An AI-based approach driven by genotypes and phenotypes to uplift the diagnostic yield of genetic diseases.

Identifying disease-causing variants in Rare Disease patients' genome is a challenging problem. To accomplish this task, we describe a machine learning framework, that we called "Suggested Diagnosis", whose aim is to prioritize genetic variants in an exome/genome based on the probability of being disease-causing. To do so, our method leverages standard guidelines for germline variant interpretation as defined by the American College of Human Genomics (ACMG) and the Association for Molecular Pathology (AMP), inheritance information, phenotypic similarity, and variant quality. Starting from (1) the VCF file containing proband's variants, (2) the list of proband's phenotypes encoded in Human Phenotype Ontology terms, and optionally (3) the information about family members (if available), the "Suggested Diagnosis" ranks all the variants according to their machine learning prediction. This method significantly reduces the number of variants that need to be evaluated by geneticists by pinpointing causative variants in the very first positions of the prioritized list. Most importantly, our approach proved to be among the top performers within the CAGI6 Rare Genome Project Challenge, where it was able to rank the true causative variant among the first positions and, uniquely among all the challenge participants, increased the diagnostic yield of 12.5% by solving 2 undiagnosed cases.

Associated decrements in rate of force development and neural drive after maximal eccentric exercise.

The present study investigated the changes in contractile rate of force development (RFD) and the neural drive following a single bout of eccentric exercise. Twenty-four subjects performed 15 × 10 maximal isokinetic eccentric knee extensor contractions. Prior to and at 24, 48, 72, 96, and 168 h during post-exercise recovery, isometric RFD (30, 50 100, and 200 ms), normalized RFD [1/6,1/2, and 2/3 of maximal voluntary contraction (MVC)] and rate of electromyography rise (RER; 30, 50, and 75 ms) were measured. RFD decreased by 28-42% peaking at 48 h (P < 0.01-P < 0.001) and remained depressed at 168 h (P < 0.05). Normalized RFD at 2/3 of MVC decreased by 22-39% (P < 0.01), peaked at 72 h and returned to baseline at 168 h. These changes in RFD were associated with a decrease in RER at 48 h-96 h (P < 0.05-P < 0.001). Accumulated changes (area under curve) revealed a greater relative decrease in accumulated RFD at 100 ms by -2727 ± 309 (%h; P < 0.05) and 200 ms by -3035 ± 271 (%h; P < 0.001) compared with MVC, which decreased, by -1956 ± 234 (%h). In conclusion, RFD and RER are both markedly reduced following a bout of maximal eccentric exercise. This association suggests that exercise-induced decrements in RFD can, in part, be explained decrements in neural drive.

Blood flow restricted and traditional resistance training performed to fatigue produce equal muscle hypertrophy.

This study investigated the hypertrophic potential of load-matched blood-flow restricted resistance training (BFR) vs free-flow traditional resistance training (low-load TRT) performed to fatigue. Ten healthy young subjects performed unilateral BFR and contralateral low-load TRT elbow flexor dumbbell curl with 40% of one repetition maximum until volitional concentric failure 3 days per week for 6 weeks. Prior to and at 3 (post-3) and 10 (post-10) days post-training, magnetic resonance imaging (MRI) was used to estimate elbow flexor muscle volume and muscle water content accumulation through training. Acute changes in muscle thickness following an early vs a late exercise bout were measured with ultrasound to determine muscle swelling during the immediate 0-48 h post-exercise. Total work was threefold lower for BFR compared with low-load TRT (P < 0.001). Both BRF and low-load TRT increased muscle volume by approximately 12% at post-3 and post-10 (P < 0.01) with no changes in MRI-determined water content. Training increased muscle thickness during the immediate 48 h post-exercise (P < 0.001) and to greater extent with BRF (P < 0.05) in the early training phase. In conclusion, BFR and low-load TRT, when performed to fatigue, produce equal muscle hypertrophy, which may partly rely on transient exercise-induced increases in muscle water content.

