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.

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.

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.

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.

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.

Thymectomy in late-onset myasthenia gravis.

Between 1977 and 1979, 12 consecutive patients with myasthenia gravis who were over the age of 55 years were treated by thymectomy. In all, their conditions improved clinically; 11 of the 12 became free of the generalized features of myasthenia gravis. Nine patients required no further medication. Acetylcholine-receptor antibody titers did not change significantly. Although five patients had atrophic thymus glands, their conditions also improved. We conclude that (1) thymectomy is a safe and effective therapy for patients with myasthenia gravis who are over the age of 55 years; (2) steroids and anticholinesterase agents are not essential in the management of late-onset myasthenia gravis; and (3) reduction in acetylcholine-receptor antibody titer is not essential for beneficial clinical response.

Electrocardiographic abnormalities in carriers of Duchenne muscular dystrophy.

Electrocardiographic (ECG) abnormalities characteristic of Duchenne muscular dystrophy (tall R waves in the right precordial leads and deep Q waves in the lateral chest leads) are rarely observed in carriers, but Emery (1969) found that the (R-S) amplitude sum in lead V1 was significantly greater in carriers than in age-matched controls. In a prospective single-blind study, we analyzed coded records from 11 carriers and 12 age-matched normal women for (R-S) amplitude sums and R/S ratios in leads V1 and V2. Values in carriers were significantly greater for all these characteristics, discrimination being most marked for R/S in V2 (p less than 0.01). This was confirmed in a further retrospective study, comparing records from 18 carriers with 100 normal ECGs from women of the same age range. Density functions for (R-S) in V1 and the R/S ratio in V2 derived from carrier and normal population can be incorporated into probability calculations to determine risk of carrier status.

No direct correlation between serum antiacetylcholine receptor antibody levels and clinical state of individual patients with myasthenia gravis.

Serum acetylcholine receptor antibodies were measured serially in myasthenia gravis patients before and after early extended thymectomy; they received no medication postoperatively. Clinical improvement occurred with little or no change in antibody level. After plasmapheresis without immunosuppressive drug therapy, we also found clinical improvement without decrease in serum antibody level.

Clinical and functional investigation of 10 missense mutations and a novel frameshift insertion mutation of the gene for copper-zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis.

Mutations of the gene SOD-1, which encodes the enzyme copper-zinc superoxide dismutase, occur in patients with a familial form of amyotrophic lateral sclerosis (ALS). We investigated 71 families with more than one individual affected by ALS for clinical features and SOD-1 mutations. Mutations were identified in 14 families, indicating the presence of SOD-1 mutations in around 20% of this population. There were 10 different heterozygote missense point mutations in eight different codons, and a novel two-base frameshift insertion (132insTT), which leads to substitution of aspartic acid for glutamic acid at codon 132, and a premature stop codon at 133, with predicted truncation of the protein. SOD enzyme activity was reduced to around 50% of normal in individuals with SOD-1 mutations, and may be a useful predictor for the presence of these mutations. A predilection for disease onset in the lower limbs appears to be a distinguishing feature of familial ALS with SOD-1 mutations, and accords with findings in transgenic mouse models. In general, the finding of an SOD-1 mutation does not accurately predict a prognosis or disease severity.

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle.

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers. There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation. These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue.

Drug-induced neurological disorders.

When a patient presents with a neurological or neuromuscular disorder, it is essential to consider drugs as a possible cause. Drugs can affect virtually any part of the neuraxis and the resulting disorders can usually be classified in terms of the anatomical site affected and the clinical presentation. In general, the signs and symptoms of drug-induced neurological disorders are virtually indistinguishable from those seen in naturally occurring disease but are usually reversible if diagnosed early enough. Cortical depression may produce coma, particularly in overdose cases, but a large number of drugs can also initiate seizures in susceptible individuals. The effects of drugs in the pathogenesis of headaches are certainly underestimated, and the eye, hearing and balance mechanisms can be severely damaged by certain drugs before symptoms prompt investigation. The long term effects of antipsychotic drugs on basal ganglia demand that these drugs are used only when absolutely essential and for as short a period as possible. Finally, there is increasing awareness of the role of drugs in the development of neuromuscular disorders such as peripheral neuropathies, myasthenic syndromes and myopathies.

Real-time intraoperative angiosonography after carotid endarterectomy.

Real-time intraoperative angiosonography is a readily available and simple means of obtaining high-resolution imaging of the carotid vessels after endarterectomy. In an experience of 60 intraoperative scans, nine abnormalities (15%) were detected, or which 4 lesions were hemodynamically significant. Three of these abnormalities were in the external carotid artery, and one was in the common carotid artery. The detection of these defects, which usually were not obvious during palpation or inspection, enabled immediate reexploration and correction of the fault to be undertaken. The considerable advantages of the intraoperative method of scanning over the transcutaneous technique and operative angiography are discussed. Immediate intraoperative angiosonography is recommended for routine use after carotid endarterectomy.

Ultrasonic indications to explore the common bile duct.

