Midline episiotomy and anal incontinence. Results should be interpreted with caution in British context.
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Biomedical subjects
Publications and source records attributed to D J Murphy.
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BACKGROUND: In patients with atrioventricular and arterioventricular discordance congenitally corrected transposition, the morphologically right ventricle may progressively deteriorate while functioning in the systemic circuit. The double switch operation has been proposed to limit this functional deterioration. METHODS: From October 1993 to August 1998, the records of 27 patients with congenitally corrected transposition were reviewed. Age at operation ranged from 3 months to 55 years. Associated defects included ventricular septal defects in 18, pulmonary atresia in 7, and pulmonary stenosis in 11 patients. Twenty-two patients had double switch operations (10 arterial switch plus Senning procedures and 12 Rastelli plus Senning procedures). Five patients were not candidates for the double switch. Before the double switch, 6 patients required pulmonary artery banding and 10 had functioning systemic to pulmonary artery or cavopulmonary shunts. RESULTS: There was no early or late mortality. Two patients required pacemaker implantation, both later regained normal sinus rhythm. Tricuspid valve function improved in all patients except one. Moderate left ventricular dysfunction developed 5 months postoperatively in 1 patient. CONCLUSIONS: The double switch operation can be performed in selected patients with minimal early morbidity and mortality. Longer follow-up is necessary to determine whether this complex approach is indeed warranted.
OBJECTIVES: The purpose of this study was to determine long-term outcome in adults with congenitally corrected transposition of the great arteries (CCTGA), with particular emphasis on systemic ventricular dysfunction and congestive heart failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF being relatively common in older adults. METHODS: Retrospective analysis of records of 182 patients from 19 institutions were reviewed to determine current status and possible risk factors for systemic ventricular dysfunction and CHF. Factors considered included age, gender, associated cardiac defects, operative history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular) regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were common in groups with or without associated cardiac lesions. By age 45, 67% of patients with associated lesions had CHF, and 25% of patients without associated lesions had this complication. The rates of systemic ventricular dysfunction and CHF were higher with increasing age, the presence of significant associated cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of any type, and particularly with tricuspid valvuloplasty or replacement. Aortic regurgitation (a previously unreported problem) was also relatively common in this patient population. CONCLUSIONS: Patients with CCTGA are increasingly subject to CHF with advancing age; this complication is extremely common by the fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular regurgitation is strongly associated with RV (anatomical right ventricle connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction and CHF; whether it is causative or a secondary complication remains speculative.
We have previously identified a rice gene encoding a 27 kDa protein with a single Ca2+-binding EF-hand and a putative membrane anchor. We report here similar genes termed caleosins, CLO, in other plants and fungi; they comprise a multigene family of at least five members in Arabidopsis (AtClo1-5). Northern hybridization demonstrated that AtClo2-4 mRNAs levels were low in various tissues, while AtClo1 mRNA levels were high in developing embryos and mature seeds. Analysis of transgenic Arabidopsis plants expressing the GUS reporter under control of the AtClo1 promoter showed strong levels of expression in developing embryos and also in root tip cells. Antibodies raised against AtCLO1 were used to detect caleosin in cellular fractions of Arabidopsis and rapeseed. This indicated that caleosins are a novel class of lipid body proteins, which may also be associated with an ER subdomain.
OBJECTIVE: To examine the management of early-onset preeclampsia and its maternal and fetal morbidity and mortality. DESIGN: Retrospective cohort study of 49,812 births at a university teaching hospital between June 1986 and March 1997. Seventy-one women were identified with a diagnosis of preeclampsia with an onset at less than 30 completed weeks of gestation. RESULTS: The incidence of very preterm preeclampsia was 1 in 682 total births. The mean diagnosis to delivery interval (range) was 14 days (0-49 days). There were no maternal deaths. Fifteen women (21%) had developed HELLP/ELLP syndrome, 9 (13%) had renal failure, 1 (1.4%) had eclampsia, and 11 (15%) had an abruption. Five women (7%) had a termination of pregnancy, 57 (80%) were delivered by cesarean section, and 4 (5%) required a classical incision. There were 12 intrauterine deaths (16%), 9 neonatal deaths (12%), and 52 neonatal survivors (72%). Two of the survivors were known to have neurological impairment at the 2-year follow-up. CONCLUSIONS: A conservative approach to the management of early-onset preeclampsia results in a good obstetric outcome for the majority of fetuses, but this must be balanced against the significant risk of morbidity to the mothers.
