Biomedical subjects

R Salvi

Publications and source records attributed to R Salvi.

At least 19 recordsLinked to original sources

PubMed2006

Salicylate- and quinine-induced tinnitus and effects of memantine.

CONCLUSION: Memantine, an antiglutamatergic drug, has been proposed as a treatment for tinnitus. OBJECTIVES: The purpose of this study was to determine if memantine would prevent salicylate-induced tinnitus. Local field potentials were also recorded from auditory cortex to determine what effect salicylate, memantine, and the combination of both drugs would have on evoked potential amplitudes. MATERIALS AND METHODS: Schedule induced polydipsia-avoidance conditioning was used to identify the doses of salicylate or quinine that reliably induced tinnitus in rats. Rats were trained to lick for water during quiet intervals and avoid licking during sound intervals. RESULTS: Rats injected with saline or a low dose of sodium salicylate or quinine failed to develop tinnitus-like behaviors. However, high doses of salicylate (150-300 mg/kg/day) or quinine (100-150 mg/kg/day) greatly reduced licks-in-quiet, behavior consistent with the presence of tinnitus. Licks-in-quiet increased slightly when memantine (1.5 or 3 mg/kg/day) was co-administered with salicylate; however, the effect was not statistically significant or dose-dependent. These results indicate that memantine does not completely suppress salicylate-induced tinnitus. Cortical auditory evoked potential amplitude increased after salicylate treatment; co-administration of memantine failed to block this salicylate-induced increase.

Analgesics, Non-Narcotic↗

PubMed2004

Physical methods for preventing deep vein thrombosis in stroke.

BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are uncommon but important complications of stroke. There is good evidence that anticoagulants can reduce the risk of DVT and PE after stroke, but this benefit is offset by a small but definite risk of serious haemorrhages. Physical methods to prevent DVT and PE (such as compression stockings applied to the legs) are not associated with any bleeding risk and are effective in some categories of medical and surgical patients. We sought to assess their effects in stroke patients. OBJECTIVES: To assess the effectiveness and safety of physical methods of preventing the onset of deep vein thrombosis and fatal or non fatal pulmonary embolism in patients with recent stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched June 2003). In addition we searched the following electronic bibliographic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1980 to June 2003) and CINAHL (1982 to June 2003). The reference lists of all relevant papers were screened for additional trials. SELECTION CRITERIA: Unconfounded randomised controlled trials comparing physical methods for the prevention of DVT with control, in which prophylaxis was started within seven days of the onset of stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched for relevant trials and three others independently checked the results. MAIN RESULTS: We identified two small trials which included 123 patients. In one trial of 97 patients, compression stockings were associated with a non significant trend towards a reduction in DVT detected by Doppler ultrasound. In one trial of 26 patients, an intermittent pneumatic compression device was not associated with a significant reduction in DVT detected by 125-I-fibrinogen scanning. Overall, physical methods were not associated with a significant reduction in DVT during the treatment period in survivors (Odds ratio (OR) 0.54, 95% Confidence Interval (CI) 0.18 to 1.57) or death (OR 1.54, 95% CI 0.5 to 4.77). REVIEWERS' CONCLUSIONS: There is insufficient evidence from randomised trials to support the routine use of physical methods for preventing DVT in acute stroke.

Bandages↗

PubMed2003

Pifithrin-alpha suppresses p53 and protects cochlear and vestibular hair cells from cisplatin-induced apoptosis.

Cisplatin, a commonly used antineoplastic agent, destroys the sensory hair cells in the cochlear and vestibular system leading to irreversible hearing loss and balance problems. Cisplatin-induced hair cell damage presumably occurs by apoptosis. Recent studies suggest that p53 may play an important role initiating cisplatin-induced apoptosis in some cell types. To determine if p53 plays a role in cisplatin-mediated hair cell loss, cochlear and utricular organotypic cultures were prepared from postnatal day 3-4 rats and treated with cisplatin or cisplatin plus pifithrin-alpha (PFT), a p53 inhibitor. Control cultures were devoid of p53 immunolabeling, caspase-1 and caspase-3 labeling and p53 protein was absent from Western blots. Cisplatin (1-10 microg/ml) caused a dose-dependent loss of hair cells in cochlear and utricular cultures, up-regulated phospho-p53 serine 15 immunolabeling, increased the expression of phospho-p53 serine 15 in Western blots from 6 to 48 h after the onset of cisplatin-treatment, and increased caspase-1 and caspase-3 labeling in cochlear and vestibular cultures. Addition of PFT (20-100 microM) to cisplatin-treated cochlear and utricular cultures resulted in a dose-dependent increase in hair cell survival; suppressed the expression of p53 in Western blots and eliminated caspase-1 and caspase-3 labeling in cultures. These results suggest that the tumor suppressor protein, p53, plays a critical role in initiating apoptosis in cochlear and vestibular hair cells. Temporary suppression of p53 with PFT provides significant protection against cisplatin-induced hair cell loss and offers the potential for reducing the ototoxic, vestibulotoxic and neurotoxic side effects of cisplatin.

