Wheat gluten structure and (non-)covalent network formation during deep-fat frying.

The aim of this work was to investigate wheat gluten protein network structure throughout the deep-frying process and evaluate its contribution to frying-induced micro- and macrostructure development. Gluten polymerization, gluten-water interactions, and molecular mobility were assessed as a function of the deep-frying time (0 - 180 s) for gluten-water model systems of differing hydration levels (40 - 60 % moisture content). Results showed that gluten protein extractability decreased considerably upon deep frying (5 s) mainly due to glutenin polymerization by disulfide covalent cross-linking. Stronger gliadin and glutenin protein-protein interactions were attributed to the formation of covalent linkages and evaporation of water interacting with protein chains. Longer deep-frying (> 60 s) resulted in progressively lower protein extractabilities, mainly due to the loss in gliadin protein extractability, which was associated with gliadin co-polymerization with glutenin by thiol-disulfide exchange reactions. The mobility of gluten polymers was substantially reduced during deep-frying (based on the lower T2 relaxation time of the proton fraction representing the non-exchanging protons of gluten) and gluten proteins gradually transitioned from the rubbery to the glassy state (based on the increased area of said protons). The sample volume during deep-frying was strongly correlated to the reduced protein extractability (r = -0.792, p < 0.001) and T2 relaxation time of non-exchanging protons of gluten proteins (r = -0.866, p < 0.001) thus demonstrating that the extent of gluten structural expansion as a result of deep-frying is dictated both by the polymerization of proteins and the reduction in their molecular mobility.

A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer.

BACKGROUND: The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach. PATIENTS AND METHODS: Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out. RESULTS: Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination. CONCLUSIONS: These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary end point was not met. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT01285557.

Pattern of hospital admission and outcome in Parkinson’s disease: A study from Punjab, India

Background: The hospitalization rates of patients with Parkinson’s disease (PD) are 1.45 times higher than for age matched controls. We studied the causes for admission, hospital course and outcomes in PD population so that preventive measures could be developed. Methods: We prospectively studied patients with the diagnosis of PD admitted to a tertiary care hospital in Ludhiana, India from January, 2012 to December, 2014. Etiology for hospitalization was determined and the patients were divided into two groups, admission due to causes related to PD or not associated with PD. The PD related admissions were further categorized into Group I: directly disease related causes and Group II: indirectly disease related causes. The primary outcome was mortality. The secondary outcome measures were duration of hospitalization, requirement for ICU, need for mechanical ventilation and complications. Results: There were 146 patients of PD out of 25,326 hospital admissions. Forty two patients (28.7%) had direct cause, 73(50%) had indirect cause and 31(21.2%) were non-PD related admissions. The mean age was 68.5+9.9 years, 97males (66.7%). There were 16(10.9%) deaths. The commonest cause of admission was infections and encephalopathy. The indirect PD related admission had significantly higher age (p= 0.0014), increased risk of ICU admission (p=0.011), need for mechanical ventilation (p < 0.005) and longer duration of hospital stay (p=0.0001) as compared to group I. Also there was a six fold increased risk of death in this group (p 0.034). Conclusion: As disease progresses, the indirect reasons for admission becomes more troublesome than the initial motor complaints.

Comparision of clonidine and dexmedetomidine for attenuation of laryngoscopy and intubation response - A randomized controlled trial.

