Search PubMed⌕ Search

Biomedical subjects

J Hardy

Publications and source records attributed to J Hardy.

At least 325 records · Page 18Linked to original sources

Cushing's disease: a correlation of radiological, surgical and pathological findings with therapeutic results.

From 1963 to 1990 78 successive patients with pituitary-dependent cortisol hypersecretion were submitted to transsphenoidal surgery. In 57 patients, a selective adenomectomy was performed. Sixteen other patients had a central hypophysectomy. Total hypophysectomy was done nine times: in five new patients and in four patients previously operated by us. Fifty-six tumors were studied in pathology. Fifty tumors were microadenomas with ten of these measuring less than 1 mm. The tumors consisted of basophilic cells giving a positive immunostaining for ACTH. Electron microscopy on 35 tumors was characteristic with perinuclear bundles of microfilaments and often large lipid vacuoles. We did not find ACTH cell hyperplasia in the pituitary gland around tumors or in specimens of central or total hypophysectomy. Adequate follow-up was obtained on 49 patients who had been cured with an average length of 6.4 years after surgery. Our longest sustained remission following selective adenomectomy is eighteen years. Surgical cure rate was 82% for microadenomas and 81% for all intrasellar tumors. 89% of patients went into remission after total hypophysectomy but only 56% when central hypophysectomy was performed. Recurrence rate was 7.6%, occurring between three and seven years after surgery.

Adenoma↗

Upper respiratory obstruction in foals, weanlings, and yearlings.

Upper airway obstruction may result from nasal, pharyngeal, or tracheal diseases. In the young horse, a relatively severe obstruction usually is present before clinical signs are evident. This article reviews the clinical manifestations, diagnostic features, treatment, and outcome of commonly encountered conditions of the nasal passages, pharynx, larynx, and trachea in young horses.

Airway Obstruction↗

Genetic characterization of a novel familial dementia.

Clinical and neuropathologic findings from a Danish family in which a dementing illness is segregating as an apparent autosomal dominant disorder were previously described (Gydesen et al. 1987). We present here genetic findings from this family in which linkage analysis has excluded Huntington's disease and chromosome 21-encoded Alzheimer's disease. None of the known prion mutations has been detected in affected individuals from this family. However, linkage analysis with the prion gene has been uninformative. This family probably represents a novel genetic dementia.

DNA Probes↗

DNA sequences of three papA genes from uropathogenic Escherichia coli strains: evidence of structural and serological conservation.

Pyelonephritis-associated pili (Pap) are important in the pathogenesis of ascending, unobstructive Escherichia coli-caused renal infections because these surface bacterial organelles mediate digalactoside-specific binding to host uroepithelial cells. Pap are composed of many different polypeptides, of which only the tip proteins mediate specific binding. The PapA moiety polymerizes to form the bulk of the pilus structure and has been employed in vaccines despite its lack of Gal alpha(1-4)Gal receptor specificity. Animal recipients of PapA pilus-based vaccines are protected against experimental pyelonephritis caused by homologous and heterologous Gal-Gal-binding uropathogenic E. coli strains. Specific PapA immunoglobulin G antibodies in urine are correlated with protection in these infection models. The nucleotide sequences of the gene encoding PapA were determined for three E. coli clones expressing F7(1), F7(2), and F9 pili and were compared with corresponding sequences for other F serotypes. Specific rabbit antisera were employed in enzyme-linked immunosorbent assays to study the cross-reactivity between Gal-Gal pili purified from recombinant strains expressing F7(1), F7(2), F9, or F13 pili and among 60 Gal-Gal-binding wild-type strains. We present data which corroborate the concept that papA genes are highly homologous and encode proteins which exhibit greater than 70% homology among pili of different serotypes. The differences primarily occur in the cysteine-cysteine loop and variable regions and constitute the basis for serological diversity of these pili. Although there are differences in primary structures among these pili, antisera raised against pili of one serotype cross-reacted frequently with many other Gal-Gal pili of different serotypes. Furthermore, antisera raised against pili of the F13 serotype cross-reacted strongly or moderately with 52 (86%) of 60 wild-type Gal-Gal-binding E. coli strains. These data suggest that there are common immunogenic domains among these proteins. These additional data further support the hypothesis that broadly cross-protective PapA pilus vaccines for the immunoprophylaxis of pyelonephritis might be developed.

Amino Acid Sequence↗

The pharmacokinetics of oral lonidamine in breast and lung cancer patients.

