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Biomedical subjects

J Hardman

Publications and source records attributed to J Hardman.

At least 19 recordsLinked to original sources
PubMed2006

Fate of embryonic stem cells transplanted into the deafened mammalian cochlea.

Spiral ganglion neurons (SGNs), the primary afferent neurons of the cochlea, degenerate following a sensorineural hearing loss (SNHL) due to lack of trophic support normally received from hair cells. Cell transplantation is emerging as a potential strategy for inner ear rehabilitation, as injected cells may be able to replace damaged SGNs in the deafened cochlea. An increase in the number of surviving SGNs may result in improved efficacy of cochlear implants (CIs). We examined the survival of partially differentiated mouse embryonic stem cells (MESCs), following xenograft transplantation into the deafened guinea pig cochlea (n=15). Cells were delivered directly into the left scala tympani via microinjection through the round window. Small numbers of MESCs were detected in the scala tympani for up to 4 weeks following transplantation and a proportion of these cells retained expression of neurofilament protein 68 kDa in vivo. While this delivery method requires refinement for effective long-term replacement of damaged SGNs, small numbers of MESCs were capable of survival in the deafened mammalian cochlea for up to 4 weeks, without causing an inflammatory tissue response.

Animals↗
PubMed2005

Intravenous antioxidant modulation of end-organ damage in L-arginine-induced experimental acute pancreatitis.

BACKGROUND: Oxidative stress mediates acinar injury in experimental acute pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the hypothesis that exogenous antioxidant supplementation ameliorates experimental AP. METHODS: Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations were: group 1 (control) no intervention; group 2 AP; group 3 early multiple antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX combination above given at 24 and 48 h. Endpoints were: serum amylase, antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase (MPO) activity and histological assessment of pancreatic injury. RESULTS: L-arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal infiltration by inflammatory cells. These features were absent when intervention was delayed. CONCLUSION: In this model, early but not late antioxidant intervention ameliorates pancreatic and pulmonary injury.

Acetylcysteine↗
PubMed2004

Memory complaints in nondemented men predict future pathologic diagnosis of Alzheimer disease.

The validity of memory complaints as a predictor of Alzheimer disease (AD) was assessed in 237 Japanese-American men autopsied at ages 74 to 97 years. These men were free of dementia at the time memory complaints were assessed 1 to 11 years earlier. Memory complaints were found to predict the neuropathologic diagnosis of AD after adjusting for age, time to death, education, depression, and cognitive functioning.

Aged↗
PubMed2003

Quantification of regional glial fibrillary acidic protein levels in Alzheimer's disease.

OBJECTIVES: Our objectives were to quantify glial fibrillary acidic protein (GFAP) in brains of Alzheimer's disease (AD) cases, and non-AD controls to determine the regions with the most severe gliosis in AD. MATERIAL AND METHODS: In a case control design, we used an enzyme-linked immunosorbent assay (ELISA) to quantify GFAP in frozen brain from four areas of neocortex in 10 AD cases, 10 age-matched controls, and 10 younger controls from the Honolulu-Asia Aging Study autopsy archive. RESULTS: Median age at death was 83.5 years for cases and age-matched controls, and 77 years for younger controls. For the AD cases compared with the age-matched controls, levels of GFAP in occipital (P=0.01), parietal (P=0.028), and temporal lobes (P=0.004) (but not frontal) were significantly higher in the cases. The median GFAP excess in AD cases compared with age matched controls was highest in the temporal lobe. CONCLUSIONS: Regional quantification of GFAP reveals that the glial response is most prominent in the temporal lobe in AD.

Aged↗
PubMed2002

The increasing role of percutaneous transluminal angioplasty in the primary management of critical limb ischaemia.

OBJECTIVE: to review the current role and results of angioplasty in the management of critical limb ischaemia (CLI) in a single institution. METHODS: data on 526 patients with 608 ischaemic limbs, treated between January 1994 and December 1999 was collected prospectively and analysed retrospectively. Patients were divided into 3 groups according to the date of presentation: group 1 (1994-95), group 2 (1996-97) and group 3 (1998-99). The groups were comparable in terms of demographics, mode of presentation and level of disease. RESULTS: Revascularisation was attempted in 87%, 81% and 91% for groups 1, 2 and 3 respectively (NS). Primary percutaneous transluminal angioplasty (PTA) rates increased from 44% (1994-95) to 69% (1998-99) (p < 0.001), and surgical revascularisation rates decreased correspondingly (p<0.01). Overall cumulative patient survival and limb salvage rates were 82% and 89% for 1 year and 45% and 87% for 5 years, respectively. No statistically significant difference existed between the three groups regarding patient survival, limb salvage rates and mean hospital stay (19, 12 and 12 days, respectively). CONCLUSION: PTA is increasingly replacing bypass surgery in the treatment of CLI, without compromising patient survival or limb salvage rates.

