We report three children with congenital anaemia after intrauterine infection with B19 parvovirus. All the fetuses developed hydrops fetalis that was treated by blood transfusion. After delivery the infants had hypogammaglobulinaemia. In all three, sera lacked B19 but viral DNA was found in bone marrow. All were treated with immunoglobulin. One child died and B19 was found in various tissues. In the other two cases, virus could no longer be detected after therapy but the patients remain persistently anaemic. Persistent B19 infection should be suspected in infants with congenital red-cell aplasia.

Somatostatin-receptor (SS-R) scintigraphy successfully shows primary cancers and distant metastases in most patients with carcinoids, islet cells tumours, and paragangliomas. Previous in-vitro studies indicated that somatostatin receptors are present in human breast cancers. We report positive scintigraphy with [111In-DTPA-D-Phe1]-octreotide in 39 of 52 primary breast cancers (75%). Parallel in-vitro autoradiography with [125I-Tyr3]-octreotide of 30 of these showed a corresponding somatostatin-receptor status in 28. Significantly more invasive ductal cancers could be shown than invasive lobular carcinomas (85% vs 56%; p < 0.05). Also the number of T2 cancers which were shown was higher than T1 (86% vs 61%; p < 0.05). Imaging of the axillae showed non-palpable cancer-containing lymph nodes in 4 of 13 patients with subsequently histologically-proven metastases. In the follow-up after a mean of 2.5 yr, SS-R scintigraphy in 28 of the 37 patients with an originally SS-R-positive cancer, was positive in the 2 patients with clinically-recognised metastases, as well as in 6 of the remaining 26 patients who were symptom-free. Raised carcinoembryonic antigen (CEA) and CA 15-3 values were observed in only 2 and 1, respectively, of these patients. Most primary breast cancers can be shown by SS-R scintigraphy, especially invasive ductal cancers. This technique may be of value in selecting patients for clinical trials with somatostatin analogues or other medical treatments. Furthermore, SS-R scintigraphy is more sensitive than measurements of the usual serum cancer markers for detecting recurrences of SS-R-positive breast cancer.

The notion that a breast-gut connection might modulate the microenvironment of breast tissue was supported by the finding that breast cyst fluid contains bile acids that are characteristically found in the intestines. To establish that the gut, rather than circulating steroid precursors, is the source of bile acids in breast cyst fluid, we gave two patients deuterium-labelled chenodeoxycholic acid (three 200 mg doses by mouth), starting 9 days before aspiration of breast cysts. The chenodeoxycholic acid concentration of seven samples of aspirated cyst fluid ranged from 42 to 94 mumol/L. The corresponding serum concentrations of chenodeoxycholic acid on the same day were 0.8 and 2.9 mumol/L, of which the labelled compound comprised 13.0% (0.38 mumol/L) and 28.2% (0.23 mumol/L). The deuterated chenodeoxycholic acid concentrations in cyst fluid were 0.79 and 1.26 mumol/L in two samples from patient 1 and 3.22 mumol/L in patient 2; these values are equivalent to 11-17% of the serum concentrations [corrected]. This study shows that intestinal bile acids rapidly gain access to cyst fluid. Further studies should investigate the mechanisms that govern the exchange processes and the maintenance of the high cyst fluid to plasma concentration gradients, and the biological half-lives of individual constituents.

Oxidised low-density lipoprotein (Ox-LDL) has been associated with arterial foam-cell formation, and autoantibodies to Ox-LDL are present in human serum. Lipid peroxidation is enhanced in pre-eclampsia. We assessed whether the titre of IgG autoantibody to an epitope of Ox-LDL, malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), was increased in the sera of pre-eclamptic patients. 16 such patients had significantly higher mean titres of autoantibodies to MDA-LDL than healthy pregnant women (p = 0.028). In a multiple regression model, pre-eclamptic patients still had a significantly higher mean titre (p = 0.048). Enhanced lipid peroxidation may be involved in the foam-cell formation of decidua and in the pathogenesis of pre-eclampsia.