We report the characterization of two members of a gene family from Arabidopsis that encode, respectively, cytosolic (cPMSR) and plastid-targeted (pPMSR) isoforms of the oxidative-stress-repair enzyme peptide methionine sulfoxide reductase. Overexpression of these proteins in Escherichia coli confirmed that each had PMSR enzyme activity with a synthetic substrate, N-acetyl-[(3)H]-methionine sulfoxide, or a biological substrate, alpha-1 proteinase inhibitor. The pPMSR was imported into intact chloroplasts in vitro with concomitant cleavage of its approximately 5-kD N-terminal signal peptide. The two PMSR isoforms exhibited divergent pH optima, tissue localization, and responses to developmental and environmental effects. Analysis of the Arabidopsis database indicated that there are probably at least two p-pmsr-like genes and three c-pmsr-like genes in the Arabidopsis genome. Expression of the p-pmsr genes and their protein products was restricted to photosynthetic tissues and was strongly induced following illumination of etiolated seedlings. In contrast, the c-pmsr genes were expressed at moderate levels in all tissues and were only weakly affected by light. Exposure to a variety of biotic and abiotic stresses showed relatively little effect on pmsr gene expression, with the exception of leaves subjected to a long-term exposure to the cauliflower mosaic virus. These leaves showed a strong induction of the c-pmsr gene after 2 to 3 weeks of chronic pathogen infection. These data suggest novel roles for PMSR in photosynthetic tissues and in pathogen defense responses in plants.
OBJECTIVE: To determine patient characteristics associated with patient and proxy perceptions of physicians' recommendations for life-prolonging care versus comfort care, and with acceptance of such recommendations. DESIGN: Cross-sectional. SETTING: Five teaching hospitals in Denver, Colo. PATIENTS: We studied 239 hospitalized adults believed by physicians to have a high likelihood of dying within 6 months. MEASUREMENTS AND MAIN RESULTS: Interviews with patients or proxies were conducted to determine perceptions of physicians' recommended goal of care and roles in decision making. RESULTS: Patients' mean age was 66.6 years; 44% were women. In adjusted analysis, age greater than 70 years and female gender were associated with a higher likelihood of believing that comfort care had been recommended by the physician (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.89 to 7.24; OR, 1.99; 95% CI, 1.04 to 3. 84, respectively). Patients and proxies gave substantial decision-making authority to physicians: 29% responded that physicians dominate decision making, 55% that decision making is equally shared by physicians and patients, and only 16% that patients make decisions. Increasing age was associated with an increased likelihood of believing that physicians should dominate decision making (P <.005). CONCLUSIONS: Among patients with advanced illness, perceived comfort care recommendations were related to patient age and gender, raising concern about possible gender and age bias in physicians' recommendations. Although all patients and proxies gave significant decision-making authority to physicians, older individuals were more likely to give physicians decision-making authority, making them more vulnerable to possible physician bias.
BACKGROUND: Despite concern about the high costs and the uncertain benefit of prolonged treatment in the intensive care unit (ICU), there has been little research examining decision-making and outcomes for patients with prolonged ICU stays. OBJECTIVES: To evaluate decision-making and outcomes for seriously ill patients with an ICU stay of at least 14 days. DESIGN: A prospective cohort study. SETTING: Five teaching hospitals. PARTICIPANTS: Seriously ill patients enrolled in the Study To Understand Prognoses and Preferences for Risks and Outcomes of Treatments (SUPPORT). MEASUREMENT: Patients, their surrogate decision-makers, and their physicians were interviewed about prognosis, communication, and goals of medical care. Based on age, diagnoses, comorbid illnesses, and acute physiology data, the SUPPORT Prognostic Model provided estimates of 6-month survival on study days 1, 3, 7, and 14. Hospital costs were estimated from hospital billing data. RESULTS: Of the 9105 patients enrolled in SUPPORT, 1494 (16%) had ICU stays of 14 days or longer. The median length of stay in an ICU was 4 days for the entire SUPPORT cohort and 35 days for patients who were treated in an ICU for 14 days or longer. Median hospital costs were $76,501 for patients who had ICU stays 14 days or longer and $10,916 for patients who did not have long ICU stays. Fifty-five percent of patients with long ICU stays had died by 6 months, and an additional 19% had substantial functional impairment. Among patients with ICU stays of at least 14 days, only 20% had estimates of 6-month survival that fell below 10% at any time during their hospitalization. For patients with long ICU stays, the mean predicted probability of 6-month survival was 0.46 on study Day 3 and 0.47 on study Day 14. Fewer than 40% of patients (or their surrogates) reported that their physicians had talked with them about their prognoses or preferences for life-sustaining treatment. Among the patients who preferred a palliative approach to care, only 29% thought that their care was consistent with that aim. Those who discussed their preferences for care with a physician were 1.9 times more likely to believe that treatment was in accord with their preferences for palliation (95% CI, 1.4-2.5) CONCLUSIONS: Prolonged ICU stays were expensive and were often followed by death or disability. Patients reported low rates of discussions with their physicians about their prognoses and preferences for life-sustaining treatments. Many preferred that care focus on palliation and believed that care was inconsistent with their preferences. Patients were more likely to receive care consistent with their preferences if they had discussed their care preferences with their physicians.
