Is there any correlation between tumor infiltrating lymphocytes and expression of EGFR in squamous cell carcinoma of head and neck? A retrospective observational study

Background: The dismal survival of one of the commonest malignancies of the world, head neck squamous cell carcinomas (HNSCC), has prompted researchers to probe into its various characteristics, especially those which reflect the outcome. Over the years, even though epidermal growth factor receptor (EGFR) and tumor-infiltrating lymphocytes (TIL) have emerged as useful biomarkers of the disease, the two parameters have rarely been considered in conjunction. Aims and Objectives: The study aimed to assess if there is any correlation between TIL levels (both stromal and intratumoral) and site, grade, stage, and EGFR score of HNSCC. Materials and Methods: A retrospective observational study was conducted in which histopathologically confirmed cases of HNSCC were included. The site of tumor, grade, stage, stromal and intratumoral TIL levels, and EGFR score were noted for each case. The data were analyzed using standard statistical tests. Results: The study population consisted of 122 patients with a mean age of 53.8 ± 9.2 years. The oral cavity was the commonest site of tumor (109 cases, 89.3%). Most cases were moderately differentiated (75, 61.5%). Pathological staging showed 66 cases (54%) to be in pT1, and 92 cases (75.4%) to be in pN0. In 68 cases (55.7%), stromal TIL level was high, and intratumoral TIL was low in 102 cases (83.6%). A statistically significant correlation was found between TIL levels and site, grade, pathological stage, and EGFR score of HNSCC. Conclusion: This pioneering study is unique in its exploration of the correlation between two significant biomarkers of HNSCC – TIL and EGFR score.

Comparative evaluation of possible ocular photochemical toxicity of fluoroquinolones meant for ocular use in experimental models.

Fluoroquinolones (FQs) are extensively used in bacterial keratitis and other intraocular infections. Since eye is constantly exposed to light, incidence of ocular phototoxicity due to commonly used FQs is of great interest for their safe use. Phototoxicity of commonly used FQs (ciprofloxacin, lomefloxacin, pefloxacin, ofloxacin, sparfloxacin and gatifloxacin), has been evaluated by using HET-CAM-UV model (Photo Hen Egg Test-C Chorioallantoic Membrane model). This study was further extended by adding lomefloxacin dissolved in bovine vitreous (0.5 ml) on the chorioallantoic membrane (CAM). Using a standard scale, the phototoxic damage was assessed at different time intervals. Respective controls were kept in dark to distinguish the toxicity of the drugs per se. The results showed that the phototoxicity induced by lomefloxacin was very high followed by gatifloxacin and sparfloxacin and least for other drugs studied. Interestingly, lomefloxacin along with vitreous showed significantly low phototoxicity. This could be due to the antioxidant property of ascorbic acid present in the vitreous.

Protection of adrenal and male gonadal functions by androgen in lead-treated rats.

The potential health hazard of the large amounts of Lead that occurs in canned baby food, domestic water from lead-lined tanks and, in printing and petroleum industries. Lead acetate administration at a does of 8 mg/kg body weight for 21 days resulted a significant increase in adrenal steroidogenic enzyme (Delta5-3beta- HSD) and serum levels of corticosterone, while serum levels of testosterone, FSH, LH and testicular spermatogenesis were decreased in albino rats. But lead-treated rats received exogenous testosterone for the last 14 days of lead treatment, showed prevention of adrenocortical hyperactivity by decreasing adrenal Delta5-3beta-HSD activity and serum level of corticosterone. Testosterone administration also increased serum level of testosterone, FSH and LH along with spermatogenesis. The results suggest that testosterone supplementation in lead-treated rats protects adrenocortical activity and testicular spermatogenesis.

Dose-dependent effect of copper chloride on male reproductive function in immature rats.

BACKGROUND: Copper is essential as a trace element for metabolic processes. Exposure to copper in industries develops toxicity among the workers. Previous findings on adverse effects of copper on male reproductive function in adult albino rats led to investigate the effects of this metal on reproductive function of maturing male rats in the present experiment. METHODOLOGY: To study these effects, immature (30 to 35 days old) Wistar strain albino rats weighing about 50-60 g were treated intraperitoneally with copper chloride at doses of 1000, 2000 and 3000 microg/kg body weight/day for 26 days. RESULT: Significant fall in accessory sex organ weight and inhibition of testicular 17beta-hydroxysteroid dehydrogenase activity along with degeneration of testicular growing spermatogenic cells and reduction in serum testosterone, FSH and LH level were observed at the doses of 2000 and 3000microg/kg/day. On the other hand, at the dose of 1000 microg/kg/day significant increase in testicular steroidogenic enzyme activity and stimulation of testicular spermatogenesis along with rise in serum testosterone and LH level were observed, though no significant change was observed in serum FSH level. This suggests that copper has got a dose-dependent effect on testicular steroidogenesis and spermatogenesis and serum testosterone and LH level in maturing male rats.