BACKGROUND: Clonidine and dexmedetomidine are alpha-2 agonists with beneficial effect on the hemodynamic response to laryngoscopy and intubation. The present study was designed to evaluate and compare the efficacy of intravenous clonidine 1 µg/kg, and dexmedetomidine in doses of 0.5 µg/kg and 1 µg/kg, for blunting the hemodynamic changes during laryngoscopy and intubation. METHOD: Adult patients of ASA physical grade I/II scheduled for surgery under general anaesthesia with endotracheal tube were randomly divided into three groups using a computer generated random number table, each group receiving one of the following drugs prior to induction of anaesthesia, by a blinded anaesthesiologist in a volume of 100 mL infused intravenously over 20 minutes: clonidine 1 µg/kg, or dexmedetomidine 0.5 µg/kg, or dexmedetomidine 1 µg/kg. General anaesthesia was induced using standard technique and intubations performed by same anaesthesiologist. Heart rate and mean blood pressure were recorded in pre-operative room (baseline) and again at 1 minute, 3 minutes, 5 minutes and 10 minutes after intubation. An increase in heart rate and/or mean blood pressure by >20% above baseline values during observation period was taken to indicate a positive intubation response. RESULTS: The incidence of intubation response was similar in all three groups (P>.05). The number of patients developing hypotension was significantly higher in group receiving dexmedetomidine1µg/kg group (P<.005) as compared to other two groups. Both the groups receiving dexmedetomidine had higher number of patients developing bradycardia as compared to patients receiving clonidine. DISCUSSION & CONCLUSION: Dexmedetomidine 0.5 µg/kg, 1 µg/kg and clonidine 1 µg/kg attenuate the laryngoscopy and intubation response but Clonidine 1 µg/kg was associated with lesser side effects.

Anesthetic management for bronchoscopy and debulking of obstructing intratracheal tumor.

Primary tracheal tumors comprise a rare group of benign and malignant tumors. Bronchoscopy is required for diagnosis and staging of tracheal neoplasms as well as debulking of the tumor. The management of anesthesia for rigid bronchoscopy in a patient with tracheal neoplasm presents with many challenges to the anesthetist. We present anesthetic management of an 18-year-old female who presented with orthopnea. Computed tomography scan of the thorax revealed a polypoidal lesion in the trachea proximal to carina and consolidation in the right middle lobe. The patient was scheduled for rigid bronchoscopy and debulking of the tumor. Case was successfully managed by providing positive pressure ventilation and oxygenation during rigid bronchoscopy using manual ventilation through the side port of the rigid bronchoscope. The procedure was uneventful, and patient improved symptomatically in the immediate postoperative period. The successful management of this case demonstrates the airway management in a patient with tracheal tumor for rigid bronchoscopy.

Shorter bevacizumab infusions do not increase the incidence of proteinuria and hypertension.

BACKGROUND: A previous study has shown that shorter bevacizumab infusions (0.5 mg/kg/min) can be safely administered without increasing the risk of infusion-related hypersensitivity reactions (HSRs). However, the risk of proteinuria and hypertension in patients receiving shorter infusions of bevacizumab is undetermined. PATIENTS AND METHODS: This was a multicenter, prospective, observational study in patients receiving <10 mg/kg of bevacizumab infused over 0.5 mg/kg/min. Patients were observed until discontinuation of bevacizumab for progression of cancer or toxicity. The incidence of hypertension and proteinuria was compared with a prior cohort of patients who had received standard duration infusions of bevacizumab. RESULTS: Sixty-three patients received a total of 392 doses of shorter bevacizumab infusions. Nineteen (30.2%) patients experienced proteinuria while receiving bevacizumab. Out of 19 patients, 13 had grade 1 and 6 had grade 2 proteinuria. None of the patients experienced grade 3 or 4 proteinuria. Hypertension was reported in 32 (50.8%) patients receiving bevacizumab. Twelve (19%) patients developed grade 3 or greater hypertension on bevacizumab. The incidence of proteinuria and hypertension was 38.3% and 56.6%, respectively, in patients (N = 120, 1347 infusions) receiving standard duration infusions of bevacizumab. CONCLUSIONS: Shorter bevacizumab infusions (0.5 mg/kg/min) do not increase the risk of proteinuria and hypertension.

Transglutaminase-2 regulation by arecoline in gingival fibroblasts.

