Malakoplakia in Thoracic Transplant Recipients.

Malakoplakia is a rare granulomatous disease characterized by the presence of Michaelis-Gutmann bodies on histopathologic analysis. Lesions manifest in a wide range of organs with cutaneous, gastrointestinal, and genitourinary systems being most common, and often result in significant comorbidities owing largely to misdiagnoses and the similar appearance to malignancy or granulomatous processes. Most patients are immunocompromised, including the solid-organ transplant population. Among organ recipients, malakoplakia is most commonly seen in renal transplantation, and only rarely reported in thoracic organ recipients. Herein we report 2 cases of malakoplakia in thoracic transplant patients that highlight the critical need for tissue diagnosis to avoid delay in management.

The integration of pharmacology and pathophysiology into locoregional chemotherapy delivery via mass fluid transfer.

The prevailing paradigm of locoregional chemotherapy has been centred around delivering chemotherapy as close to the tumour as possible and in some cases incorporating vascular isolation techniques. Strategically, the development of these techniques has been rudimentary without consideration for the interdependencies between macrovascular manipulation and the microvascular effects. This review focuses on how new capabilities offered by recent advances in vascular access technology could be exploited to facilitate the mass fluid transfer (MFT) of anticancer agents to solid tumours. A haemodynamic model of MFT is proposed using the physical laws of fluid flow, flux, and diffusion that describe the microvascular effects anticancer agents may have upon tumours through the manipulation of macrovascular blood flow control. Finally, the possible applications of this technique for several organs are discussed.

Enteric fever in the Pacific: a regional retrospective study from Auckland, New Zealand.

BACKGROUND: There are limited clinical data on enteric fever in the Pacific and New Zealand (NZ) compared with the Indian subcontinent (ISC) and South-East Asia (SEA). Our objective was to describe enteric fever in Auckland - a large Pacific city, focusing on disease acquired in these regions. METHODS: We reviewed enteric fever cases hospitalised in Auckland from January 2005 to December 2010. RESULTS: Microbiologically confirmed EF was identified in 162 patients. Travel regions: Pacific, 40 cases (25%) (Samoa, 38; Fiji, two), ISC, 72 (44%), SEA, seven (4%), other, three (2%), no travel, 40 (25%). Enteric fever rates for Auckland resident travellers were: India 50.3/100 000; Samoa 19.7/100 000.All Pacific cases were Salmonella Typhi. Of local isolates (without travel history), 38 were S. Typhi (36 fully susceptible, one multi-drug resistant (MDR) + nalidixic acid resistant (NAR), one unknown) and two S. Paratyphi (both NAR). Of non-Pacific travel, 56/82 (69%) isolates were S. Typhi, the remainder S. Paratyphi (15 isolates were fully susceptible, only 1% were MDR). Significant associations of serotype and antibiotic resistance with different travel regions and similarity of phage types (local and Pacific) were observed. Headache, vomiting and acute kidney injuries were more frequent with Pacific travel, while abdominal distension and cholecystitis with local disease. Shorter duration of treatment in the Pacific group was seen despite length of stay in hospital not being reduced. Local cases were associated with longer hospital admissions. CONCLUSIONS: One half of cases in Auckland are acquired either from Pacific or locally. Similarities mean that disease acquired locally is likely of Pacific origin.

Endovenous valve transfer for chronic deep venous insufficiency.

OBJECTIVES: The aims of the study were to test the safety and efficacy of a custom-made endovenous valve transfer stent, and delivery system in animals and humans. METHODS: The internal jugular veins of 16 sheep, weighing 45-55 kg, were used. A segment of vein with venous valve was enclosed circumferentially with a barbed stent. This segment from the internal jugular vein was introduced and deployed remotely into the contralateral internal jugular vein. Harvesting occurred acutely (one sheep) and at 1, 3, and 6 months postoperatively (five sheep per group). Operative competence testing, histological and scanning electron microscopic (SEM) examinations were performed. Four males with recalcitrant ulcers (mean age of 22 years) had axillary veins transferred from the popliteal vein and were followed for a mean of 3.8 years. RESULTS: At harvest, all the transferred valves were competent, with no evidence of thrombosis, tilting, endoleak, or migration with normal macroscopic and SEM findings. Although only 50% of the ulcers completely healed in humans, the remainder were improved, with all valves being competent and patent. CONCLUSIONS: Endovenous valve transfer with a custom-made circumferential stent produces near perfect results in sheep and encouraging results in a small pilot study.

A diagnostic dilemma of intracranial pathology: coincidence or the result of cranial trauma?

A 21-year-old man presented to the accident and emergency department at St Peter's Hospital, London, in September 2008. Following consumption of alcohol, the patient had been assaulted and had experienced facial trauma. Later, the patient had a witnessed generalised tonic-clonic seizure and the next day noted weakness of the right leg. A CT scan of the brain revealed a solitary lesion in the left presylvian region close to the vertex, involving the leg area of the primary motor cortex. A subsequent MRI scan showed the lesion to be a cavernous haemangioma. The patient had no history of epilepsy. This raised the question as to whether the assault caused the lesion to haemorrhage, resulting in the seizure and spastic monoparesis, or did the formerly asymptomatic cavernoma bleed spontaneously with the assault being coincidental?

