Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of adult tuberculous pleural effusion in Hong Kong.

INTRODUCTION: Pleural fluid adenosine deaminase level can be applied to rapidly detect tuberculous pleural effusion. We aimed to establish a local diagnostic cut-off value for pleural fluid adenosine deaminase to identify patients with tuberculous pleural effusion, and optimise its utility. METHODS: We retrospectively reviewed the medical records of consecutive adults with pleural fluid adenosine deaminase level measured by the Diazyme commercial kit (Diazyme Laboratories, San Diego [CA], United States) during 1 January to 31 December 2011 in a cluster of public hospitals in Hong Kong. We considered its level alongside early (within 2 weeks) findings in pleural fluid and pleural biopsy, with and without applying Light's criteria in multiple scenarios. For each scenario, we used the receiver operating characteristic curve to identify a diagnostic cut-off value for pleural fluid adenosine deaminase, and estimated its positive and negative predictive values. RESULTS: A total of 860 medical records were reviewed. Pleural effusion was caused by congestive heart failure, chronic renal failure, or hypoalbuminaemia caused by liver or kidney diseases in 246 (28.6%) patients, malignancy in 198 (23.0%), non-tuberculous infection in 168 (19.5%), tuberculous pleural effusion in 157 (18.3%), and miscellaneous causes in 91 (10.6%). All those with tuberculous pleural effusion had a pleural fluid adenosine deaminase level of ≤100 U/L. When analysis was restricted to 689 patients with pleural fluid adenosine deaminase level of ≤100 U/L and early negative findings for malignancy and non-tuberculous infection in pleural fluid, the positive predictive value was significantly increased and the negative predictive value non-significantly reduced. Using this approach, neither additionally restricting analysis to exudates by Light's criteria nor adding closed pleural biopsy would further enhance predictive values. As such, the diagnostic cut-off value for pleural fluid adenosine deaminase is 26.5 U/L, with a sensitivity of 87.3%, specificity of 93.2%, positive predictive value of 79.2%, negative predictive value of 96.1%, and accuracy of 91.9%. Sex, age, and co-morbidity did not significantly affect prediction of tuberculous pleural effusion using the cut-off value. CONCLUSION: We have established a diagnostic cut-off level for pleural fluid adenosine deaminase in the diagnosis of tuberculous pleural effusion by restricting analysis to a level of ≤100 U/L, and considering early pleural fluid findings for malignancy and non-tuberculous infection, but not Light's criteria.

Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Newer fluoroquinolones for treating respiratory infection: do they mask tuberculosis?

Possible masking of tuberculosis (TB) in treatment of community-acquired respiratory infection by newer fluoroquinolones has not been examined in randomised controlled trials. We undertook a randomised, open-label controlled trial involving adults with community-acquired pneumonia or infective exacerbation of bronchiectasis encountered in government chest clinics in Hong Kong. 427 participants were assigned by random permutated blocks of 20 to receive either amoxicillin clavulanate (n = 212) or moxifloxacin (n = 215). Participants were followed for 1 yr for active pulmonary TB. Excluding three participants with positive baseline culture, 13 developed active pulmonary TB: 10 (4.8%) out of 210 were given amoxicillin clavulanate, and three (1.4%) out of 214 were given moxifloxacin. The difference was significant by both proportion and time-to-event analysis. Post hoc analysis showed a significant decrease in the proportion with active pulmonary TB from 4.8% to 2.4% and 0% among participants given amoxicillin clavulanate (n = 210), moxifloxacin for predominantly 5 days (n = 127) and 10 days (n = 87), respectively. The log rank test for trend also showed a significant difference between the three subgroups. Regression models reaffirmed the linear effect; the adjusted odds ratio (95% confidence interval) of active pulmonary TB after moxifloxacin exposure up to predominantly 10 days was 0.3 (0.1-0.9). Newer fluoroquinolones appear to mask active pulmonary TB.

A longitudinal study of multimodal evoked potentials in patients following radiotherapy for nasopharyngeal carcinoma.

