Abnormal α-aminoadipic acid excretion in a newborn with a defect in platelet aggregation and antenatal cerebral haemorrhage

Summary -Aminoadipic acid (AA) is an intermediate in lysine metabolism. We report a new case with AA excess in urine and plasma, without -ketoadipic acid, in a full-term male child born to unrelated parents; he presented at 24h of life with seizures that failed to respond to phenobarbital, clonazepam, and Vigabatrin and death occurred on the 38th day of life. Brain imaging suggested antenatal haemorrhage. Small quantities of AA were also detected in the blood and urine of both parents and a healthy brother, all three of whom exhibited the same defect in platelet aggregation as the deceased child. Both parents had decreased levels of plasma neopterin, a finding that might be related to the immunodeficiency described in other cases.     

Identification of a polymorphic glutamic acid stretch in the α2b-adrenergic receptor and lack of linkage with essential hypertension

Essential hypertension, a clinically significant elevation in blood pressure with no recognizable cause, is believed to be attributable to the collective effect of genetic predisposing factors in combination with specific environmental factors, such as diet and stress. Of the genetic causes, genes coding for proteins involved in blood pressure regulation, such as the α- and β-adrenergic receptors, are obvious candidates. The α₂-adrenergic receptor plays a key role in the sympathetic nervous system by mediating the effects of epinephrine and norepinephrine. To evaluate the potential role between the α_2B receptor and essential hypertension, we scanned the α_2B-receptor gene for genetic variation in 108 affected sibling pairs. The screening revealed two major forms of the receptor. They differ by the presence of either 9 or 12 glutamic acid residues in the acidic domain of the third cytoplasmic loop of the protein. Investigation of the pattern of this variation in hypertensive sibling pairs suggests that the α_2B receptor locus does not contribute substantially to genetic susceptibility for essential hypertension.     

Ustekinumab in a patient with Crohn's disease and anti-TNF-α-induced psoriasis

Treatment with anti-tumor necrosis factor (TNF)-α for Crohn's disease is relatively safe, although various cutaneous adverse effects have been reported such as the development or exacerbation of anti-TNF- α-induced psoriasis, which can sometimes lead to treatment withdrawal. Therefore, new alternative treatments with new mechanisms of action are required. Ustekinumab, a monoclonal antibody against the p40 subunit of interleukin 12/23, could induce response in patients with Crohn's disease and has demonstrated efficacy in patients with psoriasis. We present the case of a woman with Crohn's disease who developed psoriasis after treatment with two anti-TNF- α drugs (infliximab and adalimumab). The patient was subsequently treated with ustekinumab with resolution or psoriasis lesions and maintenance of remission of Crohn's disease.     

Impaired degradation of phytanic acid in cells from patients with mitochondriopathies: Evidence for the involvement of ETF and the respiratory chain in phytanic acid α-oxidation

Summary Phytanic acid -oxidation was studied in cultures of skin fibroblasts and myoblasts from patients with various defects of the respiratory chain in order to obtain information on the subcellular site and the mechanism of this pathway. In fibroblasts from patients with complex IV (cytochromec oxidase) deficiency or glutaricaciduria type II, phytanic acid -oxidation was reduced to 14% of normal, whereas in myoblasts from patients with complex I (NADH-Q reductase) deficiency, it was normal. Apparently, at least one step of phytanic acid -oxidation occurs in mitochondria and in this process electrons are transferred to the respiratory chain via the electron-transfer flavoprotein (ETF).     

