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Biomedical subjects

H Watson

Publications and source records attributed to H Watson.

14 recordsLinked to original sources

Elevation of albumin synthesis rates in nephrotic patients measured with [1-13C]leucine.

Eight patients with a nephrotic syndrome and a histologically-proven kidney disease were compared to age- and sex-matched healthy volunteers. Albumin synthesis rates were measured after injection of 13C-labelled leucine (57 mg/kg body wt, 19.4 atoms%). Plasma volume was determined with 125I-albumin. The fractional synthesis rate of albumin was 7.9 +/- 0.4%/day in control subjects in comparison with a marked elevation to 18.4 +/- 2.0%/day (P less than 0.001) in nephrotic patients. The absolute synthesis rate was 145 +/- 9 mg/kg/day in control subjects compared with 213 +/- 17 mg/kg/day (P = 0.005) in the nephrotic patients. There was a statistically significant correlation between ASR and urinary albumin loss (P = 0.035) and serum cholesterol concentration (P = 0.007). The calculated oncotic pressure was significantly lower in the nephrotic group than in the controls (P less than 0.001), but was without correlation with ASR.

Adult

Endometrial phospholipases A2, polycystic ovaries and pelvic pain.

OBJECTIVE: To compare the activity of calcium independent phospholipase A2 in the endometrium of women with polycystic ovaries and in women with normal ovaries, and to investigate the influence of chronic pelvic pain on phospholipase A2 activity. DESIGN: A prospective descriptive study. SETTING: The Samaritan Hospital for Women and the Unit of Metabolic Medicine, St Mary's Hospital Medical School, London. SUBJECTS: 73 women attending the Samaritan Hospital for Women for clip sterilization, infertility, early recurrent miscarriage or pelvic venous congestion. 45 of these women had no pelvic pain, 22 had normal ovaries and 23 had polycystic ovaries diagnosed by ultrasound. The other 28 women had chronic pelvic pain, 14 of them had normal ovaries and 14 polycystic ovaries. INTERVENTIONS: Endometrial tissue was obtained at curettage or from the excised uterus in the proliferative or secretory phase of the menstrual cycle. The activities of calcium dependent (type 1) and calcium independent (type 2) phospholipase A2 isoenzymes were measured in all endometrial samples. RESULTS: In all the women phospholipase A2 type 1 activity, was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). There was no difference between women with normal ovaries and those with polycystic ovaries at either stage of the cycle irrespective of whether or not chronic pelvic venous congestion was present. In women with normal ovaries, both with and without chronic pelvic pain, phospholipase A2 type 2 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.02 and P less than 0.05 respectively) but in women with polycystic ovaries, with and without chronic pelvic pain, there was no significant difference in activity between the two phases of the cycle. Women with polycystic ovaries had markedly higher proliferative phase type 2 activity than women with normal ovaries (P less than 0.001). Secretory phase type 2 activity was similar in all the women investigated. CONCLUSION: These data suggest that phospholipase A2 type 2 activity is increased in proliferative phase endometrium of women with polycystic ovaries but that the increase is not associated with chronic pelvic venous congestion.

Arachidonic Acid

Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin.

OBJECTIVE: To assess the effect of moderate obesity on the outcome of induction of ovulation with low dose gonadotrophin in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective analysis of women with PCOS treated consecutively. An analysis of the impact of obesity on outcome of pregnancy using data from the North West Thames Regional (NWTR) obstetric database was included for comparison. SETTING: Induction of ovulation clinic at the Samaritan Hospital for Women (St. Mary's Hospital Group). SUBJECTS: 100 women with clomiphene-resistant anovulation associated with PCOS. 75 were of normal weight (BMI 19-24.9 kg/m2, lean group) and 25 were moderately overweight (BMI 25-27.9 kg/m2, obese group). INTERVENTIONS: Induction of ovulation using low doses of gonadotrophins with small, stepwise increments in dosage as required. MAIN OUTCOME MEASURES: Rates of ovulation, pregnancy and miscarriage; daily and total doses of gonadotrophin required for induction of ovulation. RESULTS: The proportion of ovulatory cycles was significantly greater in the lean group (77%) compared with the obese group (57%) (chi 2 9.8, P less than 0.001). Obese women required larger doses of gonadotrophin to achieve ovulation (P less than 0.001). The proportion of women who achieved at least one pregnancy was similar in the two groups (39% vs 48%) but miscarriage was more frequent in the obese group (60% vs 27%; P less than 0.05). This difference was independent of the baseline and/or mid-follicular luteinizing hormone (LH) concentration either before or during treatment. Analysis of data from the North West Thames Health Region obstetric database confirmed an increased risk of miscarriage in moderately obese women which was independent of maternal age. CONCLUSIONS: Moderate obesity in women with PCOS, treated with low dose gonadotrophin, is associated with an increased risk of miscarriage. This is reflected in the results of analysis of the effect of obesity on outcome of pregnancy in the general population. It is therefore important to encourage weight reduction in obese women with PCOS before considering therapy to induce ovulation.

