RESUMO
Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.
Assuntos
Queimaduras Químicas , Cáusticos , Lesão Pulmonar , Humanos , Lesão Pulmonar/induzido quimicamente , Trato Gastrointestinal , Queimaduras Químicas/terapia , Ingestão de AlimentosRESUMO
Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.
Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Ileostomia , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Fístula Anastomótica , Anastomose CirúrgicaRESUMO
OBJECTIVE: To investigate the changes as well as the related mechanism in cognitive function and levels of serum ß-amyloid peptide (Aß) and brain-derived neurotrophic factor (BDNF) in stroke patients. PATIENTS AND METHODS: A total of 30 patients with acute stroke treated in our hospital from June 2015 to September 2016 were selected as stroke group, while 30 volunteers during the same period were enrolled as control group. Changes in cognitive function of patients were evaluated using the Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) before and after the treatment. At the same time, the concentrations of serum Aß1-40 and BDNF were detected, and their correlations with the MMSE score were analyzed. Finally, levels of serum cyclic adenosine monophosphate (cAMP) and phosphorylated-cAMP-response element binding protein (p-CREB), and the phosphorylation level of Tau protein were detected by Western blotting. RESULTS: MoCA and MMSE scores of patients in stroke group were significantly lower than those in control group (p < 0.01), and the scores were significantly higher in stroke patients after treatment than those before treatment (p < 0.01). Compared with those in control group, the serum Aß1-40 concentration in patients in stroke group was significantly increased (p < 0.01), but the BDNF level was significantly decreased (p < 0.01). Compared with those before treatment, the serum Aß1-40 concentration in patients was significantly decreased after treatment (p < 0.01), but the BDNF concentration was significantly increased (p < 0.01). Correlation analysis showed that the MMSE score was negatively correlated with the concentration of Aß1-40 (r2 = 0.764, p < 0.01), but positively related to the level of BDNF (r2 = 0.827, p < 0.01). Compared with those in control group, the content of serum cAMP and p-CREB in stroke patients was significantly decreased (p < 0.01), but the expression of p-Tau was statistically increased (p < 0.01). CONCLUSIONS: The cognitive function in stroke patients is impaired, with the rising content of serum Aß1-40 and reduction of BDNF, the mechanism of which is related to the decrease of cAMP and p-CREB and the increase of p-Tau. This provides a theoretical basis for searching the new therapeutic targets and new drugs for stroke.
Assuntos
Peptídeos beta-Amiloides/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Cognição , Fragmentos de Peptídeos/sangue , Acidente Vascular Cerebral/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , AMP Cíclico/sangue , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Proteínas tau/sangueRESUMO
Objective: To explore the relationship between smoking and hyperuricemia in Chinese residents. Methods: Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the ORs and corresponding 95%CIs for assessing the relationship between smoking and hyperuricemia. Results: Among the 8 785 subjects, 1 435 had hyperuricemia with a prevalence rate of 16.3%, consisting of 886 men and 549 women with prevalence rates of 21.6% (886/4 110) and 11.7% (549/4 675) , respectively. Compared with never smokers, the adjusted OR (95%CI) for hyperuricemia was 0.83 (0.70-0.98) among current smokers, 0.77 (0.63-0.94) among current smokers with 20-39 years of smoking, and 0.79 (0.65-0.97) among current smokers with 11-20 cigarettes per day. When stratified by gender and compared with non-smoker, the adjusted OR (95%CI) for hyperuricemia among current smokers compared with never smokers was 0.83 (0.70-0.98) among men, while no significant association was found in female current smokers (OR=0.73, 95%CI: 0.42-1.26, P=0.260). Conclusion: In Chinese residents, there is an inverse association between smoking and hyperuricemia prevalence, and this association may be related to duration and intensity of smoking among current smokers. The findings need to be validated in large prospective cohort studies.