Radiation rhombencephalopathy and radiation myelopathy may occur in patients months or years after radiotherapy for malignancy of the head and neck. We obtained multimodal evoked potentials longitudinally in 26 patients with proven nasopharyngeal carcinoma. Recordings were made before radiotherapy and at 1 week, 3 months, 9 months, 15 months, and 24 months after radiotherapy. All absolute latencies of evoked response before and after radiation were within normal limits. However, the I-III interpeak latencies of brainstem auditory evoked potentials and the onset latencies of motor evoked potentials in the whole group of patients at 15 months after radiation were significantly longer than those before radiotherapy, whereas the latencies at 24 months were not significantly different. The N20 latencies of somatosensory evoked potentials after radiotherapy were significantly prolonged at 3 months of follow-up; the prolongation then became normal. They indicate that a subclinical reversible radiation-induced dysfunction may occur in the auditory, sensory, and motor systems.

Role of atrial natriuretic peptide in the natriuretic response to central volume expansion induced by head-out water immersion in sodium-retaining cirrhotic subjects.

PURPOSE: It is possible that abnormalities in atrial natriuretic peptide may be involved in the pathogenesis of sodium retention in edema states. We performed a study in a group of 12 sodium-retaining cirrhotic subjects to determine the role of this peptide in mediating differences in the natriuretic response to central volume expansion induced by head-out water immersion. PATIENTS AND METHODS: Each patient was maintained for seven days on a 20-mmol sodium intake, and then studied on both control and immersion days. On each day, measurements of the following were obtained: plasma atrial natriuretic peptide, hematocrit, electrolytes, creatinine, plasma renin activity, serum aldosterone, urinary cyclic guanosine monophosphate (cGMP), blood pressure, and pulse rate. RESULTS: In six subjects, immersion resulted in a marked natriuresis sufficient to induce negative sodium balance by the third hour, and these subjects were termed "responders." In these six patients, baseline pre-immersion levels of plasma renin activity and serum aldosterone were all below 3 ng/liter/second and 4 nmol/liter, respectively. In the other six subjects, the natriuretic response to immersion was markedly blunted and insufficient to induce negative sodium balance, and these subjects were termed "non-responders." In these subjects, baseline pre-immersion levels of plasma renin activity and aldosterone were all above 3.5 ng/liter/second and 5 nmol/liter, respectively, and were significantly elevated compared with the responders, and compared with the normal range for control subjects consuming the same sodium intake. In both groups of cirrhotic subjects, baseline levels of plasma atrial natriuretic peptide and cGMP excretion were significantly and comparably elevated compared with the normal range for control subjects ingesting the same sodium intake. Despite the marked difference in the natriuretic response to immersion in both responders and non-responders, there was a significant and comparable further elevation of plasma atrial natriuretic peptide and urinary cGMP excretion during immersion, compared with the control day. CONCLUSION: These results suggest that the relative resistance to the natriuretic action of atrial natriuretic peptide in the non-responders compared with the responders is mediated by anti-natriuretic factors acting at a level parallel with or beyond atrial natriuretic peptide release or coupling to its cGMP-linked receptors.

Acute effects of peritoneovenous shunting on plasma atrial natriuretic peptide in cirrhotic patients with massive refractory ascites.

Plasma immunoreactive alpha-human atrial natriuretic peptide (ANP) was measured in six cirrhotic patients with massive refractory ascites, under strict metabolic conditions, while they were receiving a 20-meq sodium diet, both before and at two-hour intervals for eight hours following peritoneovenous shunting (PVS). The mean preoperative level of ANP was 75 +/- 18 pg/ml, which was found to be significantly higher than the normal range for this laboratory (8 to 24 pg/ml) (p less than 0.05). This value was also significantly higher than the value of 21 +/- 5 pg/ml (p less than 0.05) obtained in six patients with cirrhosis but without ascites. Following shunt insertion, an immediate natriuresis and diuresis were observed in five of the six cirrhotic patients with refractory ascites. In these five, right atrial pressure and ANP rose immediately, followed by a rise in the level of urinary cyclic guanosine monophosphate. The sixth subject had a delayed rise in right atrial pressure, and correspondingly the rise in ANP, the diuresis, and natriuresis were delayed. The changes in ANP following PVS were positively correlated with changes in right atrial pressure (p less than 0.05), urinary cyclic guanosine monophosphate (p less than 0.05), urinary sodium excretion (p less than 0.05), and urine volume (p less than 0.01). These results suggest that ANP may be important in mediating the acute response to PVS.

