Porcine acellular dermal matrix (PADM) vascularises after exposure in open necrotic wounds seen after complex hernia repair.

Biological alternatives to synthetic meshes are increasingly utilised in complex abdominal wall reconstruction. There is a lack of evidence demonstrating that non-cross-linked porcine acellular dermal matrix vascularizes and integrates with human tissue in suboptimal wound conditions. We aimed to evaluate these properties in Strattice™ (Life Cell Inc., Branchburg, NJ) following ventral hernia repair. A retrospective review of patients with high-risk ventral hernia repair utilising Strattice™ as an onlay after open component separation was conducted. Patients with postoperative wound exploration and exposure of the onlay were included in this review. One patient underwent punch biopsy for histological analysis. Eleven patients with wound complications necessitating postoperative debridement and exposure of Strattice™ onlay were identified. The onlay was partially debrided in two cases, and one case required complete excision. Vascularisation was clinically evident in 10 of 11 cases (91%) as demonstrated by the presence of granulation tissue and/or the ability to support a skin graft. Histological analysis of one onlay 3 months postoperatively showed neovascularisation and collagen remodelling with minimal inflammatory response. Strattice™ demonstrated resistance to rejection, ability to undergo vascularisation and incorporation into host tissues in sub-optimal wound conditions following ventral hernia repair.

Massive localized lymphedema revisited: a quickly rising complication of the obesity epidemic.

Massive localized lymphedema (MLL) is a rising and potentially fatal complication of the obesity epidemic. Described as a benign lymphoproliferative overgrowth of obese patients, MLL is a form of secondary lymphedema, caused by the obstruction of lymphatic flow, with characteristic clinical and histological presentation. Patients have a large mass with classic skin changes often accompanied by lymphatic weeping that require complex reconstruction. Although oftentimes benign, if left untreated, MLL can progress to angiosarcoma, further supporting the need for more research into MLL and its sequelae. We present a unique case of MLL of the mons pubis in a 52-year-old man with a body mass index of 75.7 kg/m. The literature was comprehensively reviewed with a total of 65 cases of MLL being described, 9 of which resulted in angiosarcoma (10.3% of all cases), 6 of which resulted in death (9.2% of all cases). We found a female predominance of 1.24 to 1, an average weight of 183 kg, and a 48.5% majority of cases in the thigh.

Identification of novel NOTCH1 mutations: increasing our knowledge of the NOTCH signaling pathway.

BACKGROUND: Alterations in the NOTCH1 signaling pathway are found in about 60% of pediatric T-ALL, but its impact on prognosis remains unclear. PROCEDURE: We extended the previously published CoALL cohort (n = 74) to a larger cohort (n = 127) and additionally included 38 Argentine patients from ALL IC-BFM to potentially identify novel mutations and decipher a stronger discriminatory effect on the genotype/phenotype relationship with regard to early treatment response and long-term outcome. RESULTS: Overall, 101 out of 165 (61.2%) T-ALL samples revealed at least one NOTCH1 mutation, 28 of whom had combined NOTCH1 and FBXW7 mutations. Eight T-ALL samples (4.8%) exclusively revealed FBXW7 mutations. Fifty-six T-ALL (33.9%) exhibited a wild-type configuration of either gene. Four novel NOTCH1 mutations were identified localized in the C-terminal PEST domain, in the rarely affected LNR repeat domain and in the ankyrin domain. Novel LNR mutations may contribute to a better understanding of the structure of the NOTCH1 negative regulatory region (NRR) and the R1946 mutation in the ankyrin domain may represent an unusual loss-of-function mutation. CONCLUSIONS: Overall, NOTCH1 pathway mutations did not affect the relapse rate and outcome of the extended T-ALL cohort uniformly treated according to CoALL protocols, although NOTCH1 mutations were associated with good response to induction therapy (P = 0.009). Individually, HD and PEST domain mutations might exert distinct functional effects on cellular homeostasis under treatment NOTCH1 pathway activity with prognostic implications.

Incisional negative-pressure wound therapy versus conventional dressings following abdominal wall reconstruction: a comparative study.

