Sepsis in nonagenarians admitted to internal medicine departments: a comparative study of outcomes.

BACKGROUND: Elderly patients are at a higher risk of acquiring sepsis, and are largely being treated in Internal Medicine (IM) departments. AIM: To characterize the differences between nonagenarians and other age groups in patients admitted to IM departments with sepsis, and to assess predictors for survival in patients older than 90 years of age. DESIGN AND METHODS: A prospective registry of all-comers with sepsis admitted to IM departments in a community-based Medical Center was build. Patients' demographics, medical history, clinical presentation and outcomes were recorded and analyzed according to age groups. RESULTS: One thousand and eighty patients were followed for a mean of 83.63 ± 65.90 days. Nonagenarians constituted 10.93% (118/1080) of our cohort. Of these, 70.48% had a cognitive impairment and 82.60% had reduced functional state. Of these, 5.61 and 10.50% fulfilled the criteria of septic shock and severe sepsis, respectively. Sepsis category was significantly influenced by age groups (P < 0.001). Complications secondary to sepsis at admission and throughout hospitalization, and mortality rates, were higher in the nonagenarian population (61.86 vs. 51.14%, P = 0.032 and 37.29 vs. 20.06%, P < 0.001, respectively), and overall survival was significantly lower in the nonagenarian population (40.68 vs. 66.84%, P < 0.001). CONCLUSION: Patients treated in IM departments for sepsis are old, and a significant percentage is older than 90 years of age with reduced function and mental status at baseline. These frail patients are afflicted by a worse outcome, which is most likely associated with poor functional status at baseline and severe deconditioning during the acute illness. Prognostic tools are needed to address today's trends in patient-mix and disease severity, specifically for very-old patients admitted with sepsis cared for in IM departments.

Immunological arousal during acute Q fever infection.

Physicians often encounter patients who present with a vague clinical syndrome. A wide serological workup is often ordered, which may include tests for Coxiella burnetii in endemic areas. Often, the results of these tests pose new dilemma, with overlapping positive laboratory assays. The objective of this investigation was to characterise the serological overlap between acute Q fever and other infectious and immunological diseases. We retrospectively scanned the files of patients with a positive or equivocal immunoglobulin (Ig) M for C. burnetii phase II over a period of 8 years in a general hospital. Clinical and laboratory data, including antibodies to infectious agents and antibodies related to immunological states, were recorded. Anti-nuclear antibody (ANA), smooth muscle antibody (SMA) and rheumatoid factor were positive in 38%, 33.3% and 22.2% of the cases, respectively. In patients with acute Q fever, elevated IgM levels for Epstein-Barr Virus (EBV), cytomegalovirus (CMV), Mycoplasma pneumoniae, parvovirus, Bordetella pertussis, Rickettsia conorii and R. typhi were noted in 13.8%, 8.3%, 12.12%, 22.2%, 25%, 13% and 21.7% of cases, respectively. Acute Q fever induces a non-specific immunological arousal in a significant number of patients. This may interfere with diagnosis and delay treatment. Caution, clinical judgment and serological follow-up is warranted in such conditions.

Characterization of the best anatomical sites in screening for methicillin-resistant Staphylococcus aureus colonization.

