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S Somani

Publications and source records attributed to S Somani.

10 recordsLinked to original sources
PubMed2000

Effect of protective agents against cisplatin ototoxicity.

HYPOTHESIS: The goals of this investigation were to compare the efficacy of three protective agents against cisplatin-induced elevation of auditory brainstem response (ABR) thresholds and to examine whether these protective agents prevent cisplatin-induced alterations of the antioxidant defense system in the cochlea of the rat. BACKGROUND: Cisplatin is an ototoxic antitumor agent. Previous animal studies have shown that cisplatin administration causes an elevation of ABR thresholds. These auditory changes are accompanied by alterations in the concentration of glutathione and the antioxidant enzymes in the cochlea. The authors' previous work has indicated that the protective agent diethyldithiocarbamate (DDTC) prevents decrease in glutathione (GSH), alteration of antioxidant enzyme activity, and disruption of cochlear function with cisplatin administration. METHODS: Wistar rats were sedated and underwent pretreatment ABR testing using clicks and tone burst stimuli at 8, 16, and 32 kHz. Control rats received saline by intraperitoneal (i.p.) injection. Positive control rats were administered cisplatin 16 mg/kg i.p. Three groups of rats received protective agents in combination with cisplatin. The DDTC-protected rats were given 600 mg/kg of DDTC subcutaneously 1 hour after cisplatin. Animals protected by 4-methylthiobenzoic acid (MTBA) were given 250 mg/kg of this agent i.p. 30 minutes before cisplatin. Animals protected with ebselen were given 16 mg/kg i.p. one hour before cisplatin. The ABR thresholds were recorded 72 hours after cisplatin administration in all groups. Cochleas were removed, and extracts of the tissues were analyzed for GSH, activities of antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase, and glutathione reductase) and malondialdehyde (MDA) (as an index of lipid peroxidation). RESULTS: Cisplatin-treated rats had significant ABR threshold shifts, ranging from 27 to 40 dB. Rats administered each of the three protective agents in combination with cisplatin had ABR threshold shifts of <10 dB. The cochleae of rats administered cisplatin alone had nearly a 50% depletion of glutathione and about a 50% reduction in the activities of SOD, glutathione peroxidase, and glutathione reductase, while catalase activity was reduced to 70% of control values. These changes were accompanied by a reciprocal elevation of MDA of 165%. These changes, namely, the depletion of GSH and antioxidant enzyme activity and the elevation of MDA in the cochlea, were largely attenuated by the administration of the protective agents tested. CONCLUSION: These findings suggest that cisplatin ototoxicity is related to lipid peroxidation and that the use of protective agents prevents hearing loss and lipid peroxidation by sparing the antioxidant system in the cochlea. These results suggest the possibility that the clinical use of protective agents could effectively reduce or prevent damage to the inner ear of patients receiving cisplatin chemotherapy, provided that the antitumor effect is not altered.

Adjuvants, Immunologic↗
PubMed1999

Ototoxicity. Amelioration by protective agents.

The findings of studies from this laboratory are summarized to compare the efficacy of four chemoprotective agents against the effects of cisplatin-induced hearing loss and biochemical damage in the rat cochlea. A number of studies have shown that cisplatin is ototoxic, resulting in hearing loss, morphologic damage, and biochemical changes in the cochlea. These studies used Wistar rats, which underwent pre- and posttreatment ABR testing using clicks and tonebursts stimuli at 8, 16, and 32 kHz. Controls received i.p. saline injection. Cisplatin-treated rats were given 16 mg/kg cisplatin i.p. Animals received protective agents in the following dosage: DDTC protected rats received 600 mg/kg subcutaneously an hour after cisplatin. MTBA-protected animals were given 250 mg/kg i.p. 30 minutes before cisplatin. Animals protected with ebselen received 16 mg/kg i.p. an hour before cisplatin. One hundred mg/kg of alpha-lipoic acid was injected i.p. 30 minutes before cisplatin. Rats were sacrificed three days after treatment and the cochleae were harvested and frozen in liquid nitrogen and stored at -80 degrees C until analysis of glutathione (GSH), the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and malondialdehyde was performed. Cisplatin-treated rats were found to have ABR threshold shifts of 27-40 dB, and rats treated with chemoprotective agents plus cisplatin all had ABR thresholds shifts of less than 10 dB. Significant depletion of glutathione and decrease of the activities of the antioxidant enzymes were observed in cisplatin-treated rats. These changes were accompanied by a marked elevation of malondialdehyde. These changes were almost completely prevented by the use of the chemoprotective agents. These findings suggest that cisplatin ototoxicity is related to lipid peroxidation and that the use of protective agents prevents hearing loss and lipid peroxidation by sparing the antioxidant defense system in the cochlea.

Animals↗
PubMed1999

Application of antioxidants and other agents to prevent cisplatin ototoxicity.

