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Biomedical subjects

Y Shapira

Publications and source records attributed to Y Shapira.

At least 55 records · Page 3Linked to original sources

Inhibition of cyclooxygenase 2 by nimesulide decreases prostaglandin E2 formation but does not alter brain edema or clinical recovery after closed head injury in rats.

Recently, the enzyme cyclooxygenase (COX) has been recognized to exist as constitutive (COX-1) and inducible isoforms (COX-2). In previous studies, drugs that were inhibitors of both COX-1 and COX-2 failed to decrease brain edema formation or improve Neurological Severity Score (NSS) after closed head trauma (CHT), although some did decrease prostaglandin-E2 (PGE2) formation. The present study examined whether or not a specific inhibitor of COX-2 (nimesulide) exerts a beneficial effect after CHT in rats. Halothane-anesthetized rats (n = 8 in each group) were randomly assigned to one of four groups: surgery, no CHT, no drug (group 1); surgery, no CHT, nimesulide 30 mg/kg intraperitoneally (IP) (group 2); surgery, CHT, no drug (group 3); and surgery, CHT, nimesulide 30 mg/kg IP (group 4). NSS was determined at 1 and 24 h, and brain tissue PGE2 concentration and water content were determined after killing at 24 h. Treatment with nimesulide did not improve NSS (NSS at 24 h = 11+/-6 [median +/- range] in group 3 and 12+/-4 in group 4) or edema formation (brain water content at 24 h = 84.3+/-1.8% [mean +/- SD] in group 3 and 83.8+/-1.9% in group 4). However, nimesulide did decrease cortical and hypothalamic PGE2 formation by 41% and 47%, respectively during the first hour of incubation after brain tissue sampling. The authors conclude that although nimesulide does reduce tissue PGE2 formation, it does not exert a beneficial effect on brain tissue edema or functional activity after CHT in rats.

Anesthetics, Inhalation↗

NPS 1506: a novel NMDA receptor antagonist: neuroprotective effects in a model of closed head trauma in rats.

We examined whether NPS 1506, a novel uncompetitive N-methyl-D-aspartate receptor antagonist, influences neurological outcome following closed head trauma (CHT) in rats. One hundred ten rats were divided into 11 groups: CHT (yes/no), treatment with NPS 1506 (yes/no), and time of euthanization (24 h/48 h). The dose of NPS 1506 was 1 mg/kg IV at 1 and 4 hours following CHT or sham operation. Closed head trauma induced the following changes in the injured hemisphere: Decreased specific gravity (sg) (1.036 +/- 0.006) and magnesium (Mg) (0.042 +/- 0.005 microg/mg) at 24 hours, and potassium (K) at 24 (1.145 +/- 0.376 microg/mg) and 48 hours, and increased water content (W) (84.9 +/- 2.5%) and sodium (Na) (2.135 +/- 0.699 microg/mg) at 24 hours, and calcium (Ca) at 24 (0.543 +/- 0.157 microg/mg) and 48 hours. These were reversed by NPS 1506; sg of 1.043 +/- 0.004, Mg of 0.077 +/- 0.009 microg/mg, K of 1.930 +/- 0.238 microg/mg, W of 81.5 +/- 1.9%, Ca of 0.043 +/- 0.023 microg/mg, and Na of 0.688 +/- 0.110 microg/mg. In groups not given NPS 1506, a nonsignificant decrease in neurological severity score (NSS) occurred at 24 and 48 hours as compared to NSS at 1 hour after CHT. In groups given NPS 1506, NSS at 24 and 48 hours decreased significantly (improved) compared to NSS at 1 hour, but not compared to NSS at 24 and 48 hours in groups not given NPS 1506. NPS 1506 caused no significant change in ischemic tissue volume or hemorrhagic necrosis volume in the injured hemisphere at 24 hours or 48 hours. These findings indicate that NPS 1506 improved measures of brain tissue edema (at 24 hours but not at 48 hours) and ion homeostasis, and this improvement was not related to other measures of outcome.

Animals↗

Repeated thrombolysis in multiple episodes of obstructive thrombosis in prosthetic heart valves: a report of three cases and review of the literature.

