The association between renal elasticity evaluated by Real-time tissue elastography and renal fibrosis

Clinical and Experimental Nephrology - The progression of chronic kidney disease (CKD) depends on the extent of fibrosis in the kidneys; however, a renal biopsy is necessary to evaluate the...     

31P and23Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA)

³¹P and ²³Na nuclear magnetic resonance (NMR) spectroscopy was employed to study the dynamic changes in intracellular high-energy phosphates and sodium during 15min of forebrain ischemia and recirculation in in vivo rat brain. In the presence of the shift reagent Dysprosium triethylenetetramine-N,N,N,N,N,N-hexaacetic and [Dy(TTHA)], the sodium peak separated into two peaks, unshifted and shifted. During 15min of ischemia, the unshifted sodium peak decreased and the shifted sodium peak increased. With recirculation, the unshifted and the shifted sodium peaks returned to the preischemia level within 10min, but the shifted one increased during 30–60min. Intracellular high-energy phosphates and intracellular pH (pHi) decreased during 15min of ischemia and returned to the preischemia levels within 20min of recirculation. We conclude that the decrease in unshifted sodium peak during ischemia is due to the decrease in subarachnoid sodium and the cellular influx of interstitial sodium would be minimum. The increase in shifted sodium peak during ischemia is considered to be due to the dilatation of cerebral blood vessels and the increase in interstitial sodium which was transported from subarachnoid space.(Kurata M: ³¹P and ²³Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA). J Anesth 7: 325–333, 1993)     

Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin- and neuraminidase-expressing DNAs

The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from influenza virus A/PR/8/34 (PR8) (H1N1), and mixtures of these plasmid DNAs (HA + NA and HA + NA + M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1 microg of each component per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after the last immunization, mice were challenged with a lethal homologous or heterologous virus and the ability of each DNA to protect the mice from influenza was evaluated by observing lung virus titers and survival rates. The administration of a plasmid DNA mixture of either (HA + NA) or (HA + NA + M1) provided almost complete protection against the PR8 virus challenge, and this protection was accompanied by high levels of specific antibody responses to the respective components. The degree of protection afforded in these groups is significantly higher than that in mice given either HA- or NA-expressing DNA alone, which provided only a partial protection against PR8 challenge or that in mice given M1-expressing DNA, which failed to provide any protection. In addition, both of the plasmid DNA mixtures (HA + NA) and (HA + NA + M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies. Thus, there was no clear difference between the ability of the HA + NA and HA + NA + M1 plasmid DNA mixtures in providing protection against either a PR8 or heterologous virus challenge. These results suggest that in mice immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide the most effective protection against the virus challenge. The addition of the M -expressing plasmid DNA to this mixture does not enhance the degree of protection afforded.     

Phase I and pharmacologic study of oral (E)-2′-deoxy-2′-(fluoromethylene) cytidine: on a daily × 5-day schedule

(E)-2-deoxy-2-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3–4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.     

Treatment of neuroleptic induced tardive dyskinesia with cyproheptadine

Zusammenfassung Cyproheptadin ist seit Jahren als Antimetabolit des Serotonins verwendet worden. Es wurde über eine Wirksamkeit desselben bei extrapyramidalen Hyperkinesien (von den Angelsachsen als tardive dyskinesia bezeichnet) nach Neuroleptika-Medikation berichtet. Wir behandelten 11 Patienten, die wegen chronischer Schizophrenie behandelt wurden und schwere Dyskinesien aufwiesen, Cyproheptadin (Periactinol®, Periactin) verabreicht. In vier Fällen verschwand unter dieser Medikation das extrapyramidale hyperkinetische Syndrom vollständig, bei vier weiteren Fällen trat eine befriedigende Besserung auf. Im Verlaufe der Therapie wurden keine nennenswerten Nebenwirkungen beobachtet, die eindeutig auf das Cyproheptadin zurückzuführen gewesen wären.     

A reappraisal of time trends in ulcer disease: factors related to changes in ulcer hospitalization and mortality rates.

There has been a dramatic decline in reported hospitalization and mortality rates for peptic ulcer disease in the past two decades. Data from the National Center for Health Statistics and from the Commission on Professional and Hospital Activities were examined to determine the cause(s) for this decline. Gastric and duodenal ulcer mortality rates decreased by 58 per cent and 68 per cent, respectively, from 1962 to 1978; changes in criteria for selecting the underlying cause of death might account for some of this apparent decrease. Hospitalization rates for duodenal ulcers decreased nearly 50 per cent from 1970 to 1978, but hospitalizations for gastric ulcers did not decrease. During this same time period, hospitalizations for peptic ulcers as one of the "all listed" causes remained stable, and hospitalizations for a closely related diagnosis, gastritis/duodenitis, increased. Changes in coding practices, hospitalization criteria, and diagnostic procedures appear to have contributed to the decline in reported hospitalization and mortality rates for peptic ulcer disease.     

Progression of renal failure with anaemia and multiple effects of angiotensin-converting enzyme inhibitor in rats with renal mass reduction.