A multivariate analysis of prognostic factors in management of pineal tumor.

PURPOSE: A multivariate analysis of prognostic factors of treatment outcome of pineal tumor. METHODS AND MATERIALS: From February 1979 to June 1987, 25 patients with primary pineal tumors were treated in our department. Patients were treated with either AECL Co-60 unit or 10 MV linear accelerator to the primary tumor with an adequate margin or to the whole brain (median dose of 36 Gy) with or without a cone-down boost of 10 to 20 Gy. Craniospinal irradiation was performed in two patients with positive CSF cytology. Minimum follow-up was 40 months. Patients were further stratified according to tumor type. Group I consisted of seven patients with pineal germinoma. Group II included nine patients with nongerminoma, and Group III represented nine patients treated without a histological verification but clinical diagnosis. RESULTS: The relapse-free survival (RFS) of Group I patients was 100% and 86% at 2 and 5 years, respectively. Relapse-free survival was 55% and 21% at 2 and 5 years, respectively, for Group II patients. Six of 9 patients in Group II died of disease due to either local recurrence or tumor seeding. Eight of 9 patients in Group III remain no evidence of disease, and RFS was 89% at 2 and 5 years. Multivariate analysis revealed that tumor histology is the only significant prognosticator. Age, gender, type of surgical procedure, RT field, and tumor dose were not. Cox's regression model also failed to demonstrate a significant correlation of tumor seeding with the type of surgery. CONCLUSION: The type of tumors in the pineal region dictates the treatment outcome. Definitive radiation therapy is effective in controlling germinoma, whereas a more aggressive approach is needed to improve local control for nongerminoma. For a localized pineal lesion, we advocate that treatment can be tailored to the primary tumor with adequate margins. However, for locally advanced tumors whole brain or craniospinal irradiation should be considered. No definitive correlation between type of surgery and the probability of tumor seeding was identified.

High-dose-rate afterloading technique in the radiation treatment of uterine cervical cancer: 399 cases and 9 years experience in Taiwan.

Carcinoma of the uterine cervix has been the leading malignant neoplasm treated in our department. A comparative study was carried out using conventional low dose rate (LDR) with 137Cs sources (less than or equal to 100 cGy/hr) versus high dose rate (HDR) with 60Co sources (greater than 100 cGy/min) in the intracavitary (IC) application following external pelvic irradiation. A total of 399 patients were treated with external RT plus HDR radiation treatment alone from February 1980 through December 1985. Stage IIb and IIIb comprised 79.4% of cases (317 cases). The rate of initial complete response of the tumor, local control, and survival rate seemingly were better in the HDR group, but there was no significant difference statistically. The actuarial survival rates in all cases/definitive RT cases are 85%/85% for Stage 0-IIa, 53%/70% for IIb, 43%/49% for IIIa, 43%/53% for IIIb, 42%/47% for IVa, respectively. Complications were similar and the rectal complications were slightly higher in HDR group. The combination of pelvic irradiation with HDR intracavitary irradiation was more convenient for patients and also for personnel. The HDR technique may be a good substitution for IC treatment.

The clinical implications of hydronephrosis and the level of ureteral obstruction in stage IIIB cervical cancer.