The Farm and Agricultural Injury Classification (FAIC) code was developed specifically to identify and classify all agricultural injuries of interest to agricultural safety and health professionals. The FAIC code overcomes fundamental problems of classifying agricultural-related injuries by grouping incidents into categories describing actual exposures encountered on farms and in agricultural work. The successful application of the FAIC code depends largely on a researcher's ability to obtain appropriate information to correctly use the code. The purpose of this research project was to: (1) compare data obtained through a newly developed FAIC follow-up questionnaire (FQ) with data from the Penn State Agricultural Injury Database (AID); and (2) test FAIC Code utility, reliability, and construct validity with agricultural safety and health professionals. The FQ improved classification of 57% of cases in the Penn State AID. A majority of agricultural health and safety professionals understood and used the FAIC coding system, without training, to code an average of 75% of the test cases the same as the researcher. A large majority of the professionals that participated in this study judged the FAIC code and the accompanying materials to be very useful.
The Agricultural Safety and Health Best Management Practices (ASHBMP) Manual was developed as an alternative intervention tool to help identify and correct farmwork hazards. A modified pretest-posttest control group experimental design was used to test the effectiveness of the manual with three intervention groups and a control. Testing consisted of conducting baseline and post-intervention audits on 150 farms in Pennsylvania. Significant differences were found among groups of farmers who were given the ASHBMP Manual and those who were not given the manual. The results of the data analysis also showed a positive significant difference among farmers who reduced their farm hazard levels through use of the ASHBMP Manual over farmers who received the Control (traditional safety fact sheets). The data supports the conclusion that the ASHBMP Manual is an effective tool for helping farmers reduce workplace hazards.
Compliance with preventive screening tests is inadequate in the United States. We describe a computer based system for generating reminder letters to patients who may have missed their indicated screening tests because they do not visit a provider regularly or missed their tests despite the fact that they do visit a provider. We started with national recommendations and generated a local consensus for test indications. We then used this set of indications and our electronic record to determine test deficiencies in our pilot pool of 3073 patients. The computer generated customized reminder letters targeting several tests. Physicians chose any patients who should not receive letters. The response rate for fecal occult blood (FOB) testing was 33% compared with an 18% historical compliance rate within the same community. FOB reminders generated improved test compliance. Test execution must be considered when commencing a program of screening test reminders.
Fatty acids are accumulated in triacylglycerols (TAGs), in specialized organelles of seeds named oil bodies. The major site of TAG accumulation is detected in developing seed and mesocarp of certain species. We have isolated two cDNAs encoding DGAT enzymes from olives. The deduced polypeptides differ by 26 amino acids in size. However, they have high homology and almost identical hydropathy profiles. The DGAT gene is expressed in all tissues that synthesize TAGs. However, higher levels of DGAT transcripts have been detected in seed tissues of developing olive drupe. DGAT expression and mRNA accumulation in drupe tissues is developmentally regulated. Each DGAT transcript shows a distinct profile of accumulation. The existence of two different DGAT transcripts might reflect two different enzymes with discrete function and/or localization.
