Cedomir Vucetic

Synergistic interaction between ketamine and magnesium in lowering body temperature in rats

A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature via N-methyl-d-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. This study is aimed at evaluating the effects of ketamine and magnesium sulfate on body temperature in rats, and to determine the type of interaction between them. The body temperature was measured by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200-250g). Magnesium sulfate (5 and 60mg/kg, sc) showed influence neither on baseline, nor on morphine-evoked hyperthermic response. Subanesthetic doses of ketamine (5-30mg/kg, ip) given alone, produced significant dose-dependent reduction in both baseline colonic temperature and morphine-induced hyperthermia. Analysis of the log dose-response curves for the effects of ketamine and ketamine-magnesium sulfate combination on the baseline body temperature revealed synergistic interaction, and about 5.3 fold reduction in dosage of ketamine when the drugs were applied in fixed ratio (1:1) combinations. In addition, fixed low dose of magnesium sulfate (5mg/kg, sc) enhanced the temperature lowering effect of ketamine (1.25-10mg/kg, ip) on baseline body temperature and morphine-induced hyperthermia by factors of about 2.5 and 5.3, respectively. This study is the first to demonstrate the synergistic interaction between magnesium sulfate and ketamine in a whole animal study and its statistical confirmation. It is possible that the synergy between ketamine and magnesium may have clinical relevance.

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6–11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.

Simultaneous bilateral avulsion fracture of the tibial tubercle in adolescent: a case report.

Acute avulsion of the tibial tubercle is an uncommon injury, accounting for less than 1% of all physeal injuries. Simultaneous bilateral avulsion fractures of the tibial tubercle are extremely rare. Only 10 cases have been reported in the literature to date. We report a case of a 15-year-old boy who suffered from the bilateral avulsion fractures of the tibial tubercle during basketball in take-off phase of the high jump. He went through surgery and 4 years after index procedures he has no deformities, the knee is painless and he participates in sport activities on daily basis.

Pharmacological Evaluation of 3-Carbomethoxy Fentanyl in Mice

In many animal species, as well as in humans, high doses of fentanyl (F) produce marked neurotoxic effects, such as muscular rigidity and respiratory depression. The antinociception (hot-plate test), impairment of motor coordination (rotarod test) and acute toxicity of intraperitoneal newly synthesized analogs, (±)cis-3-carbomethoxy- fentanyl (C) and (±)trans-3-carbomethoxyfentanyl (T) were evaluated in mice. The compounds tested induced antinociception, impairment of performance on the rotarod, and lethality in a dose-dependent manner. The relative order of antinociceptive potency was similar to motor impairment potency, as well as lethality: F > C > T. Naloxone hydrochloride (1 mg/kg; sc) abolished all the effects observed, suggesting that they are mediated via opioid receptors, most probably of μ type. There were no significant differences between the therapeutic indices of F, C and T. It is concluded, the introduction of 3-carbomethoxy group in the piperidine ring of the fentanyl skeleton reduced the potency, but did not affect tolerability and safety of the compound.

[Legg-Calvé-Perthes disease--diagnostics and contemporary treatment].

Legg-Calvé-Perthes disease represents avascular necrosis of the femoral head in a growing child. It commonly affects children aged 2-14 years, mostly boys, and has familiar pattern. The etiology of this disease is unknown. It is based on avascular necrosis due to variations of the femoral head vascular supply, trauma, coagulation of endocrine disturbances. The disease presents with limping and pain localized in the hip with projection to thigh and knee, frequently accompanied by the limitation of abduction and internal rotation, as well as slight limitation in flexion of about 20 degrees. Plain radiography is most informative additional diagnostic procedure, enabling assessment of the stage of disease, containment of the femoral head within the acetabulum, acetabular coverage and the extent of disease. Main treatment goal is obtaining the spherical congruity of the hip joint. This can be achieved by abduction bracing, varization femoral osteotomies and various innominate osteotomies (sometimes combined with femoral osteotomies). Children younger than four years of age, with minimal femoral head involvement, do not need any treatment. These children with a larger involvement, older than four years of age, with possible containment in hip abducion, should be treated by one of the following procedures: Salter innominate osteotomy, Salter innominate osteotomy with femoral shortening, or triple pelvic osteotomy. The patients with containment of the hip is not possible in abduction (related to subluxation and femoral head crush), should be treated by Chiari pelvic osteotomy.