Transglutaminase-2 (TGM-2) stabilizes extracellular matrix (ECM) proteins by cross-linking and has been implicated in several fibrotic disorders. Arecoline present in betel quid has been proposed as one of the causative factors for oral submucous fibrosis (OSMF). Hence, we hypothesize that arecoline may regulate TGM-2 and may have a role in the pathogenesis of OSMF. The expression of TGM-2 was studied in OSMF tissues by real-time RT-PCR analysis, and significant overexpression was observed in most OSMF tissues (P=0.0112) compared with normal tissues. Arecoline induced TGM-2 mRNA and protein expression as well as TGM-2 activity in human gingival fibroblast cells. The addition of methocramine hemihydrate (M-2 muscarinic acetylcholine receptor selective antagonist) or 8'-bromo-cAMP abolished arecoline-mediated TGM-2 induction, suggesting a role for M-2 muscarinic acid receptor and a repressor role for cAMP. Our study provides evidence for TGM-2 overexpression in OSMF and its regulation by arecoline in oral fibroblasts.

Electronic and structural properties of group III nitrides and phosphides using density functional theory.

In recent years group III nitrides have gained recognition as being the most important materials for optoelectronics and electronics applications. The zinc-blende modification of GaN and AlN is receiving much attention over their wurtzite structure. Our present work deals with the detailed ab initio calculations of group III nitrides and phosphides in the zinc-blende phase. The plane wave pseudopotential approach is used to study the different properties of the material based on the concept of density functional theory (DFT). The converged plane wave cut-off energy (E(cut)) is used to set the number of plane waves, which varies from material to material. The calculated energy bandgaps are based on our theoretical equilibrium lattice constants. Our reported energy bandgap for InN (0.86 eV) is in good agreement with the recently reported experimental result (>0.7 eV and<1.0 eV).

Comparison of CT- or ultrasound-guided drainage with concomitant intravenous antibiotics vs. intravenous antibiotics alone in the management of tubo-ovarian abscesses.

OBJECTIVE: The purpose of this study was to compare the outcome of treatment of tubo-ovarian abscesses by imaging-guided drainage and antibiotics vs. intravenous antibiotics alone. METHODS: A retrospective chart review of all patients hospitalized with a diagnosis of tubo-ovarian abscess was performed. Patients were categorized into two groups. The first group consisted of subjects treated with intravenous antibiotics alone. Patients in the second group had primary image-guided drainage with concomitant intravenous antibiotics. Treatment failures in the primary antibiotics group underwent salvage drainage when feasible. The primary outcome of interest was complete response. Secondary outcomes included need for additional treatment, duration of resolution of fever, total length of hospital stay, and complication rates. We also evaluated the effectiveness of secondary drainage in patients who failed primary antibiotic therapy alone. RESULTS: A total of 58 patients were included in the study. Fifty patients were treated primarily with intravenous antibiotics; eight patients had primary drainage, which was guided by ultrasound in all cases. Complete response was noted in 29 (58%) patients treated with antibiotics alone. All eight (100%) patients in the primary drainage group responded to treatment. Of the 21 treatment failures with primary antibiotics, two underwent surgery and 19 (90.5%) had salvage drainage with either ultrasound or computed tomographic guidance; 18 of 19 salvage drainages led to complete recovery. Subjects in the primary drainage group required shorter hospital stays and showed more rapid resolution of fever. No significant morbidity was noted as a consequence of drainage procedures. A higher failure rate for secondary drainage was noted in older patients, those with larger tubo-ovarian abscesses, and those with a history of pelvic inflammatory disease. CONCLUSION: Drainage of tubo-ovarian abscesses with concomitant intravenous antibiotics is an effective and safe treatment for the primary or secondary treatment of tubo-ovarian abscesses.

The prevalence of hepatitis C virus antibodies among the voluntary blood donors of New Delhi, India.

