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1.
Tech Coloproctol ; 27(8): 673-678, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36645584

RESUMO

INTRODUCTION: Retrorectal lesions (RRLs) are rare lesions that originate from the tissue present in the retrorectal space. The gold standard of care is complete resection regardless of pathology. The traditional approaches (anterior, posterior, and combined) are relatively well described. Transanal Endoscopic Microsurgery (TEM) is a minimally invasive technique offered as an alternative approach for RRLs. AIM: To evaluate the outcomes of patients diagnosed with RRL and treated by the TEM approach, especially postoperative complications, and the recurrence rate. METHODS: Patients with RRLs treated with the TEM technique in one medical center between 2000 and 2020 were identified. Their postoperative outcomes were compared with historical controls. RESULTS: Thirty-nine patients diagnosed with RRL were operated on using the TEM platform. Thirty-seven RRLs were benign, and two were malignant. Their median size (IQR) was 20 mm (15, 32.5). The median distance (IQR) from the anal verge was 50 mm (50, 72.5). The median operative time (IQR) was 48.5 min (41.75, 60). All, except one lesion, were completely resected. The median length of stay (IQR) was one day (1, 1 day). Postoperative complications were diagnosed in three patients, two of which resolved following a second operation. CONCLUSIONS: The implementation of TEM for the resection of RRLs demonstrated excellent overall results with acceptable complication and recurrence rate and represented a viable alternative surgical approach.


Assuntos
Neoplasias Retais , Microcirurgia Endoscópica Transanal , Humanos , Microcirurgia Endoscópica Transanal/métodos , Neoplasias Retais/patologia , Resultado do Tratamento , Microcirurgia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
2.
Hand Surg Rehabil ; 40(4): 389-393, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33831625

RESUMO

Postoperative dressing protocols after clean surgery without implant vary widely. The purpose of this study was to elucidate whether early postoperative dressing removal is a valid option, as compared to untouched dressing or twice-weekly dressing change approach. A prospective randomized study was conducted on patients who underwent carpal tunnel release (CTR) or trigger finger release (TFR) between January and November 2020. Patients were randomly distributed into 3 groups: surgical dressing untouched until first follow up (SDU); surgical dressing changed twice a week in a health maintenance organization (HMO); and surgical dressing removed at first postoperative day (SDR). Data collected included patient characteristics, pre-and post-operative functional (QuickDASH) and autonomy (Instrumental Activities of Daily Living performance (IADL)) scores, Vancouver scar scale (VSS) and potential complications. Eighty-four patients were included: 28 (33.3%), 29 (34.5%) and 27 (32.1%) in the SDU, HMO and SDR groups, respectively. Deterioration in mean IADL score at 2-week follow-up was statistically significant in the HMO group (mean delta 3.35, p = 0.008). Quick DASH score improved significantly between preoperative and 2-week follow-up values only in the SDU group (mean delta 9.12, p = 0.012). Other parameters, including wound complications, did not differ significantly between groups. Early removal of postoperative dressing and immediate wound exposure was a safe option after CTR and TFR. An untouched bulky dressing correlated with early functional improvement. Finally, iterative dressing change in HMO showed no benefit and led to significant deterioration in early postoperative autonomy. IRB APPROVAL: 0548-18-TLV. LEVEL OF EVIDENCE: I.


Assuntos
Síndrome do Túnel Carpal , Mãos , Atividades Cotidianas , Bandagens , Síndrome do Túnel Carpal/cirurgia , Mãos/cirurgia , Humanos , Estudos Prospectivos
3.
Injury ; 52(2): 256-259, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33436267

RESUMO

BACKGROUND: Self-inflicted injury is a leading cause of death worldwide. It is hypothesized that due to instincts for self-preservation, the severity of abdominal injury would be decreased following suicidal self-stabbing in comparison to stab wounds from assault, and therefore a more conservative management might be considered. METHODS: All patients with isolated abdominal stab wound (SW) admitted to 19 Trauma Centers in Israel between the years 1997 and 2018 were included in the study. Patients with self-inflicted abdominal SW (Group I) were compared to victims with abdominal SW following assault (Group II). RESULTS: Group I included 9.4% (314/3324) of patients eligible for this study. Compared to Group II, Group I patients were older (median: 39 years, IQR 28,52 vs. 24 years, IQR 19,33; p<0.001), had more females (28.7% vs 4.9%, p <0.001), had longer length of hospitalization (median: 3 days vs. 2 days; p<0.001), underwent surgery more frequently (55.4% vs. 37.4%; p<0.001), and had higher mortality (2.9% vs. 0.7%; p=0.003). Possible covariates for mortality were examined and following logistic regression, self-inflicted injury remained associated with higher death rates compared to assault (OR 4.027, CI95% 1.380, 11.749; p=0.011). CONCLUSION: In this study, patients with isolated self-inflicted abdominal injuries had higher mortality and more frequently underwent abdominal surgery.


