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L Kirsch

Publications and source records attributed to L Kirsch.

17 recordsLinked to original sources
PubMed2001

A genetic analysis of the cytological region 46C-F containing the Drosophila melanogaster homolog of the jun proto-oncogene.

The cytogenetic region 46C-F on the right arm of Drosophila chromosome 2, which contains the homolog of the human jun proto-oncogene, has been genetically mapped and characterized. This project led to the identification and characterization of a Jra (jun-related antigen) mutation, which has been described in detail elsewhere. Three mutagens, EMS, DEB and gamma-rays, were used to isolate 126 lethal lines for this interval. Complementation analysis of the 126 lethal lines identified 29 lethal complementation groups in the region; nine of which have now been correlated with known genes or phenotypes. The region has been subdivided into ten intervals using various small deletions, seven intervals in 46C/D and three intervals in 46E/F. Sixteen P-element lines have been mapped to this interval and are allelic to eight of our complementation groups. The remaining unidentified complementation groups have been analyzed for critical phase, which is when the first observable defect arises and/or when death occurs. There are twelve embryonic lethal groups and seven larval lethal groups. Three lines show visible abnormalities in gut and tracheal development prior to death.

Animals↗
PubMed2001

Development of a lyophilized formulation for (R,R)-formoterol (L)-tartrate.

(R,R)-formoterol is a beta-agonist for inhalation. Aqueous instability suggested the need for a reconstitutable lyophilized dosage form. The objective of these studies was to devise a stable, rapid-dissolving, therapeutically compatible dosage form. The effects of diluents and residual moisture on the stability of thermally stressed formoterol formulations were investigated. Drug and various excipients (acetate, lactose, and mannitol) were lyophilized and placed in humidity chambers (0 to 90% relative humidity) at 25 to 50 degrees C. Stability was characterized by time-dependent changes using HPLC, pH, and XRD. Residual moisture were determined by Karl Fisher methods. Regression models were developed to quantify the effects of formulation and environmental variation on drug stability. Solid-state instability was observed as a function of high residual moisture and diluent type. Although the residual moisture in mannitol formulations were typically below 1%, the degradation rate (50 degrees C) varied from 2 to 10 mcg/day, which was 1.3- to 20-fold high than observed for lactose formulations under the same relative humidity conditions. At high relative humidity, the presence of acetate significantly increased the degradation rate (p < 0.04). The critical residual moisture content for lactose formulations was 3%. The amount of lactose was optimized by evaluating the degradation over the temperature range 25 to 50 degrees C. Mannitol and acetate were shown to be unsuitable excipients, and an optimal lactose amount was 50 mg for vials containing 50 mcg of drug.

Bronchodilator Agents↗
PubMed1999

Primary stability of different implants used in conjunction with high tibial osteotomy.

High tibial osteotomy in the varus knee has been successfully performed for a long time. Several newer operation techniques have been established in recent years. We tested the primary stability of several of these techniques in vitro. Ten human cadaveric fresh-frozen specimens were used that had a mean age of 54 years (range 29-72 years) and a weight of 55-85 kg. All specimens were harvested, frozen, and subsequently thawed under the same conditions before testing. The following implants were tested: one-third tubular plate with a cortical screw (AO, Synthes), blade plate with screws (Giebel's plate, Link), bone staples (osteotomy staples, Krackow staples, Smith & Nephew) and an external fixator (Orthofix). The specimens were mounted in metal cylinders and then loaded in two different setups: transverse forces were applied to the osteotomy site by hanging weights parallel to the osteotomy plane in a static-loading frame, and axial forces were applied by a materials testing machine (Zwick). Displacement was recorded using a linear variable displacement transducer (LVDT). The highest stability was achieved by the external fixator and the bone staples. Giebel's blade plate and the one-third tubular plate were less stable. Retention of an intact medial cortex was a decisive factor in obtaining primary stability. We found that the primary stability of the tested devices was generally comparable as long as they were correctly implanted. It was also noted that lateral spacing of the osteotomized bone should not exceed 3 mm. If the medial cortex is transected intraoperatively in lateral osteosynthesis, an additional medial implant is necessary to ensure sufficient primary stability. For practical reasons it was necessary to neglect the contribution of the soft tissues around the knee, although all implants were tested under the same conditions. Care should thus be taken when interpreting the results of this study in a clinical setting.

Adult↗
PubMed1998

The stability of bone screws in the os sacrum.

