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Biomedical subjects

J Hill

Publications and source records attributed to J Hill.

At least 163 records · Page 9Linked to original sources

Gastroesophageal reflux, motility disorders, and psychological profiles in the etiology of globus pharyngis.

The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogastroduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis.

Adult↗

A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs.

We investigated the roles of pneumolysin and neuraminidase in the pathogenesis of deafness and cochlear damage during experimental pneumococcal meningitis. Anesthetized guinea pigs were inoculated intracranially with 7.5 log10 CFU of either (i) wild-type Streptococcus pneumoniae D39 (n = 8), (ii) PLN-A, a defined isogenic derivative of D39 deficient in pneumolysin (n = 5), or (iii) deltaNA1, a new derivative of D39 deficient in neuraminidase constructed by insertion-duplication mutagenesis of the nanA gene (n = 5). To quantify hearing loss, the auditory nerve compound action potential evoked by a tone pulse was recorded from the round window membrane of the cochlea every 3 h for 12 h. The organ of Corti was intravitally fixed for subsequent examination by high-resolution scanning and transmission electron microscopy. All animals sustained similar meningeal inflammatory responses. PLN-A induced significantly less hearing loss than D39 over the frequency range of 3 to 10 kHz. Levels of mean hearing loss at 10 kHz 12 h postinoculation were as follows: D39, 50 dB; deltaNA1, 52 dB (P = 0.76 versus D39), and PLN-A, 12 dB (P < 0.0001 versus D39). The mean rates of hearing loss at 10 kHz were 4.4 dB/h for D39, 4.3 dB/h for deltaNA1, and just 1.0 dB/h for PLN-A (P < 0.0001 versus D39). Suppurative labyrinthitis was universal. PLN-A induced the accumulation of less protein in the cerebrospinal fluid (P = 0.04 versus D39). Infection with D39 and deltaNA1 induced significant damage to the reticular lamina, the sensory hair cells, and supporting cells of the organ of Corti. By contrast, after infection with PLN-A, the organ of Corti appeared virtually intact. Pneumolysin seems to be the principal cause of cochlear damage in this model of meningogenic deafness. No clear pathogenic role was demonstrated for neuraminidase.

Animals↗

Regions of Yersinia pestis V antigen that contribute to protection against plague identified by passive and active immunization.

V antigen of Yersinia pestis is a multifunctional protein that has been implicated as a protective antigen, a virulence factor, and a regulatory protein. A series of V-antigen truncates expressed as glutathione S-transferase (GST) fusion proteins (GST-V truncates) have been cloned and purified to support immunogenicity and functionality studies of V antigen. Immunization studies with GST-V truncates have identified two regions of V antigen that confer protection against Y. pestis 9B (a fully virulent human pneumonic plague isolate) in a mouse model for plague. A minor protective region is located from amino acids 2 to 135 (region I), and a major protective region is found between amino acids 135 and 275 (region II). In addition, analysis of IgG titers following immunization suggested that the major antigenic region of V antigen is located between amino acids 135 and 245. A panel of monoclonal antibodies raised against recombinant V antigen was characterized by Western blotting against GST-V truncates, and epitopes of most of the monoclonal antibodies were mapped to region I or II. Monoclonal antibody 7.3, which recognizes an epitope in region II, passively protected mice against challenge with 12 median lethal doses of Y. pestis GB, indicating that region II encodes a protective epitope. This is the first report of a V-antigen-specific monoclonal antibody that will protect mice against a fully virulent strain of Y. pestis. The combined approach of passive and active immunization has therefore confirmed the importance of the central region of the protein for protection and also identified a previously unknown protective region at the N terminus of V antigen.

Animals↗

Surgical treatment of acute manifestations of Crohn's disease during pregnancy.

When requiring surgery, acute exacerbations of Crohn's disease in pregnancy have been reported to carry high maternal and fetal mortality. We report six cases. The women presented at 30, 28, 12, 11, 31 and 25 weeks' gestation and all proved to have intraperitoneal sepsis. In three, the acute symptoms were the first indication of Crohn's disease. All the women recovered and five had healthy babies; the other had a miscarriage when a colonic anastomosis dehisced. In pregnant women with Crohn's disease, the indications for surgery are the same as in non-pregnant patients. For acute manifestations we recommend removal of the source of the sepsis and exteriorization of the bowel ends.

Acute Disease↗

Investigation of the effect of short-term change in dietary magnesium intake in asthma.

