A frog, a rock, a ritual: myth, mystery, and metaphors for an ecocaring cosmology in a universe that is turning over.
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Biomedical subjects
Publications and source records attributed to J Watson.
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OBJECTIVE: To evaluate fetal biophysical testing as a predictor of preterm delivery after preterm labor or preterm rupture of the membranes (PROM). METHODS: We studied 50 women with suspected preterm labor and intact membranes and 25 women with PROM but not in labor between 28 and 36 weeks' gestation. Before treatment, each subject had cervical Bishop scoring and 1-hour ultrasound observation of fetal heart rate, breathing, body movements, and flexion-extensions. Data were compared with t tests, chi 2 tests, or receiver operating curves. RESULTS: The mean gestational age at entry was similar in both groups. Twenty (80%) PROM and ten (18%) preterm labor patients delivered within 72 hours of admission; two (8%) PROM and 38 (76%) preterm labor patients delivered more than 7 days after admission. Absent breathing and body movements had high positive predictive values (100%) but moderate sensitivities (less than 55%) for predicting delivery within 72 hours or 7 days in the PROM and preterm labor groups. These sensitivities increased to nearly 70% with the addition of Bishop scores. The optimal diagnostic cutoffs for delivery within 72 hours or 7 days were a breathing incidence below 1% for the PROM group and a body movement incidence below 1% for the preterm labor group, and a breathing incidence of at most 5%. CONCLUSIONS: Complete absence of one biophysical variable confers limited sensitivity but high positive predictive value for early delivery in patients with preterm labor or PROM. The use of cutoff percentages for the incidence of individual variables improved sensitivity for both conditions. Cervical scoring added to biophysical monitoring by improving the sensitivity for early delivery of patients in preterm labor.
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To evaluate the question of whether or not insulin activates protein kinase C (PKC), we compared the effects of insulin and phorbol esters on the phosphorylation of the PKC substrate, i.e. myristoylated alanine-rich C-kinase substrate (MARCKS). In rat adipocytes, rat soleus muscle and BC3H-1 myocytes, maximally effective concentrations of insulin and phorbol esters provoked comparable, rapid, 2-fold (on average), non-additive increases in the phosphorylation of immunoprecipitable MARCKS. These effects of insulin and phorbol esters on MARCKS phosphorylation in intact adipocytes and soleus muscles were paralleled by similar increases in the phosphorylation of an exogenous, soluble, 85 kDa PKC substrate (apparently a MARCKS protein) during incubation of post-nuclear membrane fractions in vitro. Increases in the phosphorylation of this 85 kDa PKC substrate in vitro were also observed in assays of both plasma membranes and microsomes obtained from rat adipocytes that had been treated with insulin or phorbol esters. These insulin-induced increases in PKC-dependent phosphorylating activities of adipocyte plasma membrane and microsomes were associated with increases in membrane contents of diacylglycerol, PKC-beta 1 and PKC-beta 2. Our findings suggest that insulin both translocates and activates PKC in rat adipocytes, rat soleus muscles and BC3H-1 myocytes.
Enteroaggregative Escherichia coli (EAggEC) are associated with persistent diarrhea in young children. Some of these organisms produce a low-molecular-weight, heat-stable, plasmid-encoded enterotoxin that has been named EAggEC heat-stable enterotoxin 1 (EAST1). We have cloned a 4.4-kb DNA fragment from the virulence plasmid of prototype EAggEC strain 17-2, which expresses enterotoxic activity as measured by electrogenic response in Ussing chambers mounted with rabbit ileal tissue. DNA-sequence analysis of this fragment identified an open reading frame (ORF) encoding a cysteine-rich polypeptide of 38 amino acids (M(r), 4100). Insertional and deletional mutations in this ORF resulted in loss of enterotoxic activity. The ORF was cloned into a T7 expression vector, and postinduction culture filtrates exhibited enterotoxic activity and increased ileal tissue cGMP levels. A synthetic peptide consisting of predicted amino acid residues 8-29 also showed enterotoxic activity. These data indicate that this ORF, named astA (EAggEC heat-stable enterotoxin), represents the EAST1 structural gene. EAST1 shows significant homology with the enterotoxic domain of heat-stable enterotoxin a (STa) of enterotoxigenic E. coli and with guanylin, a mammalian analog of STa. Unlike STa, which requires six cysteines and three disulfide linkages for full biological activity, both EAST1 and guanylin contain four cysteine residues. Based on the cGMP data and the sequence homology to STa and guanylin, it is predicted that EAST1 stimulates the particulate form of guanylate cyclase through the same receptor-binding region as STa and guanylin.
During late December 1989 and early January 1990, a cluster of six unexplained deaths occurred on a paediatric intensive care unit (PICU) among children with congenital heart disease who had undergone cardiac surgical procedures. The children were all aged three years or less. In each case death was preceded by an unexpected increase in ventilatory pressure requirement followed by the development of a similar pulmonary shadowing on chest radiography. The radiological abnormality was felt to be consistent with a pneumonitis associated with some small airway disease. The clustering of these deaths, occurring in a similar unusual manner, was felt to constitute an outbreak warranting investigation. An Incident Committee was established to plan and manage a large multidisciplinary investigation during which the unit was temporarily closed. Following extensive investigation no bacterium, virus, fungus or other pathogen, toxic agent, or any other explanation for the cluster of deaths could be found. The possibility that the cluster occurred by chance remains although this was felt to be unlikely.
