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Biomedical subjects

R Grover

Publications and source records attributed to R Grover.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

Plastic surgery.

Explore the source record for details and available documents.

Guided Tissue Regeneration↗
PubMed1998

Spatial structure determination of antiarrhythmic peptide using nuclear magnetic resonance spectroscopy.

The peptide AAP10 was synthesized according to the Merrifield technique following the Fmoc-strategy and its spatial structure in aqueous solution studied with NMR principles. It is known from previous studies that the peptide has antiarrhythmic activity and inhibits cardiac ischemia induced alterations of the activation pattern, decreases the activation-recovery interval (ARI) dispersion and improves cellular coupling via enhancement of gap junction conductance (2, 2, 3, 4). The peptide was synthesized as a peptide amide. Two different semi cyclic conformations were characterized.

Anti-Arrhythmia Agents↗
PubMed1998

Measurement of invasive potential provides an accurate prognostic marker for giant cell tumour of tendon sheath.

Giant cell tumours of tendon sheath vary from solitary nodules to a multinodular variety that exhibits local infiltration. Recent advances in molecular oncology have defined a gene, nm23, expressed in normal cells which is responsible for inhibiting infiltration. The aim of this study was to investigate the expression of nm23 in a series of 52 giant cell tumours using immunohistochemistry and to assess its prognostic potential. nm23 expression was absent in 21%, of tumours and this was associated with a highly significant risk of local recurrence (P<0.0001). Multivariate analysis of outcome showed nm23 expression to be more reliable than other clinicopathological parameters for predicting outcome. This immunohistochemical test for nm23 is easily performed on standard paraffin sections and is recommended as an accurate prognostic marker for giant cell tumours of tendon sheath.

Adolescent↗
PubMed1998

Development of a simple spectrophotometric method for propylene glycol detection in tablets.

A simple spectrophotometric procedure was developed and validated to indirectly assess the quantities of propylene glycol (PG) remaining in compressed liquid/powder admixtures. Such simplified quantitation may facilitate several testing procedures related to various aspects of formulation development and material testing of pharmaceutical powder excipients using various nonvolatile liquids as the diluents. In the present study, this new and simple approach for PG quantitation was developed as an integral part of a new method termed the liquisolid compressibility (LSC) test, used to characterize the compaction behavior of powder excipients. According to LSC testing, several admixtures of a nonvolatile liquid (in this case PG) and a powder, differing in their PG/powder weight ratio, are compressed in order to assess their compactabilities. The PG content of such compacts may then be directly quantitated by the USP gas chromatographic method or, indirectly, by this new simple spectrophotometric procedure. The new approach involves the addition of a dye marker to the PG prior to its incorporation into the powder. After compression, the PG amount remaining in the compacts may be determined by simply extracting the dye from the tablets and analyzing the extracts spectrophotometrically. In this manner, the dye content thus obtained may be extrapolated to the respective net amount of PG originally added as a dye/PG solution to the powder. Statistical comparison of the results obtained from both methods revealed almost absolute correlation.

Cellulose↗
PubMed1998

In vitro release evaluation of hydrocortisone liquisolid tablets.

The potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using hydrocortisone as the model medication. The in vitro release patterns of this very slightly water-soluble corticosteroid, formulated in directly compressed tablets and liquisolid compacts, were studied at different dissolution conditions. The new formulation technique of liquisolid compacts was used to convert liquid medications such as solutions or suspensions of hydrocortisone in propylene glycol, a nonvolatile liquid vehicle, into acceptably flowing and compressible powders by blending with selective powder excipients. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Due to their increased wetting properties and surface of drug available for dissolution, liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made, directly compressed tablets containing micronized hydrocortisone. The in vitro drug dissolution rates of liquisolid tablets were found to be consistent and independent of the volume of dissolution medium used, in contrast to the plain tablets which exhibited declining drug release patterns with decreasing dissolution volumes. It has been also shown that the fraction of molecularly dispersed drug in the liquid medication of liquisolid systems is directly proportional to their hydrocortisone dissolution rates.

Chemistry, Pharmaceutical↗
PubMed1998

Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks.

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) i.v. given over 15 min for a single migraine attack (546C88:placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebo-treated patients (p = 0.01). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.

Adolescent↗
PubMed1998

Predicting the outcome of laser treatment for pigmented lesions.

