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Biomedical subjects

P Hardy

Publications and source records attributed to P Hardy.

At least 109 records · Page 6Linked to original sources
PubMed1996

Nitric oxide in retinal and choroidal blood flow autoregulation in newborn pigs: interactions with prostaglandins.

The role of nitric oxide (NO) as well as its interaction with prostaglandins (PG) in setting the limits of autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) were studied in newborn pigs (1-5 d old). Blood flows were measured by the microsphere technique. Low and high ocular perfusion pressures (OPP) were induced by inflating balloon-tipped catheters placed at the aortic root and isthmus, respectively. Animals were treated with the NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg followed by 50 mu g/kg/min; n = 12) or NG-monomethyl-L-arginine (L-NMMA, same dose as L-NAME; n = 3), or with saline (n = 12). In separate animals (n = 42), guanosine 3',5'-cyclic monophosphate (cGMP), the second messenger for NO, and PG were measured at an average OPP of 90 mm Hg and 125 +/- 6 mm Hg; cGMP levels served as an index of NO release. The effect of the NO donor sodium nitroprusside on choroidal vessel diameter was determined using video imaging of isolated eyecup preparations. In control animals RBF was constant only within a range of 30 to 80 mm Hg OPP (r = 0.03, p > 0.9). There was no autoregulation of ChBF which increased as a function of OPP (tau = 0.58-0.72, p < 0.01). L-NAME and L-NMMA prevented a change in RBF and ChBF from 30 to 146 mm Hg [the highest OPP studied (r < 0.3, p > 0.15)] and caused an increase in retinal as well as choroidal vascular resistance as OPP was raised; these agents did not affect ocular blood flow at OPP < 30 mm Hg. Elevated OPP caused increases in cGMP, 6-keto-PGF1alpha, and PGE2 in the choroid (a vascular tissue), which were prevented by L-NAME and L-NMMA. Sodium nitroprusside caused a dilatation of choroidal vessels in isolated eyecup preparations, which was significantly attenuated by indomethacin. Data suggest a role for NO in the autoregulation of RBF and ChBF in the newborn such that a release of NO during a rise in OPP prevents adequate constriction necessary for maintaining RBF and ChBF constant; data also suggest that the vasodilator effect of NO might in part be mediated through a release of PG.

Animals↗
PubMed1996

Quantification of cardiac and tissue iron by nuclear magnetic resonance relaxometry in a novel murine thalassemia-cardiac iron overload model.

OBJECTIVE: To determine whether nuclear magnetic resonance (NMR) relaxation parameters can be used to quantify iron in tissues, the relationship between NMR spectrometric T2 relaxation measurements and tissue iron concentration were verified in a novel murine cardiac iron overload model. METHODS: Congenital heterozygous thalassemic mice and controls were injected with intraperitoneal iron or saline and were sacrificed at three weeks. Samples of liver, heart and peripheral muscle were subjected to NMR relaxation measurements and continuous distribution analysis. Tissue ferritin levels were determined with immunoadsorbance techniques, and elemental iron was assayed by flame atomic absorption. Tissues were analyzed pathologically with hematoxylin and eosin and Prussian blue staining to confirm the localization of iron. RESULTS: This murine iron loading model was uniquely successful in loading iron into the major organs, especially the heart, and produced significant reductions in T1 and T2 NMR relaxation values. There was a good correlation between soluble ferritin and total iron levels (r=0.92), indicating that there is a constant and significant fraction of total iron present in ferritin irrespective of absolute iron concentrations. Regression analysis between total iron content and T2 relaxivity showed a linear relationship (r=0.96), suggesting that the T2 relaxation parameter is related to tissue iron concentration. The regression relationship suggested that NMR can detect iron levels as low as 0.1 mg/g of tissue. CONCLUSIONS: Parenteral iron loading in mice produces unique iron overload in major organs, including the heart. Local iron deposition is detectable by NMR relaxometry at 0.1 mg/g or higher. There is a linear relationship between iron concentration and T2 relaxivity. Thus, NMR may be an important and useful clinical tool to quantify iron excess in various pathobiological states of human disease due to iron overload, including heart disease.

Animals↗
PubMed1996

[Arthroscopic management of recurrent anterior shoulder dislocation by combining a labrum suture with antero-inferior holmium:YAG laser capsular shrinkage].

