Assessment of HER‐2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice?

AIMS: Since the release of Herceptin, pathology laboratories have been requested to test breast carcinomas for HER-2/neu overexpression and/or gene amplification. Standardized IHC and FISH are mandatory in order to get reliable results, but there are problems even with standardized procedures. We decided to evaluate the two methods to determine which, or possibly if both, should be the primary investigation method(s). METHODS AND RESULTS: The material consisted of 215 primary invasive breast carcinomas with complete clinical follow-up of 15 years. HER-2/neu protein expression was determined for all specimens, whereas FISH for assessing HER-2/neu gene signal number was done in 165 cases. IHC was double-checked with two or three different antibodies in 35 tumours, including all cases with discrepancies between IHC and FISH. Among these, there were discrepancies in a third. IHC overexpression of HER-2/neu was found in 13% and gene amplification in 18%. Discordance between IHC and FISH was found in 11 cases (8%). Five tumours were IHC+/FISH- and six were IHC-/FISH+. IHC and FISH positive cases as well as FISH only positive tumours had the same prognosis respecting survival. Tumours with >2 but 4 gene signals per nucleus. In contrast, cases with IHC overexpression without gene amplification had a prognosis similar to that of IHC-/FISH- tumours. CONCLUSIONS: From our data, it seems to be more important to assess HER-2/neu gene amplification than IHC overexpression. Failure to detect FISH-amplified (IHC-negative) cases would have an adverse effect on the survival of these patients. On the other hand, IHC overexpression tumours without gene amplification appear to belong to a better prognostic group, and failure to detect them would probably not have a negative effect on the survival of these women. Even though FISH is a more complex and expensive procedure, it should be considered the method of choice for primary assessment of HER-2/neu status in breast cancer patients.     

The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach

Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform.     

Organ preservation: experience with University of Wisconsin solution and plans for the future

Transplantation of organs continues to be a primary therapeutic modality for treatment of end-stage organ disease, and 1-year graft survival rates show increasing improvements for most organs. A number of transplant centers show 1-yr graft survival rates approaching 90% or more for the kidney, liver and pancreas. Rejection continues to be the major cause for loss of organs and there is still a major shortage of organs for transplantation. Additionally, many organs showed delayed graft function (or primary nonfunction) which may be related to either donor factors or preservation factors. The University of Wisconsin solution for organ preservation has increased the safe time of preservation for the liver, kidney, and pancreas and helped to increase the quality and number of organs available for transplantation. However, the long-range goal of organ preservation (unlimited preservation) is still far from being reached. In the past, preservation could accurately be categorized as an art and preservation solutions were developed based upon theoretical rationales about the mechanisms of organ injury at hypothermia and what agents would suppress injury. The utility and success of this approach is exemplified by the developments of Collins solution and the UW solution. However, further developments in methods to increase the quality and duration of preservation of all transplantable organs would appear to be dependent upon defining, systematically, how organs are injured and what can be done to suppress the injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ifosfamide, methotrexate, and 5-fluorouracil: effective combination in resistant breast cancer

Ifosfamide has definite efficacy in many malignant tumours, including breast cancer. In the present study we substituted cyclophosphamide with ifosfamide in the combination CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) regimen in 25 patients with breast cancer whose disease was refractory to CMF or who had relapsed after previous response. Ifosfamide was given in an i.v. infusion at a dose of 1.2 g/m² daily for 5 days, together with mesna as a uroprotector (at 20% of the ifosfamide dose). Methotrexate was given at a dose of 40 mg/m² and 5-fluorouracil was given at 600 mg/m², both by i.v. push. Courses were repeated every 21 days. The 24 evaluable patients received 3–12 courses (average, 5 courses); results included a complete remission in 3 patients (12.5%) and a partial remission in 3 (12.5%). Among the remaining patients, improvement was seen in 4 (16.6%); stable disease, in 7; and progressive disease, in 7 (29.2%). The complete responses lasted for 11+, 13+, and 15+ months, and partial remissions, for 2, 6, and 9 months. The responses were detected in soft-tissue as well as visceral lesions, but not in bony lesions. The responders remain under follow-up. This study shows the efficacy of ifosfamide-containing chemotherapy in breast cancer. As toxicities were tolerable, higher doses of ifosfamide could safely be used in these patients. Use of this combination as first-line therapy in breast cancer could be considered for a future study.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Effect of the frequency of transcutaneous electrical nerve stimulation on the postoperative opioid analgesic requirement and recovery profile.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) at either an acupoint or dermatome corresponding to the surgical incision produces comparable decreases in postoperative opioid requirements and opioid-related side effects. However, the effect of the frequency of the electrical stimulus on the postoperative analgesic response to TENS therapy has not been studied. METHODS: One hundred women undergoing major gynecological procedures with a standardized general anesthetic technique were enrolled in the study. Patients were randomly assigned to four groups: group I, patient-controlled analgesia (PCA) plus sham TENS (no stimulation); group II, PCA plus low-frequency (2-Hz) TENS; group m, PCA plus high-frequency (100-Hz) TENS; group IV, PCA plus mixed-frequency (2- and 100-Hz) TENS. The PCA device was programmed to deliver 2-3 mg intravenous boluses of morphine with a lockout interval of 10 min. The TENS device was used every 2 h during the day. Standard 100-mm visual analog scales were used to assess pain, sedation, fatigue, and nausea at specific intervals after surgery. RESULTS: Mixed frequency (2 and 100 Hz) of stimulation decreased morphine requirements by 53% compared with the sham group; low (2-Hz) and high (100-Hz) frequencies produced 32% and 35% decreases, respectively. All three "active" TENS groups reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and itching. CONCLUSIONS: TENS decreased postoperative opioid analgesic requirements and opioid-related side effects when utilized as an adjunct to PCA after lower abdominal surgery. Use of TENS at mixed (2- and 100-Hz) frequencies of stimulation produced a slightly greater opioid-sparing effect than either low (2-Hz) or high (100 Hz) frequencies alone.     