The purpose of this study was to identify differences in the sensitivity of anatomical sites sampling for methicillin-resistant Staphylococcus aureus (MRSA) colonization related to age, gender, clinical situation, and acquisition source as a base for screening protocols. We used a database that included all MRSA-positive cultures (Carmel Medical Center, 2003-2006) taken from nares, throat, perineum, and infection sites. The study population of 597 patients was divided into: "screening sample" (SS), which were cases of routine screening, and "clinical diagnostic sample" (CDS), which were patients with concurrent MRSA infection. MRSA acquisition sources were classified as internal medicine, surgical, referral patients, or intensive care unit (ICU). CDS patients were older than SS patients (median age 78 vs. 74 years, p = 0.0002), more commonly throat colonized (47.5% vs. 31.8%, p = 0.0001), and colonized in more multiple sites (65.7% vs. 43.3% were colonized in three sites in the CDS and SS groups, respectively, p < 0.001) than SS patients. In the SS, group throat colonization was higher in internal medicine wards than in the ICU (odds ratio [OR] = 3.98, p < 0.0001). In the CDS group, perineal colonization was more common in referral patients than in the ICU (OR = 4.52, p < 0.05). Patient age was the most influential factor on nares and multiple sites colonization in the SS and CDS groups, respectively. Our data support multiple sites sampling. Throat cultures are crucial in MRSA-infected patients and internal medicine ward patients. Multiple body sites colonization is more likely in older or MRSA-infected patients, affecting decisions regarding eradication using topical antibiotics.

The use of circular stapler for cervical esophagogastric anastomosis after esophagectomy: surgical technique and early postoperative outcome.

Stapled esophagogastric anastomosis after esophagectomy is considered to be superior to traditional handsewn techniques. Linear staplers are usually used. The aim of this study is to evaluate early postoperative results of circular stapler in cervical esophagogastric anastomosis. Records of all patients who underwent esophagectomy during the years 2003-2008 were reviewed. Patients that underwent transthoracic esophagectomy, colon transposition, or linear stapler anastomosis were excluded. Esophagogastric anastomosis was done either handsewn or using circular stapler. Patients underwent either pyloromyotomy, pyloroplasty, or no pyloric intervention. Postoperative leakage was diagnosed either clinically or radiologically. The end-point of this study was the incidence of anastomotic leak in the immediate postoperative period. Eighty-two patients (average age 66 years, male/female, 52/30) met the inclusion criteria. In 30 patients, the anastomosis was handsewn, and in 52 patients, it was done using a circular stapler. Overall operative mortality rate was 4.8% (four patients because of pulmonary or cardiac complications). Anastomotic leak occurred in five (n = 5, 16.6%) patients in the handsewn group and eight (n = 7, 13.4%) patients in the circular stapler group. Pyloric manipulation had no significant effect over the leakage rate. Routine upper-gastrointestinal (GI) series done on the fifth or sixth postoperative day did not reveal any of the leaks. Cervical esophagogastric anastomosis using an end-to-side circular stapler is feasible and safe, and has comparable outcomes to handsewn anastomosis in regard of leakage rates or other major surgical or general complications. Postoperative GI series seems to be a poor diagnostic tool for anastomotic leakage and could be omitted as a routine study for occult anastomotic leak.

Cyclosporine safety and bioavailability with two second-generation softgel capsules using serum concentrations/TDM and modeling in transplant patients--a retrospective, parallel, comparative evaluation study.

OBJECTIVE: Deximune soft-gelatin capsules (Dexcel Ltd., Hadera, Israel), the test preparation and Sandimmun Neoral (Novartis Inc., Basel, Switzerland), the reference preparation, are two cyclosporine (CyA) formulations widely used after stem cells and solid organ transplantation. A post-marketing, retrospective, parallel, comparative, multicenter survey study in transplant patients receiving these two formulations after transplantation was carried out in order to compare the toxicity profile and bioavailability. MATERIALS AND METHODS: The study was conducted in the five main leading transplantation centers in Israel and included 174 patients. A total of 1-3 CyA serum levels at different periods after transplantation were measured in each subject and the bioavailability, efficacy and toxicity profile were assessed. The blood concentrations were compared using a statistical model after adjustment for type of transplantation, dose and time after transplantation as confounding factors. RESULTS: No distinct differences were observed between the two CyA formulations. Using model-derived least squares means (LSM) of the CyA blood levels and adjusting for relevant confounding factors, no significant difference could be found between the blood levels of the test and reference formulations. Most of the side effects were mild and transient with both formulations, whereas 23% of the patients reported serious adverse events (mainly hypertension, 15%). 20% of the patients developed infectious complications during the therapy. CONCLUSIONS: Deximune administration is safe. The toxicity profile of the product, incidence and type of side effects and bioavailability are similar to those of Sandimmun Neoral.