The plasma levels of lonidamine have been studied in 24 breast or lung cancer patients as part of the Phase II evaluation of the drug. The pharmacokinetic studies were performed when the patients had been on oral lonidamine therapy for 27 to 47 days (mean 32 days) and the studies were conducted over a 24 hour period. Lonidamine was administered in three divided doses of 150 mg (t = 0h), 150 mg (t = 7h), and 150 mg or 300 mg (t = 14h). Plasma levels of lonidamine were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Lonidamine was detected in the plasma of all patients studied, and the absolute range for the peak plasma levels of the drug following the first and second doses were 4.6-33.8 and 4.8-33.3 micrograms/ml, respectively. The range of times after administration at which the peak occurred was 0.5 to 4.2 hours for the first dose and 0.5 to 4.1 hours for the second. The absolute range for the trough levels observed over the 24-hour study period was 1.0 to 12.6 micrograms/ml and in 19 of the patients it was possible to define the apparent half life of lonidamine that was found to be within the range 2.5 to 11.7 hours. In addition to lonidamine, a number of fluorescent components were detected in the plasma of patients following lonidamine treatment that were not detected in pretreatment plasma samples. One component, a compound that eluted from the HPLC more rapidly than lonidamine, was found in some patients to be sensitive to hydrolysis with beta-glucuronidase. Comparison of the pharmacokinetic data with patient characteristics and clinical biochemistry results failed to establish any clear relationship. Similarly there was no relationship between lonidamine pharmacokinetics and either drug-induced myalgia or testicular pain. Insufficient responses were seen in the patient group studied to allow the relationship between lonidamine pharmacokinetics and response to be evaluated.

Absorption↗

Prion dementia without characteristic pathology.

Gerstmann-Sträussler syndrome (GSS) was diagnosed in a family with presenile dementia by prion protein gene analysis. Extensive histological examination of the brain of an affected individual from this family showed no characteristic features of GSS or Creutzfeldt-Jakob disease (CJD). Thus "spongiform encephalopathy" (GSS or CJD) cannot always be excluded on neuropathological grounds in an individual dying of a dementing condition, and the true prevalence of these diseases is likely to be underestimated. Screening by prion protein gene analysis will help to determine the full clinical and neuropathological phenotype in familial cases. This observation may be relevant to the assessment of possible transmission of bovine spongiform encephalopathy to man.

Alleles↗

Ischemic optic neuropathy and blindness after arterial occlusion for treatment of guttural pouch mycosis in two horses.

Ischemic optic neuropathy accompanied by blindness was induced in 2 horses after surgical occlusion of the external and internal carotid and greater palatine arteries, performed as part of the management of guttural pouch mycosis. The blindness was acute and unilateral and may have been caused by ischemic retinal damage. Vascular occlusion is a recommended procedure for treatment of guttural pouch mycosis. Retinal damage and blindness are a possible complication if all possible sources of hemorrhage are occluded.

Animals↗

Antigens similar to major histocompatibility complex B-G are expressed in the intestinal epithelium in the chicken.

A monoclonal antibody directed against the erythrocytic B-G antigens of the major histocompatibility complex (MHC) of the chicken, an antiserum raised against purified erythrocytic B-G protein, and a cDNA probe from the B-G subregion were used to look for evidence of the expression of B-G genes in tissues other than blood. Evidence has been found in northern hybridizations, in immunoblots, and in immunolabeled cryosections for the presence of B-G-like antigens in the duodenal and caecal epithelia. Additional B-G-like molecules may be expressed in the liver as well. The B-G-like molecules in these tissues appear larger and somewhat more heterogeneous than the B-G antigens expressed on erythrocytes. Further characterization of these newly recognized B-G-like molecules may help to define a function for the enigmatic B-G antigens of the MHC. al. 1977; Miller et al. 1982, 1984; Salomonsen et al. 1987; Kline et al. 1988), and in the multiplicity of B-G restriction fragment patterns found in genomic DNA from different haplotypes (Goto et al. 1988; Miller et al. 1988; Chaussé et al. 1989). The B-G antigens have contributed, together with the B-F (class I) and B-L (class II) antigens, to the definition of over 27 B system haplotypes in experimental flocks (Briles et al. 1982). Yet the function of the B-G antigens remains entirely unknown. No mammalian counterparts have been identified, although the possibility remains that there may be similar antigens among the blood group systems of mammals. In an effort to define a function of the B-G antigens, a recently cloned B-G sequence (Miller et al. 1988; Goto et al. 1988) and antibodies to the B-G polypeptides (Miller et al. 1982, 1984) were used to examine other tissues for evidence of B-G expression.

Animals↗

Surgical management of giant pituitary adenomas.

During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty-sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates.

Adenoma↗

The value of computed tomographic (CT) scan surveillance in the detection and management of brain metastases in patients with small cell lung cancer.