Protection from ultraviolet radiation by spectacle lenses available in India: a comparative study.

BACKGROUND: Exposure to ultraviolet radiation (UVR) can result in several ocular ailments. We studied the UV absorption (UV-A and -B bands) in 20 lenses (11 hard resin and 9 glass) commonly available in India as uncut lenses for the purpose of prescription as well as non-prescription wear. METHODS: Using a UV-visible spectrophotometer (Thermo-Spectronic, UV-1 model, Thermo Electron Corporation, USA), the percentage transmittance was scanned between 190 and 400 nm, from which the results at 280, 320, 340, 360, 380 and 400 nm were analysed. RESULTS: At 360 nm (UV-A), 75% of the lenses studied failed to offer 95% protection as recommended by the United States Food and Drug Administration (US FDA). At 280 nm (UV-B), 35% of the lenses failed to offer 99% protection against UV-B. Hard resin lenses showed a higher degree of variation in protection from UV-A. CONCLUSONS: Most of the lenses studied failed to meet the US FDA recommendations in terms of protection from UV-A. Glass lenses afforded better protection up to 320 nm compared with hard resin lenses. As the claims of lens manufacturers regarding UVR protection fall short of international standards, certification of UVR protection for different lenses should be introduced in India.

Ocular and cardiovascular autonomic function in diabetic patients with varying severity of retinopathy.

The study was conducted to assess the ocular and cardiovascular autonomic function in diabetic patients with varying severity of diabetic retinopathy. Ocular and cardiovascular autonomic function tests were performed in 30 patients with type 2 Diabetes Mellitus (10 in each group of proliferative retinopathy, non-proliferative retinopathy and no retinopathy) of more than 5 years duration and 10 normal controls. Ocular autonomic function tests were done by measuring pupil cycle time and denervation hypersensitivity with 0.125% pilocarpine and 0.5% phenylephrine. Cardiovascular autonomic function was measured by a battery of standard tests. Denervation hypersensitivity to 0.125% pilocarpine and to 0.5% phenylephrine and pupil cycle time showed statistically significant differences (P value < 0.001) between controls and patients with proliferative retinopathy (PDR) and also between no retinopathy and PDR (P < 0.001). Systemic autonomic function tests namely expiration--inspiration ratio, difference in heart rate, 30th beat and 15th beat ratio in head up tilt and difference in diastolic blood pressure in head up tilt test also showed significant difference (P < 0.01) between controls and all 3 groups of diabetics. There was statistically significant difference found in para-sympathetic ocular autonomic dysfunction between NPDR and controls. Ocular and systemic autonomic dysfunctions are related to the severity of diabetic retinopathy.

Protection of adrenocortical activity by dietary casein in ether anaesthetized rats.

Adrenal delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and serum corticosterone level were significantly higher in rats fed with 5% casein or 4% albumin diets after 1 hr of ether anaesthetic stress as compared to the controls, 5% casein and 20% casein (equivalent to 4% albumin) respectively. Ether anaesthesia to 20% casein fed rats caused no change in adrenal delta5-3beta-HSD activity and serum corticosterone level when compared with controls fed 20% casein diet. The results suggest that high milk protein diet may prevent acute stress effects by protecting adrenocortical activity. The present investigation opens up a new area of management of stress.

Comparative randomised controlled clinical trial of a herbal eye drop with artificial tear and placebo in computer vision syndrome.

A comparative randomised double masked multicentric clinical trial has been conducted to find out the efficacy and safety of a herbal eye drop preparation, itone eye drops with artificial tear and placebo in 120 patients with computer vision syndrome. Patients using computer for at least 2 hours continuosly per day having symptoms of irritation, foreign body sensation, watering, redness, headache, eyeache and signs of conjunctival congestion, mucous/debris, corneal filaments, corneal staining or lacrimal lake were included in this study. Every patient was instructed to put two drops of either herbal drugs or placebo or artificial tear in the eyes regularly four times for 6 weeks. Objective and subjective findings were recorded at bi-weekly intervals up to six weeks. Side-effects, if any, were also noted. In computer vision syndrome the herbal eye drop preparation was found significantly better than artificial tear (p < 0.01). No side-effects were noted by any of the drugs. Both subjective and objective improvements were observed in itone treated cases. So, itone can be considered as a useful drug in computer vision syndrome.

