Correlation between magnesium pre-loading and cisplatin-induced nephrotoxicity in 5-fluorouracil/cisplatin combination therapy for esophageal cancer.

The use of cisplatin may cause nephrotoxicity in patients. Hydration solutions supplemented with magnesium could reduce cisplatin-induced nephrotoxicity. In this study, we evaluated the preventive effect of magnesium pre-loading on cisplatin-induced nephrotoxicity in patients with esophageal cancer. We retrospectively evaluated the prevalence of, and risk factors for, nephrotoxicity in 160 patients with esophageal cancer treated with the 5-fluorouracil/cisplatin regimen from 2014 to 2016 with and without magnesium supplementation. Significant differences were observed between the magnesium and non-magnesium groups in terms of frequency of estimated creatinine clearance of grade 2 or higher that was at 4% (n = 3) and 13% (n = 10) (p = 0.027), respectively. The logistic regression analysis revealed that eCcr of grade 2 or higher was significantly associated with the non-magnesium regimen (odds ratio (OR), 4.175; 95% confidence interval (CI) = 1.061-16.430; p = 0.041) and age ≥ 65 years (OR, 13.951; 95% CI = 1.723-112.974; p = 0.014). This study suggests that 20 mEq magnesium pre-loading significantly reduces the prevalence of cisplatin-induced nephrotoxicity. Furthermore, when cisplatin is administered to individuals older than 64 years, a close observation for the onset of cisplatin-induced nephrotoxicity is crucial.

Predicted trends in the supply and demand of veterinarians in Japan.

Currently in Japan, there are 32,000 active veterinarians, mainly engaged in small and large animal practice and public animal health and public health services. In the face of the notable increase in recent years in the proportion of female students enrolled in veterinary schools and in the number of households with companion animals, a model was developed to predict the supply and demand of veterinarians toward 2040 in Japan. Surveys were conducted on sampled households and veterinarians to estimate input variables used in the supply and demand model. From this data it is predicted that there might be somewhere between a shortage of 1,000 to an over-supply of 3,700 veterinarians engaged in small animal practice in 2040. This, however, will depend on possible changes in the number of visits made to veterinarians by small animal owners and the efficiency of practices in the future. The model also predicts that there will be a shortage of around 1,100 veterinarians in large animal practice in 2040. Considering the many assumptions made to estimate the input variables used in the model, the results of this study do not provide definitive conclusions, but provide a base for discussions on what will be needed in the veterinary profession in the future.

A case of refractory uremic pleuropericarditis--successful corticosteroid treatment.

We report the case of a patient with uremic pleuropericarditis who showed a marked improvement following corticosteroid therapy. A 66-year-old man who had been on hemodialysis therapy for 13 years was admitted to our hospital presenting with increases in bilateral pleural effusions and pericardial effusion. Repeated thoracentesis showed hemorrhagic and exudative findings. Pleural and pericardial fluid cytologic examination, bacterial culture and acid-fast staining showed negative findings. Despite the administration of antibiotics and antituberculosis drugs, low-grade fever continued and C-reactive protein level remained high. A pleural biopsy revealed fibrinous pleuritis without infectious disease or malignancy. He was diagnosed as having uremic pleuropericarditis on the basis of the clinicopathological features, but had been unresponsive to conventional treatments including repeated thoracentesis and the continuance of hemodiafiltration using nafamostat mesylate. Ultimately, both pleural and pericardial effusions were controlled after the treatment with prednisolone at an initial dose of 50 mg per day. In conclusion, corticosteroid therapy seems to be useful for treating patients with conventional therapy-resistant uremic pleuropericarditis.

Rapidly progressive glomerulonephritis in a patient with Chlamydia pneumoniae infection: a possibility of superantigenic mechanism of its pathogenesis.

