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.     

Delayed elevation of plasma endothelin-1 during unilateral alveolar hypoxia without systemic hypoxemia in humans

Background: The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. We investigated whether endothelin-1 (ET-1) could be detected in plasma during pulmonary alveolar hypoxia without systemic hypoxemia (one-lung hypoxia) and whether the levels could be related to hemodynamic status in humans.
Methods: Thirteen adult patients with primary lung carcinoma were studied prior to surgery. Anesthesia was induced with fentanyl, diazepam, and pancuronium iv. Differential lung ventilation was performed for 40 min. The right lung was ventilated with a mixture of 6% O₂, 5% CO₂ and 89% N₂ and the left lung ventilated with 100% O₂. Blood gas values, hemodynamic parameters, and plasma ET-1 levels were measured.
Results: Mean pulmonary artery pressure increased from 13.±3.5 to 17.·3.2mm Hg ( P <0.01) after 20 min of one-lung hypoxia. The plasma ET-1 levels in arterial blood and wedged right pulmonary arterial blood increased from 1.69M.61 to 2.13 ±0.48 μg/ml ( P <0.01) and from 1.75±.47 to 2.26±.40 μg/ ml ( P <0.001), respectively, after 40 min of one-lung hypoxia.
Conclusions: We concluded that ET-1 may play a supporting, but not a primary, role in human hypoxic pulmonary vasoconstriction.     

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.     

Effects of ATP on Phosphoinositide Hydrolysis and Prostaglandin E2 Generation in Rabbit Astrocytes

Extracellular ATP secreted from stimulated nerves plays a role in neurotransmission. This study examined the effects of extracellular ATP on phospholipase A₂ and C signalling pathways in rabbit astrocytes. ATP caused prostaglandin E₂ (PGE₂) generation and phosphoinositide hydrolysis in a time- and concentration-dependent manner. A P_2y purinoceptor-selective agonist, 2-methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE₂ generation. A P_2x purinoceptor-selective agonist, α,β-methylene-ATP did not cause either phosphoinositide hydrolysis or PGE₂ generation. Although pertussis toxin had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it markedly decreased ATP-induced PGE₂ generation, with significant inhibition of phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently inhibited ATP-induced PGE₂ generation, caused partial inhibition of phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase metabolites of arachidonic acid. These results suggest that a stimulation of P_2y receptor results in phospholipase C activation in a pertussis toxin-insensitive manner, and that a P₂ receptor other than the P_2y or P_2x subtypes is involved in ATP-induced phospholipase A₂ activation via a pertussis toxin-sensitive G protein.     

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.