Outbreak of wound botulism in people who inject drugs, Norway, October to November 2013.

In October and November 2013, four cases of wound botulism were confirmed in people who inject drugs (PWID) in Norway. Two additional cases are suspected. Because of the international distribution pathways for heroin ­ the likely source of the outbreak ­ healthcare workers and public health authorities in other countries should remain vigilant for wound botulism in PWID. This outbreak serves as a reminder that countries should ensure access to botulinum antitoxin in case of outbreak situations.

Binucleation and polyploidization patterns in developmental and regenerative rat liver growth.

The hepatocellular binucleation rate, measured as the percentage of binuclear cells amongst newly formed bromodeoxyuridine-labelled and immunostained collagenase-isolated rat hepatocytes, decreased from 12% to 4% between days 30 and 40 after birth, rose to 20% between days 50 and 60, and then declined again to the adult rate of about 10% at day 80. During regenerative growth following a two-thirds partial hepatectomy, the rate of binucleation declined to about 3%, causing the fraction of binuclear cells to fall from 27% (before hepactectomy) to 5% (at 45 h after hepactectomy) as pre-existing binuclear cells replicated and formed mononuclear daughter cells. Essentially all (97%) hepatocytes replicated at least once, starting their DNA synthesis at around 13 h and reaching a peak at 30 h, irrespective of ploidy and nuclearity. At later time points, the diploid hepatocytes had a higher labelling index than the polyploid cells, suggesting a greater tendency to go through several cell cycles.

Growth-related alterations during liver carcinogenesis: effect of promoters.

Bromodeoxyuridine labeling of DNA, binuclearity counting, and flow cytometric analysis of isolated hepatocytes and hepatocyte nuclei has been used to assess hepatocellular growth patterns related to liver carcinogenesis. Three growth patterns can be distinguished. Mononucleating growth is observed during liver regeneration and after treatment with the tumor promoter 2-acetylaminofluorene (2-AAF) and its analogue 4-AAF. In this growth mode binucleation does not occur, resulting in a decrease in the fraction of binucleated cells. Binucleating growth is observed during normal liver development and after treatment with compounds such as phenobarbital, characterized by progressive polyploidization and maintenance of a binucleated cell fraction. Diploid growth is the growth pattern of neoplastic liver hepatocytes. Most of the cells in neoplastic lesions (foci, nodules, and carcinomas) are diploid, in contrast to the normal liver. Diploid tumor cells have a much higher proliferative activity than tetraploid tumor cells, suggesting that the latter may possess a limited growth potential that makes abrogation of binucleation proliferatively advantageous.

Effects of the tumor promoter 2-acetylaminofluorene and of 4-acetylaminofluorene on rat liver growth.

2-Acetylaminofluorene (2-AAF) is a moderately cytotoxic drug which is nevertheless capable of promoting diethylnitrosamine-initiated rat liver carcinogenesis in the absence of detectable hepatotoxicity. 2-AAF does not stimulate net growth of the normal liver, but alters hepatocellular ploidy distributions (fewer binucleated and more diploid cells) in a manner indicative of altered growth control. The non-cytotoxic analogue 4-AAF induces a similar ploidy change, and also stimulates liver growth. The possibility should therefore be considered that both agents may specifically elicit a mononucleating growth response in normal liver, which in the case of 2-AAF is antagonized by a general (cytotoxic) growth inhibition. In the promotion of liver carcinogenesis, 2-AAF may act as a growth stimulant upon cytotoxicity-resistant initiated cells; cytotoxicity per se playing no causative role.

[Familial Mediterranean fever]. / Familiaer middelhavsfeber.

Familial Mediterranean fever is a hereditary disease prevalent among populations in the Mediterranean area, characterized by sporadic episodes of acute inflammation primarily of the pleural, peritoneal and joint spaces. There is no diagnostic test for routine use. The disease is still uncommon in Norway, but we expect an increased incidence because of immigration. Due to the lack of pathognomonic features many patients undergo unnecessary explorative laparotomy before the diagnosis is established. In this report we present a patient with a typical history of familial Mediterranean fever. To our knowledge this is the first case ever published in Norway. It is important to keep the disease in mind as a differential diagnosis in patients with recurrent fever and pain, as colchicine represent an efficient treatment in order to prevent both further attacks and secondary amyloidosis.

[Parvovirus B19 as a cause of acute arthritis]. / Parvovirus B19 som årsak til akutt artritt.