Aged↗
PubMed2002

Prolonged paralysis following mivacurium administration.

Mivacurium is a benzylisoquinolone, choline-like, non-depolarizing muscle relaxant. Its onset of action is similar to that of atracurium but its duration of action is shorter (approximately 10-15 minutes). Mivacurium is metabolized by plasma cholinesterases at approximately 70% of the rate of metabolism of suxamethonium. Deficiency or abnormality of plasma cholinesterase may cause the duration of action of both suxamethonium and mivacurium to be greatly prolonged. We describe a case of prolonged mivacurium paralysis after day surgery. Laboratory investigations showed a genetic tendency toward abnormal cholinesterase levels, but markedly depressed cholinesterase activity was suggestive of additional acquired causes. This patient had a history of liver disease, malnutrition and anticholinesterase use, which we believe were the most significant factors involved.

Aged↗
PubMed2001

Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study.

OBJECTIVE: To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited. METHODS: There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP). RESULTS: Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities for other groups were <3.0/mm2. Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD. CONCLUSIONS: Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

Aged↗
PubMed2000

Brain aging and midlife tofu consumption.

OBJECTIVE: To examine associations of midlife tofu consumption with brain function and structural changes in late life. METHODS: The design utilized surviving participants of a longitudinal study established in 1965 for research on heart disease, stroke, and cancer. Information on consumption of selected foods was available from standardized interviews conducted 1965-1967 and 1971-1974. A 4-level composite intake index defined "low-low" consumption as fewer than two servings of tofu per week in 1965 and no tofu in the prior week in 1971. Men who reported two or more servings per week at both interviews were defined as "high-high" consumers. Intermediate or less consistent "low" and "high" consumption levels were also defined. Cognitive functioning was tested at the 1991-1993 examination, when participants were aged 71 to 93 years (n = 3734). Brain atrophy was assessed using neuroimage (n = 574) and autopsy (n = 290) information. Cognitive function data were also analyzed for wives of a sample of study participants (n = 502) who had been living with the participants at the time of their dietary interviews. RESULTS: Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption. A similar association of midlife tofu intake with poor late life cognitive test scores was also observed among wives of cohort members, using the husband's answers to food frequency questions as proxy for the wife's consumption. Statistically significant associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios comparing endpoints among "high-high" with "low-low" consumers were mostly in the range of 1.6 to 2.0. CONCLUSIONS: In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life.

Aged↗
PubMed1998

Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal.

This study compares the clinical response to lofexidine and clonidine in the out-patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised double-blind study design. Patients were taking 40 mg or less methadone daily, or equivalent amounts of other opiates. Fifty-eight percent of those starting treatment completed detoxification, and were opiate free at 4 weeks: more patients completed withdrawal in the lofexidine group, but the difference was not significant. Clonidine produced more hypotensive effects: more home visits were also required by medical staff. There was no other significant difference in side effects. Both drugs can be used successfully in out-patient detoxification, but lofexidine is more economical in regard to staff time.

Adrenergic alpha-Agonists↗
PubMed1997

MRI of the anterior optic pathways following enucleation.

We examined five patients who had enucleation of one eye for inflammatory or neoplastic disease, using MRI at 1.5 Tesla. None had symptoms referable to the enucleated orbit. In addition, age- and-sex matched individuals were imaged as control subjects, and a further 15 subjects, referred for other than orbital disease, were reviewed. Measurements were made retrospectively of the dimensions of the optic chiasm to establish normal values. All five patients showed abnormalities on MRI following enucleation: abnormal signal within the optic nerve remnant on short tau inversion recovery (STIR) images, and atrophy of the nerve remnant and the chiasm. These findings were not apparent in the control or normal subjects. Such findings are to be expected following enucleation and should not be interpreted as indicating active pathology.

Aged↗
PubMed1989

Identification of a subset of group B donors reactive with monoclonal anti-A reagent.

Two red blood cell (RBC) units labeled group B were returned to the source blood center after they had been retyped as AB by a transfusion service. The discrepancy could be reproduced, but only with the use of the transfusion service's reagent, Ortho Diagnostic's anti-A Bioclone (a licensed, blended, murine monoclonal anti-A reagent). RBCs from 35 of 3,458 random group B donors (1%) reacted with the monoclonal anti-A after immediate centrifugation. Reactivity was associated with high serum levels of B-gene-specified transferase and was caused by the MH04 component, a potent anti-A capable of detecting some examples of Ax RBCs. It is probable that the potency of MH04 permitted detection of low levels of A determinants synthesized by the donors' unusually strong B-gene-specified transferase. Transfer of N-acetylgalactosamine by B-gene-specified transferases, reported in vitro, has not been detected previously in vivo. Use of highly sensitive monoclonal reagents may result in clinically ambiguous blood grouping results.