Current arthroscopic treatments do not address satisfactorily the capsular redundancy frequently associated with the Bankart lesion in recurrent anterior dislocation. Although the Bankart lesion heals, many of the recurrences after arthroscopic procedures are due to capsular redundancy and the laxity of glenohumeral ligaments. We propose that laser-assisted capsular shrinkage (LACS) be combined with arthroscopic labrum reattachment. As shown by Market et al., significant capsular shrinkage can be achieved by the application of non-ablative Ho:YAG laser energy without detrimental effects to the relaxation properties of the tissue. For 1 year we have used LACS together with labrum suture in 18 shoulders in 18 patients (mean age 24.6 years). All patients suffered from chronic anterioinferior recurrent dislocation. The labrum suture was realized by an anterior reattachment (REVO screws, Linvatec, USA) or by transglenoid suture. Two or three sutures were passed through the torn labrum with 2/0 non-absorbable suture material. The LACS procedure was performed with a holmium:YAG laser (VersaPulse, Coherent, USA) at an energy of 10 W (1 J, 10 Hz) with a 30 degrees curved handpiece. All patients were immobilized in a sling for 4 weeks postoperatively. Physical therapy was begun at 1 month with passive and active exercise. To date, none of the patients have had a recurrence. Seven of 18 patients returned to their previous sports activity, and at the same level. None of the patients had an iatrogenic lesion due to the laser application or labrum suture. Compared to the other shoulder, the loss of external rotation with the arm 90 degrees abducted was 30 degrees at 4 weeks and 10 degrees at 4 months. We think that the LACS procedure is a good treatment for the capsular redundancy that is frequently associated with Bankart's lesion in recurrent anterior dislocation and is probably responsible for the high failure rate in current arthroscopic procedures. Our results are short-term results, but we expect the capsular shrinkage associated with the labrum reattachment will provide a long-term success rate that is comparable to open procedures.

Adult↗
PubMed1995

Prostaglandin G/H synthase-2 is a major contributor of brain prostaglandins in the newborn.

In order to understand the molecular basis of the elevated cerebral prostaglandin levels in the newborn, we compared the expression of the mRNAs and proteins of prostaglandin G/H synthases (PGHS), PGHS-1 and PGHS-2, in various regions of the brain and the microvasculature of newborn (1-2-day-old) and juvenile (4-7-week-old) pigs and also measured the relative contribution of PGHS-2 to cerebral prostaglandin synthesis both in vivo and in vitro by using a novel inhibitor of PGHS-2, NS-398. Ribonuclease protection assays using total RNA isolated from various regions of the porcine brain revealed that, unlike PGHS-1 mRNA, PGHS-2 mRNA was abundantly expressed in the cortex and the microvasculature of the newborn compared with those of the juvenile animal. PGHS-2 immunoreactive protein comprised the majority of total PGHS enzyme in neonatal cerebral microvasculature due to a 2-3-fold lower expression of immunoreactive PGHS-1 protein. Inhibition of PGHS-2 by NS-398 decreased the rate of prostaglandin synthesis by purified cerebral microvessels of the newborn by approximately 65% and of juvenile pigs by 30%. The decrease in brain tissue prostaglandin concentrations following intravenous administration of NS-398 was greater in newborn pigs (> or = 90%) than in the juvenile animals (< or = 30%). Furthermore, NS-398 substantially reduced the net in vivo cerebrovascular production of prostaglandins in newborn pigs. Taken together, these results indicate that PGHS-2 is the predominant form of prostaglandin G/H synthase in the newborn brain and cerebral microvasculature and the main contributor to the brain prostaglandin levels in the newborn animal.

Aging↗
PubMed1995

Mechanisms of the biphasic effects of peroxides on the retinal vasculature of newborn and adult pigs.

We tested whether the ontogenic differences in the constrictor effects of peroxides on the retinal vasculature were modulated by dilator cyclo-oxygenase products. Retinal arteriole (100-200 microns) vasomotor response to H2O2, t-butyl hydroperoxide, and cumene hydroperoxide were studied in isolated eyecup preparations using video camera monitoring of vessel diameter. A time- and dose-dependent biphasic retinal vasomotor response to all peroxides was observed on tissues of newborn and adult pigs. A rapid vasoconstriction (first 2 min) was followed by a relaxation which was greater in the adult than in the newborn tissues. The constrictor as well as the dilator response to peroxides and the observed increase in prostanoids were blocked by the cyclo-oxygenase inhibitor indomethacin. The peroxide-induced relaxation was inhibited or markedly attenuated by the prostaglandin I2 synthase blockers, trans-2-phenyl cyclopropylamine and minoxidil on tissues of newborn and adult animals. These agents also prevented the increase of the prostaglandin I2 receptor-coupled second messenger, cyclic 3',5'-adenosine monophosphate. Our data indicate that prostaglandin I2 plays a major role in counteracting the initial constrictor effects of peroxides in the retinal vasculature, and that the reversal of this constriction is greater in the adult than the newborn. These findings suggest that reduced reversal of vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate vasoconstriction by the dilator prostaglandin I2 during an oxidative stress in the newborn may facilitate neovascularization in retinopathy of prematurity.