OBJECTIVE/HYPOTHESIS: To review the recent data from experiments performed in this laboratory to test the hypothesis that cisplatin ototoxicity is related to depletion of glutathione and antioxidant enzymes in the cochlea and that the use of antioxidants or protective agents would protect the cochlea against cisplatin damage and prevent hearing loss. STUDY DESIGN/METHODS: Data were reviewed from experiments performed in this laboratory. Control rats were treated intraperitoneally with cisplatin 16 mg/kg. Experimental rats were given cisplatin in combination with one of the following protective agents: diethyldithiocarbamate, 4-methylthiobenzoic acid, ebselen, or lipoic acid. Animals in each group underwent auditory brainstem response (ABR) threshold testing before and 3 days after treatment. Cochleae were removed after final ABR testing and analyzed for glutathione and activities of the enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and malondialdehyde. RESULTS: Rats in the control group receiving cisplatin were found to have significant ABR threshold shifts. This was accompanied by a reduction of glutathione and the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase) and an elevation of malondialdehyde. Experimental animals had preservation of ABR thresholds and levels of glutathione, antioxidant enzyme activity, and malondialdehyde that were similar to untreated animals. CONCLUSION: Cisplatin ototoxicity appears to be initiated by fee-radical production, which causes depletion of glutathione and antioxidant enzymes in the cochlea, and lipid peroxidation, manifested by an increase in malondialdehyde. These effects were blocked by each of a series of antioxidant compounds given in combination with cisplatin. A mechanism for cisplatin ototoxicity is elaborated with a proposed plan of chemoprevention using agents with different mechanisms of action. These substances could be used alone or in combination to reduce the severity of cisplatin ototoxicity in patients.

Animals↗
PubMed1997

Postoperative endophthalmitis: incidence, predisposing surgery, clinical course and outcome.

OBJECTIVE: To describe the predisposing surgery, clinical course and final visual outcome for patients with culture-proven and culture-negative postoperative endophthalmitis. DESIGN: Case series. SETTING: University-affiliated teaching hospital in Toronto. PATIENTS: A total of 164 patients with clinically suspected postoperative endophthalmitis admitted between January 1989 and March 1996. OUTCOME MEASURES: Type of surgery, clinical presentation, culture results, infecting organism, treatment and final visual outcome. RESULTS: An infectious agent was identified in 99 cases (60%). The organism most commonly isolated was coagulase-negative Staphylococcus (59 cases [60%]). In the culture-proven group cataract extraction was the most common predisposing surgical procedure, accounting for 85 cases (extracapsular cataract extraction [ECCE] in 60 cases and phacoemulsification in 25). The incidence rates of culture-proven endophthalmitis over the study period at our institution were 0.22% for ECCE and 0.30% for phacoemulsification. Of the 99 patients with culture-proven endophthalmitis 94 received intravitreal injections of antibiotics and 52 underwent vitrectomy. Of the 83 patients in this group for whom the final outcome was known, 29 (35%) had a visual acuity of 20/50 or better, and 15 (18%) had a vision of no light perception, with four eyes undergoing enucleation. Infection with organisms of low virulence (coagulase-negative Staphylococcus or Propionibacterium acnes) was associated with higher rates of 20/50 or better visual acuity compared with more virulent organisms (Staphylococcus aureus, streptococcal species and gram-negative bacilli) (46% vs. 10%) (p < 0.05). The culture-negative group had a significantly lower frequency of hypopyon on presentation (55% vs. 85%) and final outcome of no light perception (2% vs. 18%) (p < 0.01) than the culture-proven group. CONCLUSIONS: Endophthalmitis was most common after cataract surgery. The rates of endophthalmitis after ECCE and phacoemulsification were similar. Postoperative endophthalmitis caused by organisms other than coagulase-negative Staphylococcus or P. acnes carries a poor visual outcome.

Adult↗
PubMed1991

Effect of computer software on time required to prepare parenteral nutrient solutions.

Pharmacist and technician times required for the preparation of parenteral nutrient (PN) solutions were studied before and after the introduction of a software package that is used with an automated compounder. At a 580-bed teaching hospital, work sampling was used to collect data on how time was spent by personnel in the i.v. admixture pharmacy during six-week periods before and after the introduction of software that calculates the quantities of PN solution ingredients on a computer-generated work sheet and prints labels. The second data-collection period began when the software had been in use for four months. In the second study period, there was a significant decrease (28%) in total pharmacist time spent per PN solution; the mean +/- S.D. pharmacist times per PN solution per day for the two study periods were 14.03 +/- 3.24 minutes and 10.12 +/- 1.61 minutes, respectively. There were also significant decreases in pharmacist time spent performing calculations, checking calculations, and typing labels. After introduction of the software, technicians spent significantly less time typing labels and pumping base solutions. Overall, technicians spent significantly less time per PN solution in the second study period (20.15 +/- 3.50 versus 17.82 +/- 1.94 minutes). Use of the software allowed pharmacist staffing in the i.v. admixture pharmacy to be reduced, and the pharmacy resources were reallocated toward the provision of clinical services. The generation of PN labels and calculation worksheets by computer software reduced pharmacist and technician time requirements for PN solution preparation.

