Discontinuing life support in an infant of a drug-addicted mother: whose decision is it?
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Adult↗
Biomedical subjects
R Jain
Publications and source records attributed to R Jain.
Personality characteristics of persons addicted to heroin.
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Adult↗
Selectin inhibition: synthesis and evaluation of novel sialylated, sulfated and fucosylated oligosaccharides, including the major capping group of GlyCAM-1.
Selectins interact with glycoconjugate ligands in important normal and pathological situations. While high affinity recognition of natural ligands is associated with alpha 1-3(4)fucosylated, alpha 2-3sialylated (and/or sulfated) lactosamine sequences, small oligosaccharides that potently inhibit the selectins have not been found. One possibility suggested by other investigators is that high affinity may require unusual sequences not yet tested, for example, the "major capping group" (6'-sulfo-sialyl Le(x)) of the L-selectin ligand GlyCAM-1. To explore this possibility, we synthesized a spectrum of novel synthetic and semisynthetic oligosaccharides related to those on natural ligands. In studying these molecules, we noted that binding of recombinant soluble selectins to immobilized sialyl Le(a) or 3'-sulfo-Le(x) is markedly inhibited by concentrations of chloride above the physiological range. This indicates the ionic nature of the interactions, and shows that buffers typically used in screening assays for inhibitors are not optimal. Using parameters that more closely approximate physiological conditions, we confirmed that alpha 2-3-linked sialic acids, and alpha 1-3(4)fucosylation are important for recognition. Similar results obtained with both types of immobilized targets for the three selectins indicated that the binding sites for sialic acid and sulfate are very close, or identical. While O-sulfate esters mostly improved L- and P-selectin recognition, effects depended upon their position and number. Furthermore, sulfation can also impart some "negative" specificity: the major capping group does not interact with E-selectin. The branched Core 2 sequence seemed to enhance L- and P-selectin binding, however, the best inhibitors still appeared to be sialyl Le(a) and 3'-sulfo-Le(x), with the aglycone group of the latter affecting binding. Of particular note, the "major capping group" of GlyCAM-1 was not an unusually potent nor highly selective inhibitor of L-selectin, even when studying the interaction of L-selectin with native GlyCAM-1 itself.
Carbohydrate Sequence↗
Effect of stainless steel and titanium low-contact dynamic compression plate application on the vascularity and mechanical properties of cortical bone after fracture.
OBJECTIVES: Comparison of the effect of stainless steel and titanium low-contact dynamic compression plate application on the vascularity and mechanical properties of cortical bone after fracture. DESIGN: Randomized, prospective. SETTING: Orthopaedic research laboratory. ANIMALS: Ten large (greater than twenty-five kilogram) adult dogs. INTERVENTION: A short, midshaft spiral tibial fracture was created, followed by lag screw fixation and neutralization with an eight-hole, 3.5-millimeter, low-contact dynamic compression plate (LCDCP) made of either 316L stainless steel (n = five) or commercially pure titanium (n = five). After surgery, animals were kept with unrestricted weight-bearing in individual stalls for ten weeks. MAIN OUTCOME MEASUREMENTS: Cortical bone blood flow was assessed by laser Doppler flowmetry using a standard metalshafted probe (Periflux Pf303, Perimed, Jarfalla, Sweden) applied through holes in the custom-made LCDCPs at five sites. Bone blood flow was determined at four times: (a) prefracture, (b) postfracture, (c) postplating, and (d) ten weeks postplating. After the dogs were killed, the implant was removed and both the treated tibia and contralateral tibia were tested for bending stiffness and load to failure. RESULTS: Fracture creation decreased cortical perfusion in both groups at the fracture site (p = 0.02). The application of neither stainless steel nor titanium LCDCPs further decreased cortical bone blood flow after fracture creation. However, at ten weeks postplating, cortical perfusion significantly increased compared with acute postplating levels in the stainless steel (p = 0.003) and titanium (p = 0.001) groups. Cortical bone blood flow ten weeks postplating was not significantly different between the titanium group and the stainless steel group. Biomechanical tests performed on the tibiae with the plates removed did not reveal any differences in bending stiffness nor load required to cause failure between the two groups. CONCLUSIONS: Both titanium and stainless steel LCDCPs were equally effective in allowing revascularization, and neither provided a significant advantage in biomechanical properties of fracture healing at ten weeks.
Analysis of Variance↗
Pulmonary effects of fixation of a fracture with a plate compared with intramedullary nailing. A canine model of fat embolism and fracture fixation.
