Search PubMed⌕ Search

Biomedical subjects

J Philip

Publications and source records attributed to J Philip.

At least 55 records · Page 3Linked to original sources

InJection adaptable fine ionization source ('JaFIS') for continuous flow nano-electrospray.

Nanoelectrospray ('nanoES') tandem mass spectrometry of complex peptide mixtures has become a certified, mostly reliable technique for the identification of proteins. The typical low flow rates of nanoES, the extended analysis times for small samples, high ion transmission and its overall ease-of-use provide important practical advantages for polypeptide covalent microanalysis. We have constructed a modified nanoES ion source that is highly durable and user-friendly, and potentially allows for full auto-sampling operation. The inJection adaptable Fine Ionization Source ('JaFIS') can be operated at flow rates of 10-100 nL per minute and with sensitivities in the 25 femtomoles peptide per microliter range. The ion spray needles usually last for days, allowing for standards and multiple samples to be analyzed consecutively under similar conditions. In this configuration, quality controlled needles can also be saved and reused, providing for more consistent and reproducible day-to-day operating conditions, JaFIS-ES also permits sample recovery should any failure occur during analysis.

Databases, Factual↗

Concurrent validity of the modified Edmonton Symptom Assessment System with the Rotterdam Symptom Checklist and the Brief Pain Inventory.

As part of a longitudinal prospective study we sought a self-completed instrument of symptom assessment suitable for a population of cancer patients who were receiving palliative therapy. The modified Edmonton Symptom Assessment System (ESAS) is such an instrument, but it required validation for this population. This study represents a validation of the modified ESAS with the Rotterdam Symptom Checklist and the Brief Pain Inventory--two instruments widely used in patients receiving palliative therapy for cancer. We conclude that the modified ESAS is a valid, self-administered instrument to assess symptoms for patients from differing palliative care settings.

Female↗

Randomised study of risk of fetal loss related to early amniocentesis versus chorionic villus sampling.

BACKGROUND: Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS. METHODS: We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal. FINDINGS: We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01). INTERPRETATION: Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion.

Abortion, Spontaneous↗

Prenatal detection of chromosome aneuploidies by fluorescence in situ hybridization: experience with 2000 uncultured amniotic fluid samples in a prospective preclinical trial.

Successful rapid prenatal detection of selected numerical chromosome abnormalities by using fluorescence in situ hybridization (FISH) on uncultured amniotic fluid samples has been described by Klinger et al. (1992) and Ward et al. (1993, 1997). Using essentially the same FISH protocol and identical probes specific for chromosomes 21, 18, 13, X, and Y, we prospectively compared the results of FISH and conventional cytogenetics on 2000 amniotic fluid cell samples. The 1-day FISH assay yielded discrete differences in the signal profiles between cytogenetically disomic, i.e., normal, and trisomic samples. Due to intermittent absent Y-signals, the assay differentiated less well between samples with cytogenetically normal and abnormal sex chromosome complements. The assay efficiency, and thus the clinical utility, was affected by (1) unsuccessful hybridizations (7 per cent of all hybridizations), (2) hybridizations with less than 50 scorable nuclei (19 per cent of all hybridizations), and (3) visibly contaminated samples with possible maternal cell contamination (14 per cent of all samples). As a result, we were not able to reproduce the results of Klinger et al. (1992) and Ward et al. (1993, 1997).

Amniotic Fluid↗

Charge interactions in sperm-egg recognition.

A novel method using derivatized agarose beads for investigating the types of molecules, when isolated from all others, that can form stable adhesive bonds, was recently described by Roque et al. (1996). The findings from this study were extended to living sea urchin cell systems. Both the bead results and the experiments with sea urchin cells suggested that phosphorylated amino acids can form stable adhesive bonds with positively charged peptides (Roque et al., 1996). As these experiments only examined phosphorylated amino acids, the validity of the hypotheses developed in the earlier study was dependent on extending the experiments to additional phosphorylated molecules. In this study, effects of D-mannose, D-mannose-1-phosphate, D-fructose, D-fructose-1-phosphate, maltose and maltose-1-phosphate on embryo cell reaggregation and sperm-egg interaction using untreated, jelly coat-free and vitelline layer disrupted Strongylocentrotus purpuratus sea urchin eggs were examined. The phosphorylated sugars (50 mM), and not their non-phosphorylated counterparts, strongly inhibited fertilization of the 3 types of eggs. ATP, at concentrations as low as 0.8 mM also completely inhibited fertilization. The phosphorylated sugars had little or no effect on reaggregating sea urchin blastula cells. A likely explanation of these results is that sperm-egg interaction in the sea urchin involves positively and negatively charged receptors; the positively charged receptors are blocked by exogenously added phosphorylated molecules. These and earlier studies indicate that by extending results from bead modeling studies to living systems, interesting information can be obtained regarding bonding mechanisms that may modulate adhesive interactions.

