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.

Effect of nematode burden as assessed by means of faecal egg counts on body condition in goats farmed under resource-poor conditions in South Africa.

A longitudinal study was conducted of the nematode faecal egg counts (FECs) and body condition scores (BCSs) of goats of resource-poor farmers at Rust de Winter, Gauteng Province, Impendle, KwaZulu-Natal Province, and Kraaipan, North-West Province, South Africa. Periods of higher FECs occurred from December/January to March/April at Rust de Winter and at Impendle and from January to March at Kraaipan. Seasonal variations in body condition were evident in the goats at Impendle with the animals showing lower BCSs from June to October. The goats at Rust de Winter and at Kraaipan did not show clear seasonal variations, although the goats at Rust de Winter showed lower BCSs from mid-July to early December. The BCSs for Rust de Winter where the animals were grazed on a private farm were generally higher than those of the other sites, where communal grazing is practised.

Incidence of Haemonchus spp. and effect on haematocrit and eye colour in goats farmed under resource-poor conditions in South Africa.

The diversity and predominance of nematode genera in goats of resource-poor farmers at Rust de Winter, Gauteng Province, Impendle, KwaZulu-Natal Province, and Kraaipan, North-West Province, South Africa, was determined by means of a longitudinal study of the nematode faecal egg counts (FECs) and differential third-stage nematode larvae. The animals were bled for haematocrit determination and scored for pallor of ocular mucous membranes using the FAMACHA( Copyright) method, an assay for clinical evaluation of anaemia caused by Haemonchus spp. Animals considered to be in danger of dying from anaemia caused by haemonchosis were selectively treated with an anthelmintic. Lower haematocrit values were registered during periods of heavier Haemonchus infection, which occurred from December/January to March for Rust de Winter; from December to March/April for Impendle; and from November/December to February or April for Kraaipan. There was agreement too between the lower haematocrits and paler mucous membranes scored according to the FAMACHA( Copyright) method. The use of this system may be recommended as part of an integrated approach to worm control in goats kept in the resource-poor areas studied.

Haemonchus spp. in sheep farmed under resource-poor conditions in South Africa--effect on haematocrit, conjunctival mucous membrane colour and body condition.

A longitudinal study was conducted on the differential faecal egg counts, haematocrits and body condition scores of sheep belonging to resource-poor farmers at Rust de Winter, Gauteng province, and Kraaipan, North West Province, South Africa. The animals were scored for level of anaemia using the FAMACHA method, an assay for the clinical evaluation of anaemia caused by Haemonchus spp. Periods of higher Haemonchus egg counts occurred from October to March for sheep at Rust de Winter and from September/October to February or April for sheep at Kraaipan. Lower haematocrit values were registered during these periods as was a higher incidence of anaemic conjunctival mucous membrane colour scores compared to the period April to September. No clear relationship between the faecal egg counts and the body condition scores was evident. Although wider application of the FAMACHA system in sheep raised by resource-poor farmers should be investigated, the present study indicates that this method may certainly prove to be a valuable worm control strategy for such livestock owners.

Testing for clinical anaemia caused by Haemonchus spp. in goats farmed under resource-poor conditions in South Africa using an eye colour chart developed for sheep.

A novel clinical assay for the assessment and subsequent treatment of Haemonchus infection in sheep to slow down the development of anthelmintic resistance--the FAMACHA system--has been developed, tested and validated in South Africa. The system is based on a colour chart with five colour categories depicting varying degrees of anaemia that are compared with the colour of the mucous membranes of the eyes of sheep. The animal is then scored from severely anaemic (pale) through anaemic to non-anaemic (red) and those animals considered in danger of succumbing to the effects of haemonchosis are treated. This method was tested in goats farmed under resource-poor conditions in South Africa. Analyses in goats performed during the summers of 1998/1999 and 1999/2000 show a test sensitivity of 76 and 85%, respectively, meaning that the system may be used to identify correctly 76-85% of those animals in need of treatment with an anthelmintic. However, the test specificity remains low at 52-55%. This means that a large proportion of those animals that would not require treatment would in fact be treated. However, when the use of the FAMACHA system is compared with conventional dosing practices where all the animals are treated, using the FAMACHA system would result in a large proportion of the animals being left untreated. The untreated animals are then able to deposit the eggs of anthelmintic-susceptible worms on the pasture, while the treated ones should pass very few ova, given an effective anthelmintic. This maintains a reservoir of susceptible larvae in refugia, and should slow down the development of anthelmintic resistance. The validation of the FAMACHA system for goats for use by resource-poor farmers, which this paper describes, may have wide application in the tropics and subtropics of sub-Saharan Africa and elsewhere.

Effects of mixed grazing of first- and second-year calves on trichostrongylid infections in Lithuania.