Breast Edema after Conservative Surgery for Early-Stage Breast Cancer: A Retrospective Single-Center Assessment of Risk Factors.

Breast-conserving surgery (BCS) is the standard of care for early-stage breast cancer. We retrospectively enrolled 530 patients (mean age: 62.96 ± 12.69 years) undergoing BCS between January 1, 2018, and December 31, 2019. During the COVID-19 pandemic, all patients with at least 1 year of follow-up were telephonically asked after surgery to provide clinical signs and symptoms attributable to postoperative breast cancer-related lymphedema of the breast (BCRL-B). Thirty-one (5.8%) patients reported breast edema and were visited to measure the tissue dielectric constant (TDC) and to assess the induration of the skin. There was a difference seen in treatment with lumpectomy + ALND performed more frequently in patients with (29%) than without (12%) BCRL-B. In the subgroup of patients with BCRL-B (n=31), significantly higher values of local total water were calculated in the nine patients who underwent Lump + ALND procedure (1.86 ± 0.48 vs. 1.48 ± 0.38; p = 0.046). Among patients with BCRL-B (n=31), in eight patients (25.8%) tissue induration measured with SkinFibroMeter was >0.100 N, thus suggesting tissue fibrosis. Cumulative survival probability at 1-year after surgery was 0.992. No statistical differences in 1-year survival after surgery were found for type of surgery (p = 0.890) or absence/presence of BCRL-B (p = 0.480). In univariate logistic regression, only lumpectomy + ALND surgery (p = 0.009) and any subsequent axillary lymph node removal surgery (p = 0.003) were associated with BCRL-B. Both of these variables were also found to be statistically significant in the multivariate regression model. Further prospective research is warranted to analyze potentential predictors of BCRL-B and to reduce/ prevent this complication.

Sperm ultrastructure and spermatogenesis in the Japanese beetle Popillia japonica (Coleoptera, Scarabaeidae).

Popillia japonica is an invasive scarab beetle native to Japan that in 1916 invaded New Jersey in USA. From that moment onwards, the insect has spread invading several US states, Canada, the Azores, Italy and, recently, Switzerland. It is a severe agricultural pest included in the EU priority pest list being able to feed on more than 300 plant species and having an important biotic potential. The general morphology of the reproductive apparatus shows paired testes, each of them having six testicular lobes grouped in threes. From the ventral part of each testicular lobe, each containing about 20 follicles, an efferent vessel originates that fuses with the other efferent vessels to form the deferent duct. A pair of long tubular accessory glands is present. The deferent ducts and accessory glands fuse together into an ejaculatory duct before entering the aedeagus. The sperm is a typical pterygote sperm, 110 µm long, composed of a head and a tail. In the head a three-layered acrosome of about 6 µm in length and a nucleus of about 18 µm long are present. During sperm maturation two C-shaped structures appear in the cytoplasm from the opposite sides of the nucleus that then disappear in late spermatids. In the tail a typical 9 + 9 + 2 flagellar axoneme and two mitochondrial derivatives are present. Moreover, in the head-tail transition region the centriolar adjunct forms a sheath from which three elongated accessory bodies originate. Two of these accessory bodies are placed alongside the axoneme, whilst the third one is placed beneath the mitochondrial derivatives. Mature sperm are grouped in cysts containing about 256 sperm cells. A morphological comparison with related species is provided.

[Enzyme replacement therapy in a boy with infantile Pompe disease: cardiac follow-up]. / Enzymothérapie substitutive chez un nourrisson atteint de maladie de Pompe : évolution cardiologique.

