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Biomedical subjects

R Grover

Publications and source records attributed to R Grover.

At least 19 recordsLinked to original sources

Exposure of ground-rig applicators to the herbicide bromoxynil applied as a 1:1 mixture of butyrate and octanoate.

Bromoxynil is a herbicide used extensively on the Canadian prairies for weed control in cereal production. This is a report on exposure to and absorption of bromoxynil by farmers during handling, transferring, mixing, and then applying the herbicide to cereal crops using tractor-drawn ground-rigs. The 14 individual spray operations, in which farmers applied 9 kg of bromoxynil (phenol equivalent, p.e.) to 32 ha, lasted from 113 to 549 min and involved one to five tank fills. In five of the spray operations, the farmers wore neoprene gauntlet-style protective gloves. Tractors, equipped with cabs, were used in nine spray operations.Air sampling, hand washes, and dermal patch dosimeters served as the basis to calculate the amount of bromoxynil (p.e.) available for inhalation, deposition on the hands, and deposition under a standardized set of protective clothing. Tractors, equipped with cabs, decreased inhalation exposure by a factor of approximately 10. Use of gauntlet-style neoprene protective gloves decreased dermal exposure to the hands region of the body by 25 times, whereas two layers of laundered cotton provided a protective effect of > 15 in the chest region. The median value for the amount of bromoxynil (p.e.) inhaled was 0.018 microg x kg BW(-1)x kg (p.e.)(-1) for the 14 spray operations. The hands region of the body was the area most exposed to bromoxynil (p.e.), the median value of dermal deposition to the hands being 808 microg (p.e.) compared to 1,600 microg (p.e.) for the whole body, when protective gloves were not worn. The urinary excretion pattern of bromoxynil (p.e.) did not demonstrate an obvious maximum followed by a continuous decline to background concentrations. Instead, the amounts excreted increased over the first few days after application and then tended to remain relatively constant during the remainder of the 10-day sampling period. The median value for urinary excretion was 2.22 ng x g creat(-1) x kg BW(-1) x kg (p.e.)(-1).

Absorption↗

Structure-activity relationships of novel peptides related to the antiarrhythmic peptide AAP10 which reduce the dispersion of epicardial action potential duration.

We report the first study on short peptide structure-activity relationships (SAR) for the antiarrhythmic peptide AAP10 and its putative receptor. Synthetic improvements on the natural antiarrhythmic peptide AAPnat (H-Gly-Pro-Hyp-Gly-Ala-Gly) isolated from bovine atria led us to the synthesis of our lead molecule AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-NH(2)) which reduces dispersion of epicardial potential duration and acts antiarrhythmically in isolated rabbit hearts. The aim of our study was to elucidate structure-activity relationships for AAP10 based on Langendorff experiments and molecular modeling. Mutation of the amino acid sequence led to 11 different peptides which were tested analogous to the lead molecule. Among these new synthetic peptides various including the cyclopeptide cAAP10RG, cyclo[CF(3)C(OH)-Gly-Ala-Gly-Hyp-Pro-Tyr] showed promising activities. (supported by the DFG and Köln-Fortune)

Animals↗

A randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of a Chinese herbal product (P07P) for the treatment of canine atopic dermatitis.

A randomized, double-blind, placebo-controlled trial of P07P, a product derived from a traditional Chinese herbal remedy, was undertaken in 50 dogs with atopic dermatitis. Owners recorded a daily itch score for 4-14 days before treatment and during treatment. Packets of powder containing P07P or placebo were added to the food once daily for 8 weeks. Dogs were assessed for erythema, surface damage, overall coat condition and seborrhoea by the same investigator, as well as for pruritus and general demeanour, at 0 (visit 2), 28 (visit 3) and 56 (visit 4) days of treatment or at withdrawal. Investigator and owner assessments of response were recorded after 28 and 56 days of treatment or at withdrawal. The predefined primary outcome measure was the owners' assessment of response at the end of treatment. Nine of the 24 dogs (37.5%) in the P07P group but only 3 of the 23 dogs (13%) in the placebo group were considered to have improved, but this difference was not statistically significant (P = 0.09). There was a significantly higher withdrawal rate due to worsening of condition in the placebo group (P = 0.04). Mean daily itch score in the second 28-day period of the study was significantly higher than baseline in the placebo group (P = 0.01) but not in the P07P group (P = 0.30). Pruritus scores showed a significant deterioration from baseline at the final visit in the placebo group (P = 0.01) but not in the P07P group (P = 1.00). There was a significant difference between the groups in change from baseline in erythema score at visit 3 (P = 0.05). There were no significant differences (P > 0.05) in surface damage, seborrhoea, overall coat condition and general demeanour scores within or between the groups throughout the study. The product was well tolerated with no severe or serious adverse events recorded. P07P may be beneficial as a novel nonsteroidal therapy for the management of dogs with atopic dermatitis.