BACKGROUND AND AIM OF THE STUDY: Thrombolysis is an emerging method to open thrombosed prosthetic heart valves. However, its applicability and safety in multiple recurrent thrombotic episodes is unclear. METHODS: Among 16 patients with thrombosed prosthetic valves treated with thrombolysis during a 33-month period, three patients (one mitral and two tricuspid) experienced four episodes each, and these were treated with repeated thrombolytic therapy. Data on patient demographics, clinical presentation, diagnosis, treatment and outcome are presented. RESULTS: Thrombolysis was successful in 10/12 episodes (83%); there was delayed response in one episode (8%), and partial response in one episode (8%). There were no major complications. However, a fifth thrombotic episode occurred in two patients with tricuspid prostheses, mandating re-do surgery. CONCLUSION: Thrombolysis in re-thrombosed prosthetic heart valves is feasible, highly successful and safe, and may therefore be used judiciously in selected patients who could not, or would not, undergo redo surgery. A high recurrence rate in the tricuspid position may implicate earlier surgical intervention, which should be individualized.

Adult↗

Mid-term clinical and echocardiographic follow up of patients with CarboMedics valves in the tricuspid position.

BACKGROUND AND AIM OF THE STUDY: Debate continues regarding tricuspid valve replacement (TVR) with a mechanical prosthesis. Experience with bileaflet prostheses is limited; hence the study aim was to explore early and mid-term outcome and hemodynamic data in patients with bileaflet CarboMedics prosthetic valves in the tricuspid position. METHODS: The study population included 25 patients (21 females, four males; mean age 50.5 +/- 13.4 years) who underwent TVR with a CarboMedics valve over a six-year period. Routine clinical examinations and details of transthoracic echocardiography (TTE) were reviewed. Additional TTE, transesophageal echocardiography (TEE) and fluoroscopy were performed as indicated. The number of previous cardiac operations was zero, one and two in 36%, 32% and 32% of patients, respectively. Previous tricuspid surgery was performed in eight cases (32%); concurrent mitral valve replacement was performed in 17 (68%). The hospital mortality rate was 24% and late mortality rate 12%. Seventeen early survivors (13 females, four males) were followed up for 46 +/- 28 months (range: 4-96 months). RESULTS: Among early survivors, the mean and peak transvalvular gradients were 4.0 +/- 1.7 and 7.9 +/- 3.3 mmHg, respectively. Commonly observed INR levels were >2.5 in seven patients (41%), and >3.0 in only three (18%). Five patients (29% of mid-term survivors) experienced a total of 13 episodes of obstructive valve thrombosis, mostly with inappropriate anticoagulation. One patient required emergency re-do surgery; the others responded initially to thrombolysis or intensified antithrombotic treatment, but experienced at least two additional relapses. Aside from thrombotic episodes, all patients but two were in NYHA functional class II-III, and all but four required diuretics. CONCLUSION: TVR with bileaflet mechanical valves carries a high perioperative mortality and mid-term morbidity. Among patients with poor or fair anticoagulation, these valves were associated with a high incidence of obstructive valve thrombosis. If poor patient compliance is anticipated, insertion of a bioprosthesis should be encouraged.

Echocardiography↗

Fluoroscopy of prosthetic heart valves: does it have a place in the echocardiography era?

Fluoroscopy is the best method for delineation of the radio-opaque elements of prosthetic heart valves. It is the modality of choice for the validation and quantification of leaflet motion abnormalities, and for the identification of structural valve dysfunction. Normal values are shown. Echocardiography and fluoroscopy may be seen as complementary diagnostic techniques and, when used appropriately, may help to evaluate prosthetic valve function, integrity and associated complications.

Echocardiography↗

Association between mitral annulus calcification and peripheral arterial atherosclerotic disease.

The authors previously demonstrated a significant association between the presence of mitral annulus calcification (MAC) and aortic atheroma, carotid atherosclerotic disease, and coronary artery disease. The present study was designed to determine whether an association exists between MAC and peripheral arterial atherosclerotic disease. Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 77 patients (40 men and 37 women; mean age, 73.1 +/- 11.4 years; range, 44-90 years) underwent peripheral arterial testing for various indications, and comprised the study group. They were compared with 58 age-matched and sex-matched patients without MAC (30 men and 28 women; mean age, 73.2 +/- 11.8 years; range, 31-93 years) who underwent peripheral arterial testing during the same period for the same indications (control group). MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet detected by transthoracic echocardiography. An ankle/brachial systolic pressure index (ABI) was calculated by dividing the higher dorsalis pedis or posterior tibial Doppler-derived pressures by the higher of the 2 upper extremity systolic pressures. ABI was graded as follows: normal > or = 1, abnormal < 1, mild 0.71 to 0.99, moderate 0.41 to 0.7, and severe < or = 0.4. No differences were found between the groups in indications for referral for peripheral arterial testing and in risk factors for atherosclerosis except for hypertension, which was found to be significantly more prevalent in the study group (66% vs 41%, p = 0.004). The study group included 151 limbs, and the control group included 113 limbs. The mean ABI was significantly lower for all limbs in the MAC group (0.56 +/- 0.27 vs 0.87 +/- 0.24, p = 0.0001), abnormal ABI < 1 (94% vs 68%, p = 0.001), moderate peripheral arterial disease (44% vs 25%, p = 0.001), and a severe disease (27% vs 1%, p = 0.001). Of the 77 patients with MAC, 73 (95%) had a disease (right and/or left limbs) compared with 40 of 58 (69%) in the control group (p = 0.001). Bilateral disease (Doppler index < 1 for both right and left limbs), and severe bilateral disease (Doppler index < or = 0.4 for both right and left limb) were also found to be significantly more prevalent in the MAC group (87% vs 60%, p = 0.001; and 12% vs 0%, p = 0.007, respectively). There is a significant association between the presence of MAC and peripheral arterial disease. This information strengthens our hypothesis that MAC may be an important marker for generalized vascular atherosclerotic disease.