Animals↗

PubMed2003

Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulation.

BACKGROUND: A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism. OBJECTIVES: In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year. PATIENTS AND METHODS: Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization. RESULTS: A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36-1.41). CONCLUSIONS: The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months.

Administration, Oral↗

PubMed2003

[The protection of Tiron to the injury of organ of Corti cultured in vitro caused by exogenous H2O2 in mouse].

OBJECTIVE: In order to observe the action of H2O2 on inner and outer hair cells of organ of Corti in mouse, and discuss whether Tiron can effectively resistant the injury of free radicals in cultured cochlea in vitro or not. METHOD: Using the culture technology of organ of Corti in newborn mouse in vitro, established the model of the injury of inner and outer hair cells caused by exogenous H2O2. And observed the protection to the damage by H2O2 at different concentration of Tiron. RESULT: When the concentration of H2O2 is higher than 1.0 mmol/L, the loss of hair cells in the bottom, middle, and parietal turn of basilar membrane vary, the injury of bottom turn is more severe. In lower than 0.5 mmol/L group, the injury of hair cells is no relationship with the location. Adding Tiron (10 mmol/L) in culture can apparently decrease the injury of hair cells caused by H2O2. When the concentration of H2O2 is 0.01-1.0 mmol/L, Tiron can almost inhibit the loss of hair cells completely. CONCLUSION: There is apparently preventive effection of Tiron on organ of Corti cultured in vitro, and the mechanism of inhibiting injury caused by H2O2 is probably by clearing O2- and combining irony ion.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

PubMed2002

Physical methods for preventing deep vein thrombosis in stroke.

BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are uncommon but important complications of stroke. There is good evidence that anticoagulants can reduce the risk of DVT and PE after stroke, but this benefit is offset by a small but definite risk of serious haemorrhages. Physical methods to prevent DVT and PE (such as compression stockings applied to the legs) are not associated with any bleeding risk and are effective in some categories of medical and surgical patients. We sought to assess their effects in stroke patients. OBJECTIVES: To assess the effectiveness and safety of physical methods of preventing the onset of deep vein thrombosis and fatal or non fatal pulmonary embolism in patients with recent stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched October 2001). In addition we searched the following electronic bibliographic databases: Cochrane Controlled Trials Register (1999, Issue 3), MEDLINE (1966- Jan 2001), EMBASE (1980- Jan 2001) and CINAHL (1982-May 1999). The reference lists of all relevant papers were screened for additional trials. SELECTION CRITERIA: All completed randomised unconfounded trials or controlled clinical trials comparing physical methods in patients allocated to receive physical methods, applied within one week of onset of stroke, with patients allocated to no physical methods. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched for relevant trials and three others independently checked the results. MAIN RESULTS: We identified two small trials which included 123 patients. In one trial of 97 patients, compression stockings were associated with a non significant trend towards a reduction in DVT detected by Doppler ultrasound. In one trial of 26 patients, an intermittent pneumatic compression device was not associated with a significant reduction in DVT detected by 125-I-fibrinogen scanning. Overall, physical methods were not associated with a significant reduction in DVT (Odds ratio 0.59, 95%.CI 0.24-1.48) or death (Odds ratio 5.06, 95% CI 0.96-26.78). REVIEWER'S CONCLUSIONS: There is insufficient evidence from randomised trials to support the routine use of physical methods for preventing DVT in acute stroke.

Bandages↗

PubMed2001

Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice.

