Antiemetic Efficacy of High-Dose Intravenous Metoclopramide and Dexamethasone in Patients Receiving Cisplatin-Based Chemotherapy: A Randomized Controlled Trial

High-dose intravenous (IV) metoclopramide has shown efficacywith few side effects for the treatment of nausea and vomitingon the day of cisplatin administration. From November 1984 toJanuary 1986, two randomized trials in an antiemetic study wereconducted. In trial I, the antiemetic effect of a short courseof high-dose dexamethasone was compared with that of high-dosemetoclopramide in 29 patients with lung cancer receiving chemotherapycon taining cisplatin (80 mg/m² IV) in a randomized controlledtrial. Dexamethasone was given IV at a dose of 16 mg 1/2 hrbefore and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin.Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr beforeand 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emeticcontrol (0–2 episodes of vomiting) during the 24 hr aftercisplatin administration was achieved in 55% (6/11) and 67%(12/18) of the patients receiving dexa methasone and metoclopramide,respectively, without serious toxicity. The dura tion of nauseaor anorexia was similar for the two treatment groups. In trial11, the combination of metoclopramide and dexamethasone wascompared with metoclopramide alone to assess the additive antiemeticeffect of the two drugs in 23 patients with lung cancer receivingcisplatin at a dose of 120 mg/m IV in a randomized cross-overstudy. A major antiemetic response was observed in 27% (3/11)and 92% (11/12) of the patients receiving metoclopramide aloneand metoclopramide plus dexamethasone, respectively (p <0.005). The duration of nausea and anorexia was similar forthe two treatment groups. Pa tients tended to prefer the combinationof metoclopramide and dexamethasone; however, the differencewas not statistically significant (p = 0.14) in the small numberof patients entered in this study. Despite excellent controlof acute chemotherapy-induced emesis, 45% of 52 patients experienceddelayed nausea and vomiting more than 24 hr after cisplatinadministration even among those who had had an excellent short-termresponse to the antiemetic agents.     

Successful treatment of virus-associated haemophagocytic syndrome in adults by cyclosporin A supported by granulocyte colony-stimulating factor

Two young adult patients with typical virus-associated haemophagocytic syndrome (VAHS) were treated with cyclosporin A and granulocyte colony-stimulating factor (G-CSF). Clinical symptoms such as high fever and malaise disappeared rapidly with concurrent haematological improvement in both patients. The serum levels of interleukin-6 (IL-6), soluble IL-2 receptor, tumour necrosis factor and macrophage-CSF were all elevated before treatment but that of G-CSF was not. The dramatic effect of cyclosporin A observed implies that it efficiently and rapidly suppresses the cytokine storm caused by dysregulated T cells in VAHS. In addition, G-CSF may promote haematological recovery without syndrome regression. We believe that the combination of cyclosporin A and G-CSF may be effective, at least in selected patients with VAHS. Further studies are required to confirm its role as first-line therapy for adult patients with VAHS.     

Pneumomediastinum in newborns induced by the Elder CPR/demand valve during resuscitation

Two term and one post-term newborn infants with pneumomediastinum associated with the use of an Elder CPR (cardiopulmonary resuscitation)/demand valve during resuscitation are described. Because of apnea or irregular gasping respiration after vaginal delivery, they received repetitive positive-pressure ventilation with this resuscitator, which is designed to provide 100% oxygen with a limited pressure of up to 40 cmH₂O. Following resuscitation, the infants had tachypnea and diminished breath sounds. Roentgenograms and computed tomography of the chest revealed pneumomediastinum in all three and cervical subcutaneous emphysema in one. They required 25–30% oxygen for 3–14 days until they recovered spontaneously. Thus, pressures as low as 40 cmH₂O can cause barotrauma, and the Elder resuscitator, even when functioning properly, may injure the lungs of newborn infants.     

Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats

Abstract The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.     

Urethral metastasis from renal cell carcinoma

A case of metastasis to the prostatic urethra after transurethral resection of the prostate from a previously resected renal cell carcinoma (RCC) is reported here. Solitary urethral metastasis from RCC is extremely rare. Only four cases of urethral metastasis from RCC have been previously reported in the literature.     

Preschool sarcoidosis manifesting as juvenile rheumatoid arthritis: A case report and a review of the literature of Japanese cases

Nine Japanese cases of sarcoidosis in children of 4 years of age or younger have been reported in the literature, including the case presented here. Clinically, preschool sarcoidosis is distinctly different from that of older children; it is characterized by a triad of skin, joint and eye lesions without pulmonary involvement. It is easily confused with juvenile rheumatoid arthritis which also presents the symptoms of arthritis and uveitis. We report on a patient with preschool sarcoidosis who was initially diagnosed as having juvenile rheumatoid arthritis. We recommend prompt skin biopsy to differentiate between these conditions.     

Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress

Abstract We found inhibitory effects of antidepressants (clomipramine, maprotyline, mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating hormone (TSH) release induced by ether stress in freely moving rats. We confirmed that ether stress suppressed the plasma TSH levels after 30 min. We then injected intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine, 2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5-HTP simultaneously. These materials blocked the influences on plasma TSH levels by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and 5-HTP (precursor of serotonin) had a higher potency against the ether stress. These results suggest that antagonizing effects against the ether stress may involve the serotonergic system in the pituitary gland.     

Achondroplasia: Recent advances in diagnosis and treatment

Achondroplasia (ACH) is the most common form of chondrodysplasia in humans. This disorder is inherited as an autosomal dominant trait, though most cases are sporadic. Recent advances in molecular biology have revealed its genetic defect in fibroblast growth factor-3 gene. This may introduce a new diagnostic tool and the classification of ACH and related disorders. Recent molecular engineering techniques have made it possible to provide large amounts of the various kinds of biofactors, such as erythropoietin, granulocyte colony stimulating factor and human growth hormone (GH), for clinical use. In fact, GH has been widely used to treat non-GH-deficient forms of short stature, such as Turner's syndrome, skeletal dysplasia, intrauterine growth retardation, chronic illness and idiopathic short stature, with beneficial effects. This may also be introduced into the medical management of ACH.     

Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein-2 protein localization in primary rat hepatocytes

Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments, including primary liver non-function. However, the cellular mechanism by which HBO treatment ameliorates liver function is not understood. Therefore, the purpose of this study was to elucidate this cellular mechanism using primary cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO at 1 day after plating, and the morphological and functional characteristics of bile canaliculi formed in cultured hepatocytes were observed by time-lapse microscopy. Multidrug resistance protein-2 localization was observed by confocal laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at 2 days after treatment was significantly higher than that in the control group. In addition, the proliferating cellular nuclear antigen level in the HBO group was significantly higher than that in the control group. The contraction of the bile canaliculi in the HBO group was slower than in the control group and the dilatation of bile canaliculi in the HBO group was much larger than in the control group. Multidrug resistance protein-2 in the HBO group was localized at the apical membrane. These results show that HBO stimulates hepatocytes to proliferate and HBO normalizes multidrug resistance protein-2 localization to the apical membrane, which could dilate bile canaliculi.