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Biomedical subjects

R Becker

Publications and source records attributed to R Becker.

At least 37 records · Page 2Linked to original sources

Expression of vascular endothelial growth factor during healing of the meniscus in a rabbit model.

Our aim was to investigate vascular endothelial growth factor (VEGF) expression after lacerations of a meniscus in a rabbit model. Specimens of meniscus were examined using immunohistochemistry, enzyme-linked immunoassay and the reverse transcription polymerase chain reaction after one, two, five or ten weeks. In the periphery of the meniscus 90% of the lacerations had healed after five and ten weeks, but no healing was observed in the avascular area. Expression of VEGF protein and VEGF mRNA was found in the meniscus of both the operated and the contralateral sites but both were absent in control rabbits which had not undergone operation. The highest expression of VEGF was found in the avascular area after one week (p < 0.001). It then lessened at both the vascular and avascular areas, but still remained greater in comparison with the control meniscus (p < 0.05). Despite greater expression of VEGF, angiogenesis failed at the inner portion. These findings demonstrated the poor healing response in the avascular area which may not be caused by an intrinsic cellular insufficiency to stimulate angiogenesis.

Animals↗

Histological findings of tendon-bone healing following anterior cruciate ligament reconstruction with hamstring grafts.

BACKGROUND: The purpose of the study was the histological examination of tendon-bone healing of hamstring grafts after anterior cruciate ligament (ACL) reconstruction. METHODS: During five arthroscopies done 6-14 months after ACL reconstructions, biopsies of the wall of the former drilled femoral canal were obtained. Four patients were primarily operated on using a suspending device (Endobutton, Acufex Microsurgical, Mansfield, MA, USA, and Transfix, Arthrex, Naples, FL, USA) for femoral fixation, one patient was reconstructed with a biodegradable interference screw directly inserted between the tendon and the wall of the canal. Biopsies were obtained using a tube harvester during re-arthroscopy. Three grafts were stable, two grafts were unstable, and revision of the ACL was performed. RESULTS: Histologically, in the four cases of reconstruction with a button or a rectangular pin, biopsies resembled granulation tissue without insertion of fibers between the tendon tissue and the bony wall. A wide area of woven bone was noted adjacent to the pre-existing lamellar bone. In contrast, the tendon-bone junction in the knee reconstructed with a biodegradable interference screw resembled a zone of metaplastic fibrous cartilage between the tendon graft and the lamellar bone. Collagen fibers connecting the tendon-bone interface occurred under polarized light microscopy. CONCLUSION: We conclude that the use of hamstring grafts for ACL reconstruction can lead to different histological pattern of tendon-bone healing. Micromotion of the hamstring graft inside the drilled canal can be play a role in tendon-bone healing.

Adult↗

Epignathus: always a simple teratoma? Report of an exceptional case with two additional fetiforme bodies.

We report on a case of a fetal epignathus combined with two fetus-like structures resembling acardius acranius. The anomaly was detected at 23 weeks of gestation and led to termination of pregnancy at 24 weeks. This is the first description of epignathus with parasitic fetuses detected prenatally. It shows that the boundary between fetal teratoma and multiple pregnancy in special cases may be difficult to define.

Abnormalities, Multiple↗

Comparative follow up of patients with implanted cardioverter-defibrillators after induction of sustained monomorphic ventricular tachycardias or ventricular fibrillation by programmed stimulation.

OBJECTIVE: To investigate the prognostic value of induced monomorphic ventricular tachycardia (VT) and ventricular flutter or fibrillation (VF) during programmed electrical stimulation in patients with a high risk for sudden arrhythmogenic cardiac death. DESIGN: Prospective cohort study. PATIENTS: 102 patients at high risk for arrhythmogenic sudden cardiac death who received an automated implantable cardioverter-defibrillator (AICD) were evaluated. 56 patients received the AICD for primary prevention and 46 for secondary prevention. 58 patients had induction of a monomorphic VT (VT group) and 44 had induction of a polymorphic VT, ventricular flutter, or ventricular fibrillation (VF group) during programmed electrical stimulation. Average follow up was 20 months in both groups. MAIN OUTCOME MEASURES: Appropriate AICD protocol. RESULTS: In patients who received the AICD for primary prevention, 16 of 32 patients in the VT group, compared with only four of 24 patients in the VF group, received an appropriate AICD protocol (p = 0.02). In the entire study population, 479 appropriate AICD protocols were recorded in 28 (48%) patients in the VT group and 28 appropriate protocols in 11 (25%) patients in the VF group. Cumulative Kaplan-Meier event-free survival curves were significantly different (p = 0.02). CONCLUSION: Induction of VF during programmed electrical stimulation is of no prognostic value even in high risk patients without previously documented ventricular fibrillation.