PURPOSE: There are two criteria for the diagnosis of Stage IIIB cervical cancer in the FIGO staging system: tumor fixation to the pelvic side wall and/or the presence of hydronephrosis due to tumor. However, we often encounter hydronephrosis without tumor fixed to the pelvic side wall or the level of ureteral obstruction not corresponding to the main tumor mass in the pelvis. The clinical implication of these phenomena remains unclear. We investigated the Stage IIIB population treated at the Mallinckrodt Institute of Radiology and hypothesized that, if hydronephrosis presents without tumor fixation to the pelvic side wall or if the level of ureteral obstruction is above the main pelvic tumor mass, it most likely resulted from external compression of ureter(s) by enlarged lymph nodes and, consequently, a worse outcome is expected. METHODS AND MATERIALS: From 1959 to 1989, there were 297 patients with Stage IIIB cervical cancer who received definitive radiation therapy at the Mallinckrodt Institute of Radiology and were assessable for the presence of hydronephrosis and the level of ureteral obstruction. There were 281 patients who presented with tumor fixed to the pelvic side wall, and 62 of them were associated with concurrent hydronephrosis. An additional 16 patients presented with hydronephrosis without tumor fixation to the pelvic side wall. Among these 78 documented cases of hydronephrosis, the level of ureteral obstruction was above the true pelvis in 39 patients, and below the true pelvis in the other 39. Radiation therapy was individualized according to tumor extension and configuration; para-aortic lymph nodes were not routinely treated except in patients with clinical evidence of nodal metastasis. RESULTS: The progression-free survival (PFS) at 5 years was 35% in 62 patients with hydronephrosis and tumor fixed to the pelvic side wall vs. 43% in 213 patients with tumor fixed to the pelvic side wall only (p=0.12). However, PFS at 5 years decreased to 23% in 16 patients who presented with hydronephrosis without tumor fixation to the pelvic side wall (p < 0.001). When the level of ureteral obstruction was investigated, 5-year PFS was 39% vs. 22%, respectively, for the obstruction below vs. above the true pelvis (p=0.02). The majority of patients with ureteral obstruction above the true pelvis died of distant metastasis. CONCLUSIONS: The additional presence of hydronephrosis did not significantly worsen the PFS among Stage IIIB patients with tumor fixation to the pelvic side wall. However, hydronephrosis without tumor extending to the pelvic side wall or the level of ureteral obstruction above the true pelvis was associated with poor outcome due to a significant increase in distant failure. We propose that this population be separated from current Stage IIIB classification.

Prognostic factors of nasopharyngeal carcinoma: a multivariate analysis.

Between 1979 and 1985, 561 patients with nasopharyngeal carcinoma were reviewed to determine prognostic factors that may influence survival. Sex (p = 0.294) and histopathology (p = 0.677) had no correlation to the actuarial survival, whereas the site of cervical metastasis (p = 0.001) and the radiation doses to the nasopharynx and regional lymph nodes (p = 0.03) were both significant when one used univariate analyses. Cox's multivariate regression model revealed that the presence rather than the site of distant metastases was the single most important independent factor influencing the treatment outcome (p less than 0.0001). The addition of chemotherapy, on the other hand, did not show a survival benefit even when one took available confounding factors into account. There are, however, survival advantages associated with: (a) young age (less than or equal to 40 years), (b) asymptomatic status, (c) Stage I or II lesions, and (d) biopsy via nasopharynx instead of neck nodes. These favorable prognostic factors may be used for therapeutic guidance and end-result reporting.

Clinical significance of cranial nerve deficit in the therapy of nasopharyngeal carcinoma.

The results of radiation treatment of nasopharyngeal carcinoma (NPC) have recently been improved, but the prognosis remains relatively poor in cases with cranial nerve (CN) involvement. A total of 109 cases with histologically-proven NPC and cranial nerve involvement treated during 1979-1985 were reviewed and analysed. Definitive radiotherapy (RT) was given to patients with a high upper margin of the RT field at 2.5 cm above the base of the skull to a total dose of 70.2 Gy/39 fractions/8 weeks, with two applications of intranasopharyngeal brachytherapy. There were 37 cases (34%) in Group I (upward invasion only) and 72 cases (66%) in Group II (bidirectional invasion). Abducens, trigeminal, oculomotor and facial were the commonly involved nerves. Headache was the major symptom at diagnosis and was present in 82.6% of the patients, significantly higher than in general NPC cases (p less than 0.005). Fifty per cent (31/62) achieved complete response to definitive RT, but it did not correlate well with survival rate. The residual neurological deficit of each CN ranged from 31 to 57%. The actuarial 5-year survival rates of Groups I and II were similar in spite of neck lymph node metastasis in Group II (33% (I) compared with 24% (II); p greater than 0.05). Cases with single CN deficit did not show better results than those with multiple CN involvements. Five-year survivors were seen only in those who received a complete course of definitive RT.

Impact of prophylactic cranial irradiation in adenocarcinoma of the lung.