Herein we describe a case of a patient with rapidly progressive glomerulonephritis after Chlamydia pneumoniae infection. An 88-year-old woman who had had C. pneumoniae infection two months previously was admitted to our hospital with complaints of dyspnea and generalized edema. Laboratory tests revealed acute renal failure, polyclonal hypergammaglobulinemia, highly increased level of C-reactive protein, and hematoproteinuria. A renal biopsy revealed mesangial and endocapillary proliferative glomerulonephritis with crescents. She responded to high-dose steroids, cyclophosphamide, minocycline, and plasma exchange treatment with the remission of oliguric renal failure. The percentage of the subset of CD3+ TCR+ Vbeta11+ cells markedly increased to 9.6% (normal range: < 1.04%) at the onset of the disease and decreased to 0.1% after the treatment. These clinicopathological features were similar to those of superantigen-associated glomerulonephritis after methicillin-resistant Staphylococcus aureus infection. We suggest that the superantigenic mechanism is one of the possible pathomechanisms of this glomerulonephritis.

Roles of and correlation between alpha-smooth muscle actin, CD44, hyaluronic acid and osteopontin in crescent formation in human glomerulonephritis.

BACKGROUND: alpha-Smooth muscle actin (SMA), CD44, hyaluronic acid (HA) and osteopontin (OPN) are involved in crescent formation; however, the correlation between these molecules during the formation and progression of the crescents in human glomerulonephritis (GN) has not been fully evaluated. METHODS: To investigate the expression of alpha-SMA, CD44, HA, OPN and CD68 renal biopsy specimens from 14 patients with crescentic GN were examined by immunohistochemistry. All crescents were separated into cellular, fibrocellular and fibrous. The extent of staining in each crescent was scored semiquantitatively. The change in the expression of each molecule and its correlation with other molecules during the formation and progression of the crescents were estimated statistically. RESULTS: The expression of alpha-SMA was significantly up-regulated in the fibrocellular crescents compared with that in the cellular and fibrous crescents. The expression of CD44, OPN and CD68 was significant in the cellular crescents compared with that in the fibrocellular and fibrous crescents. The deposition of HA in the three groups of crescents was high level. However, that of HA was not significant among three groups of crescent. The expression of CD44 in the cellular crescents correlated significantly with the expression of OPN and CD68, and the deposition of HA in the cellular crescents. The expression of OPN in the cellular crescents correlated with the deposition of HA and the expression of CD68 in the cellular crescents. The expression of alpha-SMA in the cellular and fibrocellular crescents correlated with the deposition of HA in the cellular and fibrocellular crescents. CONCLUSION: The expression of CD44, HA, OPN and CD68 was up-regulated at the early stage of the crescent formation in human crescentic GN. Moreover, myofibroblasts and cell-matrix interactions mediated by the CD44-OPN and CD44-HA receptor-ligand pairs may play important roles in the formation and progression of the crescents.

A case of elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation.

Herein we describe a case of a patient with elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation. A 78-year-old man was admitted to our hospital with fever and generalized lymphadenopathy. He was diagnosed as having systemic lupus erythematosus on the basis of renal involvement, hematological abnormality and positivity for antinuclear and anti-double-stranded DNA antibodies. Renal biopsy revealed lupus nephritis (class III and V (A/C)) with focal glomerular thrombosis. He responded to hemodialysis and corticosteroid therapy with remission of serological values and renal function. Possible mechanisms underlying the coexistence of these conditions are discussed.

Perineal-onset Fournier's gangrene in a patient undergoing hemodialysis--importance of perineal-onset manifestation.

We present a rare case of perineal-onset Fournier's gangrene in a patient undergoing hemodialysis. A 51-year-old Japanese man manifested an acute-onset perineal pain with perirectal abscess; subsequently, the pain extended to the abdomen, chest, and loin despite quick treatment. His consciousness deteriorated to delirium and he died of septic shock on the third day of admission. Computed tomography (CT) revealed soft-tissue air along the right rectal wall, moreover, the infection extended to the anterior wall of the bladder and the right peripsoas muscle. On the basis of the clinical course and CT findings, the patient was diagnosed as having the complications of Fournier's gangrene, however, no scrotal lesions were detected. Fournier's gangrene is considered to be easily diagnosed on the basis of skin lesions, such as scrotal erythema and swelling. However, in the early stage, the diagnosis of Fournier's gangrene is difficult in a patient with perineal pain before the detection of skin lesions. In conclusion, definitely the key to improving the prognosis of this fulminant infection is the prompt recognition of the pathological process. Therefore, Fournier's gangrene should always be considered when patients undergoing hemodialysis manifest perirectal disorders, even when no scrotal lesions are detected, because there is the possibility of intra-abdominal and intra-retroperitoneal infections resulting in septic shock.

