The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study.

BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL who underwent both staging PET/CT and BMB were retrospectively identified in British Columbia, Aalborg, and Copenhagen. Original written PET/CT and pathology reports were retrospectively reviewed to determine Ann Arbor stage and outcomes, with and without the contribution of BMB. RESULTS: A total of 530 patients were identified: 146 (28%) had focal bone marrow (BM) lesions on PET/CT and 87 (16%) had positive BMB. Fifty-two of 146 patients (36%) with positive PET/CT had a positive BMB [39 DLBCL, 13 indolent non-Hodgkin lymphoma (iNHL)], while 35 of 384 patients (9%) with negative PET/CT had positive BMB (12 DLBCL, 23 iNHL). BMB upstaged 12/209 (6%) of stage I/II patients to stage IV, although this was the case for only 3 (1%) patients with DLBCL in the BMB. PET/CT identified BM involvement by BMB with sensitivity 60%, specificity 79%, positive predictive value 36%, and negative predictive value 91%. Concordant histological involvement of the BM by DLBCL was associated with worse overall survival and progression-free survival than discordant or no involvement in univariate and multivariate analyses. CONCLUSIONS: In patients with DLBCL, staging PET/CT can miss BM involvement with concordant DLBCL (less common) or discordant iNHL (more common). Routine BMB does not add relevant diagnostic or prognostic value over PET/CT alone in the majority of patients with DLBCL.

Rhinitis: a complication to asthma.

BACKGROUND: Asthma and rhinitis often co-occur, and this potentially increases the disease severity and impacts negatively on the quality of life. We studied disease severity, airway responsiveness, atopy, quality of life and treatment in subjects with both asthma and rhinitis compared to patients with asthma or rhinitis alone. METHODS: We examined 878 patients: 182 with asthma, 362 with rhinitis and 334 with both asthma and rhinitis. All had a clinical interview concerning severity of symptoms, treatment, and quality of life, a skin prick test, a lung function test and a bronchial provocation with methacholine. RESULTS: Patients with both asthma and rhinitis had less severe asthma based on the frequency of respiratory symptoms compared to patients with asthma alone (55%vs 66%P = 0.01). On the contrary, they were more airway responsive (P < 0.05) and had more perennial allergy (P < 0.001). Asthmatics had poor perception of the general health, independent of rhinitis (P < 0.001). No differences were found in asthma-specific quality of life, whereas rhinitis-specific quality of life was worse in those with both asthma and rhinitis compared to those with rhinitis alone (P < 0.01). Subjects with both diseases were undertreated in 85% of the cases. CONCLUSION: We encourage that these observations be used in the evaluation and treatment of patients with asthma and rhinitis and that they contribute to the understanding of asthma and rhinitis as a uniform airways disease.

Monthly gonadotropin cycles in premenarcheal girls.

Patterns of nocturnal excretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were investigated in 11 girls. Autoregressive digital filtering of low- and high-frequency variations was used to make patterns more apparent. Coincident FSH and LH surges, separated by an interval of 20 to 40 days, were seen in specimens from three of six postmenarcheal girls and three to five premenarcheal girls. This suggests that cyclic hypothalamic-pituitary-ovarian interactions occur before menarche.

Direct measurement of osteolysis in man.

Precise, direct measurement of bone calcium release (v(o-)) has been accomplished using a continuous tracer administration (CTA) technique. Dietary calcium (96.97% (40)Ca) is replaced by (40)Ca (99.991% (40)Ca) and blood levels of the naturally occuring isotope (48)Ca are monitored by neutron activation analysis as a function of time. (48)Ca abundance falls as this isotope is excreted and only partially replaced by release from bone. After a suitable period, an asymptotic abundance of (48)Ca in serum, E, is approached which is the fraction of the turnover rate of the rapidly exchangeable calcium pools coming from the skeleton (E = v(o-)/v(t)). E is determined with a standard error of 2%, providing a precise, sensitive index of v(o-). 13 studies in three normal men and one postmenopausal woman receiving maintenance estrogen show large intersubject variations in parameters of calcium metabolism using both CTA and pulse tracer administration (PTA) plus balance techniques. Induced hypercalcemia results in a prolonged decrease in v(o-). Glucocorticoid therapy initially and consistently induces a marked hypercalciuria while effects on most other parameters of calcium kinetics are variable. In two men E fell when testosterone was added to glucocorticoid treatment, consistent with the known antiosteolytic effect of androgens, despite the short period of study.

