[Six cases of acute pulmonary embolism associated with COVID-19]. / Embolie pulmonaire chez des patients atteints de COVID-19 : à propos de 6 cas.

Rising from the province of Wuhan in China, the new coronavirus SARS-CoV-2 broke out in winter 2019, causing a global pandemic. In most cases reported, COVID-19 symptoms include cough, dyspnea, myalgia and asthenia. In some cases, the disease can also cause severe respiratory distress syndrome, requiring intensive care. Recent studies suggest that SARS-CoV-2 infection predisposes to thromboembolic event such as pulmonary embolism. Moreover, there is an overlap between signs and symptoms of pulmonary embolism and COVID-19, which brings a challenge for the diagnosis and could potentially be fatal. Nevertheless, the incidence rate of pulmonary embolism in cases of COVID-19 is currently not known. In this paper we describe six cases of pulmonary embolism associated with COVID-19.

Depuis la fin de l'année 2019, le monde est frappé par une épidémie causée par le virus SARS-CoV-2. La maladie à coronavirus 2019 se manifeste dans la majorité des cas par de la pyrexie, de la toux, de la dyspnée, des myalgies et de la fatigue. Néanmoins, elle peut aussi se présenter sous des formes plus sévères, allant de la pneumopathie hypoxémiante jusqu'à l'insuffisance respiratoire et à la défaillance multiorganique. Des études récentes suggèrent que l'infection à SARS-CoV-2 prédispose aux événements thromboemboliques. Bien que l'incidence de l'embolie pulmonaire dans le cadre de la maladie à coronavirus soit inconnue, elle constitue une complication potentiellement fatale. L'embolie pulmonaire peut être difficile à mettre en évidence car les signes et symptômes peuvent être similaires et se confondre avec ceux d'une pneumopathie à SARS-CoV-2. Nous rapportons 6 cas d'embolie pulmonaire associée à une pneumopathie à SARS-CoV-2.

[Significance of 3D-ultrasonic examinations of the musculoskeletal system]. / Stellenwert von 3D-Ultraschall in der Orthopädie.

UNLABELLED: 3D-ultrasonic is gaining more and more significance in many medical disciplines, e. g., in angiology and prenatal diagnostics. AIM: The aim of this study was to make a comparison between the informative ability of conventional 2D-ultrasound with that of 3D-ultrasound for investigations of joints and to determinate whether 3D-ultrasound can reveal additional diagnostic information. METHOD: During a defined period of time all clinically necessary ultrasonic investigations of joints were done with a 3D-sonograph. However, all data recorded need a manual post-processing stage for visualisation in a 3D-mode. Due to the small impedance differences between the tissue layers, an automated tissue differentiation was not possible. RESULTS: The substantial advantage is that all the DEGUM standard levels can be derived from the scanning volume without conversion of the ultrasound head. CONCLUSION: At the current time the benefit of 3D-visualisation in the diagnostics of joints is small. The introduction of this technique to daily routine is not yet justified.

[Evaluation of potential risks of abrasive water jet osteotomy in-vivo]. / Evaluation verfahrensspezifischer Risikopotentiale der Wasserabrasivstrahl--Osteotomie in-vivo.

