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Biomedical subjects

J R Newton

Publications and source records attributed to J R Newton.

At least 19 recordsLinked to original sources

Fumarylacetoacetase activity in cultured and non-cultured chorionic villus cells, and assay in two high-risk pregnancies.

We describe further development of the fumarylacetoacetase (FAA) assay for the prenatal diagnosis of tyrosinaemia type 1 using chorionic villus sampling (CVS). We have established a reference range for FAA activity in cultured villus cells and have confirmed previously reported data on the FAA activity in uncultured chorionic villus cells. This should allow confirmation of results using CVS, without the need for further invasive procedures. We report the FAA enzyme stability at -70 degrees C, +4 degrees C, and at room temperature, and we have shown no obvious difference in enzyme activity with gestational age. We have analysed cultured and non-cultured CVS activity of FAA in two pregnancies at risk of tyrosinaemia type 1. In both, the fetus was designated unaffected, and these results were confirmed postnatally.

Cells, Cultured

Ovarian activity and bleeding patterns during extended continuous use of a combined contraceptive vaginal ring.

A combined contraceptive vaginal ring with a mean release rate of 0.015 mg of ethinyloestradiol and 0.120 mg of 3-ketodesogestrel per day was used by female volunteers, for either 28, 42, 56 or 84 days. Contraceptive efficacy was assessed by pelvic ultrasound scanning, endocrine monitoring and cervical mucus assessment. Menstrual diary cards were analysed to assess the effect on cycle control. Ovulation inhibition was seen in all treatment groups. Following removal of the ring, a return to an ovulatory cycle was observed in all volunteers. With extension of the treatment cycle beyond the recommended 21 days, there is an increase in the occurrence of bleeding and spotting episodes. This can be compared to patterns obtained during continuous use of combined oral contraceptives.

Administration, Intravaginal

The effects of a combined contraceptive vaginal ring releasing ethinyloestradiol and 3-ketodesogestrel on vaginal flora.

Fifty nine women with documented normal ovulatory cycles and with no symptoms of vaginal infection were divided into four groups. Each group used a combined contraceptive vaginal ring (CCVR) with a mean daily release rate of 0.015 mg of ethinyloestradiol (EE) and 0.120 mg of 3-ketodesogestrel (3-KDG) per day, for one cycle of either 21, 28, 42, or 56 days. Cultures from the posterior vaginal fornix and from the endocervical canal were obtained immediately before insertion of the ring and on removal of the ring. Changes in the numbers of vaginal cells, aerobic and anaerobic bacteria, Chlamydia trachomatis, Gardnerella vaginalis, yeasts and Trichomonas vaginalis were documented at the end of each treatment. Intra- and inter- group changes in the vaginal flora were assessed at the end of each treatment. The comparison between the number and type of flora showed no significant change between the pre-treatment population and the post-treatment population. The results of this study suggest that the use of this CCVR for 21, 28, 42 and 56 days is not associated with an increase in inflammatory cells or pathogenic bacteria.

Administration, Intravaginal

Clinical and pathological factors in spontaneous abortion following chorionic villus sampling.

Twenty-nine cases of spontaneous abortion following first-trimester chorionic villus sampling (CVS) were reviewed out of a series of 722 patients. Of the 29 cases, there were only four abnormal CVS results. Pathological examination was performed in 79 per cent of cases, and this did not identify any characteristic pathological feature associated with spontaneous abortion after CVS. There was no obvious difference in the pathological features following the transabdominal (TA) or the transcervical (TC) methods. The majority of miscarriages occurred within 4 weeks of the procedure, but 38 per cent of cases aborted between 7 and 14 weeks after CVS. The TC method was used in 22 patients; the TA in 6; and both methods in 1 patient. The TA method was associated with a significantly lower fetal loss rate than the TC method (TA 2 per cent, TC 9 per cent, p less than 0.001).

Abortion, Spontaneous

Effects of chlorhexidine-coated intrauterine device on the bacteriology of the uterine cavity.

