Georgetown University/Providence Hospital Family Practice Program, Washington, DC. Project test ways to coordinate medical, community services

Fragmented medical care is especially harmful for chronically ill elderly patients. Intervention designed to educate them about their diseases and available resources may result in increased self-care and decreased rates of institutionalization.     

Porous polysulfone coatings for fixation of femoral stems by bony ingrowth

Sixteen porous polysulfone-coated canine femoral stems were inserted into 14 dogs. Coatings were approximately 40% porous, with an average pore size of 125 or 250 microns. Bone was formed within at least about 30% of the surface pores of the implants. The tissue ingrowths filling the pores included marrow and fibrous tissue. Correlated roentgenographic and histologic observations revealed a trabecular "lamina dura" at the coating-bone interface and relatively dense trabeculae distal to the stem tip. These observations support the concept of coating femoral prostheses with porous material for cement-free stabilization.     

Porous polysulfone as an attachment vehicle for orthopedic and dental implants.

The mechanical properties of porous polysulfone (PSF) were determined and its performance as a surface coating on orthopedic and dental implants evaluated. Ten coated femoral prostheses were implanted in nine dogs. A second series of four uncoated "control" prostheses and all of the acetabular cups were implanted using conventional bone cement techniques. Six porous PSF coated tooth roots were implanted in healed mandibular premolar extraction sites in three Rhesus monkeys. The shear strength of porous PSF (6 MPa) was comparable to that of trabecular bone. Pushout tests of 1cm. thick sections of the prostheses yielded interfacial shear strength values over 1.4 MPa for the PSF coated hips after 14 weeks and mean values under 0.7 MPa for the bone cemented specimens after 3 and 36 weeks. Bone and fibrous tissue was identified in the pores of coated specimens. Preliminary clinical evaluation of the functioning dental implants revealed zero mobility and other favorable clinical and radiographic indications after 2 months.     

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.     

Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues

Purpose: Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca²⁺ ([Ca²⁺]_i) signalling in mammalian cells. Methods and Results: Oryzalin inhibited vasopressin, bradykinin and platelet-derived growth factor [Ca²⁺]_i signalling in Swiss 3T3 fibroblasts with IC₅₀ values of 14, 16 and 18 μM, respectively. ⁴⁵Ca²⁺ uptake into nonmitochondrial stores of saponin-permeabilized Swiss 3T3 cells was inhibited by oryzalin with an IC₅₀ of 34 μM. Oryzalin inhibited colony formation of HT-29 colon carcinoma cells with an IC₅₀ of 8 μM and inhibited the growth of a number of other cancer cell lines and primary human tumors in vitro with IC₅₀ values in the range 3 to 22 μM. A number of oryzalin analogues were studied and an association was found between the ability to inhibit [Ca²⁺]_i signalling and inhibition of the growth of HT-29 human colon cancer cells (P=0.001) and of CCRF-CEM human leukemia cells (P=0.016). Oryzalin at doses up to 600 mg/kg administered orally or subcutaneously daily to mice for 3 to 10 days beginning a day after tumor inoculation inhibited the growth of murine B16 melanoma by 63% but showed no appreciable activity when administered subcutaneously or intraperitoneally to mice beginning a number of days after tumor inoculation against a variety of human tumor xenografts. The peak plasma concentration of oryzalin following repeated subcutaneous administration of oryzalin at 600 mg/kg per day to mice was 37 μM and of its major metabolite N-depropyl oryzalin was 53 μM. Conclusion: It is unlikely that the absence of significant antitumor activity of oryzalin is a result of the inability to achieve adequate plasma concentrations. Received: 24 December 1996 / Accepted: 20 March 1997     

Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.