Pompe disease is an autosomal recessive glycogen storage disorder caused by acid-alpha-glucosidase deficiency. The infantile form is usually fatal by 1 year of age in the absence of specific therapy. We report the cardiac follow-up of a 4-month-old boy treated with enzyme replacement therapy (ERT) for 8 months. The patient had no cardiac failure at the age of 1 year. Before starting ERT, ECG showed a shortened PR interval, with huge QRS complexes and biventricular hypertrophy; echocardiography demonstrated major hypertrophic cardiomyopathy. The QRS voltage (SV1+RV6) decreased from 13 to 2.9 mV after 32 weeks of ERT, suggesting a progressive reduction of cardiac hypertrophy and intracellular glycogen excess. The PR interval increased from 60 to 90 ms. A block of the right bundle branch appeared after 13 weeks of treatment. The indexed left ventricular mass decreased from 240 to 90 g/m2 after 30 weeks of ERT. The left ventricular ejection fraction decreased transitorily between the 5th and the 15 th weeks of treatment. In summary, ERT is an efficient therapeutic approach for the cardiomyopathy of infantile Pompe disease. However, the possible occurrence of a right bundle branch block and a transitory alteration in the ejection fraction highlight the importance of cardiac follow-up.

Impact of blood flow-restricted bodyweight exercise on skeletal muscle adaptations.

This study ascertains the ability of bodyweight blood flow-restricted (BFR) exercise training to promote skeletal muscle adaptations of significance for muscle accretion and metabolism. Six healthy young individuals (three males and three females) performed six weeks of bodyweight BFR training. Each session consisted of five sets of sit-to-stand BFR exercise to volitional failure with 30-second inter-set recovery. Prior to, and at least 72 h after training, muscle biopsies were taken from m. vastus lateralis to assess changes in fibre type-specific cross-sectional area (CSA), satellite cell (SC) and myonuclei content and capillarization, as well as mitochondrial protein expression. Furthermore, magnetic resonance imaging was used to assess changes in whole thigh muscle CSA. Finally, isometric knee extensor muscle strength was evaluated. An increase in knee extensor whole muscle CSA was observed at middle and distal localizations after training (3·2% and 3·5%, respectively) (P<0·05), and a trend was observed towards an increase in type I fibre CSA, whereas muscle strength did not increase. Additionally, the number of SCs and myonuclei associated with type I fibres increased by 65·7% and 20%, respectively (P<0·05). No significant changes were observed in measures of muscle capillarization and mitochondrial proteins. In conclusion, six weeks of bodyweight-based BFR exercise promoted myocellular adaptations related to muscle accretion, but not metabolic properties. Moreover, the study revealed that an appropriate total training volume needs further investigation before recommending bodyweight BFR to patient populations.

[A monocenter experience of ventricular septal defects treated by catherization]. / Expérience monocentrique de la fermeture par cathétérisme interventionnel des communications interventriculaires.

INTRODUCTION: Studies on ventricular septal defects closure by catheterization confirm its feasibility without reporting clearly the indications and difficulties encountered. PATIENTS AND RESULTS: From 2001 to end-2006, 22 patients benefited from 26 ventricular septal defects closure (15 muscular and 7 membranous) at a median age and weight of 2.1 years and 12.5 kg, respectively. A perventricular catheterization was performed in 2 cases. Eighteen patients (82%) benefited from 21 prostheses with success. The closure was associated to surgery in 9 cases (41%) whereas it substituted surgery in the other 13 cases (59%). The median duration of the procedure was significantly longer in case of muscular ventricular septal defects (215 min (175-510) vs. 170 min (120-225), p=0.04). Major complications are reported in 5 cases out of 26 catheterization (19%), including one death related to conduction block, occurring after the implantation of two prostheses in a patient with aortopulmonary transposition. All other associated cardiac diseases have been corrected. A prosthetic emboli occurred in one case, 1.5 months after implantation. It had been retrieved by catheterization. Two patients died afterwards from non-procedure-related causes. After a median follow-up of 1.1 years, the 17 other patients remained asymptomatic. One child with a perimembranous prosthesis presents a paroxystic atrio-ventricular block. CONCLUSION: Even though indispensable for the curative treatment of several congenital cardiac diseases including non-operable ventricular septal defects, this procedure is related to a substantial rate of mortality and morbidity. The risk of atrio-ventricular block must be adequately considered in case of membranous ventricular septal defects.