A comparative approach has been used to study the role of several lipid-body-binding proteins in plants and animals. Caleosins are a newly discovered class of calcium-binding lipid-body proteins found in plants and fungi, which we now report to have separate endoplasmic reticulum- and lipid-body-associated isoforms. We also compare the lipid-body targeting of oleosin from plants and the core protein of the hepatitis C virus when they were expressed separately in lipid-accumulating animal cell lines. This is a novel and powerful approach to investigating the factors that determine the lipid-body targeting of a wide range of proteins.
Inositol phosphorylceramide synthase (IPC synthase) is an essential and unique enzyme in fungal sphingolipid biosynthesis and is the target of the cyclic nonadepsipeptide antibiotic aureobasidin A. As a first step towards understanding the mechanism of aureobasidin A inhibition, we developed a fluorometric HPLC assay for IPC synthase using the Saccharomyces cerevisiae enzyme and the fluorescent substrate analog 6-[N-(7-nitro-2,1, 3-benzoxadiazol-4-yl)amino]-hexanoyl ceramide (C(6)-NBD-cer). The kinetic parameters for C(6)-NBD-cer were comparable to those for the synthetic substrate N-acetylsphinganine used previously. Aureobasidin A acted as a tight-binding, non-competitive inhibitor with respect to C(6)-NBD-cer and had a K(i) of 0.55 nM.
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The first transgenic crop with a modified seed oil composition was released for commercial use in 1995. Many additional transgenic rapeseed varieties expressing novel seed oils or proteins are now under development. Recent research advances in Arabidopsis molecular genetics and the emerging relatedness between the Arabidopsis and Brassica genomes will enable more radical manipulation of many key agronomic traits in rapeseed. These will range from greatly improved seed oil yield to the production of seed oils with defined fatty acid contents ranging from C8 to C24 chain lengths and including many desirable functionalities including double bonds, triple bonds, hydroxy and epoxide groups. Much of the technology currently being development in rapeseed and soybean oil modification will be directly applicable to other oil crops including high yield tropical perennials such as oil palm.
The composition of the two major lipidic organelles of the tapetum of Brassica napus L. has been determined. Elaioplasts contained numerous small (0.2-0.6 micron) lipid bodies that were largely made up of sterol esters and triacylglycerols, with monogalactosyldiacylglycerol as the major polar lipid. This is the first report in any species of the presence of non-cytosolic, sterol ester-rich, lipid bodies. The elaioplast lipid bodies also contained 34- and 36-kDa proteins which were shown by N-terminal sequencing to be homologous to fibrillin and other plastid lipid-associated proteins. Tapetosomes contained mainly polyunsaturated triacylglycerols and associated phospholipids plus a diverse class of oleosin-like proteins. The pollen coat, which is derived from tapetosomes and elaioplasts, was largely made up of sterol esters and the C-terminal domains of the oleosin-like proteins, but contained virtually no galactolipids, triacylglycerols or plastid lipid-associated proteins. The sterol compositions of the elaioplast and pollen coat were almost identical, consisting of stigmasterol > campestdienol > campesterol > sitosterol >> cholesterol, which is consistent with the majority of the pollen coat lipids being derived from elaioplasts. These data demonstrate that there is substantial remodelling of both the lipid and protein components of elaioplasts and tapetosomes following their release into the anther locule from lysed tapetal cells, and that components of both organelles contribute to the formation of the lipidic coating of mature pollen grains.
Atrioventricular (AV) canal defects should be diagnosed by means of echocardiography. Infants with complete AV canal defects should undergo intracardiac surgical repair before pulmonary vascular obstructive disease develops, preferably before 6 months of age. Repair of partial AV canal defects or primum atrial septal defects can be postponed until 18 to 36 months of age if the patient does not have pulmonary hypertension or growth failure. The one- and two-patch techniques can both provide excellent results with a low mortality rate in repair of complete AV canal defects. Repair of the cleft mitral valve at the time of initial surgery is advised to preserve long-term mitral valve function. Tetralogy of Fallot with AV canal defect can also be repaired but at an older age and with a greater incidence of reoperation. Unbalanced AV canal defects associated with a hypoplastic ventricle may necessitate initial pulmonary artery banding and a subsequent decision about the suitability of two-ventricle repair. If ventricular septation is unsuitable, a single-ventricle path is chosen. Bidi-rectional cavopulmonary anastomosis and, eventually, the Fontan procedure are used.