Comparative in vivo bioequivalence and in vitro dissolution of two cyclosporin A soft gelatin capsule formulations.

OBJECTIVE: A study was conducted to establish the bioequivalence between a newly developed cyclosporin A (CsA) oral formulation, Deximune soft-gelatin capsules (Dexcel Ltd.) and Sandimmune Neoral (Novartis Inc.). MATERIALS AND METHODS: The clinical investigation was designed as a randomized, open-labeled, two-period, two-treatment crossover study, in 24 healthy fasted male volunteers. The subjects were administered a single 200 mg CsA dose of either formulation. Serial venous blood samples were obtained over 24 hours after each administration to measure CsA in whole blood by a specific TDx-immunoassay. In addition, the comparative drug release rate was assessed using a dissolution apparatus test according to the USP-24 method. RESULTS: For both treatments, a mean maximum blood concentration (Cmax) of approximately 1,200 ng/ml was obtained at about 1.6 hours (tmax) after administration and the geometric mean of the area under the blood concentration-time curve (AUC) both for test and reference was approximately 4,900 ng x h/ml. Bioequivalence was conclusively demonstrated for both rate (Cmax and tmax) and extent (AUC) of CsA absorption, between the two treatments. Moreover, the CsA blood concentration measurement at 2 hours after administration (C2), demonstrated equivalent results between the two products. The point estimates and their 90% confidence intervals were within the respective equivalence ranges for the pharmacokinetic parameters and were included in the range for drugs with a narrow therapeutic index. The comparative dissolution test for both formulations showed an in vitro release rate of more than 90% within 15 minutes. CONCLUSIONS: Based on the results, the two oral CsA formulations compared are bioequivalent and can be interchanged without need for dosage adjustment.

Evaluation and refinement of the environmental stress index for different climatic conditions.

The purpose of this study was to evaluate the recently constructed environmental stress index (ESI) for a large database comprising various climatic conditions. Data analysis of measurements from 19 locations revealed a high correlation between ESI and the wet bulb globe temperature (WBGT) index for each database. Validity from statistical analysis, including optimization procedures, slightly changed the ESI constants as follows: ESI = 0.62Ta - 0.007RH + 0.002SR + 0.0043(Ta x RH) - 0.078(0.1 + SR)(-1) where: Ta = ambient temperature (degrees C); RH = relative humidity (%); and SR = solar radiation (w x m(-2)). The refined ESI and the WBGT index were applied to databases of more than 125,000 measurements for each variable: Ta, RH, SR, black globe temperature (Tg), and wet bulb temperature (Tw). For each database, the ESI was then successfully correlated with the WBGT (P < 0.05, R2 > or = 0.899). We conclude that the refined ESI, which is constructed from fast response and commonly used weather sensors (Ta, RH, SR), is a potential index to serve as an alternative to the WBGT for heat category assessment.

Neck circumference as a simple screening measure for identifying overweight and obese patients.

