Nicholas Trost

The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. METHODS Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). RESULTS At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). CONCLUSIONS Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.

Evidence for the toxicity of bidirectional transcripts and mitochondrial dysfunction in blood associated with small CGG expansions in the FMR1 gene in patients with parkinsonism.

Purpose: Our previous results showed that both gray zone and lower end premutation range (40–85 repeats) fragile X mental retardation 1 (FMR1) alleles were more common among males with parkinsonism than in the general population. This study aimed to determine whether these alleles have a significant role in the manifestations and pathogenesis of parkinsonian disorders.Methods: Detailed clinical assessment and genetic testing were performed in 14 male carriers of premutation and gray zone FMR1 alleles and in 24 noncarriers identified in a sample of males with parkinsonism.Results: The premutation + gray zone carriers presented with more severe symptoms than disease controls matched for age, diagnosis, disease duration, and treatment. The Parkinson disease (Unified Parkinsons Disease Rating Scale) motor score and the measures of cognitive decline (Mini-Mental State Examination and/or Addenbrookes Cognitive Examination Final Revised Version A scores) were significantly correlated with the size of the CGG repeat and the (elevated) levels of antisense FMR1 and Cytochrome C1 mRNAs in blood leukocytes. In addition, the carriers showed a significant depletion of the nicotinamide adenine dinucleotide, reduced dehydrogenase subunit 1 mitochondrial gene in whole blood.Conclusion: Small CGG expansion FMR1 alleles (gray zone and lower end premutation) play a significant role in the development of the parkinsonian phenotype, possibly through the cytotoxic effect of elevated sense and/or antisense FMR1 transcripts involving mitochondrial dysfunction and leading to progressive neurodegeneration.

Tissue-Engineered Breast Reconstruction: Bridging the Gap toward Large-Volume Tissue Engineering in Humans

Background: Use of autologous tissue is ideal in breast reconstruction; however, insufficient donor tissue and surgical and donor-site morbidity all limit its use. Tissue engineering could provide replacement tissue, but only if vascularization of large tissue volumes is achievable. The authors sought to upscale their small-animal adipose tissue-engineering models to produce large volumes of tissue in a large animal (i.e., pig). Methods: Bilateral large-volume (78.5 ml) chambers were inserted subcutaneously in the groin enclosing a fat flap (5 ml) based on the superficial circumflex iliac pedicle for 6 (n = 4), 12 (n = 1), and 22 weeks (n = 2). Right chambers included a poly(L-lactide-co-glycolide) sponge. Other pedicle configurations, including a vascular pedicle alone (n = 2) or in combination with muscle (n = 2) or a free fat graft (n = 2), were investigated in preliminary studies. Serial assessment of tissue growth and vascularization by magnetic resonance imaging was undertaken during growth and correlated with quantitative histomorphometry at chamber removal. Results: All chambers filled with new tissue by 6 weeks, vascularized by the arteriovenous pedicle. In the fat flap chambers, the initial 5 ml of fat expanded to 25.9 ± 2.4, 39.4 ± 3.9, and 56.5 ml (by magnetic resonance imaging) at 6, 12, and 22 weeks, respectively. Adipose tissue volume was maintained up to 22 weeks after chamber removal (n = 2), including one where the specimen was transferred on its pedicle to an adjacent submammary pocket. Conclusion: The first clinically relevant volumes of tissue for in situ and remote breast reconstruction have been formed with implications for scaling of existing tissue-engineering models into human trials.

Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series

Paroxysmal visual manifestations may represent epileptic seizures arising from the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications and seizure semiology consistent with an occipital origin have been described, primarily in Mediterranean countries. By reporting three adult patients from an Australian outpatient clinic with visual disturbances, occipital cerebral calcifications, and CD, this study seeks to emphasise that CD should be considered even when patients of non-Mediterranean origin present with these symptoms. Seizure types included simple partial, complex–partial, and secondarily generalised seizures. The seizure semiology consisted of visual disturbances such as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of malabsorption were not always present. Neurological examination was unremarkable in two patients, impaired dexterity and mild hemiatrophy on the left was noted in one. Routine electroencephalography was unremarkable. In all cases, computed tomography demonstrated bilateral cortical calcification of the occipital-parietal regions. Magnetic resonance imaging showed no additional lesion. All patients had biopsy confirmed CD. Seizure control improved after treatment with gluten free diet and anticonvulsants. This report illustrates the association between seizures of occipital origin, cerebral calcifications, and CD even in patients not of Mediterranean origin.

Long-term stability of adipose tissue generated from a vascularized pedicled fat flap inside a chamber.