Aged↗

Induction of DNA breaks and apoptosis in crosslink-hypersensitive V79 cells by the cytostatic drug beta-D-glucosyl-ifosfamide mustard.

To study molecular aspects of cytotoxicity of the anticancer drug beta-D-glucose-ifosfamide mustard we investigated the potential of the agent to induce apoptosis and DNA breakage. Since beta-D-glucose-ifosfamide mustard generates DNA interstrand crosslinks, we used as an in vitro model system a pair of isogenic Chinese hamster V79 cells differing in their sensitivity to crosslinking agents. CL-V5B cells are dramatically more sensitive (30-fold based on D(10) values) to the cytotoxic effects of beta-D-glucose-ifosfamide mustard as compared to parental V79B cells. After 48 h of pulse-treatment with the agent, sensitive cells but not the resistant parental line undergo apoptosis and necrosis, with apoptosis being the predominant form of cell death (70 and 20% of apoptosis and necrosis, respectively). Apoptosis increased as a function of dose and was accompanied by induction of DNA double-strand breaks in the hypersensitive cells. Furthermore, a strong decline in the level of Bcl-2 protein and activation of caspases-3, -8 and -9 were observed. The resistant parental cells were refractory to all these parameters. Bcl-2 decline in the sensitive cells preceded apoptosis, and transfection-mediated overexpression of Bcl-2 protected at least in part from apoptosis. From the data we hypothesize that non-repaired crosslinks induced by beta-D-glucose-ifosfamide mustard are transformed into double-strand breaks which trigger apoptosis via a Bcl-2 dependent pathway.

Animals↗

Combined intrathecal baclofen and morphine infusion for the treatment of spasticity related pain and central deafferentiation pain.

OBJECTIVES: Complex pain syndromes due to spasticity and central deafferentation often fail to respond to medical therapy and create challenging problems in the pain management. So far, only spasticity associated musculosceletal pain has been reported to respond to intrathecal baclofen application [1, 2]. METHODS: We report the treatment of severe neuropathic pain in a patient with ED and the combined intrathecal application of baclofen and morphine in 5 patients with severe spasticity related pain. RESULTS: Continuous intrathecal baclofen infusion resulted in a pain free period of 20 months in the patient with ED. Patients with spasticity treated with intrathecal application of baclofen and morphine were pain free for a mean period of 2 years. CONCLUSION: Intrathecal baclofen and morphine application proved to be effective in spasticity related and central deafferentation pain and should therefore be considered in the management of these patients.

Afferent Pathways↗

The punctate midline myelotomy concept for visceral cancer pain control--case report and review of the literature.

INTRODUCTION: Nauta et al. first reported on a successful punctate midline myelotomy (PMM) at the spinal cord Th 10 level for the treatment of intractable pelvic cancer pain. CASE STUDY: The authors published another case history of a patient with multiple anaplastic carcinomas of the small intestine, peritoneal carcinosis and retroperitoneal lymphomas, suffering from severe visceral pain in the hypo-, meso-, and epigastrium. Nauta's PMM was successfully performed at the level Th 4. Narcotic medication was tapered from 30 mg i.v. morphine per hour preoperatively to 5 mg per hour within 5 days postoperatively. Pain intensity decreased from 10 to 2-3 on the visual analog scale. Only minor transient side effects appeared postoperatively. Pain reduction remained until the patient died from the extended disease five weeks later. DISCUSSION: Meanwhile Nauta et al. reported on 5 additional patients, in whom PMM led to a sufficient pain reduction. Another paper reported on sufficient control of visceral pain due to advanced stomach cancer after a modified Th 1-2 PMM. CONCLUSION: PMM sufficiently controls not only pelvic visceral pain, but also visceral pain generated in the meso- and epigastrium. The findings support the concept of a midline dorsal column visceral pain pathway.