Animals↗
PubMed1995

Time course of prefrontal lobe dysfunction in severely depressed in-patients: a longitudinal neuropsychological study.

The Stroop Colour-Word Test (SCWT) and the Verbal Fluency Test (VFT), two tests that have been suggested to be particularly sensitive to prefrontal dysfunction, were administered to 23 severely depressed in-patients. Both tests were impaired in patients at inclusion, but only verbal fluency normalized with successful treatment of depression. VFT impairment is consistent with the hypothesis of a left prefrontal cortex dysfunction in depression. Moreover, the persistence of an impaired performance on SCWT in patients at discharge suggests that a selective attention deficit may persist in patients beyond a clear clinical improvement.

Adolescent↗
PubMed1995

Peroxide-cyclooxygenase interactions in postasphyxial changes in retinal and choroidal hemodynamics.

To test the role of reactive oxygen species and cyclooxygenase products in the retinal hemodynamic changes induced by asphyxia, we measured retinal (RBF) and choroidal blood flows (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) in 1- to 3-day-old pigs treated with saline, the free radical scavengers U-74389F or high-dose allopurinol, the cyclooxygenase inhibitors ibuprofen or indomethacin, or the thromboxane synthase blocker CGS-13080 before and 5 and 60 min after a 5-min period of asphyxia. In saline-treated animals, RBF and ChBF increased 5 min after asphyxia and decreased at 60 min. The increases in RBF and ChBF at 5 min postasphyxia were slightly attenuated by cyclooxygenase blockers and free radical scavengers but not by thromboxane synthase inhibition, whereas all drugs prevented the decreases at 60 min. MDA, TxB2, PGE2, and 6-keto-PGF1 alpha increased 5 min after asphyxia; at 60 min, PGE2 and 6-keto-PGF1 alpha returned to nearly preasphyxial levels, but MDA and TxB2 continued to increase. Cyclooxygenase inhibition prevented the asphyxia-induced rise in MDA, and the free radical scavengers prevented that of prostanoids. In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors. The data suggest that during oxidative stresses reactive oxygen species are generated from the cyclooxygenase pathway and, in turn, also activate the synthesis of thromboxane; the latter mediates the oxidative stress-induced ocular vasoconstriction that might trigger the neovascularization of retinopathy of prematurity.

3,4-Methylenedioxyamphetamine↗
PubMed1995

[Consolidation treatment. The status in dysthymia].

It is now recognised that the treatment of depressive episodes comprises three distinct phases: the phase of acute treatment, which should lead to symptomatic remission; the phase of continuation, which aims to obtain cure by preventing relapses; and the phase of maintenance or prophylactic treatment, the object of which is to prevent recurrence, that is to say the occurrence of a new depressive episode independent of the earlier one. The application of such a therapeutic protocol to mood alterations raises a number of questions. In the first place, it should be emphasised that the fluctuating character and low intensity of the mood-changing symptoms, as well as the normally progressive action of antidepressants over time may make it very difficult to date the onset of remission. For this reason, the phases of acute treatment and of consolidation may not be discernible for a certain period of time. Furthermore, the chronicity of time-course being one of the principal characteristics of dysthymias, the only effective long-term therapeutic strategy may be to pursue continuation treatment instead of maintenance treatment, on the grounds that every new symptomatic manifestation should be regarded as a relapse rather than a recurrence. The duration of continuation treatment is poorly defined. If credence is lent to the rule which states that a depressive state should be treated for as long as the prior history has lasted, consolidation treatment of dysthymias should be continued for several years--two at least, more frequently more, and sometimes indefinitely.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗
PubMed1995

[Internal plantar flap. Apropos of 30 cases].