Epidemiological evidence suggests that a low dietary intake of magnesium is associated with impaired lung function, bronchial hyperreactivity and wheezing. This study was designed to investigate whether short-term alterations of dietary magnesium intake have an effect on the clinical control of asthma. In a randomized, double-blind, placebo-controlled, cross-over study, 17 asthmatic subjects adhered to a low magnesium diet for two periods of 3 weeks, preceded and separated by a 1 week run-in/wash-out, in which they took either placebo or magnesium (400 mg x day(-1)) tablet supplementation. Forced expiratory volume in one second (FEV1) and the provocative dose of methacholine required to cause a 20% fall in FEV1 from baseline (PD20,FEV1) were measured at the beginning and end of each treatment period, and variation in peak expiratory flow (PEF) rate, bronchodilator use and symptom scores recorded throughout. Asthma symptom scores were significantly lower during the magnesium treatment period, the median (95% confidence interval) difference from placebo being 3.8 (0.5-7.0) symptom points per 7 days (p=0.02). However, there was no significant improvement in FEV1, PD20,FEV1, log amplitude percentage mean PEF variation or bronchodilator use during magnesium supplementation. A high magnesium intake was associated with improvement in symptom scores, though not in objective measures of airflow or airway reactivity, in these stable asthmatic subjects.

Adult↗

A prospective randomized trial of feeding methods in very low birth weight infants.

OBJECTIVE: To test the hypothesis that very low birth weight infants fed by continuous nasogastric gavage (CNG) would achieve full enteral feedings (100 kcal/kg/d) at an earlier postnatal age and have less feeding intolerance (FI) than infants fed by intermittent bolus gavage (IBG). METHODS: Eighty infants were stratified by birth weight (700 to 1000 g and 1001 to 1250 g) and randomized into CNG or IBG feeding groups. CNG infants were comparable with IBG in birth weight, gestational age, sex, race, and day of onset of feeding (5.7 +/- 2.1 days vs 5.6 +/- 2.2 days, respectively). Feedings were given as undiluted Similac Special Care formula (Ross Laboratories, Columbus, OH) via a specific protocol designed for each 50 to 100 g birth weight category. Feedings were advanced isoenergetically by a maximum of 25 mL/kg/d until an endpoint of 100/kcal/kg/d for at least 48 hours was reached. An infant whose feedings were withheld for >12 hours based on predetermined criteria was considered to have an episode of FI. RESULTS: Infants in the CNG group reached full enteral feeding at 17.1 +/- 8.9 days compared with 15.5 +/- 5.5 days in the IBG group; these were not statistically different. Secondary outcome variables such as days to regain birth weight (CNG, 12.6 +/- 5 days vs IBG, 12.5 +/- 3.7 days), days to reach discharge weight of 2040 g (CNG, 60 +/- 13.4 days vs IBG, 62 +/- 13.6 days), and number of episodes of FI were not significantly different between feeding methods. FI was primarily associated with birth weight </=1000 g (71%) vs 1001 to 1250 g (38%). CONCLUSION: Feeding methods are associated with similar outcomes when feeding regimens are comparable.

Birth Weight↗

Clinical and pathological characterization of northern elephant seal skin disease.

From 1984 through 1992, staff at The Marine Mammal Center (TMMC, Sausalito, California, USA) examined 207 northern elephant seals (Mirounga angustirostris) with a condition of unknown etiology called northern elephant seal skin disease (NESSD). The skin lesions were characterized by patchy to extensive alopecia and hyperpigmentation, punctate or coalescing epidermal ulceration, and occasionally, massive skin necrosis. Microscopic lesions included ulcerative dermatitis with hyperkeratosis, squamous metaplasia and atrophy of sebaceous glands. All diseased seals were less than 2 years of age and suffered from emaciation, depression, and dehydration. Mortality from septicemia increased significantly with severity of skin ulceration. Compared to 14 apparently unaffected seals, diseased seals had depressed levels of circulating thyroxine, triiodothyronine, retinol, serum iron, albumin, calcium, and cholesterol. Levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, blood urea nitrogen, and uric acid were elevated. Morphometrically, diseased animals were approximately 15% smaller than normal seals of the same sage. Serum and blubber concentrations of 36 polychlorinated biphenyl congeners (sigma PCB) and dichloro-diphenyl-dichloroethylene (p,p'-DDE) were negatively correlated with body mass. Mean concentrations of sigma PCB and p,p'-DDE in serum in diseased seals were elevated as compared to apparently normal seals. Etiology of this syndrome remains unknown, but the possibility of PCB toxicosis cannot be ruled out.

Alopecia↗

The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes.

Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a group of rare genetic disorders of HDL metabolism that have been the subject of a large number of clinical, biochemical, and genetic studies. Of special interest are patients with LCAT-related disorders with severe HDL deficiency and the apparent absence of premature atherosclerosis. This finding is inconsistent with the general concept that low HDL cholesterol levels are an obligate risk factor for atherosclerosis. In this review, we describe 36 natural mutations in the LCAT gene that result in either familial LCAT deficiency (FLD) or the milder phenotype known as fish-eye disease (FED). We propose a new classification of the natural mutations of the LCAT gene that are described to date. The defects are divided into four classes based on both the clinical and biochemical characterization of the patient and data that were obtained from the functional assessment of the mutant proteins. We define FLD-associated mutations that underlie a complete or nearly complete loss of LCAT activity due to null mutations (Class 1), and missense mutations (Class 2), respectively. In addition, we distinguish two classes of FED-associated mutations (Classes 3, 4) that underlie a partial impairment of LCAT activity but differ in their lipoprotein substrate specificity. In addition, we review the evidence of atherosclerosis in subjects with LCAT deficiency syndromes. The observation that 6 (all males) of a total of 19 FED subjects suffered from premature CAD (as defined by < 55 years of age and < 60 years of age for women and men, respectively) challenges the earlier assumption that the FED phenotype is not associated with increased risk of CAD. However, premature CAD remains an unusual clinical complication in FLD subjects.

Adolescent↗

Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects.

BACKGROUND: Magnesium is a cation with smooth muscle relaxant and anti-inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. OBJECTIVE: To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate [AMP]) in asthmatic subjects. METHODS: Two separate randomized, double-blind, placebo-controlled crossover studies, each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. RESULTS: In the histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22-1.82) doubling doses at 5 min (P = 0.018), and 1.0 (0.3-1.7) doubling doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also significantly lower at 5 min after magnesium than after saline, by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this difference was not statistically significant after adjustment for differences in baseline FEV1 on the two study days. CONCLUSIONS: Inhaled magnesium did not protect against the effects of these direct and indirect bronchoconstrictor stimuli in subjects with asthma, and may have increased airway reactivity to histamine.

Adenosine Monophosphate↗

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.

BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Coronary Disease↗

Vascular applications of telepresence surgery: initial feasibility studies in swine.

PURPOSE: Telepresence surgery is a novel technology that will allow procedures to be performed on a patient at locations that are physically remote from the operating surgeon. This new method provides the sensory illusion that the surgeon's hands are in direct contact with the patient. We studied the feasibility of the use of telepresence surgery to perform basic operations in vascular surgery, including tissue dissection, vessel manipulation, and suturing. METHODS: A prototype telepresence surgery system with bimanual force-reflective manipulators, interchangeable surgical instruments, and stereoscopic video input was used. Arteriotomies created ex vivo in segments of bovine aortae or in vivo in femoral arteries of anesthetized swine were closed with telepresence surgery or by conventional techniques. Time required, technical quality (patency, integrity of suture line), and subjective difficulty were compared for the two methods. RESULTS: All attempted procedures were successfully completed with telepresence surgery. Arteriotomy closures were completed in 192+/-24 sec with conventional techniques and 483+/-118 sec with telepresence surgery, but the precision attained with telepresence surgery was equal to that of conventional techniques. Telepresence surgery was described as intuitive and natural by the surgeons who used the system. CONCLUSIONS: Blood-vessel manipulation and suturing with telepresence surgery are feasible. Further instrument development (to increase degrees of freedom) is required to achieve operating times comparable to conventional open surgery, but the system has great potential to extend the expertise of vascular surgeons to locations where specialty care is currently unavailable.

Animals↗

The feasibility of recording transiently evoked otoacoustic emissions immediately following grommet insertion.

The demonstration of normal hearing following grommet insertion in young or difficult to test children can be problematic. This study aims to determine whether transiently evoked otoacoustic emissions (TEOAEs), can be recorded in the operating theatre, immediately after grommet insertion, and whether this technique has any advantages over conventional testing to exclude sensorineural loss. One ear of each of 80 children was studied, using the Otodynamics ILO88 OAE analyser. Responses were normal in eight, reduced in 31 and absent in 39. Bleeding prevented the performance of the test in two children. We conclude that TEOAEs can be recorded in 50% of ears immediately after grommet insertion, but the responses are reduced compared with normal ears. This application of TEOAEs may be a useful supplement to behavioural tests, but we do not advocate it as a screening technique.

Acoustic Stimulation↗