Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.     

Conversion factor for comparison of data from Humphrey and Medmont automated perimeters

Background : Clinical experience has shown that the sensitivity indices reported by the Humphrey Field Analyser (HFA) are generally higher than those given by the Medmont Automated Perimeter (M600). It is the purpose of this paper to determine a conversion factor for the two perimeters and to confirm this prediction using clinical data. Theory predicted that HFA_sensitivity ? 5 dB = M600_sensitivity. Methods : Sensitivity versus eccentricity profiles were measured over the central visual field on 10 young subjects using both perimeters. Results : Both the HFA and the M600 operate within the realms of the Weber law and measure similar Weber fractions. The sensitivity profiles had similar slopes (about ?0.2 dB/degree) and were separated by about six decibels with the HFA reporting higher sensitivity values. This result confirmed the theoretical prediction. Conclusion : The difference in threshold sensitivities between the two perimeters is a result of differences in scaling factors and instrument luminances. A suggested clinical conversion factor is to subtract 5 dB from the HFA data to approximate those of the M600.     

Molecular analysis of lymphoid malignancies

Although lymphoid malignancies have been widely studied at the molecular level, no group has reported on the simultaneous investigation of t(14;18) chromosomal translocation, B-cell clonality and bcl2 gene expression. We have performed PCR analysis of t(14;18) translocation and B-cell clonality as well as semi-quantitation of bcl2 expression by Western blotting on a group of 41 patients treated at our institution for lymphoid malignancies. The t(14;18) translocation was observed in 10 out of 40 cases (25%) with a prevalence in the subgroup of centrofollicular lymphoma (9 out of 19, or 47%, which includes one patient in complete clinical remission). bcl2 was overexpressed in 84% of the patients (21/25) and B monoclonality was observed in 21 out of 37 B-cell neoplasia patients (57%) with or without a t(14;18) translocation. In 4 patients, bcl2 overexpression, which has been implicated in the sensitivity to a variety of cytotoxic drugs, was the only abnormality detected. Studies are currently underway to determine whether semi-quantitation of bcl2 expression provides improved prediction of a patient's response to chemotherapy.     

Renal abnormalities in sickle cell disease

Renal abnormalities in sickle cell disease. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct and papillary necrosis. Impaired urinary concentrating ability, renal acidification, hematuria, and potassium secretion are also found. There may be a causal relationship between an increase in nitric oxide synthesis and experimental sickle cell nephropathy, and some studies have indicated that the progression of sickle cell nephropathy is hemodynamically mediated. Although there are many studies showing that proteinuria, nephrotic syndrome, chronic progressive renal failure, and acute renal failure syndromes are the outcome of this disease, the pathogenic mechanism(s) and potential therapies remain to be elucidated. Survival of patients with sickle cell nephropathy who progress to end-stage renal disease (ESRD) is equal to non-diabetic ESRD patients, and graft survival rates are also similar for those who undergo renal transplantation. This article presents a historical review of the glomerular and tubular disorders associated with sickle cell nephropathy, and reviews therapeutic indications to slow its progression. Further research is needed.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.      

Inhalation of low concentrations of toluene induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat

The organic solvent toluene is widely used in industry. The threshold limit value for extended occupational exposure to toluene is presently set to 200 ppm in the United States. We have investigated the effect of an inhalation exposure of 80 ppm for 4 weeks (6 h/day, 5 days/week), followed by a postexposure period of at least 4 weeks, on behavior and brain features in the rat. Toluene exposure appeared to affect spatial memory, since toluene-exposed rats showed a longer time in the correct quadrant in a Morris swim maze. This effect may indicate that the exposed rats used their praxis strategy longer before they started to look for the platform elsewhere. Toluene-exposed rats showed trends for increases in both locomotion and rearing behaviors and a significantly reduced beam-walk performance. The area of the cerebral cortex, especially the parietal cortex, was decreased by 6-10% in toluene-exposed rats, as shown by magnetic resonance imaging of living rats and autoradiograms of frozen brain sections. The K(D) and B(max) values of the dopamine D(3) agonist [(3)H]PD 128907 were not affected by toluene, as measured in caudate-putamen and subcortical limbic area using biochemical receptor binding assays and in caudate-putamen and islands of Calleja using quantitative receptor autoradiography. Hence, previously demonstrated persistent effects by toluene on the binding characteristics of radioligands binding to both D(2) and D(3) receptors seem to indicate a persistent effect of toluene selectively on dopamine D(2) receptors. Taken together, the present results indicate that exposure to low concentrations of toluene leads to persistent effects on cognitive, neurological, and brain-structural properties in the rat.     

Urinary hyaluronic acid and hyaluronidase: markers for bladder cancer detection and evaluation of grade

PURPOSE: Specific patterns of progression and frequent recurrence of bladder tumors determine the choice of treatment, frequency of surveillance, quality of life, and ultimately, patient prognosis. The prognosis would be improved if an accurate noninvasive test was available for diagnosis. Identification of markers that function in bladder cancer progression would be helpful in designing such diagnostic tests. The glycosaminoglycan, hyaluronic acid (HA), promotes tumor metastasis. Hyaluronidase (HAase), an endoglycosidase, degrades HA into small fragments that promote angiogenesis. We have previously shown that both HA and HAase are associated with bladder cancer and may function in bladder tumor angiogenesis. In this study we examined whether urinary HA and HAase levels serve as bladder cancer markers. MATERIALS AND METHODS: Among the 513 urine specimens analyzed, 261 were from transitional cell carcinoma (TCC) patients, 9 from patients with non-TCC tumors, and 243 from controls (normals, patients with other genitourinary (GU) conditions or a history of bladder cancer (HxBCa)). The urinary HA and HAase levels were measured by two ELISA-like assays that utilize a biotinylated HA binding protein for detection. These levels were normalized to total urinary protein and were expressed as ng./mg. (HA test) and mU/mg. (HAase test), respectively. RESULTS: The urinary HA levels were elevated (2.5 to 6.5 fold) in bladder cancer patients (1173.7+/-173.4; n = 261) as compared with normals (246.1+/-38.5; n = 41); GU patients (306.6+/-32.2; n = 133), and patients with a HxBCa (351.1+/-49.1; n = 69) (p <0.001). The urinary HAase levels were elevated (3 to 7 fold) in G2/G3 bladder cancer patients (26.2+/-3.2) as compared with normals (4.5+/-0.9) and patients with either GU conditions (5.8+/-1.3), HxBCa (8.2+/-2.6) or G1 tumors (9.7+/-2.5) (p <0.001). The HA test showed 83.1% sensitivity, 90.1% specificity and 86.5% accuracy in detecting bladder cancer, regardless of the tumor grade. The HAase test showed 81.5% sensitivity, 83.8% specificity and 82.9% accuracy to detect G2/G3 patients. Combining the inferences of the HA and HAase tests (HA-HAase test) resulted in detection of bladder cancer, regardless of tumor grade and stage, with higher sensitivity (91.2%) and accuracy (88.3%), and comparable specificity (84.4%). CONCLUSION: Our results show that the HA-HAase urine test is a noninvasive, highly sensitive and specific method for detecting bladder cancer and evaluating its grade.     

Report of the ASFA apheresis registry on muscle specific kinase antibody positive myasthenia gravis

Background : Anti‐muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti‐acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. Methods : The study collected detailed de‐identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. Results : A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 − 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty‐one percent of patients responded poorly with minimal recovery. Conclusion : Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor‐responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5–11, 2017. © 2016 Wiley Periodicals, Inc.