Two field studies in Kenya and an experimental challenge study in the USA were done to assess the accuracy of a dipstick antigen-capture assay based on qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) in peripheral blood for diagnosis of P falciparum infection. In these studies, the assay was 96.5-100% sensitive for detection of greater than 60 P falciparum asexual parasites/microL blood, 70-81% sensitive for 11-60 parasites/microL blood, and 11-67% sensitive for 10 parasites or less/microL blood. Specificity was 95% (95% CI 85-105%; n = 20) among naive American volunteers, 98% (96-101%; n = 112) among volunteers exposed to the bite of P falciparum-infected mosquitoes, and 88% (84-92%; n = 285) among Kenyans living in an area with holoendemic malaria. Our results also indicated that PfHRP-2 antigen was not detectable in blood 6 days after initiation of curative chemotherapy, and suggest that such circulating antigens rarely lead to false-positive tests. The dipstick assay's sensitivity, specificity, simplicity, and speed may make it an important tool in the battle against malaria.

The J-shaped relation between diastolic blood pressure and mortality from coronary heart disease continues to provoke controversy. We examined the association between diastolic blood pressure and progression of aortic atherosclerosis in a population-based cohort of 855 women, aged 45-64 years at baseline. The women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. After 9 years of follow-up, slight progression of atherosclerosis was noted in 19% of women and substantial progression in 16%. The age-adjusted relative risk of substantial atherosclerotic progression in women with a decrease in diastolic pressure of 10 mm Hg or more was 2.5 (95% CI 1.3-5.6), compared with the reference group of women who had a smaller decrease or no change. The excess risk in this group was confined to women whose increase in pulse pressure was above the median (3.9 [1.5-9.9] vs 1.1 [0.3-4.2] in women with an increase in pulse pressure below the median). The relative risks for women with rises in diastolic pressure of 1-9 mm Hg and 10 mm Hg or more were 2.2 (1.1-4.3) and 3.5 (1.6-8.0), respectively. These findings suggest that a decline in diastolic blood pressure indicates vessel wall stiffening associated with atherosclerotic progression. They support the hypothesis that in low-risk subjects progression of atherosclerosis may be accompanied by a decrease in diastolic blood pressure rather than the opposing idea that low diastolic blood pressure precipitates the occurrence of atherosclerotic events.

Since large trials have been set up to assess whether tamoxifen decreases the risk of breast cancer in healthy women, it has become important to investigate the drug's potential adverse effects, including occurrence of endometrial cancer. We undertook a case-control study in the Netherlands to assess the effect of tamoxifen on the risk of endometrial cancer after breast cancer. Through the population-based Netherlands Cancer Registry and two older, hospital-based, registries, we identified 98 patients who had endometrial cancer diagnosed at least 3 months after a diagnosis of primary breast cancer. Detailed information about treatment was obtained for all these patients, and for 285 controls, who were matched to the cases for age, year of breast cancer diagnosis, and survival time with intact uterus. Tamoxifen had been used by 24% of patients with subsequent endometrial cancer and 20% of controls (relative risk 1.3 [95% CI 0.7-2.4]). Women who had used tamoxifen for more than 2 years had a 2.3 (0.9-5.9) times greater risk of endometrial cancer than never users. There was a significant trend of increasing risk of endometrial cancer with duration of tamoxifen use (p = 0.049), and also with cumulative dose (p = 0.046). The duration-response trends were similar with daily doses of 40 mg or 30 mg and less. These findings support the hypothesis that tamoxifen use increases the risk of endometrial cancer. This oestrogenic effect on the endometrium was not related to the dose intensity. Physicians should be aware of the higher risk of endometrial cancer in tamoxifen users.

A new arenavirus, called Sabiá, was isolated in Brazil from a fatal case of haemorrhagic fever initially thought to be yellow fever. Antigenic and molecular characterisation indicated that Sabiá virus is a new member of the Tacaribe complex. A laboratory technician working with the agent was also infected and developed a prolonged, non-fatal influenza-like illness. Sabiá virus is yet another arenavirus causing human disease in South America.

