Succinate prodrugs as treatment for acute metabolic crisis during fluoroacetate intoxication in the rat.

Sodium fluoroacetate (FA) is a metabolic poison that systemically inhibits the tricarboxylic acid (TCA) cycle, causing energy deficiency and ultimately multi-organ failure. It poses a significant threat to society because of its high toxicity, potential use as a chemical weapon and lack of effective antidotal therapy. In this study, we investigated cell-permeable succinate prodrugs as potential treatment for acute FA intoxication. We hypothesized that succinate prodrugs would bypass FA-induced mitochondrial dysfunction, provide metabolic support, and prevent metabolic crisis during acute FA intoxication. To test this hypothesis, rats were exposed to FA (0.75 mg/kg) and treated with the succinate prodrug candidate NV354. Treatment efficacy was evaluated based on cardiac and cerebral mitochondrial respiration, mitochondrial content, metabolic profiles and tissue pathology. In the heart, FA increased concentrations of the TCA metabolite citrate (+ 4.2-fold, p < 0.01) and lowered ATP levels (- 1.9-fold, p < 0.001), confirming the inhibition of the TCA cycle by FA. High-resolution respirometry of cardiac mitochondria further revealed an impairment of mitochondrial complex V (CV)-linked metabolism, as evident by a reduced phosphorylation system control ratio (- 41%, p < 0.05). The inhibition of CV-linked metabolism is a novel mechanism of FA cardiac toxicity, which has implications for drug development and which NV354 was unable to counteract at the given dose. In the brain, FA induced the accumulation of ß-hydroxybutyrate (+ 1.4-fold, p < 0.05) and the reduction of mitochondrial complex I (CI)-linked oxidative phosphorylation (OXPHOSCI) (- 20%, p < 0.01), the latter of which was successfully alleviated by NV354. This promising effect of NV354 warrants further investigations to determine its potential neuroprotective effects.

Percutaneous K-wires vs palmar locking plate fixation for different types of distal radial fractures: a comparison of the outcomes of two methods to controll our guidelines.

The objective of the study was a comparison of the outcomes of K-wire vs plate fixation for distal radial fractures used according to the proposed institutional algorithm. Fracture configurations A2, A3, B1, B2, C1 and some C2 were operated on with K-wire pinning, whereas B3 and some B2, C3 and some C2 were with locking palmar-plate fixation. PATIENTS AND METHODS: Four hundred and sixty-seven patients were non-randomly allocated for either K-wire (n = 363) or palmarplate (n = 104) fixation. The results were assessed at 3 and 12 months by the same outcome measures. RESULTS: At the 3-month assessment, statistically significant differences in grip strength and the DASH scores were noted in favour of the plate-fixation group. At the 12-month assessment, statistically significant differences were observed in the wrist palmar and dorsal flexion, favouring the plate-fixation group. Statistically significant differences were noted in radiological measures of the palmar tilt and the ulnar variance, both favouring the plate-fixation method. Meaningful secondary dislocations were noted in ten patients, all in the K-wire-fixation group. CONCLUSION: We conclude that palmar locking plate fixation in even more severe fractures leads to better radiological and clinical outcomes than K-wire fixation in less severe fractures.

[Excessive left retroperitoneal abscess of an unknown aetiology perforating into the peritoneal cavity: a case report].

Retroperitoneal abscesses present a relatively uncommon complication of diseases of various abdominal organs, although most commonly they are related to acute appendicitis of retrocoecal location. The paper presents the case of a healthy patient in whom an excessive left retroperitoneal abscess developed, perforated into the peritoneal cavity, and almost perforated through the skin in XIIth intercostal space. The patient had no abdominal symptoms or signs, but complained from slight pain in the left lumbar area. The diagnosis was established based on abdominal computed tomography scanning and an operative treatment by laparotomy. The evacuation and drainage of the abscess was effective and the patient recovered. Bacteriological examination of the pus from the abdominal cavity revealed single colonies of anaerobic Fusobacterium species. The cause of the occurrence of the abscess remained unknown.

Metastasis of renal cancer to the wrist and hand: a case report.

