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This article reviews multi-criteria QSAR applications on Acetylcholinesterase inhibitors as palliative drugs for Alzheimer's Disease, published in the period 2001-2011. It includes QSAR models for different series of compounds, comparative studies, and advances in methodologies. This period is marked by a shift in focus from palliative treatment to pathogenesis. However, we believe that research into palliative treatment should continue. More comparative studies are desirable. In order to facilitate comparative and general studies on Acetylcholinesterase inhibitors, a standard experimental protocol for measuring an inhibitor's potency is needed. Finally, we recommend chemists to work closely with system and molecular biologists.

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The long-term stability of cemented total hip replacements critically depends on the lasting integrity of the bond between bone and bone cement. Conventionally, the bonding strength of bone-cement is obtained by mechanical tests that tend to produce a large variability between specimens and test methods. In this work, interfacial fracture toughness of synthetic bone-cement interface has been studied using sandwiched Brazilian disk specimens. Experiments were carried out using polyurethane foams as substrates and a common bone cement as an interlayer. Selected loading angles from 0° to 25° were used to achieve full loading conditions from mode I to mode II. Finite element analyses were carried out to obtain the solutions for strain energy release rates at given phase angles associated with the experimental models. The effects of crack length on the measured interfacial fracture toughness were examined. Microscopic studies were also carried out to obtain the morphology of the fractured interfaces at selected loading angles.The implication of the results on the assessment of fixation in acetabular replacements is discussed in the light of preliminary work on bovine cancellous bone-cement interface.

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Two infants with Down syndrome had transient myeloproliferative disorder (TMD) during the neonatal period and subsequently acute nonlymphoblastic leukemia (ANLL). Histochemically, the blast cells in TMD were indistinguishable from those in ANLL. Only the constitutional chromosome (trisomy 21) was found in TMD, whereas new cytogenetic abnormalities emerged in ANLL. A mixed growth pattern in stem cell cultures during TMD suggested the existence of an abnormal clone that might be responsible for the evolution into ANLL at a later date. Serial cytogenetic studies and culture studies of peripheral blood cells may help to understand the pathophysiology and risk of ANLL in patients with TMD.

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To characterize the long-term effects of doxorubicin hydrochloride (Adriamycin) on left ventricular function, a total of 588 echocardiograms were obtained prospectively in 46 children who were treated for malignancy. We found shortening fraction of the left ventricle to be more useful than systolic time intervals for detecting cardiotoxic effects. Abnormal cardiac function occurred in 43% of patients but only 4% developed congestive heart failure which was irreversible. There appeared to be strong individual variation in response to the effects of doxorubicin on the heart unrelated to treatment regimen, age of onset of treatment, or total cumulative dose. If the SF remained normal it was possible to give a dose greater than 550 mg/m2. If cardiac dysfunction occurred following cessation of doxorubicin, it did so within five months in 95% of patients. Discontinuing doxorubicin therapy in patients with SF LEss than 20% who did not have clinical signs of congestive heart failure resulted in improved shortening fraction and administration of digoxin did not further improve the SF. Sequential echographic evaluation of cardiac function at frequent intervals has proven to be useful during and following treatment with doxorubicin.

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Twenty-nine of 60 boys with acute lymphoblastic leukemia survived for more than 30 months and were potential candidates for discontinuation of therapy. Six patients developed overt clinical testicular leukemia: one at 34 months from diagnosis while receiving therapy and five at three to 17 months after therapy was stopped. Elective wedge biopsy of the testes has become part of the evaluation prior to discontinuation of therapy since 1977. Six of 18 boys had microscopic evidence of leukemic infiltration of the testes: four with diffuse involvement and two with focal clusters of leukemic cells. Testicular biopsy is recommended at the time of discontinuation of therapy and perhaps early in the course of the disease, although a negative biopsy does not exclude some focal lesions. The eventual outcome of those with occult testicular leukemia remains to be determined.

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Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.

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