Recognition and assessment of critical illness

Early recognition of patients at risk of catastrophic deterioration leads to early treatment and improved prognosis. Delayed identification of critically ill patients and their delayed referral to intensive care are causes of increased mortality. Systematic assessment of patients at risk is a prerequisite for early recognition of critical illness. The assessment of the critically ill patient should follow the ‘Airway Breathing Circulation’ format. A blocked airway, raised respiratory rate and a systolic blood pressure that is smaller than the heart rate are signs of critical illness. Confusion and raised respiratory rate are the signs that most strongly indicate critical illness and are the most often missed during assessment. The assessment of critical illness is supplemented by risk factors, which result from concomitant chronic conditions, and haematological and biochemical tests, ECGs and radiographs. Lactate has a particular role in triage of patients with sepsis. For those clinicians inexperienced in critical care, simple scoring systems allow rapid assessment of the degree of physiological abnormality and the associated risk.     

Pharmacologic management of overactive bladder

Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer''s disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups has smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Galanin gene expression declines with adulthood in the cholinergic fields of the horizontal diagonal band of male rats

The neuropeptide galanin (GAL) influences leaming and memory processes, perhaps by inhibiting cholinergic function. We recently reported that, in the rat, the nucleus of the horizontal limb of the diagonal band (HDB) exhibits the highest level of GAL mRNA coexpression by basal forebrain (BF) cholinergic neurons and, in the HDB, virtually all GAL mRNA-expressing neurons correspond to the cholinergic cell type. Since GAL gene expression is induced across puberty in many brain regions, we used in situ hybridization histochemistry and quantitative autoradiography to assess GAL gene expression across the rostro-caudal extent of the HDB in prepubertal and adult male rats and to determine whether GAL gene expression is also regulated during maturation in this BF region. Our results show that the number of GAL mRNA-expressing cells per section is significantly reduced in the HDB with adulthood. Post-hoc analysis indicated that these age-associated differences in the number of GAL mRNA-expressing cells per section could be ascribed to the rostral and central subregions of the HDB. Age-related differences in the labeling intensity of GAL mRNA-expressing neurons were also detected in the rostral and central subregions of the HDB. No age-associated differences in GAL gene expression were found in the caudal HDB subregion. These results suggest that: (1) in contrast to other brain regions, GAL gene expression in the cholinergic BF may be negatively regulated by factors concomitant with puberty; and (2) the inhibition of cholinergic function by cosecreted GAL may be enhanced prior to puberty within cholinergic neurons of the rostral and central aspects of the HDB.     

Acute effects of high-dose thyrotropin releasing hormone infusions in Alzheimer's disease

Thyrotropin releasing hormone (TRH) was administered intravenously to ten patients with Alzheimer's Disease (AD) in a high-dose paradigm, thought to maximize central nervous system effects and potentially produce facilitation of cholinergic function, a known property of the neuropeptide. Acute effects of TRH on behavioral, cognitive and physiologic measures were assessed after patients received 0.1 mg/kg TRH, 0.3 mg/kg TRH and placebo, the higher TRH dose and placebo being given in a randomized, double-blind fashion. Patients showed statistically significant increases in arousal and improvement in affect, as well as a modest improvement in semantic memory, all after receiving the higher TRH dose. Both TRH doses produced transient rises in systolic blood pressure, with no effect on diastolic blood pressure, heart rate or temperature. This study suggests that high-dose TRH can be safely administered to AD patients and is neurobehaviorally active; further studies are needed to determine the extent and mechanism of the cognitive and psychobiological properties of this peptide in AD and other neuropsychiatric disorders.