BACKGROUND: Improvements in surgical techniques have allowed us to achieve primary closure in a high percentage of large abdominal hernia repairs. However, postoperative wound complications remain common. The benefits of negative-pressure wound therapy (NPWT) in the management of open abdominal wounds are well described in the literature. Our study investigates the effects of incisional NPWT after primary closure of the abdominal wall. METHODS: A retrospective chart review was performed for the period between September 2008 and May 2011 to analyze the outcomes of patients treated postoperatively with incisional NPWT versus conventional dry gauze dressings. Patient information collected included history of abdominal surgeries, smoking status, and body mass index. Postoperative complications were analyzed using χ exact test and logistic regression analysis. RESULTS: Fifty-six patients were included in this study; of them, 23 were treated with incisional NPWT, whereas 33 received conventional dressings. The rates of overall wound complications in groups I and II were 22% and 63.6%, respectively (P = 0.020). The rates of skin dehiscence were 9% and 39%, respectively (P = 0.014). Both outcomes achieved statistical significance. Rates of infection, skin and fat necrosis, seroma, and hernia recurrence were 4%, 9%, 0%, and 4% for group I and 6%, 18%, 12%, 9% for group II, respectively. CONCLUSIONS: This study suggests that incisional NPWT following abdominal wall reconstruction significantly improves rates of wound complication and skin dehiscence when compared with conventional dressings. Prospective, randomized, controlled studies are needed to further characterize the potential benefits of this therapy on wound healing after abdominal wall reconstruction.

Is Sentinel Lymph Node Biopsy Reliable After Recent Oncoplastic Breast Reduction?

An oncoplastic breast reduction may disrupt normal lymphatic drainage and make subsequent identification of the sentinel lymph nodes (SLNs) unreliable. There are little data on the success rate of sentinel lymph node biopsy (SLNB) after recent oncoplastic breast reduction, and there is no agreement on whether SLNB should be done at the time of the partial mastectomy and reduction for ductal carcinoma in situ (DCIS). The primary goals of this study were to evaluate the identification rate of SLNB after recent oncoplastic or functional breast reduction and to examine recurrence rates in this setting. Results reveal SLNB is feasible in this setting. At least one SLN was found in all patients, and there were no recurrences with an average follow-up of 34 months.

Significant predictors of complications after sternal wound reconstruction: a 21-year experience.

BACKGROUND: We sought to identify patient comorbidities that predict complications after tissue flap sternal reconstruction. METHODS: A retrospective study, December 1989 to December 2010, analyzed numerous comorbidities, including diabetes mellitus (DM), hypertension (HTN), coronary artery disease, congestive heart failure (CHF), and renal insufficiency, as independent risk factors for postoperative complications. Pearson χ2 test, Fisher exact test, 2-sample t test, and median-unbiased estimation were used for data analysis. Significance was P≤0.05. RESULTS: In all, 106 patients received 161 sternal tissue flap repairs. Nineteen patients (18%) required reoperation because of complications, including recurrent wound infection, tissue necrosis, wound dehiscence, mediastinitis, and hematoma formation. Our analysis found DM, HTN, and CHF as significant predictors of complications after sternal reconstruction (P=0.014, 0.012, and 0.006). CONCLUSIONS: Results suggest DM, HTN, and CHF may contribute to complications after tissue flap repair of sternal wounds, possibly through impaired perfusion and healing of repairs.

Closed-Incision and Surrounding Soft Tissue Negative Pressure Dressings in Post-Mastectomy Pre-Pectoral Direct-to-Implant Breast Reconstruction: A Pilot Study.

