Primary Hemiarthroplasty for Proximal Humeral Fractures in the Elderly: Long-Term Functional Outcome and Social Implications

Abstract Background: Primary shoulder hemiarthroplasty is an established treatment modality for complex fractures of the proximal humerus. Long-term functional outcome is often disappointing. However, little is known about social implications particularly in the elderly. Methods: A single-institution case series of consecutive geriatric patients (age > 70 years) treated with shoulder hemiarthroplasty for complex fractures of the proximal humerus between 1994 and 1997 was analysed. Postoperative morbidity, long-term function, radiological outcome and social implications were evaluated. Results: Seventy-seven patients fulfilled the study criteria. Median age at the time of operation was 80 years (range 70–93 years). Systemic and local postoperative complications were observed in 8% including 2 patients (3%) with revision surgery. Postoperative mortality was 1%. Forty-eight patients (62%) were available for follow-up (median 49 months, range 25–80 months), 22 (29%) died from causes unrelated to hemiarthroplasty before follow-up and 7 patients (9%) did not attend follow-up examination. Median Constant-Murley score was 41 points (range 17–77 points). Long-term results concerning pain were satisfying. The Oxford shoulder score ranged from 14 to 40 (median 30). Forty-one patients (85%) still lived in their original environment and managed their daily life independently despite poor shoulder function. Four patients (8%) lived in a retirement home and 3 (6%) in a nursery home. Eighty percent of our patients were still able to use public transportation, do the daily shopping and wash their whole body by themselves. Conclusion: Most patients managed their daily life independently despite poor shoulder function.     

A Randomized Pilot Study of Behavioral Treatment to Increase Calorie Intake in Toddlers With Cystic Fibrosis

This pilot study examined a behavioral treatment to increase calorie intake in toddlers with cystic fibrosis. Eight toddlers were randomly assigned to behavioral plus nutrition (BEH) or nutrition intervention (NTR) conditions. Calorie intake and weight were measured at pre- and posttreatment. The BEH group showed a trend for changes in calorie intake pre- to posttreatment (p = .07; 40% increase). Results for the BEH and NTR groups did not differ significantly. Most participants achieved weight gains consistent with normal growth. Seventy-five percent had not shown this pattern during the year prior to intervention. These results support the feasibility and potential for behavioral interventions in this age group.     

Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: Treatment results and prognostic factor analysis in a multi-centre trial

Background: With CHOP, the standard protocol of recent decades,about 30% of long-term survival has been reported. A numberof studies using more aggressive multidrug regimens or alternatingchemotherapies have recently suggested higher CR rates and increasedsurvival. In 1989 we reported similar results with a combined-modalitytreatment administering 6 cycles of CHOP supplemented with etoposideand an involved field irradiation for patients in PR or CR. Patients and methods: To confirm the efficacy of this approach,we initiated a prospective randomised trial comparing 4 cyclesof CHOP-VP 16 (CHOEP) with 4 cycles of two alternating regimens,‘hCHOP and IVEP’. One hundred seventy-five patientswith high-grade non-Hodgkin's lymphomas stages II-IV were stratifiedfor age, stage and LDH and randomised to receive either fourcycles of cyclophosphamide, doxorubicin, vincristine, etoposide,prednisolone (CHOEP) in arm A or four cycles of chemotherapywith a dose-intensified CHOP (hCHOP) alternating with ifosfamide,etoposide, vindesine, prednisolone (IVEP) in arm B. After fourcycles of chemotherapy an involved field irradiation with atotal dose of 35 Gy was given to all patients demonstrated tobe in complete or partial remission. Results: Of the 185 randomised patients, 175 were eligible and171 evaluable for response and survival. One hundred forty-sixof the 171 patients (85%) achieved complete remission (CR) with87% and 84% CRs in arms A and B, respectively. With a medianfollow-up of 36 months the estimated overall survival at 2 yearsis 66% and 73% for arms A and B. The percentage of all patientsin first CR is estimated to be 59% and 55% at 2 years for armsA and B, respectively. None of the differences in CR rate, survival,or relapse-free survival are statistically significant. Multivariateanalysis of subgroups incorporating the factors of sex, age,performance status, stage, B symptoms, bulky disease, LDH andhistology revealed that only stage and LDH were factors whichindependently affected outcome. The estimated 2-year survivalrate of patients with stages II, III and IV is predicted tobe 84%, 62% and 52%, respectively. Patients with LDH >250U/I have an estimated survival of 52% at 2 years versus 84%for patients with LDH     

Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta

Background: The placental transfer of the a₂ receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more %-selective agonist dexmedetomidine.
Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.
Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% ( P <0.05), while 11.3 (SD 3.3)% ( P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively ( P <0.05).
Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine.     

Antitumor activity of thaliblastine (NSC-68075) in experimental ovarian tumor cell lines sensitive and resistant to cisplatin.

Cytotoxicity of thaliblastine (thalicarpine, TBL; NSC-68075) and/or cisplatin (DDP) in DDP-sensitive (O-342) and-resistant (O-342/DDP) rat ovarian tumor cell lines was comparatively determined using the MTT assay. The 50% inhibitory dose (ID50) of DDP was found to be 6.2 microM in O-342 cells and 23.4 microM in O-342/DDP cells, while, vice versa, the ID50 of TBL was 39.3 micrograms/ml in the sensitive line and 27.3 micrograms/ml in the resistant line. Furthermore, simultaneous exposure of cells to DDP and TBL showed a significant superiority over DDP alone in O-342 cells, as evaluated with variance analysis (P less than 0.001). This enhancing effect of TBL on DDP cytotoxicity, however, was not observed in the resistant cells.     

