Search

The Water Erosion Prediction Project (WEPP) model was applied to seven paired, nested watersheds within the Mica Creek Experimental Watershed located in northern Idaho, USA. The goal was to evaluate the ability of WEPP to simulate the direct and cumulative effects of clear-cutting and partial-cutting (50% canopy removal) on water and sediment yield. WEPP was modified to better represent changes in the Leaf Area Index during post-harvest forest vegetative recovery. Good agreement between simulated and observed streamflow was achieved with minimal to no calibration over a 16-year (1992-2007) period. For the seven watersheds and the entire study period, the overall Nash-Sutcliffe Efficiency (NSE), Kling-Gupta efficiency (KGE), and deviation of runoff volume (D V ) between observed and simulated daily streamflow ranged 0.58-0.71, 0.67-0.81, and -4% to 9%, respectively. Good agreement between predicted and observed suspended sediment yield was achieved through the calibration of a single channel critical shear stress parameter. For sediment yield, NSE, KGE, and D V ranged 0.62-0.97, 0.43-0.97, and -2% to 2%, respectively, for the calibration period, and 0.61-0.93, 0.42-0.95, and -24% to 13%, respectively, for the period of model performance assessment. Regression analysis of observed- and WEPP-simulated increase in water and sediment yield following clear-cut treatment was similar; however, the WEPP-simulated increase was lower compared to observations particularly from the partial-cut watershed. The variability in the critical shear parameter for different stream channels in the study watersheds was directly related to the observed mean particle size on the stream bed and suggests that applications of the WEPP model in ungauged basins could potentially set the critical shear parameter based on particle size. Overall, the simulated results demonstrate the potential of WEPP as a modeling tool for forestland watershed management, particularly for estimating the effects of forest harvest on hydrograph fluctuations and consequently, stream sediment transport., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To identify features of BOLD signal change associated with interictal epileptiform discharges (IEDs) in a heterogeneous group of focal epilepsy patients., Methods: EEG/fMRI studies in 27 focal epilepsy patients were reviewed with attention given to the extent and location of the IED and the resulting pattern of BOLD signal change. Second order group analysis was used to identify common features., Results: fMRI results provided novel clinical information for individual patients. We identified a significant common node within the ipsilateral piriform cortex as well as patterns involving distant cortical or subcortical areas., Conclusion: Despite the heterogeneity of IEDs in focal epilepsy, there are important common features underpining IEDs with a highly significant fMRI node in the ipsilateral piriform cortex., Significance: There are important common features in the networks involved in IEDs in patients with a heterogeneous range of epileptogenic foci. We confirm that the piriform cortex is a common node underlying IEDs in patients with focal epilepsy and so provides a target for further study and potential therapy. We describe important features of BOLD signal change that accompany focal and diffuse IEDs that will help researchers and clinicians navigate the sometimes complex findings revealed by these studies., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: The goal of this study was to determine the consistency of human reviewer spike detection and then develop a computer algorithm to make the intracranial spike detection process more objective and reliable., Methods: Three human reviewers marked interictal spikes on samples of intracranial EEGs from 10 patients. The sensitivity, precision and agreement in channel ranking by activity