Unveiling denture-induced oral lesions: A comprehensive study on classification and pain assessment.

BACKGROUND: Denture-induced oral Lesions (DIOLs) often manifests shortly after the placement or adjustment of new or realigned dentures, frequently resulting in severe pain and discomfort. OBJECTIVES: This study aimed to classify DIOLs placing a particular emphasis on assessing the associated pain. METHODS: A prospective case study was conducted involving 126 patients who were fitted with a total of 193 dentures of various types at the Hadassah School of Dental Medicine. All patients underwent comprehensive intra-oral examinations within 1-8 weeks following denture delivery, completed symptom questionnaires and had their medical records reviewed. Key variables documented included age, gender, overall health status, denture type, and a detailed description of the DIOLs. The description encompassed factors such as lesion location, shape, colour, size, border characteristics, ulcerative appearance, membrane coverage, 3D morphology (elevated, immersed and flat) and patient-reported Verbal Pain Score (VPS) when touching the DIOLs, when wearing the denture, and when not wearing the denture. RESULTS: Notably, 25.4% of denture wearers required no adjustments, while 14.4% necessitated more than three revisions. A majority (71.8%) of DIOLs cases were associated with mandibular complete dentures, primarily situated on the alveolar ridge. The mean VPS indicated a pain intensity of 7 ± 2.1, with temporary dentures in both jaws causing the most discomfort. Implant-supported overdentures were particularly painful when placed in the mandible. Additionally, VPS scores were higher among older individuals and those with prior prosthetic experiences. A significant correlation was observed between pain intensity and presence of chronic health condition (0.036). CONCLUSIONS: This study revealed distinct characteristics of DIOLs and highlighted the multifactorial nature of pain experienced following the development of DIOLs. Insights into the influence of patient and denture characteristics on DIOLs and pain intensity can guide healthcare professionals in optimising patient comfort and satisfaction.

Possible proteomic biomarkers for the detection of pancreatic cancer in oral fluids.

The 80% mortality rate of pancreatic-cancer (PC) makes early diagnosis a challenge. Oral fluids (OF) may be considered the ultimate body fluid for non-invasive examinations. We have developed techniques to improve visualization of minor OF proteins thereby overcoming major barriers to using OF as a diagnostic fluid. The aim of this study was to establish a short discriminative panel of OF biomarkers for the detection of PC. Unstimulated OF were collected from PC patients and controls (n = 30). High-abundance-proteins were depleted and the remaining proteins were analyzed by two-dimensional-gel-electrophoresis and quantitative dimethylation-liquid-chromatography-tandem mass-spectrometry. Label-free quantitative-mass-spectrometry analysis (qMS) was performed on 20 individual samples (n = 20). More than 100 biomarker candidates were identified in OF samples, and 21 had a highly differential expression profile. qMS analysis yielded a ROC-plot AUC value of 0.91 with 90.0% sensitivity and specificity for a combination of five biomarker candidates. We found a combination of five biomarkers for PC. Most of these proteins are known to be related to PC or other gastric cancers, but have never been detected in OF. This study demonstrates the importance of novel OF depletion methodologies for increased protein visibility and highlights the clinical applicability of OF as a diagnostic fluid.

Procalcitonin in hemodialysis patients presenting with fever or chills to the emergency department.

We sought to assess the role of procalcitonin in discriminating severe bacterial infections requiring antibiotic treatment from non-bacterial causes of fever or chills in chronic dialysis patients. Chronic hemodialysis patients who were admitted to the emergency room due to fever and/or chills were recruited to the study. The presence or absence of bacterial infection was defined after recruitment conclusion by an infectious disease specialist who was blinded to procalcitonin results. Procalcitonin levels were compared between infected and non-infected patients. Out of 54 patients recruited, 22 (41%) patients eventually diagnosed with infection. Mean (± SD) procalcitonin values were 4.3 (± 5.5) ng/ml among cases, 1.0 (± 2.0) ng/ml among controls with no infection (p = 0.02). A cutoff PCT value of 1 ng/ml or higher had 77% sensitivity and 59% specificity for the diagnosis of severe infection. Procalcitonin cannot usefully identify hemodialysis patient with bacterial infection.