Dietary cow's milk protein does not alter the frequency of diabetes in the BB rat.

One theory of the pathogenesis of IDDM proposes that exposure to cow's milk proteins triggers the disease in genetically susceptible individuals. We tested this hypothesis in the BB/Wor rat model of human IDDM. Diabetes-prone (DP) BB/Wor rats spontaneously develop IDDM. Coisogenic diabetes-resistant (DR) BB/Wor rats do not develop diabetes spontaneously, but IDDM can readily be induced by treatment with polyinosinic:polycytidylic acid and depletion of RT6+ T-cells. Pregnant BB/Wor rats were fed one of four experimental diets or a standard Purina commercial rat chow (5010) that was certified to be free of cow's milk protein. Offspring were maintained on the maternal diet after weaning. DP-BB/Wor rats, fed either of two experimental diets based on hydrolyzed casein and free of intact milk protein (Nutramigen or D11236), developed diabetes at only half the rate of animals fed Purina 5010 chow. Neither the addition of bovine serum albumin (BSA) to Nutramigen nor the substitution of total milk protein for the hydrolyzed casein in the D11236 diet increased the frequency of spontaneous diabetes. In contrast, there was no relationship between diet and susceptibility of DR-BB/Wor rats to IDDM induction. However, the methods used to induce IDDM in DR-BB/Wor animals were found to induce antibodies against BSA. We conclude the following: 1) Dietary modification can reduce spontaneous IDDM expression in DP-BB/Wor rats, but the agent of protection is not elimination of cow's milk protein. 2) The addition of BSA or intact milk protein does not abrogate the effectiveness of a protective diet. 3) The genetic susceptibility of the DR-BB/Wor rat to autoimmune diabetes is unaffected by any of the tested diets, but a role of anti-BSA-like autoreactivity in IDDM expression cannot be excluded.

A new method simplifying collection of serial specimens for gonadotropin determinations.

Patterns of gonadotropin levels have been compared in specimens of serum, 24-h urine collections, and first morning urine voidings collected throughout a menstrual cycle from 8 sexually mature, young women. Quantities of gonadotropins in first morning voidings were found to provide a reliable estimate of 24-h excretion of these hormones and demonstrate the same patterns of change as do serum and 24-h urine specimens. Thus first morning voidings satisfactorily overcome logistical problems inherent is serial serum and 24-h urine sampling for studying gonadotropin excretion patterns.

Metabolism of 125 I-luteinizing hormone-releasing hormone.

PIP: With the use of prepared iodine-125-monoiodo-LH-RH, the disappearance rates of LH-RH (luteinizing hormone-releasing hormone) in man and in the rat were investigated, as well as the distribution of LH-RH in the rat. After 10 microcuries of iodine-125-LH-RH were injected as an iv bolus into 3 male volunteers, blood samples from the opposite arm were obtained through an indwelling venous catheter at 2, 5, 8, 11, 15, 20, 30, 45, and 60 minutes postinjection and at 6 and 24 hours postinjection. To describe the disappearance curve a 3-term exponential equation was necessary and sufficient. The ranges of the t1/2s for the first, second, and third components were 2-4 minutes, 30-55 minutes, and starting at more than 10 hours. The initial distribution space was 3-4.7 1 or 37-47 ml/kg body weight. Similar procedures in the rat (45) resulted in an equation with 2 exponentials, with the ranges of the t1/2s for the first and second components being 5-10 minutes and 150-600 minutes. In both man and rat the distribution volume approximated estimated plasma volume. Following the injection of iodine-125-LH-RH in the rat, pituitary radioactivity increased, as expected, reaching a maximum tissue/serum ratio of 1.5 at 90 minutes. 2 iodinated oligomers of LH-RH were found to have different disappearance rates and distributions in the rat than did iodine-125-LHrh. the disappearance rate of iodine-125-LH-RH in this study is consistent with values for other small peptide hormones.^ieng

Effect of age on the intestinal absorption of vitamin D3-palmitate and nonesterified vitamin D2 in the term human infant.

