How to treat proximal and middle one-third humeral shaft fractures: the role of helical plates.

PURPOSE: To evaluate the outcomes of patients affected by proximal and middle one-third humeral shaft fractures treated with humeral helical plates. MATERIAL AND METHODS: From October 2016 to June 2020, twenty-four (twenty women, four men) underwent humeral reduction and fixation with humeral helical plates (A.L.P.S.® Proximal Humeral Plating System, Zimmer Biomet) that preserve deltoid muscle insertion and reduce the risk of iatrogenic radial nerve injury. At one and six months after surgery, standard antero-posterior and lateral radiographs were obtained, and at last follow-up (eighteen months on average), clinical evaluation was performed through range of motion assessment, Constant score and DASH score questionnaires. Only descriptive statistical analysis was conducted. RESULTS: At six months, all fractures have healed. At last follow-up (average eighteen months, 13-28) mean Constant score was 71 (range 33-96), mean Dash score was 19.2 (range 1.7-63). The average range of motion was calculated as follows: flexion 137.8° (range 90-180); abduction 125.8° (range 85-180°); external rotation 55° (range 20-80°), internal rotation at L3 (range between scapulae-trochanter). Three patients experienced temporary radial nerve palsy from injury, while in one case, a temporary iatrogenic palsy occurred. CONCLUSIONS: In our opinion, the helical plate may be an effective surgical tool for management of proximal and middle one-third diaphyseal humeral fractures. The humeral helical plate allows stable fixation avoiding the deltoid tuberosity proximally and radial nerve distally, thus increasing the possibility of rapid functional recovery after surgery.

One-year follow-up after treatment of proximal and/or middle one-third humeral shaft fractures with a helical plate: healing rates, complications and functional outcome measures.

BACKGROUND: Conventional plate osteosynthesis is a valuable treatment option in displaced proximal and/or middle one-third humeral shaft fractures. Nonetheless, this procedure can be complicated by a radial nerve palsy. To date, many surgical techniques have been developed in an attempt to minimize this high-impact complication. A helical plate has the potential to avoid an iatrogenic radial nerve palsy due to its design. This article aims to evaluate safety and functional outcomes of patients treated with a helical plate compared to conventional plate osteosynthesis. In particular healing rates, complications and functional outcome measures. METHODS: We retrospectively included all patients with displaced proximal and/or middle one-third humeral shaft fractures who were treated with a helical plate from October 2016 until August 2018 at a single level-1 trauma center (AZ Groeninge, Kortrijk, Belgium). A self-molded long PHILOS plate (DePuy Synthes®) or a pre-contoured A.L.P.S proximal humeral plating system (Zimmer Biomet®) were used. Patient baseline characteristics and standard radiographs were obtained pre- and postoperatively. We retrospectively searched for complications. Patients were reassessed using the Disabilities of the Arm, Shoulder and Hand (DASH), Constant Murley (CMS) and EQ-5D-5L scores with a minimal follow-up of 1 year. RESULTS: The humeral shaft fractures of all sixteen patients consolidated within 3 months and no iatrogenic radial nerve palsies were observed. One plate had to be removed after 1 year due to a late deep infection. With a minimum follow up of 1 year, the mean DASH score was 22 ± 19 and the mean normalized CMS was 80 ± 19. CONCLUSION: Operative treatment of proximal and/or middle one-third humeral shaft fractures with a helical plate is a safe procedure with good to excellent shoulder function at one-year follow-up. Contrary to conventional plate osteosynthesis, a helical plate has the potential to completely avoid a radial nerve palsy, while maintaining similar healing rates and functional outcomes. TRIAL REGISTRATION: Retrospective cohort study. B396201939564 . Registered on 10 MAY 2019.

Aerobic and anaerobic energy production in juvenile roach (Rutilus rutilus): regulation of glycolytic process by ethofumesate at two temperatures.

