Postmortem diagnosis of chronic granulomatous disease: how worthwhile is it?

A previously healthy 11 year old boy died unexpectedly after a rapid course of progressive pneumonia. Postmortem microbiology and histopathology suggested an underlying diagnosis of chronic granulomatous disease. This was confirmed by neutrophil oxidative burst and gene mutation analysis of other family members, one of whom benefited from early bone marrow transplantation.

Commotio cordis--a report of three cases.

Commotio cordis is a recognised cause of sudden death in which an apparently minor blow to the chest causes ventricular fibrillation and cardiac arrest. It is best known for causing death during games of youth baseball in the United States, but individual cases have been recorded as a result of a wide range of activities, principally sporting. The underlying biochemical and mechano-electric causes have been well documented. However, there are few reported cases where commotio cordis is implicated as the cause of death in homicide cases. We present three cases from the north-east of England where an assault caused death by this mechanism.

Fatal hemorrhage from simple lacerations of the scalp.

Scalp lacerations are frequently seen in both living trauma victims and at post-mortem examination. In clinical circles, it is well known that even "trivial" lacerations of blood-rich areas such as the scalp may bleed profusely and persistently.It is less well known, however, that hemorrhage even from simple scalp lacerations may be fatal. We present seven cases in which hemorrhage from simple scalp lacerations was considered to be the principle cause of death.Chronic alcohol misuse, alcoholic liver disease, and the co-existence of other pathologies such as ischemic heart disease were frequently contributory factors.

Evaluation of the management of optic neuritis: audit on the neurological and ophthalmological practice in the north west of England.

The management of acute optic neuritis by neurologists and ophthalmologists in the north west of England was assessed in the light of the Optic Neuritis Treatment Trial (ONTT) recommendations. A questionnaire on a fictitious case of typical unilateral optic neuritis was mailed to all consultant ophthalmologists and neurologists working in the North West and Merseyside Health Authorities. They were then asked to comment on management of the case. Fifty two out of 86 ophthalmologists and 20 out of 28 neurologists replied. The overall response rate was 63%. Sixty five per cent of neurologists and 46% of ophthalmologists would investigate a typical case of acute optic neuritis further. Forty six per cent of neurologists and 36% of ophthalmologists were likely to arrange MRI of the brain or orbit. Significantly more neurologists (55%) than ophthalmologists (9%) chose to treat with intravenous methylprednisolone (p<0.005). Significantly more ophthalmologists (64%) than neurologists (32%) chose not to give steroids (p<0.025). Oral prednisolone alone was rarely selected for treatment. Respondents were more likely to discuss multiple sclerosis with the referring doctor than with the patient. Only 32% of ophthalmologists and 20% of neurologists would clearly mention the possibility of improvement to the patient. Clear differences in practice between ophthalmologists and neurologists remain. A consensus on practice guidelines on the issues raised might be useful.

Invasive aspergillosis in a patient with MELAS syndrome.

Invasive infection with the opportunistic fungus Aspergillus fumigatus predominantly affects people with impaired cell mediated immunity. The case of a 31 year old woman with no identified cause for immunosuppression who presented with severe refractory aspergillosis of the paranasal sinuses is reported. She subsequently developed clinical and molecular evidence of mitochondrial encephalomyopathy with lactic acidosis and stroke-like events (MELAS) syndrome. It is proposed that MELAS syndrome may represent an unusual risk factor for the development of invasive aspergillosis and mechanisms are supported by which mitochondrial dysfunction may predispose to this.

Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics.

Both in vitro and in vivo studies of scavenger receptor class B type I (SR-BI) have implicated it as a likely participant in the metabolism of HDL cholesterol. To investigate the effect of SR-BI on atherogenesis, we examined two lines of SR-BI transgenic mice with high (10-fold increases) and low (2-fold increases) SR-BI expression in an inbred mouse background hemizygous for a human apolipoprotein (apo) B transgene. Unlike non-HDL cholesterol levels that minimally differed in the various groups of animals, HDL cholesterol levels were inversely related to SR-BI expression. Mice with the low expression SR-BI transgene had a 50% reduction in HDL cholesterol, whereas the high expression SR-BI transgene was associated with 2-fold decreases in HDL cholesterol as well as dramatic alterations in HDL composition and size including the near absence of alpha-migrating particles as determined by two-dimensional electrophoresis. The low expression SR-BI/apo B transgenics had more than a 2-fold decrease in the development of diet-induced fatty streak lesions compared with the apo B transgenics (4448 +/- 1908 micrometer(2)/aorta to 10133 +/- 4035 micrometer (2)/aorta; p < 0.001), whereas the high expression SR-BI/apo B transgenics had an atherogenic response similar to that of the apo B transgenics (14692 +/- 7238 micrometer(2)/aorta) but 3-fold greater than the low SR-BI/apo B mice (p < 0.001). The prominent anti-atherogenic effect of moderate SR-BI expression provides in vivo support for the hypothesis that HDL functions to inhibit atherogenesis through its interactions with SR-BI in facilitating reverse cholesterol transport. The failure of the high SR-BI/apo B transgenics to have similar or even greater reductions in atherogenesis suggests that the changes resulting from extremely high SR-BI expression including dramatic changes in lipoproteins may have both pro- and anti-atherogenic consequences, illustrating the complexity of the relationship between SR-BI and atherogenesis.

Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice.

Recent studies have indicated that the scavenger receptor class B type I (SR-BI) may play an important role in the uptake of high density lipoprotein (HDL) cholesteryl ester in liver and steroidogenic tissues. To investigate the in vivo effects of liver-specific SR-BI overexpression on lipid metabolism, we created several lines of SR-BI transgenic mice with an SR-BI genomic construct where the SR-BI promoter region had been replaced by the apolipoprotein (apo)A-I promoter. The effect of constitutively increased SR-BI expression on plasma HDL and non-HDL lipoproteins and apolipoproteins was characterized. There was an inverse correlation between SR-BI expression and apoA-I and HDL cholesterol levels in transgenic mice fed either mouse chow or a diet high in fat and cholesterol. An unexpected finding in the SR-BI transgenic mice was the dramatic impact of the SR-BI transgene on non-HDL cholesterol and apoB whose levels were also inversely correlated with SR-BI expression. Consistent with the decrease in plasma HDL and non-HDL cholesterol was an accelerated clearance of HDL, non-HDL, and their major associated apolipoproteins in the transgenics compared with control animals. These in vivo studies of the effect of SR-BI overexpression on plasma lipoproteins support the previously proposed hypothesis that SR-BI accelerates the metabolism of HDL and also highlight the capacity of this receptor to participate in the metabolism of non-HDL lipoproteins.

The intramuscular arterial anatomy of the long head of biceps femoris muscle.

We have previously shown that the neurovascular anatomy and length of the long head of biceps femoris (LHBF) is suitable for its possible use in the creation of a dynamic perianal myoplasty to restore faecal continence. If intramuscular arterioarterial anastomoses exist between a muscle's vascular pedicles then the delay procedure, i.e. ligating the vascular pedicles to the transposed section of the muscle, 4-6 wk before transposition, can be used to improve blood flow to the distal part of the transposed muscle. The intramuscular arterial anatomy of 20 biceps femoris muscles was shown by dissection (14) or radiographically (6). The mean entry point of the upper major vascular pedicle to the LHBF was 12 cm (S.D. 3.3) and the mean length of the LHBF was 36.8 cm (S.D. 1.8). Therefore the ratio between upper major vascular pedicle entry point and muscle length in 95% of specimens was 0.33 (0.2). In the present study intramuscular arterioarterial anastomoses were found between the arterial pedicles to the nontransposed and transposed sections of the LHBF and between the long and short heads of this muscle. Using the delay procedure would therefore theoretically allow the intramuscular arterioarterial anastomoses between the arterial pedicle to the nontransposed and transposed sections of the LHBF to open up enhancing blood flow to the distal part of the myoplasty.

Debrisoquine hydroxylase gene polymorphism frequencies in patients with amyotrophic lateral sclerosis.

Using PCR and restriction digest analysis, the frequencies of the variant cytochrome P450 debrisoquine hydroxylase CYP2D6 alleles CYP2D6(A) and CYP2D6(B) were investigated in 50 patients with amyotrophic lateral sclerosis (ALS) and 13 patients with ALS and frontotemporal dementia (FTD) and compared to those frequencies in patients with FTD alone and Alzheimer's disease (AD). The CYP2D6(T) allelic frequency was also assessed in ALS and ALS + FTD. Although the frequency of a poor metabolizer genotype was not increased in any disease group, there was a significant increase in the frequency of the CYP2D6(B) allele in the ALS patient group. This suggests that possession of a CYP2D6(B) allele may be a risk factor for the development of ALS, possibly conferring a 'gain of function' imposed by the mutation or reflecting linkage disequilibrium to a nearby susceptibility gene.

Patterns of glial cell activity in fronto-temporal dementia (lobar atrophy).

Fronto-temporal dementia is a clinical syndrome with a number of pathological substrates, including frontal lobe degeneration, Pick's disease, and motor neuron disease with dementia; it also includes patients with a primary progressive language disorder. Twenty-four brains were examined, using immunohistochemistry for glial fibrillary acidic protein (GFAP) and ferritin. Five cases of fronto-temporal dementia with a Pick's disease type of histology showed marked cortical gliosis with striking microglial activity in both grey and white matter. In seven cases of frontal lobe degeneration, there was little gliosis and microglial activity was confined largely to the white matter; two of the seven cases of progressive language disorder showed similar changes to frontal lobe degeneration. Five cases of motor neuron disease with dementia showed both astrocytic and microglial activity within the white matter. We suggest that cases of fronto-temporal dementia due to Pick type histology may result from a process which primarily involves grey matter, whereas cases of frontal lobe degeneration might represent a disorder of white matter.