were calculated between reviewers. A computer algorithm was developed to parallel the way human reviewers detect spikes by first identifying all potential spikes on each channel using frequency filtering and then block scaling all channels at the same time in order to exclude potential spikes that fall below an amplitude and slope threshold. Its performance was compared to the human reviewers on the same set of patients., Results: Human reviewers showed surprisingly poor inter-reviewer agreement, but did broadly agree on the ranking of channels for spike activity. The computer algorithm performed as well as the human reviewers and did especially well at ranking channels from highest to lowest spike frequency., Conclusions: Our algorithm showed good agreement with the different human reviewers, even though they demonstrated different criteria for what constitutes a 'spike' and performed especially well at the clinically important task of ranking channels by spike activity., Significance: An automated, objective method to detect interictal spikes on intracranial recordings will improve both research and the surgical management of epilepsy patients., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to investigate the dissolution characteristics of an acetaminophen/theophylline (AT) cocrystal compared with its pure components and physical mixtures. Intrinsic dissolution studies were conducted by a rotating-disk method. Solubility studies were conducted by collecting transient samples at 5, 30, and 60 min and equilibrium samples after 72 h, both at 37 °C. The AT cocrystal had a faster dissolution rate than AT physical mixtures, and the dissolution profiles were congruent (1:1 mole ratio) under different pH conditions. Thus, the AT cocrystal dissolved congruently at short times and exhibited higher transient solubility compared with its two pure components. Equilibrium solubilities of theophylline from the cocrystal were lower than transient values due to theophylline hydrate precipitation but no precipitation of free acetaminophen occurred. The solubility behavior of acetaminophen and theophylline exhibited typical 1:1 complex formation in physical mixtures, cocrystal, and phase-solubility studies. The Levich equation was used to predict the dissolution behavior of the AT cocrystal as well as that of the single components., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: The aim of this investigation was to determine the effect of inaccurate or inconsistent marking up of events in the EEG on statistical analysis of EEG/fMRI studies of patients with epilepsy., Methods: EEGs obtained during EEG/fMRI studies conducted on 10 patients with epilepsy and six normal control subjects were reviewed. All clear epileptiform events were marked up in the patient EEGs, as were all small movement-related artefacts in the patient and control subject EEGs. We then considered the effect on the numbers of voxels above threshold in the resulting Statistical Parametric Mapping (SPM) analysis if events were omitted, mislabelled, or if event times were inconsistently marked up., Results: Omitting true epileptiform events resulted in a decrease in the number of voxels that survive statistical threshold. Mixing epileptiform and non-epileptiform events in the SPM analysis generally (but not always) decreased the number of voxels that survived threshold. Inconsistent event mark-up had little effect if the inconsistency was small (<200 ms), but had more effect if it was large (>500 ms)., Conclusion: It is important to accurately mark-up EEGs acquired during EEG/fMRI studies in order to get the best results from subsequent analyses., Significance: Our study reveals the consequences of inaccurate review of the EEG in EEG/fMRI studies and suggests guidelines for the review of EEG in these investigations which, if followed, should result in studies of acceptable quality.

Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory stimulation on brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast, which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 +/- 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects: the fractional signal change was reduced by 28 +/- 12% (P < .05). These changes were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain.

Objective: We evaluated the use of an efficient dipole source algorithm to improve performance of automated spike detection by identifying false detections caused by artefacts., Methods: Automated spike detections were acquired from 26 patients undergoing prolonged electroencephalograph (EEG) monitoring. Data from 6 patients were used to develop the method and data from 20 patients were used to test the method. To provide a standard against which to evaluate the results, an electroencephalographer (EEGer) visually categorized all automated detections before the dipole models were calculated for all events. The event categories (as defined by the EEGer) were then combined with properties of the dipole model and features were identified that differentiated spike and artefact detections. The resulting method was then applied to the testing data set., Results: Residual variance and eccentricity of the dipole models differentiated artefact and spike detections. A separate set of rules defining eye blink artefact was also developed. The combined criteria removed a mean of 53.2% of artefact from the testing data set. Some spike detections (4.3%) were also lost., Conclusions: The features of the dipole source of a detected event can be used to differentiate artefacts from spikes. This algorithm is computationally light and could be implemented on-line.

Papillary cell carcinoma of the thyroid is a relatively indolent disease, usually presenting as an asymptomatic mass in the thyroid gland that is either noted by the patient or diagnosed at routine clinical examination. Although the prognosis is generally good there are a number of controversies in the management of this condition. The significance of age at presentation, size of the tumour and the presence of lymph node metastasis are still disputed. We present the unusual case of a woman found to have papillary cell thyroid carcinoma within a lymph node during a cosmetic thyroid lobectomy. The thyroid tissue removed was not found to contain tumour. We describe the evidence behind the decision to proceed to total thyroidectomy and the finding of a tiny focus of papillary cell thyroid carcinoma within the contralateral lobe., (Copyright 2000 Harcourt Publishers Ltd.)

A near-infrared spectroscopic method to quantify drugs or excipients within polymeric matrixes is proposed. Cylindrical implants were fabricated by a melt-mold technique containing various ratios of poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG) and various loadings of lomefloxacin HCl with a constant ratio (70:30 w/w) of PCL/PEG. Near-infrared (NIR) spectra were obtained on intact sections of larger implants using a Foss NIRSystems Model 5000 monochrometer equipped with a Rapid Content Analyzer. Spectral data were treated with second derivative transformation followed by linear regression and PLS to obtain correlation with lomefloxacin or PEG content. Lomefloxacin content was separately determined by UV analysis (287 nm) using a validated extraction procedure. The NIR method was tested by comparing predicted loadings of test implants with either theoretical values based on weight (PEG) or with UV analysis results (lomefloxacin). Second derivative spectral values at particular wavelength ratios (PEG, 2064 nm/1698 nm; lomefloxacin, 2172 nm/2226 nm and 1824 nm/1862 nm) yielded linear results for PEG or lomefloxacin content. PEG content determined by NIR spectroscopy was in excellent agreement with theoretical content. Lomefloxacin content determined by NIR spectroscopy was also in excellent agreement with UV analysis. NIR analysis is interpreted through the use of corresponding mid-infrared spectral data.

Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.

To assist in the reviewing of prolonged EEGs, we have developed an automatic EEG analysis method that can be used to compress the prolonged EEG into two pages. The proposed approach of Automatic Analysis of Segmented-EEG (AAS-EEG) consists of 4 basic steps: (1) segmentation; (2) feature extraction; (3) classification; and (4) presentation. The idea is to break down the EEG into stationary segments and extract features that can be used to classify the segments into groups of like patterns. The final step involves the presentation of the processed data in a compressed form. This is done by providing the EEGer with a representative sample from each group of EEG patterns and a compressed time profile of the complete EEG. To verify the above approach, 41 6 h EEG records were assessed for normality via the AAS-EEG and conventional EEG approaches. The difference between the overall assessment via compressed and conventional EEG was within one abnormality level 100% of the time, and within one-half level for 73.6% of the records. We demonstrated the feasibility and reliability of automatically segmenting and clustering the EEG, thus allowing the reduction of a 6 h tracing to a few representative segments and their time sequence. This should facilitate review of long recordings during monitoring in the ICU.

Objectives: was to design a warning system for the pediatric intensive care unit (PICU). The system should be able to make statements at regular intervals about the level of abnormality of the EEG. The warnings are aimed at alerting an expert that the EEG may be abnormal and needs to be examined., Methods: A total of 188 EEG sections lasting 6 h each were obtained from 74 patients in the PICU. Features were extracted from these EEGs, and with the use of fuzzy logic and neural networks, we designed an expert system capable of imitating a trained EEGer in providing an overall judgment of abnormality about the EEG. The 188 sections were used in training and testing the system using the rotation method, thus separating training and testing data., Results: The EEGer and the expert system classified the EEGs in 7 levels of abnormality. There was concordance between the two in 45% of cases. The expert system was within one abnormality level of the EEGer in 91% of cases and within two levels in 97%., Conclusions: We were therefore able to design a system capable of providing reliably an assessment of the level of abnormality of a 6 h section of EEG. This system was validated with a large data set, and could prove useful as a warning device during long-term ICU monitoring to alert a neurophysiologist that an EEG requires attention.