Lactic acidosis and hypoglycemia in a patient with high-grade non-Hodgkin's lymphoma and elevated circulating TNF-α

A 71-year-old patient with high-grade non-Hodgkin's lymphoma stage IVB, severe lactic acidosis and tumor-associated hypoglycemia is described. Endocrine causes of hypoglycemic episodes were excluded because of low serum concentrations of insulin and insulin-like growth factor 1, and normal concentrations of growth hormone and thyroid hormone. Clinical conditions associated with lactic acidosis such as diabetes mellitus, biguanide intoxication, septicemia, acute hypoxemia, or circulatory insufficiency were ruled out. Enhanced glucose metabolism within the tumor was visualized by positron emission tomography employing 2-fluoro-2-deoxy-d-glucose (FDG) as a tracer. A markedly elevated tumor necrosis factor-alpha (TNF-) level was found which decreased after cytoreductive therapy paralleling the normalization of serum lactate. In contrast to the majority of cases of lymphoma-associated lactic acidoses reviewed to date, in our case lactate elimination was not reduced.     

Pituicytoma in a patient with Cushing’s disease: case report and review of the literature

There are scant prospective studies defining improvements in critical outcome measures with hormone replacement in hypopituitarism secondary to brain injury. We review the tests of cognition and physical function and summarize their use for subjects that are deficient in anterior hormone production during anterior pituitary hormone replacement in brain injury and propose these as the minimal tests that are feasible for a physician to perform in a clinical setting. We summarize the studies conducted to assess outcome measures after brain injury and also report preliminary findings for improvements in cognition and physical function in subjects with brain injury and GH deficiency.     

Endoscopic identification of Peyer's patches of the terminal ileum in a patient with Crohn's disease

We presented a 20-year-old patient with Crohn's disease(CD).Colonoscopy revealed longitudinal ulceration in theterminal ileum and rectal aphtoid ulcers.After treatmentwith mesalamine and total parenteral nutrition,repeatcolonoscopy revealed a granular elevated area in the terminalileum,which appeared as an irregular dome-like elevationwith irregularly arranged villi on magnifying endoscopy.Biopsyspecimens taken from the region showed microgranulomasand lymphoid hyperplasia,Scanning electron microscopyrevealed the presence of M cells,confirming that the areacorresponded to Peyer's patches.Peyer's patches bymagnifying endoscopy and electron microscopy may provideinsights into the pathogenesis of CD.     

Transverse myelitis in a patient with Behcet’s disease: favorable outcome with a combination of interferon-α

We report here on a 24-year-old patient with Behçets disease who had been diagnosed with acute transverse myelitis. He was successfully treated with a combination regimen of a steroids, cyclophosphamide, and interferon-. The treatment strategy with specific emphasis on interferon- is discussed in the light of the pertinent literature.     

Novel mutations in the gene encoding acid α-1,4-glucosidase in a patient with late-onset glycogen storage disease type II (Pompe disease) with impaired intelligence

A 17-year-old Japanese man was referred to our hospital because of highly elevated serum levels of creatine kinase (CK) and transaminases. On admission, the proximal muscles of the lower extremities were found to be predominantly affected, and a score of 3/5 was obtained on Medical Research Council (MRC) scale. Muscular atrophy was evident and Gowers' sign was positive. His functional vital capacity (FVC) was markedly reduced. The results of the third edition of the Wechsler Adult Intelligence Scale (WAIS-III) indicated impairment of the patient's intelligence. Muscle biopsy showed scattered intracytoplasmic vacuoles with basophilic amorphous materials inside which were strongly stained by both periodic acid Schiff (PAS) and acid phosphatase. Biochemical analysis of the muscle tissue confirmed the diagnosis of GSDII because the glucosidase activity was 1.0 nmol/4 MU/mg/30 min (control range, 7.3 ± 2.2). Genetic analysis revealed a novel compound heterozygous missense mutation in GAA--c.1814 G >A (p.Gly605Asp) and c.1846 G >A (p.Asp616Asn) both in exon 13.     