Thirty medial plantar flaps were used in twenty seven patients with large defects in soft tissues of the lower extremity. We performed that flap described in 1981 by Harrison for ankle defects (9 cases) and heel defects (21 cases). The etiology of the defect was a traumatic avulsion in 14 cases, a sole pressure in 10 cases and neurologic ulcer in 6 cases. The surgical procedure was performed in 5 operative sequences: 1--excision of the receptor site 2--disection of the posterior tibial artery and plantaris medialis artery 3--raising of the flap including plantar skin and aponeurosis, respecting the flexor hallucis brevis muscle 4--rotation of the flap and suture on the receiptor site 5--skin graft on the donor site Antibiotics were used according to the per-operative swabs. Full weight bearing was authorized on the 45th day. We observed no failure for heel localization. But in dorsal part of the ankle, we deplore 4 failures (on 9 cases). The rotation for ankle defects was rather important and the risk was squeezing the artery. We used 3 times the medial plantar flap as a cross foot. We observed 1 failure; the possibility of long pedicled flap (parallel legs), the innocuity for the donor site, the quality of the transferred skin are arguments for using that flap in a cross leg of rather small dimension. We successfully performed two more cross legs using this technique since that study. We think that the medial plantar flap is the best technique for heel reconstruction. The quality of the skin transferred is very able to make a secondary thickening reproducing exactly the consistence of the heel. The fiability of that flap is very high for the heel localisations (no failures on 21 cases).

Adolescent↗
PubMed1995

[Mental representation of drugs: construction of two questionnaires to study patients treated with psychotropic or oral hypoglycemic drugs].

We have built two questionnaires in order to study the representation of drugs. Questionnaires have been established according to the results of an open study involving 78 subjects, whether receiving a treatment or not. These questionnaires were applied on a sample of 126 (psychiatric or diabetic) patients. In the future, we expect the questionnaires to help studying relationships between drugs representation and compliance.

Adult↗
PubMed1994

[Pathological fractures of the femoral neck in hemodialyzed patients. Apropos of 26 cases].

PURPOSE OF THE STUDY: This study is based on a retrospective analysis of 26 pathological fractures of the femoral neck in 19 chronic haemodialysis patients. The purpose of this study is to analyze the epidemiological and etiological factors of these fractures in relation to osteo-arthropathy of the dialyzed patient, as well as the results of various treatments, both curative and preventive. MATERIAL AND METHODS: 26 pathological fractures of the femoral neck appeared in 19 chronic haemodialysis patients, 11 men and 8 women, 6 patients presented bilateral fractures. The patient's average age at the time of the fracture was 61 years (27 to 82). The average duration of dialysis was 11 years with a minimum of 2 years and a maximum of 21 years. Hyper parathyroidism was found in 14 patients, aluminic intoxication in 6 and amyloidosis at the level of the coxo-femoral joint 18 times. Surgical treatment consisted of 6 osteosynthesis, 2 cephalic arthroplasties, 13 modular arthroplasties and 5 total hip arthroplasties. For each case, we studied the presence of necrosis of the femoral neck due to aluminic intoxication, osteoporosis due to hyperparathyroidism and also the presence of amyloidosis without aluminic intoxication. RESULTS: Cortisonic necrosis and porosis was found 4 times out of 26 cases, hyperparathyroidism once, aluminic osteomalacy 3 times and beta-2-microglobulin amyloid 18 times. Amyloidosis remains the most frequent etiological factor. All patients had been operated for median nerve compression in the carpal tunnel, usually 2.5 years before appearance of the pathological fracture. Non surgical treatment was used 5 times in undisplaced fractures without any sign of amyloidosis and was successful 3 times and unsuccessful twice necessitating a new operation by osteosynthesis. Out of 6 osteosynthesis performed for fractures either with little or no displacement we observed 4 failures, all of them in the cases with intra-osseous amyloidosis. Best results were obtained by arthroplasties. Modular arthroplasty has given us 11 long term excellent results in 11 of 13 cases. DISCUSSION: The analysis of etiological factors shows two very different groups. The first one consisted of 8 fractures without coxofemoral amyloidosis. The average duration of dialysis was 5 years, average age, 44 years. Etiology was 3 times aluminic osteomalacy, once the only factor found was osteoporosis and 4 times necrosis and porosis as a complication, not of haemodialysis but of renal transplantation with concomittant corticosteroid treatment. The second group consisted of 18 fractures with hip amyloidosis in 14 patients. The average age was 63.5 years, the dialysis duration was 11.5 years, the two extremes 5 and 21 years. Etiology was beta-2-microglobulin amylosis. The pathological fracture was due to the presence of voluminous subchondral amyloidosis geodes. Amyloidosis always associated with hyperparathyroidism and aluminic intoxication in one of 3 cases. Osteosynthesis gave good results only in cases presenting no intra-osseous amyloidosis. Modular arthroplasty has allowed us to obtain excellent long term functional results with simpler outcome. Total arthroplasty should be used only for evident acetabular involvement. CONCLUSION: Amyloidosis remains the etiological factor most frequently found in pathological fractures of the femoral neck in chronic haemodialysis patients. The study of the etiological factors is essential since they will guide us in the choice of the mode or treatment. It is totally licit to propose conservative treatment for non displaced fractures without osseous amylosis. In all other cases, prosthetic replacement is necessary and osteosynthesis contra-indicated. When the acetabulum is not altered a modular arthroplasty must be used. We do not recommend preventive surgical treatment for patients having a threatening geode of the femoral neck as all osteosynthesis realized on amyloidotic bone, even without any displacement, resulted

