Studies on the optimal treatment period and parameters for detection of male fertility disorder in rats--introductory summary.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Akaike.
Explore the source record for details and available documents.
Pyridoxine (PN) was intraperitoneally given at 250 and 500 mg/kg to male rats for 2, 4, or 6 weeks, and its effects on male fertility evaluated in terms of the optimal treatment period and detection parameters. Animals of all PN groups showed depression of body weight gains from week I of treatment onwards, significant at all but the 250 mg/kg 2 week administration I week time point. After 2 weeks treatment, the testes demonstrated only very slight histopathological changes. The 4- and 6-week treatments caused decreased spermatozoal motility and some histopathological changes in the testes including degeneration of germinal epithelial cells with both doses and also decreases in the fertility index and mean velocity of sperm, reduction in the testes and epididymides weights, and changes in testicular proteins. In the animals undergoing a 4-week recovery period following 4 or 6 weeks exposure, changes disappeared with the 250 mg/kg dose, but still remained with 500 mg/kg. From these findings, it is concluded that a treatment period of 4 weeks is sufficient for evaluation of drug effects on male fertility and that histopathology can detect the slightest toxic effects on the testis.
An 84-year-old man was referred to our hospital on December 3, 1993, because of excessive bleeding after tooth extraction. Coagulation studies revealed thrombocytopenia (2.2 x 10(4)/microliter), increased serum levels of FDP-E (3172 ng/ml) and D dimer (42.6 micrograms/ml), and increased plasma levels of thrombin-atithrombin III complex (48.0 ng/ml) and plasmin-alpha 2-plasmin inhibitor complex (6.8 micrograms/ml). Computed tomography showed bilateral common iliac artery aneurysms. A diagnosis of DIC due to bilateral common iliac artery aneurysms was made. Heparin (10,000 U/day) administered to treat DIC resulted in good control, and operative repair of the aneurysms was successful. This is the second reported case of isolated iliac artery aneurysms associated with DIC.
The patient was a 51-year-old female, underwent total gastrectomy for gastric cancer 6 years ago. She was admitted to a local hospital with the complaint of fever, the chest X-ray showed niveau in the left pleural cavity. Fecal material flowed out by drainage. Barium enema showed fistula of diaphragma from transverse colon. She was transferred to our hospital. Partial transverse colon resection and removal of the diaphragma fistula were performed. The colon tumor was histologically determined to be metastasis from gastric cancer with thoracic empyema.
The mode of inheritance of Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) have not yet been established, since most cases are sporadic. We studied skeletal muscle pathology and mitochondrial DNA (mtDNA) in a sporadic KSS patient (proband) and examined mitochondrial function of the muscle in his asymptomatic family members. The proband was a 56-year-old male with bilateral ptosis, external ophthalmoplegia, retinal degeneration and cardiac conduction disturbance. Biopsied deltoid muscle showed 9.7% of ragged red fibers without cytochrome oxidase (COX) activity and abnormal mitochondria on electron microscopy. Analysis of muscle mtDNA revealed a 4,977 bp deletion between nt. 8,483 and 13,459. None of the family members had symptoms similar to those of the proband. However, an aerobic exercise test of 15W for 15 minutes with an ergometer induced a marked increase in serum lactate levels in the proband's mother. Histology of her biopsied deltoid muscle showed 0.3% of ragged red fibers without COX activity and morphologically abnormal mitochondria. These findings indicate that the abnormal mitochondria of the proband were transmitted from his asymptomatic mother. This also suggests that some of the sporadic KSS/CPEO cases are inherited one.
The usefulness of four spatial maze learning test methods, single T-maze, Biel water maze, Morris water maze, and radial eight-arm maze, was compared using rats with different degrees of microcephaly, which were induced by single intraperitoneal injection with 3 and 5 mg/kg of methylnitrosourea (MNU) on day 13 of gestation. The single T-maze test did not detect a learning defect in either MNU group. In the Biel water maze test, the swimming time and number of errors were increased in the 5 mg/kg group, but these parameters were comparable to the control values in the retention and path B (reverse course) tests. On the Morris water maze task, the 5 mg/kg group required longer swimming time and distance to reach the goal. In the retest with the goal set on an opposite side, the swimming distance in the 5 mg/kg group was as long as the value in the original test. The radial eight-arm maze test detected fewer correct choices in both MNU groups, which showed different responses on this task. The brain weights in the 3 and 5 mg/kg groups were approximately 80 and 60% of the control value, respectively. The cerebral cortex weights were 77 and 50% of the control value, and the hippocampus weights were 78 and 51%. Among the four maze tests, only the radial eight-arm maze test could detect the effect of both doses of MNU. This shows that the method has the highest sensitivity to spatial learning defect in MNU-induced microcephalic rats.
To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC. Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 +/- 1.3% and was significantly higher than that in patients without recurrence (1.4 +/- 0.5%, P < 0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% (P < 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.