ABO Blood-Group System↗
PubMed1987

The eosinophilic variant of acute myelomonocytic leukemia developing as a secondary leukemia in a patient with mycosis fungoides.

The eosinophilic variant of acute myelomonocytic leukemia (AMML) is highly associated with characteristic abnormalities of chromosome 16. Leukemias developing secondary to chemotherapy frequently show abnormalities of chromosomes 5 and 7. This report describes a secondary AMML, eosinophilic variant (M4Eo), developing in a patient with coexistent mycosis fungoides who had received chemotherapy, including an alkylating agent, and showing characteristic abnormalities of both chromosomes 7 and 16. This is the first reported case of the M4Eo arising secondarily in a patient treated for another hematopoietic malignancy, and the second case of treatment-induced M4Eo to show coexistent abnormalities of chromosomes 7 and 16. Additional cytochemical, ultrastructural, and cell surface marker findings are described supporting malignant transformation of the eosinophilic cell line.

Adult↗
PubMed1984

Human renin gene sequence, gene regulation and prorenin processing.

Human DNA coding for renin was identified and sequenced. The gene consisted of 10 exons corresponding to a 1500 nucleotide mRNA was broken up by long stretches of 'nonsense' DNA (introns) and spanned 12,000 base pairs. In addition, the sequence of nucleotides involved in regulation of the gene was determined by sequencing upstream. Prediction of the amino acid sequence of human preprorenin revealed likely sites of processing. This helps explain many past experimental observations. For example, the pro region contained adjacent likely cleavage sites for trypsin and pepsin and so reveals why both trypsin and pepsin can activate prorenin. The structure of human renin had features involved in its highly specific hydrolysis of the Leu10-Val11 bond unique to human angiotensinogen: in particular leucine 224 (instead of valine). Renin gene expression was studied in the mouse by quantification of both renin activity and its mRNA. Sodium depletion, captopril and spironolactone increased expression of Ren-1 in the kidney. The unusual, duplicated, mouse gene, Ren-2, which is expressed in the submandibular gland was, regulated by (dihydro)testosterone in male mice and by thyroid hormone in female mice.

Animals↗
PubMed1982

Studies of the haemodynamic effects of creatine phosphate in man.

1 The haemodynamic effects of intravenous creatine phosphate 1000 mg have been studied. 2 During the first 60 min following drug administration heart rate and blood pressure did not change but cardiac output fell significantly by approximately 18%. Calculated total peripheral resistance showed a corresponding significant rise, the maximum increase being approximately 24%. All these changes were beginning to diminish within 90 min after the injection. 3 Total limb blood flow measured in both arm and leg (using venous occlusion strain-gauge plethysmography) showed no appreciable changes following injection of creatine phosphate. 4 There was a progressive reduction in leg muscle blood flow (Xe133 clearance method) following injection which was statistically significant with respect to the initial level and reached a minimum (46% reduction) 50 min after the injection. 5 Skin blood flow, estimated by infra-red photoplethysmography, showed changes complementary to those seen with muscle flow. There was a progressive and significant rise to a peak (73% increase) 30 min after the injection. 6 No adverse reactions to the injections were noted. 7 Reduced cardiac output in the absence of altered total limb blood flow presumably reflects a reduction in visceral blood flow, which was not measured in this study. Within the limbs, creatine phosphate appears to result in a redistribution of blood flow from muscle to skin. Thus, these preliminary results suggest that intravenous creatine phosphate could be clinically useful in situations where short term improvement in skin blood flow would be advantageous and that further controlled studies would be justified.

Adult↗
PubMed1978

The noninvasive assessment of aortoiliac disease: a comparison of dynamic isotope angiology with thigh brachial pressure index.

In 41 patients with severe claudication, the time taken for an intravenously injected isotope bolus of TC99m pertechnetate to pass from the aortic bifurcation to the common femoral arteries was measured using a gamma camera and computer. This isotope transit time (ITT) then was correlated with the severity of aortoiliac disease determined arteriographically. Highly significant differences in ITT were found between normal vessels and those with minor stenosis of less than 50%, major stenosis of 50% or more, or complete occlusion. With major disease there was a longer ITT than with minor disease (P less than 0.01). ITT gave a greater degree of differentiation between disease groups than did thigh/brachial pressure index, as measured by Doppler ultrasound in the same patients, and was not influenced by superficial femoral artery occlusion.

Aorta↗