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.

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.

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.

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.

Meprobamate poisoning, hypotension and the Swan-Ganz catheter.

A case is described in which voluntary ingestion of 72 g meprobamate (mpb) was complicated by shock ascribed to cardiac failure and vasodilation, documented by hemodynamic monitoring. Forced diuresis and cardiac inotropic support were added to the therapy. We recommend Swan-Ganz monitoring in any case of mpb overdosage associated with hypotension and suggest that forced diuresis is not contraindicated if appropriate assessment of the patient's hemodynamic condition is performed.

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.

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.

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.

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.

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.

Bromism after prolonged use of carbromal.

Most of the brominated monoureide and bromide salt containing drugs are obtainable in Belgium without prescription. Apart from the regularly encountered suicidal attempts, these drugs can also, without the intention of the patient, cause bromism . We report two cases of patients recently admitted because of bromism after prolonged use of Carbromal . Bromism now has become a rather unfamiliar condition. Therefore diagnostic and therapeutic aspects are briefly discussed. Because we dispose now, for the same indications, of more efficient and much less toxic drugs, we suggest that drugs containing a significant amount of brominated monoureides or bromide salts should be removed from the market.

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.

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.

Pharmacokinetics of vancomycin in patients undergoing haemodialysis and haemofiltration.

Vancomycin is widely used for the treatment of infections with Gram-positive bacteria in patients with end-stage renal disease. The concentration of vancomycin in serum, in ultrafiltrate, and in dialysate was measured during nine haemofiltration and seven haemodialysis procedures with high-permeability membranes. The t1/2 of vancomycin was 101 +/- 19 h in the interdialytic and interhaemofiltration period. There was no significant difference between the haemodialysis clearance (55.2 +/- 18.5 ml/min) and the haemofiltration clearance (66.8 +/- 13.6 ml/min). The redistribution phenomenon was about 25% in the post haemofiltration period and only 10% in the post haemodialysis period. Approximately 270 mg of vancomycin was recovered in dialysate or ultrafiltrate. With high-permeability membranes more commonly used in patients with end-stage renal disease, continuous monitoring of vancomycin therapy is recommended.

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.

Acute and chronic intoxication with carbromal preparations.

An important number of acute intoxications can be ascribed to the abuse of, until now, non-prescription carbromal preparations. Prolonged use of these drugs also leads to chronic intoxication with bromide accumulation. The clinical features and treatment of three suicidal Obral overdoses and of two patients presenting with bromism are presented. Laboratory findings, from admission to recovery, consist of qualitative TLC and quantitative HPLC drug assays in body fluids and the determination in plasma of the two competing ions chloride and bromide. The high frequency of acute intoxications and carbromal induced bromism stresses the need to bring these preparations under prescription.

Lorazepam fast-dissolving drug formulation (FDDF) and intravenous administrations as anaesthetic premedicants: a pharmacokinetic analysis.

The pharmacokinetics of lorazepam premedication were studied in 16 patients using two different formulations (intravenous and FDDF oral administrations). Arterial blood samples were taken at intervals for up to 600 min after administration of 4 mg of each formulation, and plasma lorazepam concentrations were determined by gas-chromatography with electron capture detection. Concentration-time data for individual subjects were analysed by model-independent methods. The derived pharmacokinetic parameters indicated a rapid distribution (median T1/2 lambda 1 i.v. = 15.2 min, median T1/2 lambda 1 oral = 31.6 min) into a steady-state volume of distribution approximating total body water, with a long elimination half-life and a low clearance. Vdss and clearance were similar with both treatments. The absorption of FDDF lorazepam was rapid in half of the patients and provided a high plasma concentration of lorazepam (Cmax = 61.8 ng ml-1) in a short time interval (Tmax = 58 min), but there were considerable inter-individual differences. This variability in absorption might explain why premedication with FDDF lorazepam is sometimes less effective than expected.

The inducing and inhibiting effects of sodium valproate in vivo on the biotransformation systems of xenobiotics in isolated rat hepatocytes.

1. The induction and inhibition of some biotransformation enzymes by valproate have been studied in hepatocytes isolated from rats treated with sodium valproate either i.p. or by subcutaneous implantation of osmotic pumps. 2. When valproate was given i.p., the cytochromes P-450 and b5, and aldrin epoxidase and glutathione S-transferase activities were significantly induced. 3. In contrast, valproate administered by osmotic pumps induced 7-ethoxycoumarin-O-deethylase activity, whereas aldrin expoxidase and glutathione S-transferase activities were significantly inhibited. At a valproate serum concentration of about 100 micrograms/ml for 2 weeks a significant induction of the cytochromes P-450 and b5 was observed. 4. Since there is a large difference between the half-lives of valproate in man and rodent, constant-rate delivery of valproate represents a better model for induction studies than i.p. injection.

Disposition kinetics of propofol during alfentanil anaesthesia.

The pharmacokinetics of a constant rate infusion of propofol were studied in 11 patients who received total intravenous anaesthesia for ENT surgery. Alfentanil was administered as an exponentially decreasing infusion using a computer-assisted infusion device with a constant target plasma alfentanil concentration of 300 ng/ml. Propofol was infused at a constant rate of 6 mg/kg/hours. Plasma alfentanil concentrations were determined by gas chromatography and whole blood propofol concentrations by high-performance liquid chromatography in arterial blood samples collected at selected times during and up to 8 hours after infusion. Pharmacokinetic modelling of the blood propofol concentration-time data indicated that a three-compartment open model with central elimination was most appropriate. Derived pharmacokinetic parameters were in agreement with previous studies on the pharmacokinetics of propofol. The plasma alfentanil concentrations in 10 patients significantly exceeded the expected values at any time during the infusion. The population mean bias amounted to 20.2% (SD 12.6). Only three data sets were significantly underestimated after the infusion was stopped (mean bias 11.9% (SD 25.5]. The elimination half-life of alfentanil was approximately 75 minutes (SD 21). We conclude that alfentanil does not interfere with the pharmacokinetic profile of propofol but that propofol induces higher plasma alfentanil concentrations than expected.