OBJECTIVE: There are numerous methods of assessing overweight and obesity. We undertook an observational study to test a method of identifying overweight or obese patients solely by measuring the circumference of the neck. RESEARCH METHODS AND PROCEDURES: A test sample and a second validation sample included 979 subjects (460 men and 519 women), who visited a family medicine clinic in a southern Israeli urban district for any reason between the randomly chosen months of January and September 1998. Main outcome included neck, waist, and hip circumferences; body mass index (BMI); and waist:hip ratio measures. RESULTS: Pearson's correlation coefficients indicated a significant association between neck circumference (NC) and: BMI (men, r = 0.83; women, r = 0.71; each, p < 0.0001), age (men, r = 0.33; women, r = 0.36; each, p < 0.0001), weight (men, r = 0.7; women, r = 0.81; each, p < 0.0001), waist circumference (men, r = 0.86; women, r = 0.85; each, p < 0.0001), hip circumference (men, r = 0.62; women, r = 0.56; each, p < 0.0001), and waist:hip ratio (men, r = 0.66; women, r = 0.87; each, p < 0.0001). NC > or=37 cm for men and > or =34 cm for women were the best cutoff levels for determining the subjects with BMI > or =25.0 kg/m(2) using the receiver output curve analysis. In the validation unrelated group, the test characteristics were excellent with 98% sensitivity, 89% specificity, and 94% accuracy for men, and 100% sensitivity, 98% specificity, and 99% accuracy for women. NC > or =39.5 cm for men and > or =36.5 cm for women were the best cutoff levels for determining the subjects with BMI > or =30 kg/m(2) using the receiver output curve analysis. In the validation unrelated group, the test characteristics were excellent with 93% sensitivity, 90% specificity, and 91% accuracy for men, and 93% sensitivity, 98% specificity, and 97% accuracy for women. DISCUSSION: NC measurement is a simple and time-saving screening measure that can be used to identify overweight and obese patients. Men with NC <37 cm and women with NC <34 cm are not to be considered overweight. Patients with NC > or =37 cm for men and > or =34 cm for women require additional evaluation of overweight or obesity status.

Term infants with fetal growth restriction are not at increased risk for low intelligence scores at age 17 years.

OBJECTIVE: To assess the long-term cognitive outcome of small for gestational age (SGA) compared with appropriate for gestational age (AGA) infants. DESIGN: Data from the Jerusalem Perinatal Study was matched with information from the army draft medical board. SGA and severe SGA were defined as birth weight below the 10th and 3rd percentiles for gestational age, respectively. A multiple linear regression analysis was performed to control for clinical, perinatal, and socio-demographic confounding variables. SUBJECTS: A cohort of 13,454 consecutive singleton term infants born between 1974 and 1976. MAIN OUTCOME MEASURE: IQ at age 17 years. RESULTS: SGA infants had lower adjusted mean +/- SE IQ scores compared with their AGA peers: 102.2 +/- 0.9 versus 105.1 +/- 0.7 (P <.0001) for males and 102.5 +/- 0.9 versus 103.9 +/- 0.7 (P <.015) for females. SGA was not associated with lower academic achievements compared with AGA. CONCLUSION: After controlling for multiple confounders, being born SGA at term is associated with slightly lower intelligence test scores at age 17 years. However, the clinical significance of the small difference is not evident in academic achievements.

A new blue light-emitting phototherapy device: a prospective randomized controlled study.

OBJECTIVE: To evaluate the efficacy of a new phototherapy light source with a narrow luminous blue spectrum. The device, made with high-intensity gallium nitride light-emitting diodes (LEDs), was compared with conventional phototherapy at similar light intensities. SETTING: Two university-affiliated community hospitals in Jerusalem. DESIGN: Prospective open randomized study. PARTICIPANTS: Sixty-nine jaundiced, but otherwise healthy, term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter. MAIN OUTCOME MEASURES: The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB) concentration. RESULTS: The mean TSB concentrations at initiation and termination of treatment did not differ between newborns receiving LED and those receiving conventional phototherapy. The duration of phototherapy and the rate of decrease in TSB concentration were not statistically different in the 2 groups. The average rate of decrease in TSB after adjustment by a linear regression analysis for confounding factors was -3.16 micromol/L/h (95% confidence limits -4.81, -1.51) in newborns receiving LED phototherapy compared with -2.19 micromol/L/h (-3.99, -0.40) in those treated with conventional phototherapy (P <.14). No side effects were noted in any of the newborns. CONCLUSIONS: The blue gallium nitride LED device is as effective as conventional phototherapy and is readily accepted by nursing staff. Future LED phototherapy devices can provide much higher irradiance, and thus greater efficacy, and offer a new highly versatile approach to the treatment of jaundice.

X-Rays from the Highly Polarized Broad Absorption Line QSO CSO 755.