Acute meningo-encephalitis in pregnancy-a problem of differential diagnosis.

Two cases of Coxsackie B viral meningo-encephalitis in pregnant women are described. Both patients recovered well and delivered healthy babies, but because of delay in establishing the aetiology of their infections both mothers, and one child, received acyclovir therapy. The differential diagnosis of non-pyogenic meningo-encephalitis in late pregnancy can present particular problems: clinicians caring for such women should remain aware of the potential for enteroviral infection in their patients, and take appropriate action to prevent cross-infection in neonatal units.

The coroner's system and under-reporting of suicide.

This study investigates the under-reporting of suicide with particular reference to differences between sex and age groups and the various modes of suicide. The study was performed retrospectively using the files of H M Coroner for South Yorkshire (West) over the years 1985 to 1991. There were 536 deaths judged on the balance of probability to be suicidal in nature. Only 60 per cent of these deaths received a suicide verdict and would therefore register in official suicide statistics. A significantly smaller proportion of females (51.7 per cent) received a suicide verdict than males (64.5 per cent). Of the young females (< 45) 61.7 per cent were given a suicide verdict compared to 46.6 per cent of older females (45+). These differences are explained by different preferences for mode of suicide, in particular for poisoning using solids or liquids. Only 40 per cent of cases within this category received a suicide verdict. Drowning showed an even smaller percentage (24 per cent). Self-immolation (42 per cent) and jumping from a height (51 per cent) were also under-represented. Of these, self-poisoning, drowning and jumping from a height were relatively popular among females. In contrast, common causes of death favoured predominantly by males--hanging and carbon monoxide poisoning--received a high percentage of suicide verdicts (81 per cent and 90 per cent). Thus official suicide statistics produce a distorted view of the suicide population with relative under-reporting of females, particularly older females, and marked under-reporting of some causes of death, notably poisoning using solids or liquids, drowning, self-immolation and jumping from a height.

Tau, ubiquitin, and alpha B-crystallin immunohistochemistry define the principal causes of degenerative frontotemporal dementia.

OBJECTIVE: We investigated the use of immunostaining with antibodies to tau, ubiquitin, and alpha B-crystallin in defining a protocol for the staged neuropathologic examination of brains from patients with a progressive frontotemporal dementia. DESIGN: Brains obtained from 50 patients dying with the clinical diagnosis of frontotemporal dementia were examined histopathologically to define pathologic distinctions. SETTING: Two university hospital neuropathology departments. RESULTS: Anti-tau immunostaining defined corticobasal degeneration, Alzheimer's disease, and Pick's disease; antiubiquitin defined motor neuron disease with dementia. The remaining brains have frontal lobe degeneration: the use of alpha B-crystallin immunostaining, on these, to detect ballooned neurons may help to define two groups of patients, one of which we believe may represent a variant of Pick's disease. CONCLUSION: These findings indicate that immunostaining with these antibodies is essential for the evaluation of frontal dementia.

Allelic variations in apolipoprotein E and prion protein genotype related to plaque formation and age of onset in sporadic Creutzfeldt-Jakob disease.

Prion gene sequence is thought to affect the phenotypic expression of prion disease and the E2 variant of apolipoprotein E (Apo E) can be neuroprotective in dementia. We determined codon 129 of the prion gene and the Apo E variants in Creutzfeldt-Jakob disease (CJD) using PCR and restriction digest. We found a significant correlation between valine at codon 129 of the prion protein gene and the presence of plaque in CJD and a later age of onset in CJD cases possessing the Apo E2 allele. This study provides further evidence that sequence variations in the prion gene can modify disease pathology and the neuroprotection afforded by Apo E2 is not confined to Alzheimer's disease.

Violent suicide in South Yorkshire, England.

Differences in the characteristics of those individuals choosing violent methods of suicide in South Yorkshire were studied. With the exception of jumping from a height, these methods were more frequently used by males, with a particular male predominance in deaths due to self-immolation, railway collision, hanging, firearms, and electrocution. The most potentially painful/disfiguring methods of suicide, jumping from a height, self-immolation, and railway deaths, were favored by the young. Drowning, stabbing and cutting and electrocution were common among the elderly. Severe mental illness was common amongst those choosing some of the most painful or disfiguring modes of death (jumping from a height; self-immolation; cutting/stabbing and road traffic "accidents") particularly when compared to the principal alternative of hanging. The same group of causes of death was associated with a high proportion of individuals who had previously attempted suicide. Severe mental illness was not so obviously a feature of the railway or firearm deaths. Hanging represented more than half the cases included in the study and showed a sex ratio of over 4 to 1 in favor of males. However, all seven individuals of non-European origin, six of whom were female, chose to hang themselves. Whereas half of the females aged under 40 jumped from a height, hanging was the method of choice in the age group 40 to 59. Among males, hanging was particularly favored by those with what might be considered an impulsive reason for suicide, namely, the end of a relationship with a member of the opposite sex. A high proportion of these were intoxicated with alcohol and a high proportion left a suicide note.