C1q deficiency strongly predisposes to the development of systemic lupus erythematosus in humans and mice. We used the model of accelerated nephrotoxic nephritis in C1q-deficient mice to explore the mechanisms behind these associations. C1q-deficient mice developed severe glomerular thrombosis within 4 days of induction of disease, whereas wild-type mice developed mild injury. These findings suggest that C1q protects from immune-mediated glomerular injury. This exacerbated thrombosis was also seen in mice triply deficient in C1q, factor B, and C2, excluding a major pathogenic role for the alternative pathway of complement in this phenomenon. However, these mice did not develop elevated creatinine levels. No exacerbation of accelerated nephrotoxic nephritis was observed in mice doubly deficient in factor B and C2, suggesting a protective role for C1q against renal inflammation that is proximal to C2 activation. There were increased murine IgG deposits, neutrophil numbers, and apoptotic cells in the glomeruli of C1q-deficient mice compared with wild-type mice. Renal expression of genes encoding procoagulant proteins was also enhanced in C1q-deficient mice. The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys.

Animals↗

PubMed2001

Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints.

Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.

Animals↗

PubMed2001

Effect of inner and outer hair cell lesions on electrically evoked otoacoustic emissions.

When the cochlea is stimulated by a sinusoidal current, the inner ear emits an acoustic signal at the stimulus frequency, termed the electrically evoked otoacoustic emission (EEOAE). Recent studies have found EEOAEs in birds lacking outer hair cells (OHCs), raising the possibility that other types of hair cells, including inner hair cells (IHCs), may generate EEOAEs. To determine the relative contribution of IHCs and OHCs to the generation of the EEOAE, we measured the amplitude of EEOAEs, distortion product otoacoustic emissions (DPOAEs), the cochlear microphonic (CM) and the compound action potential (CAP) in normal chinchillas and chinchillas with IHC lesions or IHC plus OHC lesions induced by carboplatin. Selective IHC loss had little or no effect on CM amplitude and caused a slight reduction in mean DPOAE amplitude. However, IHC loss resulted in a massive reduction in CAP amplitude. Importantly, selective IHC lesions did not reduce EEOAE amplitude, but instead, EEOAE amplitude increased at high frequencies. When both IHCs and OHCs were destroyed, the amplitude of the CM, DPOAE and EEOAE all decreased. The increase in EEOAE amplitude seen with IHC loss may be due to (1) loss of tonic efferent activity to the OHCs, (2) change in the mechanical properties of the cochlea or (3) elimination of EEOAEs produced by IHCs in phase opposition to those from OHCs.

Action Potentials↗

PubMed2001

Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance.

The transforming potential of the MDM2 oncogene has been attributed to the overproduction of the protein. In order to investigate regulation of MDM2 expression in head and neck squamous cell carcinomas, we analysed MDM2 gene amplification, and mRNA and protein expression in tumour specimens from 62 patients, in cell lines, and in normal epithelium adjacent to tumours or obtained from healthy patients. Additionally, TP53-induced MDM2-P2 transcription was evaluated and compared with TP53 status. MDM2 gene amplification and mRNA over-expression is infrequent, 7 and 9%, respectively. The predominant transcript codes for full-length MDM2 protein (90kD) and the level of alternatively spliced forms is not significant. We show that only 47% of tumours exhibit MDM2 immunostaining in more than one third of the neoplastic cells, and thus more than half of the tumours display no or low levels of MDM2 protein. In contrast, MDM2 protein is always detectable in basal and parabasal cells of morphologically normal epithelium outside the invasively growing tumour, as well as in a normal uvula sample. Similarly, the total amount of MDM2 transcripts analysed by reverse transcriptase-polymerase chain reaction is reduced in tumour samples compared to normal tissues, essentially due to a decrease in P2 transcript levels. The relationship between mutated p53 status and low levels of MDM2 found in cell lines is also observed to a certain extent in primary tumour samples. Overall, there is a high frequency of TP53 mutation and under-expression of MDM2 in the head and neck tumours. Moreover, a significant association of decreased MDM2 expression is observed with advanced tumour stage and 3 years survival.

Carcinoma, Squamous Cell↗

PubMed2001

Characteristics of patients with gaze-evoked tinnitus.

