Volume 110 · Issue 09 · 1997

OBJECTIVE To investigate the nature of retinal capillary pericyte dropout in early human diabetic retinopathy. METHODS In the present study, neural retinas of 12 postmortem eyes from 6 patients (3 diabetic and 3 nondiabetic) were first fixed in buffered formaldehyde and then digested with trypsin. The preparations of trypsin-digested retinal blood vessels were stained with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique and then with perdiodic acid-Schiff technique (PAS), and counter-stained with hematoxylin to evaluate DNA fragmentation of cell nuclei and diabetic changes of retinal capillaries. RESULTS TUNEL-positive apoptotic pericytes were observed in retinal capillaries in all three diabetic patients in this study. The TUNEL-positive pericytes were presented as darker stained cells with PAS-hematoxylin staining. A few TUNEL-positive retinal capillary endothelial cells were discovered in both eyes of one of the three diabetic patients. Neither TUNEL-positive pericytes nor positive endothelial cells were found in the three nondiabetic patients. A variety of typical diabetic microvascular changes were noticeable with PAS-hematoxylin staining in trypsin-digested retinal preparations from diabetic patients. These changes included thickened capillary walls, microaneurysms, "ghost-cell"-appearance of pericytes, acellular segments of capillaries, and a decreased ratio of retinal capillary pericytes to endothelial cells. All of these changes are characteristics of diabetic retinal microangiopathy. CONCLUSIONS Retinal capillary pericyte apoptosis is a specific form of cell death which occurs during the early development of diabetic retinopathy. The significant decrease in the ratio of pericytes to endothelial cells and the predominant TUNEL-positive pericytes over endothelial cells suggest that a greater impact of apoptosis-related mechanisms occurs in pericytes than in endothelial cells and, thereby, a greater loss of pericytes takes place in early diabetic retinopathy. Apoptosis, therefore, is an important mechanism of pericyte dropout in the early diabetic retinopathy.

OBJECTIVE To demonstrate the color Doppler imaging (CDI) of intra-ocular tumors and its importance in the diagnosis of these tumors. METHODS Ninety-two patients with intra-ocular tumors (105 eyes) were examined by using CDI to observe the vasculature of these tumors, and using SAS soft ware to analyze the results. RESULTS Blood flow signal was found in retinoblastoma, melanoma of choroid, angioma of choroid, angioma of optic disc, Coats' disease, persistent hyperplastic primary vitreous (PHPV) and metastatic tumors of choroid, but not found in choroid osteoma and melanocytoma of optic disc. The blood flow decreases in central retinal artery in choroidal melanoma and also in ophthalmic artery, central retinal artery and posterior ciliary artery in angioma of choroid (P<0.01). It was found that blood velocity is much faster in choroidal melanoma than in choroidal angioma (P<0.05). CONCLUSIONS CDI is very important and helpful in the diagnosis of intra-ocular tumors.

OBJECTIVE To investigate the correlation among retinal fluorescein angiography, blood viscosity, and other factors in patients with open angle glaucoma (POAG). METHODS Multiple step regression analysis was made to investigate the correlation between each of the following blood vessel filling times: the arm-choroid (A-CT), arm-retinal artery (A-AT), and retinal artery-venous (A-VT) of the fundus fluorescein angiography (FFA) in 122 eyes with POAG and each of the following related factors in hemorrheology: whole blood apparent viscosity at low, medium and high shear rates, plasma viscosity and hematocrit. Also, the same analysis was applied to investigate the correlation between each of the A-AT, A-VT of the FFA in 70 eyes with POAG and the following factors: systolic blood pressure, diastolic blood pressure, age and whole blood apparent viscosity at low shear rate. RESULTS The whole blood apparent viscosity at low shear rate was closely related to A-CT and A-AT, while hematocrit was closely related to A-VT of the FFA. The whole blood apparent viscosity at low shear rate and age, especially the whole blood apparent viscosity, was closely related to A-AT, A-VT of the FFA. CONCLUSIONS Blood viscosity can affect the filling times of the FFA in POAG.

OBJECTIVE To identify the astigmatism changes after excimer laser photorefractive keratectomy (PRK) and the visual influence of astigmatism. METHODS 109 myopic eyes followed up for more than 1 year were analyzed by videokeratography, and their visual acuities were examined. Before the operation, the astigmatic errors with cycloplegic refractive examination were -1.00 approximately -2.00 D. RESULTS The position of astigmatism axis was basically consistent with that in corneal topography, but in astigmatism diopter there were some differences between the cycloplegic examination and topographic analysis. A stigmatism was found in 62% of the eyes, asymmetrical in 33% and against-the-rule in 5% by using topographic analysis. There was little change observed in the position of astigmatism axis after PRK observed. Some changes of postoperative astigmatism diopter were seen in different periods. It increased in the postoperative 10 days or 1 month, and afterwards gradually decreased and became stable in 6 months to 1 year. The postoperative residual astigmatism was low in degree, and did not affect the visual acuity. The actually corrected diopter was within the anticipated corrected diopter range of ±1.00 D. accounting for 97.4%. CONCLUSIONS By using spherical equivalent method of calculation in PRK, the refractive correction of the operation cases with myopia and low degree of astigmatism (<-2.00 D) was satisfactory.