Abdominal Neoplasms↗

[Drugs for supplementation in cataract surgery with a laryngeal mask].

BACKGROUND: We compared intraocular pressure (IOP), vitreous pressure and several anaesthesiological parameters for patients who underwent cataract surgery with propofol anaesthesia, laryngeal mask and different supplementations with reference to the effect of S-ketamin in particular. PATIENTS AND METHODS: In 4 groups with 15 patients cataract surgery (phacoemulsification) was carried out using anaesthesia with propofol, laryngeal masks and spontaneous breathing if possible, supplementation with propofol (0.6 mg/kg, group 1), S-ketamin (0.3 mg/kg, group 2), ketamin (0.6 mg/kg, group 3) or fentanyl (0.5 microgram/kg, group 4); IOP measurement with tonopen XL and scoring vitreous pressure at different times during anaesthesia (score 0-3). RESULTS: For IOP and vitreous pressure, none of the different supplementations showed a significant difference. Insertion of the laryngeal mask did not cause a rise in intraocular pressure. The number of patients with spontaneous breathing during the operation in group 4 was significantly lower than in groups 1-3. No significant differences were observed between the different anaesthesiological parameters. CONCLUSION: S-Ketamin had no significant effect on IOP and vitreous pressure during phacoemulsification. It offers a safe "handling" of patients because of a high spontaneous breathing rate and lower concentration compared to Ketamin.

Aged↗

Autosomal recessive type of Adams-Oliver syndrome: prenatal diagnosis.

We report on three pregnancies complicated by Adams-Oliver syndrome in a consanguineous Turkish couple. Two cases were correctly diagnosed prenatally at 22+3 and 13+0 weeks gestation following the first case of Adams-Oliver syndrome in which severe anomalies of the extremities were observed at 26+5 weeks' gestation. In this first case, the diagnosis of Adams-Oliver syndrome was made following termination of pregnancy at 27+2 weeks' gestation. In all three cases, autopsy was performed. All fetuses showed anomalies of the extremities, aplasia cutis and symmetric defects of the skull, with bone being replaced by collagenous tissue. Although there have been numerous cases of the postnatal diagnosis of Adams-Oliver syndrome following termination of pregnancy, this is the first description of the prenatal diagnosis of this disorder.

Abortion, Induced↗

Evidence for greater oxidative substrate flexibility in male carriers of the Pro 12 Ala polymorphism in PPARgamma2.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene is associated with reduced type 2 diabetes risk and increased insulin sensitivity. It is possible that the oxidative shift from lipid to glucose as a fuel is more efficient in Ala allele carriers. To test this hypothesis, we examined carbohydrate and lipid oxidation by indirect calorimetry in lean, glucose tolerant subjects with (X/Ala, n = 25) and without the Pro12Ala polymorphism (Pro/Pro, n = 73) basally and after insulin stimulation during a 2-hour eugylcaemic hyperinsulinaemic clamp. Insulin sensitivity was non-significantly greater in X/Ala (0.13 +/- 0.01 micromol/kg/min/pM) than in Pro/Pro (0.12 +/- 0.01 micromol/kg/min/pM, p = 0.27). Basally, there were no lipid nor carbohydrate oxidation differences between the groups. Interestingly, the decrease in lipid oxidation during insulin stimulation was significantly greater in male X/Ala (- 0.51 +/- 0.06 mg/kg/min) than in male Pro/Pro (- 0.35 +/- 0.04 mg/kg/min, p = 0.03). No difference was observed in females. Analogously, the change in carbohydrate oxidation in male X/Ala (1.34 +/- 0.2 mg/kg/min) was significantly greater than in male Pro/Pro (1.03 +/- 0.12 mg/kg/min, p = 0.05). The respiratory quotient increased more, but not significantly more, in male X/Ala (0.11 +/- 0.01) than in male Pro/Pro subjects (0.08 +/- 0.01, p = 0.08) but similarly in females. These results indicate that the mechanism by which the Ala allele improves insulin sensitivity might involve enhanced suppression of lipid oxidation permitting more efficient (predominantly non-oxidative) glucose disposal. It is unclear why this could be demonstrated only in males, although gender differences in substrate oxidation are well documented.