Contributions to the sociologic analysis of the impact of sickle cell disease on families from Northern Tunisia

The improvement of the conditions of care and quality of life of people living with drepanocytosis now constitutes a major concern of health authorities and voluntary groups (associations of sick people and their parents). In order to examine the conditions and methods of care for children living with drepanocytosis in the Bizerte region of Northern Tunisia and to understand the problems and difficulties experienced by them and their families in their daily lives, an anthropological study was carried out in the region between January 16 and February 12, 1997. Thirty-three interviews were carried out with families of infected children. The interviews were semi-directive using a pre-established protocol (interview guide). Thirty interviews were then analysed. A multitude of information concerning various medical and psycho-social aspects of drepanocytosis in the region were revealed. The data were regrouped into the following categories: circumstances of discovering the illness; explicative model of the illness as perceived by the people interviewed; conditions and methods of care of the sick child; degree of satisfaction with the health care system; psychological profile of the children interviewed; educational level of the children interviewed; repercussions the illness has on the family; impact of the illness on household budget; suggestions and comments of the people interviewed. In light of the information collected, various actions have been proposed with the goal of improving the conditions of care and quality of life of people living with drepanocytosis in the region.     

Treatment with danaparoid during pregnancy for a woman with a cutenous allergy to low-molecular-weight heparin]

The authors describe a case of heparin-induced skin reaction due to two preparations of low molecular weight heparin in a pregnant woman. The main characteristics of heparin-related cutaneous allergy are reported. The use of an heparinoid, usually indicated for patients with heparin-induced thrombocytopenia, appeared to be efficient and safe for the mother and her fetus. An epidural analgesia was performed for labor analgesia, 24 hours after the last injection of danaparid of sodium.     

Liver transplantation for hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.     

Prediction of Ecofriendly Concrete Compressive Strength Using Gradient Boosting Regression Tree Combined with GridSearchCV Hyperparameter-Optimization Techniques

A crucial factor in the efficient design of concrete sustainable buildings is the compressive strength (Cs) of eco-friendly concrete. In this work, a hybrid model of Gradient Boosting Regression Tree (GBRT) with grid search cross-validation (GridSearchCV) optimization technique was used to predict the compressive strength, which allowed us to increase the precision of the prediction models. In addition, to build the proposed models, 164 experiments on eco-friendly concrete compressive strength were gathered for previous researches. The dataset included the water/binder ratio (W/B), curing time (age), the recycled aggregate percentage from the total aggregate in the mixture (RA%), ground granulated blast-furnace slag (GGBFS) material percentage from the total binder used in the mixture (GGBFS%), and superplasticizer (kg). The root mean square error (RMSE) and coefficient of determination (R²) between the observed and forecast strengths were used to evaluate the accuracy of the predictive models. The obtained results indicated that—when compared to the default GBRT model—the GridSearchCV approach can capture more hyperparameters for the GBRT prediction model. Furthermore, the robustness and generalization of the GSC-GBRT model produced notable results, with RMSE and R² values (for the testing phase) of 2.3214 and 0.9612, respectively. The outcomes proved that the suggested GSC-GBRT model is advantageous. Additionally, the significance and contribution of the input factors that affect the compressive strength were explained using the Shapley additive explanation (SHAP) approach.     

Combined molecular dynamics simulations and experimental studies of the removal of cationic dyes on the eco-friendly adsorbent of activated carbon decorated montmorillonite Mt@AC

In recent years, the combination of experimental and theoretical study to explain adsorbate/adsorbent interactions has attracted the attention of researchers. In this context, this work aims to study the adsorption of two cationic dyes, namely methylene blue (MB) and crystal violet (CV), on a green adsorbent Montmorillonite@activated carbon (Mt@AC) composite and to explain the adsorption behavior of each dye by the molecular dynamics (MD) simulation method. The eco-friendly nanocomposite Mt@AC is synthesized and characterized by the analysis methods: XRD, FTIR, BET, TGA/DTA, SEM-EDS, EDS-mapping and zeta potential. The experimental results of adsorption equilibrium show that the adsorption of the two dyes is well suited to the Langmuir adsorption model. The maximum adsorption capacity of the two dyes reaches 801.7 mg g⁻¹ for methylene blue and 1110.8 mg g⁻¹ for crystal violet. The experimental kinetics data fit well with a pseudo-first order kinetic model for the two dyes with coefficient of determination R² close to unity, non-linear chi-square χ² close to zero and lower Root Mean Square Error RMSE (R² → 1 and χ² → 0, RMSE lower). Molecular dynamic simulations are run to gain insights on the adsorption process. According to the RDF analysis and interaction energy calculations, the obtained results reveal a better affinity of the CV molecule with both the AC sheet and montmorillonite framework as compared with MB. This finding suggests that CV is adsorbed to a larger extent onto the nanocomposite material which is in good agreement with the adsorption isothermal experiment observations.

Eco-friendly Mt@AC composite material was prepared and characterized for removal of cationic dyes from aqueous solutions. The Molecular dynamics simulation was applied for evaluating the adsorption mechanisms.