UNLABELLED: Fat-embolism syndrome and pulmonary dysfunction may develop in multiply injured patients who have a fracture of a long bone. Although early fixation of a fracture is beneficial, intramedullary nailing may exacerbate pulmonary dysfunction by causing additional embolization of marrow fat. We examined the pulmonary effects of the timing and method of fixation of a fracture in a canine fat-embolism model. Fat embolism was induced in forty-one adult dogs by reaming the ipsilateral femur and tibia followed by pressurization of the intramedullary canal. The animals were divided into a control group of eight dogs that had induction of fat embolism alone and an experimental group of thirty-three dogs that had induction of fat embolism and internal fixation of a transverse fracture of the middle of the contralateral femoral shaft. In the control group, four dogs each were killed four hours and twenty-four hours after induction of fat embolism. In the experimental group, a femoral fracture was created and fixation was performed four hours after embolic showering in fifteen animals and twenty-four hours after embolization in eighteen animals. The two experimental groups were subdivided according to the method of fixation of the fracture: eleven dogs each had application of a plate, nailing without reaming, and nailing with reaming. The pulmonary arterial pressure and the alveolar-arterial gradient were measured preoperatively, during induction of fat embolism, and as long as one hour after fixation of the fracture but before the animal was killed. The lungs, brain, and kidneys were examined for pathological and physiological evidence of intravascular fat. The intravascular fat persisted for twenty-four hours after induction of pulmonary fat embolism. Pulmonary arterial pressure remained elevated at four hours after the embolic showering, before creation and fixation of the fracture. By twenty-four hours after the induction of fat embolism, pulmonary arterial pressure had returned to the baseline level. Neither the creation nor the fixation of the fracture affected pulmonary arterial pressure. In the animals that had fixation of a fracture four hours after embolization, both nailing with reaming and nailing without reaming produced alveolar-arterial gradients that were higher than the baseline values, whereas fixation with a plate did not change the alveolar-arterial gradient significantly from the baseline value. In addition, the alveolar-arterial gradients in the animals that had nailing with reaming and nailing without reaming four hours after embolization were, respectively, four and 3.5 times higher than that in the animals that had fixation of the femur with a plate. In the animals that had fixation twenty-four hours after embolization, none of the methods for fixation affected the alveolar-arterial gradient. The amount of embolic fat in the lungs, brain, and kidneys was not affected by fixation of the fracture when it was performed at either the four-hour or the twenty-four-hour time-interval. Scores for pulmonary edema were increased by fixation of the fracture, but there was no difference among the scores associated with the three methods of fixation. CLINICAL RELEVANCE: The findings of the present study indicated that the amount of intravascular fat persisting in the lungs, kidneys, and brain twenty-four hours after pressurization of the intramedullary canal is not affected by the method of fixation of the fracture. Fixation of a fracture is associated with minimum evidence of acute inflammation and has no effect on pulmonary artery pressure. The development of pulmonary dysfunction from fat emboli depends on other factors, not just on the presence of fat in pulmonary vessels. It appears that the method of fracture fixation has little influence on the outcome of treatment.
Animals↗
Proliferating cell nuclear antigen immunostaining in breast carcinoma and its relationship to clinical and pathological variables.
Tumour proliferative activity of 74 breast lesions was assessed by determining mitotic index and immunostaining for proliferative cell nuclear antigen using Peroxidase antiperoxidase method. The indices were correlated with histomorphology and clinical stage of the disease. Positively stained nuclei and mitotic figures were counted per 1000 cells to calculate Proliferating Cell Nuclear Antigen (PCNA) and mitotic index respectively. Sixty four cases stained positive for PCNA. The index ranged between 0 to 98. PCNA index was significantly low in benign lesions as compared to malignant lesions (p < 0.0002). There was a linear correlation between the mitotic index and PCNA index. PCNA index also showed significant correlation with tumour size and histologic grade; however, it had no correlation with axillary lymph node status.
Breast Neoplasms↗
Pedunculated gastric teratoma: a case report with review of literature.
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Humans↗
Increase in serum free thyroxine levels related to intravenous heparin treatment.
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Angina, Unstable↗
Conformational characteristics of peptides containing alpha, beta-dehydroamino acid residues.
