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Biomedical subjects

D R Jones

Publications and source records attributed to D R Jones.

At least 127 records · Page 7Linked to original sources
PubMed1997

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P < 0.05) compared to non-iso-reperfused groups at all postmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous resistances decreased with iso-reperfusion. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

Adenine Nucleotides↗
PubMed1997

Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma of the esophagus.

BACKGROUND: Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. METHODS: From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS: Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant (p = 0.13), but the difference in recurrence-free survival was significant (p = 0.007). CONCLUSIONS: This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

Adenocarcinoma↗
PubMed1997

Anatomically sound, simplified approach to repair of "complete" atrioventricular septal defect.

BACKGROUND: There are few congenital anomalies of the heart that have benefited more from thorough anatomic analysis than the complex anomaly known as atrioventricular septal defect in the setting of common atrioventricular junction. Recent advances in understanding the anatomy of this lesion have led to alternative methods of repairing these defects. METHODS: The medical records of 21 consecutive patients undergoing repair of complete atrioventricular septal defect have been reviewed. Nine of these patients had a standard one- or two-patch repair, and 12 had direct closure of the ventricular element of the defect. RESULTS: Direct closure resulted in significantly shorter pump and cross-clamp times. Follow-up for an average of 34 months suggests that when direct closure can be performed, the results are comparable with those of the more standard technique. CONCLUSIONS: Our initial success with this approach is encouraging; however, longer follow-up is required to establish whether it will be broadly applicable.

Cardiac Surgical Procedures↗
PubMed1997

Complement coating of erythrocytes is reduced following their interaction with neutrophils in vitro without loss of complement receptor 1 (CR1).

We have investigated the interaction of complement-coated erythrocytes (E) with neutrophils, in vitro, to determine the effects of erythrocyte CR1. Complement-coating in vitro, to mimic immune complex uptake, caused a reduction in E-CR1, but subsequent interaction with neutrophils effected a removal of E-C3b and a return of E-CR1 to levels approximating that of uncoated erythrocytes. These data indicate that C3b, associated with immune complexes, may bind to E-CR1 in a reversible manner and that subsequent interaction with phagocytes need not necessarily result in cleavage (and loss of) E-CR1. Further, we conclude that E-CRI can apparently be reduced by epitope masking.

Antigen-Antibody Complex↗
PubMed1997

Contribution of human CYP3A subfamily members to the 6-hydroxylation of chlorzoxazone.

1. The capability of human CYPs other than 2E1 to catalyse the formation of 6-hydroxychlorzoxazone (6OHCHZ) was examined in vitro using human liver microsomes. 2. 4-Methylpyrazole, diethyldithiocarbamate (DDC), and rabbit anti-human CYP2E1 antibodies reduced chlorzoxazone 6-hydroxylase activity by 60, 60 and 50% respectively. The rate of formation of 6OHCHZ by DDC-treated microsomes was reduced further by the 3A inhibitors midazolam, troleandomycin and gestodene and increased by alpha-naphtholavone, a 3A4 stimulator. 3. Following preincubation with DDC there were significant correlations (p < 0.05) between the residual CHZ 6-hydroxylase activity and immunoquantified CYP3A levels, and corresponding activities (e.g. midazolam 1'-hydroxylation). Rabbit anti-human CYP3A antibodies alone and in combination with DDC reduced the formation of 6OHCHZ by 47 and 62", respectively. 4. cDNA expressed CYP3A4, 2E1 and 2D6 exhibited comparable CHZ 6-hydroxylase activity. CHZ modulated 3A4 activity as reflected by midazolam 1'-hydroxylase and 4-hydroxylase activities. 5. CYP3A may make a significant contribution to CHZ 6-hydroxylation and therefore caution should be exercized when chlorzoxazone is employed as a specific 2E1 probe in vitro and in vivo.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

Stable acetaldehyde adducts: structural characterization of acetaldehyde adducts of human hemoglobin N-terminal beta-globin chain peptides.