An immunocytochemical and electron microscopic study of the hyt mouse anterior pituitary gland.

The hyt mutant mouse used in this study has a hypoplastic thyroid gland and is characterized by retarded somatic growth, very low to undetectable levels of plasma thyroxine (T4), and increased levels of plasma thyroid-stimulating hormone (TSH). This congenital hypothyroid mouse is therefore an ideal model for studying the effects of thyroid hypofunction on the adenohypophysis. The anterior pituitary of the hyt mouse appeared less granular than that of the normal control when viewed by light microscopy, owing to a decrease in the population of somatotrophs. Many cells, in various stages of transformation into 'thyroidectomy cells', were recognized by the appearance of the characteristic granules and dilated rough endoplasmic reticulum. In some cases, the enlarged rough endoplasmic reticulum also contained spherical electron-dense secretory granules. In addition there were many cells undergoing mitosis and these were identified as thyrotrophs by their characteristic granules. Administration of T4 during the first 40 days of life prevented the abnormal changes in the hyt anterior pituitary. A reduction in immunoreactive thyrotrophin-releasing hormone (TRH) levels was seen in the median eminence of the hyt mouse. Treatment with T4 restored this to normal, suggesting that the reduced TRH content of the hypothalamus of the mutant mouse may be due to T4 deprivation.

The influence of endocrine factors on the serum concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding proteins.

Serum insulin-like growth factor-I (IGF-I) levels in lit (isolated GH deficiency), dw (panhypopituitarism), hyt (hypothyroidism) and cog (congenital goiter) mutant mice were found to be significantly lower than in control mice. In addition, liver and kidney IGF-I concentrations in mutants were also found to be significantly reduced compared with controls. These differences in IGF-I concentration were not observed in pg (genetic IGF receptor or post-receptor defect?) mice. These results indicated that serum IGF-I production is induced by thyroid hormones as well as by GH. Western blot analysis of serum IGF-binding protein (IGFBP) fractions revealed the following differences among the five mutants: the triplet of IGFBP-3 (42, 45 and 49 kDa) and IGFBP-4 (24 kDa) levels were significantly reduced. IGFBP-2 (32 kDa) levels were also reduced in the lit, hyt and cog mice, although the level in serum of dw mice was found to be greatly elevated. No differences in serum IGFBP levels were found in the pg mouse. Consequently, the ratio of IGFBP-3%: IGFBP-2% (the percentage of IGFBP-3 fraction of total IGFBP (IGFBP-3%) divided by that of IGFBP-2 (IGFBP-2%)) was decreased in GH-deficient mice but increased in hypothyroid mice, suggesting that IGFBP-3 and IGFBP-2 production in the liver is induced by GH and thyroid hormones respectively.

Reduced vasoactive intestinal polypeptide immunoreactivity in the pituitaries of hormone-deficient mutant mice.

The prolactin-producing cells of the bovine anterior pituitary were found to contain a vasoactive intestinal polypeptide (VIP) immunoreactive substance, thus suggesting a role for VIP in the regulation of prolactin release. The pituitaries of the dw and lit strains of mutant mice, congenitally deficient in prolactin-producing cells, and hyt mice, which were found to have reduced numbers of prolactin-producing cells, showed a markedly reduced VIP immunoreactivity. Hypothalamic VIP immunoreactivity, however, was found to be unchanged in the three strains of mutant mice, indicating that the high concentration of VIP in the hypothalamus does not derive from the adenohypophysis through retrograde flow. The deficiency in the mutant mice seems to be due to the lack of prolactin target cells in the pituitary.

Retarded growth of the suprachiasmatic nucleus and pineal body in dw and lit dwarf mice.

