Biomedical subjects

Rajiv Grover

Publications and source records attributed to Rajiv Grover.

11 recordsLinked to original sources

PubMed2006

CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: assessment by the use of tissue microarray.

Despite the use of sentinel node biopsy techniques, the search continues for other strategies to improve the accuracy of estimating prognosis in melanoma patients. Various biomarkers have previously been studied for use in this role, but none has yet achieved acceptance in routine practice. We have applied the novel technology of tissue microarray for the high throughput screening of a cohort of 120 primary cutaneous melanoma specimens for expression of the transmembrane glycoprotein CD44, splice variant 3 (v3), which has previously been implicated in tumor progression. A highly significant correlation between CD44v3 expression and Breslow thickness, Clark's level and patient age was demonstrated (Spearman correlation p < 0.001). Regarding clinical outcome, CD44v3 expression was shown to be significantly associated with better outcome (chi(2) = 7.2219, p = 0.0072). Furthermore, subgroup analysis revealed a sequentially improved survival probability associated with the intensity of CD44v3 staining (chi(2) = 12.5162, p = 0.0058). Analysis in a Cox multivariate model, however, did not show CD44v3 to be independently predictive of prognosis. The implications of these findings are considered, and the use of CD44v3 as a potential prognostic marker or a target for therapeutic manipulation are discussed.

Adult↗

PubMed2006

Injectable hyaluronic acid implant for malar and mental enhancement.

BACKGROUND: The use of a thicker injectable implant version of one of the hyaluronic acid dermal fillers (Restylane SubQ, Q-Med, Uppsala, Sweden) is described. OBJECTIVE: A group of treated patients has been studied for more than 1 year. Restylane SubQ was injected to the submuscular plane of the upper cheeks and chin to observe efficacy of augmentation and side effect profile, and further observations were made of the duration of benefit. METHODS: Patient details--72 patients were treated, 68 for upper cheek augmentation, 2 for chin augmentation, and 2 for both areas. Four patients received second injections 8 weeks after the first to increase augmentation. RESULTS: Patients all showed a persistence of benefit during the posttreatment observation period of up to 64 weeks. Four patients had minor side effects that resolved with local treatment and time. Four patients had second injections to complete augmentation without complications. CONCLUSIONS: Restylane SubQ is a useful injectable agent to augment and lift upper cheeks and recontour chins. Further efficacy studies seem justified.

Biocompatible Materials↗

PubMed2005

nm23 as a prognostic marker in primary cutaneous melanoma: evaluation using tissue microarray in a patient group with long-term follow-up.

The accurate estimation of prognosis in patients with melanoma is of increasing importance with novel adjuvant therapies on the horizon. The current prediction of prognosis employs techniques involving sentinel lymph node biopsy, which carries an associated morbidity and is of little use in patients who develop direct distant metastases or direct in-transit metastases. New strategies or factors are therefore needed to improve the accuracy of determination of prognosis. nm23 is a putative metastasis suppressor; however, conflicting data exist as to its role in melanoma progression and its use as a potential prognostic marker. The purpose of this study was to use the technique of tissue microarray to study a cohort of melanoma patients with long-term follow-up data in order to ascertain its potential use as a prognostic marker. One hundred and twenty patients with primary cutaneous melanoma were included in the tissue microarray and a commercially available immunohistochemical marker for nm23 was used for protein detection. nm23 expression was strongly correlated with Clark's level (P<0.001), Breslow depth (P=0.002) and patient age (P=0.014). nm23 expression was significantly associated with a poor patient outcome (chi2=7.2219, P=0.0072). Further analysis revealed that the intensity of nm23 expression also correlated with patient outcome (chi2=11.3281, P=0.0035). However, on multivariate analysis, nm23 was shown not to be an independent marker of prognosis. The results of this study, when taken with the existing literature, suggest a role for nm23 in melanoma disease progression. However, its use as a prognostic marker in routine practice does not appear to be justified.

Adolescent↗

PubMed2005

Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker.

