Myocardial protection using fructose-1,6-diphosphate during coronary artery bypass graft surgery: a randomized, placebo-controlled clinical trial

In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury through increased high-energy phosphate levels and may therefore have cardioprotective properties in patients undergoing coronary artery bypass graft (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded, sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1 required adjustment as a result of metabolic acidosis. This suggests that we achieved the intended effect of a dose-ranging study. The expected response was observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP as a cardioplegic additive (n = 15). These patients had lower serum creatine kinase-MB levels 2, 4, and 6 h after reperfusion (P < 0.05), fewer perioperative myocardial infarctions (P < 0.05), and improved postoperative cardiac function, as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h (P < 0.01) and cardiac index (CI) at 12 and 16 h (P < 0.05) after reperfusion. Overall efficacy of FDP was tested across all regimens that included IV FDP (n = 88; 44 FDP, 44 control) using 2 (FDP versus placebo) x 3 (dose size) factorial analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB levels (AUC-16h, P < 0.05) in FDP-treated patients. The internal consistency of this dataset suggests that FDP may provide myocardial protection in CABG surgery and supports previous laboratory and clinical studies of FDP in ischemic heart disease. IMPLICATIONS: Fructose-1,6-diphosphate (FDP) may increase high-energy phosphate levels under anaerobic conditions and therefore ameliorate ischemic injury. A dose-ranging safety study for FDP was conducted in patients undergoing coronary artery surgery. Preischemic provision of FDP significantly improved cardiac function and reduced perioperative ischemic injury. These myocardial protective effects may improve patient outcome after cardiac surgery.     

Initial Experience with Laparoscopic Adjustable Gastric Banding in Hungary

Background: Laparoscopic adjustable gastric banding (LAGB) was started in Hungary in 1998. We used Lap-Band and SAGB devices. In this study we present our experience through the learning curve. Methods: From Jan 1999 to Dec 2002, 54 patients underwent laparoscopic surgery for morbid obesity in our department, using the Lap-Band? and SAGB. There were 33 men and 21 women, with median age 42 (range 20-64), and preoperative BMI 50 kg/m² (range 41-66). All underwent LAGB, except one patient who had laparoscopic vertical banded gastroplasty.The procedures used the 4-trocar technique. Results: The first patient required reoperation because of gastric rupture from drinking sparkling mineral water despite of our advice. Excluding this, we had no intraoperative or short-term postoperative complications. Mean operating time was 82 minutes (range 55-192), and hospital stay was 3 days. Followup ranges from 1 to 36 months. Mean weight loss was 47 kg at 12 months and 67 kg at 36 months. Mean BMI fell to 29 kg/m². Conclusion:With its safety and effectiveness, LAGB has been a good choice for handling morbidly obese patients in our early experience.     

Strategies to Increase Smoke Alarm Use in High-Risk Households

A 3-year project was undertaken to evaluate two methods of promoting residential smoke alarm installation and maintenance in high risk households across the U.S. Five states (Arkansas, Maine, Maryland, Massachusetts, and North Carolina) participated. The two strategies under study were direct installation of smoke alarms and distribution of a voucher for free smoke alarms. The target population included occupants of high-risk households without working smoke alarms who were approached as part of a door-to-door canvassing program. Fire Safety education was provided to both groups. A follow up assessment conducted 6-12 months post intervention assessed the presence and functional status of smoke alarms in each of the two groups. Demographic and fire safety data were also collected at baseline and follow up for each group. 4,455 households were enrolled in the study [Installation Group: 2,206 (49.5%), Voucher Group: 2,249 (50.5%)]. Baseline characteristics of the groups within each state were comparable. Follow up data was obtained on 1,583 installation group households and 1,545 voucher group households. At follow up, 1,421 (89.8%) households in the installation group had working smoke alarms, compared with 997 (65%) households in the voucher group, Odds Ratio 4.82 (95% CI=3.97, 5.85) (p <.0001). On average, 47% of all households enrolled in the voucher group did not redeem their vouchers (range 26-63%). Direct installation of alarms by program staff resulted in working smoke alarms in 90% of households receiving the direct installation intervention. Only 65% of voucher households had functioning alarms at follow up, largely due to failure to redeem vouchers.     

From routine acylation towards stable sigma-complexes of pyrimidine: carbon protonation of the pyrimdine-ring

It is well known, that the ring nitrogen of pyrimidine possesses basic property, electron donating groups increase basicity. According to literature data published so far pyrimidines protonate at the ring nitrogen. The present paper gives brief account of the C(5) carbon-protonation observed among triaminopyrimidine derivatives, which in some cases results in stable sigma-complexes. Steric and electronic effects responsible for carbon-protonation are investigated in simple C(5) substituted 2,4,6-triaminopyrimidine derivatives. We show new stable sigma-complexes in the triaminopyrimidine series. The paper summarizes, in Hungarian, our recently published results (J. Amer. Chem. Soc., 125, 2535-2540, 2003) as well as our new results presented in the symposium ,,Gyógyszerkémiai Gyógyszertechnológiai Szimpózium 2003".     