Tic, Triggering, and Tearing: From CTN to SUNHA.

PREMISE: Classical trigeminal neuralgia (CTN) and the short-lasting unilateral neuralgiform headache attacks (SUNHA) are clinically similar. PROBLEM: The SUNHAs include short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). Shared clinical signs with CTN include severe, unilateral trigeminal pain that is often triggered by innocuous stimuli and accompanied by a dull persistent background pain. Recent reports on trigeminal neuralgia cases with atypical features such as autonomic signs and prolonged attack duration further blur the clinical distinction between CTN and SUNHAs. POTENTIAL SOLUTIONS: Are the similarities greater than their differences? If so, this may reflect a spectrum of disease ranging from typical CTN attacks to typical SUNHAs with a mixed phenotype in the middle. In this review they will summarize the overlap between these entities and contrast the pathophysiology and treatment approach.

An update of management of insomnia in patients with chronic orofacial pain.

In this review, we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problems. Management is based on a multidisciplinary approach, addressing the factors that modulate the pain experience as well as insomnia and including both non-pharmacological and pharmacological modalities. Parallel to treatment, patients should receive therapy for comorbid medical and psychiatric disorders, and possible substance abuse that may be that may trigger or worsen the COFP and/or their insomnia. Insomnia treatment should begin with non-pharmacological therapy, to minimize potential side effects, drug interactions, and risk of substance abuse associated with pharmacological therapy. Behavioral therapies for insomnia include the following: sleep hygiene, cognitive behavioral therapy for insomnia, multicomponent behavioral therapy or brief behavioral therapy for insomnia, relaxation strategies, stimulus control, and sleep restriction. Approved U.S. Food and Drug Administration medications to treat insomnia include the following: benzodiazepines (estazolam, flurazepam, temazepam, triazolam, and quazepam), non-benzodiazepine hypnotics (eszopiclone, zaleplon, zolpidem), the melatonin receptor agonist ramelteon, the antidepressant doxepin, and the orexin receptor antagonist suvorexant. Chronic orofacial pain can greatly improve following treatment of the underlying insomnia, and therefore, re-evaluation of COFP is advised after 1 month of treatment.

Assessment of interfering factors in non-adherence to oral appliance therapy in severe sleep apnea.

OBJECTIVE: Oral appliances (OA) are recommended for patients with severe obstructive sleep apnea who fail to comply with continuous positive airway pressure (CPAP) therapy. This mixed-methods study aimed to quantify adherence to OA therapy and evaluate subjective reasons associated with non-adherence. MATERIALS AND METHODS: The medical records of 52 patients with an apnea-hypopnea index (AHI) ≥ 40, treated with OA after discontinuation of CPAP treatment, were examined for OA adherence. Patients were divided according to usage at the time of a phone interview. The USER group included all forms of usage, whereas those who completely ceased using the OA were in the NUSE group. The timing of the phone interview was from five months to six years (average 44.63 ± 17.17 months) after OA delivery. RESULTS: The overall adherence rate was 57.7% (30/52 patients). The mean usage times were 10.07 ± 8.96 and 44.30 ± 17.3 months in the NUSE and NUSE groups, respectively. The main factors associated with non-adherence were concerns about the effects of the OA on teeth (22%) and insufficient efficacy (22%). Other factors were discomfort (15%) and improved well-being following weight loss (15%). The overall number of interfering and discontinuity factors was significantly higher in the NUSE group than in the USER group (P = 0.041). Nine (17.3%) of 52 patients resumed CPAP use. Subjective and objective outcomes, determined by using a second sleep test with OA in 69.2% of patients, were related to the continuation of treatment. CONCLUSIONS: On-adherence to OA is strongly associated with patient reservations regarding the effects of the device on teeth, possible lack of efficacy, and discomfort. Clinicians should closely monitor adherence patterns and assess potential interfering factors during their diagnostic workup. Patients should be reassured regarding device safety, particularly following dental work that may interfere with the insertion of the OA.

Trigeminal neuralgia (part II): Factors affecting early pharmacotherapeutic outcome.