In another publication, we described a set of methods for automatic detection of EEG seizures in the newborn. We describe here the evaluation of these methods using a completely new set of data, which were not used in developing the method. This testing data set consisted of recording from 54 patients, lasting an average of 4.4 h. Recordings had 8-16 channels and were obtained, in approximately equal numbers, from 3 institutions in Canada, the USA and Australia. Recording conditions varied from short recordings fully attended by a technologist to overnight recordings largely unattended. The average seizure detection rate was 69% (77%, 53%, 84% in the 3 institutions). False detections occurred at the average rate of 2.3/h (4.1, 1.0, 2.7 in the 3 institutions), with fluctuations that reflected largely the technical quality and level of supervision of the recordings. The results are similar to those obtained in the commonly used method of epilepsy monitoring in adults and allow us to envisage clinical application.

Seizures are most common in the newborn period, but at that age seizures can be very difficult to identify by clinical observation. Therefore the EEG plays an even greater role in newborns than in older children and adults. The electrographic features of seizures and EEG background in the newborn are, however, very different to those found in adults. We present a set of methods for the automatic detection of seizures in the newborn. The methods are aimed at detecting a wide range of patterns, including rhythmic paroxysmal discharges at a wide range of frequencies, as well as repetitive spike patterns, even when they are not very rhythmic. The methods were developed using EEGs obtained from 55 newborns, recorded at 3 hospitals that used differing monitoring protocols. A total of 281 h of recordings containing 679 seizures were analyzed. An initial evaluation indicated that 71% of the seizures and 78% of seizure clusters (group of seizures separated by less than 90 s) were detected, with a false detection rate of 1.7/h. The methods were developed so that they can be implemented to operate in real time.

One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, isoniazid, and pyrazinamide through unpurified CF respiratory mucus and through purified pig gastric mucus solutions were compared in order to evaluate the relative barrier properties of these mucus solutions. These model compounds, while not often used clinically in CF, are used in other pulmonary diseases and have the potential to be administered by inhalation delivery systems. Permeability studies were carried out in Side-Bi-Side diffusion cells fitted with a custom membrane holder capable of retaining the mucus solutions. Permeabilities through CF mucus solution and its fractions were compared to those measured through buffer and reconstituted purified pig gastric mucus. There were 28--75% decreases in drug permeability when pig gastric mucus was replaced by different CF mucus solutions. This indicates that optimal drug delivery directly to the lungs must take into account the decreased drug transport rate across diseased mucus in addition to drug loss due to binding to the glycoproteins or inefficient delivery via aerosolization. Transmission electron microscopy revealed minor differences in the glycoprotein strand structure between reconstituted pig gastric mucus and CF mucus primarily with regard to glycoprotein chain length and extent of branching. Similar viscoelastic behaviors between the CF gel fraction and synthetic CF mucus were observed. This model CF mucus system can simulate diseased mucus and can be utilized for in vitro studies to optimize drug permeability.

Previously, we reported that the entrapment of suramin in dipalmitoylphosphatidylcholine (DPPC, C16) multilamellar liposomes ranged from 25% to 65% and the addition of 30-50 mol% cholesterol (CHL) greatly reduced entrapment. Entrapment of small molecules similar to suramin, disodium 1,5-naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthalenedisulfonic acid (1.2%), were very low. In the present study, the entrapment and interaction of suramin with dilauroylphosphatidylcholine (DLPC, C12), dimyristoylphosphatidylcholine (DMPC, C14), and distearoylphosphatidylcholine (DSPC, C18) liposomes was investigated. DLPC and DMPC showed 2-3-fold higher entrapment percentages (95.1% and 74.2%, respectively) than DPPC (37%). However, the entrapment with DSPC (29%) was about 25% lower than DPPC. Adding 50 mol% cholesterol greatly reduced suramin entrapment for all phospholipids. The entrapment of polysulfonated dyes such as Evans blue, Direct blue 1, or Trypan blue, which are structurally similar to suramin, was found to be in the same order of DLPC > DMPC > DPPC > DSPC. Differential scanning calorimetry of aqueous dispersions of DLPC and DMPC with suramin showed more apparent interaction than for DPPC and DSPC. These results suggest that a large portion of the associated suramin and other polysulfonated compounds results from binding to the surface of the phospholipid bilayer or intercalation into the liposomal bilayer. The phospholipid chain length effect on entrapment may be due to the lower net van der Waals interaction between hydrocarbon chains for shorter acyl chains which also increases the bilayer intermolecular spacing. Such effects could then increase the ability of suramin to interact with individual phospholipid molecules.