Abortion, Spontaneous

Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort.

Markers of immune function present before infection may determine the subsequent course of disease in HIV-infected individuals. In 1983, we measured immune function in a group of haemophiliacs in Edinburgh. In 1984, 18 of these patients became infected with HIV-1 from contaminated factor VIII. We have followed-up these patients since their seroconversion. The rate of disease progression, as assessed by the appearance or not of AIDS symptoms or signs within five years of seroconversion, was related both to the concentration of total plasma IgM before exposure to infection and to the pattern of specific IgM and IgA anti-HIV response around the time of IgG seroconversion. Disease progression also correlated with concentrations of plasma interleukin-2 receptor (a marker of lymphocyte activation) and with the number and percentage of circulating DR + ve (activated) T cells. Our findings show that the extent of host immune reactivity, which may be genetically determined, is a powerful factor in the pathogenesis of HIV-associated disease.

Acquired Immunodeficiency Syndrome

Low-dose gonadotrophin therapy for induction of ovulation in 100 women with polycystic ovary syndrome.

Women with anovulation due to polycystic ovary syndrome are likely to develop multiple follicles during gonadotrophin therapy and therefore have a high risk of multiple pregnancy. We have developed a low-dose regimen for use in these women; 100 women with clomiphene-resistant polycystic ovary syndrome were treated. Ninety-five of the women ovulated at least once, 72% of the 401 cycles induced were ovulatory and the majority (73%) of these were uni-ovulatory. The overall cumulative conception rate was 55% at 6 months with only two multiple pregnancies. The rate of early pregnancy loss was 32%, which is similar to that reported by other groups. The prevalence of complications was low with no cases of severe hyperstimulation and less than 5% of cycles were abandoned because of development of multiple follicles. Analysis of baseline and mid-follicular luteinizing hormone levels showed that a raised baseline and/or mid-follicular luteinizing hormone level was associated with a poor response to treatment, i.e. anovulation, ovulation but no conception, or early pregnancy loss. There were no successful pregnancies in the women whose luteinizing hormone levels were persistently raised during ovulatory cycles. Low-dose gonadotrophin therapy is a safe and effective method of inducing ovulation; it is associated with a high incidence of single follicular development and a very low multiple pregnancy rate.

Clomiphene

Phospholipase activity in the endometrium of women with normal menstrual blood loss and women with proven ovulatory menorrhagia.

The activity of phospholipase A2 types 1 and 2 and phospholipase C was measured in the endometrium of women with ovulatory menorrhagia and in those with normal menstrual blood loss. In both groups of subjects phospholipase A2 type 1 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). The median activity (pmol/mg protein/min) for the proliferative phase was 27.6 in normal subjects and 40.4 in women with ovulatory menorrhagia and for the secretory phase the median activity was 144.5 in normal women and 138.1 in women with ovulatory menorrhagia. There was no difference between the two groups of women at either stage of the cycle. Phospholipase A2 type 2 activity was also higher in the secretory phase than in the proliferative phase (P less than 0.05 for normal subjects and P less than 0.001 for women with menorrhagia). The median activity (pmol/mg protein/min) for the proliferative phase was 94.4 (normal subjects) and 56.6 (women with menorrhagia) and for the secretory phase 148.3 (normal subjects) and 142.5 (women with menorrhagia). The activity of phospholipase A2 type 2 was significantly lower in the proliferative phase of women with ovulatory menorrhagia compared with normal subjects (P less than 0.05). Phospholipase C activity (nmol/mg protein/min) was significantly higher in women with ovulatory menorrhagia (median 8.2) compared with women with normal blood loss (median 5.5) (P less than 0.01).

Endometrium

Distribution of ventilation in normal children.

Measurements of closing volume and the distribution fo ventilation by both single-breath (SBN2) and multiple-breath nitrogen washout methods were obtained in 376 healthy boys and girls, ages 6 to 18 years. A closing volume could be demonstrated in 39 percent of the subjects, and closing volume expressed as percentage of vital capacity did not change with height. Closing capacity expressed as percentage of total lung capacity showed a slight decrease with height. The slope of phase III of the SBN2 curve decreased with height. Single compartment N2 washout curves were observed in 72 percent of the subjects, and the incidence of single compartment curves increased with age. In those subjects with two compartment N2 washout curves, the relative compartmental ventilation became more even with increasing height. Our observations suggest that parallel units among peripheral airways grow at different rates.

Adolescent

A new roentgenographic method for estimating mucous velocity in airways.

