Biomedical subjects

R Grover

Publications and source records attributed to R Grover.

At least 37 records · Page 2Linked to original sources

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗

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↗

PubMed1999

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↗

PubMed1999

Norepinephrine and nomega-monomethyl-L-arginine in porcine septic shock: effects on hepatic O2 exchange and energy balance.

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q liv), O2 exchange, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q liv nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface as well as HbScO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.

Animals↗

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↗