Acetaldehyde is the first oxidation product of ethanol in vivo. Our earlier work showed that with sufficient acetaldehyde, five of the six possible sites of the peptide pentalysine were modified as a Schiff base (Braun KP, et al: J Biol Chem 270:11263-11266, 1995). However, we were unable to deduce unequivocally which site was unmodified. Lysine residues, as well as the amine terminal valine residues, in hemoglobin have been implicated as target structures for acetaldehyde adducts resulting from ethanol consumption. Hemoglobin adducts of acetaldehyde have been used clinically as a marker of ethanol consumption, but the chemical nature of these adducts remains undefined. As part of our continuing structural characterization of acetaldehyde-protein adduct formation, we studied the peptides Val-His-Leu-Thr-Pro and Val-His-Leu-Thr-Pro-Val-Glu-Lys, from the amine terminus of the beta-globin chain of hemoglobin, in vitro. Both peptides have at least one potential site for adduct formation. In the octapeptide, the N-terminal amine group of Val as well as the epsilon-amine group of the lysine sidechain can potentially be modified by acetaldehyde. We used mass spectrometry, carbon-13 nuclear magnetic resonance, and Raman spectroscopy and characterized stable Schiff base acetaldehyde adducts of these two peptides at both reactive sites. The identification of stable Schiff base adducts with the N-terminal peptides of the beta-chain of hemoglobin as well as with epsilon-amino groups of lysine provides another possible means of monitoring ethanol consumption. The functional implications of these stable Schiff bases remains undefined.

Acetaldehyde↗
PubMed1997

Influences on breastfeeding in southeast England.

Factors associated with not exclusively breastfeeding at discharge from the obstetric hospital and with duration of breastfeeding were examined in 700 randomly sampled infants. Obstetric records were examined in 97.7% of the subjects and 73.0% of subject families were interviewed. There were 444 (66.5%) infants exclusively breastfed at discharge from the obstetric hospital. Factors associated with not exclusively breastfeeding at discharge from the obstetric hospital after adjusting for potential confounders were: mother leaving school aged less than 18 years, mother not attending antenatal classes and the use of a dummy in the 2 weeks before the interview. Bed sharing practice in the 2 weeks before the interview was associated with exclusively breastfeeding at discharge from the obstetric hospital. Factors associated with a shorter duration of breastfeeding were: mother leaving school before 18 years of age, smoking 20 or more cigarettes per day and use of a dummy. Dummy use may causally reduce breastfeeding or might be a marker for breastfeeding difficulties. There was a dose-response relationship with smoking, with heavier smokers breastfeeding for the shortest time periods. Bed sharing was associated with a longer duration of breastfeeding. This may not necessarily be a causal relationship because breastfeeding may promote bed sharing. The effect of dummy use and bed sharing on breastfeeding warrants further study.

Adult↗
PubMed1997

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P < 0.05) and sevenfold (P < 0.0001) increases in Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Adenine Nucleotides↗
PubMed1997

Physiology of diving of birds and mammals.