OBJECTIVE The reported results of intracoronary stenting with Palmaz-Schatz stents using the low dose anticoagulation protocol have been encouraging and no stent thrombosis was observed. The effectiveness of such method extending to the use of other types of stents was therefore evaluated in this study. METHODS All patients followed the anticoagulation protocol (heparin and warfarin) using non-heparin-coated stents. From September 1995, 92 patients received intracoronary stenting (69 men, 23 women, mean age 60.9 years). Altogether 117 stents were implanted in 99 target arteries and 106 lesions. RESULTS A total of 50.4% of the stents were bare stents (stents without protective sheaths). Both coil stents and slotted tubular stents were used. Stenting was performed without the guidance of intravascular ultrasonography and high-pressure poststenting inflation was used in only 24.0% of patients with less than optimal angiographic results. The mean (± SD) coronary minimum luminal diameter changed from 0.63±0.39 mm to 3.12±0.48 mm immediately after stenting. Both stent thrombosis rate and femoral bleeding complication rate remained at 0%. Four bare stents could not be deployed in the first instance but without sequels. No morbidity nor mortality was recorded. The mean hospital stay remained at a mean of 4.5 days. All patients (100%) were followed up regularly. The mean (± SD) clinical follow-up period was 229±173 days. Clinical symptoms improved in all patients. CONCLUSIONS These findings further support that the method is safe and stent thrombosis was not observed. Post-stenting recoil was more with coil stents. Dislodgment and potential risk of embolization could not be underestimated with bare stents. The restenosis rate between different types of stents remains to be determined.

OBJECTIVE To investigate the disturbance in the function of SRIF receptor, Gi protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance in the pathogenesis of pituitary hGH adenomas. METHODS All 25 patients with pituitary hGH adenoma who were involved in this study had typical acromegalic manifestation and high fasting serum hGH levels of>5.0 μg/L which were not suppressed to<3.0 μg/L by oral glucose tolerance test. The pituitary hGH adenoma tissue obtained from transphenoidal operation was digested by collagenase and the dispersed adenoma cells were cultured in the monolayer. The effects of octreotide (SMS), a long-acting agonist of somatostatin, on hGH secretion and intracellular cAMP level were observed and the influences of pertussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A23187 or KCl on the inhibitory action of octreotide on hGH secretion were also investigated in the cultured pituitary hGH adenoma cells. RESULTS A total of 16.0% (4/25) of cultured pituitary hGH adenomas did not respond to octreotide (100 nmol). The inhibitory effect of octreotide on hGH secretion was not blocked by PT (50 ng/ml) and A23187 (10 μmol) or KCl (22.5 nmol) in 31.6% (6/19) and 35% (7/20) of hGH adenomas, respectively. The effects of octreotide on hGH secretion and intracellular cAMP levels were studied in 10 cultured hGH adenomas. Octreotide suppressed both hGH secretion and cAMP levels in 5 cases; inhibited only hGH secretion or the cAMP level in 3 cases and 1 case respectively; and affected neither hGH secretion nor cAMP level in the last case. CONCLUSIONS There were abnormalities in the SRIF receptor and/or postreceptor signal transduction in 16.0% of hGH adenomas which did not respond to octreotide. The defects in Gi and/or Ca2+ channels were found in 52.4% (11/21) of hGH adenomas which had responded to octreotide. These defects might induce diminution of the inhibitory action of SRIF on hGH secretion and might be the causes of hypersecretion in some pituitary hGH adenomas.

OBJECTIVE To analyze the clonal relationship between lymphocytes in peripheral blood (PB) and myeloma cell in bone marrow (BM) for proving the existence of circulating tumor cells in multiple myeloma (MM) patients. METHODS Eighteen patients with MM who have no cytomorphologic plasma cells and CyIg+ cells in PB demonstrated by anti-kappa and anti delta MoAbs using ABC method were involved in the present study, including 3 cases in phases Ⅰ-Ⅱ and 15 cases in phase Ⅲ. The complementary determining region 3 (CDR3) of immunoglobulin heavy chain (IgH) gene was amplified by polymerase chain reaction (PCR). We further analysed the single strand conformation of the PCR products by single strand conformation polymorphism (SSCP) analysis to detect the mononuclear cells in PB and BM of the patients simultaneously. RESULTS The same PCR products of IgH-CDR3 gene with BM samples were found in PB of 11 MM patients. The same PCR products and single strand conformation in both PB and BM were found in 9 cases. CONCLUSIONS This study has proved the presence of identical clonal malignant cells in PB and BM of MM patients. B cells are involved in the pathogenesis of MM.