Background: Numerous studies demonstrate the generation and short-term survival of adipose tissue; however, long-term persistence remains elusive. This study evaluates long-term survival and transferability of de novo adipose constructs based on a ligated vascular pedicle and tissue engineering chamber combination. Methods: Defined adipose tissue flaps were implanted into rats in either intact or perforated domed chambers. In half of the groups, the chambers were removed after 10 weeks and the constructs transferred on their vascular pedicle to a new site, where they were observed for a further 10 weeks. In the remaining groups, the tissue construct was observed for 20 weeks inside the chamber. Tissue volume was assessed using magnetic resonance imaging and histologic measures, and constructs were assessed for stability and necrosis. Sections were assessed histologically and for proliferation using Ki-67. Results: At 20 weeks, volume analysis revealed an increase in adipose volume from 0.04 ± 0.001 ml at the time of insertion into the chambers to 0.27 ± 0.004 ml in the closed and 0.44 ± 0.014 ml in the perforated chambers. There was an additional increase of approximately 10 to 15 percent in tissue volume in flaps that remained in chambers for 20 weeks, whereas the volume of the transferred tissue not in chambers remained unaltered. Histomorphometric assessment of the tissues documented no signs of hypertrophy, fat necrosis, or atypical changes of the newly generated tissue. Conclusion: This study presents a promising new method of generating significant amounts of mature, vascularized, stable, and transferable adipose tissue for permanent autologous soft-tissue replacement.

Meningoencephalomyelitis with vasculitis due to varicella zoster virus: A case report and review of the literature

Summary Varicella zoster virus (VZV) encephalitis is associated with large or small vessel vasculopathy. We report the case of a 67‐year‐old woman with a history of non‐Hodgkins lymphoma and cancers of the breast and colon, who presented with a zosteriform rash and Brown‐Sequard syndrome. Despite 10 days therapy with intravenous acyclovir, meningoencephalitis developed and the patient died 15 days after onset of neurological symptoms. Autopsy showed meningoencephalomyelitis with necrotising vasculitis of leptomeningeal vessels, which is a rare complication of VZV, and we review the literature of the nine similar published cases. Polymerase chain reaction of cerebrospinal fluid for VZV was negative 6 days after onset of neurological symptoms, but became positive by day 10. Only one multinucleated giant cell with intranuclear Cowdry type A inclusions was seen within an endothelial cell in a leptomeningeal vessel involved by vasculitis.

Magnetic resonance imaging of meningiomas: a pictorial review.

Meningiomas are the most common non-glial tumour of the central nervous system (CNS). There are a number of characteristic imaging features of meningiomas on magnetic resonance imaging (MRI) that allow an accurate diagnosis, however there are a number of atypical features that may be diagnostically challenging. Furthermore, a number of other neoplastic and non-neoplastic conditions may mimic meningiomas. This pictorial review discusses the typical and atypical MRI features of meningiomas and their mimics.Teaching Points:There are several characteristic features of meningiomas on MRI that allow an accurate diagnosisSome meningiomas may display atypical imaging characteristics that may be diagnostically challengingRoutine MRI sequences do not reliably distinguish between benign and malignant meningiomasSpectroscopy and diffusion tensor imaging may be useful in the diagnosis of malignant meningiomasA number of conditions may mimic meningiomas; however, they may have additional differentiating features

The radiological fate of dermis-fat grafts in the human temporomandibular joint using magnetic resonance imaging

The purpose of this study was to investigate the radiological fate of the dermis-fat graft within the temporomandibular joint (TMJ) using magnetic resonance imaging (MRI). Fifteen patients with dermis-fat grafts placed in 17 TMJs following discectomy for severe internal derangement were divided into 3 equal groups according to the time lapse between TMJ surgery and the MRI investigation: 0-6 months, 7-23 months and 2 or more years. The radiological presence of fat was found within the joint or surrounding the condyle in all 17 operated joints. The interpositional material found within the radiologically defined joint space was mainly grey (Grade 3, 12 joints), suggesting tissue change to other than fat, i.e. scar or granulation tissue. Two joints showed interpositional material entirely composed of fat (Grade 1), while 3 joints showed heterogeneous material composed of fat interspersed with grey tissue (Grade 2). There was no statistically significant difference in size of fat graft between the time intervals studied. Fat was present in similar quantities within or surrounding all joints regardless of the time lapse since surgery. Intermittent compressive forces of the joint may act as a negative influence on the growth and maintenance of fat tissue within the joint space itself.

Trauma as a precipitant of haemorrhage in synovial cysts.

Synovial cysts have been well reported as a cause of sciatica, with a sudden acute exacerbation being attributed to haemorrhage and subsequent enlargement of the cyst. Cyst formation is attributed to facet joint degeneration associated with a defect or rupture of the joint capsule. The mechanisms of haemorrhage have not been well described previously. Two cases of haemorrhagic synovial cysts causing acute exacerbation of sciatica are described. Both cases were directly attributable to manipulation of degenerate spines. The MRI and histopathological findings are discussed and we propose a mechanism whereby excessive stress on a degenerate revascularized synovium leads to haemorrhage within synovial cysts.

Subfrontal schwannoma: a case report and literature review

Subfrontal schwannomas are rare and usually misdiagnosed preoperatively. We present the third reported case of a schwannoma arising from the olfactory nerve. The neuroradiological and pathological features of the case, as well as the origin of the tumour are discussed.