Characteristics of optic disc changes in Taiwanese patients with primary angle-closure glaucoma.

BACKGROUND AND PURPOSE: Primary angle-closure glaucoma (PACG) is the predominant form of glaucoma among Asians. Although numerous studies have been done to describe the characteristic optic disc changes in patients with primary open angle glaucoma (POAG) which is the predominant form of glaucoma among Western populations, few studies have evaluated the optic disc changes in patients with PACG. The aim of this study was to elucidate the characteristic intrapapillary and parapapillary disc changes in PACG in a cross-sectional study and to develop a practical approach to the detection of glaucomatous optic disc changes in PACG by ophthalmoscopic examination. METHODS: A total of 103 eyes in 103 PACG patients were studied. Forty one eyes of 41 age- and sex-matched healthy subjects served as controls. Three glaucoma-trained subspecialists examined stereophotographs of optic discs to evaluate the intrapapillary and parapapillary changes. The differences in PACG and control group eyes were compared. RESULTS: Concentric steep enlargement of the optic disc was found in 99 PACG eyes (96%). Local notching was noted in only 3 eyes, and vertically oval-shaped cupping of the optic disc in only 1 eye. Disc hemorrhage was not detected in any eye. Parapapillary atrophy of the alpha zone involving both temporal and nasal side of the optic disc and parapapillary atrophy of beta zone were significantly more frequent in the PACG group. The presence of an alpha zone or a beta zone simultaneously involving both the temporal and nasal side of the optic disc was associated with more severe optic nerve head damage. CONCLUSIONS: The intrapapillary change in the PACG group eyes reflected the development of cupping in PACG patients with small and compact optic discs. The parapapillary atrophy paralleled the intrapapillary optic disc cupping in eyes of the PACG group.     

A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels.

Toxins from cone snail (Conus species) venoms are multiple disulfide bonded peptides. Based on their pharmacological target (ion channels, receptors) and their disulfide pattern, they have been classified into several toxin families and superfamilies. Here, we report a new conotoxin, which is the first member of a structurally new superfamily of Conus peptides and the first conotoxin affecting vertebrate K+ channels. The new toxin, designated conotoxin ViTx, has been isolated from the venom of Conus virgo and comprises a single chain of 35 amino acids cross-linked by four disulfide bridges. Its amino acid sequence (SRCFPPGIYCTSYLPCCWGICCSTCRNVCHLRIGK) was partially determined by Edman degradation and deduced from the nucleotide sequence of the toxin cDNA. Nucleic acid sequencing also revealed a prepropeptide comprising 67 amino acid residues and demonstrated a posttranslational modification of the protein by releasing a six-residue peptide from the C-terminal. Voltage clamp studies on various ion channels indicated that the toxin inhibits the vertebrate K+ channels Kv1.1 and Kv1.3 but not Kv1.2. The chemically synthesized product exhibited the same physiological activity and identical molecular mass (3933.7 Da) as the native toxin.     

The clinical significance of venom detection in patients of cobra snakebite.

Cobra snakebites are one of the most frequent occurrences among the poisonous snakebites. The correlation between the serum concentrations of cobra venom in the victims with the severity of systemic and local symptoms after envenoming is still awaited for investigation. In this paper, we have developed an enzyme-linked immunosorbent assay (ELISA) to detect Taiwan cobra venom existed in the serum of the cobra snakebite victims. This established technique allowed us to detect as low as 1 ng/ml. Totally, 31 serum samples of 27 recognized and suspected cobra snakebite patients were analyzed by the developed ELISA technique. The highest venom level detected was 1270 ng/ml in a case 2 h after being envenomed. We found that the serum concentrations of the venom in the bitten patients were well correlated with the severity of local tissue destruction. Venom levels might remain high 48 h after snakebite. Two or more vials of specific antivenom administered soon after snakebite were effective in neutralizing the circulating venom as revealed by ELISA. Higher doses of antivenom may be indicated in cases of cobra venom-induced local tissue destruction. In conclusion, these results indicate that venom detection in snakebite victims is valuable in diagnosis and severity assessment of Taiwan cobra snakebite.     

Trace Metals' abnormalities in hemodialysis patients: relationship with medications