Schwannoma of thyroid bed. A case report and considerations on interdisciplinary collaboration.

Schwannoma of the thyroid bed is extremely rare, but is known to simulate a thyroid nodule. A retrospective review is reported of a 64-year-old female patient with a thyroid nodule who had been submitted to pre-operative fine-needle aspiration biopsy, judged inadequate, following which total thyroidectomy was performed. On histological examination, the nodule (in the thyroid bed) was found to be a schwannoma. This case report stresses the importance of interdisciplinary collaboration. Better co-operation between surgeon, pathologist and radiologist may have led to correct pre-operative diagnosis with sparing of at least half the thyroid.

Nucleotide excision repair pathway assessment in DNA exposed to low-intensity red and infrared lasers.

Low-intensity lasers are used for prevention and management of oral mucositis induced by anticancer therapy, but the effectiveness of treatment depends on the genetic characteristics of affected cells. This study evaluated the survival and induction of filamentation of Escherichia coli cells deficient in the nucleotide excision repair pathway, and the action of T4endonuclease V on plasmid DNA exposed to low-intensity red and near-infrared laser light. Cultures of wild-type (strain AB1157) E. coli and strain AB1886 (deficient in uvrA protein) were exposed to red (660 nm) and infrared (808 nm) lasers at various fluences, powers and emission modes to study bacterial survival and filamentation. Also, plasmid DNA was exposed to laser light to study DNA lesions produced in vitro by T4endonuclease V. Low-intensity lasers:i) had no effect on survival of wild-type E. coli but decreased the survival of uvrA protein-deficient cells,ii) induced bacterial filamentation, iii) did not alter the electrophoretic profile of plasmids in agarose gels, andiv) did not alter the electrophoretic profile of plasmids incubated with T4 endonuclease V. These results increase our understanding of the effects of laser light on cells with various genetic characteristics, such as xeroderma pigmentosum cells deficient in nucleotide excision pathway activity in patients with mucositis treated by low-intensity lasers.

Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures.

Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols.

Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

The neuron-derived orphan receptor 1 (NOR1) is induced upon human alternative macrophage polarization and stimulates the expression of markers of the M2 phenotype.

BACKGROUND: Atherosclerosis is an inflammatory disease in which macrophages play a crucial role. Macrophages are present in different phenotypes, with at the extremes of the spectrum the classical M1 pro-inflammatory and the alternative M2 anti-inflammatory macrophages. The neuron-derived orphan receptor 1 (NOR1), together with Nur77 and Nurr1, are members of the NR4A orphan nuclear receptor family, expressed in human atherosclerotic lesion macrophages. However, the role of NOR1 in human macrophages has not been studied yet. OBJECTIVES: To determine the expression and the functions of NOR1 in human alternative macrophages. METHODS AND RESULTS: In vitro IL-4 polarization of primary monocytes into alternative M2 macrophages enhances NOR1 expression in human but not in mouse macrophages. Moreover, NOR1 expression is most abundant in CD68+MR+ alternative macrophage-enriched areas of human atherosclerotic plaques in vivo. Silencing NOR1 in human alternative macrophages decreases the expression of several M2 markers such as the Mannose Receptor (MR), Interleukin-1 Receptor antagonist (IL-1Ra), CD200 Receptor (CD200R), coagulation factor XIII A1 polypeptide (F13A1), Interleukin 10 (IL-10) and the Peroxisome Proliferator-Activated Receptor (PPAR)γ. Bioinformatical analysis identified F13A1, IL-1Ra, IL-10 and the Matrix Metalloproteinase-9 (MMP9) as potential target genes of NOR1 in human alternative macrophages. Moreover, expression and enzymatic activity of MMP9 are induced by silencing and repressed by NOR1 overexpression in M2 macrophages. CONCLUSIONS: These data identify NOR1 as a transcription factor induced during alternative differentiation of human macrophages and demonstrate that NOR1 modifies the alternative macrophage phenotype.