Twenty-nine women, aged 31-53 years, scheduled for an abdominal hysterectomy, participated in this study. The patients were divided into three groups. The first received a Multiload MLCu250 intrauterine device (IUD); the second group received a chlorhexidine acetate medicated Multiload MLCu250 IUD; the third group acted as a control group receiving no IUD. Bacteriological cultures of the vagina and ectocervix were taken prior to insertion of the IUD. At hysterectomy, some 18 hours later, specimens were taken from the cervical canal, uterine cavity, and the device itself, for culture of anaerobic and aerobic organisms using a standardized previously validated technique. In three of the nine control patients, organisms were cultured from the uterine cavity. There were no differences between the bacteriological results of the two groups with medicated and non-medicated devices, with regard to the cultures from the cervical canal, uterine cavity or the devices themselves. Nor was there any difference between the control and the IUD group.

Adult

Main bronchial sleeve resection with pulmonary conservation.

Twenty-seven main bronchial resections (19 left, 8 right) were performed without pulmonary resection between 1975 and 1991. The patients were 17 men and 9 women with an average age of 35 years (range, 20 to 65 years). Tumors comprised 55% of the lesions, including 9 carcinoid tumors (33%), 2 mucoepidermoid tumors, 2 fibrous histiocytomas, 1 hemangiopericytoma, and 1 large cell carcinoma. Scarring and stenosis secondary to multiple causes occurred in 10 patients (37%). Two patients had miscellaneous lesions. Presenting symptoms included dyspnea (52%), wheezing or stridor (44%), cough (41%), hemoptysis (37%), and pneumonia (18%). Preoperative chest roentgenogram was abnormal in 60% of patients, whereas tomograms delineated the lesion in 94%. All patients had bronchoscopy for lesion evaluation. Anesthesia was accomplished through a long single-lumen endotracheal tube in 19 cases and a double-lumen tube in 8 cases. Mobilization and exposure techniques to create a tension-free anastomosis were critical for left main bronchial resections and included pretracheal mobilization (100%), neck flexion (100%), tracheal and main bronchial retraction (85%), aortic and pulmonary artery retraction (44%), and intrapericardial hilar release (33%). All resections were for cure; there was no operative mortality. Morbidity in 4 patients (15%) included an anastomotic stenosis (successfully reresected), prolonged air leak and pneumonia, transient recurrent nerve palsy, and atelectasis. Median 5-year follow-up revealed 92% of patients alive, with only one of two late deaths being disease-related. Main bronchial resection is an ideal technique for selected benign and malignant lesions, allowing complete pulmonary parenchymal preservation.

Adult

Pharmacodynamics of a contraceptive vaginal ring releasing 3-keto-desogestrel.

The pharmacodynamic effects of a new type of 3-keto-Desogestrel [3kDOG] releasing vaginal ring was studied in a group of 20 normally ovulating women during a period of 21 days continuous use. Peripheral blood samples were taken for the estimation of progesterone and oestradiol levels, ultrasound tracking for follicular growth and cervical mucus sampling for scoring [modified Insler] and sperm penetration testing during a control, treatment and recovery period. Additional blood samples were taken for the estimation of 3kDOG levels during the treatment period. After a control cycle, twenty normally ovulating women were selected and randomly divided into two groups. Group A were given a vaginal ring on day 5 of the menstrual cycle releasing 30 ug/24 hours of 3kDOG and group B a similar ring releasing 15 ug/24 hours of kDOG. Of the treatment cycles, none showed an ovulatory pattern in group A and there was only one in group B, the respective mean plasma levels of 3kDOG were 0.38 and 0.25 pmol/ml. The formation of "cysts" or persistent follicles was common to both groups, 6 out of 10 subjects in group A and 8 out of 10 subjects in group B had "cysts" greater than 25mm in diameter in the treatment cycle, this had become 5 out of 10 and 8 out of 10, respectively, in the recovery cycle. A comparison of the cervical mucus scores and sperm penetration of cervical mucus showed a significant reduction between the control and treatment groups but no significant difference between the two groups. The bleeding profiles showed an increase in percentage of bleeding days in both treatment groups to 25% in group A and 21.7% in group B [cf, 17.1%, 15.9%, respectively, in control month]; there being no statistical difference between groups. In conclusion, it is believed that given the efficacy demonstrated and the low level of menstrual disturbances found, this system warrants further investigation as a means of contraception as it appears to offer a better compromise than previous vaginal ring systems.