Refining current prognostic capability is essential for improving the management of melanoma. This study was undertaken to develop a tumor array for the rapid assessment of novel prognostic markers in a series of specimens from melanoma patients with 7- to 10-year follow-up. A melanoma database of 120 patients with archival specimens was created after histopathological review of original specimens. A tissue array was developed allowing 480 biopsy samples from the 120 primary melanoma specimens to be embedded into a single paraffin block. This was sectioned and stained for the adhesion marker melanoma cell adhesion molecule (MCAM); after further review, 76 of the 120 specimens were suitable for further analysis. The slides were assessed by two independent observers without previous knowledge of the clinical outcome for staining positivity and stain intensity. Assessment of association between MCAM and clinicopathological features was carried out using chi-squared analysis, and univariate and Cox multivariate analyses were performed on the data. There was a high correlation between MCAM intensity and both Clark's level and Breslow thickness (Spearman correlation p < 0.001 for both). The data revealed that MACM was a highly specific prognostic marker for survival in univariate analysis (chi2 = 18, p < 0.0001). Subgroup analysis by stratification of the staining intensity revealed a sequentially worsening survival with increasing staining intensity (chi2 = 22.33, p < 0.0001). Multivariate analysis of survival showed MCAM to be an independent prognostic marker more accurate than all other clinicopathological parameters (p < 0.0001), including the Breslow depth. Further analysis within only intermediate-thickness tumors showed MCAM intensity added further refinement to outcome prediction (chi2 = 22.33, p < 0.0001). The tissue array provided a rapid method of analyzing up to 480 specimens within a single paraffin block. This will benefit many areas of plastic surgery research. The identification of adhesion markers revealed a valuable prognostic marker for predicting outcome and a potential target for therapeutic manipulation.

Adult↗

PubMed2005

Identification of P-cadherin in primary melanoma using a tissue microarrayer: prognostic implications in a patient cohort with long-term follow up.

Sentinel lymph node biopsy is the most accurate technique for establishing melanoma patient prognosis but is associated with morbidity and is of little value in those tumors that first metastasize to sites other than the regional nodal basin. Noninvasive methods of establishing prognosis are therefore desirable. We have used the novel technology of tissue microarray to study a cohort of 120 patients with melanoma with long-term follow-up data for the expression of P-cadherin. The tissue microarray was successfully constructed and stained. Loss of P-cadherin expression was found to be significantly correlated with outcome (log rank chi2 = 10.1336, P = 0.0015). The results suggest a fundamental role for P-cadherin in melanoma progression and identify it as a potential prognostic marker and a possible target for therapeutic manipulation.

Adult↗

PubMed2004

Endoscopic brow lift: a personal review of 538 patients and comparison of fixation techniques.

Since the introduction of endoscopic brow lifting in the mid-1990s, it has become widely accepted as a method for rejuvenation of the upper third of the face. Despite the multitude of brow fixation techniques, there are few long-term studies providing accurate analysis of outcome. The aims of this investigation were to evaluate the long-term objective results of endoscopic brow lifting and to establish whether the technique of fixation altered the longevity of aesthetic outcome. The outcome of endoscopic brow lifts carried out on 538 consecutive patients over a 6-year period was assessed. For each patient, midpupil-to-brow distance was measured preoperatively and at intervals postoperatively. Two different fixation methods were compared: fibrin glue (n = 189, group 1; 104 records available) and polydioxanone sutures tied through bone tunnels (n = 349, group 2; 220 records available). In 214 patients, an upper lid blepharoplasty was performed simultaneously (85 in group 1 and 129 in group 2). At 1 month postoperatively, each fixation technique had produced a significant change in mean pupil to brow height (5.93 mm in group 1 and 6.21 mm in group 2, with no significant difference between the two methods; p = 0.17). However, when measurements were compared more than 3 months postoperatively (mean, 9.4 months), there was a significant difference, with some relapse in the patients treated with fibrin glue (p < 0.01). However, in group 2 (tunnel fixation), measurements remained stable, with 6.21 mm at 1 month compared with 6.16 mm long term (no significant difference, p = 0.34). In contrast, in group 1 (fibrin glue), measurements showed significant reduction, with a 1-month result of 5.93 mm and a long-term outcome of 3.79 mm (p < 0.01). Upper lid blepharoplasty had no effect on the long-term outcome of either group (p > 0.3 in group 1, p > 0.4 in group 2). Complications were few in both groups. In group 1, there was one infection, two instances of significant alopecia (both temporary), and one reoperation for relapse. In group 2, four patients required minor surgical revision of a lateral port scar and three minor areas of temporal alopecia, which recovered in less than 3 months. One patient had a paresis of the frontal branch that had recovered after 4 months. The endoscopic brow lift is therefore a safe and effective technique for increasing mean pupil to brow height. Fixation with polydioxanone sutures tied through bone tunnels produces a significantly more stable result than fibrin glue, without greater risk. This lends weight to experimental evidence that periosteal fixation must be maintained for at least 6 weeks to be secure.

