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.     

Lymphoedema of the lower extremities – background,pathophysiology and diagnostic considerations

Lymphoedema of the lower extremities is a chronic debilitating disease that is often underdiagnosed. Early diagnosis and treatment is paramount in reducing the risk of progression and complications. Lymphoedema has traditionally been defined as interstitial oedema and protein accumulation because of a defect in the lymphatic drainage; however, some findings suggest that the interstitial protein concentration may be low in some types of lymphoedema. Primary lymphoedema is caused by an inherent defect in the lymphatic vessels or lymph nodes. Secondary lymphoedema is caused by damages to the lymphatic system most often caused by cancer or its treatment. Many of the underlying pathophysiological mechanisms have yet to be elucidated. Many methods have been developed for examination of the lymphatic system. Lymphoscintigraphy is presently the preferred diagnostic modality. Lack of consensus regarding protocol and qualitative interpretation criteria results in a too observer dependent outcome. Methods for objectifying the scintigraphy through quantification have been criticized. Depot clearance rates are an alternative method of quantification of lymphatic drainage capacity. This method however has mostly been applied on upper extremity lymphoedema. The aim of this review is to provide a literature‐based overview of the aetiology and pathophysiology of lower extremity lymphoedema and to summarize the current knowledge about lymphoscintigraphy and depot clearance techniques. The abundance of factors influencing the outcome of the examination stresses the need for consensus regarding examination protocols and interpretation. Further studies are needed to improve diagnostic performance and understanding of pathophysiological mechanisms.     

Differences in reasons for smoking between younger and older smokers

The reasons why older people smoke have not been examined in the literature. This paper attempted to examine the differences in motivation and maintenance factors of elderly and young smokers using the Horn-Waingrow Why do you smoke questionnaire. One hundred and thirteen clinical patients and 112 non-patient controls were used in this study. The clinical group was divided into an elderly group (n = 58) and a younger group (n = 55). The results of a discriminant analysis showed that patients significantly differed from non-patients on 'automatic habit and stimulation', and 'crutch/tension reduction' factors. Elderly patients were found to be significantly differentiated from both younger patients and the control group on the 'pleasurable relaxation' factor. These findings offer support for the US Surgeon Generals' report that elderly smokers do have different motivating factors for their smoking behaviours from younger smokers.     

Cerebral vasospasm after subarachnoid haemorrhage of unknown aetiology: A clinical and transcranial Doppler study

Summary Sixteen patients (6 women, 10 men; mean age: 52.5 years) suffering from spontaneous subarachnoid haemorrhage (SAH) of unknown origin underwent a protocol of initial and then weekly computed tomography (CT), initial four-vessel digital subtraction angiography (DSA) and at least one control pancerebral DSA. Fourteen patients had magnetic resonance imaging before undergoing first control DSA. All patients had calcium-antagonists (Nimodipine) via a central venous catheter, were kept on the neurosurgical intensive care unit and followed daily with transcranial Doppler ultrasonography (TCD). One patient (6.3%) developed moderate and 5 (31.1%) developed severe cerebral vasospasm as documented with TCD and exhibited deterioration of their level of consciousness. These 6 patients were treated with induced hypertension, hypervolaemia and haemodilution. Their blood flow velocities were elevated for a mean of 8 (5–17) days with a peak after 12.5 (9–17) days following SAH. No complications due to treatment were noted. One patient of the non-vasospastic group died of pulmonary embolism, another patient had an ischaemic incident during angiography, which has led to permanent disability. On follow-up 2–24 months after SAH 14 patients had returned to their premorbid state. It is concluded that patients suffering from SAH of unknown origin should undergo repeated angiographic investigation and subsequent daily monitoring of their neurologic status including daily TCD recordings so that haemodynamic treatment can be established in the event of cerebral vasospasm, which may occur in up to one third of these patients.     

Aetiological factors of peptic ulcer: Perspectives of epidemiological observations this century

Abstract There are five known environmental, causative factors for peptic ulcer, namely, non-steroidal anti-inflammatory drugs (NSAID), Helicobacter pylori infection, cigarette smoking, environmental stress and dietary habit. There have been six factual, epidemiological observations on peptic ulcer this century: the rise and fall of ulcer frequency in Western societies; geographical variations in ulcer rates; in sex ratios; in duodenal: gastric ulcer ratios; and in placebo healing rates; and seasonal variation in ulcer frequencies. This report examines each of these epidemiological observations to see if each of the environmental factors can explain the observations. The secular trends and the variation in ulcer rates can be related to all the environmental factors. The sex ratios can be explained on the basis of cigarette smoking and environmental stress, whereas the duodenal: gastric ulcer ratios may be ascribed to NSAID use. Placebo healing and seasonal occurrence of ulcer is probably more related to environmental stress. Helicobacter pylori infection alone cannot explain the sex ratios, the duodenal: gastric ulcer ratios, the placebo healing and the seasonal occurrence of ulcer. Cigarette smoking or NSAID use alone does not tally with the seasonal variation of ulcer frequencies. Environmental stress alone does not fit into the recent fall of ulcer rates in Western countries. This report supports the concept of heterogeneity in peptic ulceration.     