Aneurysmatic dilatation of ascending aorta in a patient with β-thalassemia and a pseudoxanthoma elasticum-like syndrome

The development of a diffuse elastic tissue defect resembling pseudoxanthoma elasticum (PXE) is a recently established and frequently encountered clinical entity in -thalassemia. The clinical spectrum of this disorder is not yet completely understood as it is continuously being enriched with novel complications that are often serious. We present here a thalassemia intermedia patient with typical PXE manifestations and a fusiform aneurysmatic dilatation of the ascending thoracic aorta, a previously unknown complication in these patients. An aortic aneurysm has itself a notable morbidity, while it may also impair the particularly susceptible cardiac function of -thalassemia patients, hence affecting the overall prognosis of the main disease.     

Dietary supplementation with N-acetyl cysteine, α-tocopherol and α-lipoic acid reduces the extent of oxidative stress and proinflammatory state in aged rat brain

The present study has attempted to understand how oxidative stress contributes to the development of proinflammatory state in the brain during aging. Three groups of rats have been used in this study: young (4–6?months, Group I), aged (22–24?months, Group II) and aged with dietary antioxidant supplementation (Group III). The antioxidants were given daily from 18?months onwards in the form of a combination of N-acetyl cysteine (50?mg/100?g body weight), α-lipoic acid (3?mg/100?g body weight), and α-tocopherol (1.5?mg/100?g body weight) till the animals were used for the experiments between 22 and 24?months. Several measurements have been made to evaluate the ROS (reactive oxygen species) production rate, the levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the activation status of NF-κβ (p65 subunit) in brain of the three groups of rats under the study. Our results reveal that brain aging is accompanied with a significant increase in NADPH oxidase activity and mitochondrial ROS production, a distinct elevation of IL-1β, IL-6 and TNF-α levels along with increased nuclear translocation of NF-κβ (p65 subunit) and all these phenomena are partially but significantly prevented by the long-term dietary antioxidant treatment. The results imply that chronic dietary antioxidants by preventing oxidative stress and proinflammatory state may produce beneficial effects against multiple age-related deficits of the brain.     

A case of granuloma in the occipital lobe of a patient with Wegener’s granulomatosis

We report a case of Wegener's granulomatosis (WG) with central nervous system (CNS) involvement in a woman who complained of bilateral visual disturbance. The intracranial necrotizing granulomatous lesion was confirmed by MR imaging and brain biopsy. After high-dose oral corticosteroid treatment, not only clinical manifestations but also laboratory tests improved. Moreover, the CNS lesion completely regressed. This suggests that high-dose corticosteroid alone might be effective in treating WG with CNS involvement.     

Assessment of coronary morphology and flow in a patient with Guillain-Barré syndrome and ST-segment elevation

Patients with Guillain-Barré syndrome often have cardiac disturbances as a manifestation of autonomic dysfunction. Such abnormalities consist of arrhythmias and disturbances of heart rate and blood pressure. We report a case of a patient with Guillain-Barré syndrome who developed ST-segment elevation in the inferolateral leads, suggestive of an acute coronary syndrome. Cardiac catheterization revealed angiographically normal coronary arteries. Intracoronary ultrasound was also normal. Intracoronary Doppler flow measurements revealed an elevated baseline coronary flow velocity of up to 41 cm/s and decreased coronary flow reserve, particularly in the left circumflex artery. Myopericarditis as cause of the electrocardiographic changes could be ruled out by echocardiography and endomyocardial biopsy. We postulate that the intracoronary Doppler findings are caused by autonomic dysfunction with decrease of coronary resistance and redistribution of the transmural myocardial blood flow.     

Efficacy of etanercept in the treatment of a patient with Behçet’s disease

Behçet’s disease is a systemic inflammatory disorder without a specific treatment that is chosen on the basis of the type and severity of manifestation in the organ involved. More recently, biological agents like etanercept have emerged as possible therapeutic alternatives in patients resistant to conventional therapy. We describe the successful treatment for 1 year of resistant Behçet’s disease with etanercept. After the administration of this drug, a resolution of the clinical, laboratory and instrumental picture was achieved with a suspension of immunosuppressive treatments and a reduction of steroid dependency (5 mg/day). No side effects were observed.