Estimating the burden of early onset dementia; systematic review of disease prevalence.

Dementia is more common in older age but a number of people develop symptoms at a younger age and are said to have early onset dementia (EOD). Those with EOD face different challenges to those with onset later in life. It has been difficult to quantify this disease burden. This is a systematic review of papers reporting on the prevalence of EOD. A search of Medline and Embase was performed. This was followed by a hand search of the references of these papers. Eleven suitable studies were included. All of the data was from more economically developed countries. The studies were heterogeneous in their design hindering direct comparison. The majority of the papers looked at all types of dementia although many gave a breakdown of the prevalence of different subgroups. A variety of diagnostic criteria was employed. Figures of 38 to 260 per 100,000 are quoted by papers looking at various different types of dementia together with an onset of between 30 and 64 or up to 420 per 100,000 for those aged 55-64. Prevalence rises as age approaches 65. Epidemiological data for prevalence rates for EOD are sparse. EOD remains a rare condition with low case numbers. Assimilation and comparison of results from existing studies is difficult due to methodological heterogeneity. Cross-national standardization of methodology should be a priority for future research in this area.

Medical management of critical limb ischaemia: where do we stand today?

Critical limb ischaemia (CLI) is a severe form of peripheral arterial disease (PAD). CLI often causes disabling symptoms of pain and can lead to loss of the affected limb. It is also associated with increased risk of myocardial infarction, stroke and death from cardiovascular disease. The aims of management in patients with CLI are to relieve ischaemic pain, heal ulcers, prevent limb loss, improve function and quality of life and prolong survival. Here, current evidence regarding the medical management of CLI is reviewed. Cardiovascular risk factors should be assessed in all patients with CLI; smoking cessation and treatment of hypertension, hyperlipidaemia and diabetes all reduce the mortality rate in those with PAD. Antiplatelet agents (either aspirin or clopidogrel) are recommended to reduce both the incidence of cardiovascular events and risk of arterial occlusion. By contrast, routine use of anticoagulation (either warfarin or heparin) is not recommended. Treatment of the limbs themselves is often more challenging. Prostanoids may have some efficacy for treating rest pain and for ulcer healing, and iloprost shows favourable results in reducing the risk of major amputations, but long-term follow-up data regarding disease progression are lacking. There is insufficient evidence to support the use of naftidrofuryl or cilostazol, and pentoxifylline is not beneficial. Furthermore, there is no evidence of proven benefit of hyperbaric oxygen. A number of angiogenic growth factors have been studied in Phase I studies and randomized controlled trials (RCTs). They appear to be safe, but efficacy results have been mixed. Treatment with stem cells also shows some potential from early trials, but further larger RCTs are needed to demonstrate clear benefit. Thrombolysis may be an alternative for patients who develop acute limb ischaemia and are unsuitable for surgical intervention. However, newer endovascular techniques are likely to have a greater role in the future.

Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency.

Stroke-like episodes, defined as periods of acute localized neurological dysfunction during which brain imagery suggests cerebral ischemia but vascular anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal neurological deterioration and frontal hypodensities on cerebral computerized tomography (CT). Arteriography, performed in 1 patient during an acute episode, showed normal vascular anatomy. Nevertheless, capillary shunting was evident both in regions that appeared abnormal on the initial cerebral CT study and in regions that appeared normal but subsequently developed Leigh disease. Stroke-like episodes did not exacerbate systemic acidosis, and acidotic decompensations occurred independently of stroke-like episodes. In conclusion, stroke-like episodes occur in autosomal recessively inherited congenital lactic acidoses as well as in those caused by mitochondrial DNA mutations. In some cases, acute localized neurovascular changes occur in regions that subsequently develop Leigh disease.

Capnography for monitoring non-intubated spontaneously breathing patients in an emergency room setting.

