Etiopathogeny, prognosis and therapy of myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous and common group of clonal hematological disorders characterized by cytopenias, dysplastic changes of hematopoietic cells, and a high rate of transformation into acute myeloblastic leukemia (AML). MDS provide a clinical model for studying the emergency and progression of malignancy. The initiating events leading to MDS remain almost unknown. Imbalance of proliferative and differentiating capabilities of progenitor hematopoietic cells along with abnormalities in the normal process of apoptosis are involved in both the pathogenesis of MDS and transformation into AML. Multiple genomic lesions, comprising oncogene activation and tumor-suppressor gene inactivation, are probably required. Alkylating agents, cytotoxic drugs targeting topoisomerase II and benzene are the only clear etiological factors identified. Advanced age and great prognostic variability, not explained by the FAB subtype, complicates the design and analysis of clinical trials and therapy-planning. The use of recently developed prognostic scores for selecting the best treatment according to the expected risk is encouraged. In most patients therapy is unsatisfactory. At present, bone marrow transplantation is considered as the only curative approach. A better knowledge of the pathobiology of MDS should be valuable to develop new, more rationale and effective therapies.     

Status and prospects of the dairy goat industry in the United States

Among the major classes of U.S. livestock, dairy goats have yet to achieve USDA statistical reporting of their numbers, amounts of milk produced and processed, and cheese and other products marketed. However, the USDA has published buck proofs of approximately 16,000 does annually from Dairy Herd Improvement Association (DHIA) records of the Alpine, LaMancha, Nubian, Oberhasli, Saanen and Toggenburg breeds, thereby encouraging genetic progress. This represents a 1% participation in DHIA of the estimated 1.5 million U.S. dairy goats. Annual breed registrations are led by Nubians (11,000), and the leading states in descending order are California, Texas, Ohio, New York, and Pennsylvania. Breed average milk yields range from 960 kg of milk for Saanen to 726 kg of milk for Oberhasli. Average milk contents range from 4.5% fat and 3.69% protein for Nubian to 3.3% fat and 2.98% protein for Toggenburg. Leading lactation records are 3,023 kg of milk (Toggenburg) and 174 kg of fat (Nubian). Total annual registrations are 45,000+ animals by 16,000+ member breeders. Estimated total U.S. goat milk commercial production is 24,000+ t, with half going into commercial farm goat cheese production of 640+ t. Recent years have seen significantly increased numbers of dairy goat research projects and publications from Oklahoma, Texas, California, Georgia, Alabama, Florida, Louisiana, New York, Connecticut, Delaware, and Massachusetts. Furthermore, annual national and international symposia, annual national goat cheese judging competitions and workshops, an active national goat research foundation, representation on the National Interstate Milk Shippers Committee and Mastitis Council, and formation of a national association and council for the development and promotion of dairy goat products indicate an evolution from former emphasis on purebred breed development to a focus on market development. The conclusion is that dairy goats are emerging as a necessary and recognized U.S. industry.     

Dietary omega-3 and omega-9 fatty acids uniquely enhance allograft survival in cyclosporine-treated and donor-specific transfusion-treated rats

BACKGROUND: Both laboratory and clinical studies have shown that dietary lipids may affect immunologic responses. This study was conducted to compare different classes of long-chain unsaturated fatty acids for their effect on allograft survival in animals receiving a donor-specific transfusion and a short course of low-dose cyclosporine (CsA). METHODS: Heterotopic ACI strain cardiac allografts were transplanted to Lewis strain rat recipients given diets with different lipid composition. In experiment 1, animals received CsA for 14 days and different diets were enriched with lipids with high concentrations of omega-3, omega-6, or omega-9 fatty acids. In experiment 2, animals received CsA for only 8 days and different diets were enriched with corn oil (omega-6), canola oil (omega-3 and omega-9), fish oil (omega-3) or a mixture of sunflower oil and fish oil (omega-3 and omega-9). RESULTS: In experiment 1, animals receiving the diet with 30% sunflower oil had the best allograft survival (200+/-42 days vs. 53+/-8 days for regular chow plus donor-specific transfusion and CsA, P<0.05). In experiment 2, diets containing canola oil (a mixture of omega-3 and omega-9 fatty acids) were associated with the best survival (P=0.0011 vs. regular chow). CONCLUSION: Dietary omega-3 and omega-9 fatty acids both enhanced cardiac allograft survival in a stringent rat strain combination. Canola oil is a convenient oil for administering both alpha-linoleic acid (omega-3) and oleic acid (omega-9) in a palatable form for human consumption. Further investigation of the potential usefulness of lipids in transplant therapy is warranted.     

Rat bone marrow-derived mast cells co-cultured with 3T3 fibroblasts in the absence of T-cell derived cytokines require stem cell factor for their survival and maintain their mucosal mast cell-like phenotype

The aim of this study was to compare the accuracy of computed tomography (CT) and single photon emission computerized tomography (SPECT) in the diagnosis of dementia. Fifty-two patients with clinical diagnosis of dementia and 11 controls were studied. The scans were interpreted by one experienced neuroradiologist and one nuclear radiologist, both blinded to the clinical data. In the diagnosis of dementia, CT and SPECT showed equal sensitivity (82.7%) and statistically similar specificity (63.8 and 81.8%, respectively). The specificity of SPECT in diagnosing Alzheimer's disease (100%) was statistically superior to CT (69%). However, both methods showed similar sensitivity in detecting Alzheimer's disease. In conclusion, SPECT and CT showed similar accuracy in the diagnosis of dementia. The quite high specificity of SPECT in Alzheimer's disease may be useful for confirming that diagnosis, particularly for patients with presenile onset of the disease.     

Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium

BACKGROUND: Valproic acid is added to the lithium regimens of many patients with bipolar disorder, especially those with mania refractory to lithium treatment. METHOD: We evaluated the pharmacokinetic effects and safety of coadministration of lithium and valproate in 16 healthy volunteers in this randomized, placebo-controlled, two-period (12 days each) crossover trial. Valproate or placebo was given twice daily. On Days 6-10, lithium was added. Blood samples drawn on Days 5 and 10 were analyzed for valproate by high-pressure liquid chromatography (HPLC) and for lithium by atomic absorption spectrophotometry. RESULTS: Lithium pharmacokinetics were unchanged by valproate, but valproate C(max), C(min), and AUC rose slightly during lithium coadministration. Adverse events did not change significantly. CONCLUSION: Concomitant administration of lithium and valproate appears to be safe in patients with bipolar disorder.     

Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved

BACKGROUND: A complete immunohistochemical characterization in complicated carotid plaques is still lacking. The cellular components of 165 carotid endarterectomy specimens were analyzed to assess their role in the pathogenesis of plaque rupture and intraplaque hemorrhage without rupture. METHODS AND RESULTS: The fibrous caps at the sites of plaque rupture showed CD68+ macrophages, T-lymphocytes, and scarce B-lymphocytes. Ruptured plaques showed mononuclear infiltrates in the caps, shoulders, and bases of the plaques in 85% of the cases. Only 46% of nonruptured plaques showed such infiltrates (P <.0001). Two types of lipid cores were recognized: avascular or mildly vascularized and highly vascularized. The vessels of the latter type reacted with CD31 and CD34. In 57.5% of the cases, the base and the shoulders of the plaques showed neoformed, CD34+ vessels, often surrounded by mononuclear infiltrates. Intraplaque hemorrhage without rupture had highly vascularized lipid cores in all cases. T-lymphocytes and macrophages were in close contact with neoformed vessels. CONCLUSIONS: Plaque rupture is characterized by mononuclear cell infiltration of the caps, whereas intraplaque hemorrhage without rupture is characterized by extensive vascularization of the plaque.     

Serum dopamine-beta-hydroxylase activity in rat during post-natal development

The strength of knotted thread for 12 different types of suture knot in combination with 11 types of suture material used in surgery was investigated one week after insertion in subcutaneous tissue in rabbits. The results were compared with similar investigations on knot strength carried out with 'dry knots'. The thread dimension used in both experiments was 000 (USP). As in vitro, the weakest point of a suture loop subjected to traction was the knot. The incidence of thread rupture within the loop but outside the knot was 1.4% in vitro and 5.9% in vivo, and was commonest with plain catgut. With one exception, however, thread breakage occurred at greater strain than the average required to produce knot failure with the material in question. A greater proportion of knots slipped in vivo then in vitro (72% and 35% respectively), with reduction of the strength of the suture loop as result. There was also greater scatter of measured values under in vivo conditions (standard deviation: 11% in vitro, 23% in vivo). For 7 of 11 suture materials the results indicated a reduction in knot-holding power after one week in situ in the living animal compared with in vivo conditions. This was naturally enough most marked with the two types of catgut (chrome 48%, plain 57%). In contrast, Dexon apparently remained unchanged after one week in vivo. The non-absorbable materials tested showed an estimated average fall in knot-holding power from 100% to 88% (range 109-65%), viz, an average of 12% units. The loss of holding power in vivo was, however, apparently never greater than 1/3 compared with 'dry knots' and calculated on average for all types of knot with non-absorbable materials.     

Arthritis with an inflammatory dermatosis resembling Sweet's syndrome. Report of a unique case and review of the literature on arthritis associated with the inflammatory dermatoses

A patient with a unique case of chronic episodic arthritis coincident with flares of acneform, pustular, nodular and ulcerating skin lesions was observed over a five-year period. This patient and a review of the literature on arthritis associated with the inflammatory dermatoses provide evidence which may interrelate several of these nosologically confusing skin conditions, e.g., the family of leukocytoclastic angiitides with the newly posited acute febrile neutrophilic dermatosis of Sweet. Systemic manifestations and a variety of acneform, pustular, nodular and ulcerating cutaneous lesions in the inflammatory dermatoses are best explained by small vessel involvement, with individual syndromes being determined by the type and degree of vascular change. Perivascular neutrophilic infiltration is the unifying histologic feature of these small vessel diseases. Neutrophil infiltration differentiates these entities, and our patient, from the histologically nonspecific inflammations of the skin, e.g., Behcet's disease and pyoderma gangrenosum, which, although capable of causing identically appearing skin lesions, consist predominantly of lymphocytic dermal infiltrates even in the earlier stages. It appears important to recognized these morphologically varied acute inflammatory dermatoses with perivascular neutrophilic infiltration in view of their systemic features and the dramatic efficacy of corticosteroid therapy.     

The use of multivariable standard curves in the radioimmunoassay of testosterone and 5alpha-dihydrotestosterone

Threshold fluctuations are divided into short-term and long-term effects applying statistical methods. Sixteen normal and pathological visual fields were analysed in order to obtain values for the short-term, long-term and total fluctuations. Special attention is paid to fortuitous variations between the results obtained at successive examinations. Finally the concept of spatial correlations is introduced.