Central nervous system relapse in CD56+, FLT3/ITD+ promyelocytic leukemia.

Central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare and tends to be seen mostly following treatment with all-trans retinoic acid (ATRA), due to prolonged patient survival and poor penetration of the drug in the CNS. At least 10% of extramedullary relapses in APL involve the CNS, and associated factors include an increased age, the BCR isoform, the development of differentiation syndrome, a high white cell count at presentation and hemorrhage into the CNS during induction therapy. We present the case of a patient with high-risk APL, CD56+, CD2+ in whom a CNS relapse was diagnosed through the presence of a PML/RARα rearrangement on PCR of the cerebrospinal fluid (CSF).

Thalassemia major. A report of two cases with severe skeletal involvement.

Beta thalassemia major is rare in Serbia. Previously incurable, affected patients now live to adulthood with regular blood transfusions. The improvement in supportive treatment over recent decades has given rise to many more patients suffering from the associated metabolic complications of anaemia and iron overload, such as osteopenia and other skeletal changes. We present two patients with severe beta thalassemia major from early childhood, who encountered pathological long-bone fractures during the clinical course of their disease. One suffered a distal femoral diaphyseal fracture, and the second a distal tibia fracture. Both fractures occurred in osteopenic bone and were managed non-operatively due to the patients' general medical condition. Despite intense medical intervention, both patients died from disease progression within one year of their fractures, aged 23 and 24 years. As life expectancy rises it is anticipated that an increased number of beta thalassemia major patients will suffer pathological long-bone and other osteoporotic fractures. These fractures appear to both herald and contribute to a general clinical deterioration of this disease. Advances in stem-cell technology may hold the key for a definitive cure.

The challenge of osteo-articular tuberculosis in the twenty-first century: a 15-year population-based study.

SETTING: Serbia, an intermediate tuberculosis (TB) incidence country in socio-economic transition. OBJECTIVE: To examine the epidemiological and clinical pattern of osteo-articular TB (OATB) in Serbia over 15 years. DESIGN: This retrospective observational study included OATB cases diagnosed between 1 January 1993 and 31 December 2007, according to the National Referral Institute of Lung Diseases and TB in Belgrade and the Central TB Register. Population estimates with extrapolations were based on 1991 and 2002 census data. RESULTS: The 295 OATB cases represented 10.9% (range 5.3-20.2) of all extra-pulmonary TB cases notified in Serbia over the period. One tenth of these were relapses. The incidence rate showed a significant increasing trend (y = 0.1167 + 0.0175x, R(2) = 0.3196), with an average age-specific incidence rate of 0.26 per 100 000 population. The peak number of cases was in the 45-64 year age group for both men and women. The average male:female ratio was 0.85. The outcome was favourable for 279 of the 295 patients (94.6%). In addition to a standardised chemotherapy regimen, 25.4% patients underwent surgery. CONCLUSION: The increasing time trend of OATB is caused by increased morbidity, a higher TB detection rate and better notification. Although rare in children, OATB remains a challenge in clinical practice.

Verrucous carcinoma of the foot: a case report.

We present a case of verrucous carcinoma of the foot in a 34-year-old man. This is a rare, locally invasive, well-differentiated, low-grade squamous cell carcinoma, with human papilloma virus as a possible causative agent. It follows a chronic course and mimics a variety of skin lesions, delaying diagnosis by up to 15 years. The definitive diagnosis is made histologically, and treatment by wide local excision is recommended. Our patient underwent wide local excision and partial 5th metatarsal amputation because of invasive disease, local infection, and peripheral vascular disease. There were no postoperative complications. At the 10-year follow-up, there were no signs of tumour recurrence.

Validation of orthopaedic bench models for trauma surgery.

