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Biomedical subjects

J Hardy

Publications and source records attributed to J Hardy.

At least 307 records · Page 17Linked to original sources
PubMed1992

Constrictive pericarditis in a mare: attempted treatment by partial pericardiectomy.

Chronic constrictive pericarditis was diagnosed in a 6-year-old Thoroughbred mare based on the clinical findings of right congestive heart failure, hyperechoic pericardium without pericardial effusion, and a dip-and-plateau shape of the right ventricular pressure curve with equilibration of the diastolic pressures in all cardiac chambers. Treatment was attempted by partial pericardiectomy using a right lateral thoracotomy approach. Because of severe epicardial involvement recurrence of the constrictive pathology was noted 6 weeks after the surgical procedure. However, in selected cases in which the disease process is limited to the pericardium, partial pericardiectomy may offer a mode of therapy in horses suffering from constrictive pericarditis.

Animals↗
PubMed1992

Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model.

Little is known about delivery of aerosolised steroids to neonatal patients undergoing assisted positive pressure ventilation and after extubation. A rabbit model has been established to investigate factors influencing drug delivery. Beclomethasone dipropionate, in a metered dose inhaler, was radiolabelled with technetium 99m. The mass median aerodynamic diameter of the aerosol was 3.3 (2.0) microns and the impactor measurements confirmed that the technetium distribution corresponded with that of the drug particles. The metered dose inhaler was actuated into a collapsible spacer that was used to ventilate and deliver aerosol to anaesthetised rabbits by a tracheostomy. From each actuation of the drug 2.9 (0.4)% of the aerosol deposited in the trachea and main bronchi and 1.2 (0.4)% in the lung. When the drug was delivered by a spacer device, with face-mask attachment, to rabbits breathing freely through a tracheostomy, aerosol deposition increased to 4.4 (2.1)% in the trachea and main bronchi and 1.9 (0.9)% in the lung lobes. The maximum change in systolic blood pressure after administration of aerosol by the collapsible spacer was a decrease of 13%. The methods described may prove useful for the delivery of inhaled steroids to neonatal patients likely to develop bronchopulmonary dysplasia.

Administration, Inhalation↗
PubMed1992

[Results of tuberculosis treatment in a health district in Zaire].

The results of the treatment of tuberculosis have been evaluated among 407 patients distributed into 268 cases of pulmonary tuberculosis with positive smears (TP+), 70 pulmonary forms with negative smears (TP-) and 69 cases of extrapulmonary tuberculosis (TEP). A group 1 of 361 patients including new cases and late relapses and consisting of 236 TP+, 59 TP- and 66 TEP has been put through the treatment pattern: 2S6H7T7 + 10H7T7 or 2S6H7 + 10S2H2. Group 2, of 21 patients consisting of failures, early relapses and previously but irregularly treated cases, was given a pattern: 2R7E7H7Z7 + 10R2H2. In group 3, 25 new cases were given a short treatment: 2R7E7H7Z7 + 4R7H7. In group 1 we have recorded 68.42% cured patients, 8.59% failures and 14.40% neglects of treatment. The remaining 8.59% include deceased, transfers and patients put through extended treatment. The rate of cure was better among TEP patients (95.46%) than among TP- patients (79.66%) and TP+ patients (58.05%); failures were proved to be more frequent among TP+ patients (11.88%) than among TP- patients (3.39%) and TEP patients (1.51%). In group 2 and 3 successes have amounted to 95.24% and 84% respectively. Considering rates of cure, irregular treatments, neglects and failures with standard patterns (group 1), it appears to be desirable that rifampicin-including short patterns are added to antitubercular therapeutic strategies of developing countries.

Adult↗
PubMed1992

Adverse influence of fibrin sealant on the healing of high-risk sutured colonic anastomoses.

The effect of fibrin glue sealing on sutured colonic anastomoses was studied using a 'high-risk' colon anastomosis model in the rat. Animals (n = 104) were randomized to have their sutured anastomosis sealed with fibrin glue or left untreated. They were assessed clinically until they were killed on the fourth day after surgery when contrast radiology, detailed post-mortem examination, anastomotic bursting pressure (ABP) and assessment of adhesion formation were performed. The clinical outcome was worse in the glued group (toxic or death from sepsis: 18 versus seven in the non-glued group; P = 0.0354), which also showed a significantly higher moderate to major leak rate (17 versus two in the non-glued group; P = 0.0009). The median ABP was significantly higher in the glued anastomosis group (96 versus 68 cmH2O in the non-glued group; P = 0.0367). Excessive perianastomotic adhesion formation was significantly greater in the glued group. Microscopic examination showed an extremely intense inflammatory reaction in the glued anastomoses compared with that in the untreated group. These results indicate that sealing of a sutured anastomosis with fibrin glue containing an antiproteinase impairs healing the of anastomotic wound, probably by resisting the ingrowth of vascular granulation tissue during the early stages of repair.