Effect of casein diet on gonadotropin releasing hormone antagonist induced changes in adrenal gonadal functions in male rats.

Adult male rats received daily injections (sc) of gonadotropin releasing hormone antagonist (0.2 mg/kg(-1) x day(-1)) for 21 days when they were sacrificed on day 22, adrenal weight, adrenal A5-3beta (delta 5-3beta) hydroxysteroid dehydrogenase (Delta5-3beta-HSD) activity and serum level of corticosterone were increased significantly while testicular 17beta (17beta) hydroxysteroid dehydrogenase (17beta-HSD) activity and serum level of testosterone and spermatogenesis were decreased in the rats fed on 5% casein diet. GnRH antagonist treated rats fed on 20% casein diet, resulted significant decrease in adrenal weight, serum corticosterone and adrenal A5-3beta-HSD activity while testicular 17beta-HSD activity serum testosterone levels and the weights of sex organs were increased with respect to anti GnRH treated rats fed on 5% casein diet. But the GnRH antagonist treated rats fed on 20% casein diet showed decreased spermatogenesis quantitatively and sperm count appeared similar to anti GnRH treated rats fed on 5% casein diet. These results indicate that high casein diet protects adrenocortical activity and stimulates testosterone synthesis without effecting spermatogenic arrest in GnRH antagonist treated rats. It may be concluded that GnRH antagonist in presence of high milk protein diet may be considered to be a suitable antihormone in the development of an ideal male contraceptive.

Prevention of adrenocortical hyperactivity by dietary casein in rats exposed to forced swimming stress.

Adrenal weight, adrenal hydroxysteroid dehydrogenase activity and serum corticosterone level were significantly higher in rats fed with 5% casein diet after 7 days of swimming stress (45 min/day) as compared to their controls. All the parameters were similar to their control levels in rats receiving 20% casein diet and exposed to swimming stress. The results suggest that casein can play an important role in preventing adrenocortical hyperactivity in swimming stressed rats.

Therapy of acanthamoeba keratitis--an experimental study.

The study was conducted to determine the efficacy of various drugs/agents in the treatment of experimentally induced Acanthamoeba Keratitis (A. keratitis). Thirty rabbits were divided into 5 equal treatment groups and polyhexamethylene biguanide (PHMB) 0.02%, fluconazole 0.2%, povidone iodine 5%, aprotinin 40 IU/ml and normal saline were administered in a double blind manner, at a dose of one drop, 5 times/day. Neomycin 1700 U/ml was used as a common drug in all groups, with same frequency. Post therapy subsidence of lid oedema, mucopurulent discharge, conjunctival congestion, corneal epithelial defect and anterior chamber reactions were noted. Average healing time in days (Mean +/- S.D.) were 13.67 +/- 1.21, 22 +/- 1.41, 23.5 +/- 1.05, 17.0 +/- 1.41 and 28.0 +/- 1.90 for PHMB, fluconazole, povidone iodine, aprotinin and normal saline respectively. Lid oedema, mucopurulent discharge and conjunctival congestion improved faster in PHMB and aprotinin treated eyes. The results of this study suggest that PHMB is a better drug for A. keratitis, while aprotinin may be used as an adjuvant drug in the management of A. keratitis.

Patterns of prescriptions and drug use in two tertiary hospitals in Delhi.

The study was carried out to assess prescribing trends in outpatients at Dr. R.P. Centre for Ophthalmic Sciences (RPC) and other OPD's of All India Institute of Medical Sciences (AIIMS) and Safdarjung hospitals, two premier hospitals in Delhi. Prescriptions of 500 patients were audited and analysed under heads of average number of drugs per patient, percentages of drugs prescribed by generic name, antibiotics, injections, drugs from WHO recommended essential drug list, availability of drugs etc. using WHO basic drug indicators. Prescription analysis showed that 75 to 95% drugs were prescribed from essential drug list. The average number of drugs per prescription was 1.42 to 4.07. Percentage of antibiotics prescribed varied from 14.39% to 22.28%. The use of injections was from nil to 4.4%. Availability of drugs was however, not satisfactory. Though maximum drugs were prescribed from essential drug list, the results indicate that there is a considerable scope for improving prescribing habits according to rational drug use and to provide a feed back to hospital authority for making maximum number of drugs available to the patients.

Effect of ascorbic acid on in vitro synthesis of testosterone in rat testis.

Effect of ascorbic acid on testicular steroid dehydrogenase activity and testosterone concentration, using in vitro preparation of rat testis, was studied. A significant stimulation of enzyme activity and rise in testosterone content were observed.