OBJECTIVE To evaluate the association of the level of urine and serum soluble interleukin-2 receptor (sIL-2R) with disease activity and response to cyclosporine A (CsA) therapy in patients with lupus nephritis (LN). METHODS Sixteen hospitalized patients with LN were studied. At admission, fifteen patients had type IV-LN and one had type V-LN. All patients received CsA 6 mg/kg per day for 6-8 weeks, then tapered off gradually to 2 mg/kg per day. The levels of urinary and serum sIL-2R were determined by enzyme-linked immunosorbent assay (ELISA). Serum antinuclear antibody (ANA), anti-dsDNA antibody (A-ds-DNA), complement C3 and C4, total IgG, creatinine, urinary red blood cells and protein excretion, and lymphocyte subpopulations in the peripheral blood were also measured before and after CsA treatment. RESULTS In LN patients, both urinary (534±101 U/ml) and serum SIL-2R levels (326±148 U/ml) were higher than those in normal controls. These findings were associated with higher levels of peripheral blood CD4 + and CD8 + lymphocytes (29.3±4.24 and 28.6±9.12%), higher titer of serum anti-ds-DNA, lower levels of serum complement C2 and C4 (0.98±0.23 and 0.24±0.12 g/L), as well as more proteinuria (Upro 2.99±0.76 g/24 hrs) and hematuria (URBC 83.9±95.2 104/ml). These abnormalities were gradually ameliorated by CSA therapy. The changes in the levels of both serum (116±58.6 U/ml) and urine (136±43.2 U/ml) SIL-2R induced by CsA (at 8 weeks) were correlated with the changes in the levels of CD4 + and CD8 + cells (23.2±3.30 and 26.7±3.54%), degrees of immune abnormalities (serum C3 and C4 1.28±0.14 and 0.42±0.06 g/L), and renal injuries (Upro 1.07±0.46 g/24 hrs, URBC 5.82±3.15 104/ml). CONCLUSIONS These results suggest that serum and urinary sIL-2R are sensitive markers for the disease activity in patients with LN. CsA, a powerful immunosuppressive agent, significantly improves both immunologic disorders and renal functional impairments, the mechanism of which on patients with LN appears to inhibit the lymphocyte activation in the peripheral blood and renal tissues as indicated by the decrease in sIL-2R levels.

OBJECTIVE To make clinical analysis and pathological study on 40-case Gullain-Barré syndrome with sural nerve biopsy. METHODS A total of 90 cases of GBS were retrospectively analyzed of which sural nerve biopsies were performed in 40 cases. The type of GBS was determined according to Asbury and Ropper criteria, and its correlation with pathological findings was studied. RESULTS In the 40 biopsy cases, demyelination was the predominant pathological change in 38 cases. Mild axonal degeneration was also seen in 13 of the 38 cases. Prominent axonal degeneration was seen in only 2 of 13 cases. The increased monocyte infiltration and varied capillary permeability were observed in 19 of 25 cases. Onion-bulb like changes were seen in 6 cases. CONCLUSIONS We studied the correlation between paresthesia and the pathological findings of sural nerve biopsy and concluded that sural nerve biopsy is very useful in the diagnosis of GBS and its variant.

OBJECTIVE To observe the biliary copper content of nonhepatolenticular degeneration (HLD) controls and changes in the trace elements in the bile, cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients before and after dimercaptosuccinic acid (DMSA) treatment in order to further explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA on HLD patients. METHODS A consecutive series of 20 patients with HLD were given DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day. Their bile, cerebrospinal fluid, blood and urine samples were obtained before and after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary samples of 22 non-HLD controls were taken by drainage tube after surgical operation. Hitachi-208 atom absorption spectrophotometer was used to assay the content of copper, zinc and iron of each sample. RESULTS DMSA could effectively improve the symptoms such as dysphasia, salivation, dysphagia and darkening of the skin; limb trembling and myotonia came second; but it showed no obvious effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It was effective for the patients who were younger and had no obvious hepatic damage. No serious side effects were seen through the course of treatment. Laboratory study showed that biliary copper content of HLD patients was evidently lower than that of non-HLD controls (P<0.01); DMSA could evidently improve biliary copper excretion besides clearly increase urinary copper excretion (P<0.01) and had nothing to do with biliary zinc excretion (P>0.05). CONCLUSIONS Biliary copper excretion disturbance participates directly in the pathophysiology of copper retention of HLD patients. DMSA is a favorable cupruretic drug for patients with HLD.

OBJECTIVE To compare the effects of metoprolol and propafenone in patients with ventricular arrhythmia (VA) of positive ventricular late potential (VLP) and to discuss the effect of medicine on high risk VA. METHODS 30 A total of 128 patients (78 males and 50 females) with VA of positive VLP were randomly divided into 3 groups. Groups A and B were given metoprolol and propafenone respectively, group C was given vitamin C as placebo. Twenty-four hours dynamic electrocardiogram and VLP were examined before treatment and 4 weeks after treatment. RESULTS Propafenone could effectively control VA but could not reverse positive VLP to negative meanwhile it had proarrhythmia effect (2/40), metoprolol could effectively control VA (38/46) and reverse positive VLP to negative (39/46) with no obvious side effects. The dosage from 50 to 100 mg/day made no difference. VA and VLP had no significant changes in group C. CONCLUSIONS Metoprolol is superior to other medicine for VA of positive VLP when the patients have no contraindication of β-receptor blocking agents.