A variety of points of insertion and implantation techniques are recommended for inserting screws into the os sacrum. On the basis of 16 complete human sacrum specimens the following axial pull-out tests were performed: 1. Insertion of convergent measuring screws, 6.0 mm and 7.0 mm in outside diameter respectively, into the body of vertebra S1 using a monocortical and bicortical technique respectively with perforation of the ventral cortex. 2. Insertion of divergent screws into the ala sacralis at the level of S1 with 6-mm and 7 mm screws respectively, using a monocortical technique without perforation of the ventral cortex. 3. Insertion of convergent 6-mm screws into the body of vertebra S2 using a monocortical and bicortical technique respectively with perforation of the ventral cortex. The highest axial pull-out force was reached using convergent 6-mm screws inserted into the body of vertebra S1 using the bicortical technique with perforation of the ventral cortex (2392.4 N). The use of a 7.0-mm screw in the same implantation technique did not result in higher pull-out forces (2274.7 N). The monocortical technique reached a pull-out force of 1657.53 N with a 6-mm screw and 1505.64 N with a 7-mm screw. Convergent insertion of 6-mm screws into the body of S2 resulted in pull-out forces of 537.02 N using a bicortical and only 297.71 N using a monocortical technique. Divergent insertion of screws into the ala sacralis reached a maximal pull-out force of 495.47 N using 6-mm screws and 449.79 N using 7-mm screws. These data resulted from a monocortical implantation technique without perforation of the ventral cortex of the ala sacralis. The results of the present biomechanical study show that convergent bicortical implantation in the body of S1 is the most stable technique for screw fixation in the sacrum. The use of 7-mm rather than 6-mm screws did not lead to increased primary stability. Anatomic studies have shown that a safe area exists in the region of the ventral promontory, so this implantation technique appears to be unobjectionable.

Adult↗
PubMed1998

Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL.

Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A, CDKN2A, MDM2, MYC, RB1, REL, and TP53. The gene found to be altered most frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%) hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL without homozygous CDKN2A loss revealed methylation of the CpG island within exon 1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA expression was performed for 11 tumors and showed either no or weak signals. Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either completely negative or showed expression restricted to single tumor cells. None of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1 revealed no amplification, rearrangement or overexpression. The retinoblastoma protein was strongly expressed in all tumors. Only one PCNSL showed a mutation of the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG:Arg to Trp). No evidence of BCL2 gene rearrangement was found in 11 tumors investigated. The bcl-2 protein, however, was strongly expressed in most tumors. None of the 20 PCNSL demonstrated gene amplification of MDM2, MYC or REL. In summary, inactivation of CDKN2A by either homozygous deletion or DNA methylation represents an important molecular mechanism in PCNSL. Mutation of the TP53 gene and alterations of the other genes investigated appear to be of minor significance in these tumors.

Aged↗
PubMed1995

Evaluation of retinal toxicity of acetylcholine in rabbit eyes.

PURPOSE: In vitreoretinal surgery, pupillary constriction may be required at the termination of a procedure especially if mechanical pupillary dilation was used in eyes filled with gas or silicone oil. A miotic agent instilled into the anterior chamber will sink and come into direct contact with retina in the aphakic or pseudophakic vitrectomized eye. Therefore, the retinal toxicity of acetylcholine, a miotic used for pupillary constriction, was studied. METHODS: Eight Dutch pigmented rabbit eyes were vitrectomized, had air-fluid exchange, and were injected with a 20% mixture of SF6. Subsequently eyes were randomly selected to have injections of 0.75 ml of 10 mg/ml acetylcholine (Miochol, Iolab Corp., Claremont CA) versus 0.75 ml of lactated Ringer's solution. Short-term (2 weeks) and long-term (6 weeks) retinal toxicity was assessed by ophthalmoscopy, electroretinogram, and histology by light and electron microscopy at both times. RESULTS: Ophthalmoscopy, electroretinographic tracings, histology, and electron microscopy disclosed no significant abnormalities. CONCLUSIONS: Acetylcholine does not appear to have significant retinal toxicity even when undiluted solutions are in direct contact with the retina. We therefore postulate that intraoperative use of acetylcholine in previously vitrectomized eyes filled with gas or silicone is safe.

Acetylcholine↗
PubMed1991

[Hypercalcemia in florid pulmonary and cervical lymph node tuberculosis].

