Roles of adipose restriction and metabolic factors in progression of steatosis to steatohepatitis in obese, diabetic mice

Background and Aims: We previously reported that steatohepatitis develops in obese, hypercholesterolemic, diabetic foz/foz mice fed a high‐fat (HF) diet for 12 months. We now report earlier onset of steatohepatitis in relation to metabolic abnormalities, and clarify the roles of dietary fat and bodily lipid partitioning on steatosis severity, liver injury and inflammatory recruitment in this novel non‐alcoholic steatohepatitis (NASH) model. Methods: Foz/foz (Alms1 mutant) and wild‐type (WT) mice were fed a HF diet or chow, and metabolic characteristics and liver histology were studied at 2, 6, 12 and 24 weeks. Results: After 12 weeks HF‐feeding, foz/foz mice were obese and diabetic with approximately 70% reduction in serum adiponectin. Hepatomegaly developed at this time, corresponding to a plateau in adipose expansion and increased adipose inflammation. Liver histology showed mild inflammation and hepatocyte ballooning as well as steatosis. By 24 weeks, HF‐fed foz/foz mice developed severe steatohepatitis (marked steatosis, alanine aminotransferase elevation, ballooning, inflammation, fibrosis), whereas dietary and genetic controls showed only simple steatosis. While steatosis was associated with hepatic lipogenesis, indicated by increased fatty acid synthase activity, steatohepatitis was associated with significantly higher levels of CD36, indicating active fatty acid uptake, possibly under the influence of peroxisome proliferator‐activated receptor‐γ. Conclusion: In mice genetically predisposed to obesity and diabetes, HF feeding leads to restriction of adipose tissue for accommodation of excess energy, causing lipid partitioning into liver, and transformation of simple steatosis to fibrosing steatohepatitis. The way in which HF feeding ‘saturates’ adipose stores, decreases serum adiponectin and causes hepatic inflammation in steatohepatitis may provide clues to pathogenesis of NASH in metabolic syndrome.     

The effect of different cement insertion techniques on the bone-cement interface

Since the introduction of cemented total hip arthroplasty, the method of cement usage has evolved through several generations. These changes may have been responsible for an improvement in femoral component longevity. The nature of the bone-cement interface in first-generation cementing techniques has been described, but the bone-cement interface in more recent cementing techniques has not. This article describes the bone-cement interface after 2 different cementing techniques in a canine total hip arthroplasty model.     

ULTRASOUND SCREENING OF THE ABDOMINAL AORTA IN MALAYSIANS

Ultrasound examination of the abdominal aorta was performed on 100 patients with cardiovascular disease and a control group of 100 subjects. The objectives were to define the normal aortic size of Malaysians, to screen for aneurysms and to compare the aorta size of the different population groups. In the study group the mean anteroposterior (AP) diameter of the non-aneurysmal aortas at the level of the renal arteries was 1.82cm (range 0.9–2.6cm) in men and 1.83cm (range 1.5–2.3cm) in women. This compares with 1.61 cm (range 1.1–2.2cm) in men and 1.50cm (range 0.8–2.4cm) in women in the control group. The dimensions of the infrarenal aorta show a similar relationship between the two groups. These AP diameters were significantly smaller than the published figures from studies done on Western populations and are consistent with the smaller stature of Malaysians. Five aneurysms and one ectasia were found (mean size 5cm, range 3.5–6.0cm). all in men aged 50–75 years in the study group, and none in the control group. All the aneurysms were easily palpable in these patients who were thinner than the average Caucasian. Given the lower incidence of aortic aneurysms in Malaysians there is no role for routine ultrasound screening of the population. High risk groups can be adequately screened by clinical examination alone.     

Methotrexate for prophylaxis of choriocarcinoma

The malignancy rate in 580 cases of hydatidiform mole in Singapore was 14.8 per cent. An attempt was made to reduce this rate by giving patients with moles 3 courses of prophylactin oral methotrexate totaling 150 mg. after removal of the mole. In a study involving 380 patients, including control subjects, the treatment achieved a slight reduction in malignancy rate from 8.7 to 4.5 per cent, but it produced considerable toxicity and a significantly increased mortality rate (2.2 per cent compared with 0.5 per cent in controls). However, the tumors which developed subsequent to prophylactic methotrexate were sensitive to the same drug given in larger doses. Choriocarcinomas which were recognized within a year of hydatidiform mole were highly sensitive to chemotherapy, and a 100 per cent survival rate can be expected if close follow-up and carefully supervised treatment are instituted. There was an 80 per cent mortality rate among 5 cases of choriocarcinoma which were detected later. It is suggested that closer supervision of follow-up programs, parenteral chemotherapy, a careful, decisive rotation of chemotherapeutic agents, and selective use of radiotherapy in cases of cerebral choriocarcinoma may improve the survival rate in the late cases. Routine prophylactic chemotherapy for hydatidiform mole is not recommended.     

Epidemic hysteria in Malaysian schools: an illustrative episode.

This paper discusses the prevalence and characteristics of epidemic hysteria among predominantly rural Malay schools in Malaysia. An illustrative episode in a Malay residential girls' school is described, and contributory factors to this outbreak are elaborated. An attempt is made to analyze the complex interweaving of psychological, religious, cultural, and sociological factors in the precipitation of the outbreak.