We present results from a BeppoSAX observation of the broad absorption line (BAL) QSO CSO 755, which was observed as part of our program to investigate the X-ray properties of highly polarized BAL QSOs. CSO 755 is clearly detected by the BeppoSAX Medium-Energy Concentrator Spectrometers, making it the highest redshift (z=2.88) and most optically luminous (MV=-27.4) BAL QSO seen in X-rays. It is detected in several energy bands including the rest-frame 21-39 keV band, but we are able to place only loose constraints upon its X-ray spectral shape. Our X-ray detection is consistent with the hypothesis that the BAL QSOs with high optical continuum polarization tend to be the X-ray brighter members of the class. We examine a scattering interpretation of a polarization/X-ray flux connection, and we discuss the data needed to prove or refute such a connection. We also discuss a probable ROSAT detection of CSO 755. The observed-frame 2-10 keV flux from BeppoSAX (1.3x10-13 ergs cm-2 s-1) is high enough to allow X-Ray Multimirror Mission spectroscopy, and studies of iron K-line emission should prove of particular interest if a large amount of scattered X-ray flux is present.

Nutritional status of children with solid tumors.

BACKGROUND: The purposes of the study were to evaluate prospectively the nutritional status of children with solid tumors who were receiving chemotherapy, to find the most sensitive parameter of protein energy malnutrition, and to determine whether the stage of disease and aggressiveness of chemotherapy have any influence on nutritional status. METHODS: Fifty patients were followed prospectively from the time of diagnosis throughout chemotherapy. Serum albumin, prealbumin, and weight were measured at the time of diagnosis and before each course of chemotherapy. RESULTS: At diagnosis, only 2.7% of patients had albumin levels < 3.5 g/dL whereas 36% had prealbumin levels below the normal limit. All patients showed a weight increment of 81 g/day (P = 0.0001), an albumin increment of 0.001 U/day (P = 0.0001), and a prealbumin increment of 0.044 U/day (P = 0.0407). The change in prealbumin values was much more prominent (10-fold higher) in children age < 2 years. Changes in albumin values were not statistically significant by stage of disease but the increment of prealbumin did show statistical significance, which was most prominent in patients with Stage IV disease CCG (children's cancer group classification ) (P = 0.0003). The intensity of chemotherapy had no influence on changes in weight or albumin levels. However, it did influence changes in prealbumin levels, which were most pronounced in the group receiving high dose chemotherapy. CONCLUSIONS: Based on the results of the current study, the authors believe prealbumin is the most powerful test overall with which to evaluate the nutritional status of children with solid tumors both at the time of diagnosis and throughout chemotherapy.

Can gender differences during exercise-heat stress be assessed by the physiological strain index?

A physiological strain index (PSI) based on rectal temperature (Tre) and heart rate (HR) was recently suggested to evaluate exercise-heat stress. The purpose of this study was to evaluate PSI for gender differences under various combinations of exercise intensity and climate. Two groups of eight men each were formed according to maximal rate of O2 consumption (VO2 max). The first group of men (M) was matched to a group of nine women (W) with similar (P > 0.001) VO2 max (46.1 +/- 2.0 and 43.6 +/- 2.9 ml. kg-1. min-1, respectively). The second group of men (MF) was significantly (P < 0. 001) more fit than M or W with VO2 max of 59.1 +/- 1.8 ml. kg-1. min-1. Subjects completed a matrix of nine experimental combinations consisting of three different exercise intensities for 60 min [low, moderate, and high (300, 500, and 650 W, respectively)] each at three climates (comfortable, hot wet, and hot dry [20 degrees C 50% relative humidity (RH), 35 degrees C 70% RH, and 40 degrees C 35% RH, respectively]). No significant differences (P > 0.05) were found between matched genders (M and W) at the same exposure for sweat rate, relative VO2 max (%VO2 max), and PSI. However, MF had significantly (P < 0.05) lower strain than M and W as reflected by %VO2 max and PSI. In summary, PSI applicability was extended for exercise-heat stress and gender. This index continues to show potential for wide acceptance and application.