OBJECTIVE: The authors describe symptoms and population characteristics in subjects who can modulate the loudness and/or pitch of their tinnitus by eye movements. STUDY DESIGN: Data were obtained by questionnaire. SETTING: The study was conducted at a university center and a tertiary care center. PATIENTS: Respondents had the self-reported ability to modulate their tinnitus with eye movements. RESULTS: Ninety-one subjects reported having gaze-evoked tinnitus after posterior fossa surgery involving the eighth nerve. Eighty-seven of them underwent removal of a vestibular schwannoma (acoustic neuroma), two had bilateral eighth nerve tumors (one underwent bilateral tumor removal; the other unilateral tumor removal), one underwent removal of a cholesteatoma, and one underwent removal of a glomus jugulare tumor. Seventeen subjects who had never had posterior fossa surgery reported gaze-evoked tinnitus. Of those with vestibular schwannomas, tumor size ranged from small (<2 cm) to large (>4 cm). The gender distribution was 48.3% male and 51.7% female. In 77% of patients, the gaze-evoked tinnitus was localized to the surgical ear or side of head; 21.8% had bilateral tinnitus that was louder in the surgical ear or side of head. In 86 of 87 subjects, loudness of tinnitus changed with eye movement. Eye movement away from the central (eyes centered) position increased the loudness of tinnitus in all 86 subjects who responded to this question. Seventy-three of 85 (85.9%) patients indicated that pitch changed with eye movement, with pitch increasing in 64/72 (88.9%) of them. Eighty-three of 87 (95.4%) patients reported total loss of hearing in the surgical ear. Seventy of 83 (84.3%) patients reported facial nerve problems immediately after surgery, 52 of 87 (60%) reported persistent facial weakness, and 16 of 87 (18.4%) patients reported persistent double vision. In those 17 subjects with gaze-evoked tinnitus and no posterior fossa surgery, the majority of respondents (14/17, 82.4%) were male. CONCLUSIONS: Gaze-evoked tinnitus after cerebellar pontine angle surgery is more common than was previously believed. In addition, posterior fossa surgery is not a prerequisite for the development of gaze-evoked tinnitus. It is likely that gaze-evoked tinnitus is a manifestation of functional reorganization. Gaze-evoked tinnitus could result from an unmasking of brain regions that respond to multiple stimulus/response modalities, and/or from anomalous cross-modality interactions, perhaps caused by collateral sprouting.

Adult↗

PubMed2001

Amelioration of collagen-induced arthritis by thrombin inhibition.

The deleterious role of fibrin deposition in arthritic joints prompted us to explore the effect of the thrombin inhibition on the course of collagen-induced arthritis (CIA) in the mouse. CIA was induced in male DBA/1J mice using native chicken type II collagen. The thrombin inhibitor polyethyleneglycol-hirudin (PEG-hirudin) was given for 16 days, starting 20 days after the first immunization (preventive treatment) or at the onset of clinical signs of arthritis (curative treatment). All the mice treated with PEG-hirudin had a significantly prolonged clotting time compared with control mice. PEG-hirudin, administered in a preventive way, led to significantly reduced incidence and severity of CIA during most of the treatment period, as assessed by clinical scoring. Accordingly, histological features showed a significant diminution of synovial hyperplasia in PEG-hirudin-treated mice compared with untreated mice. There was also a significant downmodulation of the synovial proinflammatory IL-1beta and IL-12p35 cytokine mRNAs in treated mice. Intra-articular fibrin, evaluated by immunohistochemistry, was significantly reduced in treated mice compared with control mice and correlated with both clinical and histological scorings. Most importantly, once arthritis was established, PEG-hirudin also showed a curative effect. In conclusion, PEG-hirudin can both prevent the onset of CIA in a dose-dependent manner and ameliorate established arthritis, suggesting that thrombin inhibition may offer a new therapeutic approach in arthritis.

Animals↗

PubMed2000

Enhanced expression of genes involved in coagulation and fibrinolysis in murine arthritis.

STATEMENT OF FINDINGS: We have analyzed the pattern of procoagulant and fibrinolytic gene expression in affected joints during the course of arthritis in two murine models. In both models, we found an increased expression of tissue factor, tissue factor pathway inhibitor, urokinase plasminogen activator, and plasminogen activator inhibitor 1, as well as thrombin receptor. The observed pattern of gene expression tended to favor procoagulant activity, and this pattern was confirmed by functional assays. These alterations would account for persistence of fibrin within the inflamed joint, as is seen in rheumatoid arthritis.

Animals↗

PubMed2000

Induction of spontaneous otoacoustic emissions in chinchillas from carboplatin-induced inner hair cell loss.

Fifteen chinchillas were evaluated for spontaneous otoacoustic emissions (SOAEs) before and after administering carboplatin (126-200 mg/kg), an anti-neoplastic drug that selectively destroys inner hair cells (IHCs) in this species. SOAEs were absent from all animals prior to carboplatin treatment, but at 1 week post-treatment, 47% of the animals and 30% of the ears had developed SOAEs. SOAE frequencies were clustered between 5 and 10 kHz and SOAE intensity ranged from 10 to 32 dB SPL. All of the ears with SOAEs had IHC lesions exceeding 60% throughout most of the cochlea and two ears had outer hair cell lesions of 25-60% at a cochlear place associated with the frequency of the SOAE. Thus, high doses of carboplatin that cause IHC loss can be used to create an animal model with SOAEs.