The objective of this study was to examine whether susceptible calves grazing together with second-year resistant heifers are less exposed to trichostrongylid infection than are calves grazing on their own. Two groups of animals representing each age category were turned out onto pasture on 24 May 1997 and grazed at comparable stocking rates. The grazing of calves and heifers together was compared to groups of each age category grazing separately. The results indicated that herbage larval counts were significantly reduced in the second part of the grazing season on the plot grazed by the mixed group compared to the plot grazed by the first-season calves only. The mixed grazing strategy protected the young calves and no clinical signs were observed in this group, while most of the calves that grazed alone exhibited clinical signs. The availability of herbage was reduced towards the end of the season, with subsequent competition for the grass forcing all the animals to graze the tufts around the faecal pats, where the quality of the grass is poor and the numbers of infective larvae are high. The effect of this was visible in the form of increased parasite burdens in the calves that were grazed together with the heifers, confirmed by increased blood serum pepsinogen concentrations and reduced daily weight gains in the second part of the grazing season. The lower numbers of infective larvae on the pasture were probably achieved through the heifers ingesting many of the larvae but subsequently depositing relatively few eggs, since they had acquired some degree of resistance against trichostrongylid infections during their first grazing season. Thus they did not suffer any parasitological ill-effects during mixed grazing with first-season calves.

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.

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.

Biological control of trichostrongylid infections in calves on pasture in Lithuania using Duddingtonia flagrans, a nematode-trapping fungus.

The effect on the pasture contamination level with infective trichostrongylid larvae by feeding the nematode-trapping fungus, Duddingtonia flagrans at two dose levels to first time grazing calves was examined in Lithuania. Thirty heifer-calves, aged 3-6 months, were divided into three comparable groups, A, B and C. Each group was turned out on a 1.07 ha paddock (a, b and c). The paddocks were naturally contaminated with infective trichostrongylid larvae from infected cattle grazing the previous year. Fungal material was fed to the animals daily during a two month period starting 3 weeks after turnout. Groups A and B were given 10(6) and 2.5x10(5) chlamydospores per kg of live weight per day, respectively, while group C served as a non-dosed control group. Every two weeks the heifers were weighed and clinically inspected. On the same dates, faeces, blood and grass samples were collected. From mid-July onwards, the number of infective larvae in grass samples increased markedly (P<0.05)on paddock c, whereas low numbers of infective larvae were observed on paddocks a and b grazed by the fungus treated groups. However, the results indicate that administering fungal spores at a dose of 2.5x10(6)chlamydospores per kg live weight per day did not significantly prevent parasitism in calves, presumably due to insufficient suppression of developing infective larvae in the faeces. In contrast, a dose of 10(6) chlamydospores per kg lowered the parasite larval population on the pasture, reduced pepsinogen levels (P<0.05), and prevented calves from developing parasitosis.

Effect of strategic treatments with invermectin on parasitism of set-stocked calves exposed to natural trichostrongyle infection in Lithuania.

The effect of strategic treatments with ivermectin in first-season calves exposed to trichostrongyle nematodes on naturally contaminated pasture was studied. Twenty first season heifer calves were divided into 2 groups, according to live weight, and on 22nd May each group was turned out onto a 1 hectare pasture. Group A (Plot A) was treated with ivermectin at weeks 3, 8 and 13 after turn out, while group B (Plot B) served as an untreated control group. The study showed that control calves exhibited increase in trichostrongyle egg counts in August, while treated calves were excreting low numbers of trichostrongyle eggs. Pasture larval counts on Plot B (control animals) were low during the first part of the grazing season, followed by a steep rise towards the end of July. In contrast, the numbers of infective larvae recovered from Plot A remained low throughout the season. Both groups showed comparable weight gains from May up to the middle of July. However, from then on, Group B (controls) had lower weight gains than ivermectin treated Group A. From the end of July onwards, most untreated calves (Group B) showed clinical signs of parasitic gastroenteritis. It can be concluded that the strategical ivermectin treatments were successful, and faecal egg counts, pepsinogen levels and herbage larval counts clearly demonstrated that this was accomplished through suppression of pasture contamination with nematode eggs and subsequent reduction of pasture infectivity.

Can the elimination of lactose from formula improve feeding tolerance in premature infants?

OBJECTIVE: To determine whether a low-lactose formula (LLF, <5% lactose) would ameliorate feeding intolerance in premature infants. STUDY DESIGN: Prospective, randomized, controlled trial involving 306 infants <36 weeks' gestation and weighing <1800 g who received either lactose-containing formula (LCF) 24 kcal/oz or a specially prepared LLF, which was comparable to the LCF except for the functional replacement of lactose with maltose. We examined outcome variables of feeding intolerance and cases of necrotizing enterocolitis (NEC) and suspected NEC. RESULTS: One hundred forty-nine infants were assigned to receive LCF, of which 99 infants received LCF only. One hundred fifty infants were assigned to receive LLF, of which 102 infants received LLF only. The remaining infants received LCF or LLF plus some quantity of human milk or human milk alone. Infants receiving LLF had improved enteral caloric intake and weight gain, reached full feeds faster, had less gastric residual, spent less time without oral intake, and had fewer feedings stopped than the LCF group. The number of cases of NEC and suspected NEC was similar in both groups. CONCLUSION: Low-lactose premature infant formula improved feeding tolerance. There was no evidence that LLF altered the incidence of NEC, but the incidence of NEC in this study was too low to draw conclusions.

