A novel mutation in ferroportin1 is associated with haemochromatosis in a Solomon Islands patient.

BACKGROUND: A severe form of iron overload with the clinicopathological features of haemochromatosis inherited in an autosomal dominant manner has been described in the Solomon Islands. The genetic basis of the disorder has not been identified. The disorder has similarities to type 4 haemochromatosis, which is caused by mutations in ferroportin1. AIMS: The aims of this study were to identify the genetic basis of iron overload in a patient from the Solomon Islands. PATIENT AND METHODS: Genomic DNA was isolated from peripheral blood leucocytes of a Solomon Islands man with severe iron overload. The entire coding region and splice sites of the ferroportin1 gene was sequenced. RESULTS AND CONCLUSIONS: A novel missense mutation (431A>C; N144T) was identified in exon 5 of the ferroportin1 gene. A novel restriction endonuclease based assay which identifies both the N144T and N144H mutations was developed which will simplify the diagnosis and screening of patients for iron overload in the Solomon Islands and other populations. This is the first identified mutation associated with haemochromatosis in the Solomon Islands population.

Australian bat lyssavirus infection: a second human case, with a long incubation period.

In December 1998, a 37-year-old Queensland woman died from a rabies-like illness, 27 months after being bitten by a flying fox (fruit bat). Molecular techniques enabled diagnosis of infection with Australian bat lyssavirus (ABL), the second human case to be recognised and the first to be acquired from a flying fox. It must be assumed that any bat in Australia could transmit ABL; anyone bitten or scratched by a bat should immediately wash the wounds thoroughly with soap and water and promptly seek medical advice.

Non-rabies Lyssavirus human encephalitis from fruit bats: Australian bat Lyssavirus (pteropid Lyssavirus) infection.

A 39-year-old woman died of encephalitis a few weeks after being scratched by fruit bats. Autopsy disclosed meningoencephalomyelitis, and revealed neuronal intracytoplasmic inclusions which had similarities to Negri bodies of rabies. Laboratory investigations detected a Lyssavirus type previously identified only in fruit bats. This appears to be the first human case of encephalitis due to this Lyssavirus type.

Large intestinal lymphocytic phlebitis and venulitis in chronic ulcerative colitis.

Colonic vasculitis is seen in Crohn's disease and as a component of primary systemic vasculitis. It has rarely been described in chronic ulcerative colitis. Here we report a case of ulcerative colitis with prominent transmural lymphocytic phlebitis and venulitis. Although this is, to our knowledge, the first description of such an association, its recognition is important if confusion with other entities is to be avoided. The etiology of the vascular changes is unclear but they may be a secondary phenomenon induced by antigens, toxins or cytokines draining from the inflamed mucosa.

Histological patterns of prolonged hepatitis C infection.

Liver biopsies from 63 patients with hepatitis C virus (HCV) infection have been studied. 31 were asymptomatic and had been detected by a variety of screening programs, and most of the other 32 had complained of vague symptoms only. In 57 patients a confident estimate of the duration of infection was able to be made (ranging from 12 months to over 38 years) and 73% of these had been infected for over 5 years. The most common histological pattern observed was a low-grade panacinar hepatitis. This affected 74.6% of all biopsies, and 43% of this group had been infected for over 10 years. Severe chronic active hepatitis and/or cirrhosis occurred in only 8% of the whole series, and in 16.7% of those infected for over 10 years. This incidence of serious sequelae in chronic HCV infection is much lower than previously reported, probably reflecting the methods of patient selection, and may represent more accurately the natural history of the disease in this community. The occurrence of a number of characteristic histological features (lymphoid follicles and aggregates, steatosis, Kupffer cell prominence, and apoptotic or acidophilic bodies) was confirmed, the constellation of which is highly suggestive of HCV infection. It is suggested that apoptosis may play an important role in the perpetuation of HCV as a chronic infection.

Treatment of refractory ulcerative oesophagitis with omeprazole.

A 7 year old boy with ulcerative oesophagitis failed to respond to a two month course of intensive medical treatment using H2 receptor antagonist treatment in combination with domperidone and sucralfate. He demonstrated complete resolution using omeprazole 10 mg once a day for eight weeks.

Cellular events in experimental unilateral ischemic renal atrophy and in regeneration after contralateral nephrectomy.