Brief report: child-rearing practices of caregivers with and without a child with juvenile rheumatoid arthritis: perspectives of caregivers and professionals

OBJECTIVE: To evaluate predictions from professionals in pediatric rheumatology regarding the child-rearing practices of caregivers of children with juvenile rheumatoid arthritis (JRA) and healthy classmates. METHODS: Sixteen professionals identified items from the Child-Rearing Practices Report (CRPR) that were expected to differentiate between caregivers of children with JRA (64 mothers, 45 fathers) and caregivers of healthy classmates (64 mothers, 40 fathers). Families were interviewed, and physician ratings of disease severity were obtained. RESULTS: Experts predicted difficulties in protectiveness, discipline, and worry. Ratings from parents of children with JRA showed modest agreement with the professionals, surprising similarity to controls, and a limited association with disease factors. CONCLUSIONS: Contrary to expert opinion, JRA has only a modest influence on some child-rearing practices. Educating health care providers may minimize misperceptions about caring for children with JRA, and screening parents of children with more severe disease may assist in allocating education and services for families.     

Gene therapy for sarcoma

Soft tissue sarcomas are mesenchymal tumors which respond poorly to systemic therapy. Recent studies suggest a higher response rate with an increased doxorubicin dosage. However, this was parallel with a profound hematotoxicity in 75% of patients. Transfer of the human multidrug resistance 1 (MDR1) gene to normal hematopoietic stem cells and transplantation may significantly reduce the hematotoxicity of anthracyclin-based chemotherapy. To test this concept of supportive gene therapy in advance of a clinical study, we transduced mobilized peripheral blood progenitor cells (PBPC) with the retroviral vector SF91m3 containing the human MDR1 gene, transplanted these cells to immune-deficient mice, allowed 6 weeks for engraftment to occur and treated the animals with MDR1-based chemotherapy. In the MDR1-transduced group the human leukocytes were significantly protected from the toxicity of chemotherapy (p < 0.05). While the gene transfer rate was in the range of 10% and thus comparable to recent clinical trials, the gene expression was 59% of transduced cells and thus significantly higher than previously reported for less-advanced vectors. On the other hand, ifosfamide, a drug which has been used successfully for stem cell mobilization, is active in soft tissue sarcoma. Due to these favorable characteristics sarcoma is an attractive target to test the efficacy of MDR1 gene therapy in a clinical setting. Gene therapeutic strategies may also be used to directly target sarcoma cells, e.g. by transfer of suicide genes. We found that adenoassociated virus 2 (AAV-2) vectors efficiently transduce human HS-1 and HT1080 sarcoma cells (>90%) while other tumor cell lines and primary human PBPC were less susceptible. The thymidine kinase (TK) suicide gene was cloned into an AAV-2 vector and a complete kill of TK-transduced HS-1 and HT1080 cells was observed following exposure to aciclovir or ganciclovir (GCV), while >90% of mock-transduced HS-1 cells survived at these dosages. Transplantation of those sarcoma cells to nonobese diabetic (NOD)/LtSz-severe-combined immunodeficient (scid)/scid (NOD/SCID) mice resulted in a survival of >5 months in the AAV-TK-transduced/GCV-treated group, while the mice in the mock-transduced/GCV-treated group had died after 3 weeks. These data show that soft tissue sarcomas are a particularly suitable model system for the development and clinical testing of new gene therapeutic concepts.     

Circulation of the poliovirus in endemic zones with children vaccinated by the oral polio vaccine

Strategies aiming to eradicate the poliovirus and poliomyelitis seek primarily to eliminate wild strains associated with the disease, by means of world wide vaccination campaigns using the oral attenuated vaccine (OPV). OPV contains attenuated viral strains which retain their replicating capacity in the digestive tract and thus induce the development of an antiviral local intestinal immunity and limit the circulation of the virus. In such a context, poliomyelitis surveillance laboratories should study above all cases of acute flaccid paralysis (AFP), highlighting the circulation of wild strains, identifying regional reservoirs and guiding vaccination strategies. Alongside circulation, there appear to be important genetic and phenotypic shifts in vaccinating strains, since the OPV is capable of preserving a reservoir of pathogenic stains and thereby impairing vaccination efficacy and the eradication of the virus. Furthermore, non-polio enteroviruses should be considered as a source of emerging pathogenic strains. These questions are being studied by the Pasteur Institute with the objective of determining the effects of OPV campaigns on the circulation of the poliovirus. We have studied the poliovirus vaccine and the circulation of wild strains in urban and peripheral urban areas in African countries known to be endemic for poliomyelitis (Central African Republic, Madagascar, C?te d'Ivoire). The study population consisted of children who had already been vaccinated and new-borns in the course of vaccination. We also evaluated the diffusion of the vaccine strains in their immediate environment. Genetic interchanges were taken into account. For children who received the 3-4 OPV doses, asymptomatic virus excretion was insignificant (0.4-2.4%). The rate of virus excretion in the surrounding environment of children in the course of being vaccinated was relatively low (1.76-5.3%). Our study also detected variant and recombinant strains.