Effect of childbirth after treatment on long-term survival from breast cancer.

BACKGROUND: This study quantified long-term absolute and relative mortality risks of survivors of breast cancer with subsequent childbirth. METHODS: The Singapore Birth Register (n = 319,437), Swedish Multi-Generation Register (n = 11 million) and population-based cancer registries were linked to identify 492 women with childbirth after breast cancer. For these women, cumulative mortality risks and standardized mortality ratios (SMRs) were calculated and compared with those of 8529 women aged less than 40 years with breast cancer without subsequent childbirth, and with those predicted by Adjuvant! Online. RESULTS: Women with subsequent childbirth had a lower 15-year cumulative overall mortality rate than other women with breast cancer (16.8 (95 per cent confidence interval (c.i.) 13.3 to 20.9) versus 40.7 (39.5 to 41.9) per cent), but a higher relative mortality risk than the background population (SMR 13.6, 95 per cent c.i. 10.6 to 17.3). Mortality risks decreased significantly with increasing interval between diagnosis and subsequent childbirth. Mean 10-year cumulative mortality risks of women with subsequent childbirth were within the range of 10-year mortality predicted by Adjuvant! Online for women with T1 N0 tumours in otherwise perfect health. CONCLUSION: This study reinforced the view that pregnancy after breast cancer is not detrimental to survival. However, women who gave birth after this diagnosis had substantially higher mortality risks than young women in the general population. This information may be a valuable addition to routine mortality estimates.

SARS coronavirus and apoptosis.

1. The adenovirus-mediated overexpression of SARS coronavirus (SARS-CoV) spike protein (S) and its C-terminal domain (S2) induce apoptosis in Vero E6 cells. 2. Such apoptosis in Vero E6 cells is time- and dose-dependent. 3. The adenovirus-mediated overexpression of SARS-CoV N-terminal domain (S1) and other structural proteins, including E,M and N protein, do not induce apoptosis.

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. METHODS: The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). FINDINGS: Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. INTERPRETATION: The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

Measurable predictive factors for progression to AIDS among HIV-infected patients in Singapore.

INTRODUCTION: This study identifies measurable factors at the time of diagnosis that predict the progression to Acquired Immunodeficiency Syndrome (AIDS) among Human Immunodeficiency Virus (HIV)-infected patients in Singapore. MATERIALS AND METHODS: We carried out a retrospective study of 790 HIV-infected patients from 16 May 1985 to 31 December 2001. The end-point was the onset of AIDS-defining illness listed in the 1987 and 1991 revised Centers for Disease Control and Prevention criteria, but excluded CD4 cell counts as a criterion. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for age groups at diagnosis, baseline CD4 counts and periods for utilisation of antiretroviral treatment. A Cox regression model was constructed to determine independent predictors of disease progression. RESULTS: Univariate analysis showed that patients of older age at diagnosis had a significantly higher risk of progression compared to younger patients, and patients with higher baseline CD4 cell counts had a lower risk of progression to AIDS. Adjusting for the simultaneous influence of several covariates on the rate of HIV progression to AIDS, multivariate analysis using the Cox model showed a significantly higher risk of progression for older patients at diagnosis, and the progressive lowering of risk with increasing baseline CD4 cell counts. CONCLUSIONS: This study found older age at diagnosis and baseline CD4 cell counts to be measurable predictors for HIV progression to AIDS at time of diagnosis. Identification of these risk factors enables physicians to provide counselling and advice, and to start appropriate treatment early. This could lower the risk of progression and improve survival.

Does enhanced sympathetic tone contribute to angiotensin II hypertension in rats?

To determine whether enhanced sympathetic tone contributes to the maintenance of chronic angiotensin II (A II, 10 ng/min i.v. for 10 days) hypertension in rats, sympathetic activity was assessed in hypertensive and control rats by measuring norepinephrine (NE) turnover (alpha-methyl-p-tyrosine) in peripheral organs and by measuring depressor responses to ganglionic blockade in conscious rats. Pressor responses to methoxamine (1-8 micrograms/min) and arginine vasopressin (0.5-4 ng/min) were also obtained in rats with ganglionic blockade. Chronic A II infusion produced significant hypertension (mean +/- S.E. tail cuff pressure: 176 +/- 5 vs. 134 +/- 2 mm Hg in controls; n = 23 each group) but there were no significant differences in NE turnover in heart, kidney, skeletal muscle, or intestine in hypertensive rats compared with controls. Ganglionic blockade produced a significantly larger decrease in mean arterial pressure in A II-treated rats when compared with controls (73 +/- 7 vs. 38 +/- 2 mm Hg, n = 18 for each group). Dose-response curves for methoxamine and vasopressin were not significantly different between groups. The results suggest that the maintenance of chronic A II hypertension does not involve postsynaptic interactions between A II and the sympathetic system. The NE turnover data do not support the hypothesis that rats with chronic A II hypertension have enhanced sympathetic tone.

The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39).

The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5' RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.

Discrimination of an infected brain tumor from a cerebral abscess by combined MR perfusion and diffusion imaging.