OBJECTIVE: To examine the feasibility of using expiratory capnography as an indicator of airway obstruction in non-intubated resuscitation room patients. METHODS: Patients with potential respiratory compromise admitted to the resuscitation room were assessed for widespread expiratory wheeze. This was taken as clinical evidence of airways obstruction. Expiratory capnograms of these patients and patients who had no wheeze were obtained. The traces were analysed for basic morphology and where appropriate the slope ratio (SR) between phase 1 (S1) and phase 2 (S2) of the trace was obtained. RESULTS: Thirty eight patients with a variety of clinical conditions causing potential or actual respiratory impairment were studied. All patients tolerated the nasal capnogram cannulae. Twelve had no clinical evidence of airway obstruction and all had capnograms with normal morphology. Eleven of these were analysed further. The mean value for SR was 7.57 (SEM 0.18), 95% confidence interval 6.37 to 8.77. Twenty six patients had clinical evidence of airway obstruction "sharks fin" morphology. Fourteen of these were analysed to determine SR. The mean value was 31.9 (4.46), 95% CI 22.9 to 40.8. There was a significant difference in the mean value for SR between the two groups (P << 0.001). CONCLUSIONS: Capnography may be used as a means of continuous respiratory monitoring in non-intubated acutely ill patients. Capnogram analysis may be used to indicate airway obstruction in these patients. Further work is required to correlate curve indices to degree of airway obstruction.

The effect of high-dose right upper quadrant lithotripsy on normal swine tissue.

To assess the effects of high doses of shock waves to organs in the right upper quadrant of the abdomen, 36 adolescent swine were given one treatment of either 2,000 (2k), 6,000 (6k), or 10,000 (10k) shock waves at 24 kV peak pressure using a spark-gap lithotriptor. Shock waves were sonographically focused on the lumen of the gallbladder. Blood and tissue were examined for each group at 48 hours, at 35 days, and at 6 months. This study showed that administration of up to five times the accepted upper limit of shock waves produced no permanent damage. Transient injury, most commonly hematoma, was encountered. No posttreatment intra-abdominal catastrophes occurred. Although no renal injury was seen, it should be noted that the focus of maximum energy was 5 cm cephalad to the right kidney. This study suggests that an increased number of shock waves may be administered safely to this area of the abdomen.

Effect of a preprinted form on the management of acute asthma in an accident and emergency department.

OBJECTIVE: To assess the effect of a preprinted form on the documentation of clinical data and compliance with the national guidelines for the management of asthma. METHODS: Prospective audit six months before and after introduction of the form. RESULTS: Use of the form improved the documentation of past asthma history (69% v 93%, P < 0.001), current treatment (81% v 95%, P < 0.01), predicted peak flow (23% v 75%, P < 0.001), per cent predicted peak flow (1% v 62%, P < 0.001), and respiratory rate (81% v 95%, P = 0.007). Compliance with the British recommendations for treatment improved with use of the form (50% v 89%, P < 0.001) The prescription of steroids on discharge did not improve significantly (26% v 44%, P > 0.05). CONCLUSIONS: The preprinted form resulted in enhanced documentation of data and conformity with current guidelines for the management of asthma.

Chronic persistent asthma presenting to an accident and emergency department--compliance with B.T.S. guidelines.

Forty-six patients, known to suffer from asthma, attending an inner-city accident and emergency (A&E) department, were screened for the presence of chronic symptoms and their current treatment documented. The patients were asked if they knew their optimum peak expiratory flow rate (PEFR) or if they possessed a peak flow meter. The treatment being used by each of the 26 patients with evidence of chronic persistent asthma was compared to that as advised by the British Thoracic Society (B.T.S.) and it was found that only three patients were receiving adequate treatment. Most often the treatment regimes were suboptimal due to the absence of an inhaled anti-inflammatory agent. Patient awareness of their own PEFR or possession of a peak flow meter was uniformly low in both the well-controlled patients and those with chronic persistent asthma.

Allelic association and linkage studies in Wilson disease.

