Normal neuroanatomical variants that may be misinterpreted as disease entities.

Variations of normal development and benign incidental anomalies are frequently observed on diagnostic neuroimaging. It is important these are recognised for what they are, as misinterpretation may result in unnecessary further investigation, follow-up imaging and anxiety. In this article, we review benign intracranial anomalies commonly referred to our unit for specialist neuroradiology advice or multidisciplinary discussion, concerning cysts of the pineal gland and pituitary fossa, vascular anomalies, and perivascular spaces. This article outlines the embryology and development, the various imaging features as well as the clinical relevance and differential diagnoses of each normal neuroanatomical variant.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Rare case of cerebral MALToma presenting with stroke-like symptoms and seizures.

Mucosa-associated lymphoid tissue (MALT) cells are present in gastrointestinal mucosa but rarely found in the central nervous system (CNS). We describe an unusual and rare case of CNS MALT lymphoma in a patient presenting with stroke-like symptoms.

An extended role for CT in the emergency diagnosis of malignant spinal cord compression.

AIM: To evaluate the usefulness of computed tomography (CT) for triaging between urgent transfer to a neurosurgical unit and delayed magnetic resonance imaging (MRI) in the local hospital. MATERIALS AND METHODS: Radiologists blinded to the MRI findings scored CT images from 1-5 using a novel grading system based on the degree of cord compression observed in 44 patients. Seventy separate levels were scored. The observers' CT scores were compared with the MRI findings. All scoring radiologists were specialist registrars at different stages of training. RESULTS: Agreement between CT and MRI scores for metastatic spinal cord compression (MSCC) were high with Cohen's weighted Kappa score 0.70 (p<0.001, 95% CI 0.65 to 0.75). CT has a sensitivity of 89% and specificity of 92% for MSCC. Half the false-positive and false-negative results came from a single junior radiologist who would not normally report CT or MRI studies unsupervised. The best CT-MRI agreement was from the most senior trainee radiologist. CONCLUSIONS: Spinal findings on routine staging whole-body CT combined with clinical findings are sufficient to determine which patients with MSCC can safely wait for MRI the next working day at the local hospital and those who need emergency transfer to a neurosurgical unit for MRI and possible surgical decompression.

Symptomatic venous sinus thrombosis following bone wax application to emissary veins.

A retrosigmoid craniectomy was performed for acoustic neuroma during which bone wax was used to control emissary vein bleeding. Postoperatively the patient developed an extensive venous thrombosis due to wax in the sigmoid sinus from which she recovered. We discuss this rare complication of posterior fossa surgery.

Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 microg/kg) combined with ribavirin in interferon-naïve patients with chronic hepatitis C and up to moderate fibrosis.

Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon (PEG-I) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight (BW), in spite of the previously shown flat dose-response curve at doses of > or =1.0 microg/kg. Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg, both in combination with ribavirin. Open-label, randomized study in 227 patients with biopsy-proven chronic hepatitis C (Metavir < or =F2), receiving oral ribavirin (400 mg, twice daily) in combination with subcutaneous PEG-I alpha-2b (1.0 or 1.5 microg/kg, once weekly) for 24 weeks (genotype 2 or 3), or 48 weeks (other genotypes), followed by a 24-week drug-free period. Virologic response rates did not differ between the two doses of PEG-I alpha-2b: in patients infected with hepatitis C virus (HCV) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW, 38% (22/58) had a sustained virologic response compared with 39% (27/70) in the PEG-I 1.5 microg/kg BW dose group (P = ns). The corresponding values in patients infected with HCV genotype 2 or 3 were 71% (39/55) and 81% (29/36) respectively (P = ns). Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group (48/113 patients; 42%) than in the 1.5 microg/kg BW dose group (63/106 patients; 59%, P = 0.015). Furthermore, 89% of patients treated for 24 weeks but only 58% of patients treated for 48 weeks (P < 0.001) tolerated the treatment without relevant dose reduction or premature termination. In combination with ribavirin, PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis.

The molecular machinery of Keilin's respiratory chain.