Background: Closed-incision and surrounding soft tissue negative pressure therapy (cistNPT) is theorized to decrease infection, reduce tissue edema, and promote healing of the mastectomy skin flap. We report our early experience with this dressing in pre-pectoral direct-to-implant (pDTI) breast reconstruction. Methods: We retrospectively reviewed all patients who underwent post-mastectomy pDTI breast reconstruction with cistNPT between July 2019 and February 2020. All reconstructions utilized smooth round silicone gel implants and human acellular dermal matrix. Results: Thirty-five female patients underwent 58 mastectomies. Mean age and body mass index were 49.9 years and 28.9 kg/m2, respectively. Eleven (31.4%) patients had neoadjuvant chemotherapy. The mean sternal notch-to-nipple distance was 27.0 cm. The median specimen weight was 483 g, while the median implant volume was 495 cc. The mean implant-to-specimen ratio was 1.4 for nipple-sparing, 1.1 for skin-sparing, and 0.7 for skin-reducing mastectomy. Total drain volume was 483.1 cc from each breast. Post-operative complications included seroma (5.2%), peri-incisional necrosis (8.6%), and superficial skin epidermolysis (13.8%). There were no cases of surgical site infection, dehiscence, or hematoma. Rate of return to the operative room was 3.4%. Mean follow-up was 90 days. Conclusions: In our series of pDTI breast reconstructions with cistNPT, no patients experienced hematoma, dehiscence, or infection complications. Rates of seroma, skin necrosis requiring operative debridement, and total drain volumes were lower than those reported in literature.

Contexte: La thérapie par pression négative des incisions fermées et des tissus mous environnants (cistNPT) doit théoriquement diminuer l'infection, réduire l'œdème tissulaire et faciliter la guérison du lambeau cutané de mastectomie. Nous fournissons notre première expérience avec ce pansement de reconstruction mammaire prépectorale directe à l'implant (pDTI). Méthodes: Nous avons revu rétrospectivement toutes les patientes ayant subi une reconstruction mammaire pDTI post mastectomie entre juillet 2019 et février 2020. Toutes les reconstructions ont utilisé des implants en gel de silicone lisses et ronds avec une matrice dermique acellulaire humaine. Résultats: Trente-cinq femmes ont subi 58 mastectomies. L'âge moyen était de 49,9 ans et l'IMC moyen de 28,9 kg/m2. Onze patientes (31,4 %) recevaient une chimiothérapie néoadjuvante. La distance moyenne du sommet du manubrium sternal au mamelon était de 27,0 cm. Le poids médian de l'échantillon était de 483 g tandis que le volume médian de l'implant était de 495 cc. Le rapport moyen implant/échantillon était de 1,4 pour la préservation du mamelon, 1,1 pour la préservation de la peau et de 0,7 pour la mastectomie de réduction cutanée. Le volume total de drainage de chaque sein a été de 483,1 cc. Les complications postopératoires ont été, notamment, un sérome (5,2 %), une nécrose péri-incision (8,6 %) et une épidermolyse superficielle de la peau (13,8 %). Il n'y a pas eu de cas d'infection du site chirurgical, de déhiscence ou d'hématome. Le taux de reprise chirurgicale a été de 3,4 %. Le suivi moyen a été de 90 jours. Conclusions: Dans notre série de reconstructions du sein par pDTI, aucune patiente n'a eu d'hématome, de déhiscence ou de complication infectieuse. Les taux de sérome, de nécrose cutanée nécessitant un débridement chirurgical et les volumes totaux de drainage étaient inférieurs aux chiffres publiés.

Hospital-Based Same-Day Compared to Overnight-Stay Mastectomy: An American College of Surgeons National Surgical Quality Improvement Program Analysis.

Background: Enhanced Recovery after Surgery for mastectomy has resulted in increased use of outpatient same-day mastectomy (SDM). Whether SDM leads to increased readmissions or reoperations is not well documented. This study examines national data to compare outcomes of SDM to an overnight stay. Methods: We analyzed the American College of Surgeons National Surgical Quality Improvement Program Participant Use Data File from 2016 to 2018 for all mastectomy cases. Cases with a length of stay (LOS) >1 day were excluded. Cases were then categorized into 2 LOS cohorts: SDM vs 1-day LOS. Results: A total of 22,642 cases (80.8% 1-day LOS vs 19.2% SDM) were identified for the final analysis. Patients in the 1-day LOS group were more likely to be older (57.9 vs 54.0 years, P<0.01), be female (98.0% vs 79.8%, P<0.01), and have greater comorbidity (38.1% vs 30.7% American Society of Anesthesiologists classification 3 or 4, P<0.01) compared to the SDM group. Multivariate analysis demonstrated no difference in risk for 30-day wound complications between the SDM and 1-day LOS groups. The risks for 30-day medical complications (1.60 odds ratio [OR], 95% CI 1.06-2.42, P=0.02), reoperations (1.46 OR, 95% CI 1.17-1.81, P<0.01), and readmissions (1.60 OR, 95% CI 1.25-2.05, P<0.01) were higher in the 1-day LOS group. Even after excluding patients undergoing reoperation on the day of surgery, the risk for reoperations (2.3% vs 3.3%, P<0.01) remained higher in the 1-day LOS group. Characteristics associated with 1-day LOS were hypertension, steroid use, diabetes, dyspnea, dependent functional status, bilateral procedures, and breast reconstruction. Conclusion: We demonstrate that SDM is a safe procedure, with no increase in risk for 30-day postoperative complications. Appropriate patients should be offered SDM.