Forearm reconstruction after loss of radius: Case report

INTRODUCTION Osteomyelitis of the radius resulting in the radial clubhand is a very rare condition and few studies have been published about its prognosis and treatment. CASE OUTLINE This is a case report of hematogenous osteomyelitis of the radius with a complete loss of the radius leaving only the distal radial metaphysis to carry the carpus. In order to achieve best functional results, four-step operative protocol was performed for reconstruction; lengthening of the forearm by external fixator, radioulnar transposition to create a one-bone forearm, plate removal and transposition of brachioradialis to the extensor pollicis longus as well as proximal row carpectomy. After nine years of the last operation, the function of the elbow and hands is good with acceptable cosmetic result. The forearm is 5 cm shorter and there has been a persistent mild limitation of palmar flexion. CONCLUSION Creation of the one-bone forearm normalizes the elbow and wrist function, corrects forearm malalignment, and improves forearm growth potential.

Ilizarov technique as a reliable option in limb salvage surgery

Dear Editor,We read the original paper “Osteocutaneous thermalnecrosis of the leg salvaged by TSF/Ilizarov reconstruction.Report of 7 patients” with great attention [1]. The articlereports on a complication of reamed intramedullary fixationof the tibia and a solution to the problem using the Ilizarovmethod. The authors rightfully consider the Ilizarovtechnique a method of choice in severe limb salvagesituations. There is abundant experience in application ofthe Ilizarov technique in the treatment of infected defectpseudoarthrosis, and this paper further expands indicationsfor its use.Our own experience with the Ilizarov technique insituations where other treatment methods could not beapplied or had failed to provide expected outcome, is verypositive [2–4]. The technique is tissue sparing and producessignificant regenerative and stimulative effects. Therefore,it can be successfuly and simply applied in cases ofinfection, bony and soft-tissue defects, and in multiplecomorbidity situations. Its drawbacks are minimal com-pared with its advantages and possibilities. Even in themost complex limb salvage procedures following injury ordisease, the Ilizarov technique shows great impact onhealing of bony and soft-tissue defects, bone union, andcorrection of deformity.

NEUROTOXICITY EVALUATION OF FENTANYL ANALOGS IN RATS

This study aimed at evaluating the neurotoxicity of fentanyl analogs: (±)-cis-3-carbomethoxy fentanyl (C) and (±)-trans-3carbomethoxy fentanyl (T) in rats. C and T are less potent (2.4-3.1 and 8.4-12.3 times, respectively) than fentanyl (F) in producing both antinociception and morphine-like neurotoxic effects: loss of pinna reflex, Straub tail, impairment of motor coordination, catalepsy, loss of corneal reflex and loss of righting reflex. All of the effects tested were dose-dependent and they were abolished by pretreatment with naloxone, nonselective antagonist of opioid receptors, indicating that they are mediated via opioid receptors. Further, F, C and T exhibited similar relative potencies in producing all tested effects, indicating that similar receptors are involved in producing antinociceptive and neurotoxic effects, most probably of type. By using equiantinociceptive doses, C and T produced significantly shorter duration of both antinociception and neurotoxicity than F. No significant differences between therapeutic indices for F, C and T were found, indicating that these compounds are equally safe and tolerable in respect to the neurotoxic effects tested. Neurotoxicity testing presented in this paper may be useful in studying the structure-activity relationship of opioid congeners.

Flat feet in children

The authors describe flatfoot, as one of very frequent deformities in everyday medical practice. A special condition of the deformity associated with a calcaneal valgus position and complicated by a knee valgus position (as a consequence of non-treatment) is described. Also, the precise anatomy of the longitudinal foot arches (medial and lateral), definition and classification of the deformity, clinical findings and therapeutic protocols are proposed. The authors especially emphasise that the need for having extensive knowledge on the differences between a flexible and rigid flatfoot, having in mind that the treatment of flexible flat foot is usually not necessary, while the treatment of rigid flatfoot is usually unavoidable.