Anastomosis, Surgical↗
PubMed1991

Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with early onset Alzheimer's disease fails to reveal mutations in the beta-amyloid sequence.

A mutation within exon 17 at codon 717 of the beta-amyloid protein precursor (APP) gene is one cause of early onset familial Alzheimer's disease. Direct sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene in 14 families with familial early onset Alzheimer's disease without the known pathogenic mutation (APP717) failed to reveal other mutations within the beta-amyloid sequence in this form of the disorder.

Adult↗
PubMed1991

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene.

A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Alzheimer Disease↗
PubMed1991

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas.

From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Adenoma↗
PubMed1991

Screening for the beta-amyloid precursor protein mutation (APP717: Val----Ile) in extended pedigrees with early onset Alzheimer's disease.

Screening for the APP717 mutation in 5 further families with early onset Alzheimer's disease failed to reveal further cases with this variant. Screening a further 100 normal individuals for this mutation also failed to reveal further occurrences of this variant in the general population. Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene (the exons which encode the beta-amyloid fragment) in pedigree FAD4 revealed them to be of normal sequence. The significance of these observations to the genetics of Alzheimer's disease is discussed.

Alzheimer Disease↗
PubMed1991

Clinical relevance of radiographic findings in proximal sesamoid bones of two-year-old standardbreds in their first year of race training.

Radiographs of all 4 fetlocks of 71 Standardbred racehorses were obtained at 3-month intervals for 1 year. Radiographic findings in the abaxial surface of the proximal sesamoid bones were classified into 3 types according to the severity of lesions, and correlation was made with clinical findings at time of examination. Type-1 lesions (1 or 2 linear defects less than or equal to 1 mm wide) were detected in 55% of horses at the start of training; clinical signs of disease were not manifested, and lesions did not become clinically relevant. Type-2 lesions (3 or more linear defects less than or equal to 1 mm wide) were detected in horses not manifesting clinical signs of disease, and were more frequently observed after 3 months of training. However, 66% of horses affected with diseases of the suspensory apparatus, including superficial flexor tendinitis and suspensory desmitis, also manifested this type of lesion. When lameness was observed, it was associated with the soft tissue problem, and the sesamoid bone changes were considered secondary. Type-3 lesions (wide, abnormally shaped linear defects) were detected in 7 horses at the start of the study; lesions remained in horses throughout the study and were consistently associated with lameness during training. Type-3 lesions were considered clinically relevant and indicative of primary sesamoiditis.

Animals↗
PubMed1991

Effect of fibrin glues on the mechanical properties of healing wounds.

Tissue glues are important in clinical practice. Fibrin based glues have many advantages over non-biological adhesives. The optimum formulation of these glues measured by their effect on mechanical properties of healing wounds has not been determined. Using a model involving standard dorsal skin incisions in adult male Wistar rats various glue formulations were compared by varying the fibrinogen, thrombin and factor XIII concentrations. Calcium (40 mumol/ml) and aprotinin (3000 kallidinogenase inactivator units, KIu/ml) concentrations were kept constant. Animals were killed at 8 days and wounds excised. Standard strips of these wounds were mechanically tested using an Instron tensiometer and the stress, strain, elasticity and work required to rupture wounds were calculated. Results indicate that a fibrin glue with a fibrinogen concentration of approximately 39 g/l and a thrombin concentration of 200-600 units/ml with no added factor XIII will result in wounds with significantly increased stress, energy absorption and elasticity values.

Animals↗
PubMed1991

Insertions in the prion protein gene in atypical dementias.

A number of mutations have been demonstrated in the open reading frame (ORF) of the prion protein (PrP) gene in patients with familial Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome. On the basis of detecting an insertion in the ORF of the PrP gene in a patient originally suspected to be suffering from familial Alzheimer-type dementia, we screened 101 individuals with atypical dementias for the known PrP gene mutations. Insertions were found in five individuals, whereas none of the other reported mutations in the PrP gene was detected in the present study. One of the five insertions was larger than that described previously, suggesting that the individuals with these mutations are unlikely to be all lineally related and that insertions in the PrP gene may not be uncommon in prion diseases.

Alzheimer Disease↗
PubMed1991

Amyloid deposition as the central event in the aetiology of Alzheimer's disease.

While there may be many causes of Alzheimer's disease (AD), the same pathological sequence of events, described here by John Hardy and David Allsop, is likely to occur in all cases. The recent discovery of a pathogenic mutation in the beta-amyloid precursor protein (APP) gene on chromosome 21 suggests that APP Mismetabolism and beta-amyloid deposition are the primary events in the disease process. The occurrence of AD in Down syndrome is consistent with this hypothesis. The pathological cascade for the disease process is most likely to be: beta-amyloid deposition----tau phosphorylation and tangle formation----neuronal death. The development of a biochemical understanding of this pathological cascade will facilitate rational design of drugs to intervene in this process.

Alzheimer Disease↗