Assuntos
Traumatismos Abdominais , Vítimas de Crime , Ferimentos Perfurantes , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/cirurgia , Feminino , Humanos , Israel/epidemiologia , Estudos Retrospectivos , Ferimentos Perfurantes/epidemiologia , Ferimentos Perfurantes/cirurgia
5.
Eur J Trauma Emerg Surg ; 43(5): 623-626, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26660473

RESUMO

PURPOSE: Though tympanic membrane perforation (TMP) is a marker of barotrauma, relation to severity of injury has been contested based on previous observations that following an explosion many victims with significant injuries do not suffer from TMP while many victims with TMP do not suffer from significant injuries. The objective of this study was to reassess the relationship of TMP to severity of injury and resource demand in patients treated in multiple casualty incidents following terrorist bombings treated in one medical center. METHODS: Retrospective review. RESULTS: Most of the patients with TMP were mildly injured. Nevertheless, TMP was more prevalent in patients with moderate and severe injuries, 53.3 % compared to 13.6 % in mildly injured patients (p = 0.0009). Patients with TMP suffered from more body areas injured (p < 0.0001). They more often needed surgery (30.6 vs. 5.5 %; p < 0.0001), ICU hospitalization (16.1 vs. 1.3 %; p < 0.0001) and secondary transfer to a level I trauma center (12.9 vs. 1.0 %; p < 0.0001). They were hospitalized longer (p < 0.0001). Fifty-three (12.6 %) patients included in this study were not examined by the ENT service. Most of those not examined were either moderately or severely injured. CONCLUSIONS: Patients with TMP were more severely injured and more often needed surgery, ICU hospitalization and need for transfer to a level I trauma center. The observation that all those who died in hospital and most of those who were unstable were not examined by the ENT services suggests that impact of TMP as an indicator of severity may be underestimated.


Assuntos
Traumatismos por Explosões/mortalidade , Explosões , Escala de Gravidade do Ferimento , Incidentes com Feridos em Massa/economia , Perfuração da Membrana Timpânica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Traumatismos por Explosões/patologia , Criança , Pré-Escolar , Feminino , Recursos em Saúde , Humanos , Lactente , Israel , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Traumatologia , Perfuração da Membrana Timpânica/patologia , Adulto Jovem
6.
Anim Genet ; 47(6): 698-707, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27611243

RESUMO

Elucidation of the sex-determination mechanism in flathead grey mullet (Mugil cephalus) is required to exploit its economic potential by production of genetically determined monosex populations and application of hormonal treatment to parents rather than to the marketed progeny. Our objective was to construct a first-generation linkage map of the M. cephalus in order to identify the sex-determining region and sex-determination system. Deep-sequencing data of a single male was assembled and aligned to the genome of Nile tilapia (Oreochromis niloticus). A total 245 M. cephalus microsatellite markers were designed, spanning the syntenic tilapia genome assembly at intervals of 10 Mb. In the mapping family of full-sib progeny, 156 segregating markers were used to construct a first-generation linkage map of 24 linkage groups (LGs), corresponding to the number of chromosomes. The linkage map spanned approximately 1200 cM with an average inter-marker distance of 10.6 cM. Markers segregating on LG9 in two independent mapping families showed nearly complete concordance with gender (R2  = 0.95). The sex determining locus was fine mapped within an interval of 8.6 cM on LG9. The sex of offspring was determined only by the alleles transmitted from the father, thus indicating an XY sex-determination system.


Assuntos
Mapeamento Cromossômico , Ligação Genética , Repetições de Microssatélites , Processos de Determinação Sexual/genética , Smegmamorpha/genética , Alelos , Animais , Ciclídeos/genética , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Análise de Sequência de DNA , Sintenia
7.
Emerg Med J ; 32(12): 946-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26446312