Administration, Intravaginal

The in vivo release characteristics of a multi-compartment vaginal ring releasing 3-keto-desogestrel.

The results of a stage I study of a new vaginal ring releasing 3-keto-Desogestrel [3kDOG] is reported. The study design consisted of one study cycle, where the ring was used continuously for 21 days and then removed. Twenty healthy volunteers were randomly allocated to each of two study groups. On day 5 of the menstrual cycle, group A used a vaginal ring releasing 30 micrograms 3kDOG per 24 hours and group B used a 15 micrograms 3kDOG per 24 hours ring. After initial absorption of the 3kDOG a plateau phase was reached in 46 hours [group A] and 49 hours [group B]. On reaching the plateau phase, the overall decline in plasma levels during the 21 days of use was 5.24% for group A and 5.27% for group B. This represents a daily decline in plasma levels of 0.27% and 0.28% for the 30 micrograms and 15 micrograms per 24 hours rings, respectively. The plasma levels achieved by the rings were significantly different throughout (p = 0.011). On removal after 21 days, the mean removal half-life for both ring types was similar at 20.9 hours for group A and 21.1 hours for group B. It is concluded that the characteristics of the delivery system are worthy of further study as a potential means of contraception using 3kDOG delivered from a vaginal ring.

Administration, Intravaginal

Division of uterine adhesions (Asherman's syndrome) with the Nd-YAG laser.

Two women with Asherman's syndrome after postpartum curettage are presented. The diagnosis was confirmed by hysteroscopy. The adhesions were vaporized under hysteroscopic control, using a Nd-YAG laser (neodymium-yttrium-aluminium-garnet laser). The method was precise, caused minimal thermal injury and resulted in immediate return of regular menstrual cycles. The use of the Nd-YAG laser for Asherman's syndrome warrants further study.

Adolescent

Thirty years' war: a battle with insomnia.

A 72-year-old man with a 30-year complaint of intractable insomnia had a positive family history of depression. He first came to psychiatric attention in 1958, after attacking his wife. He was prescribed barbiturates, and later was given meprobamate and nitrazepam, but with no effect on his complaint. The patient tended to increase the dosage of any drug given, of his own accord. EEG sleep recording confirmed the diagnosis of nocturnal myoclonus. It was hoped that at the case conference further treatment stratagems would be suggested.

Aged

Direct and short-term culture preparation of chorionic villi. Is any one method best?

Chorionic villi from 20 diagnostic cases were prepared for cytogenetic analysis by a direct and two short-term culture methods. No significant differences were found between the methods in the quality and quantity of metaphases obtained. A further study using villi from 20 pre-termination patients indicated an inherent variation in the quality of villi resulting in inconsistent processing and variation in the response of a sample to the methods. This suggests that it would be advantageous to process the villi by more than one method.

Cells, Cultured

A study comparing transcervical with transabdominal chorionic villus sampling (CVS).

Chorionic villus sampling (CVS) was performed in 50 anaesthetized patients before therapeutic abortion by the transabdominal route and then by the transcervical route. The two methods of villus sampling were equally successful in obtaining villi but the transcervical method was significantly better at obtaining chorionic villi greater than 10 mg in weight (chi 2 13.92 P less than 0.001). Placental position did not affect villus recovery with either sampling method.

Abdomen

Spontaneous abortion rate in ultrasonographically viable pregnancies.

In a prospective study of 500 patients who had an ultrasonically viable pregnancy at less than 12 weeks' gestation, the spontaneous abortion rate was 2% overall. In those women with a history of spontaneous abortion, the abortion rate increased tenfold. Spontaneous abortion at less than ten weeks' gestation was up to three times higher than that at greater than ten weeks' gestation; this may have implications when deciding on the timing of first-trimester diagnostic procedures.

