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Biomedical subjects

B Nielsen

Publications and source records attributed to B Nielsen.

At least 91 records · Page 5Linked to original sources

Total number of cancer cell nuclei and mitoses in breast tumors estimated by the optical disector.

OBJECTIVE: The total number of cancer cell nuclei, N(nuc), and of mitoses, N(mit), in the primary lesion are potentially important indicators of tumor biology. In the present study, such estimates were obtained on breast cancers by an unbiased stereologic method. STUDY DESIGN: The total number estimates are the product of two variables: (1) the volume of tumor, V(T), estimated by the Cavalieri principle, and (2) the densities of cancer cell nuclei and of mitoses obtained in small, three-dimensional samples (i.e., optical disectors) of 40-micron-thick methacrylate sections, which were selected systematically at random from the whole specimen. RESULTS: In 93 prospectively collected tumors, N(nuc) ranged from 0.06 to 7.9 10(9) (median, 0.6 10(9)), and N(mit) ranged from 0.02 to 64 10(6) (median, 1.5 10(6)). Both N(nuc) and N(mit) correlated significantly with V(T) (r = .77 and .60, respectively); however, the steep slopes of the regression lines indicated that densities of nuclei and mitoses increased as a function of tumor size. On average, N(mit) and estimates of mitotic frequency tended to be larger in lymph node-positive patients as compared with lymph node-positive patients as compared with lymph node-negative ones (2P < or = .08), whereas no such relation was found for nuclear counts (2P > or = .40). By counting a median number of 195 nuclei and 28 mitoses per tumor, the average coefficients of error of N(nuc) and N(mit) were 17% and 32%, respectively; this gave seemingly sufficient precision as compared with the huge interpatient variation in estimates, 180% and 490%. Moreover, the intraobserver reproducibility of density estimates was excellent (r > or = .88). CONCLUSION: The present study showed the feasibility, efficiency and reproducibility of the unbiased optical disector principle applied to human breast cancer and provided data on new parameters of biologic relevance. The technique seems suitable for use in experimental oncology, but further studies are needed to investigate its clinical value.

Breast Neoplasms↗

Losartan reduces albuminuria in patients with essential hypertension. An enalapril controlled 3 months study.

BACKGROUND: Elevated urinary albumin excretion is a common feature of essential hypertension which may be reduced by ACE-inhibition through independent reductions of both systemic and intraglomerular pressure. A concurrent inhibition of bradykinin breakdown may be involved. METHODS: A double-blind, randomized, 12 weeks study of the effects on enalapril 20 mg (n = 46) vs losartan 50 mg daily (n = 47) on blood pressure, albuminuria, fasting blood glucose, and lipids in 57 male and 36 female patients with essential hypertension. RESULTS: Blood pressure was similarly reduced during both treatments: enalapril 156/102 (15/5) (mean [SD] to 142/92 [14/7]) mmHg, losartan: 159/103 (17/6) to 149/94 (21/9) mmHg, both P < 0.001. Urinary albumin to creatinine ratio was significantly reduced during losartan (from 1.14(x/divided by 2.48) (geometric mean (x/divided by antilog SD) to 0.81 (x/divided by 2.43) mg/mmol, P < 0.01), as well as during enalapril (from 0.95 (x/divided by 2.45) to 0.73 (x/divided by 2.00) mg/mmol, both P < 0.05). The effect on albuminuria was especially evident in patients with microalbuminuria. Fasting blood glucose, total cholesterol, HDL-cholesterol and triglycerides were unchanged during losartan, whereas minor reductions were found in all lipids during enalapril. No difference was observed between the groups. CONCLUSION: Enalapril 20 mg and losartan 50 mg daily reduce blood pressure equally in essential hypertensive patients. No adverse effects were seen on glucose and lipid concentrations. Losartan treatment reduces albuminuria at least as effectively as enalapril, suggesting that glomerular leakage of albumin is profoundly affected by the effects angiotensin II.