This review concentrates on the physiological responses, and their control, in freely diving birds and mammals that enable them to remain submerged and sometimes quite active for extended periods of time. Recent developments in technology have provided much detailed information on the behavior of these fascinating animals. Unfortunately, the advances in technology have been insufficient to enable physiologists to obtain anything like the same level of detail on the metabolic rate and physiological adjustments that occur during natural diving. This has led to much speculation and calculations based on many assumptions concerning usable oxygen stores and metabolic rate during diving, in an attempt to explain the observed behavior. Despite their shortcomings, these calculations have provided useful insights into the degree of adaptations of various species of aquatic birds and mammals. Many of them, e.g., ducks, smaller penguins, fur seals, and Weddell seals, seem able to metabolize aerobically, when diving, at approximately the same (if not greater) rate as they do at the surface. Their enhanced oxygen stores are able to support aerobic metabolism, at what would not be considered unusually low levels, for the duration of the dives, although there are probably circulatory readjustments to ensure that the oxygen stores are managed judiciously. For other species, such as the larger penguins, South Georgian shag, and female elephant seals, there is a general consensus that they must either be reducing their aerobic metabolic rate when diving, possibly by way of regional hypothermia, and/or producing ATP, at least partly, by anaerobiosis and metabolizing the lactic acid when at the surface (although this is hardly likely in the case of the female elephant seals). Circulation is the proximate regulator of metabolism during aerobic diving, and heart rate is the best single indicator of circulatory adjustment. During voluntary dives, heart rates range from extreme bradycardia to well above resting, reflecting metabolic performance. Efferent cardiac control is largely parasympathetic. Reflex cardiorespiratory responses are modulated by conditioning and habituation, but reflexes predominate during extended dives and during recovery, when gas exchange is maximized.

Adenosine Triphosphate↗
PubMed1997

Does angiotensin play a role in human fetal erythropoiesis?

Angiotensin affects the growth of many cell types and there have been suggestions that it could influence cells which respond to erythropoietin. During first trimester, human fetal haematopoietic cells are exquisitely responsive to erythropoietin and we have assessed the potential for angiotensin to also influence the growth of these cell types in a standard culture system. The data obtained from these studies indicate that angiotensin does not influence fetal haematopoiesis over a range of concentrations.

Angiotensin II↗
PubMed1997

Screening for diabetic retinopathy in primary care: retinal photography alone can be used efficiently and effectively to exclude those with sight threatening lesions.

BACKGROUND: Good screening performance of retinal photography and ophthalmoscopy together in screening for diabetic retinopathy in primary care have been reported. This study reanalysed the data to evaluate the screening performance of photography alone. METHODS: One thousand and ten patients screened by fundal photography and ophthalmoscopy were studied retrospectively. Fundal photographs were quality graded with poor quality pictures being excluded from the analysis. Each patient was reviewed initially by both retinal photographs and ophthalmoscopy by an ophthalmologist, the "gold standard". Six months later the fundal photographs were reviewed and reported in a blinded manner by the ophthalmologist. RESULTS: Two thousand and fourteen photographs were obtained, of which 162 (8%) had to be excluded because of poor quality. On review of the remaining 1852 photographs in isolation, of 77 cases of severe retinopathy as determined by the "gold standard", 67 had severe changes on photography--detection rate 87%. Of the 1775 cases without sight threatening retinopathy only five were judged to have sight threatening changes on photography--false positive rate 0.3%. Considering sight threatening and background retinopathy together, the detection rate was 69% (257 of 375) and the false positive rate 1.6% (23 of 1477). CONCLUSION: Good quality fundal photographs alone seem specific enough to screen for sight threatening diabetic retinopathy, but will underdetect background retinopathy.

Diabetic Retinopathy↗
PubMed1997

Heart rates of northern elephant seals diving at sea and resting on the beach.

Heart rates of northern elephant seals diving at sea and during apnoea on land were monitored to test whether a cardiac response to submergence is an important factor in their ability to make repetitive, long-duration dives. Seven juvenile northern elephant seals were captured at Año Nuevo, CA, instrumented and translocated to release sites around Monterey Bay. Heart rate and dive depth were recorded using custom-designed data loggers and analogue tape monitors during the seals' return to Año Nuevo. Heart rates during apnoea and eupnoea were recorded from four of the seals after they hauled out on the beach. Diving patterns were very similar to those of naturally migrating juveniles. The heart rate response to apnoea at sea and on land was a prompt bradycardia, but only at sea was there an anticipatory tachycardia before breathing commenced. Heart rate at sea declined by 64% from the surface rate of 107 +/- 3 beats min-1 (mean +/- S.D.), while heart rate on land declined by 31% from the eupnoeic rate of 65 +/- 8 beats min-1. Diving heart rate was inversely related to dive duration in a non-linear fashion best described by a continuous, curvilinear model, while heart rate during apnoea on land was independent of the duration of apnoea. Occasionally, instantaneous heart rate fell as low as 3 beats min-1 during diving. Although bradycardia occurs in response to apnoea both at sea and on land, only at sea is heart rate apparently regulated to minimise eupnoeic time and to ration oxygen stores to ensure adequate supplies for the heart and brain not only as the dive progresses normally but also when a dive is abnormally extended.