Comparative double blind multicentric randomised placebo controlled clinical trial of a herbal preparation of eye drops in some ocular ailments.

A double masked placebo controlled multicentric randomised clinical trial was conducted in 157 patients suffering from different eye ailments namely, cataract, dry eye syndrome, ocular asthenia, refractive errors and allergic conjunctivitis with a herbal eye drop preparation and placebo. In both dry eye syndrome and ocular asthenia the herbal eye drop preparation was found better than placebo. In a few cases of cataract, the vision seems to be improved. In early myopia it seems to correct the refractive errors while in high myopic conditions it controlled the progressive deteriorations. Subjective improvements were also noted with hypermetropia, presbyopia and astigmatism. Its healing capacity in allergic conjunctivitis was certainly better than placebo. It had no short term or long term side-effects. It is considered to be a useful drug in all conditions studied.

Comparative double masked randomised placebo controlled clinical trial of a herbal eye drop preparation in trachoma and conjunctivitis.

A double blind controlled clinical trial has been done with a herbal eye drop preparation in case of trachoma stage III and chronic conjunctivitis of the eyes. In both trachoma and chronic conjunctivitis, the herbal eye drop formulation proved its superiority over placebo. Side-effects (burning sensations) were observed with normal saline which was used as placebo. But no side-effects were observed in the patients of trachoma and conjunctivitis who got the active drug. Both objective and subjective improvements were observed with the herbal eye drop preparation.

Evaluation of antimuscarinic activity in human volunteers: a teaching aid in clinical pharmacology.

The antimuscarinic activity of oxyphenonium bromide, diphenhydramine hydrochloride and astemizole were evaluated in six volunteers. The parameters used were salivary secretion, heart rate and pupillary size. The results indicated that the changes in heart rate and pupillary size and measurements were not convenient parameters for class room demonstration. However, salivary secretion and dryness of mouth were found to be reliable parameters for measurement. It was concluded that simple procedures like evaluation of antimuscarinic activity could be introduced as teaching aids in clinical pharmacology for undergraduate students.

Effect of fatty diet on pharmacokinetics and pharmacodynamics of a liquid theophylline preparation in volunteers.

The effect of a standard breakfast and a fatty breakfast on the pharmacokinetics and pharmacodynamics of a theophylline liquid preparation (160 mg-single dose) was examined in 6 healthy, non-smoking male volunteers. The plasma theophylline concentrations after both standard and fatty diet were found to be comparable at each point of time and pharmacokinetic parameters like Cmax, Tmax, T1/2a, T1/2 beta and AUC0-alpha, were also comparable. However, the time taken to attain the therapeutic plasma concentration was earlier and sustained along with the standard breakfast in comparison to that with fatty breakfast. Peak change in PEFR and pulse rate was also observed earlier with the standard diet than with fatty diet. The plasma theophylline concentrations produced after both diets were insufficient to produce any detectable change in subjective symptoms like tremor palpitation, heart burn, nausea, restlessness and tenseness. However, theophylline after fatty breakfast was better tolerated than that after a standard breakfast.

A clinical study of intubating conditions under vecuronium bromide.

The drug vecuronium bromide, a short acting, non-depolarising agent with little side-effects, has brought much promise in the field of muscle relaxants. Fifth healthy patients were induced with injection thiopentone sodium 4 mg/kg and vecuronium bromide, 0.1 mg/kg was given IV. The earliest time at which the largest percentage of patients could be intubated satisfactorily was noted. The intubating conditions were estimated by scoring method. The duration of clinical relaxation was decided from the time of IV injection of vecuronium bromide to the return of muscle power of the non-respiratory muscles requiring repeat dose of the drug. The ideal intubating condition was achieved at 120 seconds and the duration of clinical relaxation ranged from 11-15 minutes.

Effect of lithium chloride on adrenocortical activity in male rats: evidence of dose and duration dependent response.

Changes in the adrenal weight, adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity and serum levels of corticosterone were observed in male wistar rats after the treatment of lithium chloride in the doses of 100, 200 and 400 micrograms/100 g of body weight/day for 7, 14 and 21 days. The experiments indicate that 200 and 400 micrograms/100 g.b.w. administered for 14 and 21 days caused a significant stimulation in the activities of adrenal 5-ene-3 beta-HSD along with elevation of adrenal weights and serum levels of corticosterone. 100 micrograms of lithium chloride was not able to modulate the adrenal activity. Moreover, plasma levels of lithium remain in therapeutic range in this experiment at the doses of 200 and 400 micrograms/100 g body weight. Therefore, our data suggest that lithium can alter the adrenal activity within its therapeutic range according to the duration of treatment.