Why study inner ear hair cell mitochondria?

In several systems of the body (muscle, liver, nerves), new studies have examined the internal structure of mitochondria and brought to light striking new findings about how mitochondria are constructed and how their structure affects cell function. In the inner ear field, however, we have little structural knowledge about hair cell and supporting cell mitochondria, and virtually none about mitochondrial subtypes or how they function in health and disease. The need for such knowledge is discussed in this short review.

Detection of human papilloma virus DNA in seven cases of focal epithelial hyperplasia in Iran.

BACKGROUND: Focal epithelial hyperplasia (FEH), also known as Heck's disease, is a very rare disease of the oral cavity especially in Asia. It is a disease of children and young adults. Various causes have been implicated but in majority of cases FEH is caused by some subtypes of human papilloma virus (HPV) especially 13 and 32. Polymerase chain reaction (PCR) is a useful tool to identify HPV in FEH as it is a rapid and sensitive method. OBJECTIVE: This study was designed to determine special HPV subtypes in seven cases of Heck's disease referring to our department by using PCR analysis. METHOD: Paraffin sections of seven patients clinically diagnosed as FEH with compatible histhopathological features underwent DNA extraction procedures for PCR examination. Initially, all specimens were tested for presence of HPV virus followed by specific PCR testing for 16, 18, 13, and 32 subtypes in positive samples. RESULTS: Human papilloma virus was found in all samples. In five cases HPV13 and in one case HPV32 was positive. One case showed strong reactivity for HPV but none of tested subtypes were positive. All cases were negative for HPV 16 and 18. CONCLUSIONS: Similar with other studies about FEH, most of our cases were associated with HPV 13 but other subtypes may also be implicated.

Trends in mortality and hospital admission rates for abdominal aortic aneurysm in England and Wales, 1979-1999.

BACKGROUND: The aim of this study was to investigate trends in population-based mortality, hospital admission and case fatality rates for abdominal aortic aneurysm (AAA) from 1979 to 1999. METHODS: This was an analysis of routine statistics from 79 495 death certificates in England and Wales and 3217 hospital inpatient admissions in the Oxford Region. RESULTS: Mortality rates for all AAAs increased between 1979 and 1999 from 13 to 25 per million in women and from 80 to 115 per million in men. Admission rates increased in the same time interval from three to 22 admissions per million per year in women, and from 52 to 149 per million per year in men. Case fatality rates for all non-ruptured AAAs that were operated on decreased from 25.8 to 9.0 per cent and for all ruptured AAAs from 69.9 to 54.4 per cent. CONCLUSION: Mortality rates and hospital admission rates for AAA rose in men and even more so in women between 1979 and 1999. Perioperative mortality for ruptured AAA declined a little during the study but nonetheless was still very high at the end. This reinforces the importance of detecting and treating AAA before rupture occurs.

Trends in mortality rates for death-certificate-coded diabetes mellitus in an English population 1979-99.

AIMS: Mortality statistics have customarily been coded and analysed using only one underlying cause of death. Rules for selecting the underlying cause, when more than one cause is certified on a death certificate, have changed twice in England over the past 20 years. We used data from death certificates for 1979-99 to compare mortality rates for diabetes mellitus certified anywhere on death certificates with those certified as the underlying cause. METHODS: Analysis of data from 18,917 death certificates that included diabetes mellitus in the former Oxford health region. RESULTS: Based on the underlying cause of death, mortality rates for diabetes varied substantially between the periods defined by rule changes. Based on mentions of diabetes anywhere on the death record, mortality rates were almost unchanged over time: they showed a non-significant rise of 0.1% per year (95% confidence interval -0.3, 0.6). Circulatory diseases were certified causes of death in 71% of all deaths in people with diabetes. Although mortality rates from circulatory diseases in the general population fell by 2.5% per year, rates for circulatory diseases in combination with diabetes did not fall. CONCLUSIONS: Two explanations are possible for the lack of change in mortality rates for diabetes based on all certified mentions between 1979 and 1999. Increasing prevalence and improved survival may have resulted in no net change; and/or there may have been no improvement in survival for people whose diabetes is associated with life-threatening pathology and in particular with circulatory diseases.

Trends in mortality for cancers, comparing multiple- and underlying-cause rates, in an English population 1979-1999.

In compiling official mortality statistics, rules for selecting the underlying cause of death have changed twice in the last 20 years in England. Mortality statistics for most types of cancer were not greatly affected, but there were significant effects on coding for cancers of colon, liver, breast, prostate, testis and bladder, and for lymphoma and leukaemia.