Assuntos
Hiperuricemia/epidemiologia , Fumar , Adulto , Idoso , China/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Abandono do Hábito de Fumar , Fumar TabacoRESUMO
Brain cancer stem cells are a subset of tumor cells present in several types of brain tumor that evade treatment regimens and are responsible for tumor recurrence. Recent reports on several tumors have suggested that Hoechst 33342 dye exclusion is a powerful technique for isolating cancer stem cell-like side population (SP) cells. In the present study, we attempted to isolate the SP cells from medulloblastoma, a malignant brain tumor in children. The tumor samples obtained were subjected to fluorescence-activated cell sorting analysis for SP cell isolation. Further, the SP cells were characterized by a sphere-formation assay and analyzed for expression of stem cell genes by reverse transcription-polymerase chain reaction (RT-PCR). Using flow cytometry, we isolated 2.9% of cancer stem-like SP cells from malignant medulloblastoma, which was reduced to 0.4% in the presence of verapamil, an inhibitor of ABC transporter. These SP cells undergo rapid proliferation and have a high tendency to form tumor spheres when compared with non-SP cells. Further, RT-PCR analysis revealed that the isolated SP cells have increased expression of neural stem cell markers such as nestin, Notch1, and the ABC transporter protein ABCG2. Therefore, our findings suggest that SP cells of medulloblastoma share the characteristics of cancer stem cells. The increased expression of stem cell markers and ABCG2 protein may function collectively and be responsible for drug and apoptosis resistance, as well as tumor recurrence and invasion.
Assuntos
Meduloblastoma/patologia , Células-Tronco Neoplásicas/fisiologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Pré-Escolar , Expressão Gênica , Humanos , Meduloblastoma/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Células da Side Population/metabolismo , Esferoides Celulares/metabolismoRESUMO
Protein serine/threonine phosphatases are important cellular signaling molecules and play major roles in regulating many different functions including cell proliferation, senescence, programmed cell death, and oncogenic cell transformation. Among different serine/threonine phosphatases, PP-1 and PP-2A contribute to more than 90% phosphatase activities in eukaryotes. While the functions of PP-2A in cell transformation and tumorigenesis have been well established, the role of PP-1 in carcinogenesis remains to be further explored. Moreover, PP-1 exists in different isoforms, whether these isoforms have differential functions in tumorigenesis remains to be examined. In the present study, we demonstrated that in lung cancer 1299 cells, PP1α and PP- 1 & γ exist in an antagonizing balance. In the parent H1299 cells, PP-1γ is dominant, about 4-fold higher than that of PP-1α. Overexpression of PP-1α significantly down-regulates PP-1γ at both mRNA and protein levels. In contrast, knockdown of PP-1α leads to upregulation of PP-1γ. Moreover, overexpression of PP-1α significantly attenuates the ability of the H1299 cells in promoting tumorigenicity as tested in immuno-deficient nude mice. This attenuation is derived from the halted cell cycle progression, which is largely attributed by the changed RB-E2F activity. Together, our results demonstrate that PP-1α and PP-1γ not only antagonize each other in lung cancer cells, but also display differential functions in tumorigenicity.
Assuntos
Neoplasias Pulmonares/metabolismo , Proteína Fosfatase 1/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/metabolismo , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Fosforilação , Proteína Fosfatase 1/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/ß, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aß lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aß gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/ß, are present in the proximal promoter of the mouse PP2A-Aß gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/ß all bind to PP2A-Aß gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/ß positively regulate the promoter of the PP2A-Aß gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/ß and the luciferase reporter gene driven by PP2A-Aß promoter further confirm their control over the PP2A-Aß promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/ß can all bind to the PP2A-Aß gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aß gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aß display distinct expression levels.
