Therapeutic drug monitoring of antiepileptic drugs.

Commonly used conventional antiepileptic drugs for pharmacotherapy in epilepsy are phenytoin, carbamazepine and valproic acid. These drugs have complex pharmacokinetic properties leading to fluctuation in their plasma level at given same therapeutic dose. The present study was done to monitor their plasma levels. A prospective observational study was conducted at National Public Health Laboratory. After taking detail history, blood samples were taken from epileptic patients of all age groups and both gender who were on usual therapeutic dose of one or two combined antiepileptic drugs. Plasma level of these drugs were analyzed by using Fluorescence Polarization Immuno Assay (FPIA) technique. Out of total 417 testing, 81 were tested for phenytoin , 241 for carbamazepine and 95 for valproic acid. Their levels were further analyzed to find therapeutic, subtherapeutic and toxic levels. Out of total 81 blood samples tested for phenytoin, 38.8% had plasma drug at therapeutic level, 38.8% at subtherapeutic level and 28.4% had toxic level. Carbamazepine was tested in 241 samples and 79.3% cases had at therapeutic drug level, 15.8% had subtherapeutic drug level and 4.9% had toxic level. Out of 95 samples tested for valproic acid, 62% had therapeutic level and 20% had subtherapeutic and 18% had toxic level of drug. Therapeutic drug monitoring of phenytoin showed wide fluctuation in its plasma level. Its toxic and subtherapeutic levels were quite high. It is suggested that the dose of phenytoin should be adjusted after regular plasma level monitoring only. Monitoring of carbamazepine and valproic acid were also helpful when their toxicity and efficacy are doubtful.

Salient and co-morbid features in benign prostatic hyperplasia: a histopathological study of the prostate.

OBJECTIVES: To study the salient histological features of prostatic tissues in relation to age and to analyse the co-morbid histopathological changes in benign prostatic hyperplasia. (BPH). DESIGN: Prospective study. SETTING: Histopathology unit of a busy clinical pathological laboratory in Kathmandu Metropolitan City. SUBJECTS: 106 prostatic biopsy specimens from patients diagnosed as BPH received for histopathological examination during 2001-2. MAIN OUTCOME MEASURES: Prominent histological features observed in prostatic biopsy specimens obtained from patients of various age groups and frequency of co-morbid histopathological changes in benign prostatic hyperplasia. RESULTS: Prominent histological features. All (106) specimens included in the series had BPH showing glandulostromal proliferation of which 4 cases (3.77%) (all aged below 70 years) showed predominantly stromal pattern. Corpora amylacea present in 25% (in 5th decade) increased in frequency to 100% (8th decade onwards) in the later years. Cystically dilated glands also showed age correlated increase (through 5th to 8th decade) from 50% to 100%. Other prominent features observed with an overall decreasing frequency in all age groups (taken together) were glands showing papillary infoldings (44.33%), lymphocytic collection/infiltration (31.13%), proteinaceous material (7.54%), calcification (6.60%), homogenous eosinophilic material (2.83%), and glands showing necrotic cells (1.88%).Of all these, corpora amylacea, proteinaceous material, cystically dilated glands and glands showing papillary infoldings were present in all cases beyond 7th decade. Co-morbid histopathological changes of BPH. Twenty six specimens (24.52%) showed co-morbid features in association with BPH which included inflammatory (16.98%) and neoplastic (7.54%). Acute prostatitis was observed in 2 cases (1.88%), chronic prostatitis in 16 cases (15.09%) and none showed features of both. Neoplastic changes( 8 cases) ranged from intraepithelial neoplasm (PIN) (2 cases), atypical glands (2 cases, both in 7th decade) to adenocarcinomatous changes (2 cases, one each in 6th and 7th decade) were also observed co-existent with BPH. Both PIN cases (1.88%) were grade PIN-2 and occurred one each in the 6th and 7th decade. CONCLUSION: Histological profiles of prostatic biopsy specimens were observed to correlate well with the senile changes of advancing age. A predominantly stromal proliferation was found in a relatively lower age group, while corpora amylacea and cystically dilated glands along with glandular proliferation heralded changes of senescence. Co-morbid histopathological features were associated with BPH in a quarter (24.52%) of cases. Prostatitis was twice as common as neoplastic changes. Adenocarcinomatous changes were observed (2 cases) incidentally. PIN was recorded in 1.88% of specimens examined. Peak frequency of prostatitis was noted in the 6th decade while 7 of 8 neoplastic changes occurred in those of 60-80 years.