RESUMO

INTRODUCTION: The optimal management strategy for patients with head injury admitted to a non-specialist hospital is uncertain. The aim of this study was to evaluate the outcomes of victims of head injury requiring hospitalisation but initially admitted to a rural level II trauma centre without a neurosurgical facility but with a system for neurosurgical consultation via teleradiology. METHODS: Patients admitted for head injury during 2006-2011 were included. Late transfer of patients initially hospitalised in the level II trauma centre was evaluated for treatment failure, defined as clinical or radiological deterioration. RESULTS: Five hundred and sixty-two patients were initially hospitalised in the level II trauma centre. Evaluation of late transfers showed that only 23 (4.1%) represented real treatment failures due to clinical or radiological deterioration. The clinical course was altered by primary intent to hospitalise patients in the level II trauma centre in only one patient. CONCLUSIONS: Selected patients with head trauma who have a pathological CT scan may be safely managed in level II trauma centres following neurosurgical consultation using teleradiology. Review of treatment failures is necessary to ensure proper ongoing management of a system in which neurosurgical patients are selectively transferred to trauma centres with neurosurgical capacity.


Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Hospitais Rurais/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Telerradiologia/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Traumatismos Craniocerebrais/terapia , Feminino , Seguimentos , Hospitais Gerais/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Israel , Masculino , Pessoa de Meia-Idade , Neurocirurgia/estatística & dados numéricos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Falha de Tratamento , Adulto Jovem
8.
J Fish Biol ; 84(2): 448-58, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24405471

RESUMO

This study aimed at determining whether in vitro secretion of two neuropeptides, arginine vasotocin (AVT) and isotocin (IT), from pituitary cells of gilthead sea bream Sparus aurata was affected by cortisol and urotensin (UI). Pituitary cells were exposed to 1·4 × 10(-8) , 1·4 × 10(-7) and 0·4 × 10(-6) M cortisol and 10(-12) , 10(-10) and 10(-8) M UI for 6, 24 and 48 h, respectively. AVT and IT contents were determined in the culture media by high-performance liquid chromatography (HPLC). An increase in AVT secretion and a decrease in IT secretion were observed at all cortisol doses. UI increased AVT secretion after 6 h of incubation at all doses. After 24 h, however, only the highest dose of UI still displayed an effect. IT secretion was not influenced by UI. It was thus demonstrated that cortisol does influence AVT and IT secretion from S. aurata pituitary cells, while UI regulates AVT secretion, as a component of hypothalamic-pituitary-interrenal (HPI) axis in this species.


Assuntos
Hidrocortisona/farmacologia , Ocitocina/análogos & derivados , Hipófise/citologia , Dourada , Urotensinas/farmacologia , Vasotocina/metabolismo , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Ocitocina/metabolismo , Hipófise/metabolismo
9.
Eur J Trauma Emerg Surg ; 40(4): 445-50, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26816239

RESUMO

BACKGROUND: The unique patterns of injury following explosions together with the involvement of numerous physicians, most of whom are not experienced in trauma, may create problems in the medical management of mass casualty incidents. METHODS: Four hundred patient files admitted in 19 mass casualty events following bombing incidents were reviewed and possible areas which could impact survival were defined. RESULTS: Forty-nine (9.3 %) patients had an Injury Severity Score ≥16. Of 205 patients in whom triage decisions were available, 5 of 25 severely injured patients were undertriaged by the triage officers at the door of the hospital. Following primary evaluation inside the emergency department critical injuries in two patients were missed due to distracting, less serious injuries. Of 68 (16.1 %) patients who were operated, 28 were in need of either immediate, urgent or high-priority operations. Except for neurosurgical cases which needed to be transferred to other hospitals, there was no delay in surgery. One patient underwent negative laparotomy. There were 15 in-hospital deaths, 6 of which were deemed as either anticipated or unanticipated mortality with possibility for improvement. CONCLUSION: Medical management should be evaluated following MCIs as this may illustrate possible problems which many need to be addressed in contingency planning.