Assuntos
Regulação da Expressão Gênica , Proteína Fosfatase 2/genética , Proteína Proto-Oncogênica c-ets-1/fisiologia , Receptor X Retinoide alfa/fisiologia , Receptor X Retinoide beta/fisiologia , Fator de Transcrição Sp1/fisiologia , Fator de Transcrição Sp3/fisiologia , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Imunoprecipitação da Cromatina , Genes Reporter , Luciferases de Renilla/biossíntese , Luciferases de Renilla/genética , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , Proteína Fosfatase 2/metabolismo , Análise de Sequência de DNA , Ativação TranscricionalRESUMO
The small heat shock protein, α-crystallin, exists in two isoforms, αA and αB, and displays strong ability against stress-induced apoptosis. Regarding their functional mechanisms, we and others have demonstrated that they are able to regulate members in both caspase and Bcl-2 families. In addition, we have also shown that αA and αB may display differential anti-apoptotic mechanisms under certain stress conditions. While αA-crystallin regulates activation of the AKT signaling pathway, αB negatively regulates the MAPK pathway to suppress apoptosis induced by UV and oxidative stress. Although previous studies revealed that αA and αB could regulate members in both caspase and Bcl-2 families, the molecular mechanism, especially the in vivo regulation still waits to be elucidated. In the present communication, we present both in vitro and in vivo evidence to further demonstrate the regulation of caspase-3 and Bax by αA and αB. First, Surface Plasmon Resonance (SPR) and yeast two-hybrid selection analysis demonstrate that αA and αB directly bind to caspase-3 and Bax with differential affinities. Second, immunohistochemistry reveals that αA and αB regulate caspase-3 and Bax at different developmental stages of mouse embryo. Third, coimmunoprecipitation shows that αA and αB form in vivo interacting complexes with caspase-3 and Bax. Together, our results further confirm that αA and αB regulate caspase-3 and Bax in vitro and in vivo to regulate lens differentiation.
Assuntos
Caspase 3/metabolismo , Cristalino/embriologia , Cristalino/metabolismo , Cadeia A de alfa-Cristalina/metabolismo , Cadeia B de alfa-Cristalina/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Antígenos Virais de Tumores/metabolismo , Cinética , Camundongos , Ligação Proteica , Proteína Supressora de Tumor p53/metabolismoRESUMO
We hypothesize that bovine infections are responsible for the persistence of human schistosomiasis transmission in the Yangtze marshlands of China. To test this hypothesis, we are carrying out a comparative intervention among four administrative villages in the Poyang Lake region, Jiangxi Province, two of which are experimental and two are control. The primary design involves treating, at the onset of the study, all the inhabitants in all four villages with praziquantel and all the bovines in two villages (the experimental or intervention villages). Following treatment, rates of reinfection in people of all villages, and in bovines in the experimental villages, will be assessed as will the ongoing prevalence of infection in bovines in the control villages. Before treatment, the prevalence and intensity of infection among humans and bovines was ascertained in the four villages. Our study design and baseline information are presented here, along with a description of the ecology of the study villages.
Assuntos
Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/transmissão , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/transmissão , Adolescente , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/parasitologia , Criança , Pré-Escolar , China/epidemiologia , Reservatórios de Doenças , Feminino , Água Doce/parasitologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Vigilância da População , Praziquantel/uso terapêutico , Prevalência , Recidiva , Schistosoma japonicum , Esquistossomose Japônica/tratamento farmacológico , Caramujos/parasitologia , ZoonosesRESUMO
From November 1991 to March 1993, staining test with methylene blue was applied in 30 patients with the bladder cancer during operation. Twelve patients (40%) showed positive results, and 27 specimens were obtained from the stained areas. Histological examination proved that they were carcinoma in situ (11), transitional cell carcinoma (7), squamous cell carcinoma (4), dysplasia (3), chronic cystitis (1), and normal mucosa (1). The positive rate of histological results was 96.3%. 21 specimens from the unstained areas showed negative results. Six (33%) of 18 patients with single tumor and 6 (50%) of 12 patients with multiple tumor were positively stained. Follow-up from 10 to 26 months showed one patient (3.3%) had recurrence after 8 months.
Assuntos
Azul de Metileno , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/cirurgia , Coloração e Rotulagem , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
The effects of high-energy shock wave (HESW) on testes are still unknown. We investigated Wistar rats at 3 months of age for morphologic and functional changes in the testes and in serum follicle-stimulating hormone (FSH), progesterone (Prog), and testosterone (T). In an initial study, 12 rats received 1000 shocks at 19 kV directed at their testes using the JDPN-IV lithotripter. Two animals were sacrificed, and their testes were step-sectioned for light and electron microscopic examination on the operation day and on postoperation days one, two, four, eight, and sixty. There was angiectasis and congestion (58%) and focal hemorrhage (42%) in the testicular tissue, as well as mitochondrial swelling, reduction or disappearance of mitochondrial cristae (42%), and degranulation of the rough endoplasmic reticulum (33%) in spermatocytes. In the definitive study, groups of 10 rats were exposed to the same power index directed at their testes. One week after this exposure in Group 1 and at 3 and 6 weeks in Group 2, the animals were allowed to mate (one male paired with two females). There was no statistically significant difference in pregnancy rate or fetal number and weight in the female rats mated with the two groups of treated males at 3 weeks' gestation or in serum FSH, Prog, and T, or compared with the control group. Although there were temporary histologic changes in testicular tissue, the rat testes appeared to be functionally resistant to the shock wave energy levels used in this experiment.