The aim of this study was to evaluate the coupled impact of an herbicide, ethofumesate, and temperature on the cellular energy metabolism of juvenile roach, especially on the glycolysis pathway. Juvenile roach were exposed to 0, 0.5, 5, and 50 µg/L of ethofumesate for 7 days in laboratory conditions at two temperatures (10 and 17 °C). The energy reserves (carbohydrate, lipid, and protein) were quantified, since the availability of substrates regulates the glycolysis. Then, the glycolysis was studied at the biochemical level by the measurement of the glycolytic flux and at the molecular level with the measurement of the relative expression of four genes encoding for glycolysis enzymes. This study revealed different effect of ethofumesate on the glycolysis pathway according to the temperature of exposure. Indeed, at 10 °C, it appeared that only the molecular regulation level was affected, whereas, at 17 °C, ethofumesate acted on the biochemical level. The differences observed between the two exposures imply the establishment of different strategies in order to maintain to cope with stress according to the temperature of exposure.

Bio-analysis of forensically relevant drugs in alternative matrices by liquid chromatography-tandem mass spectrometry.

Cannabis is the most frequently detected illicit drug in the Western world, e.g. in cases of driving under the influence of drugs (DUID), whereas benzodiazepines comprise the most abused licit drugs and have been linked with drug-facilitated sexual assault cases (DFSA). In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in alternative matrices such as oral fluid and hair. These specimens allow easy, non-invasive sampling, which can be achieved under close supervision to prevent adulteration or substitution of the samples. The volume is often limited and to achieve the required analytical sensitivity, liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for the detection of cannabis and benzodiazepines in oral fluid and hair were developed. After validation, these methods were applied to genuine samples to assess: (a) the validity of oral fluid to detect recent cannabis consumption, (b) the Dräger Drug Test as an on-site oral fluid test, and (c) the applicability of hair testing in forensic cases. The latter led to new insights into metabolic conversions between benzodiazepines; this knowledge may avoid potentially erratic conclusions regarding DFSA. Finally, benzodiazepines are also frequently encountered in post-mortem cases. An LCMS-MS method to detect benzodiazepines in larvae and puparia of insects rearing on corpses was developed and validated. In conclusion, this research aimed at combining the usefulness of alternative matrices with the analytical power of LC-MS-MS. Final outcome is a number of sensitive and validated methods ready for use in routine analysis.

New [99mTc]bombesin analogues with improved biodistribution for targeting gastrin releasing-peptide receptor-positive tumors.

AIM: Bombesin (BBS) receptors are potential targets for diagnosis and therapy of breast and prostate tumors. To overcome the rapid degradation of natural BBS some modifications were introduced at positions 13 and 14. Additionally, a spacer was inserted between the chelator and the binding sequence in order to further improve the in vivo uptake. The analogues were labeled with the [(99m)Tc(CO)(3)]-core and tested. METHODS: Stability was analyzed in vitro in human plasma. Binding affinity and internalization were determined in vitro in prostate carcinoma PC-3 cells. Biodistribution studies and single photon emission computed tomography/X-ray computed tomography (SPECT/CT) imaging were performed in nude mice with PC-3 tumor xenografts. RESULTS: The changes introduced in the BBS(7-14) sequence substantially increased plasma stability. Affinity for gastrin releasing-peptide (GRP) receptors on PC-3 cells was comparable to that of the unmodified analogue with Kd<1 nM. The presence of a spacer in the molecule induced an increment in the in vivo uptake in pancreas and PC-3 xenografts (GRP receptor-positive tissues). The increase in pancreas and tumor uptake was higher when both spacer and stabilization are present in the same molecule. Moreover, in vivo uptake was highly specific. The tumor was clearly visualized by SPECT/CT. CONCLUSIONS: The modifications in the BBS(7-14) sequence led to a higher plasma stability while binding affinity remained unaffected. Stabilization resulted in improved biodistribution with better tumor to non-tumor ratios. However, the insertion of a spacer had a greater influence on the biodistribution. Analogues with both spacer and stabilization are the most promising radiopharmaceuticals for targeting GRP receptor-positive tumors.