Outcomes of Margin Reexcision after Oncoplastic Breast Reduction.

Tissue rearrangement after an oncoplastic breast reduction may complicate identification of margins during reexcision. Little is known about outcomes of reoperation in this setting. Methods: This is a single-institution, retrospective analysis of outcomes of margin reexcisions after lumpectomy with concurrent oncoplastic Wise-pattern reduction from 2015 to 2020. Outcomes assessed were the rate of successful breast conservation, in-breast recurrence, wound issues or complications, effect on cosmesis, and delay to onset of adjuvant therapy. Results: From 2015 to 2020, 649 patients underwent lumpectomy with oncoplastic Wise-pattern reduction. Forty-seven patients (7.2%) had greater than or equal to one positive margin(s); of these, 28 went directly to mastectomy, and 19 underwent margin reexcision. Residual disease was found in seven of 19 patients (37%) at reexcision. The rate of successful breast-conserving therapy was 95% with a mean follow-up of 31 months. There was one (5%) in-breast recurrence (invasive ductal carcinoma [IDC] occurring 30 months after the original operation); this patient had a mastectomy for treatment of her recurrence. The overall complication rate was 37%. Radiation was administered to 18 patients (95%), and two patients (11%) had delay of radiation past 6 weeks due to wound complications. Of the 14 patients with photographs available, 12 of 14 patients (86%) were blindly assessed to have equivalent or better cosmesis after margin reexcision (versus initial lumpectomy). Conclusion: Margin reexcision after oncoplastic breast reduction with Wise-pattern is feasible and effective, and can be done without compromising the initial cosmetic results.

Rinse But Don't Repeat: Single Application V.A.C. VERAFLO Salvages Infected Breast Prostheses.

INTRODUCTION: Existing salvage protocols for infected breast prostheses using negative pressure wound therapy with instillation and dwell (NPWTi-d) require multiple returns to the operating room and prolonged length of stay. We present our expedited salvage protocol and discuss outcomes and associated costs savings. METHODS: Using a retrospective review, we identified 25 consecutive patients (27 breasts) with peri-prosthetic breast infection. Nine patients (10 breasts) underwent removal of infected breast prostheses followed by autologous or staged implant-based reconstruction. Sixteen patients (17 breasts) underwent our single application salvage protocol. A cost analysis was performed comparing the two groups, and an economic model was used to project the cost savings associated with using single application NPWTi-d protocol. RESULTS: Fifteen of the 16 patients (94%) who underwent single application NPWTi-d had successful implant salvage. Average duration of NPWTi-d was 2 days, 7 hours, and average length of stay was 4.43 days. Compared to control, patients who received the single application protocol required significantly fewer hospitalizations and office visits. A total savings of $58,275 could have been achieved by using the single application NPWTi-d protocol in the patients who did not undergo NPWTi-d. CONCLUSIONS: Single application of NPWTi-d is a simple, safe, and cost-effective technique for salvage of breast prostheses, with 94% success rate, even in immunocompromised patients and severe infection. Compared to previous protocols, ours requires fewer trips to the operating room, shorter length of stay, and more permanent implants placed during salvage. Our protocol is also associated with fewer office visits and fewer returns to the operating room.