AIMS: We conducted a cohort study to examine demographic and clinical features associated with the pharmacotherapeutic outcome in classical trigeminal neuralgia (CTN) patients. METHODS: Patients with a clinical profile indicating a diagnosis of CTN, as per the International Headache Society's published classification, were enrolled prospectively. Demographic and pain-related characteristics were carefully collected. For the purposes of the study, patients with features such as autonomic signs and longer attack duration were included. All patients were then initiated on a standardised and accepted stepped pharmacotherapeutic protocol for the management of CTN. Initial pain scores and prospectively collected pain scores from pain diaries were used to assess the treatment outcome, with a ≥50% reduction considered significant. RESULTS: A total of 86 patients were seen, of whom five had an underlying disorder that could account for the pain. The study cohort therefore consisted of 81 patients, and based on attack duration these were divided into short (≤2 minutes, n = 61) and long (>2 minutes, n = 20) groups, for further analysis. The features of these patients and a discussion on the differential diagnosis have been presented in part 1 of this report. Employing an accepted stepped pharmacotherapeutic protocol for the management of CTN, significant improvement was more frequent in the short (74%) than in the long attack group (50%, p = 0.05). In the short attack group there were statistically significant associations between a poor treatment response and longer disease duration, the presence of autonomic signs and atypical pain descriptors for pain quality (p < 0.05). CONCLUSION: This report supports previous findings that prolonged disease duration and autonomic signs are negative prognostic indicators. The present study now adds long attack duration as a further negative prognostic sign.

Trigeminal neuralgia (part I): Revisiting the clinical phenotype.

AIMS: We conducted a cross-sectional study to re-examine the clinical profile of patients with a clinical diagnosis of classical trigeminal neuralgia (CTN). METHODS: Inclusion criteria consisted of the International Headache Society's published classification of CTN. For the specific purposes of the study, features such as autonomic signs, persistent background pain, attack durations of >2 minutes and reports of pain-related awakening were included. The demographic and clinical phenotype of each patient were carefully recorded for analysis. RESULTS: The study cohort consisted of 81 patients and based on reported attack duration these were divided into short (≤ 2 minutes, n = 61) and long (> 2 minutes, n = 20) groups for further analysis. The group with short attack duration neatly fit most of the criteria for CTN while the long attack group presents a more challenging diagnosis. There were no significant differences in pain severity, quality and location between the short and long attack groups. The frequency of persistent background pain was significantly higher in the long (70%) compared to the short attack group (29.5%, p = 0.001). There were significantly more reports of pain-related awakenings in the long (55%) than in the short attack groups (29.5%, p = 0.04). There were no significant differences in the frequency of autonomic signs between the short (21.3%) and long attack groups (40%, p = 0.1). In the short attack group, the presence of autonomic signs was significantly associated with longer disease duration, increased pain-related awakenings, and a reduced prognosis. CONCLUSION: There are clear diagnostic criteria for CTN but often patients present with features, such as long pain attacks, that challenge such accepted criteria. In our cohort the clinical phenotype of trigeminal, neuralgiform pain with or without autonomic signs and background pain was observed across both short and long attack groups and the clinical implications of this are discussed.

A 2-year mean follow-up of oral appliance therapy for severe obstructive sleep apnea: a cohort study.

OBJECTIVE: Oral appliances for treating severe obstructive sleep apnea (OSA) are recommended for patients who failed to comply with continuous positive airway pressure (CPAP) treatment. The objective of this study was to evaluate medium long-term outcome and success rates of oral appliances in patients with severe OSA. METHODS: In a retrospective study, 52 OSA patients with an apnea-hypopnea index (AHI) ≥40, who did not tolerate CPAP treatment, were enrolled and fitted with a modified Herbst oral appliance. A 2-year mean follow-up including a second somnography was conducted in 36 of the patients. RESULTS: A significant reduction (P < 0.0001) in the AHI was demonstrated between the initial somnography (55.25 ± 10.79,) and the followed one (17.74 ± 11.0, n = 36). Overall, 57.7% of total study subjects (n = 52) and 63.9% (n = 36) that had sequential sonmogarphy continued using the device. The reduction in AHI in the user group was 42.4 ± 3.1 (n = 23), which was significantly higher (P = 0.013) than in the non-user group (28.9 ± 17.2; n = 13). Moreover, 53% (n = 19) reached AHI of <15. CONCLUSIONS: Oral appliances were found to be successful for treating for severe OSA after first-line treatment had failed.