We have studied 21 families with Wilson disease (WND), using restriction fragment length polymorphisms (RFLPs) in the 13q14.3 region, to measure linkage of these markers to the disease locus. In addition to previously described markers, we include linkage data for a newly isolated marker (D13S86) and an established marker (D13S56), which were previously not placed on the genetic map in the region of the WND locus. Our data, including those from two recombinant families, support the location of WND between the markers D13S31 and D13S59. We have examined the distribution of marker alleles at the loci studied and have found that D13S31 and D13S228, and associated microsatellite marker, show a non-random distribution on chromosomes carrying the WND mutation. The significant linkage disequilibrium indicates that these two markers must be close to the WND locus.

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients.

We report the clinical, electrophysiologic, ophthalmologic, and neuropsychologic features of six patients with hyperammonemia-hyperornithinemia-homocitrullinuria syndrome, an inborn error of ornithine metabolism. Pyramidal signs, decreased vibration sense, bucco-facio-lingual dyspraxia, and learning difficulties or subnormal intelligence were found in the majority. Anomalies of peripheral nerve conduction velocity and of evoked potentials were common, and one patient had markedly abnormal white matter images on cranial magnetic resonance imaging. One patient had retinal depigmentation and chorioretinal thinning. The clinical severity varied greatly among patients; in general, the three younger patients had less neurologic and intellectual impairment than did the three older patients. Only two of our patients have had episodes of symptomatic hyperammonemia. We conclude that hyperammonemia-hyperornithinemia-homocitrullinuria syndrome can be associated with widespread manifestations in the central and peripheral nervous systems. Although the control of hyperammonemia is an essential element in the treatment of these patients, the relationship of hyperammonemia to the chronic neuropsychologic problems of these patients is unclear.

Nutritional vitamin B12 deficiency: two cases detected by routine newborn urinary screening.

We describe two asymptomatic newborns with nutritional vitamin B12 deficiency in whom increased urinary methylmalonic acid was detected by routine neonatal screening at 3 weeks of age. Both infants were exclusively breast-fed. One mother suffered from pernicious anaemia, and the other was a strict vegetarian. Both mothers had no clinical or haematological abnormality, aside from a borderline mean corpuscular volume for the vegetarian mother. This report illustrates the early appearance of functional vitamin B12 deficiency in breast-fed infants of vitamin B12-depleted mothers. It also demonstrates that urinary methylmalonic acid measurement is a sensitive indicator of tissue vitamin B12 deficiency.

Controlled study of the use of local steroid injection in the treatment of trigger finger and thumb.

A controlled double-blind prospective study of injection of methylprednisolone acetate plus local anaesthetic against a control injection of a local anaesthetic in the treatment of trigger finger and thumb has shown a 60% success rate for the steroid injection against 16% for the control group (p less than 0.05). This is the first controlled trial of local steroid therapy in this condition.

Cloning and expression of rat histidase. Homology to two bacterial histidases and four phenylalanine ammonia-lyases.

Histidase (histidine ammonia-lyase, EC 4.3.1.3) catalyzes the deamination of histidine to urocanic acid. Apart from phenylalanine ammonia-lyase, which is not expressed in animals, histidase is the only enzyme known to have a dehydroalanine residue in its active site. The amino site precursor and the mechanism of formation of dehydroalanine are not known. As an initial step to determining the precursor of dehydroalanine in histidase, we have isolated a functional cDNA clone for histidase from a rat liver cDNA library using an affinity-purified antiserum. The 2.2-kilobase cDNA has a 1,971-base pair open reading frame coding for a 657-amino acid polypeptide with a predicted molecular mass of 72,165 Da. The cDNA has a rare polyadenylation signal (AAUACA) that appears to inefficiently direct polyadenylation in transfected COS monkey kidney cells. Conversion of this sequence to the consensus polyadenylation signal (AAUAAA) resulted in increased levels of stable mRNA. COS cells transfected with a histidase expression vector produce active histidase. The formation of active histidase in cells that have no endogenous histidase activity suggests either that the requisite modifying enzyme is present in these cells or that the dehydroalanine residue forms by an autocatalytic mechanism. Rat histidase was found to have 41 and 43% amino acid identity to Pseudomonas putida and Bacillus subtilis histidases, respectively. Phenylalanine ammonia-lyases from parsley, kidney bean, and two yeast strains were also found to have approximately 20% amino acid identity to rat histidase. On the basis of the similarity of function of histidase and phenylalanine ammonia-lyase, dehydroalanine at the active sites, and the sequence conservation over a large evolutionary distance (mammals, bacteria, yeast, and plants), we propose that the genes for histidase and phenylalanine ammonia-lyase have diverged from a common ancestral gene, of which the most conserved regions are likely to be involved in catalysis or dehydroalanine formation.