Effect of thyrotropin releasing hormone (TRH) on acetylcholine release from different brain areas investigated by microdialysis.

1. The effect of thyrotropin releasing hormone (TRH) administration upon acetylcholine (ACh) release in freely moving rats was investigated by means of transversal microdialysis coupled to h.p.l.c. TRH administered either s.c. or via local perfusion increased the ACh release from cortex and hippocampus but not from the striatum. The increase in ACh release was maintained after 7 days of s.c. administration of TRH. 2. After s.c. injection of the neuropeptide, the increase in ACh release was dose-dependent and reached a maximum at 40 min after administration. The maximal percentage increases were 18, 52, 66 and 89% at doses of 1, 2.5, 5 and 10 mg kg-1 and 35, 48 and 54% at doses of 2.5, 5 and 10 mg kg-1 in the cortex and hippocampus, respectively. The effect of TRH was dependent on neuronal activity since it was completely inhibited by perfusion with tetrodotoxin (TTX), 5 X 10(-7) M. 3. Perfusion with TRH, 2.5 micrograms microliters-1, caused 198% and 150% increase in ACh release 60 and 80 min after the beginning of the perfusion in the cortex and hippocampus, respectively. After this initial peak, a 100% increase in ACh release persisted throughout the perfusion. 4. Systemic TRH administration was followed by marked hyperactivity and stereotyped behaviour that showed a time course shorter than that of the increase in ACh release. 5. These findings demonstrate that TRH exerts a strong stimulant action on cortical and hippocampal cholinergic pathways.

Genetic heterogeneity in uveitis.

Eighty-nine unrelated patients with ocular inflammation (uveitis) were investigated for the HLA class I and class II genetic markers, We subdivided our patients according to: 1. the anatomical location of the lesion; 2. the temporal course of the disease; 3. the aetiology. We eliminated from our sample of patients the individuals with other systemic diseases. We could not find an association with B27, as previously described, but we did note statistically significant differences between the class II antigen distribution in the different anatomical subgroups. HLA-DR3 seems a marker of the intermediate form of uveitis (p, uncorrected 0.03); the absence of DR1 in the patient group with posterior uveitis may be a protecting factor (p. uncorrected less than 0.01); the presence of DR4 in all cases of panuveitis is statistically significant (p, uncorrected = 0.0006).

Oxiracetam and D-pyroglutamic acid antagonize a disruption of passive avoidance behaviour induced by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate.

Intracerebroventricular administration (6 micrograms/2 microliters) of D-2-amino-5-phosphonovalerate (AP-5), a specific antagonist of the NMDA receptors, prior to training impaired the passive avoidance in a retention test in rat. Pretreatment with oxiracetam and D-pyroglutamic acid at doses ranging from 50 to 500 mg/kg SC dose-dependently prevented the disruptive effect of AP-5. This finding indicates that an interaction with excitatory amino acid NMDA type receptors may be important in behavioural effects of the two pyrrolidinone derivatives.

Preoperative assessment of coronary artery disease in aortic stenosis: a dipyridamole echocardiographic study.