Metastases to the hand and wrist are rare. The lung, breast and kidneys are the most common sites of primary lesions that metastasize in the hand. Phalanges are more commonly involved than metacarpals and wrist. We report the case of a neglected, large metastatic tumour involving a patient's left wrist and metacarpus originating form renal adenocarcinoma cancer, which appeared 2 years prior to the diagnosis of the primary neoplasm. The tumour was resected, but without oncologic margins. After obtaining histological veri- 􀏐ication (clear cell renal cell carcinoma) the patient had been proposed amputation, but he refused and was given chemotherapy. Imaging towards possible other distant metastases (CT and PET scanning) was negative. At 6 months follow -up the patient showed good general condition, no local recurrence, and regained some hand function.

[A multilevel obstruction of the digestive tract in a young female patient soon after delivery: a case report].

The article reports the case of a 31-year-old patient, in whom bowel ileus developed 2 days after natural delivery, and who in the second trimester underwent laparotomy due to mechanical obstruction involving the duodenum and small bowel and caused by swallowed foreign bodies. The course of pregnancy from the operation to delivery was uneventful. Preoperative diagnostics (barium meal) showed features of mechanical obstruction involving the duodenum and small bowel. The patient underwent surgery, and abdominal exploration revealed a largely distended duodenum filled by thick contents, dilated and involved in massive adhesions in the small bowel and a largely distended proximal colon. No site of critical stenosis of the bowel was found, and no other cause of disturbed intestinal passage was identified. Intraoperatively, no peristalsis was observed in the small bowel, although it was heard at abdominal auscultation before surgery. As adhesion release did not resolve the problem, a decision was made to discharge the small bowel and proximal colon by an incision of the caecum, followed by the formation of a cecostomy. Postoperative course was complicated by short episodes of upper digestive tract bleeding and diarrhoea, which disappeared soon after conservative therapy. The patient eventually recovered, and further gastroenterological investigations were inconclusive.

Results of the treatment of major, complex hand injuries.

UNLABELLED: Complex hand injuries are associated with serious consequences including long period off-work, permanent disability, inability to return to original profession or to work at all. As these injuries are common, they create considerable economical consequences and, therefore, it is desirable their treatment would be as perfect as possible to reduce potential loss of function. The aim of the study was analysis of the structure of complex, multi-structural hand injuries and evaluation of the outcomes of the treatment of these injuries in both medical (recovery of function) and economical (period of inability to work and costs of medical care) aspects. MATERIAL AND METHODS: The study presents the results of treatment of 78 patients suffered from severe, major hand injuries, involving damage of at least two of four anatomical structures within the hand or wrist (bones, tendons, arteries or nerves) as well as severe injury involving at least two digits. Functional results were assessed at a mean of 10 months after the accident. Tendons were repaired in all 42 patients, bones were fixed in 29 (69%), nerves were repaired in 21 (50%), arteries in 14 (33%) and in two patients skin defect was covered by the flap (one local and one groin flap). RESULTS: Total active motion of affected digits amounted 2/3 of normative active motion of the healthy digits and total grip strength approximated half of the grip strength of the unaffected hand. In patients with nerve injuries, a satisfactory recovery of sensation in the affected digits was obtained. Dexterity of the hand in daily activity was scored 30 points in DASH scale. Injury-related duration of sick leave in 31 patients worked at the time of the accident amounted 4.4 months in average (range 1-12). A total of 27 subjects (87% of worked) returned to work: 24 to their previous profession and three had to qualify for a new job. Total hospital costs of the treatment in the analysed group amounted a mean of 2600 PLN. CONCLUSION: The outcomes of the treatment of major hand injuries achieved in our institution over the period of the one year were satisfactory, considering their severity and complexity. These results, in our mind, show clearly advantages coming from an existence of qualified service for hand injuries.

[A reasonable algorithm for treatment of distal radius fractures]. / "Rozsadny" algorytm leczenia zlaman dalszego konca kosci promieniowej.