A prospective comparison between operative cholangiography and operative choledochosonography has been made in 100 patients with cholelithiasis and potential choledocholithiasis. Thirty-one common bile ducts were explored, and 25 of them contained stones. Operative cholangiography was attempted in every case, but technical difficulties prevented examination of 12 common bile ducts, two of which contained stones. Both of these stones were detected by operative ultrasonography. Of the remaining 88 ducts, the sensitivity of the operative cholangiogram was 96% and the specificity 96%. Operative ultrasonography was performed for all 100 patients, with a sensitivity of 96% and a specificity of 93%. The ultrasonic findings of a sonically dense particle, shadowing, dilatation of the duct, and the persistence and meniscus signs are described with their relative incidence in the 100 patients. The time required for choledochosonography (3 to 5 minutes) compared favorably with the time needed for operative cholangiography (10 to 15 minutes). Operative bile duct scanning is a rapid, reliable technique for detecting the presence of choledocholithiasis at the time of routine cholecystectomy.

Ultraviolet-laser ablation of skin.

We report on the use of pulsed ultraviolet-laser irradiation at 193 nm from an argon-fluoride laser and at 248 nm from a krypton-fluoride laser to ablate skin. In vitro, both wavelengths performed comparably, removing tissue precisely and cleanly, and leaving minimal thermal damage to the surrounding tissue. In vivo, the 193-nm laser radiation failed to remove tissue after bleeding began. The 248-nm radiation, however, continued to remove tissue despite bleeding and left a clean incision with only minimal thermal damage. The krypton-fluoride excimer laser beam at 248 nm, which should be deliverable through a quartz optical fiber, has great potential as a surgical instrument.

The influence of graft type on patency of infrainguinal arterial bypass grafts.

Between 1985 and 1992, 328 patients underwent 392 infrainguinal reconstructions. Indications for operation were disabling claudication in 126 patients, critical limb ischemia in 246 and uncomplicated popliteal aneurysm in 20. Grafts were to the above knee popliteal artery in 134 patients, below knee popliteal artery in 176 and infrapopliteal ("distal") in 82 patients. Graft types included 160 reversed saphenous vein (RSV), 95 polytetrafluoroethylene (PTFE), 84 nonreversed saphenous vein (NRSV), 41 composite grafts (PTFE plus vein) and 12 others. Results show the five year patency rate for all grafts of 58 percent and limb salvage (for limb ischemia) of 74 percent. Above knee and below knee popliteal grafts (three year patency rates of 72 and 66 percent) performed significantly better than distal grafts (51 percent three year patency rate, p < 0.025). NRSV grafts comprised 63 ex situ ("translocated") and 21 in situ grafts. No significant difference was shown between these (two year patency rates of 62 and 65 percent). There was no significant difference between RSV and NRSV grafts in this series, although RSV tended to show higher patency rates. Composite grafts (below knee, three year patency rate of 45 percent) had significantly lower three year patency rates than below knee RSV (79 percent, p < 0.005). RSV remains the conduit of choice in this unit, with long term patency comparable with other published series. Use of NRSV (translocated and in situ) allows increased use of autogenous vein with the associated higher patency rates compared with prosthetic materials and is the graft of choice if the long saphenous vein is not suitable for use in the standard reversed method. The translocated technique allows more flexibility in the use of nonreversed vein with results comparable with the in situ technique. Composite grafts provide a useful alternative to PTFE alone for infrageniculate grafting when insufficient autogenenous vein is available.

Effects of tenotomy on muscle histology and energy metabolism in normal and dystrophic mice.

Creatine, phosphocreatine, ATP and phosphate concentrations were measured in extracts of tibialis anterior and gastrocnemius muscles from 42 normal and 39 dystrophic mice from 1 to 16 weeks of age. No differences were observed at 1 week, prior to the onset of histological abnormalities in dystrophic animals. Creatine and phosphocreatine concentrations were significantly reduced in older dystrophic mice, and phosphate levels were higher, while ATP levels generally did not differ. Tenotomy of gastrocnemius at 1 week prevented the development of dystrophy in this muscle but this was not associated with an increase in phosphogen concentrations. Serum creatine kinase levels were significantly higher in dystrophic mice than normal mice but only during the first two weeks of life; levels in older mice were not significantly different. This study shows that the reported deficits in phosphogen concentrations in dystrophic muscles are likely to reflect the results, rather than the cause, of the dystrophic process.

Absence of biochemical heterogeneity in McArdle's disease. A high resolution SDS-polyacrylamide gel electrophoresis study.

Muscle biopsy extracts from a series of 6 patients with McArdle's disease were investigated by analytical SDS-polyacrylamide gel electrophoresis, to establish the presence or absence of the myophosphorylase protein subunit. In 4 cases, the band corresponding to the myophosphorylase subunit was totally absent from the electrophoretic staining pattern, and in 2 cases was present, but with a greatly reduced staining intensity compared with control normal patients; thus in none of the cases of McArdle's disease investigated was there evidence for a myophosphorylase subunit band of comparable staining intensity to that found in control normal patients. This result contrasts with previously reported findings (Feit and Brooke 1976) which suggested that McArdle's disease exists in biochemically heterogeneous forms; in one form of the disease myophosphorylase being totally absent and in a second form present to a similar extent as normal, but in an inactive form. On the basis of the results reported in this paper, we would suggest that myophosphorylase deficiency is a single gene disorder characterized by the absence or marked reduction of the myophosphorylase protein.