Blepharoplasty↗

PubMed2004

Validation of tissue microarray for the immunohistochemical profiling of melanoma.

Tissue microarray technology allows high throughput profiling of cancer specimens by immunohistochemical staining. Protein expression varies throughout tumour specimens resulting in heterogeneous staining patterns, which has led to doubts as to the accuracy of tissue microarray. In an effort to validate the use of tissue microarray for melanoma immunohistochemical investigation, a study was conducted comparing the concordance of MCAM staining between whole tumour specimens and tissue microarray core biopsies. Data on full tissue sections were compared with the results of one to four 0.6 mm core biopsies per tumour on a tissue array. It was revealed that concordance of tissue array core biopsies in quadruplicate compared with full-section analysis for the expression and intensity of expression of MCAM.

Female↗

PubMed2004

Avoiding hematoma in cervicofacial rhytidectomy: a personal 8-year quest. Reviewing 910 patients.

Hematoma remains the most common complication of rhytidectomy and can lead to prolonged facial edema and skin necrosis. A number of ancillary procedures have been suggested to reduce hematoma, including dressings, drains, fibrin glue, tumescence, and adrenaline. The aim of this study was to investigate the statistical effect of these parameters on hematoma incidence in a large series of face lifts. Over an initial 6-year period, 678 consecutive face lifts were performed and included in the first part of the study. The effect of dressings, drains, fibrin glue, and tumescence on hematoma rate was investigated retrospectively. In the second part of the study, the specific effect of adrenaline was analyzed while all other parameters were kept constant. The 229 patients with adrenaline-containing infiltrations were compared with the 232 patients whose infiltration had no adrenaline. Retrospective analysis of both groups was performed using Fisher's exact test. In the first part of the study investigating 678 consecutive face lifts, no difference in hematoma rate (4.4 percent overall) was observed with the use of dressings (p > 0.5), drains (p > 0.4), fibrin glue (p > 0.6), or tumescence (p > 0.5). In the second part of the study, the specific effect of withdrawing adrenaline in a comparative group of 461 face lifts significantly reduced the incidence of hematoma requiring surgical evacuation (p < 0.0001). There was also a significant reduction in the incidence of minor hematoma requiring only aspiration (p = 0.02). There was no change in the incidence of any other face lift complications observed during this part of the study. This study found a significant reduction in the incidence of hematoma following face lifting. Although many of the suggested ancillary methods used to reduce hematoma did not produce any statistical reduction in the incidence of this complication, the exclusion of adrenaline had a profound effect. The technique and implications with respect to safety and outcome are described.

Anesthetics, Local↗

PubMed2004

Reducing complications in cervicofacial rhytidectomy by tumescent infiltration: a comparative trial evaluating 678 consecutive face lifts.

