Errors in the measurements of T2 using multiple-echo MRI techniques. II. Effects of static field inhomogeneity

The accurate estimation of the spin-spin relaxation time T2 is an important goal in magnetic resonance imaging particularly because it can be used for quantitative tissue characterization. The spin-spin relaxation time T2 may be estimated using multiecho pulse sequences, but the accuracy of the estimate is dependent on the fidelity of the spin-echo amplitudes, which may be severely compromised by rf pulse and static field imperfections. In this paper, the effects of static field inhomogeneities are investigated. The propagation of the errors introduced by off-resonance effects are analyzed through computer simulations and analytical solutions of the Bloch equations. A series of experiments performed on a simple tissue phantom using a whole-body imaging system operating at 6.35 MHz corroborates the simulation and analytical results. For accurate measurements of T2 using a whole-body imaging system it is necessary to correct for these inhomogeneities. A correction scheme which would enable a more accurate estimate of T2 is currently under investigation.     

Cancer of the hypopharynx — A clinical study of 290 cases

Between 1986–1990, 290 patients with squamouscell carcinoma of the hypopharynx were assessed at the S. S. K. M. Hospital Calcutta, out of the total of 1460 number of Head Neck cancer, (19.8%). The most frequent initial symptom was a foreign body sensation in the throat (70%), and males were affected more than females (9.8 : 1.2). The peak age incidence was found between 40 and 50 years (24%). Most of the patients came in advanced stages with cervical lymph node metastases (60%). One interesting fact that came out from the present study is the Right pyriform fassa was more commonly affected than the left in righthanded persons (56.9%). Though the reason is not clear it could be due to right — sided swallow, as one side may be predominant in funtion.     

Stimulation of enzyme secretion from isolated pancreatic acini by Clostridium difficile toxin B

Exposure of isolated rat pancreatic acini to increasing concentrations (10 ng - 800 ng/ml) of toxin B from Clostridium difficile produced a biphasic effect on the rate of secretion of amylase, trypsinogen, and chymotrypsinogen. Whereas doses of toxin B from 10-30 ng/ml increased enzyme secretion by 15-20%, doses between 30 ng and 60 ng/ml showed a regression of this effect, whereafter the rate of secretion of amylase, trypsinogen, and chymotrypsinogen increased with increasing concentrations of the toxin. Toxin B concentration of 800 ng/ml enhanced amylase, trypsinogen and chymotrypsinogen secretion by 119%, 185% and 195%, respectively, when compared with the basal level. Stimulation of enzyme secretion by toxin B was not affected by the presence of either actinomycin-D or cycloheximide, at a concentration which inhibited acinar RNA or protein synthesis by 80-90%. Although toxin B as well as CCK8, carbachol and secretin by themselves caused significant stimulation in amylase, trypsinogen and chymotrypsinogen secretion from isolated pancreatic acini, toxin B together with either CCK8, carbachol or secretin produced no further augmentation in enzyme secretion than what was observed with the secretagogues alone. It is concluded that toxin B of Cl. difficile exerts a direct effect on pancreatic acinar cells as evidenced by stimulation of enzyme secretion.     

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.     

Evaluation of active and passive transport processes in corneas extracted from preserved rabbit eyes

In vitro transcorneal permeability studies are an important screening tool in drug development. The objective of this research is to examine the feasibility of using corneas isolated from preserved rabbit eyes as a model for permeability evaluation. Eyes from male New Zealand White rabbits were used immediately or were stored overnight in phosphate-buffered saline (PBS) or Hanks balanced salt solution (HBSS) over wet ice. Integrity of isolated corneas was evaluated by measuring the TEER and by determining the permeability of paracellular and transcellular markers. Active transport was assessed by measuring transcorneal permeability of selected amino acids. Esterase activity was estimated using p-nitrophenyl assay. In all cases, corneas from freshly enucleated eyes were compared to those isolated from the day-old preserved eyes. Transcellular and paracellular passive diffusion was not affected by the storage medium and observed to be similar in the fresh and preserved eye models. However, amino acid transporters demonstrated lower functional activity in corneas excised from eyes preserved in PBS. Moreover, preserved eyes displayed almost 1.5-fold lower esterase activity in the corneal tissue. Thus, corneas isolated from day-old eyes, preserved in HBSS, closely mimics freshly excised rabbit corneas in terms of both active and passive transport characteristics but possesses slightly reduced enzymatic activity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1921–1930, 2010     

T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis.

With the use of monoclonal antibodies (mAb) and immunohistology, the numbers of phenotypically distinct cells infiltrating lung tissue from 15 postmortem (PM) cases of fatal asthma were quantified and compared with 6 cases of cystic fibrosis (CF) (three postmortem, three transplant) and 10 nonasthmatic cases of sudden death matched for age and sex. Tissue eosinophilia was significantly greater (p less than 0.001) in the fatal asthma group than in the CF or sudden death controls. In asthma, approximately 40% of the eosinophilic infiltrate was EG2 positive (an indication of eosinophil activation and secretion of eosinophil cationic protein). The numbers of eosinophils and EG2 positive cells were significantly elevated in the subjects with acute severe asthma who had had a duration of terminal illness exceeding, as compared with less than, 24 h (p less than 0.05). When compared with the sudden death controls, there were increases in the numbers of Dako L C positive cells (i.e., CD45 positive "total leukocytes") in both fatal asthma and CF (p less than 0.01 and 0.05, respectively). The mean number of MT-1 positive (T) cells in the asthma and CF groups was approximately twice that of the control (p less than 0.05 and 0.01, respectively). The mean number of MB2 positive (B) cells was similar for both the asthma and sudden death control groups but was significantly increased in CF (p less than 0.05). The average T:B cell ratios were 6:1, 1:1, and 2:1 in the fatal asthma, CF, and control groups, respectively. The results support a role for the T lymphocyte in the pathogenesis of fatal asthma and CF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.