Development of a rapid and sensitive method for the quantitation of benzodiazepines in Calliphora vicina larvae and puparia by LC-MS-MS.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) is emerging as the tool of choice for rapid analysis and the detection of biologically active compounds in complex mixtures. We describe the development of a sensitive method for the simultaneous quantitation of 10 benzodiazepines in Calliphora vicina (Diptera: Calliphoridae) larvae and puparia. The use of larvae for toxicological analyses offers some technical advantages over putrefied tissue. Four sample pretreatment methods for isolating the benzodiazepines out of larvae were evaluated. A simple homogenization, followed by acetonitrile precipitation yielded the highest recoveries. Puparia were pulverized and extracted by ultrasonification in methanol. All extracts were subsequently analyzed using reversed-phase LC-MS-MS. Larvae and puparia calibrators containing benzodiazepines at concentrations ranging from 25 to 750 pg/mg and 50 to 500 pg/mg, respectively, were prepared and analyzed. The method was demonstrated to be linear over the ranges investigated. Limits of detection were from 1.88 to 5.13 pg/mg larva and from 6.28 to 19.03 pg/mg puparium. The developed method was applied to the determination of nordiazepam and its metabolite oxazepam in larvae and puparia of the Calliphora vicina fly that had been reared on artificial foodstuff (beef heart) spiked with 1 microg/g nordiazepam. The larvae were harvested at day 5 for analysis of drug content. The method was sufficiently sensitive to allow the detection of nordiazepam and oxazepam in a single larva or puparium.

Cobas Mira S endpoint enzymatic assay for plasma formate.

In methanol intoxication, increased levels of the metabolite formate are associated with metabolic acidosis and an increased risk for ocular and neurological dysfunction. A simple method for plasma formate measurement by adaptation of a manual enzymatic assay to a Cobas Mira S analyzer is presented. Six microliters of sample is incubated for 5 min with buffer containing nicotinamide-adenine dinucleotide. Fifteen microliters of a suspension of formate dehydrogenase is then added. Absorbance at 340 nm is measured every 25 s. The NADH produced when formate is oxidized is stoichiometric to the amount of formate. The method is sensitive, reproducible, and specific and has a broad measurement range. The frozen reagents are stable for at least six months, so the described method can be applied to irregular and semi-urgent requests. A recent case is reported.

Pharmacokinetic model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia.

OBJECTIVE: To evaluate the prospective predictive accuracy and the quality of anesthesia of pharmacokinetic model-driven infusion of sufentanil and midazolam designed to establish and maintain a plasma level of drug during cardiac surgery. DESIGN: Prospective analysis. SETTING: Operating room at a university hospital. PARTICIPANTS: Twenty adult patients younger than 75 years old scheduled for valvular or coronary artery bypass graft surgery. INTERVENTIONS: Patients were anesthetized using a variable predicted concentration of sufentanil (1 to 10 ng/mL) combined with a stable predicted concentration of midazolam (100 ng/mL). MEASUREMENTS AND MAIN RESULTS: For each patient, arterial samples were taken before (6 samples), during (2 samples), and after (2 samples) cardiopulmonary bypass (CPB). Plasma sufentanil and midazolam concentrations were measured by specific radioimmunoassay and high-performance liquid chromatography techniques. Predicted sufentanil and midazolam concentrations were derived using the data sets of Gepts et al and Maitre et al. The predictive performance, the percentage prediction error (PE), and the absolute percentage error were calculated for each sample. The bias, inaccuracy, and dispersion were assessed by determining the median of the individual medians of the prediction errors (MDPE), the median of the individual median of the absolute prediction errors (MDAPE), and the 10th and 90th percentiles of PE. For midazolam, the inaccuracy was low (MDAPE < 21%), but CPB was associated with a dilution of the measured concentration associated with a negative bias. For sufentanil, the inaccuracy was also low before CPB (MDAPE = 18%) but increased during and after CPB (MDAPE > 40%). During the whole procedure, the hemodynamic control necessitated only a few interventions. CONCLUSIONS: Pharmacokinetic model-driven infusion of sufentanil and midazolam using the pharmacokinetic sets of Gepts et al and Maitre et al is a safe and accurate anesthetic technique before CPB in adult patients undergoing cardiac surgery when high sufentanil (1 to 10 ng/mL) and low midazolam (100 ng/mL) predicted plasma concentrations are targeted.