A new roentgenographic method is described for the estimation of mucous velocity in airways. Radiopaque discs of teflon mixed with bismuth trioxide were deposited in the trachea, and their motion was observed by a fluoroscopic image intensifier. Simultaneous measurements of disc movement were obtained by a previously reported cinebronchofiberscopic method and by the roentgenographic method in 6 anesthetized dogs. Mean +/- SD tracheal mucous velocity was 8.5 +/- 7.3 mm per min by the roentgenographic method, and 7.6 +/- 7.1 mm per min by the cinebronchofiberscopic method. Discrepancies between the 2 methods for individual disc velocities could be accounted for by the cumulative errors of both methods. The roentgenographic method was also used in 7 normal volunteers who did not have topical anesthesia of the tracheobronchial tree. The discs were blown through the inner channel of a bronchofiberscope, the tip of which was located just above the vocal cords. Placement of the discs on the tracheal mucosa generally did not produce coughing. Tracheal mucous velocity ranged from 7.4 to 19.4 mm per min as estimated from videotape recordings of the image intensifier images. There was no consistent difference in velocity between the erect or supine position, or after topical anesthesia with lidocaine.

Adult

Activation of the hypertrophic right ventricle in the dog.

Right ventricular hypertrophy (RVH) of mild, moderate, or severe degree was produced in six dogs following systolic overload of the right ventricle by surgical banding of the pulmonary trunk. Activation of the myocardium and specialized conducting tissue of the right ventricle was studied using intramural multi-electrodes or an exploring electrode, first with the heart in situ and then with the heart in a modified Langendorff perfusion circuit. Normal epicardial and intramural activation patterns were found in RVH, and the prolonged excitation time was found to be due to the increased muscle mass. No delay in activation was found in any part of the specialized conducting tissue of the right ventricle. Late activated Purkinje fibres were found in the outflow tract of the right ventricle in the dogs with hypertrophy and in a control series of normal dogs. The present electrocardiographic criteria for complete and incomplete right bundle branch block (RBBB) are based on widening of the QRS complex and the rSR pattern. This type of change can occur also in RVH. Because it has been shown here that no delay occurs in the specialized conducting system of the right ventricle in RVH secondary to systolic loading; the application of criteria to electrocardiograms that also fulfil the criteria for RVH may be misleading. It is suggested that in such cases the diagnosis of a conduction disturbance must also depend upon other methods, and that the terms "incomplete' and "complete' RBBB should be handled with care in this context.

Animals

Classification of ventricular pre-excitation. Vectorcardiographic study.

In a study of 45 cases of ventricular pre-excitation, 19 were classified as type A and 20 as type B according to Rosenbaum's criteria, which depend on the polarity of the major deflections in the right praecordial leads and not, as is commonly thought, on the direction of the delta vector. Six cases that could not be classified as type A or type B were termed intermediate. Vectorcardiograms were recorded from 29, and these showed a wide but continuous range of values for both the delta and the main QRS vectors in all three planes. Any classification based on these features must, therefore, depend on arbitrary quantitative data. Three patients in this series had associated right bundle-branch block. A review of the published reports on the association of pre-excitation and bundle-branch block failed to provide a rational basis for the classification of pre-excitation. It is emphasized that Rosenbaum's classification is empirical and its validity is questioned.

Adolescent

Automated system for measurement of mechanics of breathing.

We describe a complete automated system for measurement of total respiratory resistance and compliance, and of pulmonary resistance and compliance in humans and anesthetized animals. The device for testing the chest-lung system consists of a sinusoidal pump with a stroke adjustable from 20 ml to 600 ml over a cycling frequency of 0.3 to 30 Hz. Pressure and flow or volume are inputted into an analog network for wave shaping, then to an arithmetic unit composed of sample-and-hold amplifiers, peak, minimum and zero detecting circuits, an analog division circuit, and a digital logic processor. The computer takes the peak-to-peak amplitude of one of two sinusoidal inputs at 0.3 to 10 Hz and the corresponding amplitude of the other input in the presence of a.c. noise and d.c. shifts, divides one into the other, and displays an answer on a digital voltmeter. In addition, the analog output is displayed on the cathode-ray tube of a storage oscilloscope. Plots of total resistance and pulmonary resistance are recorded as a function of lung volume in both humans inspiring voluntarily as well as anesthetized dogs inflated by positive pressure from the test apparatus. Total and pulmonary dynamic compliance, as a function of breathing frequency, can only be measured by the computer if a symmetrical waveform is presented to it. This cannot be achieved in spontaneously breathing subjects but is accomplished in apneic animals by producing sinusoidal oscillations from the test apparatus. Our on-line method for measurement of total respiratory resistance is now used in the Clinical Pulmonary Laboratory for experimental work, and we are in the process of obtaining values in normal subjects.

Adult