First Turkish case of Bernard-Soulier syndrome associated with GPIX N45S

Bernard-Soulier syndrome (BSS) is a rare bleeding disorder characterized by giant platelets, thrombocytopenia, and a prolonged bleeding time. It is caused by homozygous defects in the glycoprotein (GP) Ib/IX/V complex, which is the receptor for the von Willebrand factor. We examined a Turkish patient with suspected BSS to identify a molecular basis. Flow cytometric analysis revealed that platelet GPIb alpha and GPIX expression was markedly reduced and DNA sequence analysis showed a homozygous N45S missense mutation in the GPIX gene. Haplotype analysis revealed that the family had the same disease haplotype associated with the GPIX N45S commonly found in Northern European BSS. This is the first non-Caucasian Turkish BSS case due to GPIX N45S and is likely the result of a recurrent mutational event.     

Bedtime administration of cilnidipine controls morning hypertension

Morning blood pressure (BP) level plays an important role in the incidence of cardiovascular disease. Recently, Kario, et al proposed the usefulness of ME difference (morning minus evening systolic BP) and ME average (average of morning and evening systolic BP) for the evaluation of antihypertensive treatment. Cilnidipine is a novel calcium channel blocker (CCB) that exerts inhibitory actions not only on L-type but also on N-type calcium channels. We investigated the effect of bedtime administration of cilnidipine (10 mg) in addition to the antihypertensive treatment for uncontrolled morning hypertension. Twenty-three hypertensive outpatients (13 males and 10 females; mean age, 66.9 years) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening. Morning SBP (P < 0.001) and DBP (P < 0.001) decreased significantly from 150.2 +/- 8.7 and 87.8 +/- 9.3 to 132.7 +/- 7.4 and 77.5 +/- 8.5 mmHg, respectively, after the addition of cilnidipine. Morning heart rate did not change (63.3 +/- 7.0 to 64.1 +/- 9.4). The evening SBP, but not DBP, decreased significantly after treatment. Both the ME average (P < 0.001) and ME difference (P < 0.01) significantly decreased from 143.0 +/- 9.2 and 14.3 +/- 12.4 to 131.3 +/- 7.2 and 2.8 +/- 9.2 mmHg after treatment, respectively. The microalbuminuria decreased from 39.6 +/- 13.2 to 27.3 +/- 8.4 mg/g Cr. In conclusion, L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension by reducing both ME average and ME difference.     

Papillary fibroelastoma in the left ventricular outflow tract

Summary We report a case of a papillary fibroelastoma originating from the left ventricular endocardium in the outflow tract which was discovered by echocardiography in an asymptomatic patient. Two echocardiographic features were observed: (1) the tumor surface was smooth, and characteristic papillary formation was not detected; and (2) the outline of the mass was clearly defined as a dense echo, with the central, radiolucent, portion surrounded by a highly refractive linear echo at the level of the maximum diameter of the mass. The excised tumor was covered with a gelatinous substance that masked multiple papillae on the surface, but its echolucent center could not be explained by the pathology of the tumor which was solid centrally. Our case indicates that a papillary fibroelastoma may sometimes show echocardiographic findings similar to those of a myxoma, although other investigators have not noted the smooth surface and the echolucent center makes it indistinguishable from a myxoma. Thus, in some cases, it is difficult to distinguish papillary fibroelastoma from myxoma by echocardiography.     

Usefulness of a novel diagnostic method of tuberculosis infection, QuantiFERON TB-2G, in an outbreak of tuberculosis

OBJECTIVE: The purpose of this study was to evaluate QuantiFERON TB-2G (QFT), a novel method of detecting tuberculosis infection among contacts of a tuberculosis patient by determining the whole-blood interferongamma response to the specific antigens. SUBJECTS AND METHODS: A teacher of a college who had been coughing for the preceding two months was diagnosed with smear-positive tuberculosis. About 270 students of the college were considered to have been exposed to tuberculosis infection, of whom 73 were in closer contact with the index case because they participated in a one-week group excursion attended by the teacher. Two of the contact students developed active tuberculosis shortly thereafter. Tuberculin tests were conducted to almost all students, and QFT was performed for only those with tuberculin reactions having erythema diameters of 30 mm or larger. RESULTS: Tuberculin tests of students, all of whom had been vaccinated with BCG at least once, revealed that the distribution of the close contact group was slightly shifted to right (larger side) than those with less close contacts. The QFT positive rate for close contacts was 45.5%, while that for less close contacts was only 7.1%, which obviously indicates that QFT is hardly affected by the tuberculin allergy due to past BCG vaccination. The distribution of interferon-gamma measurements (log-transformed) of the close contacts showed typical bimodality, one mode representing the infected, another the non-infected. This was not clear for the less close contacts. The correlation of interferon-gamma measurements (log-transformed) with tuberculin reaction erythema size was weak, if not non-significant. CONCLUSION: It was concluded that QFT was a useful method for diagnosing tuberculosis infection and was unaffected by the BCG-caused tuberculin allergy. In the case of the outbreak mentioned above, QFT greatly reduced the indication of chemoprophylaxis, from 28% of all the contacts solely based on tuberculin test to only 7%. Although there remains some problems to be overcome for QFT to be widely used with high confidence, this technology will provide a high possibility for wider and more accurate indication of chemoprophylaxis and will be one of the essential tools of tuberculosis control of the 21st century in Japan.     