Popliteal vein compression syndrome: obesity, venous disease and the popliteal connection.

OBJECTIVES: Obesity and venous disease are commonly encountered together. The aetiological relationship, however, has not been clear. Popliteal venous compression (PVC) has been encountered both on ultrasound and venographically. In this study, patients with symptoms and/or signs of chronic venous hypertension with PVC were investigated and the relationship to obesity was defined. METHODS: A total of 89 patients were included in the study, of which 49 limbs were classified as having PVC defined as a greater than 90% reduction in the maximum internal diameter (ID) of the popliteal vein (POPV) with knee locking. Forty consecutive limbs with venous disease with no evidence of PVC were used as controls. The body mass index (BMI) of each group was calculated and the clinical symptoms and signs were documented. After the failure of conservative treatment, 30 of the 49 underwent open popliteal decompression. RESULTS: Patients with PVC were found to have a BMI of 34.6 +/- 6.2 compared with 25.3 +/- 3.0 of the controls. The POPV ID in the PVC group before and after knee locking changed from 11.7 +/- 5.0 to 1.0 +/- 2.1 mm, respectively. Postoperatively, the POPV ID before and after knee locking changed from 10.2 +/- 2.2 to 9.0 +/- 1.5 mm, respectively. At 16.2 +/- 12.1 months follow-up, all the major clinical parameters improved at a statistically significant level. CONCLUSIONS: There appears to be a relationship between obesity, chronic venous disease and PVC. POPV compression syndrome may clarify the previously unexplained venous presentations. Surgical decompression provides good results in patients unresponsive to conservative treatment.

Multiple mitochondrial DNA deletions in monozygotic twins with OPMD.

BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is caused by expansions of the poly (A) binding protein 2 (PABP2) gene. Previous histological analyses have revealed mitochondrial abnormalities in the muscles of OPMD patients but their significance remains uncertain. OBJECTIVE: We had the rare opportunity to study monozygotic twins with identical expansions of the PABP2 gene but with markedly different severities of OPMD. Both had histological features of mitochondrial myopathy. We determined whether mitochondrial DNA abnormalities underlay these changes. METHODS: Clinical information was obtained by history and examination. Muscle biopsies were obtained from each subject and genetic analysis was performed using long-range PCR and Southern blotting. RESULTS: We demonstrate, for the first time, the presence of mitochondrial DNA (mtDNA) deletions by Southern blotting in individuals with OPMD. This correlates with the presence of mitochondrial myopathy in both twins. Moreover, both twins had different mtDNA deletions, which might explain their phenotypic differences. CONCLUSION: We hypothesise that mitochondrial dysfunction may occur as a consequence of PABP2 gene mutations, and that this dysfunction may affect the phenotypic manifestations of OPMD.

Recurrence rates following external valvular stenting of the saphenofemoral junction: a comparison with simultaneous contralateral stripping of the great saphenous vein.

OBJECTIVES: The incidence of recurrent varicose veins remains high despite the development of new ablative treatments for varicose veins associated with incompetence of the saphenofemoral junction. External valvular stenting (EVS) of the terminal and/or subterminal valves of the great saphenous vein (GSV) provides a reparative, physiological approach that requires long-term evaluation. The aim of this study was to compare recurrences following EVS with perforate invaginate (PIN) stripping of the GSV. METHODS: Included in the study were 193 patients (386 limbs) all of whom underwent simultaneous PIN-stripping of the GSV in one limb and EVS in the contralateral limb. Duplex scanning of the GSV and venous valves established suitability for each procedure. Only valves with visible, mobile cusps on ultrasound imaging are suitable for EVS. Stents were specifically designed Dacron reinforced silicone for left and right saphenofemoral junctions and for the subterminal valve. In a separate group of patients identified from a database where unilateral and bilateral stents had been implanted, 39 limbs with recurrent varices were examined clinically and ultrasonically to determine the aetiology of recurrences. RESULTS: Follow up was available to a maximum of 147 months. The total recurrence rate was 12.4%; stripping (22.2%) and EVS (4.6%) (P<0.01). The residual reflux as measured by postoperative Valsalva on duplex was 9% but rarely was associated with recurrences. The most common cause of recurrence was incompetent perforators and ovarian vein incompetence filling varices of the pudendal veins. CONCLUSION: This non-randomised study included more severely affected limbs in the PIN stripping limbs, favouring a better outcome in the EVS group. In those patients at an early stage of the disease process where venous valve structure is essentially intact, EVS is a physiological alternative to PIN stripping in the treatment of varicose veins.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials register (August 2005), MEDLINE (from January 1966 to August 2005), EMBASE (from January 1980 to August 2005) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The authors independently applied the selection criteria, assessed study quality and two authors performed independent data extraction. MAIN RESULTS: The search identified 23 studies for consideration but only nine studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure as the primary outcome measure, (survival at 12 months treatment). However, sufficient data were available from four studies to allow analysis of this outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed for vitamin E 500 mg twice daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of all antioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and people with amyotrophic lateral sclerosis. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Phenotypic variability in siblings with type III spinal muscular atrophy.