Keilin's classic paper of 1925 [Keilin (1925) Proc. R. Soc. London Ser. B 100, 129-151], achieved with simple, but elegant, techniques, describes the cytochrome components of the respiratory chain and their roles in intracellular respiration and oxygen consumption. Since that time, a tremendous amount of work has clarified the intricate details of the prosthetic groups, cofactors and proteins that comprise the respiratory chain and associated machinery for ATP synthesis. The work has culminated in advanced crystallographic and spectroscopic methods that provide structural and mechanistic details of this mitochondrial molecular machinery, in many instances to atomic level. I review here the current state of understanding of the mitochondrial respiratory chain in terms of structures and dynamics of the component proteins and their roles in the biological electron and proton transfer processes that result in ATP synthesis. These advances, together with emerging evidence of further diverse roles of mitochondria in health and disease, have prompted a new era of interest in mitochondrial function.

Two Menkes-type atpases supply copper for photosynthesis in Synechocystis PCC 6803.

Synechocystis PCC 6803 contains four genes encoding polypeptides with sequence features of CPx-type ATPases, two of which are now designated pacS and ctaA. We show that CtaA and PacS (but not the related transporters, ZiaA or CoaT) facilitate switching to the use of copper (in plastocyanin) as an alternative to iron (in cytochrome c(6)) for the carriage of electrons within the thylakoid lumen. Disruption of pacS reduced copper tolerance but enhanced silver tolerance, and pacS-mediated restoration of copper tolerance was used to select transformants. Disruption of ctaA caused no change in copper tolerance but reduced the amount of copper cell(-1). In cultures supplemented with 0.2 microm copper, photooxidation of cytochrome c(6) (PetJ) was depressed in wild-type cells but remained elevated in both Synechocystis PCC 6803(ctaA) and Synechocystis PCC 6803(pacS). Conversely, plastocyanin transcripts (petE) were less abundant in both mutants at this [copper]. Synechocystis PCC 6803(ctaA) and Synechocystis PCC 6803(pacS) showed increased iron dependence with impaired growth in deferoxamine mesylate (iron chelator)-containing media. Double mutants also deficient in cytochrome c(6), Synechocystis PCC 6803(petJ,ctaA) and Synechocystis PCC 6803(petJ,pacS), were viable, but the former had increased copper dependence with severely impaired growth in the presence of bathocuproinedisulfonic acid (copper chelator). Analogous transporters are likely to supply copper to plastocyanin in chloroplasts.

Nail biopsy: indications and methods.

Nail biopsy is a safe and useful technique for diagnosis and management of many nail conditions. A basic understanding of nail anatomy and biology is a prerequisite for a successful nail biopsy. The patient must be adequately prepared and there needs to be excellent anesthesia and hemostasis. The type of nail biopsy depends largely on the location of the pathology in the nail unit. The techniques of nail biopsy by location in the nail unit and by lesion type are discussed.

Tissue distribution and timing of appearance of polytropic envelope recombinants during infection with SL3-3 murine leukemia virus or its weakly pathogenic SL3DeltaMyb5 mutant.

A time course analysis was performed to identify the sites of formation and timing of appearance of polytropic recombinant viruses following infection of NIH/Swiss mice with the murine retrovirus SL3-3 murine leukemia virus (SL3) or with a weakly pathogenic mutant termed SL3DeltaMyb5. The results indicated that (i) polytropic recombinant viruses occur initially in the thymus of SL3-infected animals, (ii) the timing of appearance of polytropic recombinants in bone marrow is not consistent with their participation in the previously reported formation of transplantable tumor-forming cells at 3 to 4 week postinoculation, and (iii) the efficient generation of recombinant virus is correlated with efficient tumor induction.

The FeLV-945 LTR confers a replicative advantage dependent on the presence of a tandem triplication.

