Cotrimoxazole therapy ofToxoplasma gondii encephalitis in AIDS patients

Twenty-four consecutive HIV-positive patients affected byToxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75 % response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients withToxoplasma gondii encephalitis.Deceased.     

Molecular cloning and characterization of a novel gene of Candida albicans,CDR1, conferring multiple resistance to drugs and antifungals

By functional complementation of a PDR5 null mutant of Saccharomyces cervisiae, we have cloned and sequenced the multidrug-resistance gene CDR1 of Candida albicans. Transformation by CDR1 of a PDR5-disrupted host hypersensitive to cycloheximide and chloramphenicol resulted in resistance to cycloheximide, chloramphenicol and other drugs, such as the antifungal miconazole, with collateral hypersensitivity to oligomycin, nystatin and 2,4 dinitrophenol. Our results also demonstrate the presence of several PDR5 complementing genes in C. albicans, displaying multidrug-resistance patterns different from PDR5 and CDR1. The nucleotide sequence of CDR1 revealed that, like PDR5, it encodes a putative membrane pump belonging to the ABC (ATP-binding cassette) superfamily. CDR1 encodes a 1501-residue protein of 169.9 kDa whose predicted structural organization is characterized by two homologous halves, each comprising a hydrophobic region with a set of six transmembrane stretches, preceded by a hydrophilic nucleotide binding fold.     

Correlation between the course of the medial plantar artery and the morphology of the abductor hallucis muscle

The abductor hallucis muscle flap is commonly used as a proximally-based flap in the management of ankle, heel, and midfoot lesions, where it is ideally suited for closing defects. This study investigates the anatomical details of this muscle in 13 fresh male cadavers. The medial plantar artery (MPA) was studied by dissection and macroscopic analyses to document the relationship of its superficial and deep branches with respect to the abductor hallucis muscle (AHM). Three main patterns could be described. In Pattern A (54%) the MPA divides into two branches. The deep branch reaches the deep surface of the AHM, supplying its proximal part, and the superficial branch courses between the AHM and the flexor digitorum brevis, to end as the first plantar metatarsal artery. The latter supplies two to three small branches to the distal part of the AHM. The fibers of the AHM end symmetrically on the two sides of the tendon and the muscle presents an arciform shape. The MPA, in Pattern B (38%), lacks a deep branch and continues along the lateral border of the AHM as a superficial branch that supplies proximal and distal collaterals to the muscle. The muscle fibers of the AHM end mainly on the medial side of the tendon. The muscle belly presents an arciform shape and is located on the medial margin of the foot superomedially with respect to Pattern A. In Pattern C (8%) the MPA continues as a large deep branch on the deep surface of the AHM and ends as the medial collateral artery of the big toe. A smaller superficial branch of the MPA provides a few collaterals to the AHM from its proximal part and to the flexor digitorum brevis in its distal part. The AHM fibers end mainly on the lateral side of the tendon and morphologically the muscle presents a straight line on the sole of the foot compared to Pattern A. Although Patterns B and C, from a surgical point of view, necessitate interruption of the main trunk of the MPA, Pattern A may permit the vascularization of the muscles of the medial side of the sole of the foot by the superficial trunk of the MPA. Because preoperative radiological study of the plantar vessels correlate with the morphological characteristics of the AHM observed during surgery, such imaging may be useful in determining the appropriate flap design based on the patient's unique pattern of MPA branching.     

Hurthle cell adenoma of the mediastinum: intraoperative cytology and differential diagnosis with correlative gross, histology, and ancillary studies

A 66-year-old man was found to have a 7.5 cm mediastinal mass detected on routine chest X-rays as part of his preoperative work up for an inguinal hernia repair. An orthotopic (normally located) nongoitrous thyroid gland without evidence of connection to the mediastinal mass was also identified. The clinical differential diagnoses included lymphoma, thymoma, and germ cell tumor. Fine-needle aspiration (FNA) biopsy smears and touch imprints of the mediastinal mass showed a loosely cohesive, highly cellular population of relatively uniform cells with abundant granular cytoplasm, low nuclear to cytoplasmic (N/C) ratios, and prominent nucleoli consistent with a Hurthle cell (HC) neoplasm. Subsequently, the diagnosis of HC adenoma was confirmed on the surgically excised mediastinal mass. To the best of our knowledge, the surgical pathology and cytologic features of an HC adenoma of the mediastinum have not been reported in the literature. The gross, histologic, immunohistochemical, and electron microscopic (EM) findings, in addition to the cytologic features, are presented along with a differential diagnosis of this mediastinal neoplasm.     