Parvovirus B19 is known to cause erythema infection (fifth disease), acute and chronic arthritis, aplastic crises in chronic hemolytic anemia, chronic anemia in the immunocompromised host and hydrops fetalis. We present two patients with acute arthritis due to parvovirus infection. Both had symmetrical synovitis in wrists and ankles. Patient 1 presented with fever and rash before joint symptoms occurred; patient 2 had joint symptoms only. Arthritis due to parvovirus is usually self-limited, but may develop into a chronic disease similar to rheumatoid arthritis. Parvovirus should be considered one of the differential diagnoses while dealing with acute or chronic arthritis.

Effect of 4-acetylaminofluorene and other tumour promoters on hepatocellular growth and binucleation.

The complete liver carcinogen 2-acetylaminofluorene (2-AAF) promoted the outgrowth of large neoplastic liver nodules and hepatocellular carcinomas in diethylnitrosamine-treated rats. 2-AAF did not alter the overall proliferative activity of normal hepatocytes, but suppressed binucleation and induced, on a long-term basis, an increase in proliferative activity and in the fraction of diploid hepatocytes relative to control animals. The analogue 4-acetylaminofluorene (4-AAF) was much less effective than 2-AAF as a promoter of large nodules and carcinomas, but promoted the outgrowth of medium-sized nodules (1 < 2.5 mm). While 2-AAF specifically stimulated the growth of cells in enzyme-altered foci, the cells responding to 4-AAF were more randomly distributed throughout the liver tissue. In contrast to 2-AAF, 4-AAF strongly stimulated the growth (DNA synthesis) of normal hepatocytes, but like 2-AAF it suppressed binucleation and caused a long-term increase in the proliferative activity and in the fraction of diploid hepatocytes. Other liver tumour promoters (cyproterone acetate, alpha-hexachlorocyclohexane, methylclofenapate) likewise stimulated the growth and suppressed the binucleation of normal hepatocytes. All hepatocellular ploidy classes were affected virtually equally by mitogenic stimulation, but at low proliferation rates the mononuclear cells were more proliferative than the binuclear cells. Since this difference could be eliminated by increasing the mitogen dose, it would seem that mononuclear cells may be somewhat more sensitive towards mitogens than binuclear cells. In contrast to previously reported results [Styles et al. (1990) Carcinogenesis, 11, 1149-1152], methylclofenapate was not found to specifically stimulate binuclear hepatocytes. Our results indicate that liver tumour promoters in general tend to induce a non-binucleating, non-polyploidizing hepatocellular growth pattern, similar to that observed during liver regeneration. 4-AAF is confirmed to be, at best, a very weak promoter of liver carcinogenesis, but appears to be an effective promoter of benign tumours.

[Tropical pyomyositis]. / Tropisk pyomyositt.

Tropical pyomyositis is rarely observed among permanent residents of temperate or cold climates and is, to our knowledge, not described among Norwegians. It is a clinical entity comprising general symptoms of infection and abscesses in skeletal muscles. We present one case of tropical pyomyositis acquired in the Dominican Republic. The patient, a female, had an insidious progression of the disease with fever, chills, and general malaise. On admission she had also developed multiple abscesses affecting muscles of the extremities. She required surgical drainage in addition to antibiotics. Cultures from purulent material revealed Staphylococcus aureus.

Reduced proliferative activity of polyploid cells in primary hepatocellular carcinoma.

The proliferative activity of tumor cells differing in DNA content (ploidy) and nuclearity was investigated in primary hepatocellular carcinomas of the rat by flow cytometric analysis of collagenase-isolated cells immunostained after labelling with bromodeoxyuridine (BrdU) in vivo. The diploid cell fraction in these euploid tumours was higher than in normal liver, and the rate of binucleation as well as the proliferative activity of the binuclear cells was very low. The highest proliferative activity (BrdU labelling index) was found among the diploid tumour cells. The activity in mononuclear tetraploid and octoploid cells was reduced in inverse proportion to their increasing DNA content, possibly suggesting a loss of proliferative potential associated with polyploidization. There was a significant correlation between the proliferative activity of hepatocellular carcinoma cells and nonparenchymal liver cells in the different tumours, indicating that different cell types within a tumour may respond to common growth stimuli. Treatment of tumour-bearing rats with a promoting carcinogen (2-acetylaminofluorene) resulted in significant stimulation of tumour cell proliferation (all ploidy classes), whereas the proliferation of non-parenchymal (stromal) cells in the tumour was slightly inhibited.

[Spotted fever imported into Norway in 1997]. / Flekkfeber importert til Norge i 1997.