The liposomal entrapment of suramin and similar compounds in phospholipid vesicles was examined. For dipalmitoylphosphatidylcholine (DPPC) liposomes, entrapment percentages ranged from 25 to 65% with 3-25 mM phospholipid for aqueous solutions containing 0.07 mM of suramin. Incorporation of 30-50 mol % cholesterol (CHL) into DPPC liposomes reduced the percentage suramin entrapment. Addition of positively-charged stearylamine (5 mol %) to DPPC/CHL liposomes increased the entrapment from 2.3% to 30.3%. Entrapment was not affected by the incorporation of negatively-charged phosphatidylglycerol into DPPC/CHL liposomes. When the amount of suramin was increased from 0.07 to 0.7 mM, the entrapment percentage decreased from 37% to 11% when DPPC was held constant at 6 mM. The entrapment of 0.07 mM Evans blue, a molecule similar in structure to suramin, was 51.6% in DPPC liposomes for 6 mM phospholipid. The entrapment percentage, however, decreased by about 50% when incorporated into 7:3 (DPPC/CHL) liposomes. The liposomal entrapment of disodium 1,5-naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthalene-disulfonic acid (1.2%) was very low compared to that of suramin or Evans blue. Differential scanning calorimetry studies of suramin and an aqueous dispersion of DPPC showed an apparent interaction between them. These observations suggest that a significant portion of the entrapped suramin results from binding of suramin to the surface of or intercalation into the liposomal bilayer. Surface binding or intercalation into the phospholipid bilayer may be attributed to both ionic and hydrophobic interactions. The ionic interaction would arise from the suramin sulfonate groups associating with the cationic choline portion of the phospholipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Poly(D,L-lactide-co-glycolide, 50:50) samples of similar molecular weight were obtained from three commercial sources and were characterized by gel permeation chromatography, differential scanning calorimetry, X-ray powder diffraction, viscometry, and proton nuclear magnetic resonance spectroscopy. Pellets were prepared by melt-pressing spray-dried polymer with a 4-mm standard concave punch and die set and a thermostated holder of original design. Amaranth (5% w/w) was incorporated in pellets used for release studies. Degradation and release studies were conducted at 37 degrees C in pH 7.2 phosphate buffered saline. The molecular weights of all polymers were found to decrease continuously after exposure to phosphate buffered saline. All polymers showed two distinct regions of molecular weight decrease. Mass loss experiments for all polymers resulted in sigmoidal curves typical of polymers undergoing bulk hydrolysis. The onset of mass loss (defined as 10% mass loss) was found to differ by as much as 6 days among the three polymers studied. The release studies showed an initial burst of release followed by a period of 15-25 days during which little or no dye was released. A second phase of release followed, lasting approximately 10 days, until all dye was released. The time at which release began slightly preceded the onset of mass loss.