The suprachiasmatic nucleus (SCN) and the pineal body in 3 types of inherited hormone-deficient mice, the dw, lit and hyt mice were examined by morphological, morphometric and biochemical techniques. In the dw and lit mice the SCN was underdeveloped. In the ventral part of the SCN, where most of the retinal fibers appeared to terminate, both cell number and cell size were decreased, although the size of the SCN was unaltered. In addition, the pineal bodies of both mice were morphologically underdeveloped and showed low levels of N-acetyltransferase activity. In contrast, the hyt SCN was comparable to the normal controls in every respect. The hyt pineal was well developed and showed levels of enzyme activity comparable to the controls. However, in all the deficient mice, the optic nerve appeared to be normal in morphological and biochemical studies. These results suggest that the underdevelopment of the pineal body, the reduced levels of spontaneous locomotion and the indistinct diurnal periodicity of the dw and lit mice might be related to the retarded neuronal growth of the SCN, and that growth hormone likely is indispensable for the development of the SCN.

Faulty development of cortical neurons in the Snell dwarf cerebrum.

In the Snell dwarf motor cortex, area 6 of Caviness, the cell number, the stratification of neurons and the portion of layer-widths were absolutely identical to those of the controls. By means of the Golgi-Cox method modified by Ramon-Moliner, however, the pyramidal neuron was found to have small perikarya, short primary dendrites with sparse branchings, and a low spine density on the dendrites. The corpus callosum of the dwarf contained a reduced number of fibers compared to that of the controls, and the staining for myelin basic protein revealed a considerable reduction of positive-fibers of radiation in this area. The content of Thy-1 antigen in the cerebrum, cerebellum and brainstem, was significantly lower than that of controls, but the monoamine content was normal in the cerebrum and brainstem. From these results, it appears that the Snell dwarf cerebrum shows retarded neuronal growth; a reduction in size of neurons, an underdevelopment of axons and dendrites, and a retarded maturation of spine, in addition to arrested glial proliferation. At present, it is unclear which hormone deficient in these mutants, growth hormone or thyroxine, is the essential potentiator for neuronal growth.

Hippocalcin expression in the brain of the Snell dwarf mutant mouse.

To determine factors contributing to the expression of the brain-derived protein, hippocalcin, we mapped its distribution in the brain of Snell pituitary dwarf mutant mice (dw) by immunohistochemical and immunoblot methods. Our findings are as follows. (1) In the hippocampus, hippocalcin immunoreactivity was found in the cell body and dendrites of pyramidal neurons of the normal controls and dw mice, although the intensity of immunoreactivity in the dw mice was lower. (2) In the cerebellum, hippocalcin immunoreactivity was strongly expressed in the Purkinje cell body of both the control and dw mice. However, the Purkinje cell dendrites were found to be more intensely stained in the dw mice than in the normal controls. (3) In the dw cerebral cortex, the pyramidal neurons of layers II to VI strongly expressed hippocalcin, whereas its expression in the controls was weak. (4) The amount of hippocalcin in the dw hippocampus was less than in the normal controls, whereas the amount in the dw cerebral cortex and cerebellum was greater. These results indicate that the developmental expression of hippocalcin in the dw brain is affected by the retarded maturation of the neuronal network due to the deficient hormonal state (the lack of growth and thyroid hormones).

Alteration of cerebral ganglioside metabolism in developing Snell dwarf mice.

The ganglioside metabolism of the Snell dwarf cerebrum was examined on postnatal days 15 and 20, by monitoring the rate of incorporation of radioactivity into each ganglioside species from tritiated N-acetyl-D-mannosamine. It was found that the turnover rate of the GM3 ganglioside was reduced throughout the entire period of development, resulting in retardation of A pathway metabolism which becomes abundant during late cerebral development. In addition, the turnover rate of the GM4 species, which is considered related to myelin formation, was also found to be reduced throughout the entire period of cerebral development.

Microcephalic cerebrum with hypomyelination in the pygmy mouse (pg).