Out of 148 patients who had metastatic adenocarcinoma of the lung and were referred to Chang Gung Memorial Hospital for treatment from 1979 to 1987, 20% had symptomatic brain metastases. We have attempted to determine the subset of high-risk patients who might benefit from prophylactic cranial irradiation. In 25 patients with a complete remission, 36% (n = 9) eventually developed brain metastases after a minimum follow-up of 24 months. Patients with initial mediastinal node metastases showed a higher incidence of brain metastases (75%) than those harboring only hilar node metastases (25%, p = 0.03). Age, sex, tumor location and clinical staging had no significant correlation in the prognosis of brain metastases. Since the median recurrence-free survival rate of six months for patients with brain metastases was significantly shorter than for those without (14 months), we recommend that prophylactic cranial irradiation be conducted in complete responders with mediastinal nodal lesions to see if such treatment will prolong patients' recurrence-free survival via a reduction in brain metastases, thus improving their quality of life.

Concurrent radiotherapy and continuous 5-fluorouracil infusion in the management of locally advanced esophageal cancer.

From 1987 to 1989, a total of 22 patients with locally advanced non-metastatic esophageal cancer were treated by a combination of radiation therapy (RT) and chemotherapy (CT). RT, consisting of 250 cGy tumor dose per fraction with four fractions per week up to a total dose of 6000 cGy, was given concurrently with CT: 96 hours of continuous 5-fluorouracil (5-FU) infusion at a dose level of 250 g/kg/day. RT+CT was repeated every other week for a total of six cycles in 11 weeks. Toxicity data revealed that only mild to moderate mucositis, nausea/vomiting and myelosuppression occurred, and no patients developed unacceptable levels of toxicity necessitating discontinuation of the 5-FU infusion. Complete response (CR) was noted in nine out of 22 (41%) patients. The median progression-free survival period (MPFS) was 10 months, and the median absolute survival (MAS) was 13 months. Corresponding figures for our 61 previously RT treated patients (matched for sex, age, histopathology, tumor extent and location with current study group) were: CR rate, 8%; MPFS, three months; and MAS, six months. Kaplan and Meiers' survival curves and Log Rank test revealed a statistically significant difference in favor of the combined modality group (PFS, p = 0.0001; AS, p = 0.0001). The relatively good response rate and survival data appear to warrant further dose escalation in 5-FU since no major dose limiting toxicities were observed at 25 mg/kg/day.

Solitary plasmacytoma of bone.

From 1978 to 1992, 19 patients were diagnosed with solitary plasmacytoma of bone (SPB) accounting for 5.5% of plasma cell neoplasms in Chang Gung Memorial Hospital. Fourteen were male and five were female, with ages ranging from 21 to 71 years (median, 53 years). M-protein was detected at diagnosis in five patients, and during follow-up in three. The most common sites of SPB were the vertebral bodies, with seven involving the thoracic, four involving the lumbar and two involving the cervical spine. The remaining sites included the skull in four, and femur and pelvis in one each. Fifteen of the patients received local radiotherapy, local control was achieved in all; nine patients were alive with no evidence of disease for seven to 77 months, two patients remained in apparent remission at 14 and 92 months, two patients progressed to multiple myeloma at 12 and 84 months, one patient developed extramedullary plasmacytoma at three months, and one patient died of intercurrent disease at four months. The four patients who were not treated with radiation therapy ultimately developed local recurrence or dissemination within four years. In our series, local recurrence or dissemination was always associated with the appearance of, or an increase in, the M-component; thus, measurement of M-protein is helpful in assessing tumor control or progression. Based on our experience and a review of the literature, it is recommended that irradiation of the primary sites is the treatment of choice. Chemotherapy is indicated in those patients with disease progression, recurrence, or dissemination.

Comparison of radiotherapy and surgical results of early stage glottic cancer: a retrospective analysis.