This study was undertaken to investigate the utility of vitamin D3-palmitate as a nutritional supplement and thus define the intestinal absorption profile of vitamin D2 and vitamin D3 liberated after its cleavage from vitamin D3-palmitate in the human infant at various postnatal ages. The subjects for study consisted of 48 normal infants that were simultaneously administered 0.07 and 0.08 micromol/kg BW vitamin D as vitamin D3-palmitate and nonesterified vitamin D2 respectively, by orogastric tube. Blood samples were obtained before and 6, 12, and 24 h postadministration and analyzed simultaneously for vitamins D2 and D3. For data analysis, the infants were divided into two groups based on postnatal age: group 1, 1 day of age; and group 2, more than 10 days of age. Data were analyzed using the integrated peak area under the absorption curve for each subject. All subjects demonstrated the ability to absorb vitamin D after oral administration, although postnatal age as well as vitamin form had a profound effect on the absorption of vitamin D2 and vitamin D3 liberated from vitamin D3-palmitate. Nonesterified vitamin D2 is well absorbed both in very young and older infants, although absorption efficiency increases with age, perhaps due to increased bile acid secretion. Liberation of vitamin D3 from vitamin D3-palmitate was shown to increase, perhaps due to gastrointestinal tract maturation, beyond 10 days of age, probably coinciding with the secretion of intestinal esterases. Our data indicate that both forms of the orally administered vitamin approach equivalency in their abilities to elevate circulating vitamin D levels in the human infant at a postnatal age of approximately 89 days. Thus, vitamin D3-palmitate would appear not to be dietarily equivalent to free vitamin D as a nutritional source of vitamin D in the human neonate.

Plasma fatty acid responses, metabolic effects, and safety of microalgal and fungal oils rich in arachidonic and docosahexaenoic acids in healthy adults.

The effect of dietary supplementation with different amounts of a fungal oil containing arachidonic acid (AA, 20:4n--6) and a microalgal oil containing docosahexaenoic acid (DHA, 22:6n--3), blended to give a ratio of AA to DHA of 1.25:1.00, on plasma lipid AA, DHA, cholesterol, and triacylglycerols was evaluated in healthy men. Subjects (n = 8/group) were given 28.8 g fat/d containing 0 x (0 g AA, 0 g DHA), or 1 x (0.8 g AA, 0.6 g DHA), 3 x (2.2 g AA, 1.7 g DHA), or 5 x (3.6 g AA, 2.9 g DHA) the estimated intake of infants fed human milk with 0.5% AA and 0.4% DHA for 14 d. No clinically significant dose-related effects were seen on physical examination or from routine laboratory tests. The microalgal-fungal oil blend resulted in a significant, dose-dependent increase in plasma cholesterol and percentage phospholipid AA and DHA, and a decrease in percentage triacylglycerols and phospholipid linoleic acid. Plasma phospholipid AA and DHA increased approximately 18% and 50%, respectively, with the 1 x dose, similar to that expected at intakes provided by human milk. These oils appear to be safe dietary sources of AA and DHA for healthy adults at intakes equivalent to 0.8 g AA and 0.6 g DHA/d for > or = 2 wk.

Variable efficacy of glucocorticoids in congenital adrenal hyperplasia.

We have examined the suppression of urinary pregnanetriol and 17-ketosteroids during treatment with cortisol, cortisone, prednisone, and dexamethasone in eight patients with congenital adrenal hyperplasia. A large individual variation in response to each agent was observed. In some individuals, cortisone is less effective than its generally accepted potency would indicate. At equivalent glucocorticoid dosage, dexamethasone was twice as effective as the other steroids in suppressing urinary 17-ketosteroids and pregnanetriol. The potency of dexamethasone in suppressing adrenal function was 80 times that of cortisol, about twice its generally accepted potency as a glucocorticoid or anti-inflammatory agent.

Molecular epidemiology of antibiotic resistant Haemophilus influenzae isolated in Denmark 1981-87.