To determine whether somatomedin has a direct action on cerebral development instead of an indirect action of a growth hormone, we examined the central nervous system of the pygmy mouse (pg), a mutant with normal somatomedin activity. Our findings are: (A) the weights of the pg/pg cerebrum and cerebellum weighted were significantly less than those of the normal controls (pg/+), 14 and 15% less, respectively; (B) the total DNA content was reduced by 17% in the cerebrum and cerebellum of the pg/pg mouse; (C) the total RNA content was reduced in the cerebrum and cerebellum, proportional to the reduction in DNA; (D) CNPase activity was reduced selectively in the cerebrum of the pg/pg mouse by 25%; and (E) the pg/pg mice exhibited a strikingly reduced level of activity with an indistinct diurnal periodicity. Therefore, the present findings suggest that the action of somatomedin on the proliferation and maturation of glial cells might be a necessary precondition to myelin formation.

A case of acute diffuse interstitial nephritis due to sulpyrine.

Sulpyrine is commonly used in Japan. We report a case of acute renal failure due to acute tubulointerstitial nephritis (ATIN), which we believe was associated with the use of sulpyrine.

A case of immunotactoid glomerulopathy with unusual microtubular deposits.

A 57-year-old man with monoclonal gamma-globulinemia was admitted because of edema and proteinuria. A renal biopsy specimen showed lobular glomerulonephritis associated with deposition of material that was positive for IgG, C3, C1q, fibrin, kappa light chain, and lambda light chain but was not stained by Congo red. Glomeruli showed massive electron-dense deposits with two kinds of unusual, highly organized crystalline structures in the mesangial matrix and peripheral capillary loops. Clinically, the patient had nephrotic syndrome, microscopic hematuria, and hypertension. No Bence-Jones protein or cryoglobulin was found in the urine or serum. Immunoelectrophoresis of blood and urine revealed increased IgG-lambda paraprotein, but no free light chains were found. This case was not associated with amyloidosis, systemic lupus erythematosus, light chain deposition disease, cryoglobulinemia, or multiple myeloma. Immunotactoid glomerulopathy was diagnosed. Treatment with oral prednisone was effective for the management of nephrotic syndrome and renal dysfunction. Glomerular deposition of two kinds of microtubular structure in immunotactoid glomerulopathy has rarely been reported.

A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus.

A 38-year-old man developed severe diabetic ketoacidosis complicated with rhabdomyolysis and acute renal failure after presenting hyperglycemic symptoms for 4 days. Initial investigation showed significant hyperglycemia (blood glucose level 1,593 mg/dl) with a relatively low level of HbA1c (7.0%) and a high pancreatic enzyme concentration without any signs of pancreatitis. Diabetes-related antibodies were absent except for the anti-glutamic acid decarboxylase antibody, which disappeared later on. Pancreatic biopsy examination showed the lack of insulin-secreting cells, without insulitis. These findings were almost consistent with non-autoimmune fulminant type 1B diabetes. The patient remained dependent on dialysis for 1 month, then his renal function recovered. In patients with this type of diabetes, the onset of overt diabetes, frequently accompanied with severe diabetic ketoacidosis, is rapid, hence, early detection, quick diagnosis and immediate treatment of this novel type of diabetes are important in the rescue of these patients.

A case of lupus nephritis with alteration of the glomerular basement membrane associated with Takayasu's arteritis.

A 47-year-old Japanese woman with both Takayasu's arteritis (TA) and systemic lupus erythematosus (SLE) presented with unequal pulses in the upper extremities, diarrhea and proteinuria. In 1986, when she was 38 years old, angiography revealed stenosis of the left subclavian artery. In 1994, SLE was diagnosed on the basis of clinical and laboratory findings, including renal dysfunction, hematologic and immunologic abnormalities, a high titer of antinuclear antibody and a positive lupus band test on the skin. Renal biopsy showed lupus nephritis and glomerular lesions with a bubble-like appearance of the glomerular capillary wall with TA. Lupus nephritis coexisting with glomerulonephropathy associated with TA has rarely been reported.

[Six-month chronic subcutaneous toxicity study of cefodizime sodium in rats].

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.