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Biomedical subjects

G Burke

Publications and source records attributed to G Burke.

At least 127 records · Page 7Linked to original sources

Non-histone chromatin proteins in beef thyroid: distinct phosphorylation patterns of several protein kinases.

Non-histone chromatin protein (NHCP) fractions were extracted from purified beef thyroid nuclear preparations and tested for the presence of protein kinase activities using several known mediators of thyroid regulation, as well as potential phosphotransferase substrates using purified or partially purified protein kinase activities. The addition of cAMP/3-isobutyl-1-methylxanthine had no effect on NHCP histone kinase activity; the addition of 10 micrograms of the heat-stable cAMP-dependent protein kinase A inhibitor, however, resulted in a 47% reduction in histone H1 kinase activity. Nuclear casein kinase II activity was present in the NHCP fractions as evidenced by the capacity of spermine to stimulate (ED50 = 0.19 mM) and heparin to inhibit (ID50 = 0.09 microgram/ml) the phosphorylation of casein; further, the phosphotransferase activity could be purified by sequential casein-agarose and spermine-agarose affinity chromatography. Neither calcium-calmodulin nor calcium/phosphatidylserine/diolein had an effect on NHCP casein kinase or histone kinase activities, respectively. The addition of cAMP-dependent protein kinase A catalytic subunit, nuclear casein kinase II, calcium-activated calmodulin-dependent protein kinase and diacylglycerol-activated calcium/phospholipid-dependent protein kinase C activities exhibited distinct phosphorylation patterns when NHCP were used as substrates and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. We conclude that NHCP fraction from beef thyroid: 1) contains both cAMP-dependent protein kinase A catalytic subunit and nuclear casein kinase II and 2) substrates for cAMP-dependent protein kinase A, calcium-activated calmodulin-dependent protein kinase, protein kinase C, and nuclear casein kinase II.

Animals↗

Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition?

OBJECTIVE: To determine whether intrauterine growth retardation associated with normal umbilical artery blood flow is a benign condition. DESIGN: A prospective comparative study of growth retarded fetuses with normal and abnormal umbilical artery blood flow. SETTING: The fetal assessment clinic of a large maternity hospital in Ireland. PATIENTS: 179 Women with singleton pregnancies in which the fetal abdominal circumference, measured by ultrasonography, was below the fifth centile for gestation. MAIN OUTCOME MEASURES: Perinatal deaths, fetal distress requiring caesarean section, preterm delivery, cerebral irritation. RESULTS: Of 124 fetuses with normal flow, all physically normal fetuses survived but one baby had cerebral irritation; there were six preterm deliveries and four caesarean sections for fetal distress. Among 55 women with abnormal flow there were two midtrimester abortions, three perinatal deaths, and one case of cerebral irritation in physically normal fetuses. CONCLUSIONS: Intrauterine growth retardation associated with normal umbilical blood flow is a different entity from that associated with abnormal flow, normal flow being largely benign and abnormal flow carrying a serious risk of adverse outcome.

Cesarean Section↗

True rupture/scar dehiscence in delivery following prior section.

Fear of uterine rupture has led to the widespread practice of 'Once a section, always a section'. Between 1972 and 1982, 1498 patients with one or more previous cesarean sections were delivered at University College Hospital, Galway. Trial of labor was undertaken in 844 patients, while the remaining 654 patients underwent repeat elective section because they had two or more prior sections. Eight true ruptures and 22 scar dehiscences were found. Regional analgesia and oxytocin did not significantly affect the rate of true rupture. The mean parity with uterine rupture was five, and it occurred most frequently in the initial trial of labor. There were four perinatal deaths associated with true rupture. Failure to detect the already compromised fetus before labor and delivery, rather than the method of delivery, was responsible for fetal demise in some instances. Five true ruptures were found in the trial of labor group (i.e. a ratio of 1:169), with the loss of three babies. A further baby was stillborn in a mother who ruptured a classical scar before labor. There were no maternal deaths in trial-of-labor patients and one in the elective section group. Two patients with true rupture had their uterus repaired, and were subsequently delivered by section. Another two patients with bloodless dehiscence and no repair, had two subsequent elective repeat sections each, and the unrepaired scar dehiscence was not evident.