Since the 80's the water jet scalpel is an established tool in some surgical fields. It is used in particular in visceral surgery for preparation of parenchymatous organs. By the addition of biocompatible abrasives, this technique is able to effectively machine hard biological tissues. Free defined cutting geometries can be realised in a non contact process. Therewith this method has crucial advantages compared to conventional osteotomy techniques and gives new impulses to the development in endoprosthetics and correction osteotomies of hollow bones. In the presented work the new developed abrasive water injection jet (AWIJ) was used the first time for in-vivo osteotomies. Aim of this study was the detection of potential thrombembolic effects and wash in effects of the cutting fluid. Hollow bones of the fore and hind leg of 20 house pigs were treated with the new cutting technique. Intraoperative documentation of relevant vital parameters was performed by a multi monitoring system. Thrombembolic effects during the osteotomy were detected by transthoracic Doppler ultrasonography and transesophagale echocardiography. The hollow bones were prepared in consideration of the vascularisation's protection especially in respect to the venous flow. Thrombembolic effects with temporary haemodynamic respectively respiratory consequences could be detected exclusively by using the so called "3-component jet", which consists of 90 vol % of air. The usage of an abrasive suspension enables the airfree dosing of dry soluable abrasives. Thrombembolic effects could not be monitored in this case. Intramedullary fluid in-wash effects as well as resulting electrolytic disorders could not be proven. For abrasive waterjet osteotomies with 3 component jet a relevant risk of thrombembolic effects could be shown. This knowledge has also to be considered for abdominal and neurosurgical applications in the future. Due to the usage of an abrasive suspension this risk can fully be avoided.

Development and validation of a high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydroartemisinin in human plasma.

A sensitive method has been developed and validated for the determination of artesunate and its active metabolite dihydroartemisinin (DHA) in human plasma using artemisinin as an internal standard. Solid phase extraction (SPE) using Oasis HLB extraction cartridges was used for sample preparation and analysis was performed on a Shimadzu LCMS-2010 in single ion monitoring positive mode using atmospheric pressure chemical ionization (APCI) as an interface. Positive ions were measured using extracted ion chromatogram mode. The extracted ion for artesunate, alpha- and beta-DHA was m/z 221 and for artemisinin was m/z 283. Chromatography was carried out using a Synergi Max-RP, 4 mu, 75 mm x 4.6 mm column using glacial acetic acid 0.1%, acetonitrile and methanol mixture (38:46.5:15.5) as a mobile phase delivered at a flow rate of 0.5 mL/min. The retention times of artesunate, alpha- and beta-DHA and artemisinin were 17.4, 11.8, 18.7 and 13.4 min, respectively, with a total run time of 21 min. The assay was linear over the range 1-3000 ng/mL for artesunate and DHA. The analysis of quality control samples for artesunate 50, 300, 1300 and 2600 ng/mL demonstrated excellent precision with relative standard deviation of 14.3, 11.3, 7.5 and 12.1%, respectively (n=5). Recoveries at concentration of 50, 300, 1300 and 2600 ng/mL were 75, 94.5, 74.3 and 75.5%, respectively; similar results were obtained for precision and recovery of DHA. This liquid chromatography-mass spectroscopy (LC-MS) method for the determination of artesunate and DHA in human plasma has superior specification for sensitivity, sample throughput and robustness than previous methods and can reliably quantitate concentrations of both (artesunate and DHA) compounds as low as 1 ng/mL.

[Shoulder arthrodesis. Indications, techniques, results, complications]. / Schulterarthrodese. Indikation, Technik, Ergebnisse, Komplikationen.

Besides the paralysis of shoulder muscles, large rotator cuff tears beyond repair, persistent shoulder instability with repeat dislocations and resection cases are recent indications for shoulder arthrodesis. The fusion of the shoulder is particularly useful since, despite immobilization of the glenohumeral and acromiohumeral joints, no loss of function is experienced; on the contrary, in many cases an increase of active total mobility may occur. According to the functional outcome, the majority of reports vary between 30 degrees and 90 degrees of active abduction and forward flexion with a mean value of about 60 degrees The most generally accepted arthrodesis position is 20 degrees -40 degrees abduction, forward flexion and internal rotation in relation to the trunk. This position results in a maximum development of muscle power and ensures that the arm will rest comfortably at the side, and that the scapula will not protrude. This also allows the hand to reach the head and facial region. The literature is not confined to any uniform type of arthrodesis and it would appear that the techniques and configurations of material vary considerably. A general advantage of any one particular form of arthrodesis, and the use of plates, screws or external fixators, cannot be deduced. Pseudarthrosis appears to be less frequent in cases of plate arthrodesis compared to screw arthrodesis. However, the application of plates more often results in infections, postoperative fractures of the humerus and the necessary removal of material. Screw arthrodesis is more beneficial in that the exposed area to be operated is smaller than in plate arthrodesis. Postoperative immobilization is more time consuming and, therefore, constitutes one of the disadvantages of screw fixation.

