Quarterly Journal of Medicine最新文献

A point mutation in the apolipoprotein AI (apoAI) gene causing autosomal dominant non-neuropathic systemic amyloidosis is described in a previously unreported Canadian family of British origin with five affected individuals in three generations. Amyloid deposits in the renal biopsy from the proband, a 31-year-old female presenting with hypertension and renal failure, stained immunospecifically with antiserum to apoAI. The plasma of all family members with amyloidosis contained both wild-type apoAI and a variant bearing one additional positive charge. Sequencing of the apoAI gene demonstrated that the proband was a heterozygote for a single base substitution in exon 3, changing codon 26 from GGC(Gly) to CGC(Arg). Concordance of the mutant allele with the presence of variant plasma apoAI and clinical features of amyloidosis was demonstrated. This is the third family in which this amyloidotic mutation has been described, but the distribution of amyloid deposits and their clinical effects are clearly determined by other genetic and/or environmental factors.

Diastolic heart failure is common, particularly in patients with coronary artery disease and hypertension. Although it does not contribute to heart failure mortality to the same degree as systolic dysfunction, it is responsible for significant morbidity. Clinical suspicion is a prerequisite to the diagnosis, which should be considered in all patients with exercise intolerance due to dyspnoea, particularly if associated with a history of ischaemic heart disease or hypertension. Although invasive haemodynamic studies are the gold standard investigation, this method of assessment is limited to a very small proportion of these patients, and echocardiography remains the single most useful investigation. It is important to realize that the management of diastolic heart disease depends to a large extent on the aetiology, which contrasts with the treatment of systolic dysfunction. As indicated, a wide variety of different drugs may potentially be of benefit, although considerable further research will be needed to more clearly define this heterogenous condition and its optimal treatment.

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.

We investigated whether 'limited' or 'non-renal' Wegener's granulomatosis (WG) differs from classical or 'renal' WG. Renal WG is characterized by necrotizing granulomatosis of the upper and or lower respiratory tract, accompanied by systemic vasculitis and focal segmental necrotizing glomerulonephritis. This last feature is absent in non-renal WG. In a prospective follow-up study of all identified cases presenting to a single teaching hospital, we reviewed 22 patients with non-renal WG, and compared their presentation and outcome with that of 28 patients with renal WG. Clinical and laboratory assessment of disease activity, frequency of death, relapse and end-stage renal disease were assessed. The two groups differed in clinical presentation, laboratory features and outcome. The group with non-renal WG had less cutaneous and pulmonary disease; the haemoglobin, white cell count and platelet count tended to be normal. Residual mortality was confined to the renal group. However, the groups shared many features, particularly their requirement for immunosuppressive therapy, since WG causes major tissue destruction regardless of whether it is a localized or widespread process. At the immunopathological level, the two groups appear to be part of a single disease spectrum. Importantly, the non-renal WG group may change the pattern of their disease to involve the kidney. Long-term follow-up of such patients is therefore essential.

Sixty-five patients with a diagnosis of acute encephalitis or encephalopathy were discharged from a regional neurological unit over a 17-year period. Investigation during the acute illness, or subsequent clinical and laboratory observations, yielded a definite or probable diagnosis in 34 of these patients, including herpes simplex encephalitis (8 cases), encephalitis due to other identified viruses (7 cases), vascular disease (7 cases) and multiple sclerosis (4 cases). In these 34 patients, mortality relating to the presenting illness was 50% and a further 29% had significant long-term neurological morbidity. In the other 31 patients, no cause for the encephalopathy was identified, despite extensive investigation. These patients had an alteration in conscious state, often with recurrent seizures (45%), focal neurological signs (52%), pyrexia (65%), abnormal electroencephalogram (85%) and cerebrospinal fluid lymphocytosis (80%). During follow-up (6 months to 15 years) none had recurrent encephalopathy, and 65% eventually made a complete recovery, although delayed by seizures in 6% and psychiatric illness in 13%. The mortality in this group relating to the acute illness was 6%. Overall, nearly half the patients with a discharge diagnosis of acute encephalitis or encephalopathy had a good prognosis for recovery, following a monophasic illness of undetermined cause.