Viral and bacterial aetiology of community‐acquired pneumonia in adults

Please cite this paper as: Huijskens et al. (2012) Viral and bacterial aetiology of community‐acquired pneumonia in adults. Influenza and Other Respiratory Viruses 7(4), 567–573. Background Modern molecular techniques reveal new information on the role of respiratory viruses in community‐acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community‐acquired pneumonia who were admitted to the hospital. Methods Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community‐acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real‐time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. Results Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were positive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (≥2) were found in 16 patients. Conclusion In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.     

Fibrinogen polymorphisms are not associated with the risk of myocardial infarction

In the Study of Myocardial Infarctions Leiden, we investigated the prevalence of three polymorphisms in the alpha- and beta-fibrinogen genes among 560 patients with a myocardial infarction and 646 control subjects. Secondly, we studied the relationships between these polymorphisms and fibrinogen activity and antigen levels. The TaqI, HaeIII and BclI polymorphisms in the fibrinogen gene were not associated with myocardial infarction. As we found an association of the rare B2 allele with fibrinogen levels and a similar, but weak, effect for the rare H2 allele, we conclude that a genetic propensity to high fibrinogen levels does not affect the risk of myocardial infarction. This is evidence against a causal role for fibrinogen levels in the aetiology of myocardial infarction.     

Understanding the pathogenesis of type 2 diabetes: can we get off the metabolic merry-go-rounds?

The aetiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. The concordance of NIDDM in identical twins and differences in the prevalence rate of NIDDM between different racial groups suggest a genetic cause. Hyperglycaemia in established diabetes is caused by a combination of hepatic insulin resistance, impaired peripheral (muscle and fat) glucose uptake and a defect in glucose-mediated insulin secretion. However, it is not known if these defects are all inherited or if one can cause the others. This uncertainty is due to the fact that hyperglycaemia per se can cause defects in insulin action and insulin secretion that resemble those found in NIDDM. Furthermore the elevated free fatty acid (FFA) levels found when NIDDM is associated with obesity are known to cause both peripheral and hepatic insulin resistance. Recently we have demonstrated the mechanism by which elevated FFA levels can cause hepatic insulin resistance. However, we also have evidence that the converse holds in that genetically engineered hepatic insulin resistance in a transgenic rat model leads to obesity. Thus an understanding of the pathogenesis of NIDDM is complicated by the fact that hyperglycaemia and obesity can be both causes and consequences of insulin resistance. To overcome these difficulties, studies in young, euglycaemic diabetes-prone subjects have been conducted. Results suggest that there may be different causes for NIDDM in different racial groups.     

Discovery of rotavirus: Implications for Child health

For centuries, acute diarrhea has been a major worldwide cause of death in young children, and until 1973, no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. In 1973 Ruth Bishop, Geoffrey Davidson, Ian Holmes, and Brian Ruck identified abundant particles of a 'new' virus (rotavirus) in the cytoplasm of mature epithelial cells lining duodenal villi and in feces, from such children admitted to the Royal Children's Hospital, Melbourne. Rotaviruses have now been shown to cause 40–50% of severe acute diarrhea in young children worldwide in both developing and developed countries, and > 600 000 young children die annually from rotavirus disease, predominantly in South-East Asia and sub-Saharan Africa. Longitudinal surveillance studies following primary infection in young children have shown that rotavirus reinfections are common. However the immune response that develops after primary infection is protective against severe symptoms on reinfection. This observation became the basis for development of live oral rotavirus vaccines. Two safe and effective vaccines are now licensed in 100 countries and in use in 17 countries (including Australia). Rotarix (GSK) is a single attenuated human rotavirus, representative of the most common serotype identified worldwide (G1P[8]). RotaTeq (Merck) is a pentavalent mixture of naturally attenuated bovine/human rotavirus reassortants representing G1, G2, G3, G4, and P(8) serotypes. Preliminary surveillance of the numbers of children requiring hospitalization for severe diarrhea, in USA, Brazil, and Australia, after introduction of these vaccines, encourages the hope that rotavirus infection need no longer be a threat to young children worldwide.