[Temperature measurements during abrasive water jet osteotomy]. / Wärmeentwicklung bei der Wasser-Abrasivstrahl-Osteotomie.

Working on bone is a major aspect of orthopaedic surgery. Despite its well-known appreciable thermal effects on the edges of the bone cut, the oscillating bone saw blade the oscillating saw remains the standard instrument both for cutting long bones and creating a bed for an endoprosthesis. The application of abrasive water jets offers the possibility of achieving an extremely precise curved cut in bone with no accompanying thermal effect. The thermographically measured absolute temperature increase at the cut edges seen with the water jet was 13 K maximum. The small process forces permit the application in automated handling systems.

The kinetics of the alkaline degradation of daptomycin.

The aqueous degradation of daptomycin, a lipopeptide antibiotic, was investigated as a function of substrate concentration (0.5-10.0 mM), pH (9.0-10.5), buffer concentration (0.06-0.20 M borate, glycinate, or carbonate buffers), temperature (20-50 degrees C), and ionic strength (0.1-0.8). The primary degradation pathway was determined by electrospray-mass spectroscopy (ES-MS), Fourier transform infrared (FTIR), and fluorescence spectroscopy to be hydrolysis of the ester linkage between the C-terminus (kynurenine) and the side chain of the fourth residue (threonine). The reaction was first order with respect to time; however, the reaction order with respect to substrate concentration was <1 at substrate concentrations >1 mM. Insignificant buffer effect was observed. The reaction was subject to specific base catalysis. Activation parameters were E(a) = 13.6 kcal/K.mol, DeltaH++ = 13.0 kcal/K.mol, and DeltaS++ = -19.2 eu. The positive primary salt effect was observed with negative deviation at high concentration of salt. The magnitude of the salt effect depended on salt identities in the order sodium < potassium < calcium chloride.

Preformulation studies on the S-isomer of oxybutynin hydrochloride, an Improved Chemical Entity (ICE).

(S)-Oxybutynin HCl (S-OXY) is a white crystalline solid powder with an acicular particle morphology. Differential scanning calorimetry (DSC) thermograms revealed one characteristic endotherm at 116.2 degrees C. On rescanning a sample heated to 120 degrees C, no thermal events were distinguished in the temperature range 25 degrees C to 150 degrees C. Weight loss curves determined by thermogravimetric analysis showed a continuous, gradual weight loss of about 0.15% over the temperature range 30 degrees C to 110 degrees C, followed by a change in slope and more rapid weight loss beginning at 150 degrees C. Observation by hot-stage microscopy confirmed the melting endotherm observed by DSC. Equilibrium moisture uptake studies indicated low water vapor uptake at low relative humidities (<52.8%). At relative humidities of 75.3% and 84.3%, S-OXY first deliquesced and then converted to a lower melting point crystal form. X-ray powder diffraction (XRPD) data supported the DSC findings. S-OXY underwent degradation by ester hydrolysis at alkaline pHs. The kinetics of this reaction were studied at 25 degrees C in carbonate-bicarbonate buffers. Observed rate constants of 0.008 h(-1) and 0.0552 h(-1) were determined at pH 9.69 and 10.25, respectively. The pKa of S-OXY was 7.75. The aqueous solubility of S-OXY was described as a function of pH and the free-base solubility. The mean partition coefficient log P was 3.33 using 1-octanol. The surface tensions of aqueous solutions of S-OXY decreased with increasing concentration, but no concentration-independent region was observed, indicating that S-OXY does notform micelles in aqueous solution. The dissolution rate of S-OXY from a compressed disk in 0.1 N HCl was rapid, whereas it was considerably slower at pH 7.4. Addition of 1% hexadecyltrimethylammonium bromide (CTAB) at pH 7.4 significantly improved the dissolution rate. S-OXY displayed very poor flow properties when compared to standard pharmaceutical excipients. XRPD results indicated that S-OXY exhibited a loss in crystallinity following ball milling. Hiestand tableting indices indicated that S-OXY has good bonding properties andforms strong compacts, but is likely to be susceptible to capping on ejection from the die. This indicated the needfor a plastically deformable excipient such as Avicel PH-101 in tablet formulations.