A 57-year-old man with a history of tuberculosis (TB of the knee-joint 44 years ago and open pulmonary TB six months ago with poor patient drug compliance) had lost 10 kg in weight during the preceding six months. In addition, firm lymph-node swellings with redness of the overlying skin and a skin fistula developed on the right side of the neck. There was mild hypercalcaemia (albumin-corrected serum calcium concentration 2.59 mmol/l) and hyperphosphataemia (2.0 mmol/l) with low-normal serum concentrations of parathormone and of 25-hydroxy-vitamin D3 (14 ng/ml). Serum 1,25-dihydroxy-vitamin D3 concentration was reduced (16 ng/l). The activity of osseous isoenzyme of alkaline phosphatase was normal (19 U/l) and skeletal scintigraphy revealed no abnormality. The cervical lymph-nodes were excised (histology: active caseous lymph-node TB). Tuberculostatic treatment was begun with daily doses of 0.3 g isoniazid, 0.45 g rifampicin, 1.2 g ethambutol and 1.5 g pyrazinamide. Serum calcium concentration rose to 3.22 mmol/l (albumin-corrected) in the first two weeks, even though the patient was on a low-calcium diet. The various concentrations subsequently decreased, but remained slightly elevated throughout the period of observation (11 weeks). This is thus a case of TB-associated hypercalcaemia which was not caused by 1,25-dihydroxy-vitamin D3 or bone destruction.

Alcoholism↗
PubMed1987

Evaluation of a direct fluorescein-conjugated monoclonal antibody for detection of cytomegalovirus in centrifugation culture.

A fluorescein-conjugated murine monoclonal antibody (MAb) reactive with cytomegalovirus (CMV) was evaluated for the detection of CMV in centrifugation culture. Of 188 specimens, 90 were positive for CMV in centrifugation culture. The fluorescein-conjugated MAb detected CMV in 86 of 90 (95%) specimens at 16 h postinoculation, and 88 of 90 (98%) were positive at 36 h. The fluorescein-conjugated MAb can be used in a direct immunofluorescence assay that can be completed in 15 min following cover slip fixation. Use of this antibody in centrifugation culture provides a convenient and rapid assay for the identification of CMV.

Antibodies, Monoclonal↗
PubMed1983

Estrogen-stimulated uptake of plasminogen by the mouse uterus.

Administration of a single low dose of estradiol to the immature (4- to 5-week-old) female mouse caused a rapid, uterine-specific increase in the uptake of radiolabeled plasminogen from plasma. A significant increase in uptake was detectable within 30 min and reached a maximum 2-4 h after administration of the hormone. After 4 h, a substantial amount (42%) of the newly taken up plasminogen was found in the uterine lumen. Half-maximal stimulation of uptake occurred at a dose of 0.20 microgram estradiol/animal. Estrogen stimulation of uptake was not blocked by puromycin, indicating that new protein synthesis was not required. Similar results were obtained with mouse plasma albumin. Estrogen-stimulated uptake was not blocked by indomethacin (10 micrograms/g BW, iv), but was blocked by prednisolone. Approximately 50% inhibition of the stimulation induced by 0.5 microgram estradiol in these 10-g animals was accomplished with 50 micrograms prednisolone. This study extends our initial findings on the estrogen-stimulated uptake of plasma proteins by the mouse uterus and provides a mechanism by which uterine plasminogen levels can be elevated before implantation.

Adenosine Diphosphate↗
PubMedDate not supplied

[Surgical shortening of the Achilles tendon for correction of elongation following healed conservatively treated Achilles tendon rupture].

INTRODUCTION: Is operative shortening of the achilles tendon an adequate therapy in cases of elongation following conservative treatment of achilles tendon rupture? METHODS: From 11/89 to 12/97, 12 patients underwent achilles tendon shortening (9 male, 3 female, average age 43 years). All patients had an elongated tendon following conservative treatment of achilles tendon rupture. We were able to examine 8 patients (67%) after the operation. The average follow-up period was 35 (7-103) months with an average span between the primary trauma and surgery of 22 (8-45) months. RESULTS: Prior to surgery, all patients complained of weakness, gait disturbance and limitation of activity. At follow-up a subjective weakness of the plantar flexion remained in five and an objective weakness in all patients. We found a decrease of the isometric plantar flexion strength to 52% of the non-operated lower extremity while the maximum calf circumference was only 5% decreased. Only two patients reported of a gait disturbance and activity limitation whereas three patients were free of complaints. Using a modified Trillat score (1,967), 7 patients rated good or very good (1 poor). CONCLUSIONS: Achilles tendon shortening in case of elongation following conservative treatment of achilles tendon rupture helps to decrease gait disturbance and limitation of activity whereas a lack of the isometric plantar flexion strength persists. In our opinion an early decision for achilles tendon shortening might prevent this deficit.