Are twindemics occurring?

The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), prompted worldwide COVID-19 surveillance. To investigate the impact of COVID-19 on influenza activity, we used global surveillance data collected since 2019 to compare the number of cases positive for COVID-19 and for influenza across 22 representative countries (Australia, Brazil, Canada, China, Egypt, France, Germany, India, Israel, Italy, Japan, Mexico, The Netherlands, The Philippines, Poland, The Republic of Korea, South Africa, Spain, Thailand, The United Kingdom, The United States, and Vietnam). Our results demonstrate alternating prevalence of SARS-CoV-2 and influenza virus.     

Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis

BACKGROUND/AIMS: The presence of antibodies to the 210-kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhosis (PBC). However, the significance of anti-gp210 antibody titers for monitoring PBC remains unresolved. METHODS: We used an ELISA with a gp210 C-terminal peptide as an antigen to assess serum antibody titers in 71 patients with PBC. RESULTS: Patients were classified into three groups: Group A in whom anti-gp210 titers were sustained at a high level, Group B in whom anti-gp210 status changed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti-gp210 antibodies were negative at the time of diagnosis. The rate of progression to end-stage hepatic failure was significantly higher in group A (60%) as compared to groups B (0%) and C (4.2%). The sustained antibody response to gp210 was closely associated with the severity of interface hepatitis. The significance of anti-gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. CONCLUSIONS: The serial quantitation of serum anti-gp210-C-terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at high risk for end-stage hepatic failure.     

A localized primary sclerosing cholangitis preoperatively diagnosed as hilar cholangiocarcinoma; report of a case

The authors report herein a case of primary sclerosing cholangitis localized to the hepatic hilum which occurred in a 67-year-old male. The direct cholangiography revealed bile duct stenosis from the common hepatic duct to bilateral hepatic ducts. We could not confirm bile duct malignancy, however, hilar cholangiocarcinoma was most suspicious. We performed right trisegmentectomy of the liver with caudate lobectomy and lymph node dissection 3 weeks after right portal embolization. Pathological findings confirmed localized primary sclerosing cholangitis. Surgical resection of the affected bile duct is most effective in localized primary sclerosing cholangitis, because the prognosis of the disease is poor and secondary carcinogenesis in primary sclerosing cholangitis has high incidence.     

Invasive pulmonary aspergillosis associated with influenza B

Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised patients. However, rarely, this infection can occur in normal hosts. This review of the literature identified 13 cases of IPA associated with influenza, of which 12 had influenza A and the type of influenza was not mentioned in the other case. Reported here is a case of IPA, which was associated with influenza B, in a 63-year-old immunocompetent woman. Her lungs showed gross invasion and she was treated with itraconazole and amphotericin B. She required mechanical ventilation for about 5 months but recovered completely. This is the first reported case of IPA associated with influenza B.     

Chronic inflammatory demyelinating polyneuropathy associated with idiopathic hemochromatosis

We describe a 50-year-old woman who developed chronic inflammatory demyelinating polyneuropathy (CIDP) one year after onset of hemochromatosis. Electrodiagnostic studies showed evidence of multifocal demyelination. Marked hypergammaglobulinemia with positive anti-nuclear and anti-DNA antibodies was found. Corticosteroid treatment resulted in a significant lessening of neurological symptoms. This is the first case of CIDP with hemochromatosis. The association may be coincidental, but the altered immune system by hemochromatosis was possibly related to the development of CIDP in this patient.     

Different effects of amlodipine and enalapril on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase pathway for induction of vascular smooth muscle cell differentiation in vivo.

Although recent clinical trials have shown that amlodipine exerts antiatherogenic effects, the mechanism of these effects remains unknown. This study was designed to examine which signal transduction pathway might be important for the antiatherogenic property of amlodipine, as assessed by aortic smooth muscle cell (SMC) phenotypes in hypertension in vivo. Stroke-prone spontaneously hypertensive rats (SHRSP) were randomly treated with a vehicle, amlodipine, or enalapril while Wistar-Kyoto rats (WKY) used as controls were treated with only the vehicle. Both drugs were equally effective at reducing systolic blood pressure, and inhibiting the progression of aortic remodeling and fibrosis in comparison to those of vehicle-treated SHRSP. In the aortas of vehicle-treated SHRSP, the level of contractile-type smooth muscle (SM) myosin heavy chain (MHC) SM2 was significantly lower, whereas the level of synthetic-type MHC NMHC-B/SMemb was significantly higher compared with those in the WKY aortas. Compared to the vehicle-treated SHRSP group, both drugs significantly and equally shifted the aortic SMC phenotype in SHRSP toward the differentiated state by reducing NMHC-B/SMemb and increasing SM2. The levels of MKK6, p38 MAPK, MEK1 and p-42/44 ERK were significantly higher in the vehicle-treated SHRSP than in the WKY. Both drugs significantly reduced these values in the SHRSP aorta. Furthermore, the levels of MEK1 and p-42/44 ERK were significantly lower in the amlodipine- than in the enalapril-treated SHRSP group, whereas enalapril was more effective than amlodipine at increasing p-Akt and endothelial NO synthase in SHRSP aortas, which were significantly lower in the vehicle SHRSP group than in the WKY group. Thus, the MEK-ERK pathway might be one of the crucial determinants of the aortic SMC phenotype activated by amlodipine treatment of hypertension in vivo.