Simultaneous determination of granisetron and its 7-hydroxy metabolite in human plasma by reversed-phase high-performance liquid chromatography utilizing fluorescence and electrochemical detection

A highly sensitive and selective high-performance liquid chromatographic method was developed for the determination of granisetron and its active metabolite, 7-hydroxygranisetron (7OH-G) in human plasma. Granisetron is a selective 5-hydroxytryptamine receptor antagonist used in the treatment of cytotoxic drug-induced emesis. The method involves isolation of granisetron, 7OH-G and the internal standards from plasma by solid-phase extraction prior to reversed-phase ion-pair chromatographic separation on an octyl silica column with subsequent quantification of analytes simultaneously either with electrochemical (7OH-G) or fluorescence (granisetron) detectors which are placed in series. The recovery of granisetron and 7OH-G from human plasma was quantitative. Using 1 ml of plasma, the limits of quantification for granisetron and 7OH-G were 0.1 and 0.25 ng/ml, respectively. Linear responses in analyte/internal standard peak-area ratios were observed for analyte concentrations ranging from 0.1 to 50 ng/ml plasma. Precision and accuracy were within 13% across the calibration range for both granisetron and 7OH-G. The method was sufficiently sensitive, accurate and precise to support pharmacokinetic studies for granisetron and 7OH-G, in both normal and patient populations.     

Heterophyid eggs in human stool samples in Assam: first report for India

Two cases from a Muslim family in upper Assam were found to pass trematode eggs morphologically similar to the members of the family Heterophyidae Odhner, 1914. The eggs characteristically yellowish brown in colour, ovoid, have a thick shell and are operculate. They measured 31.5 +/- 2.0 um SD x 22.4 +/- 1.9 um SD with well developed miracidium. This is the first record of human heterophyid infection from India.     

A phase II trial of interleukin-2 and interferon-alpha in the treatment of metastatic colorectal carcinoma

A total of 29 patients with stage IV colorectal cancer were entered into a phase II trial of bolus interleukin-2 (IL-2) and interferon-alpha (IFN alpha) (3 x 10(6) U/m2 of each cytokine given i.v. q8h x 15 doses and repeated in 2 weeks). Immunologic parameters measured on isolated peripheral blood lymphocytes revealed increased activated T cells with upregulated natural killer and lymphokine-activated killer activity. Among 24 evaluable patients, there were 4 partial responses (17%) of short duration ( < or = 6 months). Three of the responding patients had been refractory to prior chemotherapy. Overall median survival in the 24 evaluable patients was 18.5 months. Therapy necessitated an inpatient setting, with the most common toxicities being hypotension, hepatic insufficiency, fever, hypocalcemia, nausea/vomiting, and renal insufficiency. There were two treatment-related deaths. Because neither IL-2 nor IFN alpha alone has significant activity against colorectal cancer, the responses observed in this study suggest a potential synergistic effect between the two cytokines. However, the toxicity and short duration of response without survival benefit do not support the routine use of this regimen as a therapeutic modality for this tumor histology.     

An alternative approach to the surgical correction on malpositions of the uterus]

Endosurgical correction of the uterus was carried out in 57 patients. Indications for surgery were improper positions of the uterus-retroversio, retrodeviatio uteri, excessive mobility of the uterus, and complaints of heaviness at the bottom of the abdomen, leukorrhea, pain of different type in the lower portions of the abdomen, profuse and long menses, dyspareunic pain upon deep penetration, reduced libido, a sensation of a foreign body in the vaginal cleft, urine incontinence upon strain. The mean age of the patients was 35 +/- 3 years. The disease duration varied from 1 to 8-9 years. In 9 women endosurgical correction of the uterus was combined with other interventions on the pelvic organs: colpoperine-orrhaphy with levator plasty was carried out in 5, laparoscopic myomectomy in 2, and dissection of intraperitoneal adhesions in 2 patients. In addition, surgical sterilization was carried out in 54 patients. After surgery the patients were administered only nonnarcotic analgetics. All the patients were discharged on days 2-3, those subjected to combined treatment on days 8-9. The patients were followed up for up to 2 years. The general and psychoemotional status of the majority of patients improved, and the incidence of such symptoms as leukorrhea, pain at the bottom of the abdomen, profuse and long menses was 4, 6, and 5 times reduced, respectively. Endosurgical correction of the uterus in women of a reproductive age should be a method of choice; it can be carried out separately or in combination with plasty of the vaginal walls.     

Use of subunit-specific antisense oligodeoxynucleotides to define developmental changes in the properties of N-methyl-D-aspartate receptors

Antisense oligodeoxynucleotides were used to determine whether alterations in the expression of N-methyl-D-aspartate (NMDA) receptor subunit mRNA are responsible for developmental changes in the sensitivity of receptors to agonists and antagonists. Xenopus laevis oocytes were injected with mRNA prepared from neonatal and adult rat cerebral cortex, and the effects of agonists and antagonists were determined under voltage-clamp conditions. Glycine-site antagonists like 7-chlorokynurenate and glutamate-site antagonists like CGP-39653 were more potent at NMDA receptors expressed from mRNA from adult rat cerebral cortex than those expressed from mRNA from 1-day-old rat. NMDA receptors from 1-day-old rat cerebral cortex were more sensitive to activation by glycine than were receptors from adult rat cerebral cortex. 7-Chlorokynurenate and CGP-39653 were more potent inhibitors of responses seen with heteromeric NR1/NR2A receptors than with NR1/ NR2B receptors. Conversely, heteromeric NR1/NR2B receptors were more sensitive to activation by glycine than were NR1/NR2A receptors. We previously described a delay in the expression of the NR2A subunit in developing rat brain. Anti-sense oligodeoxynucleotides were used to determine whether the delayed expression of the NR2A subunit underlies changes in pharmacological properties observed during development. The properties of receptors seen when adult brain mRNA was coinjected with antisense oligodeoxynucleotides against the NR2A subunit were similar to those found in receptors from 1-day-old rat brain. These data suggest that changes in the sensitivity of NMDA receptors to antagonists and to glycine seen during development are a result of alterations in the expression of different species of NR2 subunit mRNA.     

Cytomorphologic panorama of cysticercosis on fine needle aspiration. A review of 298 cases

Definitive identification of detached hooklets, scolex and fragments of the spiral wall of Cysticercus cellulosae on fine needle aspiration smears was documented. A critical review of aspirates from 200 diagnosed and 98 suspected lesions of soft tissue and intramuscular cysticercosis was done. Characteristic fragments of bladder wall cytomorphologically corresponding to viable or partially necrotic lesions were seen in 203 cases. Identification of fragments of an invaginated larva (i.e., hooklets, scolex or spiral wall) established the diagnosis in 33 of the suspected lesions. Cytomorphologically all these cases were from either necrotic or calcified lesions. In necrotic lesions with eosinophils, a careful search for fragments of the invaginated portion of the larva should be made.