BACKGROUND: The aim of this study was to establish the feasibility, safety, and diagnostic accuracy of the dipyridamole echocardiography test in patients with severe aortic valve stenosis for noninvasive detection of coexisting coronary artery disease. METHODS: The high-dose dipyridamole echocardiography test was performed in 52 patients with severe aortic stenosis; all patients also underwent coronary angiography, independent of test results, before cardiac operation. RESULTS: The dipyridamole echocardiography test was completed without major complications. One patient had transient atrial fibrillation that was reversed by aminophylline. Thirty-one patients (60%) had a negative test result; all had normal coronary arteries. Ten of the 21 patients (48%) with a positive test result had coexisting coronary artery disease. The positive predictive value of the dipyridamole echocardiography test for detection of coronary disease in patients with severe aortic stenosis was 48%. The negative predictive value was 100%. The sensitivity was 100% and the specificity was 74%. CONCLUSIONS: Dipyridamole echocardiography is a safe and feasible tool in patients with severe aortic stenosis eligible for a cardiac operation. A negative test result reliably rules out a significant stenosis, whereas a positive one is much less accurate in predicting coronary artery disease.

Mechanisms of regional ischaemic changes during dipyridamole echocardiography in patients with severe aortic valve stenosis and normal coronary arteries.

OBJECTIVE: Vasodilator stress echocardiography can cause myocardial ischaemia in patients with severe aortic valve stenosis and angiographically normal coronary arteries. The aim of the study was to determine the mechanism of ischaemia in this clinical model. METHODS: The study group comprised patients with severe aortic valve stenosis and normal coronary arteries: 25 patients (17 males, eight females; age 63 (SD 11) years) underwent a high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography test both before (2-4 d) and after (10-15 d) aortic valve replacement. Mean aortic pressure gradient was 96 (15) mm Hg, with a left ventricular mass index of 228 (49) g/m2. The dipyridamole echocardiography test was well tolerated and interpretable in all patients. RESULTS: Dipyridamole infusion induced chest pain in seven patients before and in no patient after surgery (28 v 0%, P < 0.01), ST segment depression in 12 patients before and two after surgery (48 v 8%, P < 0.01), and a transient regional dyssynergy in 10 patients before and two after surgery (40 v 8%, P < 0.01). In the preoperative evaluation, patients with an echocardiographically positive dipyridamole echocardiography test were comparable with patients with negative test as far as left ventricular mass index [240 (67) v 230 (64) g/m2, NS] and mean aortic pressure gradient [95 (22) v 92 (21) mm Hg, NS] were concerned. When compared to the preoperative assessment, the resting echo assessment in the postoperative evaluation showed unchanged values of left ventricular mass index [pre 228 (49) g/m2 v post 220 (36) g/m2, NS], but markedly decreased values of mean aortic gradient [pre 95 (15) mm Hg v post 22 (5) mm Hg, P < 0.01] and left ventricular wall stress index [pre 134 (30) g/cm2 v post 89 (19) g/cm2]. CONCLUSIONS: Dipyridamole echocardiography is a suitable clinical technique for assessing the ischaemic vulnerability of the left ventricle in severe aortic valve stenosis with angiographically normal coronary arteries. The frequent disappearance of the ischaemic response early after aortic valve replacement suggests that haemodynamic factors such as compressive diastolic wall stress or afterload reduction are important components of myocardial ischaemic vulnerability under these circumstances.

Development of a densitometric method for the determination of cephalexin as an alternative to the standard HPLC procedure.

A HPTLC-densitometric method was developed in order to obtain a reliable procedure for routine analysis of cephalexin in pharmaceutical formulations. Optimization of TLC conditions for the densitometric scanning was reached by eluting HPTLC silica gel plates in an horizontal developing chamber. Quantitation of cephalexin was performed in single beam reflectance mode by using a computer-controlled densitometric scanner and applying a five-point calibration. A linear regression has been found in the 200-1000 ng range. The setup method is precise, reproducible and accurate. Recovery was also assessed by comparison with the HPLC USP XXIII alternate method. In this case HPTLC-densitometry appears worth of consideration as being relatively inexpensive and time-saving (up to 12 samples can be determined simultaneously in less than 15 min with a solvent consumption of about 15 ml). The results suggest that the proposed method may be used in place of HPLC for the routine quantitation of cephalexin in both pure and dosage forms.