Orphenadrine poisoning in a child: clinical and analytical data.

Orphenadrine is an anticholinergic drug used mainly in the treatment of Parkinson's disease. It has a peripheral and central effect and a known cardiotoxic effect when taken in large doses. We report the successful outcome of the treatment of a 2 1/2-year-old girl who accidentally ingested 400 mg of orphenadrine hydrochloride (Disipal). One hour after ingestion she presented neurological symptoms: confusion, ataxic walking, and periods of severe agitation. Generalized tonic-clonic seizures appeared resistant to the administration of multiple antiepileptics. They ceased after a supplementary dose of intravenous diazepam, endotracheal intubation, and mechanical ventilation. An episode of ventricular tachycardia responded well to i. v. lidocaine. Physostigmine was administered in three successive doses. The initial orphenadrine plasma level (3,55 microg/ml) was in the toxic range, associated with high mortality. The calculated elimination half-life was 10.2 h and the molecule and/or its metabolites were found up to 90 h after ingestion.

Classification of medicines according to their influence on driving ability.

Within the scope of an information campaign of the Belgian Institute for Road Safety an attempt was made to classify 179 medicinal drugs from 9 therapeutic groups, listed in the Belgian "Commented Repertory of Drugs--1997", according to their effect on driving performance. The categorisation was based on literature data from about 500 references and used the system proposed by Wolschrijn et al [1]: 7 classes ranging from no effect (I) over minor and moderate (II.1,II.2) to severe effects (III), completed with the respective* categories (I*,II*,III*) for presumed classes with insufficient scientific data. Forty-two drugs (24%) were considered having severe effects (III/III*). Only 28/179 molecules (16%) were classed in I/I*: no hypnotics-sedatives (33), anticonvulsants (10), antidepressants (25), neuroleptics (29), nor narcotic analgesics and antitussives (18) were listed in this no-effect category, while for 7/24 antihistamines (5/20 H1 and 2/4 H2), 12/20 beta blockers and 9/10 central stimulants the effect was considered negligible. Antidiabetics were not classified, as the danger lies in the risk of hypoglycemia due to inadequate use. The classification of the molecules proved to be problematic due to the lack of study data (42% of molecules in presumed categories) and the diversity in the study protocols. The effect on driving ability is dose-dependent and time-related, which makes the use of a single category inadequate; the effect further depends on co-ingestion of other medicines or alcohol, the development of tolerance and the condition of the subject. Physicians and pharmacists can use the proposed categorisation as a scientific base for guiding their patients, but should take into account the factors involved for each patient when estimating the driving ability.

Gitaloxin poisoning in a child.

Gitaloxin is a digitalis glycoside used for the same indications as digoxin and digitoxin. The successful outcome for a 2 1/2-year-old boy who accidentally ingested 3 mg of gitaloxin (100 times the normal therapeutic dose) is reported. At admission the child presented with irregular heart rhythm. He subsequently started vomiting, even after continuous gastric feeding. Only 48 h after ingestion of gitaloxin he became somnolent and developed bradyarrhythmia. The symptoms disappeared 96 h later; the bradyarrhythmia, however, (second-degree atrioventricular block) decreased progressively only after 120 h. The initial clinical presentation of gitaloxin poisoning may be misleading and careful observation in a pediatric intensive care unit is mandatory. A cross-reaction between the fluorescence polarization immunoassay for digitoxin and the radioimmunoassay for gitaloxin was found and was used as a helpful, but rough, estimate of the severity of gitaloxin poisoning, in the absence of a specific measurement of gitaloxin.

Automation of toxicological screenings on a Hewlett Packard Chemstation GC-MS system.