Cesarean Section↗

Alcohol intake and blood pressure in young adults: the CARDIA Study.

Associations between self-reported average daily alcohol intake and blood pressure were assessed in 5031 black and white men and women ages 18-30 from the Coronary Artery Risk Development in Young Adults Study (CARDIA). In general, intake was positively but weakly related to both systolic and diastolic blood pressure. Associations with systolic pressure were generally stronger than those with diastolic pressure. With average daily alcohol intake categorized as none, 0.1-9.9 ml, 10.0-19.9 ml, 20.0-29.9 ml, and 30.0+ ml, mean systolic pressure, adjusted for age, body mass index, education, smoking, and physical activity, increased progressively with increasing intake in black and white men and in white women. Mean diastolic pressure increased progressively with increasing intake only in white men and women, but was highest for those averaging 30.0+ ml per day in black women as well as white men and women. Mean pressures were also compared for those averaging 75.0+ ml per day (men) or 50.0+ ml per day (women) vs those reporting no intake. Differences in adjusted mean pressures for white men were 3.2 mmHg (95% confidence limits (CL) -0.3, 6.8) for systolic pressure and 1.7 mmHg (-1.6, 5.0) for diastolic pressure. In black men differences were 4.4 mmHg (1.4, 7.4) and 3.4 mmHg (0.6, 6.3), respectively. Differences in white women were 1.4 mmHg (-2.5, 5.3) for systolic pressure and 0.9 mmHg (-2.7, 4.5) for diastolic pressure and for black women, -0.2 mmHg (-4.3, 3.8) and 1.9 mmHg (-1.9, 5.8). Separate analyses in smokers and nonsmokers of the associations between alcohol intake and blood pressure suggested that associations may differ by smoking status in some sex-race groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

An unusual case of pulmonary emboli.

The authors present an interesting case of pulmonary embolus serendipitously diagnosed during an evaluation for a presumed metastatic pulmonary nodule.

Diagnosis, Differential↗

OKT3 induction via idiotypic networks of mirror-image immunosuppressive antiimmunoglobulins in renal transplant recipients.

Four of 21 renal transplant recipients treated with OKT3 for rejection episodes developed a second sustained (approximately 2 weeks) depression in CD3 peripheral blood lymphocyte cell-surface-marker expression. This occurred after OKT3 therapy had ceased, subsequent to a return toward baseline CD3 levels seen before OKT3 therapy was instituted. The second decrease in CD3 T cell counts was dissociated from CD2 marker T cell counts using flow cytometry and coincided with transient cytomegaloviral infections. Three phases of immunosuppression were defined in these 4 patients: phase I (during OKT3 treatment); phase II (after treatment when CD3 counts were reconstituted); and phase III (when CD3 counts again were depressed). During phase III, serum of the 4 affected patients could transfer a blocking effect on the expression of the CD3 marker of peripheral blood T cells of "normal" laboratory volunteers. Contained in these sera were human IgG antibodies that bound on Western blot analysis and by radioautography after immunoprecipitation to a protein band of a T cell membrane lysate with an m.w. of 23 kD. The reaction was identical to that seen with OKT3 (immunoprecipitation). Moreover, this Western blot binding could be virtually (but not completely) eliminated by multiple absorptions of the T cell membrane lysate with OKT3. By using an affinity-purified human anti-OKT3 IgG from one of the 4 patients, it was possible to immunoabsorb from phase III sera the CD3 blocking activity as well as the binding to the 23 KD protein band. A reverse immune absorption by the phase III sera with the anti-OKT3 IgG after ultracentrifugation prevented the anti-OKT3 IgG from binding to OKT3 coated plates in solid-phase radioimmunoassay. These data support the notion that autoimmune human anti-anti-id (Ab2) antibodies can occasionally be generated by treatment with OKT3, which are directed against CD3 complex epitopes similar to the ligand of OKT3.