Adjuvant chemotherapy following surgery in the management of uterine sarcomas

OBJECTIVE: The aim of this study was to investigate the use of imaging tools in the diagnosis of uterine sarcomas, and to evaluate the effect of the adjuvant chemotherapy for uterine sarcomas. PATIENTS AND METHODS: The data of 29 patients with uterine sarcomas who received cytostatic polychemotherapy between 1990 and 2000 at the Oncological Division of the Ist Department of Obstetrics and Gynecology, Semmelweis University were evaluated by the authors. Symptoms leading to diagnosis and methods of diagnosis were examined. Vascular changes shown by two-dimensional, color and pulsed Doppler ultrasonography were observed. For staging the currently accepted FIGO method was adopted. Most of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). In each case we administered adjuvant combination chemotherapy according to the CYVADIC-protocol. The effect of adjuvant chemotherapy was evaluated. RESULTS: Six patients had Stage I, ten had Stage II, 11 had Stage III, and two had Stage IV disease. The mean age of the patients was 53.6 years with a range of 22 to 77 years. Histopathologic distribution included nine leiomyosarcomas (LMS), 13 mixed mesodermal sarcomas (MMS), and seven endometrial stromal sarcomas (ESS). Although most patients experienced neutropenia following cytotoxic chemotherapy, other non-hematologic adverse effects were easy to control. The average progression-free interval was 22.14 months, in which no significant difference was found between the histologic types. Different stages showed highly varied responses: surprisingly, patients in Stage IV with lung metastases were documented to have the longest progression-free survival. The three-year survival rate for all stages was demonstrated in 34.4% of cases. Patients with progressive disease had an average survival period of 4.4 months. CONCLUSIONS: These findings suggest that adjuvant cytostatic therapy for patients with distant metastasis confined to a single organ may produce better results than expected.     

Outcome of pregnancies after cold-knife conization of the uterine cervix during pregnancy

OBJECTIVE: To determine the incidence of cervical intraepithelial neoplasia (CIN) in pregnancy and to determine the outcome of pregnancies in women treated by cold knife conization during pregnancy. METHODS: The authors retrospectively studied the cases of 19,807 pregnant patients, who presented to the 1st Department of Obstetrics and Gynecology Semmelweis University Faculty of Medicine between January 1, 1993 and December 31, 1997. Of these, there were 1,513 spontaneous abortions, 6,170 artificial abortions and 12,124 deliveries. Cytological evidence of a high-grade squamous intraepithelial lesion (LGSIL) was found in 48 pregnant patients. A low-grade squamous intraepithelial lesion (LGSIL) was found in 55 pregnant patients. All pregnant patients with HGSIL including those with satisfactory and nonsatisfactory colposcopical examinations underwent diagnostic cold knife conization during pregnancy in the second trimester. A gynecologic pathologist (Dr. Zs. Csapó) reviewed the histopathological sections. RESULTS: Overall, 44 patients had CIN, three patients had microinvasive carcinoma (FIGO stage I/A1), and one patient had neither CIN nor invasive carcinoma in the HGSIL group. Among the 48 pregnant patients with HGSIL, there were two spontaneous abortions occurring during the 21st and the 22nd gestational weeks respectively, so the pregnancy loss rate was 4.2%. Forty patients (83%) delivered at term and six patients (12.5%) at preterm. Twenty-four patients (52%) delivered vaginally and 22 (48%) by cesarean section. Comparing this data with the control group consisting of pregnant patients who had LGSIL, the difference between the two group as regards the total number of adverse pregnancy outcome cases was not significant. In the three patients with microinvasive cervical carcinoma (FIGO stage I/A1), elctive cesarean section was performed, followed by an immediate abdominal hysterectomy at term. CONCLUSION: The incidence of CIN in pregnancy was 0.22%. The incidence of microinvasive cervical carcinoma was 0.015%. Pregnant patients with CIN who underwent cold knife conization during pregnancy were not at increased risk of adverse pregnancy outcome, however they were at increased risk of cesarean delivery.     

Does heart rate identify sudden death survivors? Assessment of heart rate, QT interval, and heart rate variability

The objective was to test whether the circadian variability of several electrocardiographic variables distinguishes sudden cardiac death survivors from heart disease patients without a history of cardiac arrest and from normal subjects. Heart rate, heart rate variability, and QT interval have been reported to identify survivors of sudden cardiac death. Computer-assisted continuous QT measurement and heart rate variability analysis were performed on 24-hour Holter records for three groups: (1) 14 sudden death survivors; (2) 14 control patients with diagnosis and therapy matched to survivors; and (3) 14 healthy subjects. There were no significant differences in 24-hour mean RR and QT intervals between groups. However, heart rate was significantly different between the three groups at night but not during the day because the expected nighttime decline was markedly blunted in survivors and somewhat blunted in control patients. The QT interval and frequency domain heart rate variability measures followed a similar circadian pattern. The mean QTc was significantly longer in control patients. The QTc had a wide range in all groups, but less in sudden death survivors. Of ten common time and frequency domain heart rate variability indices, only SDANN and SDNN were significantly lower in sudden death survivors. Reduced circadian variation of heart rate, with marked blunting of the nighttime heart rate decline, identifies sudden cardiac death survivors as well as does SDANN and SDNN, and, in contrast to heart rate variability measures, can easily be obtained from a Holter report without complex calculations.     