Proximal humerus fracture.

A thirty-five-year-old man who fell from a tree is admitted to the emergency department with the x-rays shown below. Physical examination reveals that the patient is neurologically intact and has good pulses. Management of this case is described in the following opinions.

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.

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.

The degradation pathways of glucagon in acidic solutions.

OBJECTIVE: Glucagon is a 29 amino acid peptide hormone that exhibits degradation via both chemical and physical pathways. The objective of the studies reported herein was to identify the degradation products and scheme for glucagon hydrolysis in acidic solutions. METHODS: Solutions of glucagon in 0.01 N HCl (pH 2.5) were degraded at 60 degrees C for 70 h. One isocratic and two gradient RP-HPLC methods were developed to separate the degradation products. Structure elucidation of the separated peaks was achieved using amino acid sequencing, amino acid analysis, and mass spectrometry. Degradation was carried out in the pH range 1.5-5 to check for changes in degradation scheme with pH. Authentic samples of degradation products were degraded under similar acidic conditions to confirm precursor successor relationships in the degradation scheme. RESULTS: Sixteen major degradation products were isolated and identified. The major pathways of degradation were found to be aspartic acid cleavage at positions 9, 15, and 21 and glutaminyl deamidation at positions 3, 20, and 24. Cleavage occurred on both sides of Asp-15 but only on the C-terminal side of Asp-9 and Asp-21. Deamidation of the Asn residue at position 28 was not detected.

Pharmaceutical container/closure integrity. VI: A report on the utility of liquid tracer methods for evaluating the microbial barrier properties of pharmaceutical packaging.

The relationship between a liquid tracer package leak test (Mg ion ingress) and microbial immersion challenge test was demonstrated by direct and indirect correlation techniques. Rubber-stoppered glass vials with micropipette leaks were evaluated by a helium leak rate method, filled with broth, sterilized, and immersed in a bath containing microorganisms (E. coli/B. diminuta) and liquid tracer (Mg ions). After exposure and incubation, each unit was evaluated for liquid tracer ingress by atomic absorption spectrophotometry and for microbial ingress by visual inspection and blood agar streaking. Two hundred and eighty sterile broth-filled test units were challenged with microorganisms and liquid tracer. One hundred and fourteen units showed neither liquid tracer nor microbial ingress. One hundred and eight units were positive for both microbial and liquid tracer ingress. No test units were positive for microbial ingress but not for liquid tracer ingress. Fifty-eight units were positive for liquid tracer ingress but failed to show microbial ingress. Logistical regression was used to demonstrate that the probability of liquid tracer ingress was greater than microbial ingress at all leak sizes. The results indicate that the liquid tracer method studied herein was a useful indicator of the microbial barrier properties of pharmaceutical packaging. Additionally, the results support the contention that liquid penetration of a leak is required for microbial ingress.

[Surgical shortening of the Achilles tendon for correction of elongation following healed conservatively treated Achilles tendon rupture]. / Die operative Achillessehnenverkürzung zur Korrektur der in Verlängerung ausgeheilten konservativ behandelten Achillessehnenruptur.

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.

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.

[High tibial osteotomy--primary stability of several implants]. / Zur Berechtigung von verschiedenen Osteosyntheseformen bei der Tibiakopfumstellungsosteotomie.

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.