Infection with hepatitis C virus (HCV) is a major cause of transfusion-associated hepatitis, cirrhosis and hepatocellular carcinoma. The present study was conducted with an objective to evaluate the prevalence of anti-HCV antibody in New Delhi, India using a large number of healthy voluntary blood donors. A total of 15,898 healthy voluntary blood donors were subjected to anti-HCV testing (using a commercially available third generation anti-HCV ELISA kit) and 249 were found to be reactive for anti-HCV antibody, yielding an overall prevalence of 1.57%. No significant difference was found between the HCV positivity rate of male (1.57%; 238/15,152) vs. female (1.47%; 11/746) donors, family (1.58%; 213/13,521) vs. altruistic (1.51%; 36/2377) donors and first-time (1.55%; 180/11,605) vs. repeat (1.61%; 69/4293) donors. The age distribution of anti-HCV reactivity showed a maximum prevalence rate of 1.8% in the age group of 20-29 years. In addition, there was a clear trend of decreasing positivity for anti-HCV with increasing age and this trend was statistically significant. The results of the present study show that the prevalence of anti-HCV antibodies in the healthy voluntary blood donors of New Delhi, India is considerably higher than the reported seroprevalence of HCV in majority of the industrialized nations and this represents a large reservoir of infection capable of inflicting significant disease burden on the society. In addition, donors of New Delhi, India showed a trend of decreasing seroprevalence with increasing age, possibly implying a higher exposure rate to HCV in younger subjects.

Regulation of beta-catenin function by the IkappaB kinases.

Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway. Here we present evidence that these kinases are also important in the regulation of beta-catenin function. IKKalpha- and IKKbeta-deficient mouse embryo fibroblasts exhibited different patterns of beta-catenin cellular localization. IKKbeta decreases beta-catenin-dependent transcriptional activation, while IKKalpha increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta interact with and phosphorylate beta-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of beta-catenin with IKKalpha and IKKbeta may in part be responsible for regulating beta-catenin protein levels and cellular localization and integrating signaling events between the NF-kappaB and Wingless pathways.

IKKgamma /NEMO facilitates the recruitment of the IkappaB proteins into the IkappaB kinase complex.

IKKgamma/NEMO is an essential regulatory component of the IkappaB kinase complex that is required for NF-kappaB activation in response to various stimuli including tumor necrosis factor-alpha and interleukin-1beta. To investigate the mechanism by which IKKgamma/NEMO regulates the IKK complex, we examined the ability of IKKgamma/NEMO to recruit the IkappaB proteins into this complex. IKKgamma/NEMO binding to wild-type, but not to a kinase-deficient IKKbeta protein, facilitated the association of IkappaBalpha and IkappaBbeta with the high molecular weight IKK complex. Following tumor necrosis factor-alpha treatment of HeLa cells, the majority of the phosphorylated form of endogenous IkappaBalpha was associated with the high molecular weight IKK complex in HeLa cells and parental mouse embryo fibroblasts but not in IKKgamma/NEMO-deficient cells. Finally, we demonstrate that IKKgamma/NEMO facilitates the association of the IkappaB proteins and IKKbeta and leads to increases in IKKbeta kinase activity. These results suggest that an important function of IKKgamma/NEMO is to facilitate the association of both IKKbeta and IkappaB in the high molecular weight IKK complex to increase IkappaB phosphorylation.

Antenatal steroids and neonatal periventricular leukomalacia.

OBJECTIVE: To evaluate the effect of antenatal steroid treatment on the development of neonatal periventricular leukomalacia. METHODS: This retrospective cohort study included 1161 neonates with gestational ages of 24-34 weeks and birth weights of 500-1750 g, divided into two groups on the basis of antenatal steroid treatment. Neonatal neurosonograms were done on days 3 and 7 of life and labeled normal or abnormal. The abnormal outcomes evaluated were periventricular leukomalacia or intraventricular hemorrhage, periventricular leukomalacia with intraventricular hemorrhage, and isolated periventricular leukomalacia. The group treated with antenatal steroids was compared with the untreated group for these outcomes. RESULTS: Antenatal steroids were associated with significantly less periventricular leukomalacia or intraventricular hemorrhage (23% versus 31%, P =.005), periventricular leukomalacia with intraventricular hemorrhage (5% versus 11%, P =.001), and isolated periventricular leukomalacia (3% versus 7%, P =.009). Logistic regression analysis of antenatal steroid treatment, controlling for confounding maternal and neonatal characteristics, indicated that neonates treated with antenatal steroids had a 56% lower likelihood of periventricular leukomalacia with intraventricular hemorrhage (adjusted odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77) and a 58% lower likelihood of isolated periventricular leukomalacia (adjusted OR 0.42, 95% CI 0.20, 0.88). CONCLUSION: Antenatal steroid treatment was associated with over 50% reduction in the incidence of periventricular leukomalacia in preterm neonates. Increased use of antenatal steroid therapy might improve long-term neonatal neurologic outcomes.