10.
Eur J Trauma Emerg Surg ; 40(4): 451-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26816240

RESUMO

PURPOSE: To review the frequency, different patterns, anatomic severity, management, and prognosis of abdominal injuries in survivors of explosions, according to the main mechanism of injury. METHODS: A MEDLINE search was conducted from January 1982 to August 2013, including the following MeSH terms: blast injuries, abdominal injuries. EMBASE was also searched, with the same entries. Abdominal blast injuries (ABIs) have been defined as injuries resulting not only from the effects of the overpressure on abdominal organs, but also from the multimechanistic effects and projectile fragments resulting from the blast. Special emphasis was placed on the detailed assessment of ABIs in patients admitted to GMUGH (Gregorio Marañón University General Hospital) after the Madrid 2004 terrorist bombings, and in patients admitted to HYMC (Hillel Yaffe Medical Centre) in Hadera (Israel) following several bombing episodes. The anatomic severity of injuries was assessed by the abdominal component of the AIS, and the overall anatomic severity of casualties was assessed by means of the NISS. RESULTS: Abdominal injuries are not common in survivors of terrorist explosions, although they are a frequent finding in those immediately killed. Primary and tertiary blast injuries have predominated in survivors from explosions in enclosed spaces reported outside of Israel. In contrast, secondary blast injuries causing fragmentation wounds were predominant in suicide bombings in open and/or semi-confined spaces, mainly in Israel, and also in military conflicts. Multiple perforations of the ileum seem to be the most common primary blast injury to the bowel, but delayed bowel perforations are rare. Secondary blast injuries carry the highest anatomic severity and mortality rate. Most of the deaths assessed occurred early, with hemorrhagic shock from penetrating fragments as the main contributing factor. The negative laparotomy rate has been very variable, with higher rates reported, in general, from civilian hospitals attending a large number of casualties. CONCLUSIONS: The pattern, severity, management, and prognosis of ABI vary considerably, in accordance with the main mechanism of injury.

12.
Gen Comp Endocrinol ; 175(1): 55-64, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22015989

RESUMO

A controlled-release implant loaded with GnRH agonist (GnRHa) was used to induce spawning in Atlantic bluefin tuna (Thunnus thynnus) during two consecutive reproductive seasons. The fish were implanted underwater and sampled between days 2 and 8 after treatment. At the time of GnRHa treatment, females were in full vitellogenesis and males in spermiation. There was a rapid burst of pituitary luteinizing hormone (LH) release at day 2 after treatment in GnRHa-treated fish, and circulating LH remained elevated up to day 8 after treatment. In contrast, control fish had significantly lower levels in the plasma, but higher LH content in the pituitary, as observed in many other cultured fishes that fail to undergo oocyte maturation, ovulation and spawning unless induced by an exogenous GnRHa. Plasma testosterone (T) and 17ß-estradiol (E(2)) were elevated in response to the GnRHa treatment in females, while 11-ketotestosterone (11-KT) but not T was elevated in males. Even though oocyte maturation and ovulation did occur in GnRHa-induced fish, no significant elevations in 17,20ß-dihydroxy-4-pregnen-3-one (17,20ß-P) or 17,20ß,21-trihydroxy-4-pregnen-3-one (20ß-S), in either the free, conjugated or 5ß-reduced,3α-hydroxylated forms was observed in fish sampled within 6 days after treatment. Interestingly, a significant peak in plasma free 17,20ß-P levels occurred in both males and females at day 8 after treatment. Histological sections of the ovaries in these females contained oocytes at the migrating germinal vesicle stage, suggesting the role of this hormone as a maturation-inducing steroid in Atlantic bluefin tuna. In conclusion, the GnRHa implants activated effectively the reproductive endocrine axis in captive Atlantic bluefin tuna broodstocks, through stimulation of sustained elevations in plasma LH, which in turn evoked the synthesis and secretion of the relevant sex steroids leading to gamete maturation and release.


Assuntos
Sistema Endócrino/fisiologia , Hormônio Liberador de Gonadotropina/agonistas , Reprodução/fisiologia , Maturidade Sexual/fisiologia , Atum/fisiologia , Animais , Sistema Endócrino/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Masculino , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Reprodução/efeitos dos fármacos , Estações do Ano , Testosterona/metabolismo
14.
Eur J Trauma Emerg Surg ; 38(2): 113-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26815827

RESUMO

PURPOSE: The National Committee for Hospital Preparedness for Conventional Mass Casualty Incidents and the Hospital Preparedness Division of the Home Front Command are in charge of preparing live exercises held yearly in public hospitals in Israel. Our experience is that live exercises are limited in their ability to test clinical decision making and its influence upon incident management. A live exercise was designed upon real patient data and tested in several public hospitals. The aim of the manuscript is to describe the impact of this new format on clinical decision making in large-scale live exercises. METHODS: A database of histories, physical examination findings, laboratory results and imaging results for 420 patients treated following terrorist explosions was created using information derived from actual patient encounters. Similar information for 100 patients treated following motor vehicle accidents was also collected. Information from the database was used to create victim profiles used during the course of exercises held in eight public hospitals with 60-800-bed capacities. RESULTS: Before implementing the new injury tags, no conclusions could be made concerning the quality of clinical decision making. Conducting the exercise using the new format helped identify deficiencies in the hospital disaster plan in triage, emergency department management and in the proper utilisation of resources such as radiology, operating rooms and the secondary transfer of patients. CONCLUSION: Previous knowledge of patient diagnoses and resource needs allow the identification and quantification of deficiencies and problems identified in clinical decision making, resource utilisation and incident management.