Adolescent↗

Triage considerations in medical intensive care.

As an initial step toward improving admission criteria to the medical intensive care unit (MICU), we examined Acute Physiologic and Chronic Health Evaluation scores and the diagnosis-adjusted mortality rates of 2419 medical patients, including those who received MICU consultation over a 6-month period. There was considerable overlap in the physiologic scores and the predicted mortality rates between those patients who were admitted to the MICU and those who were not. There was no discrete score or mortality rate at which triage to the MICU would have included most MICU patients but excluded most patients who survived without admission to the MICU. While uniform MICU admission criteria would be desirable, current scoring systems may not have the desired sensitivity or specificity to establish such criteria. Using a receiver operating characteristic curve, we demonstrated that diagnosis-adjusted mortality rates could predict as well as Acute Physiologic and Chronic Health Evaluation scores which patients would receive MICU admission and intervention. This suggests that, for different diagnoses, specific clinical variables and laboratory tests may have different predictive importance for MICU admission. Prospective models of clinical variables using receiver operating characteristic curves in various medical diseases may improve triage procedures.

Diagnosis-Related Groups↗

Impact of crime on the rural elderly.

Two hundred and seven persons over 65 years of age were interviewed to determine the impact of crime on their lives. The setting was during a much publicized series of assaults on the rural elderly in their homes. Seventy two per cent were upset, 40% of the total were moderately upset and 26% suffered a major upset. Females and those over 75 years old were most upset. Some aspect of change of lifestyle was found in the vast majority.

Age Factors↗

Update on delivery following prior cesarean section: a 15-year review 1972-1987.

Fear of true rupture remains the main indication for repeat section. Between 1972 and 1987 there were 2434 patients with one or more prior section and 1350 (55%) were permitted trial of labor, the remainder, having had two or more previous sections (maximum number, 10), had repeat surgery. Induction was employed in 31% and oxytocin for induction or acceleration in 32% patients. The first period (1972-1982) had 844 and the second period (1982-1987) had 506 trial of labor patients. Improved management resulted in the true rupture rate falling from 0.6% (1:169) to 0.2% (1:506) and the elimination of procedure-related perinatal death. There were two maternal deaths with repeat section and none with trial of labor. We have achieved a plateau for cesarean section (10-11%) and a continuing fall in the uncorrected hospital perinatal mortality, which has averaged 10.6/1000 for the years 1982-1986 inclusive.

Cesarean Section↗

Trial of labour following prior section; a 5 year prospective study (1982-1987).

Between 1982 and 1987, 506 women previously delivered by Caesarean section were subjected to a trial of labour. Vaginal delivery was achieved in 78.6% with only 1 true rupture of the scar (0.2%). There were no intrapartum or neonatal deaths. Moreover, 7 of the 8 antepartum stillbirths were due to asphyxia, and, as the perinatal mortality rate for the study group was higher than for the overall population, the need for antenatal surveillance in previously sectioned patients is emphasized. Induction of labour was performed in 127 patients with 74.1% achieving vaginal delivery. Oxytocin was administered to 162 patients for either induction or augmentation of labour and 80.3% had a vaginal delivery, with 1 true rupture and 4 bloodless dehiscences. It is concluded that trial of labour following prior section is associated with little risk of true rupture, and with no added risk to the fetus. Our policy and management has helped maintain over the past 5 years an overall moderate Caesarean section rate (10-11%) with a low perinatal mortality rate.

Cesarean Section↗

Delivery following cesarean section and perinatal mortality.