The physiological strain index applied to heat-stressed rats.

A physiological strain index (PSI) based on heart rate (HR) and rectal temperature (Tre) was recently suggested to evaluate exercise-heat stress in humans. The purpose of this study was to adjust PSI for rats and to evaluate this index at different levels of heat acclimation and training. The corrections of HR and Tre to modify the index for rats are as follows: PSI = 5 (Tre t - Tre 0). (41.5 - Tre 0)-1 + 5 (HRt - HR0). (550 - HR0)-1, where HRt and Tre t are simultaneous measurements taken at any time during the exposure and HR0 and Tre 0 are the initial measurements. The adjusted PSI was applied to five groups (n = 11-14 per group) of acclimated rats (control and 2, 5, 10, and 30 days) exposed for 70 min to a hot climate [40 degrees C, 20% relative humidity (RH)]. A separate database representing two groups of acclimated or trained rats was also used and involved 20 min of low-intensity exercise (O2 consumption approximately 50 ml. min-1. kg-1) at three different climates: normothermic (24 degrees C, 40% RH), hot-wet (35 degrees C, 70% RH), and hot-dry (40 degrees C, 20% RH). In normothermia, rats also performed moderate exercise (O2 consumption approximately 60 ml. min-1. kg-1). The adjusted PSI differentiated among acclimation levels and significantly discriminated among all exposures during low-intensity exercise (P < 0.05). Furthermore, this index was able to assess the individual roles played by heat acclimation and exercise training.

Predicting the risk of jaundice in full-term healthy newborns: a prospective population-based study.

OBJECTIVE: The need to recognize infants that are at high risk for developing significant jaundice is apparent in the era of routine early discharge. The aim of the present study was to prospectively determine the ability to predict severe hyperbilirubinemia in term healthy newborns (defined as total serum bilirubin of > 10.0 mg/dl at day 2, > 14.0 mg/dl at day 3, and > 17.0 mg/dl at days 4 and 5 of life). DESIGN: Prospective study of 1177 healthy term newborns. SETTING: Two university-affiliated community hospitals in Jerusalem. RESULTS: Using a multiple logistic regression analysis, neonatal jaundice was best predicted (p < 0.0001) by day 1 serum bilirubin (adjusted odds ratio of 3.1 [per mg/dl] [95% confidence limits of 2.4 to 4.1]) and by a change in serum bilirubin from the first to the second day of life (2.4 [per mg/dl] [1.9 to 3.0]). Maternal blood type 0 (2.9 [1.5 to 5.8]), age (1.1 [per year] [1.0 to 1.2]), schooling (0.8 [per year] [0.7 to 0.9]), and full breastfeeding (0.4 [0.2 to 0.9]) were also associated with jaundice (p < 0.005). Other factors considered in the regression model but not found to be significantly related to jaundice included maternal ethnic origin, smoking, hypertension, diabetes mellitus, intranatal administration of oxytocin, meperidine, anesthesia, premature rupture of the membranes, parity, newborn sex, birth weight, gestational age, presentation. Apgar scores, blood type, hematocrit, cephalohematoma, and history of jaundice in other siblings. A model for predicting neonatal jaundice based on the above factors had a sensitivity of 81.8%, a specificity of 82.9%, a false positive rate of 80.2%, and a false negative rate of 1.1%. CONCLUSION: Individual risk assessment on discharge in association with day 1 total serum bilirubin is of value in identifying infants at greater risk for neonatal jaundice.

Existing and new criteria for bioequivalence evaluation of new controlled release (CR) products of carbamazepine.