The effect of self-association of the antihistaminic drugs pheniramine, chlorpheniramine, and brompheniramine as their maleate salts on the solubilization of salicylamide and acetaminophen in aqueous solution has been investigated. The total solubility of salicylamide increased nonlinearly at lower antihistamine concentrations (less than 0.4 M), but reached limiting linearity (slope = 0.34 mol/mol of antihistamine) at higher concentrations (up to 0.8 M). Salicylamide solubility increases are approximately 10-fold at high concentrations (0.6-0.8 M) of antihistamine, while acetaminophen solubility increases are about fivefold at similar antihistamine concentrations. The solubilization data were analyzed with a stepwise self-association model. Based on a dimer model, the experimental and theoretical log excess salicylamide solubility profiles were in good agreement (r2 = 0.982) except at the lowest chlorpheniramine maleate concentrations. Such deviation at the lowest concentrations increased when trimer and 11-mer models were utilized. To account for this deviation, a monomer-dimer model based on interaction with both the chlorpheniramine maleate monomer and dimer was proposed. This model was in excellent agreement (r2 = 0.996) with the solubility data.

The antibiotic cephalexin was formulated as an oral prolonged-release tablet and evaluated by in vitro dissolution testing as well as in vivo in 10 human subjects. Comparisons were made of the time course of the blood levels among the prolonged-release formulation, the commercially available capsule, and intravenous administration. Even though lower peak blood levels were attained in the prolonged-release tablet, absorption continued for at least 6 hr. Comparison with in vitro dissolution data showed that absorption was dissolution rate limited. Bioavailability comparisons showed that the prolonged-release formulation was completely available, as was the commercial oral capsule.

The dissolution rates of each component in compressed spheres consisting of three components were measured under sink conditions. The observed dissolution rates of benzoic acid, salicylic acid, and salicylamide compare favorably to the predicted dissolution rates according to a previously presented kinetic model.

beta-Arteether (1) is a new antimalarial drug derived from artemisinin (2, quinghaosu). Compound 1 is quite water insoluble, but very soluble in a variety of organic solvents. Solubilization in a variety of surfactants was investigated to obtain higher concentrations of 1 in aqueous solutions. Anionic and cationic surfactants exhibited dramatic solubilizing ability for 1, while nonionic surfactants showed significantly lower solubilizing ability. The solubilization data are analyzed on the basis of a pseudo-phase model with 1 exhibiting a high partition coefficient into the micellar phase. An empirical model is presented to identify the possible sites of solubilization of 1 in the micelle.

The mechanisms that control the dissolution rates of chemical compounds in liquids have long been of interest to pharmaceutical scientists. Generally, control of the dissolution rate can be classified as being by interfacial reaction rate or by the rate of mass transport. Little work has been done in the area of sparingly soluble compounds dissolving in nonpolar organic solvents. In this study the dissolution of three isomers of methylacetanilide was investigated in three nonpolar organic solvents (hexane, heptane, and cyclohexane). The dissolution apparatus used a flat plate into which the nondisintegrating tablet could be placed so that dissolution occurred only from one face of the tablet. Agitation was provided by a four-bladed stirrer whose outer edge was 2 cm from the tablet surface. Dissolution data were collected only for concentrations less than 5% of the saturation solubility of the given compound in the given solvent. All dissolution profiles were linear. Dissolution rates were obtained from the slopes of these plots. Plots of In (dissolution rate) versus In (stirring speed) were also linear and yielded slopes that were close to the value of 0.50 predicted by the convective diffusion model employed.

The transport of three p-aminobenzoate esters (ethyl, butyl, and hexyl) through a tubular dimethyl polysiloxane membrane into a flowing liquid was investigated. The tubular configuration permits the exact determination of the convective diffusional contribution to membrane transport with models that account for fluid hydrodynamics. The observed transport behavior ranged from complete convective diffusion control for the hexyl ester to complete membrane control for the ethyl ester; the butyl ester exhibited a change in control with flow rate. The implications of convective diffusional considerations to intestinal absorption and dissolution studies are discussed.

A rapid and sensitive fluorometric analysis for cephalosporins, which can also be applied to penicillins, is presented. The method involves reaction with 0.1 N sodium hydroxide at 100 degrees, producing stable fluorescent products. This method was applied to cephalexin and ampicillin with detection at concentrations as low as 0.01 mug/ml.