The molecular basis of antibiotic resistance was studied in 32 epidemiologically unrelated Danish clinical isolates of Haemophilus influenzae. Both non-encapsulated and capsulated type b strains were represented as well as four different biotypes. Plasmid DNA was found in 11 strains, all of which were antibiotic resistant. Antibiotic resistance was transferred to an Rd Haemophilus influenzae recipient from 5 of 6 prospective donors. Ampicillin and chloramphenicol resistance were linked markers while tetracycline resistance--when unselected--was lost in 18% of the transconjugants. Loss of Tcr was associated with loss of a plasmid DNA segment. Restriction enzyme profiles of plasmid DNA lead to the conclusion that the drug resistance plasmids are derivatives of a common, not too distant, ancestor. There is evidence of both clonal spread and horizontal transmission of related drug resistance plasmids in H. influenzae in Denmark.

Past and present national tick control programs. Why they succeed or fail.

The historical reasons for the introduction of tick control during the nineteenth century are reviewed. Background and concepts for the choice between long-term tick control and tick eradication are compared. Case studies of large-scale tick control or eradication programs in Africa, Australia, the United States, and the Caribbean are used to highlight successes and failures. The main reasons for lack of sustainability, or failure, of programs are discussed. These include the economic constraints that were faced in several African countries, or technical shortcomings such as were perceived as a major problem in Puerto Rico. The successes are generally associated with enforcement of appropriate legislation and good management, such as occurred in Zimbabwe. These case studies are analyzed to identify features that may assist in the implementation of the ongoing tropical bont tick eradication program in the Caribbean. The paper concludes with some practical suggestions for the future, and the need to reassess the economics of control and the potential additional animal health benefits derived from tick control programs.

Eradication and surveillance of the tropical bont tick in the Caribbean. An international approach.

The Caribbean Amblyomma program (CAP) is a multidonor funded effort involving several technical organizations and national governments in the eradication of the tropical bont tick. The Food and Agriculture Organization (FAO) is the lead technical agency, providing both technical and administrative support to the CAP Regional Coordination Unit (RCU) based in Barbados. All collaborating agencies, donors, and national representatives are members of the Amblyomma Program Council (APC), the overall governing body of the CAP. In addition to FAO, the other organizations involved are the Caribbean Community (CARICOM), the European Union (EU), the Inter-American Institute for Cooperation on Agriculture (IICA), the International Fund for Agricultural Development (IFAD), and the United States Department of Agriculture (USDA). Several agencies (EU, FAO, IFAD, and USDA) are also major donors. The CAP cooperates with the complementary Plan POSEIDOM Veterinaire Program in the French West Indies. The University of the West Indies (UWI), the International Institute for Biological Control (IIBC), and the Departement d'Elevage et de Medecine Veterinaire des Pays Tropicaux (EM-VT) in Guadeloupe are other collaborators.

Dysplastic cutaneous osteomatosis. A unique case of true osteoma.

A unique cas of dermal calcification occurred in a 14-month-old femal infant. Results of all pertinent laboratory data obtained on this patient were within normal limits except for an elevation of the heat labile fraction of alkaline phosphatase. A skin biopsy specimen showed irregularly shaped deposits of calcified osteoid with osteoblasts. As yet, neither the cause nor the prognosis of this disease has been delineated.

Insulin receptors in the developing fetal lung.

Fetal lung insulin receptor numbers and affinities were studied in rat pregnancies from 15 to 22 days gestation. Insulin receptor binding capacities were found to increase six-fold from approximately 100 fmoles insulin bound/mg lung DNA at 15 days gestation to approximately 600 fmoles bound/mg DNA at 22 days gestation. However, the affinity constants of the receptors were unchanged during this same period (high affinity, 1.9 +/- 0.4 S.E. and low affinity, 0.03 +/- 0.01 S.E.). The results suggest that the lung may become increasingly more sensitive to insulin as development progresses.

Comparative bacteriological studies on summer mastitis in grazing cattle and pyogenes mastitis in stabled cattle in Denmark.

A total of 143 secretions from clinical cases of summer mastitis (SM) in grazing cattle and from 89 cases of pyogenes mastitis (PM) in stabled cattle were examined bacteriologically. The typical bacteriological finding was a mixed flora in which the predominant organisms were Actinomyces pyogenes (SM-70%, PM-85%), Peptostreptococcus indolicus (54%, 54%), a microaerophilic coccus (Stuart-Schwan coccus) (26%, 25%), Fusobacterium necrophorum biovar B (22%, 12%), Bacteroides melaninogenicus (20%, 9%) and Streptococcus dysgalactiae (21%, 5%). All except six cases occurred in non-lactating animals or within three weeks after parturition. The majority of animals (about 90%) had only one quarter affected and no differences in quarter distribution were observed between the two groups.