Thrombolytic therapy in Missouri hospital emergency departments: compliance with the National Heart Attack Alert Program guidelines.

A self-administered questionnaire concerning the current practice of thrombolytic administration, and the use of National Heart Attack Alert Program (NHAAP) guidelines was mailed to the medical directors of Missouri acute care emergency departments (EDs). Responses from 75% of the EDs surveyed were received. There were standing orders to perform an electrocardiogram at 92% of the EDs surveyed. Thrombolytics were stocked in 80% of EDs and thrombolytics were administered in the ED rather than the ICU or CCU at 98%. The emergency physician (EP) was authorized to make thrombolytic treatment decisions at 87% of the institutions; however, in 24% of the hospitals EPs were required to contact another physician prior to giving thrombolytics. An Acute Myocardial Infarction (AMI) Continuous Quality Improvement (CQI) program was in place at 67%, and 44% of the institutions had an interdepartmental AMI protocol. Less than half of the EDs reported a door-to-drug time of less than 30 minutes. The primary delay in starting thrombolytic therapy was identified as decision-making on the part of the emergency physician and/or consultants. Missouri EDs report that they generally follow the NHAAP guidelines for rapid identification and treatment of AMI, but, there were still significant delays reported in the administration of thrombolytics.

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.

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.

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.

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: general overview.

South America has a large population of small ruminants. Currents estimates are approximately 100 million sheep and 23 million goats. A large percentage of these flocks are raised in the humid tropics/sub-tropics. Nematode parasitism is singly the most important disease of these animals and typically farmers resort to frequent anthelmintic treatment in attempts to control this problem. Because of this reliance on drugs, price consideration is an important determinant in a farmer's choice of anthelmintic. In some circumstances, this has led to unethical practices of drug adulteration and substitution, or the offering to farmers of cheap, sub-standard generic products. The prevalence of anthelmintic resistance has not been investigated in any widespread sense in South America, although some of the first reports of resistance were made in southern Brazil almost 30 years ago. The following series of papers outline surveys conducted in the humid topics/sub-tropics of southern Latin America to assess the significance of resistance to the broad-spectrum anthelmintic groups in nematode parasites of sheep flocks.

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Argentina.

Sixty-five sheep farms in the northern provinces of Buenos Aires, Entre Rios, Corrientes, Cordoba and Sante Fe were used in this survey on anthelmintic resistance. Anthelmintic groups tested were the benzimidazoles, levamisole, the combination levamisole + benzimidazole product and the avermectins. The overall level of resistance was 46% of properties, with resistance to the individual drug groups being 40%, 22%, 11% and 6%, respectively. On a large proportion of farms the resistance recorded was to two, or more, anthelmintic groups. Haemonchus contortus, Ostertagia spp. and Trichostrongylus spp. were the most abundant parasite species recorded. Resistance was greatest in the province of Corrientes where the frequency of treatment is generally high due to the endemic nature of H. contortus. Management practices were also important with resistance greatest on farms where frequent drenching is carried out and on farms carrying only sheep.

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Brazil.

This survey was conducted in the southern Brazilian state of Rio Grande do Sul and involved 182 farms located in 26 counties. In addition to the three major broad-spectrum anthelmintic groups (viz. benzimidazole, levamisole and ivermectin) the combination benzimidazole and levamisole and the H. contortus specific anthelmintic, closantel, were tested by the faecal egg count reduction method for the prevalence of anthelmintic resistance. Resistance was found to be 90%, 84%, 13%, 73% and 20%, respectively. This is a crisis situation. Immediate, drastic action needs to be implemented, otherwise the sheep industry in this region (approx. 10 million head) will soon face a lack of any effective anthelmintics with the inevitable consequences of major restructuring or abandonment.

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Paraguay.

This survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 11 farms in the Occidental and 26 farms in the Oriental Regions of Paraguay using the faecal egg count reduction test (FECRT). The anthelmintic groups tested were the benzimidazoles, levamisole and avermectins (both oral and injectable). Overall the levels of resistance were 73%, 68%, 73% and 47%, respectively. Levels of resistance were similar for all three important nematode genera, viz. Haemonchus contortus, Ostertagia and Trichostrongylus. This survey clearly indicates that a large, and ever increasing, proportion of sheep farmers are rapidly approaching the time when they will have exhausted all chemotherapeutic options to control parasites. Unless they face having to abandon their sheep farming operations, radical changes will need to be implemented with urgency.