Anticonvulsant syndrome with multiple symptoms, including porphyria, IgA deficiency, and liver dysfunction

A 19-year-old Japanese female who had been treated for epilepsy with a combined phenytoin-phenobarbital preparation for the past three years presented with increasing skin pigmentation and hirsutism. She had suffered two attacks of loss of consciousness after bilateral partial oophorectomy at the age of 16. Investigations revealed a marked increase in coproporphyrin levels in the urine and feces, a marked decrease in her serum IgA level, and liver dysfunction. All these manifestations gradually improved upon the withdrawal of her antiepileptic treatment. In vitro studies revealed B cell dysfunction producing IgA deficiency, which normalized within one year after discontinuation of the antiepileptic therapy. It was assumed that her treatment had worsened preexisting porphyria, which was misdiagnosed as epilepsy because of abnormal EEG findings. The type of porphyria appeared to be hereditary coproporphyria, despite the lack of a family history.     

Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes

OBJECTIVE: Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT). RESEARCH DESIGN AND METHODS: Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal. RESULTS: Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002). CONCLUSIONS: Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.     

Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site

Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose–basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation.     

Nontargeted stable integration of recombinant adeno-associated virus into human leukemia and lymphoma cell lines as evaluated by fluorescence in situ hybridization

A number of studies on human epithelial cells of varying origin have demonstrated integration of recombinant adeno-associated virus (AAV) vectors into a variety of chromosomes compared with the site-specific integration on chromosome 19 predominantly observed for wild-type (wt) AAV. We have constructed a recombinant AAV (rAAV) vector and tested the integration into hematopoietic cells, using the human acute myeloid leukemia cell line AML5 and the human non-Hodgkin's lymphoma cell line OCI-LY18 as targets. The integration sites were visualized by fluorescence in situ hybridization (FISH). Positive signals were observed for chromosomes 1, 2, 3, 8, 14, 15, 19, and Y. The majority of cells demonstrated integration into one specific site. A minority showed simultaneous integration into more than one chromosome. The frequency of observed integrations was not uniformly distributed among chromosomes; for instance, in AML5 chromosome 2 seemed to be favored. Colony-derived AML5 clones bore unique integration patterns indicating successful transduction of clonogenic progenitor cells with high proliferative potential. The integration was stable and observed for more than 12 months after transduction. FISH has been shown to be a powerful tool for detailed analyses of rAAV integration patterns and can be used to evaluate targets and transduction conditions.     

Utility of perioperative skin perfusion pressure measurement for treatment of ulcers caused by arteriovenous access ischaemic steal

Arteriovenous access ischaemic steal is a serious complication following arteriovenous fistula (AVF) construction. The aim of treatment is to improve distal circulation without impairing the function of the fistula. Therefore, any repair should be performed with intraoperative monitoring. We report 2 cases of this disorder treated using perioperative measurement of skin perfusion pressure (SPP) for preoperative surgical planning and intraoperative guidance. A 73‐year‐old woman with a left cubital AVF developed gangrene of the tip of the left little finger. Arteriovenous access ischaemic steal was suspected. The SPP of the little finger was 18 mm Hg, which increased to 65 mm Hg after manual occlusion of the fistula. A 58‐year‐old woman with a left antebrachial AVF had gangrene of the tip of the left middle finger. The SPP was 19 mm Hg, and steal syndrome was suspected based on angiography and the SPP with manual occlusion of the fistula. In both cases, serial plication of the fistula was performed based on intraoperative perfusion pressure monitoring, leading to the successful resolution of the ischaemic steal syndrome. In both cases, haemodialysis could be continued through the repaired fistula.     

Breast masses with mixed cystic-solid sonographic appearance

Retrospective analysis was performed for 56 breast masses with mixed cystic and solid sonographic patterns encountered in the last 5 years at Keio University Hospital, with the objective of elucidating their significance. The lesions were classified into two major groups: tumor with cyst (TWC—solid mass with cystic component) and intracystic tumor (ICT—cystic mass with solid component). According to the pathological diagnosis, 57% were benign and 43% were malignant. Fifty eight percent of malignant lesions were shown to have a TWC pattern and 42% an ICT pattern. Among benign lesions, 66% were shown to be TWC and 34% ICT. In malignant tumors, 96% of the cases showed irregular shape and heterogeneous internal content. Even in benign lesions, a high incidence of irregular shape and rough border was found, although the predominant internal echo texture was homogeneous, and threedimensional (3-D) contour was not clear. In conclusion, we observed that in the TWC group, the lack of a defined 3-D contour is the most important criterion, and tumors with multiples cysts tend to be benign. © 1993 John Wiley & Sons, Inc.     

Neural substrates participating in acquisition of facial familiarity: an fMRI study

The amygdala is related to recognition of faces and emotions, and functional magnetic resonance imaging (fMRI) studies have reported that the amygdala is habituated over time with repetition of facial stimuli. When subjects are presented repeatedly with unfamiliar faces, they come to gradually recognize the unfamiliar faces as familiar. To investigate the brain areas participating in the acquisition of familiarity to repeatedly presented unfamiliar faces, we conducted an fMRI study in 16 healthy subjects. During the task periods, the subjects were instructed to see presented unfamiliar faces repeatedly and to judge whether the face was male or female or whether the face had emotional valences. The experiment consisted of nine sessions. To clarify the brain areas that showed increasing or decreasing activation as the experimental session proceeded, we analyzed the fMRI data using specified linear covariates in the face recognition task from the first session to the ninth session. Imaging data were investigated on a voxel-by-voxel basis for single-group analysis according to the random effect model using Statistical Parametric Mapping. The bilateral posterior cingulate cortices showed significant increases in activity as the experimental sessions proceeded, while the activation in the right amygdala and the left medial fusiform gyrus decreased. Thus, the posterior cingulate cortex may play an important role in the acquisition of facial familiarity.     

In vivo mapping of temporospatial changes in manganese enhancement in rat brain during epileptogenesis

Mesial temporal lobe epilepsy is associated with structural and functional abnormalities, such as hippocampal sclerosis and axonal reorganization. The temporal evolution of these changes remains to be determined, and there is a need for in vivo imaging techniques that can uncover the epileptogenic processes at an early stage. Manganese-enhanced magnetic resonance imaging may be useful in this regard. The aim of this study was to analyze the temporospatial changes in manganese enhancement in rat brain during the development of epilepsy subsequent to systemic kainate application (10 mg/kg i.p.). MnCl(2) was given systemically on day 2 (early), day 15 (latent), and 11 weeks (chronic phase) after the initial status epilepticus. Twenty-four hours after MnCl(2) injection T1-weighted 3D MRI was performed followed by analysis of manganese enhancement. In the medial temporal lobes, there was a pronounced decrease in manganese enhancement in CA1, CA3, dentate gyrus, entorhinal cortex and lateral amygdala in the early phase. In the latent and chronic phases, recovery of the manganese enhancement was observed in all these structures except CA1. A significant increase in manganese enhancement was detected in the entorhinal cortex and the amygdala in the chronic phase. In the latter phase, the structurally intact cerebellum showed significantly decreased manganese enhancement. The highly differentiated changes in manganese enhancement are likely to represent the net outcome of a number of pathological and pathophysiological events, including cell loss and changes in neuronal activity. Our findings are not consistent with the idea that manganese enhancement primarily reflects changes in glial cells.