While the three classical pharmacokinetic (PK) parameters, AUC, Cmax and tmax are adequate to assess bioequivalence of immediate release (IR) formulations, they are not designed to fully characterize the pharmacokinetic (PK) performance of controlled release (CR) formulations and provide only limited insight into the function of carbamazepine (CBZ) CR products. Thus, for reliable assessment of bioequivalence in CR formulations, there is a role for the use of additional criteria (parameters). The following are the proposed new parameters: MRT (mean residence time), Cmax/AUC, plateau time or POT (the time span associated with the concentrations within 25% of Cmax), tapical (the arithmetic mean of the times associated with POT) and Capical (the arithmetic mean of the concentrations within 25% of Cmax). The above proposed parameters, were utilized in a recent PK study of new CR products of CBZ (600 mg) designed for once daily dosing. The comparative PK analysis was conducted in a three-way crossover single dose studies of three CBZ CR formulations (Teril 600 CR tablet, CBZ 600 granulate and Timonil 600 Retard tablet). Teril 600 CR was found to be bioequivalent to Timonil 600 Retard while CBZ 600 granulate was not. This conclusion was reached utilizing both the classical and the proposed new parameters. The new parameters showed that CBZ 600 granulate has similar rate of absorption as the two 600 mg CR tablets, but its extent of absorption was lower. The new parameters examined in this paper are more attractive than the single point parameters, Cmax and tmax, for assessment of rate of absorption and the flatness of the plasma concentration versus time curve. Their potential benefit and practical utility was confirmed in this study, which demonstrated bioequivalence between a new CR and an innovator CBZ (600 mg) tablet. Absorption rate assessment is important in light of concentration-related side effects associated with CBZ therapy and the impact of fluctuations and the flatness of the CBZ plasma concentration curve on the drug efficacy and tolerability.

The outcome of twin pregnancies after IVF.

It has been suggested that the high rates of prematurity, low birth weight, perinatal morbidity and mortality in in-vitro fertilization (IVF) infants are due to the increased frequency of multiple gestations in this population. The aim of our study was to test this hypothesis by comparing the outcome of IVF twins with that of twins born after spontaneously conceived pregnancies. The perinatal outcome of 40 IVF twins was compared with that of 80 control twins, matched for maternal age, parity and ethnic origin. IVF twins had a higher rate of prematurity (P = 0.03), their mean birth weight was significantly lower (P < 0.01) and the frequency of very low birth weight infants was much higher (P < 0.003). There was no neonatal mortality in the control group, whereas four IVF twins died (P < 0.01). Neonatal morbidity was significantly greater in IVF twins (P < 0.05). Oxygen therapy and mechanical ventilation were administered more frequently to IVF twins (P < 0.007 and P < 0.05). We conclude that twins conceived by IVF are at a significantly higher risk for prematurity and associated neonatal morbidity and mortality than spontaneously conceived twins.

Comparison of sodium bicarbonate, Carbicarb, and THAM during cardiopulmonary resuscitation in dogs.

OBJECTIVES: During cardiopulmonary resuscitation (CPR), elimination of CO2 was shown to be limited by low tissue perfusion, especially when very low perfusion pressures were generated. It has therefore been suggested that sodium bicarbonate (NaHCO3), by producing CO2, might aggravate the hypercarbic component of the existing acidosis and thereby worsen CPR outcome. The objectives of this study were to evaluate the effects of CO2 producing and non-CO2 producing buffers in a canine model of prolonged ventricular fibrillation followed by effective CPR. DESIGN: Prospective, randomized, controlled, blinded trial. SETTING: Experimental animal research laboratory in a university research center. SUBJECTS: Thirty-eight adult dogs, weighing 20 to 35 kg. INTERVENTIONS: Animals were prepared for study with thiopental followed by halothane, diazepam, and pancuronium. Ventricular fibrillation was electrically induced, and after 10 mins, CPR was initiated, including ventilation with an FIO2 of 1.0, manual chest compressions, administration of epinephrine (0.1 mg/kg every 5 mins), and defibrillation. A dose of buffer, equivalent to 1 mmol/kg of NaHCO3, was administered every 10 mins from start of CPR. Animals were randomized to receive either NaHCO3, Carbicarb, THAM, or 0.9% sodium chloride (NaCl). CPR was continued for up to 40 mins or until return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Buffer-treated animals had a higher resuscitability rate compared with NaCl controls. Spontaneous circulation returned earlier and at a significantly higher rate after NaHCO3 (in seven of nine dogs), and after Carbicarb (six of ten dogs) compared with NaCl controls (two of ten dogs). Spontaneous circulation was achieved twice as fast after NaHCO3 compared with NaCl (14.6 vs. 28 mins, respectively). Hydrogen ion (H+) concentration and base excess, obtained 2 mins after the first buffer dose, were the best predictors of resuscitability. Arterial and mixed venous Pco2 did not increase after NaHCO3 or Carbicarb compared with NaCl. CONCLUSIONS: Buffer therapy promotes successful resuscitation after prolonged cardiac arrest, regardless of coronary perfusion pressure. NaHCO3, and to a lesser degree, Carbicarb, are beneficial in promoting early return of spontaneous circulation. When epinephrine is used to promote tissue perfusion, there is no evidence for hypercarbic venous acidosis associated with the use of these CO2 generating buffers.

