A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

Obesity and type 2 diabetes are important risk factors underlying previously undiagnosed cirrhosis in general practice: a cross-sectional study using transient elastography.

BACKGROUND: Rising cirrhosis incidence and mortality in the United Kingdom has been attributed predominantly to excess alcohol consumption. However, metabolic risk factors such as Type 2 diabetes and obesity may also be important. AIM: To screen at-risk individuals in general practice for undetected cirrhosis using transient elastography and study the risk factors underlying these cases. METHODS: The study was undertaken in 4 general practices (adult patient population 20 868) between February 2012 and September 2014. Patients with defined risk factors for chronic liver disease (hazardous alcohol use and/or Type 2 diabetes) were identified from the General Practice electronic records and invited for transient elastography. Elevated liver stiffness was defined as ≥8 kPa. Cirrhosis was confirmed by established histological, radiological and biochemical methods. RESULTS: Two thousand three hundred and sixty eight patients were invited for transient elastography and 899/919 who attended (97.8%) had valid measurements. Of these 230 patients had elevated liver stiffness (25.6%) and 27 had cirrhosis (2.9%). Risk factors for new cirrhosis diagnoses were obesity and/or Type 2 diabetes in 16 patients (59.3%), alcohol alone in 3 (11.1%) and both alcohol and obesity and/or diabetes in eight (29.6%). Presence of cirrhosis was significantly increased in obese patients with Type 2 diabetes or hazardous alcohol use compared to non-obese (odds ratio 9.4 [95% CI 2.2-40.9] and 5.6 [95% CI 1.6-19.7] respectively). CONCLUSIONS: The number of new cases of cirrhosis diagnosed clearly demonstrates that existing estimates of prevalence are likely to be gross underestimates. Obesity was an important risk factor for cirrhosis within both alcohol users and diabetics.

Ocular histopathology in animals experimentally infected with Mycobacterium leprae and M. lepraemurium. 1. Mycobacterium leprae and M. lepraemurium infections in the mouse. 2. Mycobacterium leprae infections in the 9-banded armadillo (Dasypus novemcinctus L.).

At varying periods of time following the successful establishment of systemic infections with Mycobacterium leprae or M. lepraemurium in the mouse and the nine-banded armadillo eyes were examined by light microscopy. Inoculation of bacilli was by the intravenous or intraperitoneal route or directly into the hind footpads; eyes were not directly inoculated in this study. During periods of up to 3 years under laboratory conditions no animal showed evidence of impaired vision or blindness, and the external appearance of both eyes was normal. The ocular histopathology and the sites of accumulation of bacilli are described. In immunologically normal mice infected with M. lepraemurium bacilli were much commoner in extraorbital tissues, but they were, nevertheless, found in various tissues within the orbit, including the ciliary body and sclera. In immunologically normal mice (and one rat) injected with M. leprae of human origin no bacilli were found in the eye, but in mice immunologically depressed by thymectomy and total body irradiation considerable numbers of bacilli were present in the iris and ciliary body and also in the limbal cornea. In the armadillo bacilli were found in large numbers in virtually all tissues except the lens, retina, optic nerve, and aqueous and vitreous humours, but the uveal tract was heavily involved. Findings are discussed in relation to the great frequency of ocular involvement and the importance of immune-complex disease in patients with lepromatous leprosy, and to factors wihch may favour the localisation and multiplication of Mycobacterium leprae in the eye.

Leprosy in peripheral nerves: histopathological findings in 119 untreated patients in Nepal.

From a series of 343 nerve biopsies taken by one clinician over a period of 12 years in Nepal, this paper describes the histopathological findings in 153 biopsies from 119 patients suffering from tuberculoid, borderline (dimorphous) or lepromatous leprosy, who were untreated at the time of first presentation and diagnosis. They were taken during the course of other studies, mainly concerned with the mode of transmission of leprosy, and which included biopsies of skin, dartos muscle, nasal mucous membrane and nipple, results of which have already been published. Examination of serial sections by light microscopy revealed a density of cellular infiltration in non-lepromatous cases, or of bacilli in macrophages and Schwann cells in lepromatous cases, which was marked in degree and usually widespread from one end of the biopsy to the other. Intraneural caseation was recorded in four patients with tuberculoid or borderline-tuberculoid leprosy, and many others in this part of the spectrum showed extensive disruption of perineurial and endoneurial structure. In lepromatous patients, the numbers of bacilli in the endoneurial area not infrequently exceeded one thousand per oil immersion field. Although well known to histopathologists familiar with this disease, it is considered that the significance of these findings, in patients presenting for the first time, is not well appreciated by those working in general medicine, neurology, epidemiology, or even in leprosy control.

Clofazimine (Lamprene, B663) in the treatment of lepromatous leprosy in the United Kingdom. A 12 year review of 31 cases, 1966-1978.

This paper records the results of treatment with clofazimine of a group of 31 patients of mixed racial origin in the United Kingdom suffering from lepromatous or borderline-lepromatous leprosy. Progress was assessed by clinical and histopathological examination for periods up to 12 years after starting treatment. Although given mainly for dapsone resistance, either proven on mouse foot pad inoculation or strongly suspected on clinical grounds, clofazimine was also used in some patients for the suppression of reactions, notably those due to the formation of immune-complexes, the manifestations of which included erythema nodosum leprosum (ENL). Four patients, all of whom had taken clofazimine in relatively high dosage for many months, usually for ENL, complained about pigmentation. in the remaining patients, on doses of the order of 100 mg three times weekly, pigmentation was not a problem. None of the 31 patients suffered from gastro-intestinal symptoms or signs of any significance during the period of study. Many of the patients started taking dapsone in the 1940s; most had a long, complex, and unsatisfactory history of previous treatment with many drugs. This made assessment of response to clofazimine difficult in some cases. The general impression is that clofazimine has been outstandingly valuable both as regards treatment of the bacillary infection and the suppression of reaction. No patient relapsed during the period of study. The authors express the opinion that no other drug currently available for the treatment of leprosy could have achieved such good results in a comparable group of patients.

Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia.

In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.