Two-stage Prosthetic Prepectoral Breast Reconstruction: Comparing Tissue Expansion with Carbon Dioxide and Saline.

BACKGROUND: The AeroForm tissue expander is a carbon dioxide-filled breast tissue expander that allows gradual, needle-free expansion using a hand-held remote controller. This study evaluates 2-stage, prepectoral tissue expander-to-implant breast reconstruction with the carbon-dioxide tissue expanders and compares the outcomes to our recent experience with saline tissue expanders. METHODS: This was a retrospective study of consecutive patients from a single institution. The subjects consisted of women who underwent mastectomy and either immediate or delayed breast reconstruction with AeroForm or saline tissue expanders. Outcomes encompassed postoperative complications including mastectomy flap necrosis, infection requiring readmission and/or intravenous antibiotics, capsular contracture, hematoma, seroma, skin dehiscence, extrusion, premature explant, and loss of communication with the device (AeroForm) or rupture of the device (saline). RESULTS: This study evaluated 115 patients with 185 breast reconstructions. Of the 185 breast reconstructions, 74 (40%) utilized AeroForm tissue expanders and 111 (60%) utilized traditional saline tissue expanders. Treatment was successful in 100% and 94% in the AeroForm and saline groups, respectively (P = 0.025). The incidence of adverse events was greater in the saline group (45.9% versus 32.4%). Surgical-site infection occurred more commonly in the saline group (5.4% versus 0%). Full-thickness skin necrosis occurred at a significantly higher rate in the saline cohort as compared with AeroForm (5.4% versus 0%). CONCLUSIONS: The use of AeroForm tissue expanders offers notable advantages for breast reconstruction. This device when employed in the prepectoral space may be associated with reduced infection rates and decreased utilization of healthcare and patient resources.

Acellular dermal matrix compared with synthetic implant material for repair of ventral hernia in the setting of peri-operative Staphylococcus aureus implant contamination: a rabbit model.

BACKGROUND: Implant infection is a common clinical complication of abdominal hernia repair. Our objectives were to determine if acellular dermal matrix (ADM) grafts resisted Staphylococcus aureus infection better (as measured by ability to reduce or clear bacterial counts) than synthetic (polytetrafluoroethylene [PTFE]) mesh when used in abdominal wall reconstruction, and to determine whether vascularization of the implant occurred. We hypothesized that the ability of the ADM grafts to vascularize and allow cellular ingrowth would allow the immune system to clear the infection better in these animals. METHODS: In New Zealand White rabbits (average weight, 3.0 kg), a full-thickness 3 x 3 cm(2) abdominal defect was created, then repaired with an interpositional implant (ADM, n = 62; PTFE, n = 57). Before skin closure, the epidermal surface of each implant was inoculated with 1 mL of S. aureus at various concentrations (10(4) colony-forming units [CFU]/mL, n = 82; 10(6) CFU/mL, n = 27; 10(9) CFU/mL, n = 10), and the rabbits were harvested at either day 7 or day 21. RESULTS: At day 7, ADM grafts inoculated with 10(4) CFU had lower counts or no bacteria (p = 0.006), fewer adhesions (p = 0.005), and fewer abscesses (p = 0.008) than PTFE grafts. By day 21, more ADM (n = 12) than PTFE (n = 0) grafts were free of bacteria (p = 0.002). Fewer rabbits with ADM grafts formed abscesses (13 vs. 19; p = 0.03). When evaluating the 7- and 21-day 10(4) CFU groups combined, a total of 15 rabbits with ADM cleared the bacteria completely vs. none of those with PTFE grafts (p < 0.001). There was no significant difference in bacterial counts or wound complications at days 7 or 21 between PTFE and ADM implants when inoculated with 10(6) CFU. All rabbits inoculated with 10(9) CFU died of sepsis within 48 h. Herniation did not occur in any of the animals. CONCLUSIONS: Our study demonstrates that ADM resists surgical site infection caused by S. aureus in an animal model without compromising the ventral hernia repair. This ability of ADM grafts to perform well in the setting of infection is most likely attributable to their capacity to vascularize and aid clearance of bacteria.