Adult↗

Public health and pork and pork products: regional perspectives of Denmark.

An ambitious programme to eliminate pork as an important source of human salmonellosis was initiated in Denmark in 1993 by the Ministry of Food, Agriculture and Fisheries. The programme comprises control of feedmills, breeding and multiplying herds, slaughter herds and slaughter plants, as well as the final product, fresh pork. As a consequence, the level of occurrence of Salmonella spp. in fresh pork produced in Denmark is approximately 1%. Yersinia enterocolitica 0:3 infections are common in slaughter pig herds in Denmark, and pork is considered to be the only source of human infection in the country. The incidence of pork-related occurrences of human salmonellosis and yersiniosis in 1996 was approximately nine cases per 100,000 inhabitants for both diseases. All swine in Denmark are screened for Trichinella spp. infection, although no positive results have been obtained since 1930. Swine are not considered to be a source for Campylobacter jejuni or enterohaemorrhagic Escherichia coli in Denmark. Listeria monocytogenes can be detected in relatively high rates in pork: however, the incidence of human listeriosis is only 0.5 cases per 100,000 inhabitants. Toxoplasma gondii antibodies have been demonstrated in 3% of slaughter pigs, though the importance of pork as a source of infection is probably very low. Denmark is officially free from Brucella abortus, B. melitensis and Mycobacterium bovis.

Abattoirs↗

[Ambulatory treatment of alcoholics. A prospective study].

The present study covers 130 consecutive patients referred to the two outpatient clinics for alcoholism in Odense over a ten-month period from January to October 1993. The aim of the study was to describe the process of treatment over 12 months and assess the condition of the patients 12 months after the admission for treatment. All patients were assessed by means of the Addiction Severity Index at admission and after 12 months. While female alcoholics typically had psychiatric complaints, the drinking pattern was, however, alike for both sexes. Patients who themselves terminated their treatment had a significantly worse drinking pattern than those who completed treatment. Twelve months after the admission there was a significant decrease in the alcohol abuse and an improvement in psycho-social function for both sexes.

Adult↗

[Atypical cervix uteri smears--consequences?].

Among 37,992 cervical smears (725 (1.9%)) were found to be atypical. All atypial smears were referred for colposcopically guided biopsies and cervical abrasio within three months. This is an expensive and cumbersome procedure. In order to obtain a more differentiated follow-up procedure the atypical smears were divided into two groups without knowledge of the later histological diagnosis on biopsy: "Atypia, probably reactive" and "atypia, probably CIN (cervical intraepithelial neoplasia)". In the latter group the subsequent biopsies showed significantly more CIN than in the former (60.4% against 15.7%). We find it useful to divide the atypical smears into two groups in our daily routine work with a different follow-up procedure: "Atypia, probably reactive" to be followed by a repeat smear and "atypia, probably CIN" to be followed by colposcopically guided biopsies and cervical abrasio.

Biopsy↗

Hamster to rat kidney transplantation: technique, functional outcome and complications.

Hamster to rat kidney transplantation has only recently been introduced as model of concordant xenografting. The kidney model offers unique possibilities for studying both immunological and functional aspects of xenografts as opposed to the widely used heterotopic heart model. This article provides a detailed description of surgical technique as well as data on functional outcome and complications. The renal artery with a small segment of the aorta is sutured end-to-side to the abdominal aorta of the recipient, and the renal vein is anastomosed end-to-side to the inferior vena cava. The urinary system is reconstructed by bladder-to-bladder anastomosis. Xenografts will maintain close to normal serum-creatinine levels for 2-3 days, after which they are rejected. Complications occurred in 22% of xenografts. Postrenal obstruction due to severe hematuria or ureter stenosis was the most frequent problem encountered.

Animals↗

Time course of the serological response to Yersinia enterocolitica O:3 in experimentally infected pigs.

