Cranial melioidosis presenting as a mass lesion or osteomyelitis

OBJECT: Melioidosis is caused by Burkholderia pseudomallei and causes multiple abscesses in different organs of the body. Cranial melioidosis, although uncommon, is sometimes confused with tuberculosis and is therefore under-recognized. The authors report on 6 cases of cranial infections caused by Burkholderia pseudomallei, presenting as mass lesions or cranial osteomyelitis, and review the literature. METHODS: The authors performed a retrospective review of the records of patients with cranial melioidosis treated at their institution between 1998 and 2005 to determine the presentation, management, and outcome of patients with this infection. RESULTS: Of the 6 patients diagnosed with cranial melioidosis during this period, 4 had brain abscesses and 2 had cranial osteomyelitis. All patients were treated surgically, and a diagnosis was made on the basis of histopathological studies. All patients were started on antibiotic therapy following surgery and this was continued for 6 months. One patient died soon after stereotactic aspiration of a brain abscess, and the other 5 patients had good outcomes. CONCLUSIONS: Cranial melioidosis is probably more prevalent than has been previously reported. A high index of suspicion, early diagnosis, initiation of appropriate antibiotic therapy and treatment for an adequate period are essential for assuring good outcome in patients with cranial melioidosis. The authors recommend surgery followed by intravenous ceftazidime treatment for 6 weeks and oral cotrimoxazole for 6 months thereafter in patients with cranial melioidosis.     

DBU mediated one-pot synthesis of triazolo triazines via Dimroth type rearrangement

Herein we report an efficient one-pot synthesis of [1,2,4]triazolo[1,5 a][1,3,5]triazines from commercially available substituted aryl/heteroaryl aldehydes and substituted 2-hydrazinyl-1,3,5-triazines via N-bromosuccinimide (NBS) mediated oxidative C–N bond formation. Isomerisation of [1,2,4]triazolo[4,3-a][1,3,5]triazines to [1,2,4]triazolo[1,5-a][1,3,5]triazines is driven by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affording both isomers with good to excellent yields (70–96%).

We demonstrate a simple yet efficient one-pot synthesis of two triazolotriazine isomers via DBU mediated Dimroth type rearrangement with excellent yields.

Purines are nitrogen-containing heterocycles and are structural motifs in the nucleobases adenine and guanine of DNA as well as RNA. Purine nucleotides (ATP, GTP, cAMP, cGMP, NAD, FAD) also act as co-factors, substrates, or mediators in the functioning of numerous proteins.¹ Therefore, bioisosteres of purines are widely explored and exploited by pharmaceutical chemists in developing new drug entities. Heterocycles containig the 1,3,5-triazine ring act as bioisosteres of purine, which exist as two isomers, namely [1,2,4]triazolo[4,3-a][1,3,5]triazine and [1,2,4]triazolo[1,5-a][1,3,5]triazine (Fig. 1), which have been extensively studied as adenosine receptor antagonists,^2,3 as well as for other pharmacological activities^1,4,5 (Fig. 2). Literature reports suggest that [1,2,4]triazolo[1,5-a][1,3,5]triazine has been exploited extensively in drug discovery as compared to its corresponding isomer. Further, from the literature it is evident that symmetrical disubstituted triazines,^6–9 especially morpholine^10–12 substituted, have displayed broad pharmacological activities.Open in a separate windowFig. 1Structure of isomers of triazolo–triazine.Open in a separate windowFig. 2Biologically active molecules of [1,2,4]triazolo[4,3-a][1,3,5]triazine (1) and [1,2,4]triazolo[1,5-a][1,3,5]triazine (2, 3, 4).Various synthetic methods have been reported for the C–N bond formation by employing different starting materials^13–15via oxidative cyclisation,¹⁶ high temperature condition^17–19 and/or metal-catalysed reactions.²⁰ However, the current reported protocols were environmentally unfriendly as they suffered from drawbacks such as, multistep, and tedious procedures, use of carcinogenic solvents, high-temperature, expensive and toxic metal-catalysts, and other hazardous reagents.Furthermore, there is very less reported research on these heterocycles, and that can be because of the unavailability of the efficient and cheaper methods. Thus, there is a need to develop new versatile synthetic method for the synthesis of disubstituted triazolotriazine heterocycles of pharmacological interest.In 1970, for the first time Kobe²¹et al. (scheme a) reported the synthesis of [1,2,4]triazolo[4,3-a][1,3,5]triazine utilizing lead tetraacetate in benzene under reflux conditions (Fig. 3). However, no further Isomerization was carried out and resulted low to moderate yield. Deshpande²²et al. reported (scheme b) the reaction of 2-hydrazinyl-1,3,5-triazine with various substituted benzoic acids. The product formed was treated with P₂O₅, refluxed in xylene for 10h to yield [1,2,4]triazolo[4,3-a][1,3,5]triazine. Further, Isomerization of the resulting product was carried out in 2% methanolic-NaOH solution resulting in poor yields. Recently, Stefano²³et al. (scheme c) reported, a multistep protocol by reacting the intermediate with bis(methyl-sulfanyl)methylenecyanamide at 180 °C under N₂ for 3h resulting in low yield due to the formation of several side products. In addition no isomerization studies were carried out, and only the [1,2,4]triazolo[1,5-a][1,3,5]triazine analogs were reported.Open in a separate windowFig. 3Different approaches for the synthesis of triazolo triazines.Herein, we report an economical one-pot synthesis of [1,2,4]triazolo[1,5-a][1,3,5]triazine analogs via Dimroth type rearrangement of [1,2,4]triazolo[4,3-a][1,3,5]triazine derivatives. This one pot novel methodology was carried out by reacting readily available, inexpensive starting materials such as substituted aryl/heteroaryl benzaldehydes and substituted 2-hydrazinyl-1,3,5-triazine in methanol (a mild solvent)²⁴ at room temperature giving excellent yields of the desired product. For cyclization reaction, an eco-friendly reagent NBS²⁵ was used and the resulting product was treated with DBU to yield its corresponding desired isomer. To the best of our knowledge this is the first report for the greener synthesis of symmetric disubstituted triazolotriazine heterocycles via Dimroth type rearrangement. We believe that this simple, yet novel methodology could be further exploited by the researchers in pharmaceutical industries and academics settings in drug discovery.Formation of the Schiff base was initiated reacting 4,4′-(6-hydrazinyl-1,3,5-triazine-2,4-diyl)dimorpholine 1a and unsubstituted benzaldehyde as shown in

