Improving Metabolic Control Reverses the Histomorphometric and Biomechanical Abnormalities of an Experimentally Induced Bone Defect in Spontaneously Diabetic Rats

Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and to impair fracture-healing in both humans and animals. The objective of this study was to examine changes in the histomorphometric and mechanical parameters of bone and remodeling during bone-defect healing, depending on the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in humans.A standardized bone-defect model was chosen and based on blood-glucose values at the time of surgery (mg%), postoperative blood-glucose course (mg%), and postoperative insulin requirements (IU/kg). A total of 120 spontaneously diabetic BB/OK rats were divided into groups with a well-compensated (n = 60; 169 ± 102 mg%; 230 ± 126 mg%; and 2.2 ± 1.1 IU/kg) or poorly compensated (n = 60; 380 ± 159 mg%; 359 ± 89 mg%; and 5.4 ± 1.1 IU/kg) metabolic state. Sixty LEW.1A rats served as the normoglycemic controls (93 ± 19 mg%). Fifteen animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were processed undecalcified for quantitative bone histomorphometry and for biomechanical testing.Our study showed in terms of bone histomorphometry, within the first 14 days, that severe mineralization disorders occurred exclusively in the rats with a poorly compensated diabetic metabolic state with a highly significant (P < 0.001) or significant (P < 0.01) decrease of all fluorochrome-based parameters of mineralization, apposition, formation and timing of mineralization, as well as significantly decreased values of biomechanical properties (P < 0.05) in comparison to the spontaneously diabetic rats with a well-compensated metabolic state and to the control rats.Bone-defect healing in spontaneously diabetic BB/OK rats is retarded exclusively in a poorly compensated diabetic metabolic state. This study suggests that strictly controlled insulin treatment resulting in a well-compensated diabetic metabolic state will ameliorate the impaired early and late parameters of IDDM bone-defect healing.     

Knochenheilung in Bohrlochdefekten spontandiabetischer BB/OK-Ratten

The objective of this study was to examine changes in the histomorphometric and mechanical evaluation of the influence of the diabetic metabolic state on defect healing depending on the defect size in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats. Based on blood glucose levels and postoperative insulin requirements, 120 spontaneously diabetic BB/OK rats were divided into groups with well-compensated or poorly compensated metabolic state. Sixty LEW.1A rats served as the normoglycemic controls. Bone defects of different sizes were created proximal to the knee joint space and then allowed to heal for 2, 4, and 6 weeks. Bone defect sizes > or =0.8 mm showed significant differences in the structural calculations and bone defect sizes > or =1.2 mm showed a significant decrease of all fluorochrome-based parameters of mineralization exclusively in the rats with poorly compensated diabetic metabolic state as well as significantly decreased values of biomechanical properties in comparison to the spontaneously diabetic rats with well-compensated metabolic states and to the control rats. Bone repair of minor bone defects is independent of the diabetic metabolic state in the spontaneously diabetic BB/OK rats. With controlled insulin therapy and resultant well-compensated diabetic metabolic state, severe mineralization and biomechanical disorders in healing of larger bone defects in the poorly compensated diabetic metabolic state of the experimental animal can be avoided.     

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs

BACKGROUND: Amino-penicillins are a major cause of delayed-type reactions to penicillins. OBJECTIVES: The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. METHODS: We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. RESULTS: A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. CONCLUSIONS: These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.     

Allergische Berufsdermatosen

Zusammenfassung In kürzlich veröffentlichten Begutachtungsempfehlungen für Berufskrankheiten Nr. 5101 der Anlage zur BKV wird als In-vitro-Test nur ein Atopiescreening im Sinne von Pricktestungen und/oder IgE-Diagnostik zur Diagnosesicherung als notwendig bezeichnet. Weitere Indikationen sind Latexsensibilisierung, berufsbedingte Penizillinsensibilisierung und Insektengiftallergie. Der Lymphozytentransformationstest kann hilfreich sein in der Differenzierung Sensibilisierung vs. Irritation, Ersatz des Patchtestes mit toxikologisch bedenklichen Substanzen und bei berufsbedingter Arzneimittelsensibilisierung.     

Influence of intertrochanteric varisation osteotomy on the gait of children with Perthes disease

BACKGROUND: The purpose of this study was to investigate possible effects of intertrochanteric varisation osteotomy on the gait of children with Perthes disease. PATIENTS: Clinical and radiographic examinations and gait analysis were conducted on 50 children. METHOD: Gait analysis was conducted using the GANGAS system. RESULTS: Despite predominantly very good or good results shown by the clinical and radiographic examinations, gait analysis detected various functional deficits. CONCLUSIONS: The examinations show that for the group of patients described, gait analysis is a valuable method of recording functional deficits and early recognition of the need for postoperative, physiotherapeutic treatment, thus helping to avoid chronificating alterations of the gait and, consequently, potential secondary damage.     

Reconstruction of bone defect by vascularized fibular transfer after failed wrist arthroplasty

A bone defect of 14 cm resulted after wrist implant removal because of loosening in a 46-year-old patient.Performing wrist arthrodesis the defect was reconstructed by a vascularized fibular transfer.Solid bone fusion was complete in six weeks.Free function of the digits was seen because of length reconstruction.     

Intratumoral induction of thymidylate synthase mRNA by 5-FU in colorectal cancer patients: association with survival

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism. Thymidylate synthase (TS) is inhibited to form an inactive ternary complex by 5-fluoro-dUMP and is considered to be a target enzyme of 5-FU treatment. Two enzymes, DPD and TS, have been reported to be major determinants of individual sensitivity to 5-FU, and it has been reported that TS mRNA levels are modified by 5-FU treatment. We investigated their impact on treatment efficacy in colorectal cancer patients. TS and DPD mRNA levels, which correlated to the corresponding enzyme activities, were quantified in tumor tissues before and after treatment in 40 advanced colorectal cancer patients who had been treated with Doxifluridine (5'-DFUR) for 14 days before surgery. Furthermore inter-individual variations of TS mRNA levels after 5-FU treatment were found, and the individual TS induction varied between patients (0.2-2.4). Increased TS mRNA levels were found in 19 out of 40 cases. The samples were divided into two groups according to their TS mRNA induction (< or >1; TS/beta-actin ratio after treatment divided by values prior treatment) and compared with tumor reduction and survival. TS and DPD mRNA levels in tumor biopsies before treatment were not related to 5-FU responses by histological evaluations in this study. However the efficacy of 5-FU treatment was enhanced in patients with no or low TS mRNA induction (odds ratio: 6.2, p<0.05). Furthermore, longer periods of survival were observed in the group without increased TS mRNA levels. These findings suggest that TS mRNA was induced by 5-FU treatment, and the overall induction level varied between individuals. Therefore, the estimation of TS mRNA induction may be useful to predict the efficacy of 5-FU treatment.