Autosomal recessive spinal muscular atrophy (SMA) shows substantial phenotypic variability, presenting at a variety of ages from infancy to adult life. Diagnostic difficulties may arise because SMA sometimes produces a dystrophic or myopathic phenotype rather than classical neurogenic abnormalities. Two brothers are described who illustrate this principle and highlight the increasing importance of molecular genetics in investigating patients with neuromuscular diseases. The findings are discussed in the light of recent observations in a mouse model of SMA.

Enterovirus related metabolic myopathy: a postviral fatigue syndrome.

OBJECTIVE: To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients. METHODS: Quadriceps muscle biopsy samples from 48 patients with CFS were processed to detect enterovirus RNA by two stage, reverse transcription, nested polymerase chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct nucleotide sequencing of PCR products was used to characterise the enterovirus. Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma lactate was measured immediately before and after exercise, and 30 minutes after testing. An abnormal lactate response to exercise (SATET+) was defined as an exercise test in which plasma lactate exceeded the upper 99% confidence limits for normal sedentary controls at two or more time points. RESULTS: Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET- patients. PCR products were most closely related to coxsackie B virus. CONCLUSIONS: There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of CFS patients.

Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis.

We report a 32-year-old man who presented with a 2-year history of unexplained weight loss and symptoms of Raynaud's phenomenon. Clinical examination and investigations were consistent with a diagnosis of acquired partial lipodystrophy (Barraquer-Simons disease). This patient also exhibited an associated cutaneous vasculitis and peripheral perniotic changes. He had normal renal function and glucose tolerance and no immunological abnormality has been detected in his serum to date. The absence of C3-nephritic factor in the presence of overt lipodystrophy suggests that there may be another factor or immunological mediator responsible for the subcutaneous changes seen in patients with lipodystrophy.

Clinical characteristics of SOD1 gene mutations in UK families with ALS.

Five to ten percent of patients with ALS have a family history of the disease, inheritance is usually autosomal dominant. Mutations of the SOD1 gene were first identified in a proportion of families with ALS by Rosen et al. The SOD1 gene encodes the enzyme copper zinc superoxide dismutase. Patients were studied from throughout the UK, where more than one individual in the family had ALS. Clinical history and examination of the individual and family were obtained, and DNA extracted from leukocytes of whole blood samples. Mutations were identified by standard sequencing methods. To date, 12 different mutations of SOD1 have been identified in 17 different families, representing around 20% of all ALS families studied. The mutations were mainly single base substitutions - H48Q, G72S, G93R, G93V, E100G, D101N, D101G, G108V, I113T, D125H, I149T - and also an insertion mutation - 132insTT - leading to a premature stop codon. The mutations were present in exons 2-5. We did not identify mutations in exon 1, although these have been identified by others in different patient samples. We have identified SOD1 mutations in around 20% of UK families with ALS studied. This is similar to that reported in other populations. Mutations have now been identified in all exons of SOD1. The individual mutations do not precisely predict disease severity, and generally it is difficult to give a specific prognosis based on the individuals' SOD1 mutations. We continue to investigate the possible pathogenic mechanisms of the SOD1 mutations. We have studied the neuropathology in patients with SOD1 mutations. We are also performing linkage studies to identify the genes involved in the 80% of families where an SOD1 mutation has not been identified.

Dermatomyositis in association with transitional cell carcinoma of the bladder.

We report a case of dermatomyositis occurring in association with transitional cell carcinoma of the bladder. The case illustrates the importance of a thorough search for neoplasms in elderly patients with dermatomyositis and is a reminder that bladder cancer may be a rare cause of dermatomyositis. The case also shows that successful treatment of an underlying tumour may lead to resolution of paraneoplastic dermatomyositis, and relapse of cutaneous and muscle symptoms and signs may indicate recurrence of tumour.

A case of multiple system atrophy with hyperglycinaemia due to a selective deficiency of glycine transporter mRNA.

A patient presented with features of olivopontocerebellar atrophy and was found to have marked hyperglycinaemia. Severe atrophy of the cerebellum and brain stem was found at post-mortem, with numerous glial cytoplasmic inclusions (GCIs) in atrophic areas, characteristic of multiple system atrophy. In situ hybridization studies of the spinal cord demonstrated a selective reduction in expression of glycine transporter mRNA. We suggest that the resulting impairment of regulation of glycine concentrations at synaptic level resulted in excitotoxic damage to neurons.

Familial cramp due to potassium-aggravated myotonia.

Clinical, electrophysiological, and molecular genetic features were investigated in two patients from a family a with dominantly inherited myotonic disease, characterised by painful cramps, stiffness without weakness, fluctuation of symptoms, and cold sensitivity. A reduction in amplitude of the compound muscle action potential was demonstrated on cooling and administration of potassium, although no clinical exacerbation was seen. A heterozygote mutation Val1589Met was identified in the alpha-subunit of the skeletal muscle sodium channel gene in both patients, consistent with the diagnosis of potassium-aggravated myotonia. The phenotype in this family is much milder than that previously described in another family with a mutation at this site.