Two related morphological studies were undertaken in rats. In the first, cellular events involved in the development of ischemic renal atrophy induced by renal artery stenosis were recorded. One primary objective was to document the pathogenetic role that a distinct form of cell death, termed apoptosis, played in the development of renal tubular atrophy. A small, partially closed ligating clip was used to produce stenosis of the left renal artery, or a sham operation was performed. Animals were killed 2-28 days after operation. The ensuing ischemic renal atrophy was studied histologically and ultrastructurally, and apoptosis was counted in paraffin sections, using established criteria for its identification. Nuclear [3H]thymidine uptake was used as an indicator of cell proliferation. Morphometric studies recorded changes in area of transected tubular profiles. Correlation was sought between the morphological changes, data gained by the above quantitations, and the progressive reduction in renal mass that occurred during the experiment. Our results showed that during the acute phase (2-8 days), cell death was effected by both apoptosis and necrosis and increased tubular epithelial cell labeling and mitoses provided evidence of epithelial repair. During the chronic phase (10-28 days), when the mass of the ischemic kidney underwent significant reduction, cell death was effected by apoptosis alone, and the level of tubular epithelial cell labeling and mitosis returned to near normal. Intraepithelial macrophages were significant in removing the apoptotic bodies. Area of tubular epithelium was reduced in atrophic tubules, and it is proposed that this reduction may be explained by apoptotic cell deletion, as well as cell shrinkage. In the second study, evidence of regeneration was sought in atrophic kidneys after surgical reversal of renal artery stenosis and, in other animals, after unilateral nephrectomy of the contralateral kidney. Our results showed that regeneration, involving both hypertrophy and hyperplasia, was stimulated only by removal of the hypertrophied contralateral kidney and occurred whether or not stenosis of the renal artery was reversed.

Progressive encephalomyelitis with rigidity: a case report with magnetic resonance imaging findings.

A 52 year old woman presented with pain in the back and upper limbs and progressive weakness and sensory impairment of the upper and lower limbs. She developed frequent episodes of severe generalised muscle spasms associated with piloerection and hyperventilation. Nerve conduction studies and electromyography were normal. MRI demonstrated a lesion of the cervical spinal cord and lower brainstem. A biopsy of the cord revealed perivascular cuffing with mononuclear cells and inflammatory changes in the parenchyma, with increased numbers of microglia, reactive astrocytes and plasma cells. Following treatment with corticosteroids she showed substantial improvement.

Virilizing adrenal adenoma in an adult with the Beckwith-Wiedemann syndrome: paradoxical response to dexamethasone.

An adult woman with Beckwith-Wiedemann syndrome, hemihypertrophy and an androgen-secreting adrenal adenoma is described. She presented with a 7-year history of progressive virilization and was found to have high plasma levels of testosterone and dehydroepiandrosterone (DHEA) sulphate and elevated levels of urinary metabolites of testosterone and its precursors. Administration of dexamethasone was associated with progressive rises in plasma 17 alpha OH progesterone, 11 beta-desoxycortisol, DHEA sulphate, androstenedione and testosterone, together with increased urinary excretion of androsterone, 11 beta OH androsterone, etiocholanolone, DHEA, and 16 alpha OH DHEA. Hormone levels fell to normal following removal of the tumour.

Successive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation.

In rats with castration-induced ventral prostatic atrophy, testosterone treatment resulted in reconstitution of the normal weight and histological structure of the gland within 10 d. Subsequent withdrawal of the hormone was followed by rapid involution, which was effected by a combination of extensive loss of epithelial cells by apoptosis and decrease in the size of the cells that remained. The wave of apoptotic deletion was similar to that accompanying the initial involution after castration, and in both cases the rate of apoptosis fell to very low levels by 20 d. Two further consecutive episodes of involution produced by sequential administration and withdrawal of testosterone were also accompanied by similar waves of apoptosis. The results provide quantitative evidence supporting suggestions that apoptosis may be of major kinetic significance in the involution of endocrine-dependent glandular tissues. The majority of the epithelial cells remaining after the completion of involution were able to survive continuing androgen deprivation, but with renewed testosterone stimulation they repeatedly generated populations that once again responded to withdrawal with massive cellular death. The factors determining the selective susceptibility of individual cells in these populations clearly merit investigation.

Rapid progression of oxalosis-induced cardiomyopathy despite adequate haemodialysis.

Crystals of calcium oxalate (CaC2O4) were found at autopsy in the heart of a patient who, over a period of 11 months, appeared to receive adequate haemodialysis and yet died of rapidly progressive heart failure. Calcium oxalate crystals were not present in the kidneys which had been removed at the time of commencing haemodialysis. No secondary cause of oxalosis was evident. X-ray fluorescence analysis of the heart tissue revealed, as well as large amounts of calcium, excess strontium and markedly reduced amounts of potassium and rubidium.