A total of 25 pigs inoculated with Yersinia enterocolitica serovar O:3 and 25 un-inoculated controls were followed weekly by sampling blood and faeces for 70 days post infection (p.i.). All inoculated pigs were faeces culture positive from day 5 to 21 p.i., whereafter shedding of bacteria declined to < 10% of the pigs at day 49 p.i. and to 0% at day 68 p.i. All control pigs remained Y. enterocolitica O:3 culture negative. When examined in an indirect ELISA using purified LPS from Y. enterocolitica 0:3, sera from all inoculated pigs showed significantly higher optical densities (OD) as compared to the control group. All inoculated pigs had seroconverted at day 19 p.i. and remained seropositive until slaughter at day 70 p.i. The maximum mean anti-LPS response was observed at day 33 p.i. with a positive/negative ratio of 780. No cross-reactions were observed with sera from 21 pigs, infected with Salmonella typhimurium. At necropsy at day 70 p.i., Y. enterocolitica O:3 was isolated from the tonsils of 20 inoculated pigs, whereas the rest of the gastrointestinal tract and associated lymph nodes were culture negative. The remaining inoculated pigs and all control pigs were culture negative at necropsy at day 70 p.i. The ELISA seems to be a promising alternative to bacteriological culture for detection of Y. enterocolitica O:3 infection in pig herds.

Animals↗

Myeloid progenitors in remission bone marrow in patients with malignant blood diseases: clues for slow hematopoietic regeneration after ABMT?

Slow hematopoietic recovery is a well-known feature in patients undergoing autologous bone marrow transplantation (ABMT), and here we demonstrate that compared with patients with other malignant blood diseases, the thrombocytopenia in acute myeloid leukemia (AML) patients stands out, with the median time to recovery of > 50 x 10(9) platelets being 101 days for AML patients and 22-37 days for other patient groups. We have consequently evaluated the content and fate of myeloid progenitor cells (BFU-E, CFU-GM, and CFU-GEMM) in bone marrow preparations from cancer patients in an attempt to uncover factors of importance for their slow hematopoietic recovery after ABMT using three experimental setups. First, we analyzed progenitors in marrow samples from 36 patients [18 AML, 5 acute lymphoblastic leukemia (ALL), and 13 non-Hodgkin's lymphoma (NHL)] exposed to multiple doses of severely myelotoxic cytoreductive regimens and observed that AML patients had suppressed numbers of CFU-GEMM and BFU-E (80% that of normal volunteers) but increased levels of CFU-GM. In contrast, the decrease in ALL patients was more pronounced (50% that of normal volunteers) and demonstrable for all progenitors. NHL patients exhibited normal progenitor frequencies of CFU-GM and CFU-GEMM, whereas their BFU-E counts were found to be increased nearly two-fold. Second, we followed the fate of progenitors through the laboratory manipulations of marrow grafts and found no evidence for selective losses in terms of disease (7 AML, 5 NHL, 1 ALL, and 2 testicular germ cell tumor patients) and progenitor type. Third, we retrospectively evaluated the cell yields of grafts from 121 cases [39 AML, 20 ALL, 22 NHL, 9 Burkitt's lymphoma (BL), 18 Hodgkin's disease (HD), and 13 testicular germ cell tumors] and found those of heavily treated AML, HD, and germinal tumors most affected, with a clear negative correlation in AML patients between age on the one hand and mononuclear cell yield and CFU-GM content on the other. We conclude that the amount of previous chemotherapy and age of patients appear to be among the determining factors on the number of myeloid progenitor cells in cancer patients and that thresholds for acceptability of grafts should take these variables into account.

Adolescent↗

Distinct circulation patterns in peripheral blood of leukocyte subpopulations during the first 24 hours following autologous bone marrow transplantation.

