Pharmacological and biological effects of tin-protoporphyrin on neonatal hyperbilirubinemic Gunn rats

Our study was undertaken to examine the pharmacological and biological effects of tin-protoporphyrin, a competitive inhibitor of heme oxygenase, on 5- or 6-day-old homozygous (j/j) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j/j neonates were injected subcutaneously with 20 mumol of tin-protoporphyrin/kg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j/j rats was strikingly reduced by the administration of 1 to 100 mumol of tin-protoporphyrin/kg; the most effective dose was 5 mumol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed.     

The micronucleus test and erythropoiesis. Effects of erythropoietin and a mutagen on the ratio of polychromatic to normochromatic erythrocytes (P/N ratio)

It is considered that a decrease of the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) (P/N) in the micronucleus test is an indicator of bone marrow toxicity induced by mutagens. However, the exact meaning of fluctuation in the P/N ratio is not yet known. We have studied this point by counting the total number of erythrocytes and nucleated cells in the bone marrow following various treatments. The P/N ratio decreased gradually with time after administration of mitomycin C. Our data suggest that the decrease of P/N ratio was attributable to an increase in the numbers of the denominator, i.e. NCE, caused by rapid differentiation and multiplication or denucleation of erythroblasts which remained in the bone marrow instead of entering the peripheral blood stream. A decrease of P/N ratio was also observed in the early phase after administration of erythropoietin, an agent which induces differentiation and multiplication of erythroblasts. This phenomenon might result from an increase of PCE delivery into the blood circulation. However, following the initial decrease, the P/N ratio increased gradually 48 h after administration of erythropoietin. It is supposed that this increase probably resulted from an increase in PCE in the bone marrow due to the direct effects of erythropoietin on erythropoiesis. The drastic change in erythropoiesis in the bone marrow induced by either mutagen or erythropoietin treatment will affect the fluctuations of the P/N ratio or the number of micronucleated erythrocytes per non-micronucleated erythocytes in the micronucleus test. This contrasts with the original explanation for such fluctuations which attributed them to replenishment of the marrow by peripheral blood.     

Ultrasonographic features of chromophobe cell renal carcinoma

Chromophobe cell renal carcinoma is an uncommon type of renal cell carcinoma, and the number of reported cases in Japan is small. The ultrasonographic (US) features of this rare tumor are not defined. We reviewed the imaging findings of four pathologically proven chromophobe cell renal carcinomas. US, color Doppler US (DUS), computed tomography (CT) and magnetic resonance imaging (MRI) were performed preoperatively. The internal echo patterns of the tumors were homogeneous in all cases, and the lesion usually was hyperechoic even if the tumor was large, although one tumor was isoechoic. DUS revealed no color flow in any tumor. Both CT and MRI showed a relatively homogeneous, hypovascular tumor. These tumors had characteristic US findings, probably because they had a uniform growth pattern of tumor cells and none of them had necrosis or hemorrhage. When US shows a homogenously hyperechoic and hypovascular tumor of the kidney, we should suspect chromophobe cell renal carcinoma.     

Tubular surgery with the assistance of endoscopic surgery via midline approach for lumbar spinal canal stenosis: a technical note

Purpose

We devised a tubular surgery with the assistance of endoscopic surgery via midline approach to the spinal canal to preserve the bilateral facet joints and the paravertebral muscles when treating lumbar spinal canal stenosis. We report details of this operative procedure.

Methods

A 2-cm incision is made in the skin in the midline of the intervertebral level to be decompressed. The spinous process on the cranial side is partially excised, and incisions along the ligament fiber are made in the midline of the supraspinous and interspinous ligaments to expose the ligamentum flavum. After the lamina and the inferior parts of the bilateral facet joints are adequately excised, the microendoscopic discectomy system is inserted. With this procedure, no muscular tissue is seen in the surgical site. The portal approach is small, but if full advantage is taken of the spinal microendoscope’s merits, the bilateral facet joints are preserved and wide decompression of deep parts is possible. The microendoscope is positioned above the spinal canal to provide a good symmetrical field of view to enable easy anatomical orientation.

Results

Bilateral intervertebral joints were satisfactorily preserved in ten patients who received this surgery. All became ambulatory on the day after surgery and the clinical results remained favorable 3 years after the operation.

