Objective assessment of the effect of surgery on limb function after medial femoral condyle free flap harvest: biomechanical parameters.

The aim of this study was to evaluate the influence of medial femoral condyle (MFC) free flap harvest on donor site muscle strength and kinematic parameters of gait. The study included 30 patients treated for head and neck squamous cell carcinoma who underwent reconstruction with an MFC free flap. In each case, the donor site was the left thigh. A dynamometer was used to measure muscle strength, in isokinetic bilateral mode and with concentric contraction for the extension/flexion knee pattern, at 18 months postoperative. In addition, kinematic data were obtained and evaluated. On statistical analysis, no significant difference in muscle strength of the quadriceps muscle was found between the left involved and right uninvolved lower extremities (P = 0.124). Also, when comparing hamstring strength, no statistically significant difference was found between the left involved and right uninvolved sides (P = 0.210). Moreover, spatiotemporal gait parameters did not differ significantly between the involved and uninvolved legs (all P > 0.05), and no differences in kinematic or kinetic parameters were observed. This study reports the effects of MFC free flap harvest on the knee muscle strength and locomotion of patients. For most biomechanical parameters investigated, there was no effect (positive or negative).

The EXIT (ex-utero intrapartum treatment) procedure - from the paediatric ENT perspective.

The main principle of the EXIT procedure is to maintain uteroplacental circulation with neonatal anaesthesia by controlled uterine hypotonia. This enables securing the foetal airways and decompress or resect large neck and mediastinal foetal masses. The authors present their experience with use of the EXIT procedure in 7 foetuses in whom evaluation and management of the airways were performed. In 4 patients, the neck mass was surgically removed in the neonatal period, in 1 the propranolol treatment was introduced. Two newborns died shortly after the EXIT procedure. The EXIT procedure allows the paediatric otolaryngologist to provide airway patency of newborns during delivery. Both ultrasound and MR imaging are crucial in the prenatal assessment of foetal head and neck masses. Their application in the evaluation of any foetal anomaly is essential for proper prognosis and treatment. Maternal monitoring for complications such as polyhydramnios and preterm labour are important in planning and desirability of the EXIT procedure.

Cytotoxic activities of Mannich bases of chalcones and related compounds.

Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines. The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells. In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes. Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared. In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells. A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar. For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group. In addition, the IC50 values in all three screens correlated with the redox potentials of a number of Mannich bases. X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity. While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro. Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties. Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule.

Conformational and quantitative structure-activity relationship study of cytotoxic 2-arylidenebenzocycloalkanones.

Various 2-arylideneindanones 1, 2-arylidenetetralones 2, and 2-arylidenebenzosuberones 3 were synthesized with the aim of determining the relative orientations of the two aryl rings which favored cytotoxicity. Molecular modeling of the unsubstituted compound in each series revealed differences in the spatial arrangements of the two aryl rings, and evaluation of these compounds against P388, L1210, Molt 4/C8, and CEM cells as well as a panel of human tumor cell lines indicated that in general the order of cytotoxicity was 3 > 2 > 1. In particular 2-(4-methoxyphenylmethylene)-1-benzosuberone (3k) had the greatest cytotoxicity, possessing 11 times the potency of the reference drug melphalan when all five screens were considered. Series 3 was considered in further detail. First, excision of the aryl ring fused to the cycloheptanone moiety in series 3 led to some 2-arylidene-1-cycloheptanones 4 which had approximately one-third of the bioactivity of the analogues 3. Second, in some screens cytotoxicity was correlated negatively with the sigma values and positively with the MR constants of the substituents in the arylidene aryl ring of 3. Third, X-ray crystallography of five representative compounds (3i,k-n) revealed differences in the locations of the aryl rings which may have contributed to the variations in cytotoxicity. Finally three members of series 3 inhibited RNA and protein syntheses and induced apoptosis in human Jurkat T cells. This study has revealed that 2-arylidene-1-benzosuberones are a group of useful cytotoxic agents, and in particular 3k serves as a prototypic molecule for subsequent structural modifications.

Cytotoxic 2,6-bis(arylidene)cyclohexanones and related compounds.

A number of 2-arylidenecyclohexanones 1, 2, 6-bis(arylidene)cyclohexanones 2 and related Mannich bases 3-5 were prepared. Various torsion angles as well as atomic charges on olefinic carbon atoms were determined by molecular modelling on all compounds. These molecules showed cytotoxicity towards murine P388 and L1210 cells as well as to human Molt 4/C8 and CEM T-lymphocytes. The average cytotoxicity of the dienones 2 was more than three times greater than was found with the monoarylidene analogues 1, and, in general, were slightly more cytotoxic than the Mannich bases 3-5. A number of the compounds displayed potency towards a panel of human tumour cell lines and most of the representative compounds in series 2-5 were selectively toxic to colon cancers and leukaemic cells.