Seromuscular gastrocystoplasty in dogs

INTRODUCTION: The aim of this study was to investigate the feasibility of seromuscular gastrocystoplasty (SGCP) in an animal model and to compare it to conventional gastrocystoplasty (CGCP). MATERIALS AND METHODS: CGCP and SGCP (using gastric segments without mucosa) were each performed in 6 dogs. In both procedures, two-thirds of the dome of the bladder were excised and the gastric segment anastomosed to the bladder remnant. Cystography, cystomanometry, measurements of urine pH, and gross and microscopic pathological studies were carried out preoperatively, and postoperatively, at 6 and 12 weeks. RESULTS: All seromuscular gastric segments proved viable, and 6 weeks after the operation they were covered by a thin layer of transitional epithelium, which had gradually thickened by the end of the 12-week follow-up. There was no difference in bladder capacity and compliance between the two groups, however, fasting urinary pH values were higher (less acidic) in the SGCP group. CONCLUSIONS: Stripping off the mucosa of the gastric segment appears to stop hydrochloric acid secretion, thereby lessening the possible risk of ulceration, perforation, dysuria-haematuria, metaplasia and malignancy. The uroepithelium overgrowth of the seromuscular gastric segments might provide a more physiological neo-bladder than when using full-thickness gastrocystoplasty.     

A treadmill ramp protocol using simultaneous changes in speed and grade

INTRODUCTION: A treadmill exercise test requiring a low initial metabolic rate that then increments the work rate linearly to reach the subject's limit of tolerance in approximately 10 min would have significant advantages for exercise testing and rehabilitation of subjects with impaired exercise tolerance. METHODS: We developed such a treadmill protocol that uses a linear increase in walking speed coupled with a curvilinear increase in treadmill grade to yield a linear increase in work rate. RESULTS: Twenty-two healthy, sedentary subjects performed both this new treadmill protocol and a standard cycle ergometry ramp protocol eliciting similar work rate profiles. The low initial treadmill speed and grade resulted in a low initial metabolic rate, commensurate with unloaded pedaling on a cycle ergometer (average [OV0312]O2 = 0.54 +/- 0.16 vs 46 +/- 0.12 l x min(-1)). This combination of simultaneous increase in speed and grade yielded a linear work rate and its oxygen uptake response (R2 = 0.96 +/- 0.03) with a slope of 11.4 +/- 2.4 ml x min(-1) x W(-1)-slightly, but significantly, higher than on the cycle (9.6 +/- 2.0 ml x min(-1) x W(-1)). This difference was attributed to unmeasured work associated, for example, with additional limb movements and frictional losses. As previously demonstrated, both the peak oxygen uptake and the estimated lactate threshold were higher on the treadmill than for cycle ergometry (averaging 23% and 27%, respectively, in these subjects). CONCLUSION: This treadmill protocol provides a linear profile of work rate as is currently standard for cycle ergometry and is appropriate for testing of subjects with low exercise tolerance.     

Association between gastric cancer mortality and nitrate content of drinking water: Ecological study on small area inequalities

The carcinogenic feature of N-nitroso compounds has been well established. Similarly, the transformation of ingested nitrate to N-nitroso compounds in the stomach has been thoroughly documented, nevertheless nitrates' carcinogenic effect has not been proved convincingly in human. The present study was aimed to investigate a population of small villages provided by drinking water with high and widely variable nitrate content (72 mg/l median, 290.7 mg/l 95-percentile concentration). Empirical Bayes estimates for settlement-specific age-, sex-, and year-standardised mortality ratios of gastric cancer (GC) were related to the settlement level average nitrate concentrations in drinking water controlling for confounding effects of smoking, ethnicity and education. The log-transformed average nitrate concentration showed significant positive association with stomach cancer mortality in linear regression analysis (p = 0.014). The settlements were aggregated according to the nitrate concentration into 10-percentile groups and the standardised mortality ratios (SMRs) were calculated. Those groups with higher than 88 mg/l average nitrate concentration showed substantial risk elevation and the log-transformed exposure variables proved to be significant predictors of mortality (p equals; 0.032) at this level of aggregation also. The association seemed to be fairly strong (r ² equals; 0.46). Although this investigation constituting an ecological study has certain limitations, it supports the hypothesis that the high level of nitrate in drinking water is involved in the development of GC.