Laser treatment of pigmented lesions requires melanocytes to lie within the range of penetration of the laser, and to contain melanin in order to absorb and covert light energy into heat by photothermolysis. This study investigated whether these limitations could be tested by immunohistology and used to predict the outcome of treatment. Punch biopsies were taken from 32 patients prior to laser treatment. Immunohistology targeting the S-100 antigen allowed measurement of melanocytic depth and the presence of amelanosis. These parameters provided an accurate method of predicting good results (sensitivity 81%, specificity 93%) and were particularly useful in delineating the likelihood of a poor/very poor outcome (sensitivity 100%), even beyond the predictive capacity of the test patch. No complications were associated with the biopsy technique which reliably provided sufficient material for histological assessment. This study reports the clinical applications of this test to laser treatment.

Adolescent↗
PubMed1998

A quantitative method for the assessment of facial rejuvenation: a prospective study investigating the carbon dioxide laser.

Laser resurfacing has been reported to have a useful role in the treatment of facial rhytides, however the results of published series have relied on subjective methods of assessment. The aim of this investigation was to develop an accurate method of measuring wrinkle depth and secondly to use this to assess the efficacy of laser rejuvenation. Wrinkle depth was measured in 30 patients with perioral rhytides using a silicone mask to provide a negative replica. Depth was measured using simple light microscopy and the accuracy of this was confirmed with the electron microscope. A highly significant correlation was found between these two methods of measurement (R2 = 0.97, P < 0.0001) with an accuracy of 0.03 mm. Using this method laser rejuvenation was evaluated in a prospective series of 30 patients with perioral rhytides (median follow-up 11.5 months, range 5-20 months). Resurfacing was found to achieve a significant reduction in mean wrinkle depth of 91% (paired t-test, P < 0.00001). The only complication reported was erythema which was always transient. The use of light microscopy on silicone moulds therefore provides a simple and accurate method for assessing the outcome of facial rejuvenation. Using this technique, the carbon dioxide laser was objectively found to provide a safe and effective treatment for facial rhytides.

Aged↗
PubMed1998

The clinical significance of c-myc oncogene expression in melanomas of the scalp.

Melanomas of the scalp are rare and have a poorer prognosis than melanomas arising at other cutaneous sites. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 25 patients with scalp melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene activity provided a prognostic marker with shorter overall survival (log rank test, chi 2 = 3.9, P = 0.05) in tumours with high nuclear c-myc oncoprotein positivity. These results support our previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical significance in identifying high risk patients.

Adult↗
PubMed1998

Melanoma of the face: the safety of narrow excision margins.

Recent studies have shown that narrower excision margins may be safe, but the optimal or minimum margin for melanoma is unknown. Wide margins of excision are possible on the trunk and limbs, but functional and cosmetic constraints often limit the extent of excision on the face. A collaborative study from two continents (Cape Town, South Africa and Northwood, England) investigated the outcome of different excision margins of 106 patients with stage I melanoma of the face. The margin of excision was measured from the records of the pathological specimen. Thirty patients had margins of less than 1 cm, 64 had margins of between 1 and 2 cm, and 12 had margins greater than 2 cm. Primary apposition or flap closure was possible in 85 patients. Seven patients developed local recurrences and these were not influenced by the excision margin. This study supports the contention that the primary treatment of cutaneous melanoma on the face should be histologically confirmed complete excision, and that this can be achieved with margins of excision less than 1 cm. Local recurrence is not related to the margin of excision or to tumour thickness.

Adult↗
PubMed1998

An analysis of p16 protein expression in sporadic malignant melanoma.

Inactivation of p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactivation in melanocytic progression by measuring the level of p16 protein in a range of sporadic, benign and malignant melanocytic lesions. Using dual parameter flow cytometry, p16 protein expression was measured in 30 benign melanocytic naevi, 38 primary and 51 metastatic melanomas. A high level of p16 expression was demonstrated in benign melanocytic naevi (96% median nuclear positivity), with a significant reduction in primary melanomas (69%, P < 0.001). The median nuclear positivity of primary melanomas was significantly higher (P < 0.03) than the level of expression in metastatic lesions (median positivity 37%). A progressive loss of p16 expression was demonstrated from benign melanocytic naevi through to primary and metastatic lesions. These data suggest that loss of p16 protein expression is not only associated with the early transformation of benign lesions, but also with the later stages of malignant progression.

Adolescent↗
PubMed1998

Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.

Adult↗
PubMed1997

Environmental fate of trifluralin.