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI.

Brain Neoplasms↗

Ventricular cerebrospinal fluid monoamine transmitter and metabolite concentrations reflect human brain neurochemistry in autopsy cases.

Concentrations of dopamine (DA), its metabolites 3-methoxytyramine and homovanillic acid (HVA), noradrenaline (NA), its metabolites normetanephrine (NM) and 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT, serotonin), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 14 brain regions and in CSF from the third ventricle of 27 human autopsy cases. In addition, in six cases, lumbar CSF was obtained. Monoamine concentrations were determined by reversed-phase liquid chromatography with electrochemical detection. Ventricular/lumbar CSF ratios indicated persistence of rostrocaudal gradients for HVA and 5-HIAA post mortem. Ventricular CSF concentrations of DA and HVA correlated positively with striatal DA and HVA. CSF NA correlated positively with NA in hypothalamus, and CSF MHPG with levels of MHPG in hypothalamus, temporal cortex, and pons, whereas CSF NM concentration showed positive correlations with NM in striatum, pons, cingulate cortex, and olfactory tubercle. CSF 5-HT concentrations correlated positively with 5-HT in caudate nucleus, whereas the concentration of CSF 5-HIAA correlated to 5-HIAA levels in thalamus, hypothalamus, and the cortical areas. These data suggest a specific topographic origin for monoamine neurotransmitters and their metabolites in human ventricular CSF and support the contention that CSF measurements are useful indices of central monoaminergic activity in man.

Adult↗

Vertebro-PICA aneurysms: midline suboccipital approach and laminectomy of the atlas.

Vertebro-PICA aneurysms represent a particular technical challenge because of the extremely narrow operative field and the presence of numerous vital neural and vascular structures. The lack of exposure still remains the limiting factor in most cases. During the 9-year period from January 1980 to October 1989, 8 vertebro-PICA aneurysms have been treated microsurgically. Of these, 2 underwent a pure suboccipital approach while 6 underwent a midline suboccipital approach with deliberate removal of the arch of the atlas in the park bench position. Seven patients did well and regained full activities while one patient died from complications related to vasospasm with brainstem infarction. One patient developed symptomatic obstructive dilation of the fourth ventricle requiring ventriculo-cisternostomy. The authors recommend the midline suboccipital approach with deliberate C1-laminectomy in ventrolateral decubitus for vertebro-PICA aneurysms. The main advantages are: constant access to the proximal vertebral artery, less medullary retraction in ventrally located aneurysms, improved exposure of the laterobulbar cisterns and the lateromedullary and tonsillar segments of the PICA, thus facilitating dissection of the aneurysm.

Adult↗

Links between passive smoking and disease: a best-evidence synthesis. A report of the Working Group on Passive Smoking.

We reviewed the toxicologic, clinical, and epidemiologic evidence on the health effects of environmental tobacco smoke (ETS). For each type of exposure to environmental tobacco smoke we have sought articles in the English language reporting studies of effects on human health. Formal criteria that stressed study design, quality of execution and generalizability of results were used to select 116 scientifically admissible reports from over 2,900 articles. We concluded that: (a) there is strong evidence of an association between residential exposure to environmental tobacco smoke and both respiratory illness and reduction of lung function, and also between maternal smoking and reduced birth weight; (b) the weight of evidence is compatible with an association between active maternal smoking during pregnancy and increased infant mortality, and also between residential exposure to environmental tobacco smoke (primarily spousal smoking) and the risk of lung cancer; (c) there is evidence consistent with a relationship between exposure to environmental tobacco smoke in the workplace and respiratory symptoms, (d) the evidence is insufficient to implicate residential exposure to environmental tobacco smoke in relation to other forms of malignant disease or congenital malformations; (e) there is no evidence in the literature of an association between nonresidential exposure to environmental tobacco smoke and any form of cancer. Further studies are required to address the effects of exposure to environmental tobacco smoke, especially nonresidential exposure, in carcinogenesis and as a risk factor for atherosclerosis. Further work is also needed to improve measurement of exposure in such studies and to assess the importance of confounding factors.

Adolescent↗

[Traumatic C1-C2 luxation in children. Prognostic study and therapeutic indications apropos of 13 cases].

The authors reviewed the cases of 13 children with C1-C2 traumatic dislocations. A particular interest was given to the elements which seemed to have an influence on the conservative treatment. Two points are of determining importance: the type of dislocation and the delay since the trauma. Pure rotatory dislocations generally occurring after a slight trauma healed thanks to a strict and necessarily early immobilization. On the contrary anterior dislocations due to violent traumas and all C1-C2 dislocations which treatments were delayed required an arthrodesis.

Adolescent↗