Human melanoma cells expressing the alphavbeta3 integrin are partially protected from necrotic cell death induced by dynamic matrix detachment.

Anchorage-independence is a hallmark of metastatic cancer cells. In previous studies we characterized a novel model for anchorage-independence employing dynamic matrix detachment (DMD) using rotation in low shear stress conditions. We observed that in contrast to the classical apoptosis-inducing static matrix detachment (SMD) model, the venous circulation-mimicking DMD model induced necrosis in transformed cells. In the current study we revisited the mechanism of DMD-induced cell death and evaluated the contribution of alphavbeta3 integrin overexpression in human melanoma cells to anchorage-independence in DMD. DMD cell culture induced primarily necrosis in the melanoma cells studied. alphavbeta3, but not the control related alphaIIbbeta3 integrin, could confer survival advantage in DMD. While apoptosis was unaffected, constitutive, unligated alphavbeta3 overexpression was associated with attenuation of necrosis in DMD. alphavbeta3 overexpressing melanoma cells manifested AKT activation that was independent of DMD conditions. Furthermore, while a small molecular inhibitor of AKT phosphorylation induced apoptosis in adherent cells, in DMD conditions it had no effect on cell outcome. Thus, alphavbeta3-overexpressing melanoma cells are partially protected from DMD-induced cell death in an apoptosis-independent mechanism. This finding may be one of the factors accounting for anchorage-independence in circulating metastatic melanoma cells.

A novel system to study adenovirus tropism to normal and malignant colon tissues.

We describe here a new organ culture system for the evaluation of viral tropism to colon carcinomas and normal colon tissues. Organ cultures of mouse and human colon retained viability for several days and thus facilitated studies of viral tropism. Two adenoviral vectors (AD) were compared in the study: AD5, that utilizes the CAR receptor, demonstrated poor infectivity to both normal and carcinoma tissues, while a capsid-modified-AD, recognizing haparan-sulfate receptor, demonstrated efficient infectivity of both tissues. Immunohistochemistry analysis demonstrated different viral tropism; while AD5 infected only the colon epithelia, the capsid-modified-adeno infected both the epithelia and mesothelial layers. To investigate other determinants in the tissue that influence viral tropism, human cancer tissues were pretreated with collagenase and infected with the AD viruses. Increased infectivity and altered tropism were noted in the treated tumor tissue. Taken together, this ex vivo system indicated that receptor utilization and extracellular-matrix components influence AD viral tropism in solid tissues.

Outcome of patients with scleroderma admitted to intensive care unit. A report of nine cases.

OBJECTIVE: Patients with systemic rheumatic disease constitute a small percentage of admissions to the medical intensive care units (ICUs). Systemic sclerosis (SSc) is one of the rheumatic diseases that together with secondary complications may lead to a critical illness requiring hospitalization in the ICU. We present the features, clinical course and outcome of critically ill patients with scleroderma that were admitted to the ICU. METHODS: The medical records of nine patients with diagnosis of scleroderma (8 female, 1 male), admitted to the intensive care unit of Sheba Medical Center during the 11-year interval between 1991 and 2002, were reviewed. RESULTS: The mean age of the patients at the time of admission to the ICU was 48 +/- 13 [SD] years. The mean duration of SSc from diagnosis to the ICU admission was 8 +/- 8 years. Six patients had diffuse SSc, two patients had limited SSc and one patient had juvenile diffuse morphea. The main reasons for admission to the ICU were: infection/ septic syndrome (n = 4), scleroderma renal crisis (SRC) with pulmonary congestion (n = 2), acute renal failure associated with diffuse alveolar hemorrhage namely scleroderma- pulmonary - renal syndrome (SPRS) (n = 1), iatrogenic pericardial tamponade (n = 1), mesenteric ischemia (n = 1). The patients had high severity illness score (mean APACHE II 25 +/- 3). Eight out of nine patients (89%) that were admitted to the ICU died during the hospitalization, six (66.6%) of them died in the ICU. Septic complications as the main cause of death were determined in five patients (62.5%), while four of them had pneumonia and acute respiratory failure along with underlying severe pulmonary fibrosis. Lungs and kidneys were the most common severely affected organs by SSc in our patients. CONCLUSION: The outcome of scleroderma patients admitted to the ICU was extremely poor. Infectious complication was the most common cause of death in our patients. Although infections are treatable, the high mortality rate for this group of patients was dependent on the severity of the underlying visceral organ involvement, particularly severe pulmonary fibrosis. The severity of this involvement is a poor outcome predictor. An early diagnosis and an appropriate treatment of such complications may help to reduce the mortality in scleroderma patients.

Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy.

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.

Heparin-induced recurrent anaphylaxis.

BACKGROUND: Heparin-related immediate-type hypersensitivity reactions like urticaria, angio-oedema or bronchospasm are very rare, and only a few cases of anaphylaxis-like responses because of heparin have been described. However, the mechanisms underlying these reactions and the role of mast cells in their pathogenesis have not been elucidated. OBJECTIVES: We report a patient with end-stage renal disease who presented with recurrent anaphylaxis after receiving heparin during haemodialysis. The underlying aetiology was obscured by the initiation of haemodialysis with its known anaphylactic-like side-effects. The diagnosis of hypersensitivity to heparin was confirmed by the clinical picture, positive skin tests and elevated serum tryptase levels. MATERIALS AND METHODS: We performed prick and intradermal skin tests with heparin, enoxaparin and danaparoid heparinoid. Total and mature tryptase levels were measured in serum by ELISAs at 1, 24 and 36 h following the reaction. RESULTS: An elevated mature tryptase level was found at 1 h, which returned to normal levels at 24 and 36 h. A high total tryptase level was detected at 1 h, but remained somewhat elevated at 24 h. Prick tests were negative with the three compounds. Intradermal skin tests with heparin and enoxaparin were both positive, while with danaparoid negative. Following negative skin test results, danaparoid was used as an anticoagulant during dialysis for the next 3 years without any adverse effects. CONCLUSIONS: In conclusion, we report the first case of heparin-induced anaphylaxis confirmed by an elevated level of mature tryptase in serum. Following skin tests, the patient was treated with danaparoid during haemodialysis sessions three times a week without any adverse effects. Because of increasing use of heparin in daily medical practice, physicians should be aware of possible immediate hypersensitivity reactions to this medication and know how to diagnose and treat them.

Prediction of premolar tooth lengths based on their panoramic radiographic lengths.

OBJECTIVE: Establishing a linear regression model for the determination of first premolar lengths based on panoramic radiographs. MATERIALS AND METHODS: The real lengths of 112 first premolars extracted for orthodontic reasons were measured and compared with their panoramic lengths. The teeth were divided into four groups according to their intraoral quadrant locations (T14, T24, T34, T44) and regression analysis was conducted for each group. RESULTS: A linear regression model for the prediction of tooth length (mm) based on the panoramic length was established (P < 0.0001): For group T14 the predicted length = (panoramic length x 0.698) + 2.61. For group T24 the predicted length = (panoramic length x 0.5056) + 7.844. For group T34 the predicted length = (panoramic length x 0.5075) + 9.282. For group T44 the predicted length = (panoramic length x 0.436) + 11.298. CONCLUSION: Prediction of all first premolar lengths using their panoramic images is both feasible and reliable.

Shortening and migration of Wallstents after stenting of central venous stenoses in hemodialysis patients.

PURPOSE: To report our results for the placement of central venous stents in patients undergoing hemodialysis. METHODS: Ten Wallstents (Schneider, Bülach, Switzerland) were placed in 10 patients with shunt thrombosis, shunt dysfunction or arm swelling associated with central vein stenosis or occlusion. Technical success, patency and complications were evaluated. RESULTS: Stent deployment was successful in all cases. In seven cases (70%) there was significant delayed stent shortening. In two of these cases there was also stent migration. All these cases required additional stents. Primary patency rates at 6, 12 and 24 months were 66%, 25% and 0. Twenty-three additional procedures (percutaneous transluminal angioplasty or stenting) were required to achieve secondary patency rates at 6, 12 and 24 months of 100%, 75% and 57%. CONCLUSION: Stent placement in the central veins of dialysis patients has a high technical success rate resulting in symptomatic relief and preservation of access. Repeat interventions are required to maintain patency. Significant delayed shortening of the Wallstent occurred in 70% of patients which may have affected the patency rates. Strategies are suggested to avoid this problem.