Animals↗
PubMed1996

Do differences in the prevalence of risk factors explain the higher mortality from sudden infant death syndrome in New Zealand compared with the UK?

AIMS: To compare the prevalence of risk factors for the sudden infant death syndrome (SIDS) in New Zealand (SIDS mortality 3.53/1000) with that in the South West Thames (SWT) region of the United Kingdom (SIDS mortality 1.36/1000). METHODS: The methodology of the study was essentially identical in New Zealand and SWT. The subjects in both countries were randomly selected from all births in the study regions. The subjects were randomly allocated an age at which to be interviewed using the same questionnaire in the two study areas. Obstetric records were also examined. Eighteen hundred subjects were selected in New Zealand and 700 subjects in SWT. RESULTS: Younger and unmarried mothers were slightly more common in New Zealand than in SWT. The prevalence of maternal smoking, prone sleeping position and infants' sharing of beds with another person were all higher in New Zealand than SWT, thus increasing the risk of SIDS (maternal smoking in pregnancy: 31.0% vs 23.8% respectively, chi 2 = 11.6, p = 0.001; prone sleeping position: 32.9% vs 25.9%, chi 2 = 18.9, p < 0.001; bed sharing: 10.5% vs 6.8%, chi 2 = 6.0, p = 0.14). However, New Zealand infants were breast fed more frequently and for longer than infants in SWT, which would tend to reduce the risk of SIDS in the New Zealand population. In combination the differences in the prevalences of these four risk factors explain only 20% of the excess risk of SIDS in New Zealand. CONCLUSIONS: The high SIDS mortality rate in New Zealand is not simply explained by a high prevalence of known and modifiable risk factors for SIDS.

Breast Feeding↗
PubMed1996

Quantification of dextromethorphan and metabolites: a dual phenotypic marker for cytochrome P450 3A4/5 and 2D6 activity.

A sensitive and selective liquid chromatographic procedure using fluorimetric detection was developed to quantify dextromethorphan (DTM), 3-methoxymorphinan (3MM), dextrorphan (DT), 3-hydroxymorphinan (3OH) and two internal standards, codeine (COD) and ethylmorphine (ETM), in urine. Precision and accuracy of the assay were determined over a concentration range of 5-3200 ng/ml urine for DTM, 5-400 ng/ml urine for 3MM, 400-40 000 ng/ml urine for DT and 200-16 000 ng/ml urine for 3OH, by assaying freshly prepared calibration standards and replicates of six quality control (QC) samples on separate days. All of the inter-day and intra-day coefficients of variation (C.V.s) were less than 20% except for a low QC for 3MM. The inter-day and intra-day accuracies were less than 20% for the low QCs, less than 15% for the medium QCs and less than 12% for the high QCs, for all compounds. The limit of quantification (LOQ) was 2 ng/ml urine for DTM and 3MM, 250 ng/ml urine for DT, and 100 ng/ml urine for 3OH. Absolute recovery was 76% for DTM, 74% for 3MM, 77% for DT, 46% for 3OH, 73% for ETM, and 57% for COD. The frequency distribution of the CYP2D6 metabolic ratio (DTM/DT) illustrated a bimodal distribution whereas, the CYP3A metabolic ratio (DTM/3MM) exhibited a unimodal distribution in overnight urine samples of volunteers who ingested 30 mg dextromethorphan hydrobromide. The CYP2D6 metabolic ratio significantly correlated with 3MM/3OH (r=0.82) and DTM/3OH (r=0.95) but did not correlate with the CYP3A metabolic ratio (r=0.27).

