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W Collins

Publications and source records attributed to W Collins.

At least 19 recordsLinked to original sources
PubMed2001

Potential fertility--defining the window of opportunity.

The ClearPlan Easy Fertility Monitor predicts the times of high potential fertility, i.e. the times when sexual intercourse is most likely to result in conception. The test procedure identifies the times of specified changes in the concentration of urinary hormone metabolites during each ovarian cycle. The results are displayed in terms of prior knowledge about the time-specific probabilities of conception. This paper contains a summary of the scientific background that led to the development of the ClearPlan Easy Fertility Monitor.

Cervix Mucus↗
PubMed2000

Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1.

The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP1(19)) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP1(19) constructs elicited high levels of antibodies to MSP1(19) but only one construct, the 19-kDa fragment expressed as a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1(19)), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP1(19) in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

Adjuvants, Immunologic↗
PubMed2000

A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077.

This Phase I study was performed to evaluate the tolerability and pharmacokinetic behavior of MKT-077, a water soluble rhodacyanine dye analogue, which partitions into tumor cell mitochondria where it is thought to act as a metabolic poison, leading to G1 arrest and apoptosis. Thirteen patients with advanced solid malignancies were treated with MKT-077 administered as a 30-min i.v. infusion weekly for 4 weeks every 6 weeks at doses ranging from 42 to 126 mg/m2/week. The principal toxicity was renal magnesium wasting, which was dose-limiting (grade 3) in one patient at each of the 84- and 126-mg/m2 dose levels. The other three patients at the 126-mg/m2 dose level developed grade 2 hypomagnesemia, which was cumulative in nature, improved with i.v. magnesium supplementation, and was controlled in two patients by the administration of prophylactic magnesium before and after treatment with MKT-077. Given the requirement for extensive monitoring of serum magnesium levels, dose escalation >126 mg/m2 was not considered feasible. Thus, the recommended dose for disease-oriented studies with this schedule of MKT-077 is 126 mg/m2/week. Pharmacokinetic studies revealed a prolonged terminal half-life (37 +/- 17 h) and a large volume of distribution (685 +/- 430 liters/m2). Clearance averaged 39 +/- 13 liters/h/m2. Peak MKT-077 plasma concentrations (1.2 +/-0.31 to 6.3 +/- 5.3 microg/ml) exceeded the IC50 concentrations required for human CX-1 colon, MCF-breast, CRL-1420 pancreas, EJ bladder, and LOX melanoma tumor cell lines in vitro (0.15-0.5 microg/ml). These results indicate that at the recommended dose level of 126 mg/m2/week of MKT-077, the toxicity profile was consistent with the preferential accumulation of the agent within tumor cell mitochondria, and biologically relevant plasma concentrations were achieved.

Adult↗
PubMed1998

The safety of topical anaesthetic and analgesic agents in a gel when used to provide pain relief at split skin donor sites.

Post operative pain from split skin donor sites is a recognised problem. This study was carried out to assess the safety of a 'depot' preparation of bupivacaine and ketoprofen when applied to denuded dermis of a split donor site. Two groups of six patients each received either bupivacaine gel (2.5 mg/ml) or ketoprofen gel (1.6 mg/ml). One patient from each group was excluded as protocol was not followed. The mean surface area for bupivacaine was 106 cm2 (range 64-160) and the mean for ketoprofen was 130 cm2 (range 64-180). Blood samples were obtained before application and at 10, 20, 30, 60, 120, 240 and 480 min after application. Serum levels were assayed using Gas Liquid Chromatography and High Pressure Liquid Chromatography. Bupivacaine levels peaked at 120 min, mean level obtained was 0.07 microgram/ml (range 0.03-0.1). Ketoprofen levels also peaked at 120 min and the mean level obtained was 0.20 microgram/ml (range 0.12-0.27). The reported toxic serum level for bupivacaine was 4 micrograms/ml and for ketoprofen is 1128 micrograms/ml. In conclusion, these preparations, when applied to denuded dermis of a split skin donor site, are unlikely to result in toxic levels.