Trifluralin, a preemergence, soil-applied and soil-incorporated herbicide, has been in agricultural use since 1963. The environmental chemistry and fate of dinitroaniline herbicides, including trifluralin, has been studied extensively in agricultural soils. Probst et al. (1975) and Helling (1976) have summarized pre-1975 data on the mobility, persistence, and degradation or metabolism of dinitroaniline herbicides as a group. Since then, numerous studies have been carried out on the fate of dinitroanilines, especially trifluralin, in the environment to understand further their degradation in soil, potential for mobility and persistence, and environmental concentration in water and air. The present review, while summarizing briefly earlier data, concentrates primarily on the post-1975 data on degradation, mobility, and persistence of trifluralin in soils and its potential concentrations in water and air. Trifluralin is readily degraded under sunlight in all media, with half-lives (t1/2) of minutes to several months, depending on the substrate. In addition, other dissipation processes, such as microbial and chemical, are also operative in soils, water, and sediments. Several degradation products of trifluralin have been identified and characterized, both under photolysis and following aerobic and anaerobic metabolism in soils and water-sediment systems. The differences between various degradative pathways of trifluralin appear to be more quantitative than qualitative in nature, leading eventually to the same end products that are subject to binding or mineralization with time. The general lack of accumulation of the breakdown products of trifluralin suggests that these are also subject to the same degradative mechanisms as the parent compound. Trifluralin has low water solubility and is strongly bound to soil components; mean Koc values range from 4,000 to 13,000. Once applied and incorporated into the soil, trifluralin remains relatively immobile with minimal or no potential for contamination of groundwaters under or near the treated zones. Trifluralin residues in soil surface layers are subject to loss via transport in runoff water or volatilization into the air. Seasonal losses in surface runoff are consistently less than 0.5% of the amounts applied, with concentrations in edge-of-the-field run-off water typically < 1.0 microgram L-1. Consequently, trifluralin is infrequently detected in surface waters and, if present, usually occurs below levels of quantification. Seasonal trifluralin losses into the atmosphere can be as high as 25% of that applied. Maximum trifluralin residues in the air above treated fields are in the 2-3 micrograms m-3 range following application, decreasing to < 100 ng m-3 in ambient air of intensive use areas, indicating its rapid dissipation in air. Trifluralin residues at < 100 pg m-3 in the atmosphere of remote nonuse regions have been reported, suggesting its potential for long-range transport. However, there is a general lack of understanding of the mechanisms controlling its potential for long-distance transport, especially considering its rapid photodegradation in vapor and solution states. The persistence of trifluralin in agricultural soils following incorporation is highly variable, depending on several factors such as depth of incorporation, soil moisture, soil temperature, soil air, and soil organic matter content. Estimated half-lives under a variety of agronomic conditions range from 25 to > 201 d, thus categorizing its persistence from 'moderate' to 'persistent'. The estimated half-life data for trifluralin under agronomic conditions, however, cannot be extrapolated to other potential scenarios, such as its dissipation in nontarget areas where trifluralin residues, if any, are essentially deposited on surfaces. Surface deposits on nontarget areas, unlike soil-incorporated residues, would be subject to volatilization and photolysis and thus more short lived. (ABSTRACT TRUNCATED)

Canada↗
PubMed1997

The clinical significance of oncogene expression in subungual melanoma.

Subungual melanoma is a particularly aggressive tumour. However, biological investigations of its behaviour are presently lacking due to its comparative rarity. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 24 patients with subungual melanoma using the technique of flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis revealed that stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (log rank test, chi 2 = 6.6, P = 0.01) and overall survival (log rank test, chi 2 = 3.6, P = 0.07) in tumours with high oncoprotein levels. This is the first study to investigate oncogene expression in subungual disease and supports its potential application as a prognostic marker.

Adult↗
PubMed1997

Measurement of c-myc oncoprotein provides an independent prognostic marker for regional metastatic melanoma.

Patients with melanoma who develop nodal metastatic disease represent a group with heterogeneous clinical outcome. Nodal positivity remains the most accurate prognostic marker for regional melanoma although it fails to predict outcome in a significant number of patients. Recent studies have illustrated the prognostic potential of c-myc oncogene expression in melanoma. The aim of this study was to measure c-myc oncoprotein in a series of regional metastatic specimens from 48 patients, and evaluate its use as a marker of clinical outcome. Oncoprotein expression was detected in 46 (96%) of the tumours with a median positivity of 68% (range 0-98%). Survival analysis revealed a significant association between oncoprotein positivity and survival (Long-Rank test, chi 2 = 15.2, P < 0.001). Multivariate analysis of outcome showed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including nodal positivity (chi 2 = 8.34, P = 0.003). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for regional metastatic melanoma.

Aged↗