We have studied the recirculation patterns of leukocyte subpopulations during the first 24 h at 5 min before and 5, 15, 180, and 1440 min after autologous bone marrow transplantation (ABMT) in 14 patients with cancer (6 with AML, 5 with malignant lymphomas, 2 with ALL, and 1 with Ewing's sarcoma) using multiparameter flow cytometry and measurements of myeloid progenitors (CFU-GM). Although the great majority of the injected cell populations were undetectable 5 min after graft infusion, the number of CD3+ T lymphocytes increased at 5 and 15 min and again at 24 h post-ABMT. In contrast, the number of CD56+ natural killer (NK) cells decreased rapidly after ABMT to remain low throughout the observation period. Mature myeloid and monocytic cells (identified by their expression of CD66 and CD14, respectively) were present before, as well as after ABMT in numbers indicating that they were probably of endogenous origin. Immature myeloid cells were identified in a three-color flow cytometric assay as CD13+ CD14- CD66- and tended to increase during the first 15 min after ABMT. Finally, when CFU-GM were followed longitudinally, they were found to be practically absent before ABMT but were clearly detectable in 12 of 14 patients throughout the observation period. We conclude that leukocyte subsets exhibit different recirculation patterns after ABMT, and in light of the increased knowledge about leukocyte-endothelial interactions, these data could provide a platform for attempts to control leukocyte recirculation during stem cell infusion.

Adolescent↗

Olympics in Atlanta: a fight against physics.

Environmental stress can become so severe that athletes, in spite of proper training, heat acclimation, and hydration level, are unable to maintain thermal balance. Such incompensable conditions occur when air temperature exceeds 35 degrees C and relative humidity becomes higher than 60%. At these high environmental temperatures, the heat liberated during exercise can only be lost by evaporation of sweat, and therefore water vapor pressure sets limits on the possible rate of evaporation. Calculations are presented for the required and the maximal possible sweat evaporation rate for high-intensity, long-duration events, using marathon racing as an example. The consequence of the environmental heat stress is that the athlete must reduce the speed of running considerably to prevent potential heat injury. In certain extreme environmental conditions, sporting events should be canceled or postponed.

Acclimatization↗

Stereologic estimation of breast tumor size.

OBJECTIVE: The largest tumor diameter, D(T), is a variable of great clinical value in breast cancer but a biased and imprecise estimator of real tumor size. Three-dimensional, shape-independent estimates would more realistically reflect the tumor bulk and provide more accurate clinical staging. For experimental oncology, the measurements may be useful for precise assessment of tumor burden. STUDY DESIGN: In 64 prospectively collected breast cancers, unbiased stereology was used for estimating the gross tumor volume, V(T), cutting specimens into parallel, equally thick sections with subsequent determination of total tumor sectional area. For comparison, the volume of invasive tumor epithelium, "V"(epi), was obtained by microscopic examination of systematically sampled tissue fractions of the same tumors, embedded in both methacrylate and paraffin. RESULTS: The median D(T) was 2.2 cm, and the median V(T) was 6.72 cm3. The correlation between these variables was not very close (r = .77), and the slope of the regression line was steeper than expected, presumably reflecting a change in tumor shape with growing size. The sampling scheme used for estimation of V(T) proved highly efficient, yielding a mean error coefficient of 9%. The median "V"(epi) in methacrylate was 1.19 cm3, 21% larger than in paraffin. Estimates of "V" (epi) were highly reproducible (r = .97) and correlated highly with point counting-based estimates of the feature (r = .96). "V"(epi) correlated with V(T) (r > or = .75), but the slopes of the regression lines were steeper than expected, corresponding with the correlation found between epithelial volume fraction and tumor size (r = .26). On average, about 25% of the gross tumor was composed of invasive epithelium, but with a wide range. CONCLUSION: In breast cancer, realistic estimates of tumor volume, volume of invasive epithelium and epithelial volume fraction can be obtained by efficient stereologic techniques, which seem useful for clinical and experimental oncology. In the present methodologic study, baseline data were generated. Further studies are needed to assess the clinical value of stereologic tumor size estimates as compared with traditional staging parameters.

Breast Neoplasms↗