A rise in the percentage of large unstained cells in the peripheral blood determined by the Hemalog D90 automated differential counter is a feature of impending myeloid engraftment following bone marrow transplantation

The early phase of bone marrow regeneration has been monitored by automated differential counts on the peripheral blood using a Hemalog D90, following 107 transplant procedures. An elevated percentage of large unstained cells (LUCs) was detected in over 98% of cases and in 72% of cases the rise in percentage LUCs preceded the rise of the total leucocyte count into the detectable range on a Coulter counter (greater than 0.3 X 10(9)/1) by an average of 4 days. These LUCs are shown to be CD8 + T lymphocytes. The ability to detect the earliest signs of regeneration is particularly useful when regeneration is delayed and repeat marrow infusion is considered.     

Shock Wave-Induced Pancreatic Trauma

A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed.     

The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits

OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol.     

Hepatocellular carcinoma and chemoembolization

Abstract
Background : Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting.
Aims : To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria.
Methods : Selective catheterization of the right or left hepatic arteries was performed. A mixture of cis-platin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1–3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival.
Results : CT response rates: partial response 19% ( n = 7), median duration 11 months (range 2+ to 37+); minor response 17% ( n = 6), median duration 7 months (1+ to 12+); stable disease 42% ( n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% ( n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0–37+). Median overall survival was 15 months (range 6–50+).
Conclusion : Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour. (Intern Med J 2001; 31: 517–522.     

The roles of phosphatidylethanol,ethyl glucuronide,and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs

Direct alcohol biomarkers, including urinary ethyl glucuronide (EtG), urinary ethyl sulfate (EtS), and blood phosphatidylethanol (PEth), are used to monitor alcohol abstinence in individuals who are mandated to abstain. In this consecutive case series study, we examined 1000 forensic reports of participants enrolled in a professionals health program who were contractually obligated to abstain from alcohol and who underwent recovery status evaluations. We identified 52 evaluations in which urinary EtG, EtS, and blood PEth were measured and which produced a positive result for at least one of these analytes. PEth, at a cutoff concentration of 20 ng/mL, revealed alcohol use more frequently than EtG or EtS at our laboratory's cutoff concentrations of 100 and 25 ng/mL, respectively. This was true, as well, at alternative EtG/EtS cutoff concentrations of 200/50, 300/75, and 400/100 ng/mL. PEth was more likely than EtG/EtS to be positive in participants previously diagnosed with alcohol use disorders (AUD), whereas EtG/EtS was more likely than PEth to be positive in participants without AUD. In this study, blood PEth was the most sensitive biomarker for evidencing alcohol use.     

Dysregulation of the epigenome in triple-negative breast cancers: Basal-like and claudin-low breast cancers express aberrant DNA hypermethylation

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers.     

A ‘Textbook Pattern’? Malaria Control and Eradication in Jamaica, 1910–65

In 1965 Jamaica was declared free of malaria by the World Health Organisation (WHO), thus ending centuries of death and suffering from the disease. This declaration followed the successful completion of the WHO’s Malaria Eradication Programme (MEP) on the island, initiated in 1958. This account first explores the antecedent control measures adopted by the government up to the MEP. These, as advocated by the previous malaria ‘experts’ who had reported on the disease on the island concentrated on controlling the vector and the administration of quinine for individual protection. Although Jamaica suffered no catastrophic epidemics of island-wide scope, malaria was a constant cause of mortality and morbidity. Major change came in the wake of the Second World War within the changing political context of national independence and international development. In 1957 the Jamaican government joined the global WHO programme to eradicate malaria. The Jamaican campaign exposes many of the problems noted in other studies of such top–down initiatives in their lack of attention to the particular circumstances of each case. Despite being described as ‘a textbook pattern’ of malaria eradication, the MEP in Jamaica suffered from a lack of sufficient preparation and field knowledge. This is most obviously illustrated by the fact that all literature on the programme sent to Jamaica in the first two years was in Spanish. That the MEP exploited the technological opportunity provided by dichlorodiphenyltrichloroethane (DDT) with advantage in Jamaica is not disputed but as this analysis illustrates this success was by no means guaranteed. Keywords : Jamaica, Malaria, Control, Eradication, World Health Organisation