OBJECTIVES: To optimize the interpretation of GC-MS toxicological screenings (i.e., to facilitate ion specific queries, create custom reports specifically adapted to each confirmation procedure, and eliminate redundant and/or inaccurate data on library search reports). DESIGN AND METHODS: The MS Chemstation software of the Hewlett Packard 5972 is constructed in a modular way. We made extensive modifications to two modules, the data analysis and the report modules, using the built-in MS Chemstation macro language. RESULTS: Ion specific queries were automated for over 60 commonly encountered analytes. Custom reports were created for the confirmation of positive drugs-of-abuse immunoassay results. With the incorporation of decision support rules into the data processing and the reporting phases, we obtained sensitive, accurate, and concise reports. CONCLUSIONS: The MS Chemstation software can be tailored to the needs of each individual application. The incorporation of a rule-based decision support system enhances the quality of the GC-MS toxicological screenings and results in faster, easier, and more reliable processing.

Combined intoxication with a tricyclic antidepressive agent and a neuroleptic.

We report the case of a patient who co-ingested a tricyclic antidepressant (2500 mg of doxepin) and a neuroleptic drug (3500 mg of prothipendyl). Following overdose either agent can affect the central nervous and cardiovascular systems, inducing arrhythmias, conduction disturbances and hypotension. The presented case illustrates that a combined overdose of tricyclic antidepressants and neuroleptics enhances the possible toxic effects of each drug and especially the risk for adverse cardiac events. The clinical features and management of this combined intoxication are discussed. Treatment with sodium bicarbonate readily corrected a potentially life-threatening cardiac arrhythmia and is therefore suggested to be imperative in the treatment of these cases.

Positive interference of merthiolate in the TDx digoxin assay in control samples used in the Belgian External Quality Assessment (EQA) Scheme.

We investigated the possible origin of the spuriously high results observed with the Abbott TDx Immunoassay in the 1991 Belgian external quality assessment scheme for digoxin. The present work ascribes this discrepancy to a matrix effect induced by the addition of merthiolate as preservative to the control samples. It consequently stresses the importance of avoiding the use of this compound for preparing such samples.

Analytical and clinical evaluation of creatine kinase MB mass assay by IMx: comparison with MB isoenzyme activity and serum myoglobin for early diagnosis of myocardial infarction.

We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin.

Prophylactic diclofenac infusions in major orthopedic surgery: effects on analgesia and acute phase proteins.

The influence of diclofenac, given by continuous i.v. infusion starting preoperatively, on postoperative pain and inflammation was assessed in a double-blind, randomized, placebo-controlled study in 40 patients scheduled for major orthopedic surgery. Starting 30 min before induction the patients received either diclofenac (0.35 mg.kg-1 bolus followed by a constant-rate infusion of 90 micrograms.min-1) or placebo for 24 h. The pain intensity (VAS) and the amount of rescue narcotic (piritramide on demand) were significantly lower in the diclofenac group from 4 and 6 h postsurgery, respectively, till end of infusion. Acute phase proteins used as inflammation markers (C-reactive protein, alpha 1-chymotrypsin, alpha 1-acid glycoprotein, haptoglobin and coeruloplasmin) showed similar variations in both groups for 24 h. The diclofenac treatment had no influence on hematological and coagulation profiles, nor on muscle and liver enzymes in comparison with placebo. Both patients and observer rated the diclofenac treatment as significantly superior to the placebo treatment.

Streptomycin pharmacokinetics in relapsing Mycobacterium xenopi peritonitis.

Relapsing peritonitis due to Mycobacterium xenopi developed in an 80-year-old man undergoing continuous peritoneal dialysis after appropriately treated concurrent bacterial peritonitis. The patient presented with a lymphocytic exudative peritoneal drainage fluid. The diagnosis of tuberculous peritonitis was made by identification of acid-fast bacilli in peritoneal effluent and culture of M. xenopi. Oral antituberculous drugs in combination with intraperitoneal streptomycin achieved suppression of the disease, permitting peritoneal dialysis to be continued with satisfactory clearance and ultrafiltration capacity during a follow-up period of up to 35 months. Streptomycin kinetics revealed that 75% of the intraperitoneally administered dose of streptomycin is absorbed from the dialysate.