The early induction of cyclooxygenase 2 associated with neurofibrillary degeneration in brains of patients with Fukuyama-type congenital muscular dystrophy

Brains of thirteen patients with Fukuyama-type congenital muscular dystrophy (FCMD) were evaluated regarding the expression of cyclooxygenase 2 (COX2), an enzyme involved in the synthetic pathway of prostaglandins and thromboxanes, as well as neurofibrillary tangles (NFT). The neuronal induction of COX2 was demonstrated with immunohistochemistry and Western blotting confirmed the up-regulation. Preceded by COX2 immunoreactivity, NFT-containing neurons appeared in the majority of FCMD patients without beta-amyloid deposition or senile plaques. The hippocampus did not demonstrate neurodegeneration, while, in other areas, neurons with NFT spread in a similar manner to Alzheimer's disease. NFT-bearing neurons were concomitantly shown to be immunoreactive to COX2. The precedent induction of COX2, therefore, may be related to the formation of NFT in this genetic disorder.     

New method of bladder biopsy using combined aspiration and snare

A method of multiple random biopsy combined with bladder wall aspiration and snare in bladder cancer is presented. Our method was used on 23 patients with clinically superficial bladder cancer and was found to have advantages in obtaining an adequate amount of tissue with minimal thermal degeneration.     

Less invasive surgery for early gastric cancer based on the low probability of lymph node metastasis

BACKGROUND: Less invasive treatment is the current trend in many surgical fields. Most patients with early gastric cancer do not have lymph node metastasis. Thus extensive resection of the stomach and extended lymph node dissection do not appear to be necessary. METHODS: In a retrospective study, 890 consecutive patients with early gastric cancer who had undergone standard gastrectomy were assessed for depth of invasion, gross appearance, and maximum diameter of the tumor to examine the possibility of limiting the extent of lymph node dissection. A variety of limited gastrectomies have been developed and now include endoscopic mucosal resection, wedge resection, segmental gastrectomy, limited proximal gastrectomy, and distal hemigastrectomy. RESULTS: A retrospective study revealed that extensive lymph node dissection did not improve the survival of patients with early gastric cancer. Endoscopic mucosal resection was suitable for cancers of the depressed type of less than 1 cm in diameter and the elevated type of less than 2 cm in diameter. Wedge, segmental, or limited proximal gastrectomy was suitable for the elevated type of 2 to 3 cm in diameter. The elevated type of more than 3 cm in diameter and the depressed type of 1 to 3 cm in diameter sometimes involved metastasis to group 1 nodes. The depressed type of more than 3 cm in diameter sometimes involved metastasis to group 2 nodes. Thus such cases should be treated by gastrectomy with dissection of potentially metastatic lymph nodes. CONCLUSIONS: Limitation of the extent of gastrectomy and lymph node dissection may be possible, depending on the gross appearance and size of the tumor.     

Serum C-reactive protein level and the impact of cytoreductive surgery in patients with metastatic renal cell carcinoma

PURPOSE: The prognosis of metastatic renal cell carcinoma is extremely poor. In this type of metastatic tumor cytoreductive surgery of the primary tumor is often performed to confirm the histological type or improve the response to immunotherapy with agents such as interferon or interleukin-2. However, the timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We determined the type of metastatic renal cell carcinoma for which cytoreductive surgery is beneficial. MATERIALS AND METHODS: We retrospectively reviewed the records of 58 patients in whom metastatic renal cell carcinoma was diagnosed at our hospital between 1986 and 1997. Three patients were excluded from study because they were judged to be poor candidates for surgery due to poor performance status. Of the remaining 55 patients 34 consented to cytoreductive surgery of the primary tumor and 21 did not. All except 1 patient were treated with interferon therapy. We evaluated the association of pretreatment serum C-reactive protein and the effect of surgery. RESULTS: We noted no significant difference in age at diagnosis, pretreatment serum immunosuppressive acidic protein, site of metastasis or performance status in 34 patients who underwent cytoreductive surgery and 21 who did not. Of the 21 patients in whom pretreatment serum C-reactive protein was within normal limits (less than 1.0 ng./ml.) no significant difference in disease specific survival was observed in those who did and did not undergo surgery (p = 0.4133). On the other hand, of 34 patients in whom pretreatment serum C-reactive protein was elevated (1.0 ng./ml. or greater) the prognosis was significantly better in those who did versus those who did not undergo surgery (p = 0.0054). Particularly the prognosis in patients in whom postoperative nadir C-reactive protein decreased to within normal limits was markedly better than in those in whom it remained elevated (p = 0.0025). CONCLUSIONS: Our study suggests that cytoreductive surgery is beneficial to patients in whom pretreatment serum C-reactive protein is elevated. Particularly, those in whom serum C-reactive protein decreases to within normal limits may expect longer survival when surgery is combined with postoperative immunotherapy. Currently to our knowledge the prognostic factor that predicts postoperative nadir C-reactive protein has not been identified, indicating that cytoreductive surgery of the primary tumor should be performed in patients with elevated pretreatment C-reactive protein and as performance status permits.     