Adult↗

Thrombosis of bileaflet tricuspid valve prosthesis: clinical spectrum and the role of nonsurgical treatment.

BACKGROUND: Thrombosis of a mechanical tricuspid valve prosthesis is a potentially hazardous event. This study aimed to explore the incidence and the clinical presentation of tricuspid valve thrombosis occurring in bileaflet valves and to evaluate the diagnostic and the therapeutic approach. METHODS AND RESULTS: Tricuspid valve thrombosis was sought in 22 late survivors with the CarboMedics valve in a follow-up period of 36.0 +/- 20.8 months. Limited leaflet motion and/or a visible thrombus were considered diagnostic of valve thrombosis. Eight episodes of tricuspid valve thrombosis were diagnosed among 5 patients (12.1 episodes per 100 patient-years). Anticoagulation was inadequate in 3 patients and fair in 2. Florid right heart failure occurred in 3 episodes. Common physical findings included increased jugular venous pulse (5 patients), diastolic tricuspid murmur (4 patients), and peripheral edema (4 patients). The diagnosis was suspected in all clinically and by transthoracic echocardiography and confirmed by fluoroscopy and/or transesophageal echocardiography. In 4 patients, both leaflets were involved. No thrombi were visualized. Three patients received thrombolytic therapy in 4 episodes (complete success in 3, partial success in 1) without hemorrhagic or embolic complications. One patient responded to aggressive anticoagulant therapy. One patient required an emergent repeat surgery. In 1 patient, valve thrombosis recurred thrice. CONCLUSIONS: In patients with fair or poor anticoagulation, a bileaflet valve in the tricuspid position is associated with a high incidence of valve thrombosis. Hinge entrapment requires only a small amount of thrombotic material. Valve thrombosis may be asymptomatic. Involvement of both leaflets is usually required to produce symptoms. A nonsurgical approach (thrombolysis or intensified anticoagulation) is usually successful. Patients should be instructed about heralding signs of valve thrombosis.

Adult↗

Central palatal burns associated with the eating of microwaved pizzas.

Burns of the oral mucosa can be caused by heat, cold, radiation, electricity and mechanical or chemical stimuli. Acids, alkalis and salts can cause considerable damage to the oral mucosa, membranes and lips. Most damage is found in the oropharynx, besides the pharynx and tonsils, the alveolar mucosa of the tongue and the masticatory mucosa of the palate or gingiva show localized or diffused damage. The clinical appearance depends on the severity of the tissue damage and the destructive properties and mode of application of the causative agent. We present an illustrative case of central palatal burn associated with the eating of microwaved pizzas and discuss similar mechanisms of injury.

Adult↗

The natural history of aortic valve disease after mitral valve surgery.