Adult↗

[Anterior cruciate ligament reconstruction - graft options and fixation techniques].

With the introduction of arthroscopy most of the surgeon have changed their technique in ACL-reconstruction from open to arthroscopically performed techniques. Several new techniques have been developed in the past, including new fixation devices and different grafts. The cruciate ligament reconstruction comprises a composition of both, the graft and the fixation to the bone. Well accepted autografts are the patellar midthird, the semitendinosus/gracilis or the quadriceps tendon. In special cases allografts are alternatives. The fixation can cause failure due to overstrain or creep during the postoperative period of healing. Considering their biomechanical properties, cruciate ligament reconstruction should aim for a graft behavior comparable with the native cruciate ligament. Results gained from basic science and clinical studies are reviewed in the following article.

Anterior Cruciate Ligament↗

[Gait anlysis in patients with osteoarthritis of the knee before and after total knee replacement].

AIM: The reduction in quadriceps femoris muscle activation is considered to be one of the major mechanisms involved in pathological motion patterns in patients with osteoarthritis (OA) of the knee. These activation deficits are, at least in part, reversible after total knee arthroplasty (TKA). The purpose of this study was to investigate the effects of TKA on motion patterns in patients with OA of the knee. METHOD: 50 patients with knee OA were investigated prior and at 33 +/- 8 months after unilateral TKA. The control group comprised 17 healthy volunteers matched to the study group with respect to age. The gait analysis was performed with an optoelectronic motion analysis system (Elite(R), Italian). RESULTS: Step length, step duration and velocity increased after surgery (p < 0.05), but remained lower than the values of the controls (p < 0.05). Extension angles in stand and swing phase remained unchanged and significantly lower when compared to control values (p = 0.01, p = 0.04). Flexion angles in swing (p = 0.02) and stand phase (p = 0.01) increased on the operated side and were significantly higher than the flexion angle in the control group (p = 0.02, p = 0.03). Reextension in stand phase, which was investigated for quantification of functional range of motion, increased bilaterally after surgery (p < 0.01), but remained lower than the reextension of the controls (p </= 0.01). CONCLUSION: Although a significant improvement of pathological motion patterns in patients with OA of the knee after unilateral TKA occurred, a deficit persisted 33 +/- 8 months after surgery. The improvement of functional range of motion in stand phase was only caused by increased flexion. No influence was found with gait analysis on extension after TKA.

Aged↗

Phase I clinical trial on adjuvant active immunotherapy of human gliomas with GD2-conjugate.

The objective of this study was to determine the feasibility, toxicity, and potential therapeutic benefits of an adjuvant active immunotherapy using a tumour specific ganglioside (GD2) conjugate for the adjuvant treatment of recurrent or progressive gliomas. Seven patients with proven GD2 expression in surgical specimens underwent a vaccination course with GD2-KLH/MPL-A conjugate. The follow-up was performed according to WHO guidelines regarding common toxicity criteria. Antibody titres against the ganglioside and the adjuvants were analysed. All patients developed a local type 4 reaction. Anti-GD2-antibody titres could not be detected, despite high titres against the immunoadjuvants. No tumour regression was observed. The disease remained stable for a median of 21.5 weeks (6-34 weeks). The median survival time after the first immunization was 47 weeks. The medial total survival time was 76 weeks. Adverse effects have not been observed. Active GD2-KLH/MPL-A immunization was technically feasible, but did not elicit anti-GD2 antibody generation.

Adjuvants, Immunologic↗

Examination of young children with Lea symbols.

AIMS: In order to establish normal values and interocular differences of visual acuity, Lea symbols were applied to neurologically and ophthalmologically normal children. METHODS: 385 children (21-93 months old) were examined, within a routine check up in an urban paediatric practice where Lea symbol acuity (LS) was measured. Of these children, 90 were re-examined in hospital comparing Lea symbol acuity (LS) and Landolt C acuity (LC). Strabismus, ametropia, and any organic eye disease were excluded. RESULTS: In the paediatric practice, LS could be measured on both eyes in 54% of the children. In the age group above 36 and 48 months the success rate was 76% and 95%, respectively. Acuity in the paediatric practice ranged from 0.1 to 2.0 (median 1.25) in the whole group. Interocular acuity difference was one line or less in 80%. In the hospital, LS and LC could be measured on both eyes of 77% and 48% of the 90 children, respectively. Cooperation increased with age. LS in the hospital ranged from 0.32 to 2.0 (median 1.0) and LC from 0.16 to 1.25 (median 0.8). Interocular difference of LS acuity was one line or less in 90%. CONCLUSION: Lea symbols were found to be useful for visual acuity assessment in early childhood. Significant variability of visual acuity in this age group is caused by cooperation. When monocular measurements are possible on both eyes, however, the intraindividual interocular difference of visual acuity usually does not exceed one line.

