Oral tuberculosis associated with a treatment with anti-rheumatic drugs

BACKGROUND: The use of immunosuppressive medication is a dominant risk factor for infection in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is one of the traditional disease-modifying antirheumatic drugs. Adalimumab [a human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody] represent an important advance in the treatment of RA and has been recently come in use. TNF-alpha plays a role in the host defense against Mycobacterium tuberculosis and notably in granuloma formation. Infections occur at a high rate among those who use one or the combination of the two medications. METHOD: We examined a female patient that was referred to our department for evaluation and treatment of a granular lesion on the soft palate and uvula, complaining of mild dysphagia. The patient was treated for 4 months with MTX and adalimumab for RA before the oral lesion appeared. RESULTS: The histopathological examination of a specimen of the oral lesion, taken by biopsy, showed a chronic inflammation characterized by tuberculous granulomas. Polymerase chain reaction test and culture of a new specimen was positive for M. tuberculosis. CONCLUSIONS: The therapeutic use of MTX or/and adalimumab for the treatment of RA or few others diseases, can cause oral tuberculosis.     

Vestibular syndromes in the roll plane: Topographic diagnosis from brainstem to cortex

Central vestibular syndromes may be classified according to the three major planes of action of the vestibuloocular reflex, secondary to a lesional tone imbalance in either the horizontal yaw plane or the vertical pitch or roll plane. The clinical signs, both perceptual and motor, of a vestibular tone imbalance in the roll plane are ocular tilt reaction (OTR), ocular torsion, skew deviation and tilts of the perceived visual vertical (SVV). Either complete OTR or skew torsion without head tilt indicates a unilateral peripheral deficit of otolith input or a unilateral lesion of graviceptive brainstem pathways from the vestibular nuclei (crossing midline at the pontine level) to the interstitial nucleus of Cajal (INC) in the rostral midbrain. SVV tilts are the most sensitive sign of a vestibular tone imbalance in roll and occur with peripheral or central vestibular lesions from the labyrinth to the vestibular cortex. All tilt effects, perceptual, ocular motor and postural, are ipsiversive (ipsilateral eye undermost) with unilateral peripheral or pontomedullary lesions below the crossing of the graviceptive pathways. All tilt effects are contraversive (contralateral eye undermost) with unilateral pontomesencephalic brainstem lesions and indicate involvement of the medial longitudinal fasciculus or the rostral midbrain (INC). Unilateral lesions of vestibular structures rostral to the INC typically manifest with deviations of perceived vertical without concurrent eye–head tilt. OTR in unilateral paramedian thalamic infarctions indicates simultaneous ischemia of the paramedian rostral midbrain including the INC. Unilateral lesions of the posterolateral thalamus can cause thalamic astasia and moderate ipsiversive or contraversive SVV tilts, thereby indicating involvement of the vestibular thalamic subnuclei. Unilateral lesions of the parietoinsular vestibular cortex cause moderate, mostly contraversive SVV tilts. An SVV tilt found with monocular but not with binocular viewing is typical for a trochlear or oculomotor palsy rather than a supranuclear graviceptive brainstem lesion.     

Mechanism of hydrolysis and structure-stability relationship of enaminones as potential prodrugs of model primary amines

The objective of this work was to investigate the chemistry and the structure-stability relationship of enaminones (a class of enamines formed between a primary amine and a 1,3-dicarbonyl compound) and to evaluate their potential usefulness as prodrugs of primary amines. The acid-catalyzed degradation of the enaminones was found to be very sensitive to minor differences in the structure of the 1,3-dicarbonyl compound used to form the enaminone, but relatively insensitive to changes in the amine portion of the enaminones. A correlation was found between the rate of enaminone hydrolysis and the pKa of the 1,3-dicarbonyl compound, suggesting that the rate-controlling step in the hydrolysis of the enaminones was the proton addition to the vinyl carbon of the enaminone. Enaminones formed with cyclic 1,3-dicarbonyl compounds were significantly more stable than those formed with structurally similar acyclic compounds. Based on chemical stability considerations alone, enaminones do not appear to be good candidates as prodrugs of primary amines. Evidence is presented, however, that enaminones formed between amines and 1,3-ketoesters or lactones may be subject to enzyme-catalyzed degradation. Further research on the design of enaminones destabilized by a triggering enzymatic event that results in the loss of conjugation (e.g., ester or lactone hydrolysis or an oxidation/reduction event) may prove worth pursuing.     

Success rate and duration of orthodontic treatment for adult patients with palatally impacted maxillary canines.