Tick-borne rickettsioses are important zoonoses in many tropical and subtropical areas. There has recently been an increase in the number of reported cases among tourists returning to Scandinavia. In this article we present all five serologically confirmed cases of tick-borne rickettsioses imported into Norway in 1997. The patients were Norwegian tourists who had visited South Africa (three cases), Zimbabwe, and Italy. Four cases had typical eschar and three had maculopapular exanthema. The patients were treated with either doxycycline or ciprofloxacin. No complications were reported. The diagnosis of tick-borne rickettsiosis was confirmed by the detection of specific IgM antibodies to Rickettsia conorii using micro-immunofluorescence in serum samples.

Flow cytometric investigation of a possible precursor--product relationship between oval cells and parenchymal cells in the rat liver.

The question of a possible precursor--product relationship between oval cells and hepatocytes was examined in rats treated for 2 weeks with 2-acetylaminofluorene (2-AAF) with a two-thirds partial hepatectomy (PH) performed after the first week of 2-AAF treatment (modified Solt-Farber model). Liver cells were pulse-chase labelled with bromodeoxyuridine (BrdU) on day 6 post PH. On day 7 post PH the nonparenchymal (NPC) fraction, which contains the oval cells, exhibited a labelling index (LI) approximately 10 times higher than that of the hepatocytes as analysed by flow cytometry (FCM), the majority of the proliferating cells being oval cells. At later time points, there was no significant increase in the LI of diploid hepatocytes, and no detectable shift of BrdU-labelled cells from the NPC fraction to the hepatocyte fraction, suggesting that no extensive conversion of BrdU-labelled oval cells to hepatocytes was taking place. Throughout the experimental period there was a significant increase in the diploid hepatocyte cell fraction, from 12% on day 7 to 25% on day 13 post PH. Diploid hepatocytes pulse-labelled on days 7 or 9 post PH had a high LI (7-8%), in contrast to the low LI (1%) of tetra- and octoploid cells. Proliferation of diploid hepatocytes may thus explain the large increase in the diploid hepatocyte fraction observed from days 9 through 15 post PH. Our results, therefore, provide no reason to invoke oval cells as precursors of hepatocytes in the modified Solt-Farber carcinogenesis model.

Analytical methods for the study of liver cell proliferation.

Various cytometric methods for analysis of regenerating rat liver growth (DNA ploidy distributions, binucleation, and DNA synthesis by in vivo BrdUrd incorporation) were evaluated. The overall hepatocellular growth rate (labeling index), the binucleation rate, and separate indices for mononuclear and binuclear cells could be measured simply by microscope counting of collagenase-isolated hepatocytes immunostained for BrdUrd. Flow cytometry of cells stained for BrdUrd and DNA provided labeling indices for the various hepatocellular DNA ploidy classes as well as for nonparenchymal cells (identified by their size-dependent light scatter), but could not distinguish between mononuclear and binuclear hepatocytes. Image cytometry, using fluorescence or Feulgen staining, was inferior to flow cytometry in terms of speed and DNA resolution, but allowed a complete analysis of all hepatocellular DNA ploidy and nuclearity classes. It may therefore be the method of choice, particularly for analysis of liver cell cultures from which single cells are not easily obtained. Fluorescence staining would seem to be preferable to Feulgen staining, since the latter could not be used simultaneously with BrdUrd staining and therefore required a two-step analysis. A non-immunological method, based on the ability of incorporated BrdUrd to quench DNA staining by a Hoechst dye, could only be applied to isolated nuclei, thus giving no information about binucleation. The latter method may be useful for analysis of tumors which are difficult to dissociate to intact whole cells.

[South American blastomycosis--a differential diagnosis to tuberculous meningitis]. / Søramerikansk blastomykose--en differensialdiagnose til tuberkuløs hjernehinnebetennelse.

BACKGROUND: South American blastomycosis is primarily a lung infection often complicated by multiorgan or intracranial disease. MATERIAL AND METHODS: We describe the clinical and pathological findings of fatal cerebral blastomycosis occurring in a woman that immigrated to Norway from Brazil 23 years earlier. RESULTS: The clinical symptoms together with the radiological findings of multiple cerebral lesions and thickening of the basal meninges were interpreted as cerebral tuberculosis. Examination of cerebral spinal fluid was inconclusive. A diagnosis of cerebral fungal infection was subsequently established by brain biopsy. INTERPRETATION: This case history stresses the importance of confirming a clinical diagnosis by brain biopsy and extended investigation of the cerebrospinal fluid when intracranial lesions may have an infectious origin.