Fracture of the distal radius is one of the commonest injuries affecting upper limb, particularly in the older age. To date, no optimal treatment of these fractures was determined, although in the past twenty years an increased tendency to operative treatment with stable plate fixation is observed. Authors personal observations indicate a common malpractice associated with treatment of these fractures in our country, resulting from unjustified acceptance of some false preconceptions. Hence, a proposal of a "reasonable" algorithm of the treatment appeared, a scheme allowing for management of many patients with the method providing acceptable reduction of the fracture and its maintenance until fracture union, and, performable in limited logistic and economical conditions. Suggested algorithm. Conservative treatment of distal radius fractures confined only to non- or minimally displaced fractures. All other cases with exceeding acceptable dislocation are candidates for surgery. The fractures no requiring--in assumption--a stable fixation: A2, A3, B1, C1 and C2 in AO classification we propose to treat with percutaneous K-wire pinning. Those, more unstable: B2, B3, C3, metaphyseal and high-energy A3 and C2 fractures in young adults we suggest to fix with volar locking plate. In C3, comminuted fractures and with severe soft tissue damage should be given external fixation. The proposed algorithm is a result of an experience collected in authors' institution, supported by evidence form literature. It confirmed its effectiveness in the reference department for hand injuries and it seems that it may contribute to improving the level of the treatment of distal radius fractures in our country.

[A comparison of the results of the conservative vs operative by percutaneous Kirschner-wiring treatment of fractures of the distal radius]. / Porównanie wyników leczenia zlaman nasady dalszej kosci promieniowej metoda zachowawcza i przezskórnym zespoleniem drutami Kirschnera.

UNLABELLED: The objective of this study was comparing the results of the conservative (close reduction and immobilisation in the plaster splint) vs operative (percutaneous Kirschner-wiring) treatment of fractures of the distal radius. Sixty patients, 49 women (82%) and 11 men (18%), who sustained an isolated, displaced fractures were randomly allocated to operative (30 patients) or conservative (30 patients) treatment. All patients were followed up at 1.5, 3 and finally at 6 months after fracture. The following variables were analysed: rate of secondary displacement, wrist range of motion, fingers loss of flexion, total grip strength, dorsal or volar tilt, radial angulation and radial length on the X-ray. Function of the hand was assessed with DASH questionnaire, cold sensitivity with McCabe scale and final outcome in Gartland-Werley and Castaing complex scales. The rate of secondary displacement was considered a primary outcome measure. RESULTS: Secondary displacement was noted in 8 patients (27%) treated conservatively, of whom 7 required surgery and those were withdrawn from the trial. Three fractures (10%) treated operatively displaced secondarily, but none required additional operation and all completed the follow-up. The rate of secondary displacement was statistically significantly (chi2 test, p < 0.05) more frequent in conservatively treated group. With regard to other analysed parameters, the statistically significant differences was found in total grip strength at 3 and 6 months assessments, and in DASH score at 6 months assessment, both favouring operative method. The remaining variables did not differ significantly between the groups treated conservatively and operatively. CONCLUSION: Our results have demonstrated, that percutaneous Kirschner-wiring of fractures of the distal radius is superior to the conservative treatment, because statistically significantly reduces the risk of secondary displacement and allows to obtain a stronger grip and better hand function within 6 months after fracture.

[An instability of the fractures of the distal radius--a review]. / Niestabilnosc zlaman nasady dalszej kosci promieniowej--przeglad pismiennictwa.

Many fractures of the distal radius, particularly articular and comminuted are considered unstable what result in secondary displacement in the course of the treatment, necessity of repeated reduction or delayed operative treatment. These fractures should be primarily given surgery, since their conservative treatment will probably fail. The objective of this article was to review literature about criteria of instability of the fractures of the distal radius, an attempt to define instability pattern and to propose a practical approach to the problem. Of the analyzed factors indicating instability, the following: radial shortening, degree of dorsal or volar tilt, dorsal comminution, articular involvement and older age of the patient revealed their greatest prognostic significance. The degree of the radial inclination or radial shift had a minor prognostic value. Greater number of factors elevates the risk of instability of the fracture, however the presence of the only one or two factors does not warrant maintenance of the adequate reduction. In more than half of the fractures of the distal radius, secondary displacement occur later than 2 weeks after the reduction, what suggest need of radiological control during the full period of the immobilization. An operative treatment of distal radius fractures significantly reduces rate of secondary displacements and risk of malunion. An increase of indication to surgery of the majority of fractures of the distal radius meeting at least one of above mentioned criteria of instability seems to be reasonable, although difficult therapeutic algorithm.