Aetiology of Autism — Focus on the Biological Perspective

Autism has been classified as a pervasive developmental disorder (PDD), with abnormalities in verbal and non-verbal communication, and social interaction. Characterized by repetitive and obsessive behavior, repetitions of speech (echolalia), and an insistence of sameness, it is most commonly diagnosed in early childhood (from 24 months onwards), and affects two to four in every 10,000 children (APA, 1994). Kennels (1943, cited in Volkmar, 1996) original Investigation of the disorder addressed the influence of parent-child interaction in syndrome pathogenesis. This was at first misinterpreted as suggestive of a deficit in parenting. With continuing research however, this view has now changed and biological factors are seen as the main underlying causes of autism. Research into biological factors implicated in autism focused on four areas: neurological, biochemical and genetic abnormalities, and problems during pregnancy and/or birth. A long list of potential factor implies that autism is a heterogeneous disorder, and to date there is no unified model that would explain its aetiology. The aim of this paper is to review literature concerning biology of autism.     

Characteristics of 2000 patients who visited a halitosis clinic

Aims: The aim of this paper was to analyse the aetiology and characteristics of 2000 patients who visited a multidisciplinary bad breath clinic in Leuven, Belgium and to correlate organoleptic ratings with portable device measurements.
Materials and Methods: The characteristics and aetiology of breath malodour of two thousand consecutive patients who visited a halitosis consultation were explored by means of a standard questionnaire and a clinical examination, including organoleptic scores provided by a trained and calibrated judge, and a portable bad breath detector (Halimeter^®).
Results: Most patients came without referral and had complaints for several years (mean: 7 years, SD: 8 years). For 76% of the patients, an oral cause was found [tongue coating (43%), gingivitis/periodontitis (11%) or a combination of the two (18%)]. Pseudo-halitosis/halitophobia was diagnosed in 16% of the cases; and ear, nose and throat/extra-oral causes were found in 4% of the patients. Most patients had an organoleptic score <3 and a Halimeter^® value <240 p.p.b.
Conclusions: Even though it was observed that halitosis has a predominantly oral origin, a multidisciplinary approach remains necessary to identify ear, nose and throat or extra-oral pathologies and/or pseudo-halitosis/halitophobia.     

The aetiology of dento-alveolar injuries and factors influencing attendance for emergency care of adolescents in the North West of England

Abstract – The aims of the study were to determine the main aetiological factors involved in injuries to anterior teeth and to identify factors influencing the attendance for emergency care. This information is essential, first, for planning dental health education programmes aimed at reducing the incidence of dental trauma and, second, to devise strategies for its effective treatment. Of 2022 schoolchildren examined for evidence of dental trauma, 696 (34%) had experienced injury and were interviewed regarding this injury. Of these, 403 knew about their damaged front tooth, but only 330 recollected the incident causing the injury. Over one third of accidents occurred at home and a further 25% at school. The most common cause of injury was falling onto a hard surface or object (34%) with accidents involving bicycles or other sporting activities accounting for a further 30%. Factors found to be significantly related to attendance for emergency care were experience of pain, unattractive appearance of the injured tooth and social classification, with children from higher income, more affluent areas being more likely to seek treatment. The majority of dental injuries were the result of genuine accidents which were almost impossible to prevent. This study highlighted the need for attention to be brought to parents, children, lay people and health care professionals that all dental injuries should be examined by a dentist, not just those injuries resulting in pain or poor aesthetics.     

Orofacial granulomatosis: review on aetiology and pathogenesis

Orofacial granulomatosis (OFG) is considered as an uncommon disease and nomenclature of the disease was subjected to debate for a long time. Although various aetiological agents such as food substances, food additives, dental materials and various microbiological agents have been implicated in the disease process its precise pathogenesis is yet to be elucidated. Delayed type of hypersensitivity reaction appears to play a significant role, although the exact antigen inducing the immunological reaction varies in individual patients. However, evidence for the role of genetic predisposition to the disease is sparse. The underlying immunological mechanism appears to show some similarities between OFG and Crohn's disease, emphasizing the need for more comparative studies of the two entities. Therefore, we propose the term idiopathic OFG as a better term for those cases restricted to oral region without any identifiable known granulomatous disease and the diagnosis should not be changed until the patient develops systemic manifestations of a specific granulomatous condition. This review attempts to discuss the role of different aetiological agents and certain aspects of pathogenesis of OFG.     