Maternal-infant transmission of HIV-1 occurs in 13-40% of pregnancies. Studies on transmission of maternal immunity to HIV antigens have used antigens from viruses not representative of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgG1 antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (p = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.

Oxidative modification of low-density lipoprotein (LDL) may be atherogenic. We studied the time of onset of LDL oxidation (lag) in 18 postmenopausal women before and after intraarterial infusion of 17 beta-oestradiol, after 3 weeks' patch administration in 12 of these women, and 1 month after discontinuation in 10. The lag increased from baseline after acute infusion (from 134 [SD41] to 167 [36] min, p = 0.01) and after the patch (132 [31] to 178 [45] min, p = 0.009). After discontinuation of oestradiol, the lag returned to baseline. This study shows an antioxidant effect of physiological levels of 17 beta-oestradiol, which may contribute to an anti-atherogenic action.

We examined time trends and geographical variations in the detection and treatment of prostate cancer in USA, based on information from white men aged 50 to 79 who resided in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program of the United States National Cancer Institute. Prostate-cancer incidence and treatment rates were determined for the 9 population-based cancer registries which participate in the SEER program. Prostate-cancer mortality rates were assessed from data compiled by the National Center for Health Statistics. Prostate cancer incidence rates increased by 6.4% per year between 1983 and 1989. The increase appeared to be due to detection of early-stage disease; there was no increase in the incidence rate of metastatic cancer. Incidence rates varied widely among the SEER program areas: in 1989 from 267.9 per 100,000 in Connecticut to 606.8 in Seattle. Radical prostatectomy rates more than tripled between 1983 and 1989 in the SEER areas as a whole. Among men aged 70-79, the rate of prostatectomy increased by nearly 35% per year. There was a five-fold variation among SEER areas in radical prostatectomy rates in 1989, with a low of 43.4 per 100,000 in Connecticut and a high of 224.4 in Seattle. Prostate cancer mortality rates did not increase during the period of study; there was little variation among areas in prostate-cancer mortality rates, and no apparent correlation between the incidence and mortality rates for an area. Increases in rates of prostate cancer incidence and prostate surgery have occurred in the United States without clear evidence that screening and prostectomy are effective in reducing mortality. Moreover, much of the growth in incidence and radical prostatectomy rates has occurred among older men, who appear least likely to benefit from early detection and surgery of occult prostate cancer.

The pathogenesis of Raynaud's disease is unclear; an enhanced response to catecholamines has been hypothesised to contribute to this vasospastic disorder. Impaired endothelium-dependent dilation occurs in other diseases associated with vasospasm, such as coronary atherosclerosis. We investigated both endothelium-dependent and endothelium-independent venodilatory function in Raynaud's disease using the hand-vein compliance technique. Full dose-response curves to noradrenaline were constructed in 10 subjects with primary Raynaud's disease and 10 age and sex matched control subjects. The two groups did not have a different response to noradrenaline. Mean (SD) log values of ED50s (the dose producing half maximum response) were 1.00 (0.59) (geometric mean 10 ng/min) in Raynaud's disease compared with 1.29 (0.66) (20 ng/min) in control subjects (p = 0.16). The efficacy of noradrenaline as a venoconstrictor was similar in the two groups: mean maximum dilation (Emax) to noradrenaline was 81 (14)% in the Raynaud's group and 89 (8)% in the control group (p = 0.08). Full dose-response curves to the endothelium-dependent dilator bradykinin were constructed. Emax to bradykinin was significantly lower in the Raynaud's group than in the control group (65 [21] vs 91 [29%], p = 0.02). ED50 values (doses producing half maximum response) for bradykinin were similar in the two groups. Maximum dilation with nitroprusside, a direct releaser of the vasodilator nitric oxide, was not diminished in the Raynaud's group (94 [23] vs 102 [15]% in controls, p = 0.26). These results suggest that endothelium-dependent venodilation is impaired in peripheral vessels in Raynaud's disease, possibly due to diminished release of nitric oxide, and may contribute to the pathogenesis of the disorder.