Administration, Cutaneous↗
PubMed1998

Microencapsulated octreotide pamoate in advanced gastrointestinal and pancreatic cancer: a phase I study.

Fourteen patients suffering from advanced colorectal (n = 7), pancreatic (n = 4) or gastric (n = 3) carcinomas received treatment with microencapsulated octreotide pamoate 90 mg i.m. every 4 weeks (n = 4), 160 mg i.m. every 4 weeks (n = 4) or 160 mg i.m. every 2 weeks (n = 6). Two patients had stable disease, one for 4 and one for 6 months. Plasma insulin-like growth factor (IGF)-I decreased by 49-53%, IGF-II by 27-37% and total IGF-binding protein (IGFBP)-3 by 16-19%, whereas IGFBP-1 increased by 35-55%. Insulin and C-peptide levels decreased by 29-38% and 41-46% respectively. A non-significant decrease in urinary GH secretion and an increase in the ratio of fragmented to intact IGFBP-3 as well as IGFBP-3 protease activity was seen. The increase in IGFBP-3 fragmentation correlated negatively with alterations in IGF-I and IGF-II (P < 0.05). We conclude that microencapsulated octreotide administered in doses up to 160 mg every 2 weeks is well tolerated and has pronounced effects on several components of the IGF system in plasma. In addition, changes in IGFBP-3 protease activity because of cancer may contribute to alterations in IGF-I and -II, indicating the importance of measuring this parameter in addition to IGFs and IGFBPs when evaluating alterations in IGF-I.

Aged↗
PubMed1998

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo.

Tamoxifen (tam) is used extensively for treatment of patients with breast cancer and is being evaluated for chemoprevention in healthy women. It has, however, been reported to increase the risk of endometrial cancer in post-menopausal women, probably by an oestrogenic effect on the endometrium. It also causes endometrial cysts and polyps. The aims of this study were to identify the incidence of endometrial thickening, polyps and cysts by transvaginal ultrasound (TVUS) screening of a population of post-menopausal healthy women in the Royal Marsden tamoxifen chemoprevention trial and to evaluate the possible benefit from the use of intermittent norethisterone (NE) in women with persistent changes. Since 1990, we have undertaken regular TVUS, using an endovaginal B mode probe, of the 463 post-menopausal women in the trial randomized to tam (20 mg day(-1)) or placebo (plac), without breaking the randomization code. Endometrial thickening (ET) was defined as > or = 8 mm at the widest point across the myometrial cavity in the longitudinal plane, including any stromal changes. Cystic changes were defined as more than one hypoechogenic area > 1 mm. Polyps were identified using saline hydrosonography. Oral NE (2.5 mg day(-1)) was used for 21 days out of 28 for three consecutive cycles by women with persistent endometrium > or = 8 mm, including cystic and polypoid changes. TVUS was repeated after the three courses to evaluate any change caused by NE and endometrial biopsies, including hysteroscopy, was performed on those women with persistent abnormalities. A persistent ET > or = 8 mm was identified in 56 (24%) of the 235 women on tamoxifen compared with only 5 (2%) of 228 women on placebo (P <0.0005). Stromal changes, including cysts, were detected in 36 (15%) and polyps in 26 (11%) of the women on tamoxifen compared with only two (< 1%) of the women on placebo (P << 0.0005). After 3 months of cyclical norethisterone, 39 of 47 women (83%) on tamoxifen had persistent ultrasound changes. However, 45 (96%) had a progesterone withdrawal bleed. Hysteroscopy was performed in 39 women on tamoxifen (28 endometrial biopsy, 15 polypectomy), five of whom had histological evidence of a proliferative endometrium and a further three had an atypical hyperplastic endometrium (one of whom had a focus of invasive carcinoma). The cysts and polyps which were detected in women on tam could not be reversed by NE and were presumably stromal and not of malignant risk. However, 96% of the women had withdrawal NE bleeding, indicating an oestrogenically primed endometrium which could be a mechanism for an increased risk of endometrial cancer. Further studies are required to ascertain whether a progestin would protect against this risk. As in other studies, these results indicate that any increased risk of endometrial cancer caused by tamoxifen is low, and that TVUS screening is probably not justified for asymptomatic women on tamoxifen.