The aim of this study was to validate the use of three models of fracture fixation in the assessment of technical skills. We recruited 21 subjects (six experts, seven intermediates, and eight novices) to perform three procedures: application of a dynamic compression plate on a cadaver porcine model, insertion of an unreamed tibial intramedullary nail, and application of a forearm external fixator, both on synthetic bone models. The primary outcome measures were the Objective Structural Assessment of technical skills global rating scale on video recordings of the procedures which were scored by two independent expert observers, and the hand movements of the surgeons which were analysed using the Imperial College Surgical Assessment Device. The video scores were significantly different for the three groups in all three procedures (p < 0.05), with excellent inter-rater reliability (alpha = 0.88). The novice and intermediate groups specifically were significantly different in their performance with dynamic compression plate and intramedullary nails (p < 0.05). Movement analysis distinguished between the three groups in the dynamic compression plate model, but a ceiling effect was demonstrated in the intramedullary nail and external fixator procedures, where intermediates and experts performed to comparable standards (p > 0.6). A total of 85% (18 of 21) of the subjects found the dynamic compression model and 57% (12 of 21) found all the models acceptable tools of assessment. This study has validated a low-cost, high-fidelity porcine dynamic compression plate model using video rating scores for skills assessment and movement analysis. It has also demonstrated that Synbone models for the application of and intramedullary nail and an external fixator are less sensitive and should be improved for further assessment of surgical skills in trauma. The availability of valid objective tools of assessment of surgical skills allows further studies into improving methods of training.

Postoperative fall after the use of the 3-in-1 femoral nerve block for knee surgery: a report of four cases.

We present a serious postoperative complication related to the use of femoral nerve block in 4 patients, each of whom fell and sustained further injury. Preoperatively, all patients underwent a 3-in-1 femoral nerve block with 30 to 35 ml of 0.25% levobupivacaine with 1:200,000 epinephrine, with guidance by a nerve stimulator. After the falls, neurological examination of the operated legs revealed reduced 2-point discrimination, pain, and/or light touch sensation. All patients underwent further operation for the fall injury and had delayed full weight bearing. We recommend that, after having a femoral nerve block, patients should undergo enhanced postoperative evaluation of blockade and proprioceptive function to ensure safe neurological function before mobilisation.

Malignant intraosseous peripheral nerve sheath tumour of the proximal femur: a case report.

We report a rare case of an intraosseous malignant peripheral nerve sheath tumour of the femoral head and neck. The tumour presented as a well-defined radiolucent lesion on plain radiography. Computed tomography showed aggressive destruction of the bone with no involvement of the adjacent soft tissues. Magnetic resonance imaging revealed an isointense signal intensity on T1-weighted images, hyperintensity on T2-weighted images, and non-homogeneously increased signal intensity after administration of contrast media. The final diagnosis was based on pathohistologic analyses due to the non-specific nature of the lesion.

Left-sided gallbladder associated with congenital liver cyst.

BACKGROUND: A left-sided gallbladder is a rare congenital anomaly defined as a gallbladder attached to the lower surface of the left lateral segment of the liver, i.e. to the left of the interlobar fissure and round ligament. CASE OUTLINES: In two women aged 42 and 70 years a left-sided gallbladder was associated with a congenital cyst of the liver. In the first patient, the ectopic gallbladder was an incidental finding at operation for a symptomatic liver cyst; as the gallbladder was normal it was not removed. The second patient underwent operation for chronic calculous cholecystitis, when the left-sided gallbladder and congenital liver cyst were found. An operative cholangiogram was normal, the cystic duct joining the common bile duct from the right side. The gallbladder was removed, and the cyst was de-roofed. Both patients had an uneventful recovery and remain symptom-free at 12 and 9 years respectively. DISCUSSION: To the best of our knowledge, the association of these two congenital anomalies has not been described previously.

In vitro sensitivity of hematopoietic progenitors to tiazofurin in refractory acute myeloid leukemia and in the blast crisis of chronic myeloid leukemia.

The effect of Tiazofurin (TR) on the in vitro growth of bone marrow (BM) and peripheral blood (PB) leukemic progenitors was investigated in 29 patients. Nineteen of the patients were suffering the blast crisis of chronic myeloid leukemia (bcCML) and ten patients refractory acute myeloid leukemia (AML). PB and BM mononuclear cells were cultured in methylcellulose alone or with concentrations of TR ranging between 10 and 200 microM. TR produced a dose dependent inhibition of colony forming unit (CFU)-blast growth in all the samples tested from BM and PB. The most effective concentrations of TR used were 150 and 200 microM, while concentrations of less than 50 microM TR were not adequate for 50% inhibition of cell growth (IC50). Differences were found in the response of CFU-blasts to TR related to the type of underlying leukemia. Inhibition of CFU-blast growth was more pronounced in bcCML than in AML in both the BM and PB samples. The concentration of TR required to induce IC50 in bcCML was 50 microM, while the same effect in AML required a concentration of 150 microM. Analysis of the control samples also revealed that CFU-blasts from bcCML produced smaller numbers of colonies, though these differences were not statistically significant. It has therefore been demonstrated that TR has strong in vitro anti-leukemic activity, more pronounced in bcCML than in refractory AML. We thus feel this study gives further rationale for the clinical application of TR, and would strongly support this.