We report a patient with Takayasu's arteritis associated with antiphospholipid antibodies. An 84-year-old woman gradually developed gait and visual disturbances, dementia, myocardial infarction, and gangrene in all four limbs during a period of 8 years. Persistent inflammatory signs also continued for at least 8 years. Positive reaction for lupus anticoagulant by the diluted Russel viper venous time and positive reactions for cardiolipin antibodies were confirmed. However, she did not develop SLE. MR angiography revealed multiple and extensive occlusive changes in large vessels such as the aorta and its major branches. We believe antiphospholipid antibodies may have been related to severe occlusive vasculopathy in this patient.
To clarify the natriuretic action of endogenous atrial natriuretic peptide (ANP) in patients with essential hypertension (EHT), we examined the relationship between ANP release and urinary sodium excretion in response to hypertonic saline infusion. Plasma ANP levels increased from 13.3 +/- 2.0 pg/ml to 37.0 +/- 3.0 pg/ml in patients with EHT and from 9.2 +/- 1.5 pg/ml to 21.1 +/- 4.0 pg/ml in normal subjects after the infusion. The area under the curve (AUC) of plasma ANP response was significantly higher in patients with EHT than in normal subjects (P < 0.05). There was a significant positive correlation between AUC and urinary sodium excretion in both groups (P < 0.01). However, the ratio of urinary sodium excretion to AUC was significantly lower in patients with EHT than in normal subjects (P < 0.01). These results suggest that impaired natriuretic response to endogenous ANP is one of the factors responsible for the development of EHT and that enhanced secretion of ANP in response to hypertonic saline infusion is a compensatory mechanism to the impaired natriuretic action of ANP in patients with EHT.
Patients with Becker muscular dystrophy (BMD) have milder muscular impairment and better prognosis than patients with Duchenne muscular dystrophy (DMD). Another difference is that while cardiac failure due to myocardial involvement is a frequent cause of death in BMD, respiratory failure is the most common cause of death in DMD. We examined cardiac function and the mechanism of cardiac failure in 21 BMD patients aged 3 to 63 years (mean, 40.4) by electrocardiography, mechanocardiography, echocardiography, and post-mortem examination. Diagnosis of BMD was made by characteristic symptoms, dystrophic change in muscle histology, and the followings: 1) a deletion in the dystrophin gene, 2) "patchy" staining of dystrophin on immunocytochemical analysis, 3) abnormal dystrophin size on Western blotting, and 4) presence of a definite carrier in the family. To be diagnosed as BMD, patients exhibited one or more of 1)-3). Patients who were diagnosed only by 4) had a relative who had been diagnosed as BMD by one of 1)-3). The control group included 43 DMD patients (age 4-26 years, mean 16.2) and 20 healthy males (age 15-60 years, mean 33.3). Electrocardiogram showed prominent Q waves in leads II, III, aVF and V6, and tall R in V1, suggesting myocardial injury in the posteroinferior and lateral walls. The ratio of ejection time to pre-ejection period (ET/PEP) decreased to 2.0-3.3 in BMD, and was significantly lower than that in DMD patients with comparable muscle weakness. Left ventricular dilatation became more prominent with age, and end-diastolic left ventricular dimension (EDLVD) averaged 52.3 mm.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
A 54-year-old man was admitted to our hospital because of exertional dyspnea. A second heart sound with fixed splitting and a systolic ejection murmur along the left sternal border was audible. The chest roentgenogram showed increased pulmonary vascularity, and the electrocardiogram showed incomplete right bundle branch block. Two-dimensional echocardiography in the parasternal view demonstrated a partition defect between the left atrium and the coronary sinus. Furthermore, transesophageal echocardiography revealed a left-to-right shunt flow into the coronary sinus through the defect. At these points, the patient was diagnosed as having a partially unroofed mid-portion of the coronary sinus. Unroofed coronary sinus is a cardiac anomaly rarely diagnosed prior to surgical operation. Two-dimensional echocardiography, especially transesophageal echocardiography, is useful for the preoperative diagnosis of unroofed coronary sinus.
We analyzed a postoperative respiratory management using a respirator with nasal intubation in 55 patients who underwent subtotal esophagectomy through thoracic and abdominal approach between April 1984 and December 1989. In 21 cases (38%) the period using a respirator was within 3 days, in 24 cases (44%) during 4-7 days, and in 10 cases (18%) over 8 days. Postoperative pulmonary complications occurred in 20 cases (36%); pneumonia in 7 cases (13%), lung edema in 12 cases (22%), atelectasis in one case (2%). Two patient died after surgery, one from acute myocardial infarction, another from multiple organ failure after anastomotic leakage. The period using a respirator was positively correlated with the operative blood loss, transfusion and post-operative infusion, postoperative pulmonary complications positively correlated with the operative time, the anesthetic time, operative blood loss, transfusion and postoperative infusion as well as with preoperative complications and renal dysfunction too. In 120 cases before 1984, postoperative pneumonia occurred in 42 cases (36) and 19 cases (16%) of them died. These results suggest that our respiratory management using a respirator is effective in perioperative period of esophageal cancer.