Acute renal failure complicating rifampicin therapy.

BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced acute renal failure (ARF) have been published. Covic et al described 60 consecutive cases of rifampicin-induced ARF during a period of eight years (1987-1995) from Iasi Dialysis Centre, Romania. The systenic data on this condition are not available, in view of the anecdotal nature of the observation from our country. OBJECTIVE: The aims of study were to analyze clinical features, course and outcome of ARF complicating rifampicin therapy at our centre. METHODS: We retrospectively studied prevalence, clinical presentations and renal histology and outcome of 11 cases (eight males, three females, aged 42-72 years) who were referred to Nephrology Unit of University Hospital, Varanasi for acute renal failure following retreatment with rifampicin between period of 1994-1999. RESULTS: The gastrointestinal symptoms (abdominal pain, nausea and vomiting) and 'flu like' (fever, weakness and body ache) syndrome were the most frequent presenting features. The clinical signs of intravascular hemolysis were observed in four cases. The commonest laboratory findings included: Anaemia (7), leukocytosis (5), thrombocytopenia (3) and toxic hepatitis in (2) patients. Toxic hepatitis, hemolysis and ARF was seen in one patient in combination. The typical clinical features of allergic interstitial nephritis and acute tubular necrosis were seen in six and two patients respectively. Renal biopsy in three cases revealed; crescentic GN (1) and ATN in (2) patients. Acute renal failure complicating rifampicin accounted for 1.8% (11/607) of all ARF cases hospitalized in our centre during the study period. Renal function returned to normal in nine cases and one patient died on account of hepatic failure (toxic hepatitis). The patients with crescentic GN remained anuric and became dialysis dependent. Thus, clinical course of rifampicin induced ARF was favourable; with only one mortality, compared to a 18% mortality rate among all ARF patients. CONCLUSION: Acute renal failure complicating rifampicin therapy is not an uncommon condition, and typically occurs after reintroduction of rifampicin. The renal prognosis is usually favourable. Intermittent or interrupted therapy appears to be a significant risk factor for the development of acute renal failure.

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.

OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. METHODS: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. RESULTS: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with 16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.

Reduced risk of low weight births among indigent women receiving care from nurse-midwives.

STUDY OBJECTIVE: To examine the effect of a comprehensive prenatal and delivery programme administered by nurse-midwives on the risk of low weight births among indigent women. STUDY DESIGN: Historical prospective study. Birth outcomes among the cohort were compared with all county births during the same period, adjusting for maternal age and race. Results are expressed as relative risks with 95% confidence intervals. SETTING: An enhanced Medicaid funded pre-natal programme administered by nurse-midwives from 1992 to 1994 in Westchester County, New York. PARTICIPANTS: Indigent mothers (n = 1443), between the ages of 15 and 44, who were residents of Westchester County and indicated having Medicaid or no health care coverage. RESULTS: There were 1474 live births among cohort mothers. Mean (SD) gestational age was 39.4 (1.9) weeks. Less than 6% of births occurred before 37 weeks gestation. The mean birth weight of cohort infants was 3365.6 (518.6) g. Only 4.1% of the cohort births were less than 2500 g. Compared with all county births, the cohort showed a 41% reduction in the risk of low weight births (RRlbw = 0.59, 95% CI: 0.46 to 0.73, p < .001) and a 56% reduction when compared with county Medicaid births only (RR = 0.44, 95% CI: 0.34 to 0.57, p < .005) adjusting for maternal age and race. Larger reductions were found for very low weight births. CONCLUSIONS: Mothers need not be considered at high risk for adverse pregnancy outcomes based on their socioeconomic status alone. Moreover, a comprehensive prenatal programme administered by nurse-midwives may promote a reduction in adverse pregnancy outcomes among indigent mothers.