Risk factors for intrahepatic cholangiocarcinoma: a possible role of hepatitis B virus

Summary. There are several established risk factors for intrahepatic cholangiocarcinoma (ICC), namely primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, intrahepatic biliary stones and chemical carcinogen exposure. However, the majority of patients with ICC do not have any of these risk factors. Therefore, identification of other risk factors is warranted for the prevention and early detection of ICC. We evaluated the risk factors for ICC in a large‐scale cohort study in the province of Osaka, Japan. This retrospective cohort study included 154,814 apparently healthy individual blood donors, aged 40–64 years at the time of blood donation in the period 1991–1993. The average observation period was 7.6 years, resulting in 1.25 million person‐years of observation. Incident ICC cases were identified by linking the blood‐donor database to the records in the population‐based cancer registry for the province. There were 11 incident ICC cases during follow‐up, with an incidence rate of 0.88 per 100 000 person‐years. Compared with subjects aged 40–49 years, the subjects aged 50–54 years and 55–59 years had a significantly higher risk for ICC (hazard ratio [HR] = 5.90; 95%CI:1.08–32.31 and 11.07; 95%CI:1.98–61.79, respectively). Compared with those with ALT level of 19 Karmen Units (KU) or less, subjects with ALT level of 40 KU or higher had a significantly higher risk for ICC (HR: 8.30; 95%CI:1.47–46.83). Compared with those who tested negative for both HBsAg and anti‐HCV, those who tested HBsAg‐positive had a significantly higher risk for ICC (HR: 8.56; 95%CI: 1.33–55.20). Our results suggest that HBV infection and liver inflammation are independently associated with ICC development. These findings need to be verified by further large cohort studies.     

B cells behaving badly

The pathogenesis of B-cell lymphoproliferative disorders in general and B-cell chronic lymphocytic leukaemia in particular appears to involve dysfunctional regulation of humoral and cellular immunity with the subsequent development of genetic aberrations in B cells. In theory, either component may arise de novo or may be influenced by environmental exposures including infectious agents, antigens, genotoxic chemicals, or radiation. As an intermediary within the exposure-disease continuum, monoclonal B-cell lymphocytosis may be a helpful biomarker for teasing out these various contributions to risk. This article introduces a series of papers that resulted from an International Workshop held in May 2007 entitled 'Monoclonal B-cell Lymphocytosis and Chronic Lymphocytic Leukemia: Environmental and Genetic Risk Factors'. Research efforts, such as those described in this issue, should lead to improved interventions, more predictive biomarkers, more effective treatments, and a greater appreciation of how the immune system functions over the entire human lifespan.     

Hepatic granulomas: histological and molecular pathological approach to differential diagnosis–a study of 442 cases

Background/Aims: The incidence of hepatic granulomas is reported in 2–15% of liver biopsies. This study was carried out to evaluate the incidence and aetiology of hepatic granulomas in a German Institute of Pathology with specialization in liver diseases. Methods: A retrospective case review was performed on 12 161 liver biopsies of the Institute of Pathology (University of Cologne) between 1996 and 2004. Aetiology was determined according to histomorphological changes, clinicopathological data and liver tissue polymerase chain reaction (PCR) for detection of diverse putative pathogens in the liver tissue. Results: Four hundred and forty‐two liver biopsies revealed granulomatous lesions (3.63%). Two hundred and fifteen cases (1.77% of all biopsies and 48.64% of granulomatous lesions) were diagnosed as primary biliary cirrhosis. In 37 cases (0.3% of all biopsies and 8.37% of granulomatous lesions), the diagnosis of sarcoidosis was established. A positive PCR result for an infectious pathogen was obtained in 15 samples (3.39%) [Bartonella henselae (n=2), Listeria (n=3), Mycobacterium tuberculosis (n=3), Yersinia pseudotuberculosis (n=1), cytomegalovirus (n=2), Epstein–Barr virus (n=4)]. In six cases, a putative diagnosis was established according to the report of clinical conditions. In 11 cases (2.48%), drugs were the putative causative agent. In 158 cases (36%) a definite diagnosis could not be established. Conclusions: Hepatic granulomas have a broad range of underlying aetiologies. With a combined histological, clinical, serological, and molecular approach, we were able to clarify the cause in 64% of the cases. Owing to the diverse prognosis and therapeutic implications, a detailed interdisciplinary workup of all liver biopsies with granulomatous lesions is mandatory.     

Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis

In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.     

Human papilloma virus is associated with breast cancer

Background:

There is increasing evidence that high-risk human papilloma virus (HPV) is involved in cancers in addition to cervical cancer. For example, it is generally accepted that HPV has a role in a significant proportion of head and neck tumours, and it has long been hypothesised that hormone dependent oncogenic viruses, such as HPV may have causal roles in some human breast cancers. A number of reports have identified HPV DNA in breast tissue and breast cancer specimens, but these rely on standard polymerase chain reaction (PCR), which is criticised for its propensity for contamination.

Methods:

We have used two different technologies, in situ and standard PCR (with sequencing), and histology based on light microscopy.

Results:

We unambiguously demonstrate the presence of high-risk HPV in the cells of breast cancer specimens and breast cancer cell lines. In addition, we also show that the oncogenic characteristics of HPV associated breast cancer are very similar to HPV-associated cervical cancer. Specifically, that putative koilocytes are present in some HPV associated breast cancers.

Interpretation:

The above observations indicate a likely causal role for high-risk HPV in human breast cancer and offer the possibility of primary prevention of some breast cancers by vaccination against HPV.