Chromatography, High Pressure Liquid↗
PubMed1996

Selective lung ventilation during thoracoscopy: effects of insufflation on hemodynamics.

BACKGROUND: Positive-pressure insufflation during thoracoscopy has been advocated by some authors to facilitate exposure of the intrathoracic structures by expediting collapse of the lung. We hypothesized that insufflation during thoracoscopy may result in hemodynamic compromise despite selective lung ventilation. METHODS: After placement of invasive monitoring lines, six adult swine underwent selective lung ventilation and thoracoscopy. Baseline measurements of hemodynamic indices were taken before selective lung ventilation. The right lung then was collapsed; data were obtained at insufflation pressures up to 10 mm Hg and were compared with baseline values using Student's t test. RESULTS: Cardiac index, mean arterial pressure, and left ventricular stroke work index decreased, whereas pulmonary artery and central venous pressures increased (p < 0.05) at insufflation pressures of 5 mm Hg and greater. CONCLUSIONS: Positive-pressure insufflation during thoracoscopy resulted in significant hemodynamic compromise despite the use of selective lung ventilation. Conversion to thoracotomy may be an alternative if positive-pressure insufflation is necessary to perform the thoracoscopic procedure.

Animals↗
PubMed1996

Reduction in erythrocyte complement receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55) during normal pregnancy.

RBC-membrane CR1 has been assayed in pregnancy and at 48 h postpartum. It has been shown that RBC CR1 is reduced as pregnancy progress, reaching a nadir in the third trimester and that it returns to levels approaching normal within 48 h postpartum. Further, there is a reduced expression of RBC decay accelerating factor (DAF) during pregnancy but no change in expression of RBC CD59. We suggest that the reduction in RBC CR1 and DAF may reflect increased levels of circulating immune complexes and consequent increased complement activation in pregnancy.

Antibodies, Monoclonal↗
PubMed1996

Determination of cytochrome P450 3A4/5 activity in vivo with dextromethorphan N-demethylation.

Dextromethorphan is used widely in vivo to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Dextromethorphan is N-demethylated in vitro to 3-methoxymorphinan by human CYP3A4/5. We examined whether the dextromethorphan/3-methoxymorphinan urinary metabolic ratio (MR) could be used as an in vivo probe of CYP3A. Urinary excretion of 3-methoxymorphinan was excretion rate-limited in extensive metabolizers of CYP2D6, which necessitated a longer urine collection, 0 to 72 hours, to obtain true MR values for CYP3A. The urine excretion of dextromethorphan and 3-methoxymorphinan was delayed in poor metabolizers of CYP2D6 but appeared to be formation rate-limited. The delayed excretion in poor metabolizers necessitated longer urine collection intervals, 0 to 11 days, to estimate the true CYP3A MR and 0 to 8 days to estimate the true CYP2D6 MR. However, a 72-hour collection in poor metabolizers was used as an index of the true dextromethorphan/3-methoxymorphinan MR. Rifampin (300 mg b.i.d. for 7 days) significantly reduced the 0- to 72-hour dextromethorphan/3-methoxymorphinan MR consistent with an 830% (+/- 1808%) induction of CYP3A activity (n = 8), whereas erythromycin (250 mg q.i.d. for 7 days) significantly increased the dextromethorphan/3-methoxymorphinan MR, corresponding to a 34% +/- 44% inhibition of activity (n = 7) in extensive metabolizers and poor metabolizers. The changes in CYP3A activity were independent of CYP2D6 phenotype and were also observed after 24- and 48-hour urine collections in extensive metabolizers and poor metabolizers. In addition, MRs reflecting CYP2D6 and CYP3A were not significantly correlated. We conclude that the commonly used antitussive dextromethorphan can be used as an in vivo marker of CYP3A and CYP2D6 activity.

Administration, Oral↗