Is neo-adjuvant chemotherapy a better option for management of cervical cancer patients of rural India?

OBJECTIVES: To explore alternate modality of treatment in patients of advanced cancer cervix by neo-adjuvant chemotherapy (NACT) followed by External Beam Radiotherapy (ERT) and Brachytherapy (BT). Short- (6 months) and long- (12 months) term follow-up data from these patients were compared with the retrospective data from an urban cancer centre, where standard protocol of concurrent chemo-radiotherapy is practiced. MATERIALS AND METHODS: Two hundred patients of advanced cervical cancer, treated at our rural cancer centre between January 2007 and December 2007, were included in the study arm (Group A). These patients received three cycles of neo-adjuvant chemotherapy with Cisplatin, Bleomycin, and Vincristine before External-Beam Radiotherapy (EBT) followed by brachytherapy. Patients in the control arm (Group B) of an urban cancer centre, received EBT with weekly concomitant Cisplatin, followed by brachytherapy. Short- (6 months) and long- (12 months) term follow-up data from our patients were compared with the retrospective data from the urban cancer centre. RESULTS AND ANALYSIS: Complete response rate was comparatively higher among patients of Group A, also correspondingly proportion of patients showing progressive disease and stable disease was lower among them. Local treatment failure was 87.5% among patients from Group A and 94.4% in Group B patients. Concomitant chemoradiation (CRT) was associated with more GI toxicities. CONCLUSION: Our result suggests NACT arm is as effective as CRT arm in respect of complete response with less pelvic failure and G.I toxicities. Further follow-up data are needed before arriving at a definite conclusion.

Distinguishing thermodynamic and kinetic views of the preferential hydration of protein surfaces.

Motivated by a quasi-chemical view of protein hydration, we define specific hydration sites on the surface of globular proteins in terms of the local water density at each site relative to bulk water density. The corresponding kinetic definition invokes the average residence time for a water molecule at each site and the average time that site remains unoccupied. Bound waters are identified by high site occupancies using either definition. In agreement with previous molecular dynamics simulation studies, we find only a weak correlation between local water densities and water residence times for hydration sites on the surface of two globular proteins, lysozyme and staphylococcal nuclease. However, a strong correlation is obtained when both the average residence and vacancy times are appropriately taken into account. In addition, two distinct kinetic regimes are observed for hydration sites with high occupancies: long residence times relative to vacancy times for a single water molecule, and short residence times with high turnover involving multiple water molecules. We also correlate water dynamics, characterized by average occupancy and vacancy times, with local heterogeneities in surface charge and surface roughness, and show that both features are necessary to obtain sites corresponding to kinetically bound waters.

Balancing local order and long-ranged interactions in the molecular theory of liquid water.

A molecular theory of liquid water is identified and studied on the basis of computer simulation of the TIP3P model of liquid water. This theory would be exact for models of liquid water in which the intermolecular interactions vanish outside a finite spatial range, and therefore provides a precise analysis tool for investigating the effects of longer-ranged intermolecular interactions. We show how local order can be introduced through quasichemical theory. Long-ranged interactions are characterized generally by a conditional distribution of binding energies, and this formulation is interpreted as a regularization of the primitive statistical thermodynamic problem. These binding-energy distributions for liquid water are observed to be unimodal. The Gaussian approximation proposed is remarkably successful in predicting the Gibbs free energy and the molar entropy of liquid water, as judged by comparison with numerically exact results. The remaining discrepancies are subtle quantitative problems that do have significant consequences for the thermodynamic properties that distinguish water from many other liquids. The basic subtlety of liquid water is found then in the competition of several effects which must be quantitatively balanced for realistic results.

Late-onset left diaphragmatic hernia after group B streptococcal sepsis: An unusual presentation.

There are several reported cases of late presentations of right diaphragmatic hernia with early- as well as late-onset group B streptococcal (GBS) infections. The authors describe the first case of late-onset left diaphragmatic hernia with late onset GBS infection in a preterm infant. The diagnosis was prompted by a dramatic clinical deterioration during the recovery phase of GBS sepsis.

Ovarian cyst in a premature infant treated with spironolactone.

We describe the late occurrence of an ovarian cyst in a premature infant, the second of a set of monochorionic diamnionic twins, during treatment with spironolactone. Spironolactone is commonly used in the management of neonatal chronic lung disease in combination with other diuretics because of its potassium-sparing effect. It has progestational activity and has been reported to cause gynecomastia. It is used widely for its antiandrogenic properties in the treatment of female hirsutism and hyperandrogenism and it has a role in the management of familial male-limited precocious puberty. However, the estrogenic influence induced during therapy may significantly alter the hormonal milieu in newborn females, resulting in the formation of ovarian cysts. Simple ovarian lesions <5 cm merit close ultrasonographic surveillance for resolution while larger complex masses may warrant surgical intervention.