Administration, Oral↗

The prevention of haematoma following rhytidectomy: a review of 1078 consecutive facelifts.

Haematoma remains the most common complication of rhytidectomy and can lead to prolonged facial oedema or skin necrosis. The factors leading to haematoma formation remain unclear, and studies establishing causal relationships are lacking. The aim of this study was to determine which parameters were significantly associated with haematoma formation in a consecutive series of facelifts performed by two high-volume operators. The records of 1078 patients who underwent facelifting between 1994 and 1999 were reviewed and the parameters associated with haematoma formation were investigated using multivariate statistical analysis. In this series of 1078 patients, 45 haematomas occurred (4.2%). Analysis revealed significant associations between haematoma formation and anterior platysmaplasty (P= 0.009), systolic pressure (P= 0.02), gender (P= 0.03), aspirin or non-steroidal anti-inflammatory intake (P= 0.04) and smoking (P= 0.049). In addition the relative risk of each parameter was calculated. This allowed the haematoma risk for individual patients to be calculated and haematoma-prone patients were identified preoperatively. This is the first study to establish independent statistical risk factors for haematoma after rhytidectomy and to present a scoring system that calculates the haematoma risk preoperatively. The implications of these findings and possible measures for the prevention of haematoma are also presented.

Anti-Inflammatory Agents, Non-Steroidal↗

The prognostic importance of c-myc oncogene expression in head and neck melanoma.

Melanomas of the head and neck have a poorer prognosis than melanomas arising at other cutaneous sites. To study the biology of this disease, the expression of the c-myc oncogene was studied in tumors from 97 patients with head and neck melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene expression provided a prognostic marker with shorter overall survival in tumors with high nuclear c-myc oncoprotein positivity (log-rank test, chi2 = 8.77, p < 0.005). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker (log-rank test, chi2 = 8.82, p = 0.005). These results support the authors' previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical importance in identifying high-risk patients.

Adolescent↗

Duplicate sampling reproducibility of atmospheric residues of herbicides for paired pan and high-volume air samplers.

The reproducibility of collection of atmospheric residues of the herbicides 2,4-D and triallate as bulk (wet plus dry) deposition samples by paired pan samplers and as particulate (filter) and vapour (PUF/XAD-2 resin cartridge) samples by paired high-volume air samplers was determined. Variability of herbicide concentrations in paired bulk deposition samples was within 25% for 65 and 80% of the samples for 2,4-D and triallate, respectively, with approximately 90% of the paired samples being within a factor of 2 for both herbicides. The vapour samples of 2,4-D and triallate showed similar reproducibilities. The highest reproducibility was observed for the filter samples with 92% of the paired data sets for 2,4-D being within 25% variability. No triallate was detected in the filter samples.

2,4-Dichlorophenoxyacetic Acid↗

The Merkel cell carcinoma: survival and oncogene markers.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and malignant tumour. Survival data and prognostic factors are scarce. AIM: To investigate the usefulness of biological markers to predict the prognosis for these aggressive tumours. METHODS: C-myc oncoprotein and proliferation was analysed in specimens from 13 patients with MCC, treated between 1983 and 1997. The average age at presentation was 68.3 years. Overall follow-up ranged from 14 to 158 months, with a mean of 68.2 months. Specimens were analysed by immunohistochemistry for proliferation (mib-1) and flow cytometry for oncogene activity (c-myc). RESULTS: The median positivity was 52% for the c-myc oncogene and 50% for proliferation, but these did not correlate to survival as analysed by the Kaplan-Meier method. Other parameters such as median age at presentation, sex, site of tumour and adjuvant radiotherapy were also analysed, but none were found to be significant. CONCLUSIONS: This study showed that neither c-myc oncogene activity or mitotic index in MCC can be related to patient survival.

Aged↗

An analysis of p16 tumour suppressor gene expression in acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive melanocytic lesion but, due to its comparative rarity, biological investigations into the behaviour of this subtype of melanoma are lacking. The activity of the recently described p16 tumour suppressor gene, thought to be the 'familial melanoma gene', was studied in 24 patients with subungual melanoma and 44 patients with plantar melanoma. Lower levels of p16 oncoprotein were demonstrated than that found in other histogenetic types of melanoma. Stratification of patients of all disease stages revealed a poorer survival in patients with low p16 expression (log rank test, chi(2)= 3.9, P = 0. 05). These data suggest that p16 inactivation may play an important role in the development and progression of acral lentiginous melanomas. However, the level of p16 expression was not prognostic since survival analysis on stratification of stage I patients according to p16 level did not reach statistical significance for both survival and disease free interval.

