting to the Neuropathology Department in Beaumont Hospital, Dublin, was carried out for the period 1997-2006. Cases were selected with headache as the presenting clinical feature. Traumatic head injuries or known central nervous system (CNS) disorders were excluded. Autopsy and medical reports were reviewed to identify associated red flag features at initial presentation according to the International Classification of Headache Diseases, second edition (ICHD-II) criteria. RESULTS: Fifty-five autopsy cases out of a total of 499 complying with selection criteria were reviewed. Over the 10-year-study period, the number of cases of fatal headaches over time were negatively correlated. The most commonly associated red flag symptoms included age over 50: loss of consciousness and collapse, and worst/thunderclap character of headache. Cause of death at autopsy comprised vascular events 60.4% (N = 29), primary brain tumours/cysts 16.7% (N = 8) and meningitis 6.25% (N = 3). Aneurysms accounted for the majority of vascular cases 22.9% (N = 11), with loss of consciousness, occipital headache, neck pain and a focal neurological deficit seen more commonly in this subset of cases. CONCLUSIONS: Sudden-onset headache is a common and often alarming presentation. The majority of cases are of a benign nature; however, a small proportion may be indicative of a catastrophic etiology. Documenting "red flags" on initial presentation is crucial to acutely identify and treat those at highest risk. The results demonstrate an improving trend among clinicians in recognizing and initiating appropriate interventions in these patients, and highlights particular red flag features common in cases of fatal headaches.

Co-prescription of gastro-protectants in hospitalized patients: an analysis of what we do and what we think we do.

BACKGROUND: Proton pump inhibitors (PPIs) reduce the risk of upper gastrointestinal hemorrhage (UGIH) associated with the use of many medications. GOALS: To examine how clinicians perceive such risk and whether PPI co-prescribing is based on an accurate assessment. STUDY METHODS: Clinicians in a single teaching hospital were asked to estimate risk of UGIH and comment on PPI co-prescription in hypothetical patients. Records of 160 hospital in-patients (median age; 74 y) were then reviewed to examine PPI prescribing and risk factors for UGIH. RESULTS: In general, clinicians estimated UGIH risk accurately and reported low thresholds for PPI co-prescription. Prescribing records showed regular PPI use increased between admission and discharge of patients from 61/160 (38%) to 93/160 (58%). Ten percent had a prior history of peptic ulcer disease. Proton pump inhibitor prescription was significantly associated with the use of aspirin and clopidogrel. Half of the patients with multiple risk factors for UGIH on admission and almost a third at discharge were not co-prescribed a PPI. CONCLUSIONS: Clinicians generally estimate correctly the risk of UGIH and report a low threshold for prescribing gastro-protection. Despite this, prescribing practice does not consistently take account of relative risk of UGIH. Targeted PPI co-prescribing on the basis of risk factors would lead to more rational PPI use.

Isolated mononeuropathy multiplex--a rare manifestation of intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.