The aim of this study was to investigate the signal characteristics of the abscess wall and tumor wall on diffusion-weighted and perfusion-weighted images and thus to evaluate the feasibility of using combined MR diffusion and perfusion imaging to differentiate pyogenic cerebral abscess from infected brain tumor. The tumor wall of various types of cystic or necrotic brain tumor was significantly hyperintense relative to that of cerebral abscess wall on both diffusion-weighted images and regional cerebral blood volume maps. Sixteen patients who had cerebral masses with large cystic or necrotic cavities were imaged to generate diffusion-weighted images and regional cerebral blood volume maps using single-shot echoplanar imaging (EPI) pulse sequences. Apart from qualitative analysis, apparent diffusion coefficients (ADC) as well as regional cerebral blood volume (rCBV) ratios were calculated from the abscess wall and peripheral tumor wall and comparison was made by using Student's t-test. The tumor wall of various types of cystic or necrotic brain tumor had significantly lower ADCs relative to those of the abscess wall (P<0.005) and thus appeared relatively hyperintense on diffusion-weighted images. The mean rCBV ratio relative to normal white matter (2.90+/-0.62) of the peripheral tumor wall of various types of cystic or necrotic brain tumor were significantly larger than the mean rCBV ratio (0.45+/-0.11) of the pyogenic cerebral abscess wall (P<0.001) by Student's t-test. It is concluded that the combined MR diffusion and perfusion imaging might be capable of differentiating an infected brain tumor from a pyogenic cerebral abscess.

Singapore cancer trends in the last decade.

In this review, we examine the trends in cancer incidence, mortality and survival in the last decade, using published data from the Singapore Cancer Registry in the period 1998 to 2009. While overall cancer incidences have remained stable, overall cancer mortality rates have declined for both genders. Thus, it is not surprising that there was an improvement in cancer survival. A steady decrease in lung cancer among males and females was observed, thereby leading to a drop in its cancer ranking. In the last five years, the most frequently occurring cancer was colorectal cancer among the male population and breast cancer among females. Survival for both cancers remained relatively optimistic. There is good reason to pay special attention to colorectal cancer due to its high frequency of occurrence among the Singapore population and because it is amenable to early detection via screening.

Effect of short-term administration of vasopressin on arterial pressure and norepinephrine turnover in Long-Evans rats.

Vasopressin (AVP) in acute experiments has been shown to influence cardiovascular reflexes, but the effect of a more prolonged administration of AVP on the sympathetic nervous system has not been investigated. Long-Evans rats were treated for 7 days with AVP (Pitressin tannate in oil, with single daily doses of 100 or 500 mU.100 g-1, s.c.) to determine whether AVP alters norepinephrine (NE) turnover in kidney, intestine, or skeletal muscle. Control rats were given equal doses of peanut oil daily. NE turnover was determined by measuring the decline in tissue levels of NE for 8 h after inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (300 mg.kg-1, i.p. every 4 h). Measurements of water intake, urine output, and urine osmolality showed that chronic administration of the high dose, but not the low dose, of AVP produced maintained increases in urine osmolality and decreases in water intake and urine output. Body weight, plasma osmolality, plasma electrolytes, and hematocrit were not significantly altered by AVP treatment, but mean arterial pressure was elevated significantly (control, 105 +/- 3 mmHg versus AVP, 119 +/- 4 mmHg, p less than 0.05) (1 mmHg = 133.3 Pa) in the high dose group. Plasma renin activity was decreased slightly, but significantly in rats treated with the high dose of AVP. Compared with results in control animals, there were no statistically significant changes in NE turnover after chronic administration of either the low or the high dose of AVP. The results indicate that administration of AVP for 7 days to rats in normal fluid balance does not result in a decrease in NE turnover in peripheral organs.

Bites by the white-lipped pit viper (Trimeresurus albolabris) and other species in Hong Kong. A survey of 4 years' experience at the Prince of Wales Hospital.

The case records of 242 snake bite victims admitted to the Prince of Wales Hospital in Hong Kong between September 1984 and October 1988 were studied retrospectively. When the snake was identified, the White-lipped pit viper (Trimeresurus albolabris) was by far the commonest species involved. In addition to local oedema and inflammation, evidence of a significant blood clotting disturbance was present in at least 10% of cases, defibrination and thrombocytopenia being the commonest findings. Since such abnormality was not always sought the true figure is likely to be higher. Three fatalities occurred, one of which was secondary to a probable White-lipped pit viper bite, one to a bite by Chinese cobra and one to a bite by Russell's viper.

Role of the T-type Ca2+ current on the contractile performance of guinea pig detrusor smooth muscle.

AIMS: The importance of the T-type Ca(2+) current in determining detrusor contractile function was investigated by using guinea pig muscle in vitro. METHODS: NiCl(2) (200 microM) was used to block selectively the T-type Ca(2+) current, and 20 microM verapamil was used to block the L-type Ca(2+) current in this tissue. The selectivity of these agents at such concentrations has been previously demonstrated. RESULTS: In normal extracellular solution (4 mM KCl) 200 microM NiCl(2) and 20 microM verapamil reduced electrically stimulated contractions by 17 +/- 6% and 65 +/- 10%, respectively. At high concentrations of the two agents, the contraction was completely abolished by NiCl(2) but by only 74 +/- 18% in the case of verapamil; this finding suggests that NiCl(2) has additional negative inotropic actions at higher concentrations. Carbachol and KCl contractures were attenuated to a similar extent to that of electrically stimulated contractions by NiCl(2) and verapamil, which suggests that they act on the muscle rather than the motor nerve. The dependence of the membrane potential on the relative ability of NiCl(2) and verapamil to attenuate the contraction was tested by varying the extracellular [KCl], [KCl](o). Varying [KCl](o) between 2 and 10 mM depolarised detrusor myocytes from (-65.1 +/- 4.7 mV to -42.7 +/- 4.0 mV (a slope of 32 mV per 10-fold change of [KCl](o)). In low [KCl](o),blockade by NiCl(2) was more effective and that of verapamil less effective; at high [KCl](o), the reverse potency was recorded. CONCLUSIONS: The data are consistent with the hypothesis that Ca(2+) influx through both T-type and L-type Ca(2+) channels determines the contractile status of detrusor smooth muscle and that T-type channel activity is more important at membrane potentials near the resting level. A significant role for T-type channel activity in the resting state was evident in that spontaneous contractions were attenuated to a greater extent than evoked contractions.