A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma.

A randomized prospective clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated, short course radiotherapy in poor prognosis patients with high grade glioma. The primary endpoint was overall survival.     

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Induction of CYP1A in the beagle dog by an inhibitor of kinase insert domain-containing receptor: differential effects in vitro and in vivo on mRNA and functional activity.

Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A.     

Supravital staining: It's role in detecting early malignancies

The efficacy of supravital staining in the detection of malignancies in oro and oropharyngeal lesions and its role in the detection of malignant changes in premalignant lesions were studied. This prospective study comprises 90 cases of clinically suspicious lesions and it was done over a period of 3 years. Most of the patients had multiple risk factors for the development of malignancy. All underwent staining with a modified solution of 1% toluidine blue (TB). In our study the overall sensitivity was 97.29% and the specificity was 62.5%.     

Evaluation of wound healing activity of Lantana camara L. - a preclinical study

Lantana camara is used in herbal medicine for the treatment of skin itches, as an antiseptic for wounds, and externally for leprosy and scabies. The objective of our study was to investigate excision wound healing activity of the leaf extract of L. camara in rats. The animals were divided into two groups of 12 each in both the models. The test group animals were treated with the aqueous extract of L. camara (100 mg/kg/day) topically and the control group animals were left untreated. Wound healing efficacy was measured by determining the morphological and biochemical parameters. Wound healing time, wound contraction and synthesis of collagen were monitored periodically. Antimicrobial activities of the extract against the microorganisms were also assessed. Treatment of the wounds with extract enhanced significantly the rate of wound contraction (98%), synthesis of collagen and decreased mean wound healing time. These studies demonstrate that L. camara is effective in healing excision wounds in the experimental animal and could be evaluated as a therapeutic agent in tissue repair processes associated with skin injuries.     

Indirect immunofluorescent antibody diagnosis of herpes simplex with upper tarsal and corneal scrapings

Indirect immunofluorescent techniques were used to diagnose active herpes simplex virus ocular infections in 84 patient observations (41 with ocular lesions suspicious clinically for herpes simplex and 43 with lesions suspicious clinically for other ocular inflammatory conditions). We found indirect immunofluorescent antibody techniques to have a high sensitivity (97%) and specificity (73%) when compared to herpes simplex virus cultures. Similarly, we found the sensitivity (98%) and specificity (77%) of indirect immunofluorescent antibody techniques to be high when compared to the clinical diagnosis of herpes simplex viral infection. Significantly, there were no false negative tests by indirect immunofluorescent techniques. Both corneal and upper tarsal scrapings by indirect immunofluorescence were used and the upper tarsal scrapings were an excellent source of cells exhibiting herpes simplex virus antigens. All cases in which corneal scrapings were positive by indirect immunofluorescence for herpes simplex ere also positive by upper tarsal scrapings, although the converse was not true.     

Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors

Cyclooxygenase-2 (COX-2) is an enzyme expressed primarily in pathologic states, such as inflammatory disorders and cancer, where it mediates prostaglandin production. Its overexpression is associated with more aggressive biologic tumor behavior and adverse patient outcome. Increasing evidence shows that agents that selectively inhibit COX-2 enhance tumor response to radiation or chemotherapeutic agents. This article gives an overview of some of this evidence. In addition, we describe new results showing that celecoxib, a selective COX-2 inhibitor, enhanced response of A431 human tumor xenografts in nude mice to radiation by an enhancement factor (EF) of 1.43 and to the chemotherapeutic agent docetaxel by an EF of 2.07. Celecoxib also enhanced tumor response when added to the combined docetaxel plus radiation treatment (EF = 2.13). Further experiments showed that selective COX-2 inhibitors enhanced tumor cell sensitivity to ionizing radiation, involving inhibition of cellular repair from radiation damage and cell cycle redistribution as mechanisms for some cell types. The results show that selective COX-2 inhibitors have the potential to improve tumor radiotherapy or radiochemotherapy, and this therapeutic strategy is currently under clinical testing.     

Shoulder dystocia related fetal neurological injuries: the predisposing roles of forceps and ventouse extractions

On the basis of 333 documented cases of permanent perinatal neurological damage, associated with arrest of the shoulders at birth, the authors conducted a retrospective study in order to evaluate the predisposing role, if any, of the utilization of extraction instruments. The investigation revealed that 35% of all injuries occurred in neonates delivered by forceps, ventouse or sequential ventouse–forceps procedures. This frequency was several-fold higher than the prevailing instrument use in the practices of American obstetricians during the same years. A high rate of forceps and ventouse extractions was demonstrable in all birth weight categories. Average weight and moderately large for gestational age fetuses underwent instrumental extractions more often than grossly macrosomic ones. This circumstance indicates that forceps and ventouse are independent risk factors, unrelated to fetal size. Their use entailed central nervous system injuries significantly more often than did spontaneous deliveries. The findings suggest that extraction procedures may be as important as macrosomia among the factors that lead to neurological damage in the child in connection with shoulder dystocia. Because they augment the intrinsic dangers of excessive fetal size exponentially, the authors consider their use in case of ≥4,000 g estimated fetal weight inadvisable. Sequential forceps–ventouse utilization further doubles the risks and is, therefore, to be avoided in all circumstances.     

hCG administration offers no outcome benefit over spontaneous ovulation in anovulatory women treated with clomiphene citrate

This randomized controlled trial compared spontaneous ovulation versus hCG-triggered ovulation in anovulatory women treated with clomiphene citrate. No statistically significant differences were observed between the two groups in terms of ovulation and pregnancy rates.