A new CARD15 mutation in Blau syndrome

The caspase recruitment domain gene CARD15/NOD2, encoding a cellular receptor involved in an NF-kappaB-mediated pathway of innate immunity, was first identified as a major susceptibility gene for Crohn's disease (CD), and more recently, as responsible for Blau syndrome (BS), a rare autosomal-dominant trait characterized by arthritis, uveitis, skin rash and granulomatous inflammation. While CARD15 variants associated with CD are located within or near the C-terminal leucine-rich repeat domain and cause decreased NF-kappaB activation, BS mutations affect the central nucleotide-binding NACHT domain and result in increased NF-kappaB activation. In an Italian family with BS, we detected a novel mutation E383K, whose pathogenicity is strongly supported by cosegregation with the disease in the family and absence in controls, and by the evolutionary conservation and structural role of the affected glutamate close to the Walker B motif of the nucleotide-binding site in the NACHT domain. Interestingly, substitutions at corresponding positions in another NACHT family member cause similar autoinflammatory phenotypes.     

Evaluation of the Determine Rapid Syphilis TP assay using sera

The Abbott Determine Rapid Syphilis TP assay is a treponemal test that can be used in resource-poor settings that lack laboratory facilities. However, this test has not been extensively evaluated. We measured its sensitivity and specificity by using stored serum specimens (n = 567) from all persons who tested Treponema pallidum hemagglutination assay (TPHA) positive (n = 250) or TPHA indeterminate (n = 17) in the year 2001 and the first 300 patients in 2001 who tested TPHA negative at the Evandro Chagas Research Institute in Rio de Janeiro, Brazil. This rapid assay was independently interpreted by three different observers. With TPHA results as the reference, sensitivity ranged between readers from 95.6 to 98.4% and specificity ranged from 97.3 to 95.7%. There was little interreader variability in the interpretation of results, with approximately 98% agreement for all reader combinations. Of samples from persons with human immunodeficiency virus (HIV) infection (n = 198), sensitivity was 96.9 to 99.2% and it was 94.4 to 96.3% among HIV-negative persons (n = 127). Specificity was 92.4 to 95.5% among HIV-positive persons and 97.2 to 100% among HIV-negative persons. We found this test to have high sensitivity and specificity and little interreader variability, indicating that it may be easily used in resource-poor settings without laboratory facilities. Further studies are needed using this test on whole blood and under the clinical conditions for which it is intended.     

Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function

We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in which the mouse axonal glycoprotein F3/contactin was misexpressed from a regulatory region of the gene encoding the transient axonal glycoprotein TAG-1, exhibit a transient disruption of cerebellar granule and Purkinje cell development [Development 130 (2003) 29]. In the present study we explore the neurobehavioural consequences of this mutation. We report on assays of reproductive parameters (gestation length, litter size and offspring viability) and on somatic and neurobehavioural end-points (sensorimotor development, homing performance, motor activity, motor coordination and motor learning). Compared with wild-type littermates, TAG/F3 mice display delayed sensorimotor development, reduced exploratory activity and impaired motor activity, motor coordination and motor learning. The latter parameters, in particular, were affected also in adult mice, despite the apparent recovery of cerebellar morphology, suggesting that subtle changes of neuronal circuitry persist in these animals after development is complete. These behavioural deficits indicate that the finely coordinated expression of immunoglobulin-like cell adhesion molecules such as TAG-1 and F3/contactin is of key relevance to the functional, as well as morphological maturation of the cerebellum.