The structural preferences of synthetic peptides containing alpha, beta-dehydroamino acid residues, as determined by theoretical studies, x-ray diffraction analyses, and spectroscopic studies, are reviewed. The role of delta ZPhe residues in stabilizing type II beta-turn structures in small peptides and in nucleating helical structure in longer peptides is exemplified by several crystal as well as solution structural studies. From the few studies reported so far it appears that delta ZLeu influences the peptide backbone, much like the delta ZPhe residue, whereas delta Ala prefers the extended conformation, suggesting that the nature of beta substituents might influence the conformation restriction behavior of the dehydroresidues. Conformational studies on synthetic peptides containing delta E, delta ZAbu, and delta Val have also been described.
Amino Acid Sequence↗
How accurate is glucose analysis in the presence of multiple interfering substances in the neonate? (glucose analysis and interfering substances).
Whole blood glucose testing by reagent sticks is inaccurate at low plasma glucose concentrations and with varying hematocrit. Both conditions are frequently seen in newborn infants. Therefore plasma glucose analysis is the preferred method for newborn glucose monitoring. We encountered unanticipated difficulties in plasma glucose measurement by the automated hexokinase method caused by the combinations of plasma free hemoglobin, bilirubin, and plasma triglycerides, which are frequently elevated in newborn plasma. We determined the adverse effects of various combinations of these interfering substances on glucose analysis by the hexokinase method and demonstrated that accurate analysis is possible by a 1:1 plasma dilution only at high plasma glucose levels but not at the more critical low plasma glucose concentration. The dilution reduced the number of repeat specimens required in newborns. But 1:1 plasma dilution overestimated the glucose levels at low plasma glucose values, and therefore this automated hexokinase method is not suitable for glucose analysis in the newborn. Glucose-oxidase remains the method of choice for plasma glucose analysis in neonates. This information is important because using this hexokinase methodology, one might miss hypoglycemia in the newborn.
Autoanalysis↗
Assessment of the relationship between standard probe and implantable fiber measurements of cortical bone blood flow: a canine study.
Laser Doppler flowmetry (LDF) has been used to assess cortical bone blood flow in various clinical situations, such as osteomyelitis and osteonecrosis. Standard metal-sheathed probes containing optical fibers, applied to cortical bone for perfusion measurements, require direct exposure of the bone surface for each measurement, making nonanesthetized assessments over time impractical. Implantable optical fibers offer a noninvasive method for evaluating cortical bone perfusion without repeated surgical exposure of the bone after initial surgical implantation of the fibers. In vitro studies have shown the reliability of laser Doppler (LD) fibers compared with those of the standard probe. This investigation studied the relationship between measurements of cortical bone perfusion obtained by implanted optical (LD) fibers and standard (LDF) probes in vivo. Midshaft tibial fractures were created in the right hindlimb of 11 adult, large (>25 kg) dogs and stabilized by low contact-dynamic compression plate fixation. Cortical bone blood flow was measured by LDF using standard probes and implantable fibers at five sites along the tibia prefracture, postfracture, immediately postplate application, and at 10 weeks postplating, immediately prior to euthanasia. The implantable fibers were secured onto the cortical bone via the plate and led through a percutaneous exit site. Histological examination of the inguinal and popliteal lymph nodes and soft tissue surrounding the fibers revealed mild inflammation. No significant correlation of blood flow assessed by the implantable fibers and standard probe occurred immediately postfracture (r < 0. 13, p > 0.62). However, a statistically significant correlation was seen postplate application at one of the measurement sites in the distal fracture fragment (r = 0.78, P < 0.003). The fibers remained intact and functional until an average of 3 weeks at which time they either fractured or were removed by the animals. This is the first in vivo study assessing the reliability of implantable fibers for the measurement of cortical bone blood flow. Further modification of the fibers will be necessary to improve their longevity and durability for assessment of cortical bone blood flow.
Animals↗
Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysis model.
This study was performed to evaluate the potential costs of a hypothetical novel biological agent (BIO) as a therapy for rheumatoid arthritis (RA), compared with oral methotrexate (MTX) and intramuscular gold (IMG). A decision analysis model was used to compare the total costs of treating a cohort of 10,000 RA patients with each agent for 6 months. Total costs included direct costs and indirect costs. Baseline estimates were subjected to sensitivity analysis. Total costs per person were: MTX, $5,430; IMG, $6,725; BIO, $9,411. In sensitivity analysis, the primary cost drivers for MTX and IMG were the indirect costs of RA and monitoring costs. In contrast, total costs of the BIO were driven predominantly by medication costs. Sensitivity analysis showed, even when efficacy and safety were optimized, costs for the BIO still substantially exceeded those of MTX and IMG. Medication costs will be an important consideration in the development of novel BIOs for RA.