Aged↗

Reducing postoperative morbidity after the insertion of gold weights to treat lagophthalmos.

Paralysis of the orbicularis oculi muscle leads to an unopposed action of the levator of the upper eyelid (lagophthalmos) in facial nerve palsy. The resultant exposure of the cornea may lead to keratitis, corneal ulceration, and eventual blindness. Although many surgical options exist in the treatment of lagophthalmos, upper lid loading with a gold weight implant has become one of the preferred methods to reduce the complications that may follow. The problems encountered after gold lid loading and methods to reduce postoperative morbidity are not well documented. The objective of this study was to determine the range of morbidity seen after gold weight insertion and to evaluate the effect of supratarsal fixation on subsequent morbidity. After retrospective reviews by questionnaire and case note analysis, supratarsal fixation was found to noticeably reduce the rate of implant ulceration and extrusion. This study demonstrates upper lid loading to be an effective method for the treatment of lagophthalmos, and it supports fixation of gold weights in reducing surgical morbidity.

Adolescent↗

Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: effects on intestinal oxygen exchange and energy balance.

OBJECTIVES: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. MEASUREMENTS AND MAIN RESULTS: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. CONCLUSIONS: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.

Animals↗

Changing scenario of cryptococcosis in a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: With the increase in the number of patients of AIDS, the incidence of cryptococcosis is on the rise in India. It was therefore considered important to evaluate the predisposing factors, laboratory investigations and outcome of patients with cryptococcosis in this changed scenario. METHODS: We assessed 58 patients with cryptococcosis retrospectively over a five year period (January 1995-December 1999) at the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. RESULTS: The annual incidence of cryptococcosis in PGIMER, Chandigarh has increased about 15 fold from 1970-1982 (pre AIDS era) to 1995-1999 (present series). Of the 47 patients studied for predisposing factors, 36 patients were identified with predisposing factors, HIV infection (57.4%) was the commonest followed by haematologic malignancies (6.3%) and renal transplant (4.2%). Forty one patients were diagnosed by isolation of the organism as well as antigen detection in cerebrospinal fluid/serum, 9 by isolation alone and 8 by antigen detection alone. Quantitative antigen titres were done in 38 patients and a significantly higher (P < 0.01) antigen titre (> 512) was observed in HIV positive patients as compared to HIV negative patients. All isolates tested were of Cryptococcous neoformans var neoformans biotype and no resistance to antifungal agents was noted. Twenty of 41 patients receiving treatment improved. The results were compared with other studies available from India. INTERPRETATION & CONCLUSION: The incidence of cryptococcosis is on the rise in this part of north India and this can be attributed to an increase in AIDS cases.

Adult↗

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Adult↗

Measurement of c-myc oncogene expression provides an accurate prognostic marker for acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive tumour with a worse prognosis than other varieties of primary cutaneous melanoma. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 45 patients using flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis with stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (Log-Rank test, chi 2 = 16.7, P < 0.0001) and overall survival (Log-Rank test, chi 2 = 8.9, P = 0.002) in tumours with high oncoprotein levels. Multivariate analysis revealed c-myc oncogene expression to be more accurate in predicting clinical outcome than all existing clinicopathological parameters including the Breslow depth (Cox's proportional hazards model, P = 0.0011). This study provides biological evidence to explain the aggressive behaviour of acral melanoma and supports the application of oncogene measurement as an accurate prognostic marker.

Adult↗

The removal of unwanted hair using a ruby laser.

A ruby laser has been developed to remove unwanted hair. Melanin within the hair is used as a natural chromophore. It is postulated that photothermal damage destroys the hair itself and also key cells surrounding the hair follicle to prevent regrowth. A prospective study of laser depilation in 116 patients or 175 sites was performed over a period of 18 months. All the patients had tried other methods of hair removal and found them to be unsatisfactory. Hair counts (follicles/cm2) were used to judge the outcome. The mean follow-up time was 23.25 weeks (range 12-76 weeks). After a mean number of treatments of 1.92 (range 1-20) there was a 56.4% reduction in hair density. Comparing pre- and post-treatment hair density, there was a highly significant reduction (paired t-test: P < 0.00001). Laser removal of hair is now a realistic treatment option.