Feline leukemia virus (FeLV), like other naturally occurring retroviruses, is characterized by a high degree of genetic diversity. FeLV-945 is a natural isolate derived from non-B-cell non-T-cell lymphomas classified anatomically as multicentric. FeLV-945 exhibits a unique structural motif in the LTR composed of a 21-bp tandem triplication downstream of a single copy of enhancer. The unique FeLV-945 LTR is precisely conserved among eight independent multicentric lymphomas collected in a geographic cluster. Previous studies using reporter gene constructs predict that the FeLV-945 LTR would confer a replicative advantage on the virus that contains it, particularly in primitive hematopoietic cells. Such an advantage may account for the precise conservation of the unique LTR sequence. To test that prediction, a set of recombinant, infectious FeLVs was developed that are isogenic other than the presence of the FeLV-945 LTR or mutations of it. Replication assays show that the FeLV-945 LTR confers a distinct growth advantage in K-562, FEA, and 3201 cells and implicate the 21-bp triplication in that function. Replacement of two copies of the triplicated element with random sequence greatly diminished the replicative capacity, thus implicating the triplicated sequence itself in LTR function. The 21-bp triplication was shown to contain specific nuclear protein binding sites, which may account for the selective pressure to conserve the sequence.

Stereotactic 14G core biopsy of non-palpable breast cancer: what is the relationship between the number of core samples taken and the sensitivity for detection of malignancy?

AIM: Percutaneous 14-gauge core biopsy (CB) guided by digital stereotactic mammography is now an established technique in the investigation of women with non-palpable suspicious mammographic lesions. Diagnostic sensitivity of CB is affected both by the nature of the mammographic abnormality and by the number of core samples taken. METHODS AND RESULTS: A retrospective review of 500 women who have undergone CB in our institution showed that in 235 cases, invasive or non-invasive carcinoma was found on final surgical histology. Correlation between CB result and surgical histology revealed a significant increase in sensitivity for the diagnosis of malignancy if a larger number of cores were taken (84.3% for two cores and 90.2% for five cores vs. 97.9% for six or more cores). This trend was maintained when patients were subdivided according to mammographic abnormality, either soft tissue mass or microcalcifications. The effect on diagnostic sensitivity of increasing the number of tissue cores obtained was most pronounced in patients with microcalcifications graded as low or moderately suspicious for malignancy (70.1% for two cores and 79.1% for five cores vs 94.0% for six or more cores). The presence of an invasive component in a malignant lesion was correctly diagnosed using CB in 79.2% overall if at least six cores were taken. If the mammographic lesion was a soft tissue mass, this figure rose to 95.7%, but was only 35.7% if the visible lesion was composed of microcalcifications alone. CONCLUSION: Our series confirms the reliability of stereotactic CB in the diagnosis of breast carcinoma. Diagnostic sensitivity is improved by increasing the number of cores taken (to six or more), particularly in women with mammographic microcalcifications of an equivocal nature.

Sonographic detection and characterization of musculoskeletal and subcutaneous tissue abnormalities in sickle cell disease.

Pain due to bone marrow infarction is common in homozygous sickle cell disease (SS disease). Musculoskeletal pathology may be responsible for persistent atypical symptoms. We have assessed the frequency and ultrasound appearances of soft tissue and joint abnormalities in SS disease. SS disease patients with atypical musculoskeletal symptoms were examined with ultrasound over a 2 year period. Ultrasound findings were correlated with those at surgery or percutaneous drainage. 31 episodes in 23 patients were referred for ultrasound. There were 36 abnormalities in 18 patients: abscess (n = 15), effusions (n = 5), soft tissue induration (n = 12), fat necrosis (n = 2), haematoma (n = 1) and reactive lymph node (n = 1). Five examinations were normal. Soft tissue abnormalities in patients over the age of 14 years were associated with intramuscular injections: fat necrosis (n = 1), haematoma (n = 1), indurated soft tissue (n = 1) and abscess (n = 7). Soft tissue abnormalities with no underlying cause were seen in seven patients: abscess (n = 4), indurated soft tissue (n = 2) and fat necrosis (n = 1). Ultrasound is the imaging modality of choice for delineating these abnormalities and allows percutaneous drainage.

Can the clearance of tumor necrosis factor alpha and interleukin 6 be enhanced using an albumin dialysate hemodiafiltration system?