Adenosine Triphosphate↗

The role of total parenteral nutrition for patients with irreversible bowel obstruction secondary to gynecological malignancy.

Two patients received total parenteral nutrition (TPN) to manage irreversible bowel obstruction secondary to gynecological malignancy. The use of TPN prolonged their lives considerably, but also led to complications, both from the TPN and from the natural progression of the cancers. Although TPN is increasingly considered as a possible treatment for selected patients with malignant bowel obstruction who are not suitable for surgery, the literature regarding this practice is conflicting. It should be considered only in those patients with good performance status, and then after careful attention to not only the likely medical and symptomatic outcomes, but also the ethical implications of such a management strategy.

Adult↗

The effect of anesthetic techniques on blood coagulability in parturients as measured by thromboelastography.

Anesthetic techniques may affect blood coagulability and the subsequent incidence of thromboembolic events. The purpose of this study was to evaluate the effect of spinal and general anesthesia on blood coagulability in normal pregnant women undergoing cesarean section, using thromboelastography. In the spinal anesthesia group (n = 15), thromboelastography was performed after crystalloid preloading and during the immediate postanesthesia course. In the general anesthesia group (n = 15), thromboelastography was performed before induction and during the immediate postanesthesia course. Values for all thromboelastographic variables (reaction time [r], clot formation time [K], coagulation time [rK], maximum amplitude [MA], elastic shear modulus [G], clot formation rate [alpha angle], and coagulation index [CI]) in the preanesthesia period were similar in both the spinal and general anesthesia groups. However, in the postanesthesia period, r and K significantly decreased (P < 0.05), and alpha angle (P < 0.05) and CI significantly increased (P < 0.01) in the general anesthesia group when compared with the spinal anesthesia group. In the postanesthesia period, MA and G were similar in both groups. In the spinal anesthesia group, thromboelastographic variables did not change significantly in the postanesthesia compared with the preanesthesia period. We conclude that the use of general anesthesia for cesarean section is associated with accelerated coagulability when compared with spinal anesthesia.

Adult↗

Thromboelastographic changes in healthy parturients and postpartum women.

Thromboelastography (TEG) using disposable plastic cups and pins was performed with native whole blood (native group) in 17 nonpregnant volunteers, 134 healthy term pregnant women (>36 wk gestation), and 69 postpartum women. Thromboelastography was also performed with celite-activated whole blood (celite group) in 15 nonpregnant female volunteers, 38 healthy term pregnant women, and 34 postpartum women. The thromboelastographic parameters r and K were significantly decreased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The maximum amplitude MA, elastic shear modulus, and alpha angles were significantly increased in pregnant and postpartum women compared with nonpregnant women in both groups (P < 0.05). The TEG coagulation index was significantly greater in pregnant and postpartum women compared with nonpregnant women in both groups. In this study, TEG showed that pregnancy is a hypercoagulable state and that postpartum women remain hypercoagulable through the first 24 h postdelivery. The use of celite in TEG accelerated the speed of TEG analysis.

Blood Coagulation↗

Cold haemagglutinin disease in systemic lupus erythematosus.

A 34-year-old lady presenting with features of cold agglutinin disease during the course of systemic lupus erythematosus is described. Cold antibody titer was very high (1 in 4096) with specificity for 'I' antigen. Even though she had poor prognostic factors like high titer of cold antibodies with low thermal amplitude, she responded well to prednisolone.

Adult↗

Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to evaluate tissue specimens from 16 seminomas in order to elucidate the pathogenesis of germ cell tumours in males. A characteristic pattern of losses and gains within the entire genomes was detected in 94% of the seminomas by comparing the ratio profiles of the tumours with a standard of cytogenetically normal genomic DNA. Losses represented 43% of the total number of alterations often affecting chromosomes and chromosome arms 4, 5, 11, 13q, and 18q. Gains amounted to 57% and were often observed on 1q, 7, 8, 12, 14q, 15q, 21q, and 22q. Aberrations of 12p and 21q appeared most consistently. Results from CGH analysis displayed no relationship to the clinical stages of the malignancy. Some rare aberrations appeared, however, only in clinical stage II and in tumours showing relapse in the contralateral testis following orchiectomy, although the alterations were not present in all of the tumours in question. Losses of 16q13-21 and gains of 9q22.1-22.2 were demonstrated in both groups, while loss of 16p12 and gains of 6p21 and 6q23.3-24 were detected in the latter group as well. In conclusion, a specific pattern of chromosomal alterations was demonstrated in the seminomas by improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in clinical stage II and relapsed tumours, may be linked to tumour progression, invasiveness, and bilateral disease.