Conclusion

Tubular surgery with the assistance of endoscopic surgery via a midline approach is a minimally invasive surgical procedure with favorable results that enables preservation of paravertebral muscles and bilateral facet joints.     

Clinical and immunological study on the high incidence of malignant neoplasms in patients with chronic renal failure

With the advancement of dialysis techniques, rehabilitation and high morbidity are becoming serious problems for patients with chronic renal failure. The authors, with the purpose of investigating the carcinogenic state of such patients, studied the incidence of malignant neoplasms and their immunity both clinically and fundamentally. Out of 499 patients with chronic renal failure, malignant neoplasms were found in 17 cases (3.40%), which is obviously a high rate with a statistically significant difference from that of the ordinary healthy population. In the fundamental immunity study, OKM1+ cells of the patients were significantly lower than those of healthy people, and a decrease in NK and K cells was inferred. Incidentally, the lymphocytes of patients strongly inhibited the mitogen response of healthy subjects. This decline in cellular immunity is considered to be closely related to the carcinogenicity of patients with chronic renal failure.     

Dysprosody associated with environmental auditory sound agnosia in right temporal lobe hypoperfusion--a case report]

A 60-year-old right-handed man showed dysprosody and agnosia for environmental sounds. His mother tongue was Japanese, and he could not speak foreign languages. He gradually developed difficulty in speaking from the age of 57 years, speaking non-native Japanese. In addition, he often complained of difficulty in hearing sounds, but audiometry showed no abnormalities. At the age of 60 years, the standard language test of aphasia showed no abnormalities in repetition, verbal comprehension, or reading, suggesting the absence of aphasia. However, in speaking, marked abnormality in rhythm, and occasional lack of postpositional particles and syllable-stumblings were observed. Writing was almost accurate, but a few grammatical errors were observed in speaking were observed. There were no cerebellar symptoms, pyramidal signs, pathologic reflexes, or abnormalities in phonation-related organs. Though the recognition of verbal sounds was maintained, impairment in the recognition of non-verbal sounds was observed. An environmental sound perception test showed correct answers only in 8 of 21 non-verbal sound sources (such as a car starting, glass breaking and so on), suggesting agnosia for environmental sounds. He insisted that the difficulty in perception was due to hearing impairment. However, re-examination with an increase in the sound volume showed similar results. He had no inconvenience in daily life and was not aware of agnosia for environmental sounds. He could recognize and differentiate sounds he heard once. His intelligence was normal, and neither apraxia nor frontal lobe symptoms were observed. MRI of the brain revealed slight atrophy of the right temporal lobe. Cerebral blood flow SPECT showed decreased blood flow from the superior temporal gyrus to the area around the arcuate fasciculi in the right temporal lobe. We considered that the lesion responsible for environmental auditory sound agnosia was present in the area around the secondary auditory area of the right temporal lobe and this patient differed from slowly progressive aphasia characterized by decreased blood flow in the left temporal lobe. Although the pathological process occurring in the area of hypoperfusion remained unclear, early stage of some degenerative disorders was more likely than cerebrovascular disease.     

Chromophobe cell renal carcinoma: report of two cases

We report two cases of chromophobe cell renal carcinoma. Case 1 was in a 62-year-old man with the chief complaint of hematospermia. Ultrasound incidentally detected a left renal mass. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a relatively homogeneous, hypovascular tumor of the left kidney. We performed radical nephrectomy after making a clinical diagnosis of possible renal carcinoma. Case 2 was in a 66-year-old woman who was admitted to our hospital after a left renal mass was incidentally found by ultrasonography during a health check. We performed laparoscopic radical nephrectomy after making a diagnosis of renal cell carcinoma by CT and MRI. Both of the tumors were shown to be chromophobe cell carcinoma by microscopic examination after H & E staining and immunohistochemistry using Hale's colloidal iron stain. Chromophobe cell carcinoma is an uncommon type of renal cell carcinoma and the number of reported cases is limited in Japan. The clinical features and management of this rare tumor are discussed.     

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective

Purpose

The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention.

Methods

We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination.

Results

Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 ± 5 mL) compared with controls (71 ± 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis.

Conclusions

In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.