Breast-feeding, self-exam, and exercise practices before and after reduction mammoplasty.

The current indications for reduction mammoplasty include the relief of painful physical symptoms of macromastia. Numerous studies have demonstrated not only improvement in physical symptoms following reduction mammoplasty, but postoperative psychological benefits as well, including increased ability to participate in physical activity as a result of pain relief and decreased breast mass. Reduction mammoplasty may have additional effects on the patient's ability to breast-feed and perform breast self-exam. The present study is a retrospective study of the effects of reduction mammoplasty on breast-feeding, breast self-exam, physical symptoms, and physical activity. One-hundred and forty-one patients who underwent reduction mammoplasty at our institution between the years 1996-2005 agreed to participate in the study. Each was asked a series of questions in order to assess changes in symptoms and behaviors including breast-feeding and breast self-exam practices before and after the surgery. Patients were also asked questions regarding their pain symptoms and physical activity profiles. Ninety-seven percent of the participants claimed to have back, neck, and/or shoulder pain that was either significantly improved or completely resolved. Moreover, 100% of patients report that physical activity such as exercise was easier following reduction mammoplasty. Ninety-three percent of participants reported that performing breast self-exam following surgery was either the same (68%) or easier (25%) as a result of having less breast tissue. Eighty-nine percent of participants had no children following surgery, therefore effects on breast-feeding practices following reduction mammoplasty were not statistically significant. However, we suggest that when patients are seen in consultation or in the perioperative period, there is an opportunity to teach patients about the benefits of breast-feeding, and to assure patients that a pedicle flap reduction will likely allow breastfeeding. This is also a chance for physicians to teach patients how to perform breast self-examination and explain the importance of early breast mass detection.

Osteoarthritis of the elbow: results of arthroscopic osteophyte resection and capsulectomy.

Primary osteoarthritis of the elbow involves formation of bony spurs, loose bodies, and capsular contracture. This article presents the results of an arthroscopic technique for treatment of elbow arthritis in a series of patients. A retrospective chart review identified 41 patients with primary osteoarthritis in 42 elbows who underwent arthroscopic osteophyte resection and capsulectomy and who had more than 2 years of follow-up. Preoperative motion, pain, and Mayo Elbow Performance Index scores were compared with those at the latest follow-up. At an average follow-up of 176.3 weeks, significant improvements occurred in mean flexion, from 117.3 degrees preoperatively to 131.6 degrees (P < .0001); extension, from 21.4 degrees to 8.4 degrees (P < .0001); supination, from 70.7 degrees to 78.6 degrees (P = .0056); and Mayo Elbow Performance Index scores (P < .0001), with 81% good to excellent results. Pain decreased significantly (P < .0001). Complications were rare (n = 2) and included heterotopic ossification and ulnar dysesthesias. This procedure addresses the pathologic processes associated with arthritis of the elbow and was safe and effective in this series.

Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

BACKGROUND: Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use. METHODS: Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child. RESULTS: After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn. CONCLUSIONS: In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.

Expression of atrial myosin light chains but not alpha-myosin heavy chains is correlated in vivo with increased ventricular function in patients with hypertrophic obstructive cardiomyopathy.

The adult rodent heart adapts to increased work load by reexpression of its fetal genes, for example, beta-myosin heavy chain (MHC), in order to improve contractile function. However, the human ventricle regulates contractility by expression of atrial essential myosin light chain (ALC-1) rather than beta-MHC. We evaluated the impact of both mechanisms in patients with hypertrophic cardiomyopathy. MHC isoform expression was quantified at the mRNA and protein levels by reverse transcriptase polymerase chain reaction and immunoblotting, respectively. Although alpha-MHC mRNA was detected in control and hypertrophied human ventricular tissue, alpha-MHC protein was not observed. Similarly, we investigated the expression of ALC-1 by two-dimensional polyacrylamide gel electrophoresis and the clinical and hemodynamic parameters of the patients with hypertrophic cardiomyopathy. We found a significant positive correlation between ALC-1 protein expression and dP/dtmax in the hypertrophied human ventricle in vivo. Correlations between dP/dtmax and expression of protein for the ryanodine receptor and L-type Ca2+ channel were excluded. Our data suggest that reexpression of ALC-1 improves the contractile state of the adult human heart. We propose that two evolutionarily divergent compensatory mechanisms for increased work demand exist in the mammalian heart: MHC regulation in rodents and essential MLC regulation, of cardiac contractility, in humans.

Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.

Human acellular dermal matrix for repair of abdominal wall defects: review of clinical experience and experimental data.

The use of prosthetic mesh for the tension-free repair of incisional hernias has been shown to be more effective than primary suture repair. Unfortunately, prosthetic materials can be a suboptimal choice in a variety of clinical scenarios. In general, prosthetic materials should not be implanted into sites with known contamination or infection because they lack an endogenous vascular network and are thus incapable of clearing bacteria. This is of particular relevance to the repair of recurrent hernias, which are often refractory to repair because of indolent bacterial colonization that weakens the site and retards appropriate healing. Although fascia lata grafts and muscle flaps can be employed for tension-free hernia repairs, they carry the potential for significant donor site morbidity. Recently, a growing number of clinicians have used human acellular dermal matrix as a graft material for the tension-free repair of ventral hernias. This material has been shown to become revascularized in both animal and human subjects. Once repopulated with a vascular network, this graft material is theoretically capable of clearing bacteria, a property not found in prosthetic graft materials. Unlike autologous materials such as fascial grafts and muscle flaps, acellular dermal matrix can be used without subjecting the patient to additional morbidity in the form of donor site complications. This article presents a thorough review of the current literature, describing the properties of human acellular dermal matrix and discussing both animal and human studies of its clinical performance. In addition to the review of previously published clinical experiences, we discuss our own preliminary results with the use of acellular dermal matrix for ventral hernia repair in 46 patients.

Alpha 1-adrenergic receptor antibodies in patients with primary hypertension.

Autoimmune mechanisms have been proposed to play a role in the pathogenesis of primary (essential) hypertension. Autoantibodies against the alpha 1-adrenergic receptor have been described in patients with malignant and secondary hypertension. To investigate the incidence of autoantibodies against the alpha 1-adrenoceptor in patients with primary hypertension, we examined the immunoglobulin fractions of sera from 54 patients with primary hypertension and 26 normotensive control subjects for the presence of autoantibodies against the alpha 1-adrenoceptor. Sera from 24 patients (44%) and 3 subjects (12%) were positive. An epitope analysis of 16 autoantibody-positive immunoglobulin fractions revealed that in two thirds of the cases, the antibodies were directed against the first extracellular loop of the alpha 1-adrenoceptor and in one third, against the second. The autoantibodies had a positive chronotropic effect on isolated neonatal rat cardiomyocytes, an effect that was blocked by alpha 1-adrenergic antagonists. Since the functional characteristics of the autoantibodies showed no desensitization phenomena, they may play a role in elevating peripheral vascular resistance and promoting cardiac hypertrophy in patients with primary hypertension.

Sun exposure and sun protection in young European children: an EORTC multicentric study.

Most European children experience exposure to the sun during the summer holidays. The aim of this study was to examine the behaviour of European children when in the sun during their holidays. In 1995-1997, a total of 631 young children were recruited during a multicentric study in Belgium, Germany, France and Italy. For each holiday period from birth, parents gave detailed information on sun exposure and child behaviour. Predictors and trends over time of sun protection were investigated. Forty percent of children were exposed to sunlight in the first and 86% in the sixth year of life. At the same time, the number of children who experienced sunburns rose from 1 to 23%. In the whole period of 6 years, only 8% of children always wore trousers and shirt when in the sun, while 25% children always used a sunscreen. The proportion of sun-exposed children who used sunscreen was stable with age (approximately 50%), while those who always wore trousers and shirts dropped from 46% (1st year) to 19% (6th year). Multinomial logistic regression showed that sunscreen use, but not the wearing of clothes was associated with sun-sensitivity. In summary, sun exposure increases steadily, while sun protection decreases in the first 6 years of life in our cohort of children. In this cohort, use of a sunscreen was much more frequent than the wearing of clothes and a reduction in sun exposure.