The common mutations C677T and A1298C in the human methylenetetrahydrofolate reductase gene are associated with hyperhomocysteinemia and cardiovascular disease in hemodialysis patients.

BACKGROUND: Plasma total homocysteine (tHcy) level might be an important risk factor for the development of cardiovascular disease (CVD) in dialysis patients. While both renal failure and mutations of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct roles of the thermolabile MTHFR mutation at nucleotide C677T and the more recently described mutation at nucleotide A1298C have not been evaluated concurrently in patients on hemodialysis. METHODS: A cross-sectional study was performed in 120 maintenance HD patients to determine the prevalence of MTHFR C677T and A1298C mutations and their relative association to hyperhomocysteinemia and CVD. RESULTS: Both mutations, the C677T and the A1298C, were highly prevalent in HD patients with allele frequencies of 0.41 and 0.27, respectively. The prevalence of CVD in HD patients was 55% and its significant risk factors included, in descending order, hyperhomocysteinemia, MTHFR C677T mutation, low serum folate levels, diabetes mellitus, hypertension, and double heterozygote state for both MTHFR mutations (677CT/1298AC). MTHFR A1298C mutation alone and gender were not associated with either hyperhomocysteinemia or increased CVD risk, but the HD patients with homozygotes 1298CC and wild alleles 677CC (677CC/1298CC) have significant increase of tHcy (37.7 +/- 12) and high prevalence of CVD. CONCLUSIONS: Hyperhomocysteinemia, serum folate levels and both C677T and A1298C MTHFR mutations are associated with CVD in HD patients.

Conditional gene targeting for cancer gene therapy.

Current treatment of solid tumors is limited by severe adverse effects, resulting in a narrow therapeutic index. Therefore, cancer gene therapy has emerged as a targeted approach that would significantly reduce undesired side effects in normal tissues. This approach requires a clear understanding of the molecular biology of both the malignant clone and the biological vectors that serve as vehicles to target cancer cells. In this review we discuss novel approaches for conditional gene expression in cancer cells. Targeting transgene expression to malignant tissues requires the use of specific regulatory elements including promoters based on tumor biology, tissue-specific promoters and inducible regulatory elements. We also discuss the regulation of both replication and transgene expression by conditionally-replicative viruses. These approaches have the potential to restrict the expression of transgenes exclusively to tissues of interest and thereby to increase the therapeutic index of future vectors for cancer gene therapy.

Heat shock and heat shock protein 70i enhance the oncolytic effect of replicative adenovirus.

Replication-competent viruses are currently being evaluated for their cancer cell-killing properties. These vectors are designed to induce tumor regression after selective viral propagation within the tumor. However, replication-competent viruses have not resulted heretofore in complete tumor eradication in the clinical setting. Recently, heat shock has been reported to partially alleviate replication restriction on an avian adenovirus (Ad) in a human lung cancer cell line. Therefore, we hypothesized that heat shock and overexpression of heat shock protein (hsp) would support the oncolytic effect of a replication-competent human Ad. To this end, we tested the oncolytic and burst kinetics of a replication-competent Ad after exposure to heat shock or to inducible hsp 70 overexpression by a replication-deficient Ad (Adhsp 70i). Heat-shock resulted in augmentation of Ad burst and oncolysis while decreasing total intracellular Ad DNA. Overexpression of hsp 70i also enhanced Ad-mediated oncolysis but did not decrease intracellular Ad DNA levels. We conclude that heat shock and Adhsp 70i enhance the Ad cell-killing potential via distinct mechanisms. A potential therapeutic implication would be the use of local hyperthermia to augment oncolysis by increasing the burst of replication-competent Ad. The role of hsp in Ad-mediated oncolysis should be additionally explored.