Risk factors for squamous cell carcinoma of the oesophagus in women: a case-control study.

Oesophageal cancer rates in women in the UK are more than 3 times higher than in most other European populations. A population-based matched case-control study of histologically confirmed squamous cell carcinoma of the oesophagus in women was carried out in 4 regions in England and Scotland. Interviews were carried out in hospital or at home and topics included: smoking; alcohol; tea and coffee consumption; medical and obstetric history; and diet. Response rates were 62% for cases and 65% for first-chosen controls. There were 159 case-control pairs. Significant results were found for: eating salads (odds ratio (OR) 0.42, 95% CI 0.20-0.92 in the highest quartile of consumption) and a light (as distinct from no) breakfast (OR 0.18, 95% CI 0.07 - 0.48) were protective; quantity of tea was a risk factor and there was a significant positive trend with temperature at which hot drinks were consumed (P = 0.03). Alcohol consumption was unrelated to risk, but there was a significant trend with years of smoking (P = 0.015). A protective effect of aspirin consumption was confined to the English centres (OR 0.08, 95% CI 0.01-0.56). Comparison with a parallel study of adenocarcinoma indicated a common protective effect of a healthy diet but otherwise distinct risk factors.

A case-control study of oesophageal adenocarcinoma in women: a preventable disease.

The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a significant dose-response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.

The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic.

Estimated incidence rates are presented for three human immunodeficiency virus (HIV)-associated cancers [Kaposi's sarcoma (KS), Burkitt's lymphoma (BL) and other non-Hodgkin's lymphomas (NHLs)] from across the African continent, based on data collected before the HIV epidemic. Mapping of the rates and comparisons with a range of geographical variables indicate completely different distributions for KS and BL but a degree of similarity in the occurrence of Burkitt's lymphoma and other NHLs. Comparisons with rates elsewhere in the world suggest, most notably, that KS was as common in some regions of sub-Saharan Africa as was cancer of the colon in much of Western Europe. Comparison with data from the era of AIDS indicates 20-fold increases in the occurrence of Kaposi's sarcoma in Uganda and Zimbabwe. The highest rates for BL were three to four times the rates for leukaemia at young ages in Western populations, but the general incidence of other NHL was no higher than in the West and very low rates were indicated for much of southern Africa.

Cancer and fluoridation.

Early geographical studies of cancer in areas that have naturally-occurring fluoride at different levels gave no indication of an effect on cancer rates associated with higher intakes of fluoride. Following widespread fluoridation to improve dental health in the United States and Britain, non-epidemiologists presented analyses of cancer data which they claimed demonstrated such an effect. However, subsequent large-scale comparisons of cancer rates in fluoridated and non-fluoridated areas for successive periods following fluoridation have not indicated any increase, either for all cancer or for malignancies across the range of individual sites. Studies undertaken specifically to examine the claims of the non-epidemiologists have, time-and-again, shown that, with the use of accurate data and correct statistical methods, the purported effects cease to be apparent. Details of the earlier evidence and claims are given in the 'Report of a Working Party on the Fluoridation of Water and Cancer' by Professor George Knox (1985) and of more recent analyses in Hoover et al. (1991a; 1991b; unpublished internal US PHS Memo, 1993). The present paper gives a brief overview of the evidence that fluoride in drinking water has not been shown to cause an increase in the risk of developing cancer and of the errors in the analyses that purport to show such an increase.

Occupation and bladder cancer: a death-certificate study.

Occupational statements on death certificates of 2,457 males aged 25-64 who died from bladder cancer in selected coastal and estaurine regions of England and Wales during 1965-1980 were studied. Excess mortality was found for deck and engine room crew of ships, railway workers, electrical and electronic workers, shoemakers and repairers, and tobacco workers. An excess of cases also occurred among food workers, particularly those employed in the bread and flour confectionary industry or involved in the extraction of animal and vegetable oils and fats. Use of a job-exposure matrix revealed elevated risk for occupations in which most workers were exposed to paints and pigments, benzene and cutting oils.

Cancer near potential sites of nuclear installations.

Mortality and census data for 400 districts of England and Wales were analysed with respect to existing sites of nuclear power stations and sites where the construction of such installations had been considered or had occurred at a later date (potential sites). Excess mortality due to leukaemia and Hodgkin's disease in young people who lived near potential sites was similar to that in young people who lived near existing sites. Areas near existing and potential sites might share unrecognised risk factors other than environmental radiation pollution.