This study was undertaken to examine the success rate and the length of orthodontic treatment of impacted maxillary canines in adult patients. A sample of 19 adults (mean age, 28.8 +/- 8.6 years; range, 20-47 years), who had been treated for a total of 23 impacted maxillary canines, was compared with a younger control group (mean age, 13.7 +/- 1.3 years; range, 12-16 years). The control subjects were chosen for a similar degree of impaction difficulty by carefully matching the positions of the impacted canines in the 3 planes of space. The success rate among the adults was 69.5% compared with 100% among the younger controls. The lower success rate was due to 5 canines that had failed to erupt and 2 canines that had been partially extruded but could not be aligned in the arch. The duration of treating the overall malocclusion of the adults and young subjects did not materially differ. However, the adults showed significant increases in the duration and number of treatment visits required for resolving the canine impaction, in both the simpler and the more difficult cases. When further divided by age, all the failed canines were found in the older (over 30) adult subgroup. It was concluded that the prognosis for successful orthodontic resolution of an impacted canine in an adult is lower than that in a younger patient and that the prognosis worsens with age. Furthermore, when such treatment is undertaken, its successful completion should be expected to take considerably longer.     

Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.     

Could bipolar vessel sealers prevent bile leaks after hepatectomy?

BACKGROUND AND AIMS: The aim of this work was to test the feasibility of using a bipolar low thermal acting system inducing collagenic sealing but not protein coagulation to secure hepatic parenchyma cutting. MATERIALS AND METHODS: Thirty consecutive hepatectomies were carried out using kellyclasy plus ligatures and clips (controls), while the following 50 hepatectomies used kellyclasy plus bipolar vessels sealer (BVS). Blood loss, duration of hepatic pedicle clamping, length of hospital stay, and complications were recorded. RESULTS: There was no statistically significant difference in blood loss and duration of clamping between controls and BVS. Specific complications (9/21 in the control group vs 1/49 for the BVS group, p<0.00045) and length of hospital stay (14 days in the control group vs 11 days in the BVS group, p<0.014) were statistically lower in BVS group than in the controls, mainly due to prevention of bile duct leakages. CONCLUSIONS: Our data suggest that BVS may be particularly efficient to achieve bilistasis leading to the highest level of safety in performing hepatectomies. Further studies are now needed to confirm its superiority on the classical biliary ducts occlusion techniques.     

Common carotid agenesis and internal carotid stenting.

Agenesis of common carotid artery is rare and no report of stenting procedures (carotid artery stenting) for associated stenosis of the internal carotid have been published. We report a case of internal carotid stenosis associated with this anomaly. A 73-year-old male with left internal carotid artery originating from the arch, with significant stenosis, was referred to us. Wallstent was deployed with success. Carotid artery stenting should be reserved to uncomplicated arch anatomy and plaques with low fragmentation risk.     

Synthesis procedure for routine production of 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380).

2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380) was among the first subtype selective radioligands to visualise the in vivo distribution of alpha4beta2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in human brain. We developed a one-pot synthesis for the preparation of 2-[18F]F-A-85380 in a commercially available TRACERlab FXF-N synthesis module. The synthesis comprises a nucleophilic substitution followed by hydrolysis of a t-butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous application up to 20 G Bq 2-[18F]F-A-85380 were produced from a starting activity of 100 G Bq [18F]fluoride in 60 min with a specific activity of about 4.10(5)GBq/mmol and a mean radiochemical purity of more than 99%.     

Degradation of Paclitaxel and Related Compounds in Aqueous Solutions III: Degradation Under Acidic pH Conditions and Overall Kinetics

Paclitaxel and related taxanes are complex molecules with numerous hydrolysable ester groups, possible epimerization at the 7‐position, and possessing a strained oxetane ring, a possible site for acid‐catalyzed cleavage. Presented here is the stability of paclitaxel, 10‐deacetylbaccatin III, baccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester in aqueous solution over a pH range of 1–5 at various temperatures. Analysis of various samples was by HPLC–UV and LC–MS. Baccatin III, 10‐deacetylbaccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester were found to undergo acid catalysis since pH‐rate profiles all followed a first‐order dependency in hydrogen ion concentration. No evidence of any epimerization was noted at acidic pH values. Baccatin III and 10‐deacetylbaccatin III showed similar degradation rates with possible products being possible dehydration around the 13‐hydroxy group and cleavage of the oxetane ring. Cleavage of the 10‐acetyl group of baccatin III was a minor initial pathway. N‐Benzoyl‐3‐phenylisoserine ethyl ester degraded significantly slower than both 10‐deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate between that of N‐benzoyl‐3‐phenylisoserine ethyl ester and 10‐deacetylbaccatin III. The pH of maximum stability for all compounds appeared to be around pH 4. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1288–1298, 2010