OBJECTIVES: The present study evaluates the long-term course of aortic valve disease and the need for aortic valve surgery in patients with rheumatic mitral valve disease who underwent mitral valve surgery. BACKGROUND: Little is known about the natural history of aortic valve disease in patients undergoing mitral valve surgery for rheumatic mitral valve disease. In addition there is no firm policy regarding the appropriate treatment of mild aortic valve disease while replacing the mitral valve. METHODS: One-hundred thirty-one patients (44 male, 87 female; mean age 61+/-13 yr, range 35 to 89) were followed after mitral valve surgery for a mean period of 13+/-7 years. All patients had rheumatic heart disease. Aortic valve function was assessed preoperatively by cardiac catheterization and during follow-up by transthoracic echocardiography. RESULTS: At the time of mitral valve surgery, 59 patients (45%) had mild aortic valve disease: 7 (5%) aortic stenosis (AS), 58 (44%) aortic regurgitation (AR). At the end of follow-up, 96 patients (73%) had aortic valve disease: 33 AS (mild or moderate except in two cases) and 90 AR (mild or moderate except in one case). Among patients without aortic valve disease at the time of the mitral valve surgery, only three patients developed significant aortic valve disease after 25 years of follow-up procedures. Disease progression was noted in three of the seven patients with AS (2 to severe) and in six of the fifty eight with AR (1 to severe). Fifty two (90%) with mild AR remained stable after a mean follow-up period of 16 years. In only three patients (2%) the aortic valve disease progressed significantly after 9, 17 and 22 years. In only six patients of the entire cohort (5%), aortic valve replacement was needed after a mean period of 21 years (range 15 to 33). In four of them the primary indication for the second surgery was dysfunction of the prosthetic mitral valve. CONCLUSIONS: Our findings indicate that, among patients with rheumatic heart disease, a considerable number of patients have mild aortic valve disease at the time of mitral valve surgery. Yet most do not progress to severe disease, and aortic valve replacement is rarely needed after a long follow-up period. Thus, prophylactic valve replacement is not indicated in these cases.

Adolescent↗

Congenitally missing second premolars in cleft lip and cleft palate children.

Panoramic and periapical radiographs of 278 patients with cleft lip, cleft palate, or both (158 males and 120 females), age 5 to 18 years, were examined to determine the frequency of missing second premolars and the possible association between the cleft side and the side from which the premolar was absent. The prevalence (18%) of missing premolars found in this study is significantly higher than is found in the general population. A considerably higher incidence of missing second premolars was found in the maxilla compared with the mandible both for unilateral and bilateral missing teeth. The second premolar was absent more frequently on the left than on the right side, both in males and females and in both jaws. Interestingly but consistent with our previous reporting, this corresponded to the side where clefts occurred more often. The cause of the higher prevalence of left-sided clefts and missing second premolars in human beings is not known at the present time.

Adolescent↗

Telomerase activity in ductal carcinoma in situ of the breast.

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.

Adult↗

The distribution of clefts of the primary and secondary palates by sex, type, and location.

The frequency and patterns of distribution of cleft lip, cleft lip and alveolus, cleft lip and palate, and isolated cleft palate, together with the possible association between sex, type of cleft, and affected side were studied from records of 278 individuals with clefts. These records were obtained from four cleft centers in the New York City area and constituted a racially mixed urban sample. The type of the cleft varied between sexes. Males had significantly higher rates of cleft lip and palate (p<0.0001), and females had higher rates of isolated cleft palate (p<0.0001). No sex differences were found for cleft lip or cleft lip and alveolus. Unilateral clefts of both the primary and secondary palates were found to occur over three times more frequently than bilateral clefts, and left side predominance was demonstrated.

Adolescent↗

Effect of LF 16-0687MS, a new nonpeptide bradykinin B2 receptor antagonist, in a rat model of closed head trauma.

Bradykinin is an endogenous nonapeptide which potently dilates the cerebral vasculature and markedly increases vascular permeability. These effects are mediated by B2 receptors located on the vascular endothelium. Previous experimental studies have shown that blockade of the kallikreinkinin system, which mediates the formation of bradykinin, afforded a reduction of the brain edema that developed following a cryogenic cortical lesion. In the present study, we investigated the effect of LF 16-0687MS, a novel nonpeptide B2 receptor antagonist, on cerebral edema and neurological severity score (NSS) after closed head injury to rats. LF 16-0687MS or its vehicle (NaCl 0.9%) was continuously infused at 10, 30, and 100 microg/kg/min over 23 h starting 1 h after a focal trauma to the left hemisphere was induced using a weight-drop device. The extent of edema formation was evaluated 24 h after trauma from left and right hemispheres samples by measurement of specific gravity and water content. In a separate study, a neurological severity score based on scoring of behavioural and motor functions was evaluated 1 h and over 1 week after trauma. LF 16-0687MS at 100 microg/kg/min markedly reduced the development of brain edema as indicated by a 68% increase in specific gravity (p<0.05) and a 64% decrease of water content (p<0.05) in the left hemisphere. In addition the recovery of neurological function was significantly improved by 100 microg/kg/min LF 16-0687MS from day 3 to day 7 after CHT. In a separate experiment, we also showed that LF 16-0687MS at 100 microg/kg/min given either 1 h before or 30 min after CHT did not affect mean arterial blood pressure. These results show that blockade of bradykinin B2 receptors is an effective approach to reduce cerebral edema and to improve neurological outcome after a focal contusion to the cranium.

Animals↗

Diffusion and perfusion magnetic resonance imaging following closed head injury in rats.