Several factors such as proteinuria and renal fibrosis may be important in the progression of many forms of chronic renal diseases. The purposes of the current study were to investigate the progressive renal failure of the rats with surgical renal mass reduction (RMR) and the effect of the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and to document correlation of several factors associated with progressive renal failure. Rats were subtotal (5/6) nephrectomized by resection of the renal poles and sham-operated. The functional, histological and haematological changes of the rats were studied for up to 10 weeks. After 2 weeks of RMR, oral administration of lisinopril (10 mg kg(-1) per day) was performed for 8 weeks. RMR resulted in progressive renal failure with proteinuria, monocyte/macrophage (ED1+) infiltration, anaemia as assessed by haemoglobin and haematocrit (Htc), renal hypertrophy as assessed by left kidney to body weight ratio (BKW/BW), and renal fibrosis as assessed by glomerular lesions and tubulointerstitial changes. Lisinopril exhibited renoprotection with antiproteinuric effect and inhibition of monocyte/macrophage (ED1+) infiltration. However, beneficial effect of lisinopril on anaemia was not observed. At 10 weeks after surgery, severity of proteinuria positively correlated with plasma creatinine (Pcr), BKW/BW, histological damage, and systolic blood pressure, and negatively correlated with haemoglobin. Severity of tubulointerstitial changes positively correlated with Pcr and blood urea nitrogen, and negatively correlated with haemoglobin and Htc. Moreover, monocyte/macrophage (ED1+) infiltration positively correlated with severity of proteinuria and tubulointerstitial changes. These findings strongly support that proteinuria, monocyte/macrophage infiltration and renal fibrosis appear to play principal roles in the progressive renal failure with anaemia and renoprotection of ACE inhibition may be mediated by multiple actions of ACE inhibitor. The present study confirms that rats with RMR is useful to explore target molecules for renoprotective drugs and evaluate renoprotective effect of new molecular entities.     

Three cases of severe hyponatremia under taking selective serotonin reuptake inhibitor (SSRI)

The association between selective serotonin reuptake inhibitors(SSRIs) and hyponatremia has been documented throughout the world. In Japan, since SSRIs have recently come into use for patients with depression, there are only a few reports of hyponatremia associated with SSRIs. We present here three cases of the syndrome of inappropriate secretion of antidiuretic hormone(SIADH) associated with the administration of fluvoxamine for depression. They were admitted to our hospital because of deep coma, and revealed severe hyponatremia. Their serum sodium levels were 103-112 mEq/l, serum osmolalities were 227-241 mmol/kg, urine sodium levels were 38-107 mEq/l, and urine osmolalities were 352-781 mmol/kg. These patients were started on fluvoxamine 3 days-3 months previously. The diagnosis of SIADH in these patients was made based on hyponatremia, and low serum and high urine osmolalities. The fluvoxamine treatment was discontinued, and hypertonic saline was infused. Their serum sodium levels and osmolalities were subsequently normalized. None of the other known causes of hyponatremia, including diuretic therapy, tumors, and respiratory and central nervous system diseases, were present. High plasma AVP levels observed in the two cases suggest that SSRIs stimulate AVP secretion, thereby causing SIADH. Many reports have shown that people older than 70 years were at a particularly high risk of developing hyponatremia when SSRIs were used. In the future, since the use of SSRIs will be increasing, the water and electrolyte balance of elderly patients should be monitored carefully during SSRIs therapy.     

Macroscopic assessment of nodal metastasis is not reliable in colon cancer

Background Japanese surgeons have to macroscopically assess nodal metastasis from colon cancer according to the general rules established in Japan. Adjuvant therapy is sometimes started after macroscopic assessment of nodal metastasis. Macroscopic assessment, however, is difficult in many cases. Methods We evaluated the reliability of macroscopic assessment of nodal metastasis in colon cancer by (1) comparing the number of nodes picked up macroscopically with that of nodes recognized microscopically, and (2) by comparing the number of metastatic nodes found between macroscopic and microscopic examination. Results The number of nodes found during macroscopic examination was equal to that found in microscopic examination in only 52 of 206 cases (25%). Although 120 of 206 cases (58%) were judged macroscopically to have metastatic nodes, 61 had no metastatic nodes found microscopically. Sensitivity and specificity for the recognition of cases with nodal metastasis was 85.5% and 55.5%, respectively. The number of metastatic nodes in macroscopic examination was equal to that in microscopic examination in 90 cases (44%). Conclusion Because macroscopic assessment of nodal metastasis is not reliable, physicians should not rely on macroscopic assessment to indicate the need for further therapy, such as adjuvant chemotherapy. The recommendation for macroscopic assessment of nodal metastasis should be eliminated from the general rules in Japan.     

Mediastinal mature teratoma perforated into the pericardial sac: a case report

Mature teratomas occasionally rupture into adjacent organs such as lung, bronchus, mediastinum and pericardial sac. However, perforation into the pericardial sac is rare. We experienced a case of mediastinal mature teratoma perforated into the pericardial sac. A 16-year-old man was admitted to our hospital due to sudden severe anterior chest pain. Chest X-ray showed a mass shadow in the right middle lung field. Chest CT scan and MRI demonstrated a heterogeneous mass with fat component in the right anterior mediastium adjacent to the pericardium. Some squamous cells were obtained from the mass by CT guided percutaneous needle biopsy. Operation was performed with the diagnosis of mediastinal teratoma. The mass adhered to the pericardium and turbid pericardial effusion was noted. The mass was removed with the pericardium. The mass was 9 x 6.5 x 6 cm in size, which contained yellow sebaceous material and a tuft of white hair. The pathological diagnosis of the mass was mature cystic teratoma with perforation into the pericardial sac.