Antirheumatic Agents↗
Disseminated herpes simplex virus infection presenting as fever in the newborn--a lethal outcome.
The clinical course of a neonate who presented with fever and tachypnea on day 6 of life is described. He developed disseminated intravascular coagulopathy, hepatic failure, coma and expired at 14 days of age. The post mortem viral cultures from liver, adrenal and lungs were positive for HSV type 2. The fatal outcome of this case of fever, due to HSV infection, emphasizes the need for early treatment of suspicious cases of HSV infection. HSV should be considered in the differential diagnosis of the newborn with persistent fever unresponsive to antibiotics.
Fatal Outcome↗
A 69-year-old man with cholestatic liver disease.
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Aged↗
Mesenteric plexiform neurofibroma: computed tomography appearance.
Gastrointestinal involvement in von Recklinghausen's disease is usually in the form of neurofibromas and leiomyomas. Very rarely, plexiform neurofibromas may be seen involving the bowel wall and myenteric plexus with secondary minor involvement of the mesentery. This report describes the computed tomography morphology of a plexiform neurofibroma extensively involving the mesentery with minor involvement of the bowel wall.
Child↗
Occlusive arterial disease of the upper extremity: colour Doppler as a screening technique and for assessment of distal circulation.
A prospective study was performed to evaluate the sensitivity of colour Doppler flow imaging (CDFI) in the detection of occlusive arterial disease in the upper limb (using angiography as the standard) and to quantify the severity of the disease. Twenty-one ischaemic and 15 healthy limbs were studied by intra-arterial digital subtraction angiograms (IADSA) and CDFI. Selective subclavian digital subtraction angiograms were performed by the percutaneous transfemoral route. CDFI was performed from the brachial artery superiorly to the subclavian artery origin. Special attention was paid to the study of spectral waveforms and peak systolic velocities at various levels. In each subject, IADSA and CDFI were performed by different radiologists without knowledge of the results of the other investigation. In normal limbs, all arteries demonstrated a characteristic sharp triphasic spectral pattern with mean peak systolic velocity of 105, 80 and 57 cm/s for the subclavian, axillary and brachial arteries, respectively. In ischaemic limbs, reduction in peak systolic value and broadening of the spectral trace with filling in of the spectral window were noted. More characteristic was the finding of a loss of diastolic flow reversal, which was the earliest sign of significant arterial stenosis. The pattern of diastolic blood flow correlated well with the degree of collateral formation and distal vascular runoff. In conclusion, CDFI has a high sensitivity and specificity in the detection of significant arterial stenosis and is thus an ideal, inexpensive screening procedure. Analysis of the diastolic wave-form distal to the stenosis is an indicator of the degree of collateral circulation and distal runoff and thus acts as a prognostic indicator, guiding further investigation and management.
Angiography, Digital Subtraction↗
A new cholestane derivative of Abutilon bidentatum Hochst. and its bioactivity.
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Antifungal Agents↗
Capillary electrophoretic separation and laser-induced fluorescence detection of the major DNA adducts of cisplatin and carboplatin.
Micellar electrokinetic capillary chromatographic separation of a dansylated mixture of normal nucleotides and platinated cross-link adducts of d(pGpG) and d(pApG) was optimized with baseline resolution. The introduction of a laser-induced fluorescence (LIF) detector overcame the lack of sensitivity characteristic of capillary electrophoresis (CE) due to the small injection volume and the short optical path length. CE/LIF was able to detect 1 adduct/10(4) normal nucleotides/micrograms DNA by fluorescence postlabeling assay. The enrichment of the adduct, prior to dansylation, enhanced the detection limit to 1 adduct/10(7) normal nucleotides/micrograms DNA. Calf thymus DNA was reacted in vitro with cisplatin and carboplatin with total input drug/nucleotide ratios of 0.05 and 0.5, respectively. A2780 human ovarian carcinoma cells were exposed in culture to 25 microM cisplatin for 2 h. The cells were incubated with drug-free medium for 3 h before harvesting. The identification of the cross-link adducts in modified DNA was confirmed by cochromatography with authentic markers. The same 1,2-intrastrand cross-link adducts were induced by both cisplatin and its second-generation drug carboplatin. This report has demonstrated, for the first time, the utility of CE/LIF as an analytical tool for assaying DNA damage [corrected].
Animals↗