Diffusion-, perfusion-, T1-, and T2-weighted magnetic resonance imaging (MRI) were performed at 1-2 h, 24 h, and 1 week following closed head injury (CHI) in rats, and data was compared with hematoxylin and eosin histology. At 1-2 h, large areas of low perfusion in the damaged hemisphere overestimate the histological damage. In the first 2 h, the histological damage seems to be a superposition of abnormalities in the T1- and diffusion-weighted images. In areas with more than 10% reduction in the apparent diffusion coefficients (ADCs), reduced regional cerebral blood volume (r-CBV) was also observed. The decrease in ADCs and rCBV correlated with r = 0.78. Changes in the MRI parameters revealed the following: (a) Further reduction in ADC occurred from 83+/-15% at 1-2 h after trauma to 69+/-9% at 24 h, and 1 week later a marked elevation in the ADC values is observed. (b) Blood perfusion measurements performed 1-2 h posttrauma revealed a pronounced reduction in r-CBV (53+/-18%) in the damaged hemisphere in all rats. At 24 h postimpact, areas of hyper- and hypoperfusion were observed. One week later, similar perfusion was found in both hemispheres of all rats. (c) T2 hyperintensity at 24 h overestimated the histological damage found at 1 week. At one week following the trauma, the T2 hyperintensity underestimated the histological damage. It is concluded that CHI, which is a heterogeneous insult, should be studied by a combination of MRI techniques. The superposition of the abnormalities seen on T1 and on the diffusion-weighted MR images at early time point represents best the histological damage. Both T2 and rCBV images are less informative in terms of actual histological damage.

Animals↗

Treatments to support blood pressure increases bleeding and/or decreases survival in a rat model of closed head trauma combined with uncontrolled hemorrhage.

UNLABELLED: Hemorrhagic hypotension may aggravate the detrimental effects of head trauma on neurologic outcome. Our study examined whether using phenylephrine or large volumes of saline IV to increase mean arterial blood pressure (MAP) to 70, 80, or 90 mm Hg during the combination of head trauma and uncontrolled hemorrhage would improve neurologic outcome. Rats were assigned to one of 17 groups. In Groups 1-5, the variables were head trauma (yes/no), hemorrhage (yes/no), 0 or 3 mL saline per milliliter of blood lost, and no target MAP. In Groups 6-11, hemorrhage was or was not combined with head trauma, and large volumes of saline were given IV to achieve target MAPs of 70, 80, or 90 mm Hg. Groups 12-17 were similar to Groups 6-11 except that phenylephrine was used rather than saline to achieve target MAPs. Saline increased blood loss at 2 h to approximately 16 and 25 mL at a MAP of 80 and 90 mm Hg respectively, increased (worsened) the neurodeficit score but not cerebral edema at 24 h, and decreased survival rate at 2 and 24 h. Because phenylephrine was fatal for 62 of 63 rats, group mean values for blood loss, neurodeficit score, and brain tissue specific gravity could not be calculated. We conclude that supporting MAP with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage. IMPLICATIONS: The results of this study indicate that maintaining mean arterial blood pressure at 70, 80, or 90 mm Hg with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage.

Analysis of Variance↗

Preparing hospitals for toxicological mass casualties events.

OBJECTIVE: For most hospital staffs, treatment of chemical casualties presents an obscure and even frightening situation. We report our unique experience from hospital drills in order to improve hospital preparedness for patient management under mass casualty conditions involving hazardous chemicals. SETTING: Twenty-one major hospitals in Israel. INTERVENTIONS: A unique hospital deployment plan for the management of chemical casualties was developed, and hospitals were required to have a full chemical practice drill every 3 to 5 yrs. These drills were designed as realistically as possible, and all included the use of personal protective equipment, decontamination, and treatment of simulated patients. Twenty-five percent of these patients, simulating children and adults, required intensive care and ventilation support. Hospitals were inspected and reviewed on the quality of treatment given and the overall continuity of care as well as on their administrative performance. RESULTS: Between 1986 to 1994, 30 full chemical practice drills were conducted in 21 major hospitals. Each drill included treatment of 100 to 400 simulated patients. The lessons from the hospital drills are described and were incorporated in the proposed revised hospital deployment plan. All hospitals significantly improved their ability to respond appropriately to these incidents. CONCLUSIONS: The level of preparedness for a chemical mass casualty scenario should be established according to the existing threat and the available resources. The proposed plan can serve as a basis for hospital planning and staff training worldwide, thus facilitating optimal care in the event of an incident involving toxic chemicals. A cost-effective scale for hospital preparation levels according to the existing threat is suggested.

Adult↗