The Heartstart Scotland project for out-of-hospital defibrillation covers the whole of Scotland, a population of approximately 5,102,400 (14.9% > 65 years, 48.3% male). All 395 ambulances in Scotland have been equipped with an automated external defibrillator and crews are trained in basic cardiopulmonary resuscitation and defibrillator use (EMT-D). Between 1 May 1990 and 30 April 1991 a total of 1700 cardiac arrests was reported by the ambulance service. Of the 1676 arrests which we could trace, 63% were witnessed. A total of 1383 (83%) of all patients were declared dead on arrival at hospital or in the emergency department, 119 (7%) died in hospital and 174 (10%) were discharged alive. Of the 174 survivors, 87% were conscious and normal at discharge, 9% had moderate residual disability and 2% severe disability. Survival of patients discharged alive from hospital was 85% at 1 year. Defibrillation was undertaken in 71% of the reported cardiac arrests. Survival of bystander witnessed arrests was increased from 7 to 15% with bystander CPR (P < 0.005). If the cardiac arrest was witnessed by the ambulance crew and required defibrillation, survival to discharge was 39%. Of bystander witnessed arrests reached while still in VF (n = 643), 11% were discharged alive. Patients who were defibrillated within 4 min of arrest had a 43% survival rate to hospital discharge.
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As the number of human immunodeficiency virus (HIV) infected patients has increased in the U.S., the number of infected patients treated for end-stage renal disease (ESRD) has stabilized at about 1 to 2% of the hemodialyzed population. Little has been written regarding the role of continuous ambulatory peritoneal dialysis (CAPD) in the treatment of HIV infected patients with ESRD. To evaluate the effectiveness of CAPD as a long term therapy for HIV infected patients with ESRD, we reviewed our ESRD program's experience. We entered 392 patients from its inception in February 1984 until April 1992. Thirty-one, or 7.9% of our population were HIV infected. Twenty, or 64.5% had stage IV infection. Patients were entered into our chronic hemodialysis (HD) or CAPD program according to standard clinical criteria. Eight HIV infected patients elected to start CAPD, while 23 patients were treated exclusively with HD. The proportion of stage IV infected patients was similar in both treatment modality groups. HIV infected ESRD patients were younger than non-HIV infected patients (37.5 +/- 9.7 vs. 49.8 +/- 15.7 years, respectively, P < 0.0001) at the start of treatment. We used Cox regression techniques to analyze survival data. Mean survival time for our entire non-HIV infected ESRD population (N = 361) was 44.0 +/- 33.9 months. Mean survival time for HIV infected patients with ESRD was 15.5 +/- 9.9 months. Median survival for HIV infected ESRD patients was 13 months compared to 38 months for the non-infected population. As expected, mean survival time in HIV infected ESRD patients was significantly diminished compared to non-infected ESRD patients (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
In this study, dietary supplements of blackcurrant seed oil (BCO) rich in the n-6 polyunsaturated fatty acid (PUFA) gamma-linolenic acid were fed to both RA patients and healthy volunteers with sunflower seed oil being fed to control subjects. A significant improvement in morning stiffness was noted in the RA patients receiving BCO. Monocytes were isolated from all subjects and cultured in the presence of lipopolysaccharide. It was observed that the production from the cultured monocytes of the cytokines IL-1 beta, TNF alpha and IL-6 as well as the prostaglandin PGE2 was markedly altered in those subjects given BCO. The results suggest that the numerous beneficial effects of PUFAs in inflammatory diseases such as RA may be due to a reduction in the secretion of the inflammatory cytokines IL-1 beta and TNF-alpha via redirection of eicosanoid metabolism although the possibility cannot be excluded that the PUFAs may be altering cytokine release directly through an effect on monocyte membranes.
Serum soluble interleukin 2 receptor (sIL-2R) concentrations reflect lymphocyte activation in vivo. An investigation was carried out to determine if sIL-2R concentrations correlate with existing disease activity parameters in patients with rheumatoid arthritis (RA) and whether these concentrations are modulated by treatment with second line drugs. Seventy nine patients with rheumatoid arthritis with active disease were prospectively treated with sodium aurothiomalate, auranofin, or sulphasalazine. Sequential concentrations of sIL-2R were measured by enzyme linked immunosorbent assay (ELISA). No correlations were observed between sIL-2R concentrations and clinical parameters and there were only moderate associations with concentrations of C reactive protein and the erythrocyte sedimentation rate. Concentrations of sIL-2R did not significantly change with treatment. It is concluded that sIL-2R probably measures an aspect of rheumatoid synovitis distinct from acute phase reactants and is not influenced by treatment with second line drugs.
In rheumatoid synovium interleukin 6 (IL-6) is the most abundantly expressed cytokine. Increased serum levels have been previously reported in patients with rheumatoid arthritis (RA). In this study serum IL-6 levels were measured in a well defined cohort using a bioassay (B9 cells) and levels were correlated with conventional clinical and laboratory indices of disease activity. Levels were significantly higher in serum from patients with RA (median 55 IU/ml; interquartile range 28-139) compared with serum from disease (median 7 IU/ml; 1-23) and normal controls (median 10 IU/ml; 7-12). No difference was observed between men and women. Levels did not correlate with disease duration. Significant associations were observed between IL-6 and C reactive protein and between the Ritchie articular index and duration of morning stiffness. No other correlations were observed. The value of these findings in the monitoring of RA and as an indicator of response to second line treatment needs to be established.
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