Geographical variation in mortality from leukaemia and other cancers in England and Wales in relation to proximity to nuclear installations, 1969-78.

The distribution of mortality from 11 causes of death (lymphoid leukaemia, other leukaemia, leukaemia of all types, Hodgkin's disease, other lymphomas, all lymphomas, multiple myeloma, lung cancer, other malignancies, all malignancies and all other causes) has been examined in three age groups throughout England and Wales over the period 1969-78. The reorganisation of local authority administration in 1974 meant that the smallest areas that could be examined were 400 county districts or (in some cases) approximate county districts formed by aggregating pre-1974 local authority areas. The variation in the numbers of deaths observed about the numbers expected was assessed using log-linear models to estimate the effect on the relative risk in each district associated with social class, rural status, population size, health authority region and proximity to one of 15 nuclear installations. Trends in risk with increasing proximity to an installation (as judged by the proportion of the population resident within 10 miles) were examined after adjustment for the other four variables. The results showed that in districts near to an installation there were significant excess mortalities in persons under 25 years of age from leukaemia (RR = 1.15, P = 0.01) and especially from lymphoid leukaemia (RR 1.21, P = 0.01) and from Hodgkin's disease (RR 1.24, P = 0.05) and a significant deficiency of mortality from lymphoid leukaemia in persons aged 25-64 years. No significant trends were observed with an increasing proportion of the population near to the installations and the greatest excess mortality from lymphoid leukaemia in young persons was observed in the districts with the intermediate proportion of the population (10.0-65.9%) near an installation.

Cancer near nuclear installations.

The OPCS report on cancer incidence and mortality in the vicinity of nuclear installations in England and Wales provides a mass of information that is so large that it should be possible to detect quite small changes in disease levels with considerable confidence. The data on cancer mortality are less subject to selective bias than the registration data on which incidence rates are based, and they provide the firmest grounds on which evidence of any effect can be obtained. These data show conclusively that there has been no general increase in cancer mortality in the vicinity of nuclear installations in a 22-year period beginning several years after the opening of the installations that have released the largest amounts of radionuclides to the environment. On the contrary, the mortality from cancer has tended to be lower in the LAAs in the vicinity of nuclear installations than in control LAAs selected for their presumed comparability with the former. This is unlikely to be due to a protective effect of ionizing radiation and suggests that, despite the efforts that were made to choose comparable control areas, there were non-installation differences between the populations relevant to the risk of dying from one or other type of cancer. Detailed examination of the few types of cancer that were relatively more common in the installation areas suggest that several of the differences were most likely to be due to chance, diagnostic artefacts or social factors rather than to any hazard specifically related to the installations. One disease provides a possible exception: namely, leukaemia in the age group 0-24 years. Two other diseases need further investigation, multiple myeloma and Hodgkin's disease in the older age group 25-74 years. The excess mortality rates recorded from these cancers were not large, and it has yet to be established that they are not due to general confounding by other environmental or socio-economic factors.

Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei.

Estimations of the incidence of hepatocellular carcinoma (HCC) for the period 1968-74 in the Province of Inhambane, Mozambique, have been calculated and together with rates observed in South Africa among mineworkers from the same Province indicate very high levels of incidence in certain districts of Inhambane. Exceptionally high incidence levels in adolescents and young adults are not sustained at older ages and suggest the existence of a subgroup of highly susceptible individuals. A sharp decline in incidence occurred during the period of study. Concurrently with the studies of incidence, 2183 samples of prepared food were randomly collected from 6 districts of Inhambane as well as from Manhica-Magude, a region of lower HCC incidence to the south. A further 623 samples were taken during 1976-77 in Transkei, much further south, where an even lower incidence had been recorded. The mean aflatoxin dietary intake values for the regions studied were significantly related to HCC rates. Furthermore, data on aflatoxin B1 contamination of prepared food from 5 different countries showed overall a highly significant relationship with crude HCC rates. In view of the evidence that chronic hepatitis B virus (HBV) infection may be a prerequisite for the development of virtually all cases of HCC and given the merely moderate prevalence of carrier status that has been observed in some high incidence regions, it is likely that an interaction between HBV and aflatoxin is responsible for the exceptionally high rates evident in parts of Africa and Asia. Various indications from Mozambique suggest that aflatoxin may have a late stage effect on the development of HCC. This points to avenues for intervention that could be more rapidly implemented than with vaccination alone.