Adult↗
PubMed1994

Free radicals in retinal and choroidal blood flow autoregulation in the piglet: interaction with prostaglandins.

PURPOSE: To study the role of free radicals in autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) and the contribution of the cyclooxygenase pathway in free radical formation during blood pressure changes in 1- to 3-day-old pigs. METHODS: Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and the aortic root to induce hypertension and hypotension, respectively. Blood flow was measured using the microsphere technique. Also, the effects of peroxides on retinal artery diameter were studied on eyecup preparations using time-frame photography processed by digital imaging. RESULTS: Blood gases and intraocular pressure (13 +/- 1 mm Hg) remained stable throughout the experiments. In control animals, RBF was constant only between 30 and 75 mm Hg of ocular perfusion pressure and ChBF increased as a function of ocular perfusion pressure (tau = 0.58, P < 0.01). Inhibition of peroxidation with the free radical scavenger 21-aminosteroid U74389F (2.5 mg/kg) widened the range of RBF and ChBF autoregulation (ocular perfusion pressure from 30 to 131 mm Hg). Hypertension caused an increase in the products of peroxidation, malondialdehyde, and hydroperoxides, as well as in prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in the retina and choroid of control animals; these changes were inhibited by the free radical scavengers U74389F (2.5 mg/kg) and high-dose allopurinol (140 mg/kg) as well as by the cyclooxygenase inhibitors ibuprofen (40 mg/kg) and indomethacin (5 mg/kg). In isolated eyecup preparations, H2O2 and cumene hydroperoxide dilated retinal vessels, and this effect was completely blocked by indomethacin. CONCLUSIONS: These findings indicate that free radicals play a major role in setting the upper limit of RBF and ChBF autoregulation of the newborn animal. In addition, there exists a positive feedback interaction between free radicals and cyclooxygenase activity in ocular tissues, such that during hypertension the cyclooxygenase pathway is an important producer of free radicals and in turn is also activated by them.

Animals↗
PubMed1993

A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infection.

A comparative double blind trial was undertaken of the efficacy of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar abscesses. Patients were admitted to the trial with acute dentoalveolar abscesses with systemic involvement and assessments were made of pain, swelling, temperature and lymphadenopathy. After admission to the trial appropriate surgical therapy was undertaken. The patients were then given either phenoxymethylpenicillin 250 mg four times daily, cephradine 500 mg twice daily or amoxycillin 250 mg three times daily, all for 5 days. The patients were assessed after 2 days and 5 days. All the patients recovered with those taking cephradine showing the best recovery in the first two days of treatment.

Actinomyces↗
PubMed1993

[Impact of life events in the course of depression].

The impact of recent life events in the provoking of depressive episodes is well-established, but their weight in the course of depression has not been frequently studied. Some data can nevertheless be extracted from published research: First, life events occurring before the beginning of the episode are predicative neither of the response to treatment, nor of the long-term evolution of major depressive episodes. Reactional depression seem to be more sensitive to placebo than non-reactional depressions, and, minor reactional depression could have a better spontaneous course. Second, stressful life events and long-lasting difficulties contemporary with the episode are some of the more important clues for durability, and sometimes chronicity, of depressive symptoms. Some of those events are independent (not controlled by the subject), but some are also dependent, produced by the subject and his depressive state. On the other hand, certain types of life events (like "neutralizing events" or "fresh start events") and the stress reduction of long-lasting difficulties, seem to favour remission of minor depressions. Third, weight of life events in relapse and recurrence of depression is significant, but seems to be less important than in the release of first depressive episodes. The interaction between life events and the genesis of depression can be observed from sociological, psychological or biological point of view. Future analysis should be based on the distinction between vulnerability factors, which modulate the impact of life events, and susceptibility factors, which can have a sensibilization role.

Adjustment Disorders↗