Macrosomia does not predict overweight in late adolescence in infants of diabetic mothers.

OBJECTIVE: To determine the predictive value of macrosomia for overweight later in adult life in infants of diabetic mothers. DESIGN: Data from the computerized records of the Jerusalem Perinatal Study were matched to measurements made at age 17 obtained from the military draft medical examination records. PARTICIPANTS: 10,891 infants born in Jerusalem between November 1974 and February 1976. MAIN OUTCOME MEASURES: Macrosomia based on 90th percentile birth weight for gestational age and overweight defined as the 90th percentile for body mass index at age 17. RESULTS: Diabetes was diagnosed in 87 (0.8%) of the mothers. Thirty-one (35.6%) of the infants of the diabetic mothers were macrosomic compared to 1012 (9.4%) of the siblings of nondiabetic mothers (p < 0.001). At 17 years of age 10.3% vs. 9.4% of the siblings of diabetic vs. nondiabetic mothers were overweight (p > 0.05). The rate of adolescent overweight in macrosomic vs. nonmacrosomic subjects was 12.3% vs. 9.7% (p < 0.01) in siblings of nondiabetic mothers, and 16.1% vs. 7.1% (p > 0.05) for diabetic mothers. The sensitivity and specificity, in diabetic mothers, of macrosomia for overweight at age 17 was 44.4% and 66.7%, respectively. The positive and negative predictive value of macrosomia for overweight at age 17 was 16.1% and 92.9%, respectively. CONCLUSIONS: The risk of adolescent overweight was significantly increased among macrosomic infants, although this trend did not reach statistical significance in the smaller group of infants born to diabetic mothers. Macrosomia among infants of diabetic mothers had little predictive value for overweight in late adolescence.

Exercise testing in patients with chest pain and normal coronary arteries: improving test specificity by use of a simple logistic model.

Despite an exercise electrocardiogram (ECG) positive for ischemia by established criteria, many patients referred for coronary angiography to evaluate chest pain are found to have angiographically normal coronary arteries (NCA). Exercise ECG were analyzed from 27 patients with chest pain and angiographically NCA and 28 patients with chest pain and coronary artery disease (CAD) using univariate and multivariate logistic regression analysis. We derived the following logistic model for the logit probability of CAD: 3 + SEX x 4 - METs x 0.7 + STDV5 x 0.8, where SEX = 0 for female and SEX = 1 for male, METs = maximal estimated work load (metabolic equivalents) and STDV5 = horizontal or downsloping ST depression (mm) in V5. A logit probability > or = 0 identified CAD with a sensitivity of 79% and a specificity of 89%. The model correctly identified 28/36 (78%) patients with CAD, and 7/10 (70%) patients with NCA (correct diagnosis 76%; p < 0.02) in a separate random group of 46 unselected patients with positive exercise tests undergoing diagnostic coronary angiography.