The perinatal mortality in 1498 patients with one or more previous cesarean section scars delivered between 1972 and 1982 was analyzed. Repeat elective cesarean section was performed in 654 (44%) patients and 844 (56%) were subjected to a "trial of scar." Successful vaginal delivery occurred in 702 (83%) patients and 142 (17%) had emergency repeat operations. There were 46 perinatal deaths, giving a perinatal mortality rate (PMR) of 30.3/1000. It was lowest in patients who electively had a cesarean section (10.6/1000). The corrected PMR was twice as high in the trial of scar group. The PMR for the overall hospital population (27,072 babies) during the study period was 22.5/1000. There were four perinatal deaths in association with dehiscence of the uterine scar. The PMR in trial of scar patients decreased from 40/1000 to less than 20/1000 without a major change in policy. Meanwhile the unit cesarean section rate increased from 5 to 10%, but the repeat section rate was consistent at around 38.5%. Regional analgesia was used in 192 patients, for repeat section in five and trial of scar in 187. Oxytocin was given to 546 (65%) patients. Scar rupture is considered the major contraindication to a trial of scar, but emphasis was not laid on the possible increased perinatal mortality with this procedure before the 1980s. In view of the improvement in the PMR and the added risk to the mother with cesarean delivery, we advocate a policy of trial of scar with informed consent in selected cases.

Cesarean Section↗

Long-term results of kidney transplantation at the University of Miami.

Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.

Adolescent↗

Posttransplant hyperglycemia. Increased incidence in cyclosporine-treated renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in two groups of renal allograft recipients. These were all nondiabetic patients who had been transplanted between 1979 and 1987 and received either azathioprine-methylprednisolone (group 1) or cyclosporine-methylprednisolone (group 2) therapy as maintenance immunosuppression. The incidence of PTDM in group 1 was 9.1% vs. 18.6% in group 2 (P less than .05). The mean daily dose of methylprednisolone during the initial 2 months posttransplant was not greater among the PTDM patients of groups 1 or 2. Cyclosporine levels and mean daily CsA doses during the initial 2 posttransplant months were also not different among the CsA-PTDM and euglycemic CsA patients. Posttransplant diabetes mellitus occurred rapidly (less than 2 months) and required insulin therapy in the majority of cases. Increased age (greater than 40 years) was associated with a higher risk for PTDM, however, the greater incidence accompanying increased body weight only approached significance. Patient gender and donor source were not associated with significant risk for PTDM. The development of PTDM was accompanied by a significant decrease in graft survival at 3 years in the entire PTDM population and at 4 years in the CsA-PTDM subgroup. Actuarial patient survival was not adversely affected. The current study suggests that CsA may be diabetogenic when administered with methylprednisolone to renal allograft recipients. The adverse effect on allograft survival requires further investigation. These results may also have important implications for pancreatic and islet cell transplantation.

Actuarial Analysis↗

Purification of a 107 kilodalton (kDa) casein kinase G substrate from thyroid cytosol.

A 107 kDa (pp107) casein kinase G (ck-G) substrate has been purified from mouse and beef thyroid cytosol; ck-G was purified from beef thyroid cytosol. Ck-G and pp107 were found to co-elute on DEAE cellulose chromatography at approximately 300 mM NaCl. Ck-G and pp107 were separated by spermine-agarose affinity chromatography; pp107 is eluted with a stepped gradient at 250 mM NaCl and ck-G is eluted at 500 mM NaCl. Ck-G was subsequently purified by casein-agarose and GTP-agarose affinity chromatography. The 107 kDa protein was purified using heparin-agarose affinity chromatography. Phosphorylation of purified pp107 by ck-G was stimulated by spermine (ED50 = 0.2 mM) and inhibited by low concentrations of heparin (0.1-5 micrograms/ml). The Km and Vmax for the reaction were 1.46 microM and 32.2 nmoles P transferred/20 min/mg protein, respectively; 1 mole pp107 incorporated 0.81 mole phosphorus. pp107 was found to be an acidic substrate with a pI of 3.87 and was absorbed to wheat-germ agglutinin-agarose. The specificity of pp107 phosphorylation was studied using diacylglycerol-activated calcium/phospholipid-dependent protein kinase C, calcium-activated calmodulin-dependent protein kinase, and the catalytic subunit of cAMP-dependent protein kinase A. Phosphorylation of pp107 by the other protein kinases tested never exceeded 4% of that of ck-G. Our data show that pp107 is an acidic glycoprotein which may serve as a high-affinity and specific substrate for ck-G.

Animals↗