Animals↗

PubMed2000

Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea.

Action Potentials↗

PubMed2000

Coagulation indicators in patients with paroxysmal atrial fibrillation: effects of electric and pharmacologic cardioversion.

The aim of this study was to determine whether paroxysmal atrial fibrillation (PAF) and/or restoration to sinus rhythm with electric or pharmacologic cardioversion induce modifications to the coagulation system. Thirty-five patients with PAF undergoing either electric (n = 11) or pharmacologic (n = 24) cardioversion were studied. Fibrinopeptide A and D-dimer blood samples were taken immediately before and after cardioversion at different intervals. When compared with the control group (n = 70), the precardioversion fibrinopeptide A plasma values were significantly elevated (11.8 vs 2.5 ng/mL). Fibrinopeptide A plasma values were significantly reduced 5 minutes after cardioversion (11.8 vs 5.3 ng/mL) and remained stable throughout the follow-up sequential measurements. D-dimer plasma values were significantly increased (measured at 12 hours and at day 7) in patients who underwent electrical cardioversions only. A positive correlation (R(2) = 0.76) was found between the energy delivered for cardioversion to sinus rhythm and D-dimer plasma values on day 7. In patients with PAF, levels of fibrinopeptide A, an indicator of coagulation activation, are elevated and soon reduced by the restoration of sinus rhythm. Electric, but not pharmacologic, cardioversion induces an early activation of the fibrinolytic system.

Aged↗

PubMed2000

Left atrial and appendage mechanical function after pharmacological or electrical cardioversion in patients with chronic atrial fibrillation: a multicenter, randomized study.

BACKGROUND: Transient atrial and appendage dysfunction occurs after cardioversion of atrial fibrillation. It has been suggested that one component of early dysfunction is related to the method of restoration of sinus rhythm and it is less severe in patients undergoing pharmacological than electrical cardioversion. The aim of this study was to compare left atrial chamber and left atrial appendage mechanical function before and after 48 hours from electrical or pharmacological cardioversion in patients with chronic atrial fibrillation. METHODS: We studied the effects of the mode of cardioversion on Doppler left atrial and appendage function in 19 patients with persistent atrial fibrillation (> or = 4 weeks), who were randomized to pharmacological (quinidine) or electrical cardioversion (protocol: 200, 300, 360 J) after pre-treatment with verapamil. Transthoracic and transesophageal echocardiography were performed before and 48 hours after the restoration of sinus rhythm. To determine left atrial and appendage mechanical dysfunction, the peak A wave velocities were obtained from transmitral flow velocity profiles recorded in the apical 4-chamber view, and peak emptying and filling appendage velocities were measured by the transesophageal approach with the sample volume placed at the orifice of the left atrial appendage. All the patients were pre-treated with verapamil before cardioversion in order to achieve a satisfactory control of heart rate. RESULTS: Mean peak A wave velocities were 0.52 +/- 0.12 m/s in the patients treated electrically and 0.54 +/- 0.08 m/s in those treated pharmacologically (p = NS). Before and after electrical cardioversion, the peak filling velocities of the left atrial appendage were 0.42 +/- 0.17 and 0.43 +/- 0.17 m/s respectively, and the peak emptying velocities 0.30 +/- 0.14 and 0.36 +/- 0.17 m/s respectively; before and after pharmacological treatment, the peak filling velocities were 0.38 +/- 0.1 and 0.43 +/- 0.1 m/s respectively, and the peak emptying velocities were 0.30 +/- 0.13 and 0.43 +/- 0.24 m/s respectively (p = 0.08). CONCLUSIONS: Even a long period of atrial fibrillation does not lead to a marked depression of global left atrial and left atrial appendage function 48 hours after the restoration of sinus rhythm by means of electrical or pharmacological cardioversion. There is no evidence that electrical cardioversion causes greater post-cardioversion atrial and/or appendage dysfunction than pharmacological treatment after 48 hours. Pre-treatment with verapamil may have reduced the dysfunction (probably because of a reduction in mechanical remodeling during atrial fibrillation).

Aged↗

PubMed1999

Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection.

Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.

Action Potentials↗