Comparative study of CT and MRI in patients with seizures and a solitary cerebral cysticercus granuloma

We hypothesized that when contrast-enhanced CT reveals a solitary cerebral cysticercus granuloma, MRI would not usually provide additional information that might assist in management. We retrospectively compared visualisation of solitary cysticercus granulomas on contrast-enhanced CT and MRI in 16 patients presenting with seizures; gadolinium (Gd) enhancement was used in 6 patients. The granuloma was delineated well on both CT and MRI in 15 patients; in one patient, in whom CT was performed with 10-mm slices, it was seen only on contrast-enhanced MRI, CT and unenhanced MRI revealing only the surrounding oedema. On CT the granuloma was seen best on thin (2–5 mm) contrast-enhanced sections (in 10 patients). On MRI, Gd-enhanced images showed the granuloma best, as a ring-enhancing lesion, in all 6 patients. In the other 10 patients, the granuloma was seen only on T2-weighted images in 8 and on both T1- and T2-weighted images in 2. On T2-weighted images a characteristic low-signal ring with a high-signal centre was seen in 12 patients. Sensitivity of the imaging techniques was: contrast-enhanced CT (5 and 10 mm slices) 93.8% (15/16); thin (2–5 mm) section contrast-enhanced CT 100% (10/10); Gd-enhanced MRI 100% (6/6); unenhanced MRI 93.8% (15/16). MRI did not reveal additional granulomas or cysts in any patient. In patients strongly suspected to be harbouring this lesion, when 10-mm contrast-enhanced CT reveals only oedema, thin (2–5 mm) slice CT is a cost-effective alternative to MRI.     

Cysticercosis of the cerebellopontine angle cistern mimicking epidermoid inclusion cyst

We report a case of a cystic lesion in the left cerebellopontine (CP) angle cistern. The magnetic resonance (MR) imaging features closely resembled an epidermoid inclusion cyst, and was interpreted as such. However, at surgery and on histopathological examination the lesion was found to be a cysticercus cyst. It may be impossible to distinguish between the two by imaging. The MR imaging findings of cysticercosis, epidermoid and other common differentials are discussed.     

Management and outcome of brain abscess in renal transplant recipients

Although infection is the commonest central nervous system complication following renal transplantation, brain abscess is uncommon. Over the last 11 years, five renal transplant recipients who had brain abscesses were treated by computed tomography (CT)-guided stereotactic aspiration. Three patients had a fungal abscess, one a tuberculous abscess and the other had a methicillin-resistant Staphylococcus aureus abscess. One patient required a craniotomy for the excision of a fungal abscess which was persistent after two CT-guided stereotactic aspirations. The survivors in this group are the patient with a tuberculous abscess who is alive and well 5 years after diagnosis, and another with a dematiaceous fungal abscess (phaeohyphomycosis). CT-guided stereotactic surgery is minimally invasive, and can safely be performed in these patients. It often leads to an aetiological diagnosis in renal transplant recipients with brain abscesses. Specific antibiotic management directed towards the causative organism rather than empirical treatment can be instituted following the procedure. Although the ultimate prognosis in these patients is bleak even with specific antibiotic therapy, an occasional patient might have a good outcome with prompt and appropriate therapy.