Choledochal cysts in adults and their complications.

BACKGROUND: Despite refinements in the management of choledochal cysts in children, an increasing number of patients present with ongoing symptoms in adult life. The aim of this study was to review the management of adult patients with choledochal cysts in a tertiary referral centre. METHOD: A retrospective review was carried out of all adult patients presenting with choledochal cysts to this department between 1992 and 2000. Patient records were reviewed and detailed analyses were made of the clinical presentation, radiological and biochemical findings, anatomical anomalies, management, complications and outcomes. RESULTS: Of 16 patients (12 women and 4 men; median age 23 years), 8 had undergone previous upper gastrointestinal operations before referral, including 5 who had had previous cyst drainage procedures. All patients underwent elective complete cyst excision with Roux-en-Y hepaticojejunostomy. There were no operative deaths and there was a low early postoperative morbidity rate (25%). There was no evidence of biliary malignancy in any cyst. During a median postoperative follow-up of 44 months, five patients (31%) continued to experience cholangitis and two of these required additional revisional procedures, but are now symptom-free. CONCLUSION: Patients with choledochal cysts should be referred to specialised tertiary surgical units. Total choledochal cyst excision with Roux-en-Y hepaticojejunostomy is the treatment of choice. Patients with previous inadequate cyst excisional procedures should undergo revisional surgery, to reduce recurrent symptoms and the risk of developing cholangiocarcinoma.

Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein and sulphated glucuronyl paragloboside.

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.

Secondary myelofibrosis in visceral leishmaniasis--case report.

A 39-year-old woman with a history of travel to the Montenegrin coast presented with a 9-month long history of fever and weakness, and on examination was found to be emaciated with hepatosplenomegaly and pancytopenia. Marrow aspiration showed poor cellularity with abundant Leishman Donovan (LD) bodies in the macrophages. Bone marrow trephine biopsy revealed a marked myelofibrosis (Manoharan classification: grade III) with osteosclerosis. The impression smears of a trephine biopsy stained with Güiemsa also showed LD bodies. The patient did not exhibit evidence of any risk factors for visceral leishmaniasis (VL). She was treated with meglumine antimoniate (Glucantime) without any adverse effect. The spleen returned to a normal volume after 4 months and bone marrow trephine biopsy performed 6 months after initiation of the therapy had returned to normal. A diagnosis was difficult to establish as VL is rarely encountered in the continental parts of Yugoslavia, and with the presence of associated myelofibrosis it could easily have been mistaken for chronic idiopathic myelofibrosis. The association of myelofibrosis with visceral leishmaniasis has been reported in the literature only three times; we thus feel that documentation of this case is merited.

Ketamine potentiates the responses of the rat superior cervical ganglion to GABA.

The responses of the rat superior cervical ganglion to gamma-aminobutyric acid (GABA) were recorded in vitro using extracellular electrodes. Ketamine was found to increase the amplitude of these responses by up to 100%. This potentiation was seen at ketamine concentrations as low as 18 microM, reached maximum at 180 microM and then declined as the concentration was raised further. Ketamine (90 microM and over) depressed the nicotinic responses of the ganglia. The log concentration-effect curve to GABA was shifted to the left, and the maximum response increased, by ketamine. Inhibition of glial uptake of GABA did not prevent the effect of ketamine. The effects of 3-aminopropane sulphonic acid, which has a very low affinity for this GABA uptake mechanism, were also increased by ketamine. We conclude that ketamine, at concentrations which are found during general anaesthesia, potentiates the responses of the ganglion to GABA, by a mechanism other than inhibition of uptake, and suggest this may be due to action at the GABA receptor site.