Aged↗
PubMed1998

Complications of mandibular fractures.

Timely repair of mandibular fractures remains an effective means to reduce pain, restore function, and prevent complications. This study addresses the effect of the time interval between injury and treatment on the overall complication rate, the complication rate between various treatment modalities (mandibular-maxillary fixation [MMF] alone, MMF with intraosseous wire bone fixation, and MMF with rigid internal fixation), and the relationship of inpatient vs. outpatient management. Cost was also examined with respect to choice of management. We report a retrospective series of 308 consecutive patients managed at the University of Miami/Jackson Memorial Hospital. Patients who received treatment 3 to 10 days following injury were found to have a lower complication rate than earlier or later repair. We postulate that most patients with mandibular fractures may be managed on an outpatient basis, which represents a considerable savings in cost.

Adolescent↗
PubMed1997

Regression of a distal bile duct carcinoma after treatment with octreotide for 6 months.

We report the case of a 66-year-old male who was admitted for obstructive jaundice presenting with an enlargement of the pancreatic head on CT scan. During exploratory laparotomy an invasion of the retropancreatic mesenteric vessels was found. Subsequently, the patient was included in a multi-center trial of subcutaneous high-dose octreotide in irresectable pancreatic cancer. After 6 months there was no tumour detectable on routine CT follow-up. One year after commencing octreotide treatment the patient underwent Whipple resection; the specimen showing a small T1N0M0 distal bile duct carcinoma. Taking into account that somatostatin receptors have been found on bile duct cancer cells our observation might warrant a controlled clinical trial.

Adenocarcinoma↗
PubMed1996

Blood flow changes in the intraovarian arteries during the periovulatory period: relationship to the time of day.

Intraovarian blood flow was assessed by transvaginal color and pulsed Doppler ultrasound prospectively in six women during the periovulatory period. All patients had regular ovulatory menstrual cycles and a mid-luteal serum progesterone level consistent with spontaneous ovulation in the preceding cycle. Each patient underwent serial transvaginal ultrasound examination and Doppler assessment of blood flow in the ovarian stroma and in the wall of the dominant follicle or corpus luteum. When the mean follicular diameter was > 16 mm or day -2 from the estimated day of ovulation was reached, patients were scanned at 6-h intervals at 06.00, 12.00, 18.00 and 24.00 until follicular rupture, to investigate the presence of circadian rhythms. The pulsatility index (PI) and the maximum peak systolic blood flow velocity (Vmax) were calculated as Doppler indices of impedance to blood flow and velocity, respectively. A venous blood sample was taken at each visit for subsequent hormonal analysis. There was no significant circadian fluctuation in either mean follicular Vmax or mean follicular PI before or after the luteinizing hormone (LH) surge. Similarly, mean Vmax and mean PI in the non-dominant ovarian stroma did not show any significant fluctuation over the same periods. The mean PI in the dominant ovarian stroma showed daily fluctuations with the highest values occurring most commonly at 06.00 and the nadir in the afternoon and late evening. This fluctuation was the reverse of the circadian variation previously demonstrated in the uterine artery. However, in contrast to the uterine artery, comparison between the mean PI values in the dominant ovarian stroma at 06.00 and 18.00 only approached significance after the LH surge. The dominant ovarian stroma Vmax tended to rise during the day, although the differences between 06.00 and 18.00 were also not significant. Although there are fluctuations in Doppler blood flow indices in the dominant ovarian stroma, further studies are necessary to demonstrate whether this represents a significant circadian rhythm.

Adult↗
PubMed1996

Blood flow changes in the ovarian and uterine arteries during the normal menstrual cycle.