Summer mastitis in heifers: studies on the seasonal occurrence of Actinomyces pyogenes, Peptostreptococcus indolicus and Bacteroidaceae in clinically healthy cattle in Denmark.

With the aim of investigating the seasonal occurrence of Actinomyces pyogenes, Peptostreptococcus indolicus, Bacteroides melaninogenicus ss. levii and Fusobacterium necrophorum, and thus the potential for development of summer mastitis, clinically healthy Danish Holstein-Friesian heifers due to calve in the autumn were sampled from the teat tip, the conjunctiva and the oral cavity at 2-6 week intervals from 1979 to 1981. The overall isolation rates of F. necrophorum, P. indolicus and B. melaninogenicus ss. levii, in order of significance, were significantly higher during the pasture period whereas no differences in isolation rates of A. pyogenes between housed and pastured animals were detected. F. necrophorum was recovered almost exclusively from the oral cavity, P. indolicus and A. pyogenes occurred most frequently in samples from the teat skin, whereas isolates of B. melaninogenicus ss. levii were evenly distributed between conjunctiva and teat tip samples. A distinct seasonal pattern of the isolation rates of summer mastitis pathogens was recorded, which corresponded closely to the seasonal activity of symbovine insects, in particular the headfly Hydrotaea irritans (Fallén). However, the high proportion of clinically healthy bacterial carriers as compared with the incidence of clinical disease strongly suggests that as yet unknown contributing or triggering factors, apart from the mere presence of the relevant bacterial species, are required for the establishment and development of clinical summer mastitis.

Challenges of matching human milk fatty acid patterns technically and functionally.

A vegetable oil fat blend resulting in formula major fatty acid levels similar to human milk is appropriate for infant feedings even though the palmitic acid may have a somewhat different positional distribution. Growth, bone mineral content, and visual acuity (as measured by the Teller acuity card procedure) achieved in normal infants consuming such formulas are at least as good as those from human milk. The quantitatively minor LC-PUFA levels may also be important in infant development and useful once safety of their sources has been adequately demonstrated. Such formula fat blends mimicking the major fatty acid profiles of human milk are appropriate for infants with relatively normal fat absorptive mechanisms including infants with allergy or inborn errors of metabolism. Formulas designed for such infants (e.g., extensively hydrolyzed protein products for allergic infants) do not need to have MCT oil included in the formulation which alters the fatty acid profile. On the other hand, those infants with immaturity, gastrointestinal disease, and/or fat malabsorption often do benefit by the inclusion of MCT oil in the fat blend of the formula.

The effect of parasite control on fertility in beef heifers.

The effect of anthelmintic treatment on the growth and conception rate in beef heifers was studied in southwestern Virginia, USA. Forty mixed-breed heifers were divided into two groups at weaning and placed on experimental pastures. Control heifers did not receive anthelmintic treatment, while animals in the treatment group were given ivermectin (200 micrograms kg-1) at the time of allocation to groups in October and again in April the following year. Supplemental feed was provided throughout the winter to ensure adequate weight gains. In May, the heifers were exposed to bulls for natural breeding for a period of 6 weeks. Weight gains, fecal egg counts, serum pepsinogen levels and pasture larvae counts were monitored throughout the experiment. No difference in conception rate was observed between the two groups, although the cumulative weight gain was significantly greater in treated than non-treated animals. Serum pepsinogen levels and fecal egg counts were also generally lower in treated than non-treated heifers.

Grazing pressure and acquisition of Ostertagia ostertagi in calves.

The effect of stocking rate on the acquisition of Ostertagia ostertagi infection and performance of yearling calves grazing a marshland area in the southwest of Jutland (Denmark) was examined. During the early part of the grazing season, when grass growth was high and pasture infectivity low, there was little stocking rate effect on performance. However, during the late part of the grazing season (characterized by poorer grass growth and high pasture infectivity) gains were significantly lower at high, compared with moderate stocking. At both stocking rates, the beneficial effect of moving animals to aftermath in mid-summer was significant, but was most pronounced at the high stocking rate. Interactions between stocking rate and acquisition of parasitism are discussed in the light of grazing behaviour and climatic factors.