Cytotoxic and anticancer properties of some 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinols and related compounds.

A previous investigation revealed that various 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinols and related vinylogs were cytotoxic to both murine and human tumour cell lines. In particular, 1a and 2a were identified as useful prototypic molecules. Structural modifications of 1a and 2a were accomplished leading to 1b-e and 2b-d which displayed cytotoxicity towards murine P388 and L1210 leukemic cells as well as human Molt 4/C8 and CEM T-lymphocytes. Among the new compounds, the greatest average potencies against these four cell lines were displayed by 1b and 2b, having approximately one quarter and one half of the potency of the reference drug melphalan, respectively. The synthesis and bioevaluation of three open chain analogues of 1b-d, namely 3a-c, did not reveal unequivocally whether this molecular modification led to increases in cytotoxicity or not. Compounds 2a-d were substantially more active than melphalan using a panel of human tumour cell lines. In addition, several compounds displayed selective toxicity to both colon and leukemic cancer cells. The 4-piperidinol 2d was active in the in vivo hollow fibre assay. This study revealed compounds with greater potency than 1a and 2a and it has confirmed that 1,3,4-trisubstituted-4-piperidinols and related compounds are novel groups of candidate antineoplastic and anticancer agents.

The use and cost of health services prior to death: a comparison of the Medicare-only and the Medicare-Medicaid elderly populations.

Lack of data has limited research into the high cost and ethical dilemmas associated with care of the dying elderly. This study is based on a five-year, person-specific file of Medicare and Medicaid use and cost data for residents of Monroe County, New York, over the age of 65. It examines and compares utilization and expenditure patterns of the Medicare-only and the Medicare-Medicaid (dually eligible) decedents in 1988. Examination of reimbursement for nonacute services, not covered by Medicare, reveals that services for the "older old" may be less costly immediately prior to death than for younger decedents. However, when expenses in the year prior to the year of death are also counted, services for the dually eligible, older old decedents appear to be neither more nor less costly than for younger decedents. Distribution of expenses does, however, vary considerably with age. The younger decedents, aged 65 to 74, use 55 percent of their medical resources on hospital care, paid for by Medicare; the older old use 26 percent for hospital services and pay 67 percent for supportive care, reimbursed by Medicaid. The study suggests that medical intervention associated with dying is utilized more often and at a higher cost by younger decedents.

Spending-down to Medicaid in the nursing home and in the community. A longitudinal study from Monroe County, New York.

Medicaid spend-down continues to be of considerable interest in public policy discussions regarding long-term care financing reforms. Yet, "measuring" of spend-down has been difficult because of data limitations. This study focuses on patterns of spend-down affecting those who become Medicaid eligible both in nursing homes and in the community. The study uses a longitudinal, person-specific, merged Medicare and Medicaid claims and eligibility file constructed for Monroe County, New York. The analyses show that 27% of those who enter nursing homes as private pay can be expected to spend-down to Medicaid while in a nursing home. The spend-downers remain in nursing homes for a prolonged time, with 63% staying for more than 3 years. On admission, spend-downers appear somewhat more likely than those who remained private pay or Medicaid throughout to have been less disabled in terms of activities of daily living (ADL). The community-based spend-down group is larger, younger, and more heavily represented by those who are poor or marginally poor, than the nursing home-based spend-down population. Their spend-down to Medicaid appears to have been triggered principally by the cost of acute medical care not covered by Medicare or another third-party payer. It is this population of the elderly that would have been the principal beneficiary of the short-lived 1989 Medicare Catastrophic Coverage Act. The results of this study indicate that neither the existing private long-term care insurance policies nor the currently circulating public coverage proposals alone are sufficient to protect older persons, at risk of spend-down to Medicaid, from impoverishment. Effective long-term care financing reform will need to create partnerships between public and private insurance, rather than look at them as competing options.

[Expert evaluation of temporary disability of workers performed by physicians in health care and prevention]. / Expertise de l'incapacité temporaire de travail effectuée par les médecins de l'assistance de cure et prophylaxie.

By means of the inquiry method, informations were obtained regarding the appraisement of temporary working incapacity, performed by 76 doctors, of whom 45 general practitioners and 31 factory doctors. In addition to the data related to the inquiry, the questionnaire contained also the description of five clinical cases. The conclusions of the appraisement and the causes for refusal to deliver a medical certificate are discussed.