Abortion, Spontaneous

Physiologic determinants of coronary blood flow during external cardiac massage.

Adequate coronary blood flow is a major determinant for successful resuscitation from cardiopulmonary arrest. To develop compression techniques that optimize coronary blood flow, we implanted in eight dogs electromagnetic flow probes that measured circumflex coronary blood flow and ascending aortic blood flow. Micromanometers measured left ventricular and aortic pressures. Each dog was anesthetized and intubated, and the heart was fibrillated electrically. High-impulse manual chest compressions were performed with the dog in the supine position, and compression rate was varied from 60/min to 150/min. Antegrade coronary blood flow occurred primarily during artificial diastole, and there was a brief period of retrograde coronary blood flow with compression during artificial systole. Cardiac output and diastolic aortic pressure increased with compression rate, significantly augmenting peak coronary blood flow velocity. However, diastolic perfusion time decreased linearly with compression rate and limited coronary perfusion at rates greater than 120/min. As a result, net coronary blood flow during high-impulse manual chest compression was determined primarily by diastolic aortic pressure and diastolic perfusion time. Coronary blood flow was optimized in this model at a compression rate of 120/min.

Animals

A physiologic comparison of external cardiac massage techniques.

On the basis of recent investigation, controversy has arisen regarding which of several cardiopulmonary resuscitation methods optimizes hemodynamics. The present study was designed to compare five recently described chest compression techniques: high-impulse manual chest compression at 150/min, mechanical compression at 60/min with simultaneous ventilation, mechanical compression at 60/min with simultaneous ventilation and either systolic or diastolic abdominal compression, and pneumatic vest compression at 60/min. Eight dogs were chronically instrumented with electromagnetic flow probes in the ascending and descending aorta while matched micromanometers measured aortic, left ventricular, and pleural pressures. At study, each dog was anesthetized with morphine, intubated, and the heart was fibrillated by rapid ventricular pacing. The five cardiopulmonary resuscitation methods were performed randomly in each preparation within 7 to 10 minutes of arrest. In four dogs, brachiocephalic blood flow was computed as total cardiac output minus descending aortic blood flow, and in all dogs coronary perfusion pressure was calculated as mean diastolic aortic pressure minus mean diastolic left ventricular pressure. Average cardiac output for seven studies was 662 +/- 61 ml/min with high-impulse manual compression, 340 +/- 46 ml/min with mechanical compression and simultaneous ventilation, 336 +/- 45 ml/min with mechanical compression and simultaneous ventilation with systolic abdominal compression, 366 +/- 52 ml/min with mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 196 +/- 29 ml/min with vest resuscitation (high-impulse manual compression significantly greater than other techniques by multivariate analysis, p less than 0.05). Brachiocephalic blood flow generally followed cardiac output and was statistically the greatest with high-impulse manual compression at 273 +/- 47 ml/min (p less than 0.05). Finally, high-impulse manual compression provided the highest coronary perfusion pressure of 31 +/- 4 mm Hg (p less than 0.05) compared to 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation, 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation with systolic abdominal compression, 23 +/- 3 mm Hg for mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 11 +/- 2 mm Hg for vest resuscitation. These data demonstrate that high-impulse manual compression generated physiologically and statistically superior hemodynamics when compared with other methods in this model of cardiopulmonary resuscitation.

Animals

Characteristics and incidence of dysfunctional ovulation patterns detected by ultrasound.

The nature and incidence of normal and abnormal spontaneous ovarian cycles, identified with ultrasound and endocrine tracking, were examined in 45 regularly cycling infertile women with no definitive cause and 15 women who were apparently normal and were receiving donor insemination because of clearly infertile partners. In 136 cycles, four apparently distinct abnormal patterns were detected. The total incidence in the infertile group was 58% compared with 23% in the donor insemination group (P less than 0.005). Twelve of 26 subjects who had at least three cycles tracked showed two different abnormalities, and 1 subject had three different abnormalities in five abnormal cycles. These results suggest that abnormal cycles are a significant factor in unexplained infertility and that diagnosis and treatment cannot be based on the study of a single cycle.

Adult