Patients with acute hepatic failure (AHF) have elevated levels of inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Recently, we have shown selective hemodiafiltration with albumin dialysis, as an extracorporeal liver support device (ECLVS), to be effective in the clearance of multiple toxins that are elevated in AHF. Our objective was to evaluate whether ECLVS would be effective in the clearance of TNF-alpha and IL-6. An in vitro continuous hemodiafiltration circuit was used with single pass counter-current dialysis. A known amount of recombinant rat TNF-alpha and IL-6 was added to heparinized bovine blood and filtered across a polyalkyl sulfone hemofilter using matched filtration and dialysate flow rates. During 4 hours, the serial TNF-alpha and IL-6 concentrations were measured in the circulating blood, and the content of each cytokine was calculated using mass balance. For each cytokine, clearance was determined for two dialysate groups at constant temperature and pH (group 1: dialysate = 0.9 normal saline, n = 5; group 2: dialysate = albumin 2 gm/dl, n = 5). Analysis of data was performed using ANOVA and Student's t-test. There was improved clearance of TNF-alpha and IL-6 when albumin was used in the dialysate (81+/-0.09% of the initial TNF-alpha and 77+/-0.04% of the IL-6 quantities) compared with when 0.9 normal saline was used as the dialysate (58+/-0.14% of the initial TNF-alpha and 56+/-0.18% of the IL-6 quantities); p < 0.03. An ECLVS utilizing hemodiafiltration with albumin dialysis is more effective than conventional hemofiltration in the clearance of TNF-alpha and IL-6 and, therefore, may benefit patients with acute hepatic failure.

Nail disorders. Diagnosis and treatment of infectious, inflammatory, and neoplastic nail conditions.

Nail disorders are very common, and about 50% of all nail conditions are of fungal etiology. A proper diagnosis is essential because many nail conditions look alike. Diagnosis and treatment of other nail disorders, such as psoriasis, lichen planus, and neoplasms, are discussed.

A prospective comparison of atrio-femoral and femoro-atrial flow in adult venovenous extracorporeal life support.

INTRODUCTION: In the United States, venovenous extracorporeal life support has traditionally been performed with atrial drainage and femoral reinfusion (atrio-femoral flow). Although flow reversal (femoro-atrial flow) may alter recirculation and extracorporeal flow, no direct comparison of these 2 modes has been undertaken. OBJECTIVE: Our goal was to prospectively compare atrio-femoral and femoro-atrial flow in adult venovenous extracorporeal life support for respiratory failure. METHODS: A modified bridge enabling conversion between atrio-femoral and femoro-atrial flow was incorporated in the extracorporeal circuit. Bypass was initiated in the direction that provided the highest pulmonary arterial mixed venous oxygen saturation, and the following measurements were taken: (1) maximum extracorporeal flow, (2) highest achievable pulmonary arterial mixed venous oxygen saturation, and (3) flow required to maintain the same pulmonary arterial mixed venous oxygen saturation in both directions. Flow direction was then reversed, and the measurements were repeated. Data were compared with paired t tests and are presented as mean +/- standard deviation. RESULTS: Ten patients were studied, and 9 were included in the data analysis. Femoro-atrial bypass provided (1) higher maximal extracorporeal flow (femoro-atrial flow = 55.6 +/- 9.8 mL/kg per minute, atrio-femoral flow = 51.1 +/- 11.1 mL/kg per minute; P = .04) and (2) higher pulmonary arterial mixed venous oxygen saturation (femoroatrial flow = 89.9% +/- 6.6%, atrio-femoral flow = 83.2% +/- 4.2%; P = .006); (3) furthermore, it required less flow to maintain an equivalent pulmonary arterial mixed venous oxygen saturation (femoro-atrial flow = 37.0 +/- 12.2 mL/kg per minute, atrio-femoral flow = 46.4 +/- 8.8 mL/kg per minute; P = .04). CONCLUSIONS: During venovenous extracorporeal life support, femoro-atrial bypass provided higher maximal extracorporeal flow, higher pulmonary arterial mixed venous oxygen saturation, and required comparatively less flow to maintain an equivalent mixed venous oxygen saturation than did atrio-femoral bypass.