Adolescent↗

Time-course analysis of type II cell hyperplasia and alveolar bronchiolization in rats treated with different particulates.

In this study, we compared the morphological reaction patterns in rat lungs following a single intratracheal instillation of 20 mg quartz, 20 mg coal mine dust (15.3% quartz), or 25 mg talc. Control animals received a single dose of 0.5 ml saline solution intratracheally. Investigations by light microscopy, morphometry, and DNA image cytometry were carried out 3, 6, 12, and 18 mo after dust administration. During the investigation period, we observed a temporary increase in the number, area, and proliferative activity of the type II cells, which differed in intensity among the three dusts. After 18 mo, however, type II cells in treated animals did not differ from control animals. On the other hand, the expansion of a multifocal alveolar bronchiolization as putative preneoplastic lesion had progressed enormously by the end of the test (1-3% of the investigated lung area). Consistent with this, the proliferative activity of the epithelial cells in terminal bronchi of the coal mine dust- and quartz-treated animals was enhanced by the end of the 18-mo investigation period, while the reaction to talc was minimal (0.2% of totally investigated lung area). Our data suggest that in bronchiolo-alveolar regions, especially in the epithelium of terminal bronchi, there is an overshoot regeneration after cell damage that leads to an alveolar bronchiolization.

Air Pollutants↗

Effect of powder substrate on the dissolution properties of methyclothiazide liquisolid compacts.

The effects of powder substrate composition on the in vitro release properties of methyclothiazide liquisolid compacts were evaluated. The dissolution patterns of this water-insoluble drug formulated in liquisolid tablets were also compared to those of commercial products. According to the new liquisolid technique, liquid medications such as solutions or suspensions of water-insoluble drugs in suitable nonvolatile liquid vehicles can be converted into acceptably flowing and readily compressible powders by a simple admixture with certain powder substrates, which are selected powders referred to as the carrier and coating materials. Enhanced release profiles may be exhibited by such systems due to the increased wetting properties and surface of drug available for dissolution. Liquisolid tablets of methyclothiazide containing a 5% w/w drug solution in polyethylene glycol 400 were prepared using powder substrates of different excipient ratios. The release rates of such products were assessed using the USP dissolution test and were compared to those of their commercial counterparts. It was observed that maximum drug dissolution rates can be exhibited by systems that have powder substrates with optimum carrier-to-coating ratios. In addition, liquisolid tablets displayed significantly enhanced dissolution profiles compared to those of marketed products.

Chemistry, Pharmaceutical↗

An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVE: To assess the effects of the nitric oxide synthase inhibitor, 546C88, in patients with septic shock and to evaluate the range of dose rates that sustain mean arterial pressure (MAP) of > or =70 mmHg. DESIGN: Multicenter, open-label, uncontrolled, dose range finding study. SETTING: Ten intensive care units in Europe and the United States. PATIENTS: Thirty-two patients with septic shock diagnosed within <24 hrs. INTERVENTIONS: Patients received a fixed dose rate of 546C88 at either 1(n = 6), 2.5 (n = 6), 5 (n = 4), 10 (n = 5), or 20 mg/kg/hr (n = 11) by intravenous infusion for up to 8 hrs. Conventional vasoactive therapy was restricted to norepinephrine and/or dobutamine. During 546C88 therapy, MAP was to be maintained between 70 and 90 mm Hg, while attempting to withdraw any concurrent norepinephrine. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics, blood gases, and plasma nitrate were assessed. Infusion of 546C88 (1-20 mg/kg/hr) for up to 8 hrs enabled a 60 to 80% reduction of the norepinephrine dose rate in all cohorts, while MAP was sustained at >70 mm Hg. There was an increase in vascular tone and a decrease in cardiac index within the 1st hr of therapy. Systemic vascular resistance returned toward baseline with reduction of concomitant administration of norepinephrine. The decline in oxygen delivery was associated with an increase in extraction and, therefore, the maintenance of oxygen consumption. There was a sustained reduction of venous admixture within the 1st hr of therapy. 546C88 was not associated with any major or dose-dependent adverse effect on pulmonary, hepatic, or renal function. CONCLUSIONS: Treatment with the nitric oxide synthase inhibitor, 546C88, can restore the balance of vasomotor tone, thereby, maintaining blood pressure and reducing or eliminating the requirement for norepinephrine therapy in patients with septic shock. Infusion of 546C88 (1-20 mg/kg/hr) appears to have a satisfactory overall safety profile.

Adult↗