Ambulance services: a logical, effective and economic solution

Ambulance services tend to be over-manned and under-productive. Metropolitan services, run by regions, cost more and are less sensitive to local needs than those run by areas. In offering his strictly personal views, Terry Ball, staff officer, West Yorkshire Metropolitan Ambulance Service, suggests that in future DHAs should run the ambulances.     

Development of a new controlled-release formulation of chlorpheniramine maleate using in vitro/in vivo correlations

Development of a controlled-released formulation of chlorpheniramine maleate is described, using in vitro/in vivo correlates, according to a process that has been termed "biorelevant dissolution". The process begins with simulations using several possible input rates combined with known disposition parameters of chlorpheniramine maleate. Based on desired plasma concentrations, an input rate is selected for further development which consists of a combination of clinical bioequivalence studies and further in vitro testing and simulations. The method is designed to reduce the requirements for trial and error clinical bioequivalence testing of a new controlled-release formulation.     

Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathologic distinction from normal aging

We compare clinicopathologic data from 10 subjects identified in the very mild stage of senile dementia of the Alzheimer type with findings from similar studies in four cognitively normal subjects. We based the diagnosis of very mild dementia in the 10 subjects on informant reports and the judgment of experienced clinicians. Deficits of some psychometric measures of memory, language, and speeded psychomotor performance were observed for these subjects. The histologic markers of Alzheimer's disease, including neurofibrillary tangles and both the "diffuse" and classic subtypes of senile plaques, were present in the neocortex in all 10 subjects but essentially were absent in the four controls. These findings indicate that even "questionable" dementia can be diagnostic for Alzheimer's disease. Furthermore, because truly normal aging may be unaccompanied by neocortical senile plaques and neurofibrillary tangles, the presence of these lesions should suggest the possibility of clinically undetected Alzheimer's disease.     

The trapped temporal horn: a trap in neuroradiological diagnosis.

Although the advent of computerized cranial tomography (CT) has decreased the number of pneumoencephalograms performed for the diagnosis of hydrocephalus and lesions of the posterior fossa, brain stem, and ventricles, there are some patients in whom pneumoencephalography should still be done because it adds valuable information to that obtained with CT. When the temporal horn becomes obstructed, the choroid plexus and ependymal surface "upstream" from the obstructing mass continue to produce cerebrospinal fluid (CSF). The temporal horn can thus enlarge enough to appear as a mass on CT because of its reduced x-ray attenuation coefficient. Pneumoencephalography is effective in this situation because air will flow past a mass that obstructs CSF and because the ventricular system dilates during pneumoencephalography. When pneumoencephalography is used in a patient with a trapped temporal horn, the partially trapped horn may enlarge approximately 24 hours later. With that precaution in mind, the neurosurgeon should find pneumoencephalography to be a useful adjunct to CT in delineating the cause of a trapped temporal horn. In the three patients reported here CT had indicated a unilateral trapped temporal horn; pneumoencephalography confirmed that finding and demonstrated both the location and the nature of the lesion. One patient had a Grade II astrocytoma fungating into the atrium of the right lateral ventricle, one had a mass extending into the right ventricle from the medial and superior ventricular wall with nodular encroachment on the ventricle, and one had a meningioma in the atrium of the right lateral ventricle.     

Neurofibrillary tangles in the dementia of "normal pressure" hydrocephalus.

Routine neuropathological examination could not explain the dramatic improvement exhibited by one patient with "normal pressure" hydrocephalus after shunting. The improved patient contrasted remarkably with the unchanged condition of four others also shunted successfully. The five brains were analysed by quantitative morphometry to determine the degree of neurofibrillary tangle formation in mesial temporal neurons. The density of tangle-bearing nerve cells in the four unimproved cases was markedly greater than in age-matched control brains from nineteen normal subjects, and fell in the same range as that of eight dements with neuropathologically confirmed Alzheimer's disease. The density of the one who recovered was within normal limits. The duration of dementia before shunting, and the total duration of dementia in these five patients rank in the same order as their degree of neurofibrillary formation. Furthermore, a positive linear correlation exists between the Tangle Indices and the total duration of dementia. The data suggest that early diagnosis may improve the chances of reversing the dementia of normal pressure hydrocephalus before histological alterations prove too severe.     

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.