Achilles Tendon↗
PubMedDate not supplied

[High tibial osteotomy--primary stability of several implants].

INTRODUCTION: High tibial osteotomy in varus knee has been performed for a long time. Several newer operation techniques have been established in recent years. We tested the primary stability of several of these techniques in vitro. MATERIAL AND METHODS: 10 human cadaveric fresh-frozen specimens were tested with a mean age of 61 years (range 50-72 years), and weight of 65 to 78 kg. The following implants were tested: One-third-tubular plate with cortical screw (AO, Synthes), blade plate with screws (Giebel's plate, Link), bone staples (osteotomy staples, Krackow staples, Smith & Nephew), external fixateur (Orthofix). The specimens were fixed in metal cylinders and then loaded in two different apparati: Shear forces were applied to the osteotomy site by hanging weights parallel to the osteotomy plane in a static-loading frame, and axial forces were applied by a materials testing machine (Zwick). Load displacement was recorded by inductive displacement transducers. RESULTS: The highest stability was achieved by the external fixateurs and the bone staples. Giebel's plate and the one third tubular plate were less stable. Receipt of the medial corticalis was decisive for primary stability of the implants. CONCLUSION: The clinical significance of the results is limited by the relevance of the protocol, which for practical reasons did not account for the soft tissue situation around the knee. Thus, primary stability of the tested devices was generally comparable as long as they were correctly implanted. It was found, that lateral distance of the osteotomized bone should not exceed 3 mm. If the medial cortical is sawed, another medial implant is necessary to ensure sufficient primary stability.

Aged↗
PubMedDate not supplied

[Measurement of glenohumeral joint translation with a dynamic shoulder model].

Translation of the glenohumeral joint was measured with a dynamic shoulder model, during elevation of the arm in eight cadaveric specimens. Controlled hydrodynamic actuator forces were applied to the deltoid muscle and the rotator cuff through wire cables. Using a constant force ratio, the glenohumeral joint was elevated to 90 degrees. The position of the arm in all spatial orientations was measured with an ultrasonic device. Reproducibility of glenohumeral joint motion was demonstrated on the basis of five cycles of glenohumeral joint elevation. The rotational center of the humeral head was used as the reference point for translation. Translation during elevation of the glenohumeral joint between 20 degrees and 90 degrees averaged 9.0 mm +/- 5.2 mm superiorly and 4.4 mm +/- 1.3 mm anteriorly. In vivo, this may be diminished by coordinated activity of the rotator cuff. The presence of significant glenohumeral joint translation underlines the importance of active, muscular guidance at the shoulder. Physiologic translation of total shoulder arthroplasty, in shoulder instability and in the impingement syndrome.

Adult↗
PubMedDate not supplied

[An in vitro model for producing femoral fractures and for the study of primary stability of cerclage].

PURPOSE: Intraoperative femoral fracture is a well recognized intraoperative complication of cementless total hip arthroplasty (THA). This study was designed to establish an in-vitro model for initiation of fractures of the femur in cementless THA and to assess the effect of fracture fixation by cerclage wiring using steel wire (Protasul). METHODS: Ten human femur specimens were studied. Longitudinal cracks were created by pressing a well fixed conical stem deeper into the femur in a material testing machine. RESULTS: The force necessary to propagate a longitudinal crack in the femur was 1915 N to 9288 N (median 6531 N). This forces are according to 3 to 15 times (median 11 times) body weight. There was no difference of force between left and right femurs from the same individual (U-test). The femoral cortex fractured in 5 cases ventrally, in 6 cases medially and in 1 case laterally. After monofile cerclage wire application the force required to press prosthesis 5 mm deeper into the medullary canal was 0.3 to 2.7 times body weight. After monofile cerclage wire application pressing in the prosthesis 30 mm needed 1.8 to 8.1 times body weight. CONCLUSIONS: During insertion of a conical stem the orthopaedic surgeon should look for fractures of the medial cortex of the femur which is the most frequent location for fractures. This in-vitro model provides a reproductable method for the initiation and propagation of longitudinal femoral fractures in press-fit noncemented THA system and to assess the effect of fracture fixation in the form of cerclage wiring.

Adult↗
PubMedDate not supplied

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