Results of irradiation treatment in patients with non-resectable oesophageal cancer

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (Group A: Stage I/II, 32; Group B: Stage III/IV, 16) underwent intraluminal Iridium-192 high dose-rate afterloading therapy (5-7 Gy/session, total dose: 5-21 Gy, mean: 12.4 Gy) and external beam irradiation (Karnofsky > or = 80% 50-60 Gy/2 Gy per day; Karnofsky 60-79%: 30 Gy/3 Gy per day). Durable satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B, 6.9 months, with a 12-month survival rate of 66% (group A) and 0% (group B) (P < 0.001). Local tumour response and complication rate were significantly dose-related with a predicted response rate of 70.5%, and a complication rate of 50% at ERD 129.3 Gy.     

Effects of the Na+/H+-exchange inhibitor Hoe 642 on intracellular pH, calcium and sodium in isolated rat ventricular myocytes

The inhibitors of the Na+/H+-exchange (NHE1) system Hoe 694 and Hoe 642 possess cardioprotective effects in ischaemia/reperfusion. It is assumed that these effects are due to the prevention of intracellular sodium (Nai) and calcium (Cai) overload. The purpose of the present study was to investigate the effects of Hoe 642 on intracellular pH, Na+ and Ca2+ (pHi, Nai and Cai) in isolated rat ventricular myocytes under anoxic conditions or in cells in which oxidative phosphorylation had been inhibited by 1.5 mmol/l cyanide. In cells which were dually loaded with the fluorescent dyes 2, 7-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and Fura-2, anoxia caused acidification of the cells (from pHi 7.2 to pHi 6.8) and an increase in Cai from about 50 nmol/l to about 1 micromol/l. The decrease in pHi began before the cells underwent hypoxic (rigor) contracture, whereas Cai only began to rise after rigor shortening had taken place. After reoxygenation, pHi returned to its control value and Cai oscillated and then declined to resting levels. It was during this phase that the cells rounded up (hypercontracture). When 10 micromol/l Hoe 642 was present from the beginning of the experiment, pHi and Cai were not significantly different from control experiments. At reoxygenation, pHi did not recover, but Cai oscillated and returned to its resting level. To monitor Nai, the cells were loaded with the dye SBFI. After adding 1.5 mmol/l cyanide or 100 micromol/l ouabain, Nai increased from the initial 8 mmol/l to approximately 16 mmol/l. Hoe 642 or Hoe 694 (10 micromol/l) did not prevent the increase in Nai. In contrast, the blocker of the persistent Na+ current R56865 (10 micromol/l) attenuated the CN--induced rise in Nai. The substance ethylisopropylamiloride was not used because it augmented considerably the intensity of the 380 nm wavelength of the cell's autofluorescence. In conclusion, the specific NHE1 inhibitor Hoe 642 did not attenuate anoxia-induced Cai overload, nor CN--induced Nai and Cai overload. Hoe 642 prevented the recovery of pHi from anoxic acidification. This low pHi maintained after reoxygenation may be cardioprotective. Other possible mechanisms of NHE1 inhibitors, such as prevention of Ca2+ overload in mitochondria, cannot be ruled out. The increase in Nai during anoxia is possibly due to an influx of Na+ via persistent Na+ channels.     

Unresolved issues in the pathogenesis of Bartter's syndrome and its variants

Recent physiologic information concerning the renal response to potassium deprivation has been used to reevaluate potassium wasting in Bartter's syndrome. Experimental patient data support the notion that failure of potassium conservation is due to an imbalance between tubular secretory and reabsorptive processes. Suggestions are presented for the further evaluation of potassium reabsorptive pathways in the distal tubule.     

Effects of the combinations propofol/alfentanil and midazolam/fentanyl on blood pressure and contact phase system during coronary surgery

Perioperative haemodynamic changes leading to severe circulatory problems during open-heart surgery still represent dreaded complications. The aim of this study was to examine the relationship between the use of applied anaesthetic agents and alterations of the contact phase of the intrinsic blood-clotting system, as changes within the kallikrein-kinin system can lead to a fall in blood pressure. In a randomized study, parameters of the kallikrein-kinin system, coagulation and fibrinolysis were determined for 36 patients with aortocoronary bypass operations. The patients had been given either midazolam/fentanyl or propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values were registered at seven fixed points. The measured values of the factor XIIa-like activity and the kallikrein-like activity suggested a higher activation of the contact phase, when propofol/alfentanil was given. From the start of the extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like activities in the propofol/alfentanil group were significantly higher than those of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a stronger activation of the contact phase--at least at the beginning of recirculation--and as a result of it, a stronger fibrinolysis within the propofol/alfentanil group. In addition, the hypotensive side-effects differed significantly between the two groups. Patients receiving propofol/alfentanil needed the triple amount of antihypotonicum to maintain the mean arterial blood pressure above 75 mmHg. With the results of this study, a correlation between the application of propofol/alfentanil, contact phase activation, with activation of the kallikrein-kinin-bradykinin system and the observed hypotension, can be presumed.     