Child, Preschool↗

cAMP-dependent phosphorylation of CYP2B1 as a functional switch for cyclophosphamide activation and its hormonal control in vitro and in vivo.

An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in vitro and in vivo. We found first that only part of the total CYP2B1 pool undergoes phosphorylation. This part is fully inactivated. Second, phosphorylation of CYP2B1 in intact hepatocytes reduced by up to 75% toxification of CPA to mutagenic metabolites (totally dependent on the same preferentially CYP2B-catalyzed 4-hydroxylation of CPA as is the generation of highly cytotoxic species). Third, the phosphoacceptor-serine 128 of CYP2B1 in the consensus sequence for interaction with the protein kinase A represents an on/off switch for the activation of CPA depending on the phosphorylation conditions in the cell. Fourth, evidence is presented that the above-described events also occur in vivo. In conclusion, a successful therapy with CPA, helped by forced expression of CYP2B1 in tumor cells (as recently proposed) will, in addition, be profoundly modified by its phosphorylation status.

Animals↗

Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting.

BACKGROUND: Evidence-based clinical practice guidelines recommend the use of warfarin sodium for stroke prevention in most patients with atrial fibrillation (AF) who do not have risk factors for hemorrhagic complications, irrespective of age. METHODS: The medical records of all residents of a convenience sample of long-term care facilities in Connecticut (n = 21) were reviewed. The percentages of all patients with AF (AF patients) and ideal candidates for warfarin therapy (ie, AF patients with no risk factors for hemorrhage) who received warfarin were determined; for patients receiving warfarin, the percentage of days spent in the therapeutic range of international normalized ratio (INR) values (2.0-3.0) was also assessed. The relationship between receipt of warfarin and the presence of stroke and bleeding risk factors was assessed in multivariate models. RESULTS: Atrial fibrillation was present in 429 (17%) of the 2587 long-term care residents. Overall, 42% of AF patients were receiving warfarin. However, only 44 (53%) of 83 ideal candidates were receiving this therapy. In residents who received warfarin therapy, the therapeutic range of INR values was maintained only 51% of the time. The odds of receiving warfarin in the study sample decreased with increasing number of risk factors for bleeding and increased (nonsignificant trend) with increasing number of stroke risk factors present. CONCLUSIONS: Atrial fibrillation is very common among residents of long-term care facilities. Even among apparently ideal candidates, warfarin therapy is underused for stroke prevention in patients with AF. Prescribing decisions and monitoring related to warfarin therapy in the long-term care setting warrant improvement.

Aged↗

Frequency of HPRT mutants in humans exposed to vinyl chloride via an environmental accident.

The mutant frequency (MF) in the hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) locus of peripheral blood T-lymphocytes was measured in a population environmentally exposed to vinyl chloride - a toxic and carcinogenic substance through an accidental release into the atmosphere. It was compared to MF in a control group of unexposed individuals. Both groups were re-investigated in a follow-up study, 2 years later. No significant difference could be observed in MF between exposed and controls either at the accident nor in the follow-up study. Approximately the same mean HPRT mutant frequencies were observed for both groups in T-lymphocytes from blood samples obtained shortly after the accident and from the follow-up blood samples. Both groups showed a higher mean MF in the re-investigation samples which is most probably due to the significantly lower average cloning efficiency (CE) under non-selective conditions and because of the inverse relationship between CE and MF. The exposed population showed a higher mean T-cell CE at the initial blood sampling as compared to the control group. The concurrent cytogenetic analyses of peripheral lymphocytes showed a significant increase in cells with aberrations in the exposed population. Clastogenic but not mutagenic activity of vinyl chloride was observed in our study.

Adult↗