15.
Cytopathology ; 22(3): 174-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20482717

RESUMO

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA-cytology and FNA-biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. METHODS: One hundred and two consecutive patients underwent EUS-FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. RESULTS: Male/female ratio was 61/41. Mean age was 65±12 years (range, 22-94). Mean lesion size was 3.1±1.8 cm (range, 0.6-10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1-4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty-two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS-FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. CONCLUSION: EUS-FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS-FNA.


Assuntos
Citodiagnóstico/métodos , Endossonografia , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
Eur J Trauma Emerg Surg ; 37(3): 259-67, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26815108

RESUMO

PURPOSE: Most gastrointestinal fistulae commonly occur following surgery. A minority is caused by a myriad of other etiologies and is termed by some as "uncommon fistulae". The aim of this study was to review these fistulae and their treatment. METHODS: A literature review was carried out. Searches were conducted in Pubmed and related references reviewed. RESULTS: Except for Crohn's disease and diverticulitis, "uncommon fistulae" are described in case reports or very small case series. Most of the patients were treated by surgery. CONCLUSIONS: The anatomic features of the fistula and the etiology usually dictate the approach. Most patients will eventually need surgery to resolve this pathology.

18.
Injury ; 38(9): 1065-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17716603

RESUMO

OBJECTIVE: To determine whether infrared spectroscopy allows early recognition of epidural and subdural haematomas among trauma patients. METHODS: Injured people admitted to two trauma units were enrolled in a prospective multicentre observational study, and infrared spectroscopy was performed before computed tomography of the head as a part of their initial evaluation. Subsequent CT findings suggestive of epidural or subdural haematoma served as controls. RESULTS: Over 12 months, 110 patients were enrolled; 64 (58.1%) were men and 46 (41.9%) were women. Mean age was 56.2 years, and mean Glasgow Coma Scale on admission was 12.6. Infrared spectroscopy was 90.5% sensitive and 95.5% specific for epidural and subdural haematoma. Positive and negative predictive values were 82.6% and 97.7%, respectively. CONCLUSIONS: Infrared spectroscopy allows early recognition of epidural and subdural haematomas in trauma cases. Further studies are needed to evaluate whether immediate confirmation or exclusion of epidural and subdural haematomas with portable near-infrared spectroscopy devices improves the decision-making process in the treatment of severely injured people.


Assuntos
Hemorragias Intracranianas/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Feminino , Escala de Coma de Glasgow , Humanos , Hemorragias Intracranianas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
20.
Life Sci ; 76(16): 1825-34, 2005 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-15698860

RESUMO

Efficacy of chemotherapy may be maximized and its toxicity can be minimized if drugs would be administered at specified daily times. The present study was aimed to examine if the protection of amifostine against cisplatin toxicity is time dependent. Amifostine is an organic thiophosphate that protects selectively normal tissues, but not tumors, against the cytotoxicity of DNA binding chemotherapeutic agents such as cisplatin. ICR male mice which were entrained to Light:Dark (L:D) 14:10 were injected (intrapritoneal bolus) for 5 consecutive days with either: cisplatin, cisplatin plus amifostine (administered 30 minutes prior to cisplatin). Injections were given at either 08:00, 13:00, 20:00 or 01:00. Five days later, on day 10, each set of mice was sacrificed (at the same hour corresponds to the injection hour), blood count, blood creatinine and blood urea nitrogen (BUN) were assayed. Cisplatin treated mice exhibited nephrotoxicity, as indicated by increased blood urea nitrogen values and by high blood urea nitrogen to creatinine ratios, as well as myelotoxicity that was indicated by low levels of hemoglobin and platelets. Co-administration of amifostine-cisplatin reversed both, the nephrotoxicity of cisplatin, and its myelosuppressive effects. For BUN, hemoglobin and platelets, maximal protections were observed at 08:00, (p <0.05, p <0.01 and p <0.01 respectively). For BUN/Cr ratio (p <0.05), maximal protections was observed at 13:00. These findings show that amifostine exhibits time dependent protection against cisplatin toxicity and thus it is recommended to use the protector when treatments are given during morning hours. The results also further validate the notion that chronochemotherapy is advantageous at least in reducing drug toxicity and thus should be integrated in the design of clinical protocols.


Assuntos
Amifostina/uso terapêutico , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Rim/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Animais , Contagem de Células Sanguíneas , Nitrogênio da Ureia Sanguínea , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Injeções Intraperitoneais , Rim/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fatores de Tempo
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