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Biomedical subjects

T Wheeler

Publications and source records attributed to T Wheeler.

At least 19 recordsLinked to original sources

Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens.

Positive surgical margins have been reported with disturbing frequency in radical prostatectomy specimens and may portend an increased risk of eventual treatment failure. We determined the location of any cancer, extracapsular extension and positive surgical margins in 144 consecutive step-sectioned radical prostatectomy specimens. Of the 46 stage A cancer patients 98% had residual cancer in the prostate after transurethral resection and in 76% cancer was found posteriorly in the gland. Extracapsular extension was identified in 10 patients (22%): anteriorly in 5, posterolaterally in 5 and on the most apical transverse section in 4. Positive margins were found in 10 patients (22%) and half of these occurred posterolaterally. Of the 98 stage B cancer patients tumor was located posteriorly in 97%. Extracapsular extension was found in 62 patients (63%) and in 87% of these it was located posterolaterally. Positive margins were found in 23%, most commonly in the posterolateral and rectal areas (57% and 26%, respectively), and in more than half of these the positive margin resulted from incision into the capsule. In 18 of the 144 patients (13%) a single positive surgical margin was the only pathological indicator of treatment failure and half of these occurred in the area of the neurovascular bundle. Some of these patients with extraprostatic tumor might have been cured if wide excision of the neurovascular bundle had been performed. Overemphasis on preservation of potency during radical prostatectomy may leave some patients with persistent local disease.

Humans

A CD4-derived peptide carrier blocks acute HIV-1 infection in vitro and binds to gp120 in the presence of Walter-Reed stage 1-6 HIV+ sera.

A peptide containing amino acid residues 41-84 of the CD4 molecule was synthesized and coupled through a thioether bond to human serum albumin. This conjugate bound to gp120 with an affinity that was half that of CD4 and blocked the HIV infection in vitro with an efficacy tenfold lower than that of CD4. More importantly, the CD4 peptide-human serum albumin conjugate could bind to gp120 in the presence of HIV+ sera from 18 Walter Reed stage 1-6 patients.

Acquired Immunodeficiency Syndrome

Antenatal cardiotocogram quality and interpretation using computers.

OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention.

Cardiotocography

Comparison of the T/QRS ratio of the fetal electrocardiogram and the fetal heart rate during labour and the relation of these variables to condition at delivery.

The T/QRS ratio of the fetal electrocardiogram (ECG) was recorded to within 30 min of delivery from 105 women in labour. There were no significant differences in the mean T/QRS ratio in the last hour of record between those with normal and intermediate, or abnormal fetal heart rate (FHR) patterns. In 66 labours the mean T/QRS ratio in the first hour of record was compared with that of the last hour; the only significant change was a small decrease in the mean ratio from 11% to 7% in a group of 11 fetuses with an abnormal FHR pattern throughout the recording time. Eight babies were born with evidence of acidosis (umbilical artery pH less than or equal to 7.16), and another four were born in poor condition (1 min Apgar score less than 4) without evidence of acidosis; none had a mean last hour T/QRS ratio significantly different from the previously established normal range.

Apgar Score

Fetal heart rate and intrauterine growth.

OBJECTIVE: To assess whether fetal heart rate in early and late pregnancy relates to size at birth. DESIGN: Prospective study of fetal heart rates in early and late pregnancy. SETTING: Princess Anne Hospital, Southampton. SUBJECTS: 63 primigravid women. MAIN OUTCOME MEASURES: Anthropometric measurements made on the newborn infant. RESULTS: There were no differences in heart rate between the sexes at 18 weeks gestation but by 36 weeks the boys had rates which were 4.4 beats lower than those of the girls. Higher fetal heart rate at 18 weeks was associated with lower ponderal index, smaller head circumference and smaller mid-arm circumference. There were no trends in fetal heart rate at 36 weeks with any birth measurements. CONCLUSION: Babies born at term who have a pattern of neonatal measurements which reflect growth retardation have raised heart rates in early pregnancy. Influences which impair fetal growth appear to take effect early in gestation.

Anthropometry

Computer analysis of fetal heart rate variation during normal pregnancy.