The dimensionality of schizophrenia concepts in first-episode psychosis

OBJECTIVE: To evaluate the efficacy of unreamed retrograde intramedullary (IM) nailing of fractures of the femoral shaft in a second series of patients using modifications suggested from our initial study. DESIGN: Prospective. SETTING: Level I trauma center. METHODS: Based on the findings of a previous study, we began a clinical series incorporating changes consisting of (a) inclusion of any patient with a femoral shaft fracture amenable to IM nailing (i.e., closed physes), (b) primary use of a split patellar tendon intercondylar distal femoral entry portal, and (c) the use of a full-length femoral implant having variable size availability and dynamization capability. Over a twelve-month period, thirty-four patients with thirty-five femoral shaft fractures were treated. The protocol called for planned dynamization in statically locked stable fractures and unstable fractures showing minimal healing at six to twelve weeks. Functional outcome was assessed by using the Knee Society clinical rating system. RESULTS: Incorporating the concepts of canal fill and early dynamization, there were only two nonunions (6 percent) in this series as compared with 14 percent in the previously reported series with an overall shorter time to union (12.6 versus 15 weeks). There were no infections or malunions. Postoperative complaints of knee pain were minimal (knee score average: 98 points) and knee function was excellent (knee score average: 97 points). CONCLUSIONS: Although not advocated as a replacement for other techniques, unreamed retrograde nailing is presented as a safe and beneficial fracture fixation method that should be added to the orthopaedic surgeon's treatment armamentarium. The operative technique is quick and simple, and blood loss is minimal. Early nail dynamization and early weight-bearing are important in minimizing the risk of nonunion.     

Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses

In an in-vitro preparation of gastric mucosae of Rana pipiens, the effect of adding melittin to a concentration of 5x10-6 M in the secretory solution on the transepithelial potential difference (PD), resistance (R) and short-circuit current (Isc) was studied. In 20 min, melittin decreased the PD by 9.3 mV and R by 148 ohm cm2. These changes can be explained by a decrease in the resistance, RP, of the paracellular pathway. To determine whether specific-ion pathways were responsible for the decrease in R, the effect of melittin on the partial conductances of Cl-, K+ and Na+ was also studied using the ion substitution method. Melittin decreased the PD response to changes in nutrient Na+, K+ and Cl- and the PD response to changes in secretory Cl-, but did not affect PD responses to changes in secretory Na+ or K+. Therefore, melittin decreased the nutrient membrane partial conductances of Cl-, K+ and Na+ and secretory membrane partial conductance of Cl-, without affecting the secretory partial conductances of Na+ or K+. Initially, melittin increased Isc in regular and Cl--free but not in Na+-free solutions. There was a delayed decrease in Isc. The results indicate that melittin decreases RP, increases the Na+ conductance of the secretory membrane and inhibits, eventually, the Na+/K+-ATPase pump.     

Familial transmission of a serious disease--producing group A streptococcus clone: case reports and review

Invasive group A streptococcus (GAS) infections are emerging diseases; however, person-to-person transmission of invasive GAS producing life-threatening infection has been observed rarely. We report a small intrafamilial cluster of life-threatening GAS infections. A previously healthy 47-year-old father developed necrotizing fasciitis of the neck. Two days later, his 16-year-old daughter developed streptococcal angina, pneumonia, and pleural empyema. Both patients had signs of streptococcal toxic shock syndrome. Pulsed field gel electrophoresis revealed that the M6 strains of GAS isolated from the father and daughter had identical patterns. Cases of person-to-person transmission of invasive GAS infection reported in the literature are also reviewed.     

Potential prognostic value of C-erbB-2 expression in medulloblastomas in very young children

PURPOSE: The expression of the c-erbB-2 oncogene was studied in childhood medulloblastoma to evaluate its prognostic value, which has been claimed previously. PATIENTS AND METHODS: Tumor material from 45 patients < 15 years old at diagnosis was studied using 3 monoclonal antibodies against the internal and external domains of the c-erbB-2 oncogene product. RESULTS: Six of the 45 (13%) tumor specimens were found to be positive. C-erbB-2 expression was found more often in patients < 3 years old at diagnosis (4 of 15 patients, 27%) than in older patients (2 of 30, 6.6%). During the follow-up period (5.8 +/- 2.8 years) all patients with c-erbB-2 expression died of disease (after 1.2 +/- 0.7 years). Kaplan-Meier estimation revealed a highly significant correlation of c-erbB-2 expression and survival (p = 0.002). A further study of the expression of synaptophysin and the glial fibrillary acidic protein (GFAP) in the 45 tumors revealed a negative correlation of the expression of c-erbB-2 and these proteins. CONCLUSION: C-erbB-2, which may be predominantly expressed by less differentiated tumors, was found to delineate a poorer prognostic subgroup, especially when diagnosed in patients < 3 years old.