We report a family of mitochondrial myopathy which appeared to be interited as an autosomal dominant trait. The proband is a 58-year-old Japanese male, who presented with bilateral ptosis, chronic progressive ophthalmopletia, dysphagia, and atrophy of proximal muscles in the upper extremities. There was no cataract or retinal degeneration. Serum creatine kinase (CK) and lactic acid levels were normal. Cardiac evaluations were normal. Muscle biopsy revealed 7% of ragged red fibers. Cytochrome c oxidase activity in the muscle was decreased to 50% of the control value. PCR analysis of muscle mitochondrial DNA revealed 3 large-scale deletions in the non-D-loop regions, ranging in size from 4.2 kb to 5.2 kb. His father, three siblings, and the two children had symptoms similar to the proband. We have reviewed forty-five individuals from six families, including our family, who had mitochondrial myopathy with autosomal dominant inheritance. Frequent manifestations include chronic progressive ophtalmoplegia (91.2%), ptosis (95.6%), hearing loss (72.7%), dysphagia (60.0%), limb weakness (74.1%), and respiratory muscle weakness (75.0%). Interestingly, there is no individual with retinal degeneration or cardiac involvement. Serum CK and lactic acid levels may be elevated. CT of the head is normal. Muscle biopsy shows ragged red fibers and the frequency of cytochrome c oxidase-negative fibers ranges from 0 to 38%. Multiple large-scale deletions of mitochondrial DNA, ranging in size from 4.2 to 8.3 kb, are found in the muscle, all of which are located in the non-D-loop region of the mitochondrial DNA. The multiplicity of deletions may be one to the characteristic features of this form of mitochondrial myopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
We evaluated the effect of hepatic arterial infusion chemotherapy (HAI) and intraportal infusion chemotherapy (IPI) for liver metastasis of colorectal cancer. Since 1980, 89 patients with colorectal cancer showed liver metastasis. Seven of these cases had undergone curative resection of colon tumor and hepatectomy (5 cases with HAI). Eleven cases had undergone colon tumor resection and HAI. Among the former, 3 cases with HAI are alive, and the postoperative survival rate after 2 years improved among the latter. Curative removal was carried out in 567 patients in the same period. Recurrence of liver metastasis was observed in 30 cases, in 13 cases of which hepatectomy with HAI was performed, with HAI only in another 9 cases. The three-year survival rate among the former was 41.1% and the one-year survival rate of the latter was 16.2%. From 1986 to 1988, we performed IPI in 24 cases of colorectal cancer to prevent liver metastasis. They had undergone curative resection. Recurrence of liver metastasis was observed in one case (4.2%), which was less than in the control group (9.3%). It is concluded that HAI and IPI are effective treatment for liver metastasis in colorectal cancer.
Two cases of abdominal true aortic aneurysm (AAA) associated with disseminated intravascular coagulation (DIC) were reported. Case 1 was an 81-year-old male who was admitted because of hematoma on the left leg and in whom was found by MRI an aortic aneurysm of 14 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia, hypofibrinogenemia and increased level of FDP. DIC was well controlled by surgical repair of the aneurysm after the administration of a small dose of heparin. Case 2 was a 60-year-old male who was admitted because of lumbago and hematoemesis and in whom was found by CT and echography an aortic aneurysm of 5.5 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia and an increased level of FDP. On the 2nd hospital day, he suddenly died due to the rupture of the aortic aneurysm. In most of 9 cases with AAA without DIC, plasma levels of thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and FDP-D dimer were also elevated. These findings indicate that the coagulation and fibrinolysis systems were generally activated in patients with AAA, and that DIC tends to occur in patients with a giant aortic aneurysm or an impending ruptured aneurysm.
To evaluate direct secretion from the left atrium and pulmonary extraction of human atrial natriuretic peptide (hANP), we measured plasma hANP levels in the pulmonary artery, pulmonary vein, and left atrium in patients with either mitral stenosis or atrial septal defect. Left atrial pressure in patients with mitral stenosis was significantly higher than that in patients with atrial septal defect (7.5 +/- 1.0 mm Hg vs 3.1 +/- 0.5 mm Hg, p less than 0.01). The significant increase in the hANP level in the left atrium was recognized only in patients with mitral stenosis (149 +/- 33 pg/ml in the left atrium vs 130 +/- 28 pg/ml in the pulmonary vein, p less than 0.05). The plasma hANP level in the pulmonary vein was significantly lower than that in the pulmonary artery in both patients with mitral stenosis and those with atrial septal defect, which suggests that hANP is extracted in the lung. We conclude that hANP is secreted not only through the coronary sinus but also directly from the left atrium, stimulated by high left atrial pressure, and that circulating hANP is partially extracted in the pulmonary circulation.
An autopsied case of Takayasu's arteritis associated with complete atrioventricular (AV) block is described for the first time. The findings of scar formation and diffuse infiltration of lymphocytes into the cardiac conduction system, particularly the AV node, were similar to those in patients with connective tissue diseases or congenital complete heart block. The degree of AV block progressed with aggravation of the disease. These findings suggest that complete AV block may have been induced by acquired autoimmunity involving the cardiac conduction system.