Chromosome Aberrations↗

Early filtration amniocentesis for further investigation of mosaicism diagnosed by chorionic villus sampling.

In 44 pregnancies where chorionic villus sampling (CVS) had shown mosaicism, early amniocentesis using a filter technique was carried out with the purpose of clarifying the fetal karyotype and reducing the waiting time for a final karyotype. Since the filter technique increases the cell yield of the amniotic fluid sample, it was hypothesized that this technique could be applied as soon as the mosaic CVS result was available, without compromising the culturing of the amniotic fluid cells. The mean gestational age at amniocentesis was 12.5 weeks and the mean gestational age at the time of the final karyotype was 13.9 weeks. All amniotic fluid sampling procedures and cultures were successful. Four pregnancies were terminated due to abnormal karyotypes (9.1 per cent). Two spontaneous abortions occurred in the second trimester (5.0 per cent), and one infant was lost at term due to unexplained intrapartum death. The total fetal loss rate was 7.5 per cent. This loss rate is concordant with other reported series where the outcome of pregnancies with placental mosaicism has been evaluated. We conclude that early amniocentesis with the filtration technique is a useful method for follow-up on CVS, mosaicism, providing results prior to 14 weeks of gestation.

Adult↗

Cell adhesion mechanisms: modeling using derivatized beads and sea urchin cell systems.

Agarose beads derivatized with amino acids, peptides, carbohydrates and lectins were used to systematically determine what types of molecules, isolated from all others, can make adhesive bonds strong enough to hold cell-like beads together. The results indicated that strong adhesion occurred when at least one of the two members of certain bead pairs was derivatized with molecules that were dimers or trimers but not monomers. Also, beads derivatized with phosphorylated amino acids, but not their non-phosphorylated counterparts, adhered to beads derivatized with positively charged peptides. Adhesion was sensitive to ionic strength and pH of the medium. It was proposed that adhesion occurred between the phosphate groups of the phosphoamino acids and amino and guanidinium groups of the peptides. Cooperative bonding can explain the stability of the adhesion observed in this system. Information gained from the bead modeling work was used to design experiments to examine the role of phosphorylated molecules in modulating adhesion in sea urchin systems. Phosphoamino acids inhibited sperm-egg interaction, but not reaggregation of blastula cells. Inhibitors of alkaline phosphatase, however, did inhibit reaggregation. The results suggest that cell surface phosphorylated molecules may modulate cellular adhesiveness, in some systems promoting, while in others inhibiting adhesion.

Amino Acids↗

Dignity in dying: a preliminary study of patients in the last three days of life.

The final three days of life of 50 consecutive patients on a busy integrated palliative care service is described, with regard to final cause of death, symptom control, drug prescription, retention of personal function, and other measures possibly relevant to dignity in dying. Good symptom relief was maintained without rapid or high escalation of doses of morphine or sedatives. Personal function was maintained in at least a moderate degree in the majority of patients. This study also illustrates some of the difficulties in describing and evaluating the concept of "dying with dignity".

Activities of Daily Living↗

Prenatal detection of chromosome aneuploidies in uncultured chorionic villus samples by FISH.

We developed a 1-d FISH assay for detection of numerical chromosome abnormalities in uncultured chorionic villus samples (CVS). Probes specific for chromosomes 13, 18, 21, X, and Y were used to determine ploidy by analysis of signal number in hybridized nuclei. Aneuploidy detection using this assay was directly compared with the results obtained by conventional cytogenetic analysis in a consecutive, clinical study of 2,709 CVS and placental samples. The FISH assay yielded discrete differences in the signal profiles between cytogenetically normal and abnormal samples. On the basis of these results, we generated FISH-assay cutoff values that discriminated between karyotypically normal and aneuploid samples. Samples with mosaicism and a single sample with possible heritable small chromosome X probe target were exceptions and showed poor agreement between FISH results and conventional cytogenetics. We conclude that the FISH assay may act as a more accurate and less labor-demanding alternative to "direct" CVS analysis.

Aneuploidy↗