Tumescent infiltration has been widely used in body-contouring surgery to facilitate dissection and reduce blood loss. Although its use in facial surgery has been suggested, there are presently no comparative studies of its efficacy. The aim of this study was to investigate the long-term outcome in a large series of consecutive face lifts performed with and without tumescence. During a 6-year period, 678 consecutive face lifts were performed: 449 without tumescence and 229 with tumescent infiltration using 200 ml on each side of the face. The spectrum of techniques included the extended superficial musculoaponeurotic system (SMAS) procedure, the lateral SMASectomy, the extended supraplatysmal plane lift, and the cutaneous face lift. Complications, such as hematoma, skin necrosis, alopecia, and scar quality, were compared between groups using Fisher's exact test. The use of tumescent infiltration facilitated dissection, particularly in the neck. Postoperative swelling and bruising were reduced in the tumescent group. In comparisons of major complications between groups, no difference was seen in hematoma rate (p > 0.5), although the incidence of other complications was significantly reduced by tumescent infiltration. Significant reduction was observed in the rate of skin necrosis (p = 0.03), alopecia (p = 0.006), hypertrophic scarring (p = 0.001), stretched scarring (p = 0.003), and scar revision (p < 0.001). This is the first comparative study of tumescent infiltration in facial rejuvenation surgery. Tumescence made dissection easier and significantly reduced the incidence of troublesome complications. The surgical technique and aesthetic implications for rejuvenation surgery are discussed.

Anesthetics, Local↗

PubMed2003

Use of oncogene expression as an independent prognostic marker for primary melanoma.

For 25 years, the Breslow depth of primary tumors has remained the most accurate prognostic test of survival for primary melanoma. However a number of studies have indicated that outcome for intermediate-thickness melanomas (0.75-2.49 mm) is often at variance with that predicted by the Breslow depth. This study investigated c-myc oncogene expression in 92 primary tumors of intermediate thickness using flow cytometry. Oncoprotein expression was detected in 87 tumors (95%) with a median positivity of 48% (range, 0%-96%). Survival analysis performed using the Kaplan-Meier method revealed a significant association between oncoprotein positivity and clinical outcome (p < 0.01, log-rank test). Multifactorial analysis of survival using Cox's proportional hazards model revealed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including the Breslow depth (chi(2) = 9.68, p< 0.01). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for intermediate-thickness primary melanoma.

Biomarkers, Tumor↗

PubMed2002

Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation.

Antiarrhythmic peptides enhance gap junction current in pairs of cardiomyocytes and coupling in cardiac tissue. To elucidate the underlying mechanisms, we investigated the effects of the antiarrhythmic peptide AAP10 (GAG-4Hyp-PY-CONH2) on pairs of adult guinea pig ventricular cardiomyocytes and pairs of HeLa cells transfected with rat cardiac connexin 43 (Cx43). By using a double-cell voltage-clamp technique in pairs of cardiomyocytes, we found that under control conditions the gap junction conductance (gj) steadily decreased with time (by -0.292 +/- 0.130 nS/min). Use of 50 nmol/L AAP10 reversed this rundown and increased gj (by +0.290 +/- 0.231 nS/min, Pa). In HeLa-Cx43 cells, AAP10 exerted the same electrophysiological effect. In these cells, AAP10 activated PKC (determined by using ELISA) in CGP54345-sensitive manner and significantly enhanced incorporation of 32P into Cx43 with dependence on PKC. If G-protein coupling was inhibited with 1 mM GDP-BS, we found the effects of AAP10 on 32P incorporation were also completely abolished. Next, we performed a radioligand binding study with 14C-AAP10 as radioligand and AAPnat as competitor. We found saturable binding of 14C-AAP10 to cardiac membrane preparations, which could be displaced with AAPnat. The Kd of AAP10 was 0.88 nmol/L. We conclude that 1) AAP10 increases gj both in adult cardiomyocytes and in transfected HeLa-Cx43 cells, 2) AAP10 exerts its effect via enhanced PKC-dependent phosphorylation of Cx43, 3) AAP10 activates PKCa, and 4) a membrane receptor exists for antiarrhythmic peptides in cardiomyocytes.

Animals↗