Oral administration of sepimostat mesilate prevents acute alcohol pancreatic injury in rats.

The preventive effect of a novel synthetic serine protease inhibitor, sepimostat mesilate (sepimostat), on acute alcohol pancreatic injury, induced by exocrine hyperstimulation and ethanol administration, was assessed and compared with that of a similar protease inhibitor, camostat mesilate (camostat). Conscious rats were infused with 1 microg mL(-1) h(-1) caerulein intravenously for 6 h and with 0.1 g mL(-1) h(-1) ethanol for 9 h, with the latter infusion beginning 3 h after the start of the caerulein infusion. Sepimostat or camostat was administered orally 1 h before the caerulein infusion. Rats infused with caerulein plus ethanol showed increased plasma amylase and lipase activities, and aggravated pancreatic interstitial oedema when compared with rats given caerulein alone. Sepimostat at 10 and 30 mg kg(-1) prevented the increase in plasma amylase and lipase activities caused by caerulein plus ethanol infusion. Sepimostat at 30 mg kg(-1) suppressed the histological change. Camostat did not show any preventive effects at the equivalent dose. When conscious rats were infused with 1 microg mL(-1) h(-1) caerulein alone intravenously for 6 h, plasma amylase and lipase activities were increased compared with rats given saline. Neither drug prevented the increase in these activities at 30mg kg(-1). Our results suggest that sepimostat has superior preventive effects on alcohol-induced acute pancreatic injury compared with camostat. Sepimostat may thus be a useful drug in the therapy of alcohol-induced pancreatitis.     

Glucose intolerance during prolonged sevoflurane anaesthesia

Purpose

The effects of prolonged sevoflurane anaesthesia on insulin sensitivity were investigated by two successive intravenous glucose tolerance tests (IVGTT) in eight patients who underwent prolonged surgery.

Methods

The first IVGTT was administered (25 g glucose as 20% dextrose in water iv) over two minutes 35 min after initiation of surgery. Arterial blood samples were obtained at 0, 5, 10, 30, 60, and 120 min after glucose administration for blood glucose and plasma insulin determination. A second IVGTT was performed six hours following the initiation of surgery.

Results

The disappearance rate of glucose (k-value) for the first IVGTT was 0.887 ± 0.436 (mean ± SD) % · min^?1, and 0.784 ± 0.289 for the second IVGTT. Both k-values are lower than the normal value. The maximum insulin response to glucose (ΔIRI · ΔBS^?1) of the second IVGTT was lower than the first IVGTT (0.124 ± 0.092 vs 0.071 ± 0.056, P < 0.05). The total insulin output of the first IVGTT was higher than the second IVGTT (1,161 ± 830 vs 568 ± 389 μU · min · ml^?1, P < 0.05).

Conclusion

Glucose intolerance is enhanced by diminished insulin output in response to blood glucose elevation during prolonged anaesthesia and surgery.     

Serial diffusion-weighted imaging in MELAS

Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS. Received: 13 September 1999/Accepted: 7 January 2000     

Porous apatite-wollastonite glass-ceramic as an intramedullary plug

We evaluated the efficacy and biocompatibility of porous apatite-wollastonite glass ceramic (AW-GC) as an intramedullary plug in total hip replacement (THR) for up to two years in 22 adult beagle dogs. Cylindrical porous AW-GC rods (70% porosity, mean pore size 200 microm) were prepared. Four dogs were killed at 1, 3, 6 and 12 months each and six at 24 months after implantation. Radiological evaluation confirmed the efficacy of porous AW-CG as an intramedullary plug. Histological evaluation showed osteoconduction at one month and resorption of the porous AW-GC, which was replaced by newly-formed bone, at 24 months. Our findings indicate that porous AW-GC can be used clinically as an intramedullary plug in THR.     

A case of adult moyamoya disease progressed after vascular reconstructive surgery

We report an adult onset patient with moyamoya disease showing acute progress after contralateral vascular reconstructive surgery. A 47-year-old female developed cerebral infarction in the left corona radiata. A magnetic resonance (MR) angiography and a cerebral angiogram revealed severe stenosis extending from the terminal portion of left internal carotid artery (ICA) to the M1 portion. The right ICA showed slight stenosis. We performed direct bypass surgery (STA-MCA anastomosis) on the affected left side. MR angiography 1 month after surgery revealed the progressive stenosis of the C1 portion of the right ICA. While measurement of cerebral blood flow (CBF) showed a slight impairment of vascular reactivity to acetazolamide loading in the region of the right MCA, we continued without vascular reconstructive surgery for the right side because there was no ischemic attack. The patient had a transient sensory disturbance of the left upper extremity 16 months after surgery. MR angiography and a cerebral angiogram revealed more progressive stenosis extending from the right ICA to the M1 portion. CBF study showed a low CBF at rest and a negative response to acetazolamide loading in the region of the right MCA. Direct bypass surgery was performed on the right hemisphere. Follow-up study revealed an increment of rest CBF and improvement of vascular reactivity. We underlined the necessity for careful postoperation observation of progressive contralateral arterial stenosis using MR angiography and CBF study in adult onset patients with moyamoya disease.