From March 1977 to October 1989, 85 patients with early stage glottic cancer were treated with either radiotherapy or surgery at Chang Gung Memorial Hospital (CGMH). Patients were excluded from the analysis of local control if they died or remained disease-free with a follow-up period of less than two years. Of the 26 patients treated with definitive radiotherapy, initial control of the primary lesions was achieved in 100% of stage T1s, 76% of T1, and 57% of T2 patients. Surgical salvage of radiation failure was achieved in 83% of the patients, giving the ultimate local control of 100% for T1s, 94% for T1, 86% for T2 patients. Of the 44 patients treated with definitive surgery, initial control of the primary lesions was achieved in 100% for T1s, 95% for T1, and 78% for T2 patients. Salvage of the surgical failure was 50%, giving the ultimate control in this group of 100% for T1s, 95% for T1, 83% for T2. There was no difference in either initial or ultimate control of T1 and T2 lesions between patients treated with primary radiotherapy and primary surgery. Voice preservation rates were 73% and 34% in the radiotherapy and surgery group, respectively. When divided into two groups according to the times they were being treated, we found that surgery preserved a comparable number of larynges as radiotherapy did after 1988 (60% vs 77%, p = 0.33). It is concluded that radiotherapy and surgery could achieve the same good local control results and long-term survival and comparable functional results of early stage glottic cancer, if conservative surgery is carefully selected for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptive rival penalized competitive learning and combined linear predictor model for financial forecast and investment.

We propose a prediction model called Rival Penalized Competitive Learning (RPCL) and Combined Linear Predictor method (CLP), which involves a set of local linear predictors such that a prediction is made by the combination of some activated predictors through a gating network (Xu et al., 1994). Furthermore, we present its improved variant named Adaptive RPCL-CLP that includes an adaptive learning mechanism as well as a data pre-and-post processing scheme. We compare them with some existing models by demonstrating their performance on two real-world financial time series--a China stock price and an exchange-rate series of US Dollar (USD) versus Deutschmark (DEM). Experiments have shown that Adaptive RPCL-CLP not only outperforms the other approaches with the smallest prediction error and training costs, but also brings in considerable high profits in the trading simulation of foreign exchange market.

Peak plasma rifampicin level in tuberculosis patients with slow culture conversion.

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion.

Fluorogenic nanocrystals for highly sensitive detection of C-reactive protein.

A solid-phase sandwich fluorescence immunoassay using nanocrystals of a fluorogenic precursor, fluorescein diacetate (FDA), conjugated with monoclonal antibodies for the detection of C-reactive protein (CRP), is described. FDA nanocrystals were coated with distearoylglycerophosphoethanolamine (DSPE), modified with amino(poly(ethylene glycol))(PEG(2000)-Amine) as an interface for coupling biomolecules. CRP was chosen as a model analyte because of its widely accepted role as a marker for acute inflammation and prospective heart failure. A low limit of detection (1.10 microg l(-1)) and high precision (CV = 2.72-9.48%) were achieved. Following the immunoreaction, the monoclonal anti-CRP conjugated nanocrystals were released by hydrolysis and dissolution instigated by the addition of a large volume of organic solvent-sodium hydroxide mixture. Using human serum samples from 66 patients with high heart attack risk and 19 healthy blood donors, this CRP fluorescence immunoassay showed a good correlation to the commercially available, turbidimetric immunoassay for CRP. This result was corroborated by the Bland-Altman plot that showed a mean difference between the two methods of only 0.36+/-1.46 mg l(-1). The study demonstrates that the organic fluorogenic FDA nanocrystals can be applied for the detection of CRP, which is a clinically interesting plasma protein with a low limit of detection.

A morphological and morphometric analysis of the optic nerve in the hypothyroid rat.

This investigation was designed to morphologically evaluate the effects of hypothyroidism on the development of myelin and axons in the rat optic nerve. Four pups from each group of normal and propylthiouracil-induced hypothyroid rats were sacrificed at 14, 21, 28, and 35 postnatal days. Optic nerves were studied by both light and electron microscopes. The hypothyroid animals had significantly reduced body and brain weights compared to those of their age-matched controls. In the hypothyroid animals, the cross-sectional area of the optic nerve, the fiber density, and fiber occupancy were significantly diminished compared to those of the controls. The mean individual fiber size was unaffected. However, the relationship between the total axonal area to myelin thickness was similar in the control and experimental groups, implying that the feedback mechanism between myelinating cells and axons was not affected by hypothyroidism. Thus, this study indicates that the principal insult of neonatal hypothyroidism results in a delay in myelin acquisition of myelinated fibers, resulting in diminished cross-sectional area of the optic nerve, fiber density, and fiber occupancy.