[Hypocarnitinemia in patients affected by a primary defect of ammonia metabolism treated with sodium benzoate]. / Hypocarnitinémie chez les patients atteints d'un défaut primaire du métabolisme de l'ammoniaque traités avec le benzoate de sodium.

We have studied the plasma and urinary levels of free and esterified carnitine in 18 patients affected by a primary defect of ammonia metabolism, which had been managed with or without a therapy of sodium benzoate. None of these patients presented with any acute neurologic or digestive symptoms during the study. Our group of non-treated patients showed an increase in the levels of plasma esterified carnitine and an elevation of urinary concentration of free carnitine, while the levels of urinary esterified carnitine clearly approached the superior limits of normal values. The group treated with sodium benzoate showed a more profoundly disturbed plasma and urinary carnitine profile: a significantly lower plasma and urinary free carnitine, accompanied by a clearly increased esterified/free carnitine ratio. We did not find any evidence of a relationship between the plasma levels of free or esterified carnitine and the protein intake or the plasma ammonia concentration. We are proposing a hypothesis to explain the hypocarnitinemia seen in our patients being treated with benzoate, along with other modifications observed in the carnitine profile. We believe that a supplement of carnitine could be beneficial in the management of some of these patients.

An arresting injury.

Three cases of branchial plexus injury due to handcuffing with the hands behind the back are presented.

Pasteurella caballi, a new species from equine clinical specimens.

The name Pasteurella caballi is proposed for a group of organisms represented by 29 strains isolated from respiratory and other infections in horses. P. caballi strains are gram-negative, oxidase-positive, nonmotile, fermentative rods with the key characteristics of the genus Pasteurella. These strains differed from other Pasteurella species in that all were aerogenic and catalase negative, and some strains produced acid from myo-inositol and L-rhamnose. The levels of DNA relatedness of 28 P. caballi strains with labeled DNA from the proposed type strain averaged 91 and 85% (hydroxyapatite method at 55 and 70 degrees C). P. caballi was 13 to 53% related to strains representing 22 other species of the family Pasteurellaceae. The guanine-plus-cytosine content of the DNA of four strains was 41 to 42 mol%. The type strain is 83851 (=ATCC 49197).

The role of pulse oximetry in the accident and emergency department.

Prompt recognition and treatment of hypoxia is an important part of management in the accident and emergency (A & E) department. Until recently the only reliable method of detecting hypoxia was by estimation of the arterial blood gases (ABG). Continuous monitoring of the arterial oxygen saturation (Sao2) is possible using an infra-red pulse oximeter. This study assessed the usefulness of this instrument in the A&E setting. The Sao2 was measured in 50 patients using a pulse oximeter. In 15 patients simultaneous ABG estimations were obtained. The Sao2 correlated closely with calculated values for Sao2. The use of the oximeter identified 21 patients (42%) with clinically unsuspected hypoxia. The pulse oximeter proved simple to use, accurate and a useful addition to our resuscitation equipment.

Molecular structure of the human asparagine synthetase gene.

The human gene for asparagine synthetase has been isolated and the molecular organization has been determined by mapping and DNA sequencing of intron-exon boundaries. The gene spans 35 kb and contains 13 exons. The structure of the human gene has a high degree of similarity to that of the hamster asparagine synthetase gene, with identical positions for all but one of the intron regions. The 5' upstream region of this gene, like other housekeeping genes, lacks conventional TATA and CAAT boxes. Comparisons of the 5' upstream sequences of the human and hamster genes show limited similarity; however, both have a very high G + C content which may play a role in expression through DNA methylation.