Anaerobic bioventing of unsaturated zone contaminated with DDT and DNT.

Initial degradation of highly chlorinated compounds and nitroaromatic compounds found in munition waste streams is accelerated under anaerobic conditions followed by aerobic treatment of the degradation products. The establishment of anaerobic environment in a vadose zone can be accomplished by feeding appropriate anaerobic gas mixture, i.e., "anaerobic bioventing". The gas mixture contains an electron donor for the reduction of these compounds. Lab scale study was conducted to evaluate potential of anaerobic bioventing for the treatment of an unsaturated zone contaminated with 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and 2,4-dinitrotoluene (DNT). Hydrogen was used as the electron donor. Using the soil columns innoculate with anaerobic microorganisms, it was observed that by feeding a gas mixture of 1% hydrogen, 1% carbon dioxide and nitrogen, methanogenic conditions were established and DDT was reductively dechlorinated. 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) accumulated as the intermediate product. The half life of DDT was calculated to be 8.5 months. DNT completely disappeared after six months of operation and no intermediates could be detected.

Achondroplasia-hypochondroplasia complex in a newborn infant.

We describe the case of an 8-month-old girl with achondroplasia-hypochondroplasia complex. The diagnosis was suggested antenatally when obstetrical ultrasonography at 27 weeks of gestation showed short limbs, small chest, and macrocephaly. The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. Neither had had genetic counseling or molecular testing prior to the pregnancy. Antenatal ultrasound study at 29 weeks of gestation showed a large head, very short limbs, and a small chest; the findings were more severe than in achondroplasia or hypochondroplasia alone. The patient was born by cesarean section at 37 weeks of gestation and had rhizomelic shortness of limbs with excess skin creases, large head, and small chest, diagnostic of achondroplasia. Radiographs showed shortness of the long bones and flaring of the metaphyses. She had mild hypoplasia of lungs. Molecular testing showed both the G1138A and the C1620G mutations in FGFR3, confirming the diagnosis of achondroplasia-hypochondroplasia complex. At 8 months, she has disproportionate shortness of the long bones and a large head with frontal bossing and a depressed nasal bridge. Her chest remains small, and she is on home oxygen at times of respiratory stress. She has a large gibbus. She is delayed in her motor development and has significant head lag. To our knowledge, there is only one previously published report of achondroplasia-hypochondroplasia complex.

Surrogate burns in deactivation furnace system.

The deactivation furnace system at the Deseret Chemical Depot in Utah is designed for processing explosive components from munitions containing nerve and mustard agents. The system was installed during the period of 1989 through 1993. The Utah Division of Solid and Hazardous Waste (UDSHW) required that trial burns be conducted using surrogate chemicals prior to introducing chemical agents into the system. The selected surrogate chemicals were monochlorobenzene and hexachloroethane based on the criteria established by the UDSHW. Three surrogate runs were conducted in October, 1995. The gaseous emissions and liquid and solid effluents were sampled and analyzed using approved EPA methods. The trial burns demonstrated the desirable destruction and removal efficiency for the selected surrogate chemicals. The pollution abatement system demonstrated the desired scrubbing efficiency for acid gases generated during incineration of chlorinated surrogate chemicals. The particulate removal efficiency during the trial burns was also considerably higher than required by regulations. After comprehensive review of the performance of the deactivation furnace system during the surrogate trial burns, UDSHW approved introduction of GB nerve agent into the system to prepare it for agent trial burns.

Growth and body composition of preterm infants: influence of nutrient fortification of mother's milk in hospital and breastfeeding post-hospital discharge.

We examined the influence of multi-nutrient fortification of mother's milk (MM + MNF) compared to supplementation with calcium and phosphorus (MM + CaGP) alone in hospital (in a randomized trial), and of breastfeeding (post-MM) compared to formula feeding (post-FF ) after hospital discharge with a descriptive analysis of growth and body composition to 1 y corrected age in preterm infants. Anthropometry, nutrient intakes and whole body bone mineral content, lean and fat mass were determined at four time points in the first year after term corrected age. Body composition was determined with dual energy X-ray absorptiometry. MM + MNF compared to MM + CaGP for preterm infants in the early neonatal period did not appear to influence growth or body composition in the first year. Growth in post-MM and post-FF groups was within the normal range of growth references derived from term infants fed mother's milk. Post-MM infants had lower whole body bone mineral content (132.3 +/- 10.4 g) at 6 months corrected age when compared to post-FF infants (159.4 +/- 14.1 g) and greater percent fat mass to 12 months corrected age. These differences may result from the lower calcium, phosphorus and protein intakes in post-MM compared to post-FF infants. Our findings demonstrate that dietary practices after hospital discharge likely have a greater impact on body composition in prematurely born infants than dietary practices in hospital. Whether the observed differences in body composition between breastfed and formula-fed preterm infants have any long-term consequences requires further investigation.

Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial.

Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone.

Longitudinal assessment of growth and bone mineral accretion in prematurely born infants treated for chronic lung disease with dexamethasone.

The objective of this study in premature infants was to assess the relationship between dexamethasone, growth and bone mineral accretion. Nine appropriate size for gestational age premature infants treated for chronic lung disease with tapering doses of dexamethasone (0.5-0.1 mg/kg/day over 37 +/- 7 days) were individually matched to a comparison infant by sex, gestational age, birth-weight, and type of feed. Infant growth and bone mineral accretion were measured at equivalent gestational ages from recruitment until 6 months corrected age. During hospitalization, mean rate of weight, length and head circumference growth and bone mineral accretion in the distal radius were significantly lower in the dexamethasone-treated infants in spite of similar nutrient intakes. Dexamethasone infants had significantly lower plasma phosphorus, and urinary calcium, pyridinoline and N-telopeptide excretion. Dexamethasone affected absolute length, but not weight, throughout the study. No significant differences were observed in body composition or absolute radial and whole body bone mineral content. The results indicate that dexamethasone therapy compromises growth and bone mineral accretion in small premature infants. 'Catch-up' linear growth was not evident at 6 months of age and reflects the importance of early nutrition interventions.

A multi-element isotopic tracer assessment of true fractional absorption of minerals from formula with additives of calcium, phosphorus, zinc, copper and iron in young piglets.

True fractional absorption of minerals was measured to determine the bioavailability of Zn, Fe, Mn and Se from liquid formulas fortified with stepwise additions of Ca and P (as Ca glycerophosphate and carbonate, Ca*P), and Zn, Cu and Fe (as sulfate salts). Growth, deposition of tracers in organs and bone mineral content of femurs as assessed by single photon absorptiometry were measured. Four-day-old piglets (n = 36) were randomly assigned to groups fed a basal diet or additions of Ca*P (Ca = 25, P = 18 g/kg dry diet), Ca*P+Zn (Zn = 0.04 g/kg), Ca*P+Zn+Cu (Cu = 0.007 g/kg) or Ca*P+Zn+Cu+Fe (Fe = 0.008 g/kg). Oral and intravenous administration of extrinsic isotopes of 59Fe, 54Mn, 65Zn, 75Se and 47Ca was followed by fecal monitoring for 15 d and true absorption calculated after accounting for endogenous excretion. Addition of Ca*P+Zn reduced Zn absorption (P < 0.05) and Ca*P+Zn+Cu reduced Fe absorption (P < 0.01), but Mn and Se absorptions were not altered. Uptake of only Zn tracer into heart was significantly different (P < 0.05) among diet groups. Weight gain and linear growth were similar in all groups. Addition of Ca*P produced higher bone mineral density, but its effect on Zn absorption warrants further investigation.

Thrombin inhibition is impaired in plasma of sick neonates.

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

ENL. quantification - a proposal

The authors propose a method of quantification of type II reactions, which will give to the clinicians and research workers common parameters for evaluatin the severity of a reactions as well as the criteria dor assessing the efficacy of a given drug.

Mineral excretion in premature infants receiving various diuretic therapies.

The association of various diuretic therapies with the renal handling of minerals, important factors in the development of nephrocalcinosis and osteopenia, was studied in low birth weight infants. Twenty-four-hour urine specimens (n = 65) were collected from 30 patients who were treated with (1) furosemide with or without spironolactone and hydrochlorothiazide (2) spironolactone with hydrochlorothiazide, (3) spironolactone alone, or (4) no diuretic (control; i.e., after diuretic). Hypercalciuria (urinary calcium greater than or equal to 0.15 mmol/kg/day) was observed in all but the control group. Covariate analysis demonstrated a significant effect of sodium, calcium, and vitamin D intakes (p less than 0.01) and sodium excretion (p less than 0.05) on urinary calcium excretion. Treatment with any of these diuretics in neonates may be associated with abnormal renal losses of calcium, sodium, chloride, and potassium. From a nutritional perspective, neonates requiring long-term diuretic therapy thereby require special consideration, including monitoring of mineral excretion and renal ultrasonography.