A multicenter collaborative study was performed to investigate the prevalence of abnormal blood contents of 6 trace metals, copper (Cu), zinc (Zn), aluminum (Al), lead (Pb), cadmium (Cd), and mercury (Hg), in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, Al containing phosphate-binding agents, 1,25-dihydroxy vitD3, 1-hydroxy vitD3, and erythropoietin (EPO), as well as hematocrit level, by chi-square statistics. From 6 medical centers in Taiwan, we included 456 patients in maintenance HD for more than 4 months for this study, and they had continued the previously mentioned medications for at least 3 months. Blood samples were collected before initiating HD, and atomic absorption spectrophotometry was used to measure plasma levels of Cu, Zn, and Al as well as whole blood levels of Pb, Cd, and Hg. Three hundred seventy-five (78%) of the HD patients had low plasma Zn levels, that is, <800 microg/L, and the mean (+/-SD) concentration was 705.8 (+/-128.23) microg/L in all subjects. One hundred forty-one (31%) of the HD patients had high plasma Al, that is, >50 microg/L, and the mean (+/-SD) was 44.30 (+/-28.28) microg/L in all subjects. Three hundred thirty-three (73%) of the dialysis patients had high Cd levels, that is, >2.5 microg/L, and the mean (+/-SD) was 3.32 (+/-1.49) microg/L in all subjects. The majority of HD patients had normal blood levels of Cu, PB, and Hg. Only 21 (4. 6%), 5 (1.1%), and 3 (0.06%) patients had elevated blood levels of Cu, Pb, and Hg, respectively. Their mean (+/-SD) blood concentration of Cu, Pb, and Hg were 1,049.78 (+/-233.25) microg/L, 7.45 (+/-3.95) microg/dL, and 3.17 (+/-25.56) microg/L, respectively. Three patients had elevated plasma Hg concentrations, that is, 546, 12.6, and 24.0 microg/L, respectively. In the 152 normal healthy age and sex matched control group, the blood levels of Al, Cd, and Pb were all significantly lower than the HD patients. However, the levels of Cu and Zn were higher in the control group. The Hg level was not significantly different in both groups. There was no statistical difference between patients with normal and abnormal blood levels of trace metals in various medications except Al containing phosphate binder. The Al containing phosphate binder users had significantly higher plasma Al levels (54.71 +/- 26.70 versus 41.15 +/- 28.03 microg/L, p < 0.001) and hematocrit levels (29.61 +/- 4.61 versus 27. 81 +/- 3.91, p < 0.0005). There was no statistical correlation between erythropoietin (EPO) dose and hematocrit level in these patients. In conclusion, the blood level of trace metals of these HD patients except Al was not related to their medications. However, caution must be exercised in interpreting this result as dose and duration of medication; efficiency of HD and water treatment may play an important role. Otherwise, environmental factors, diet, and the aging process may contribute to the trace metal burden in uremia. Thus, Zn and Cu are abundant in seafood, and Cd is abundant in contaminated plants such as rice.     

Natural changes in peritoneal equilibration test results in continuous ambulatory peritoneal dialysis patients: a retrospective, seven year cohort survey

We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long-term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty-two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P-cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high-average (HA), low-average (LA), or low (L) transporters with the dividing ratios (D:P-cre) of >0.81, >0. 65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P-cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P-cre was strongly and inversely correlated with the initial D:P-cre value (r = -0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = -0.752; p < 0. 01) and between the change in the final UF and the initial UF (r = -0.875; p < 0.01). No correlation was found between the change in D:P-cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non-diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, chi2 test). We demonstrated a natural "centralization" migration of PET results after long-term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.     

FLT3-TKD mutation in childhood acute myeloid leukemia.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.     

Clinical evaluation of HER-2/neu protein in malignant pleural effusion-associated lung adenocarcinoma and as a tumor marker in pleural effusion diagnosis.

PURPOSE: Lung adenocarcinoma presenting as malignant pleural effusion (MPE) is common in Taiwan. Microscopically, the involved pleurae are infiltrated by numerous tumor foci, which suggests that the cancer cells are highly invasive. Overexpression of HER-2/neu has been related to proliferation, antiapoptosis, and the high invasiveness of various cancer cells. We therefore were interested in studying the role of HER-2/neu in MPE-associated adenocarcinoma cell lung cancer (ADCLC). Experimental Design: The expression of HER-2/neu in pleural effusion was measured by ELISA. The HER-2/neu protein expression on tumor cells was evaluated by immunohistochemical (IHC) staining, and gene amplification was assayed by fluorescence in situ hybridization. RESULTS: The mean value of HER-2/neu in pleural effusions of patients with ADCLC and other nonmalignant lung diseases was 9.9 and 2.7 ng/ml, respectively. The difference is statistically significant (P < 0.001). Compared with cytokeratin 19 fragment CYFRA 21-1, the performance of HER-2/neu as a tumor marker in pleural effusion diagnosis was better. Overexpression of HER-2/neu in tumor tissues was found in 70% (23 of 32) of patients with MPE-associated ADCLC, 30% (13 of 43) with stage I/II non-small cell lung cancer (NSCLC), and 44% (14 of 32) with stage III NSCLC. The incidence of HER-2/neu overexpression in tumor tissues of patients with MPE-associated ADCLC was significantly higher than that of patients with stage I-III NSCLC without MPE. HER-2/neu gene amplification was uncommon (1.9%). The correlation between the IHC H-score in tumor samples and the pleural effusion level of HER-2/neu was significant (P < 0.01). A higher incidence of HER-2/neu expression beyond the cutoff point (5.5 ng/ml) in pleural effusions was also found in patients whose IHC H-scores were >50. CONCLUSIONS: These findings indicate that HER-2/neu is important in the pathogenesis of MPE-associated ADCLC and is a potential tumor marker for a diagnosis of pleural effusion.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Hemorrhagic disease in a newborn due to inadequate vitamin K prophylaxis: case report

Vitamin K prophylaxis for all neonates has been recommended to prevent hemorrhagic disease of the newborn (HDN), but it is still an uncommon practice in most developing countries throughout the world. In the United States and Canada, where vitamin K injections continue to be recommended in the newborn period, HDN is not a major concern. The risk factors for HDN include inadequate vitamin K prophylaxis, exclusively breast-fed infants, diarrhea, and alternative causes of vitamin K deficiency, such as liver disease and cystic fibrosis. We present an exclusively breast-fed 3-week-old infant with diarrhea for 2 days who died from intracranial hemorrhage related to HDN despite having received a single intramuscular injection of 0.2 mg of vitamin K at birth. Hemorrhage in the infant from vitamin K deficiency should be a concern for pediatricians and obstetricians. We emphasize the importance of administering an adequate dosage of vitamin K for prevention of HDN, particularly in an exclusively breast-fed infant.