Effectiveness of multidose antenatal steroids.

OBJECTIVE: To compare effectiveness between single and multiple courses of antenatal steroids in preterm births and determine adverse effects attributable to multiple courses. METHODS: We studied retrospectively the neonatal outcomes of infants who weighed 1750 g or less at birth between January 1990 and December 1997. Infants exposed to a single course were compared with those exposed to two or more courses of antenatal steroids, with respect to various perinatal outcome variables. RESULTS: Ninety-three neonates were exposed to two or more courses of antenatal steroids and 261 neonates had been given single courses. The mean (+/- standard deviation) gestational age (29.6 +/- 2.8 weeks compared with 28.7 +/- 2.7 weeks; P = .007) and birth weight (1252 +/- 321 g compared with 1159 +/- 339 g; P = .013) were significantly higher among neonates exposed to multiple courses. There were no significant differences between groups in perinatal outcomes; however, those exposed to multiple courses had a significantly lower rate of respiratory distress syndrome (RDS) (17 [18%] compared with 107 [41%]; P < or = .001) and surfactant use (40 [43%] compared with 149 [57%]; P = .02). Adjusting for confounding variables, multiple courses of steroids were significantly associated with a 65% reduction in the incidence of RDS (odds ratio 0.35; 95% confidence interval = 0.18, 0.70; P = .003). CONCLUSION: Compared with single courses, multiple courses of antenatal steroids reduced significantly the incidence of RDS with no apparent increase in neonatal sepsis or disturbances in fetal growth.

A pilot trial of GM-CSF and MDX-H210 in patients with erbB-2-positive advanced malignancies.

MDX-H210 is a chemically, cross-linked, half-humanized bispecific antibody composed of F(ab') fragment from monoclonal antibody (mAb) H22 that binds to the high-affinity receptor Fc gamma RI and F(ab') of mAb 520C9 that recognizes the erbB-2 (HER2/neu) oncoprotein. In a previous trial, the murine bispecific, MDX-210 at a dose of 7 mg/m2, was well tolerated and activated monocytes and macrophages in vivo in doses as low as 0.35 mg/m2. In our multidose trial, granulocyte-macrophage colony-stimulating factor, which increases and activates potential effector cells, was given on days 1-4 at 250 micrograms/m2 s.c. and MDX-H210 was given on day 4 weekly for 4 consecutive weeks. Thirteen patients were treated at dose levels of 1, 3.5, 7, 10, 15, and 20 mg/m2 without dose-limiting toxicity. Fever, chills, and rigors occurred during and up to 2 h postinfusion and correlated with the time to peak levels of tumor necrosis factor-alpha (median 88.2 pg/ml; range 15.6-887 pg/ml) and interleukin-6 (median 371 pg/ml; range 175-2,149 pg/ml). By the fourth consecutive week of treatment the side effects and cytokine levels decreased significantly. Human antibispecific antibody (HABA) levels were increased by 200- to 500-fold above pretreatment levels in 5 of 11 evaluable patients after 3 weeks of treatment. The monocyte and granulocyte population increased on days 4 and 11 (median 44%; range 18-68% and 42%; 19-71%), respectively, for monocytes and (60%; 43-75% and 74%; 54-82%) on days 4 and 11 for granulocytes. There was a significant decrease in the monocyte populations immediately after MDX-H210 administration (median decrease 73%; range 42-94%) and (52%; 12-72%) on days 4 and 11, respectively. Ten patients completed 4 weeks of treatment. One patient had a 48% reduction in an index lesions and six patients had stable disease at the time of evaluation. Three patients progressed before the fourth week. The therapy was generally well tolerated with toxicity, primarily, limited to the days of treatment.