Data Collection↗
PubMed1990

Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home.

Amantadine, in a dose of 100 mg/day, is recommended for influenza prevention in older nursing home residents. We studied an influenza prevention protocol in a 98-bed community nursing home (96% female; mean age = 87.4 years). Fifty-five residents received amantadine when influenza A was confirmed. Although no further influenza cases were diagnosed, 22% experienced adverse events. Dose in mg/kg/day was significantly higher in the group experiencing adverse events (2.24 +/- 0.98 vs 1.76 +/- 0.35; P less than .01). Amantadine concentrations in 32 residents ranged from 128-5,810 ng/mL. Six residents had amantadine concentrations greater than 1,000 ng/mL. Seventy-eight percent would have qualified for further dose reduction on the basis of estimated creatinine clearance. The results suggest that adverse events may be an important problem with the 100 mg/day dose, and this dose may be excessive for influenza prophylaxis in many nursing home residents.

Accidental Falls↗
PubMed1987

Pharmacokinetics and pharmacodynamics of physostigmine after intravenous administration in beagle dogs.

The time course of physostigmine (Phy), its metabolites and activity of cholinesterase (ChE) in plasma were studied after intravenous bolus administration of [3H]Phy (100 micrograms/kg) to beagle dogs. The maximal inhibition of ChE (78%) in plasma at 2 min correlated with the largest concentration of physostigmine (124 ng/ml). The concentration of physostigmine decreased by 88% to 16 ng/ml at 45 min when the activity of ChE was still 59% inhibited. Acetylcholinesterase activity in four regions of the brain (medulla, striatum, cerebellum and cortex) was not significantly different from controls at 70 +/- 5 min after administration of physostigmine. Concentrations of physostigmine and its metabolites determined by HPLC were not significantly different in different regions. In plasma, physostigmine was found, together with eseroline and two other metabolites M1 and M2. At 45 min, only 18% of total radioactivity was due to physostigmine and 52% was due to the major metabolite M1. On the contrary, in regions of the brain, metabolite M1 represented only 1.9-3.37% of total radioactivity at 70 +/- 5 min. Pharmacokinetic parameters, obtained in the dog, were compared to previously published data in rat and man. The elimination half-life (beta) was 30.7 min in the dog as compared to 15 min in rat and and 21.7 min in man. The Vd (ml/kg) was higher than total body water volume in all three species: dog (1832), rat (1352) and man (664), indicating sequestration of the drug in body compartments. Clearance (ml/min/kg) was found to be 41.2 in dog, which compares to 62 in rat and 22 in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

The effect of repeated desipramine administration on water intake in rats.

Rats were maintained on a regimen of restricted access to water. Desipramine (DMI) IP 1 h prior to the access period dose-dependently reduced water intake. Following completion of the dose-response determination for the effect of desipramine or water intake, rats were divided into three groups for repeated administration. Rats in each group were injected both 1 h before and 15 min after the access period. The SAL-SAL group received saline both before and after the session, the DMI-SAL group received 10 mg/kg DMI before and saline after the session, and the SAL-DMI group received saline before and 10 mg/kg DMI after the session. Average water intake for rats in the DMI-SAL group decreased progressively during the first 5 days of repeated administration and then began to return toward baseline levels. Average water intake for rats in the SAL-DMI group decreased progressively from days 4-18 of repeated administration and then began to increase toward baseline levels. Rats repeatedly administered DMI (DMI-SAL and SAL-DMI groups) became tolerant to its effect on water intake, as indicated by a diminution of the DMI effect during repeated treatment and by a shift to the right in the DMI dose-response function after discontinuation of repeated DMI administration. Both groups of rats administered DMI repeatedly were less sensitive to amitriptyline-induced reduction of water intake than controls, thereby indicating the development of cross-tolerance to amitriptyline. Cross-tolerance to scopolamine did not develop. These findings demonstrate a behavioral effect of DMI that results in the development of tolerance. The lack of cross-tolerance to scopolamine suggests that tolerance development is not due to altered central cholinergic function.

Amitriptyline↗
PubMedDate not supplied

Plasmodium falciparum and hepatitis E virus co-infection in fulminant hepatic failure.

Acute hepatitis E and falciparum malaria can each present with fulminant hepatic failure and are common in tropical countries. However, co-existence of these two conditions has not been reported. We report a 20-year-old girl who presented with fever and altered sensorium. Peripheral smear was positive for Plasmodium falciparum, and IgM anti-HEV was positive. She died despite antimalarial drugs and supportive management. Postmortem liver tissue showed changes suggestive of acute viral hepatitis.

Acute Disease↗