Ninety-seven one-hour recordings of the abdominal fetal electrocardiogram (ECG) were made from 59 normal patients between 21 and 41 weeks of gestation. The heart intervals, measured between successive R-waves, were analysed by computer. The signal-to-noise ratio of the fetal ECG limited the precision of the interval measurements to approximately one millisecond. The characteristics of the baseline heart rate changed significantly as gestation advanced, the mean R-R interval, the standard deviation of the intervals and the standard deviation of the interval differences all increasing with gestation (p less than 0.001). In later gestation the baseline heart rate during periods of fetal rest differed significantly from that during periods of fetal activity; during rest the mean R-R interval was greater (p smaller than 0.001) and the standard deviations of the intervals and interval differences were smaller (p smaller than 0.001). Examination of the coefficient of variation of the heart intervals gave a result which contradicted the significance of this measurement as an index of fetal welfare as proposed by Curran and MacGregor (1970).

Analysis of Variance

Measurement of the fetal heart rate during pregnancy by a new electrocardiographic technique.

An external technique for recording the fetal heart rate (FHR) during pregnancy is described. The system is based upon the detection of the fetal electrocardiogram (ECG) from the maternal abdomen and elimination of the maternal QRS complexes by a new system of subtraction. Fetal QRS complexes with an amplitude of 10 microvolts or more were processed to produce heart rate recordings of much higher quality than previously obtained with the phonocardiographic and ultrasonic systems. The proportion of successful recordings was reduced between 27 and 34 weeks of gestation due to the decrease in size of the fetal QRS complex which occurred at this time; this was a major drawback of the ECG system.

Electrocardiography

Polyoma virus complementary RNA directs the in vitro synthesis of capsid proteins VP1 and VP2.

Polyoma virus complementary RNA, synthesized in vitro by using highly purified Escherichia coli RNA polymerase and nondefective form I polyoma DNA, was translated in a wheat germ cell-free system. Polypeptides were synthesized that comigrated on sodium dodecyl sulfate-polyacrylamide gels with the polyoma capsid proteins VP1 and VP2, although most of the cell-free products were of smaller molecular weights. The VP1-size protein specifically immunoprecipitated with anti-polyoma virus serum, and upon digestion by trypsin yielded [35S]methionine-labeled tryptic peptides that co-chromatographed with the [3H]methionine-labeled tryptic peptides of virion-derived VP1 on both cation-exchange and anion-exchange resins. The VP2-size in vitro product contained all the virion VP2 methionine-labeled tryptic peptides, as shown by cation- and anion-exchange chromatography and two-dimensional fingerprinting on cellulose. We conclude that full-length polyoma VP1 and VP2 are synthesized in response to complementary RNA and consequently that the viral capsid proteins VP1, VP2, and VP3 are entirely virus coded.

Capsid

Cell-free synthesis of polyoma virus capsid proteins VP1 and VP2.

Polyadenylated RNA isolated from the cytoplasm of mouse 3T6 cells 28 h after infection with polyoma virus has been isolated and translated in vitro. Polyoma capsid proteins VP1 and VP2 have been identified in the cell-free product by polyacrylamide gel electrophoresis, specific immunoprecipitation, and tryptic peptide fingerprinting. Polyoma mRNA species have been isolated by preparative hybridization to purified viral DNA immobilized on cellulose nitrate filters and shown to code for both VP1 and VP2. These experiments establish conditions for the isolation of late polyoma mRNA and the cell-free synthesis of polyoma capsid proteins and indicate that the active mRNA species are at least partially virus coded.

Capsid

Location of the sequences coding for capsid proteins VP1 and VP2 on polyoma virus DNA.

The 19S and 16S polyoma virus late mRNAs have been separated on sucrose-formamide density gradients and translated in vitro. The 16S RNA codes only for polyoma capsid protein VP1, while the 19S RNA codes in addition for capsid protein VP2. Since the 19S and 16S species have been previously mapped on the viral genome, these results allow us to deduce the location of the sequences coding for VP1 and VP2. Comparison of the chain lengths of the capsid proteins with the size of the viral mRNAs coding for them suggests that VP1 and VP2 are entirely virus-coded. Purified polyoma 19S RNA directs the synthesis of very little VP1 in vitro, although it contains all the sequences required to code for the protein. The initiation site for VP1 synthesis which is located at an internal position on the messenger is probably inactive either because it is inaccessible or because it lacks an adjacent "capped" 5' terminus. Similar inactive internal initiation sites have been reported for other eucarotic viral mRNAs (for example, Semliki forest virus, Brome mosaic virus, and tobacco mosaic virus), suggesting that while eucaryotic mRNAs may have more than one initiation site for protein synthesis, only those sites nearer the 5' terminus of the mRNA are active.

Base Sequence