Assuntos
Litotripsia , Testículo/citologia , Testículo/fisiologia , Animais , Retículo Endoplasmático/ultraestrutura , Feminino , Fertilidade/fisiologia , Hormônio Foliculoestimulante/sangue , Masculino , Microscopia Eletrônica , Mitocôndrias/ultraestrutura , Progesterona/sangue , Ratos , Ratos Wistar , Reprodução/fisiologia , Testículo/ultraestrutura , Testosterona/sangueRESUMO
Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Arginina Vasopressina/sangue , Sangue Fetal , Hipercapnia/sangue , Prenhez/sangue , Análise de Variância , Animais , Pressão Sanguínea , Eletrólitos/sangue , Feminino , Frequência Cardíaca Fetal , Hidrocortisona/sangue , Hipercapnia/fisiopatologia , Concentração Osmolar , GravidezRESUMO
Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hormônio Adrenocorticotrópico/sangue , Hemorragia/fisiopatologia , Fibras Nervosas/fisiologia , Renina/sangue , Sistema Nervoso Simpático/fisiologia , Nervo Vago/fisiologia , Vasopressinas/sangue , Animais , Feminino , Feto , Hemodinâmica , Hemorragia/sangue , Concentração de Íons de Hidrogênio , Gravidez , Ovinos , Fatores de Tempo , Gêmeos , VagotomiaRESUMO
Drug containing biodegradable poly(+/-)lactide microparticles were prepared by using a spray-drying technique. Formulations containing model drugs in either a dissolved (progesterone) or dispersed state (theophylline) were spray-dried. The spray-drying method was less dependent on the solubility characteristics of the drug when compared with traditional microencapsulation techniques such as phase separation or solvent evaporation techniques. Differential scanning calorimetry and scanning electron microscopy were used to characterize the microparticles. The drug release profiles were characterized by a rapid release phase (burst effect) followed by a slow release phase, the extent of each phase being dependent on the drug loading.
Assuntos
Poliésteres/análise , Biodegradação Ambiental , Química Farmacêutica , Microscopia Eletrônica de Varredura , Microesferas , Progesterona/análise , Solventes , Temperatura , Teofilina/análiseRESUMO
The effect of renal failure on melphalan pharmacology and toxicity has been poorly understood. Such information is of interest because melphalan is the most commonly used anticancer drug in the treatment of multiple myeloma, which is frequently associated with renal failure. We have studied the disposition and marrow toxicity of parenteral melphalan in dogs before and after induction of renal failure with subtotal nephrectomy. The surgical procedure decreased the creatinine clearance by an average of 62% (P = 0.001). The lowest neutrophil counts following i.v. melphalan (1 mg/kg) averaged 4.9 x 10(3)/mm3 pre-nephrectomy and 0.9 x 10(3)/mm3 post-nephrectomy, respectively (P = 0.002). The mean lowest recorded platelet counts after melphalan (1 mg/kg) were 115 x 10(3)/mm3 in the pre-nephrectomized dogs, and 9.7 x 10(3/mm3 in those who had been nephrectomized (P = 0.002). Following nephrectomy, i.v. melphalan's terminal-phase plasma half-life and renal clearance were both raised (P = 0.02) to 75% over pre-nephrectomy values. These studies show that i.v. melphalan-induced myelosuppression is markedly increased and its plasma elimination and renal clearance significantly decreased in the presence of renal dysfunction in dogs. These data suggest that parenteral melphalan's starting dose be decreased by at least 50% when used in myeloma patients with renal failure.