OBJECTIVE: Our purpose was to study the hemodynamic changes in the uterine and intraovarian vessels during the normal menstrual cycle and to relate the vascular changes to hormonal index values. STUDY DESIGN: Seven women who had bilateral tubal patency, a normal pelvis on laparoscopy, and regular ovulatory cycles underwent serial transvaginal ultrasonography on menstrual cycle day 2, daily from estimated day of ovulation-6, hourly from estimated day of ovulation-2, or when the mean follicular diameter was > 16 mm (whichever was earlier) until 6 hours after follicular rupture and once 7 days after follicular rupture. At each scan uterine and intraovarian blood flow was assessed with transvaginal color Doppler ultrasonography and serum concentrations of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone assessed by fluoroimmunoassay. RESULTS: In one case there was evidence of a luteinized unruptured follicle and the patient was therefore excluded from analysis. In the other six women there was spontaneous ovulation at a mean of 39 hours after the onset of the luteinizing hormone surge. On the side with the dominant follicle, follicular and ovarian stromal peak systolic blood flow velocity rose significantly during the menstrual cycle with no significant change in pulsatility index. The changes in blood flow velocity correlated significantly with changes in serum follicle-stimulating hormone, luteinizing hormone and progesterone concentrations. There were no significant changes in either blood flow velocity or pulsatility index in the contralateral ovary. Uterine artery time-averaged maximum velocity on the side of the developing ovarian follicle increased during the menstrual cycle with no significant change in the contralateral vessel. Uterine artery pulsatility index on the side of the developing follicle declined during the midluteal phase and was significantly lower than on the contralateral side. The changes in time-averaged maximum velocity correlated with the changes in serum estradiol and progesterone concentrations. CONCLUSION: The vascular changes in the wall of the dominant ovarian follicle and ovarian stroma during the menstrual cycle are consistent with activity of angiogenic-like factors. The decline in uterine artery resistance during the midluteal phase may reflect optimal vascularity for implantation of the blastocyst.

Adult↗
PubMed1996

Associations between ultrasound indices of follicular blood flow, oocyte recovery and preimplantation embryo quality.

The aim of this study was to elucidate possible relationships between ultrasound indices of follicular blood flow, oocyte recovery and the subsequent production and morphological quality of preimplantation embryos. A total of 27 women with bilateral tubal occlusion, undergoing treatment for infertility by in-vitro fertilization and embryo transfer, contributed data from 29 cycles. Transvaginal ultrasonography with colour Doppler imaging and pulsed Doppler spectral analysis was used to obtain indices of blood flow for each follicle immediately before it was aspirated. The main outcome measures for each follicle were the pulsatility index, peak systolic velocity, recovery or non-recovery of an oocyte and the subsequent production or non-production of an embryo. A total of 126 follicles were studied, 102 oocytes were recovered and 58 embryos (49 at grades I or II) were produced. There were six clinical pregnancies (pregnancy rate 27.3% per embryo transfer, 22.2% per patient). There was a significant correlation (P < 0.0001, chi2 test) between whether or not follicular blood flow was detected and whether or not an oocyte was recovered. The sensitivity of a test based on the presence of detectable blood flow and the subsequent recovery of an oocyte was 74% and the positive predictive value was 93%. The peak systolic velocity (PSV, measured in cm/s, mean +/- SD) in follicles with detectable blood flow was significantly higher in follicles that were associated with the production of a preimplantation embryo (19.7 +/- 10.8) compared with those that were not (9.9 +/- 5.3, P < 0.0001, Student's t-test). There was a 70% chance of producing a grade I or II embryo if the follicular blood velocity was >/=10 cm/s, compared with 14% if the PSV was <10 cm/s, or 18% if no blood flow was detected. We conclude that there is a physiological relationship between follicular blood velocity, oocyte recovery and the production of a high-grade preimplantation embryo, which may form the basis of a useful clinical test.

Adult↗
PubMed1996

Serum and urinary myoglobin following an aborted malignant hyperthermia reaction.

A 13-year-old boy presenting for correction of bat ears was anaesthetised with thiopentone and suxamethonium, the administration of which was followed by jaw spasm, poor peripheral perfusion (without cyanosis) and marked tachycardia. The procedure was abandoned, dantrolene and Ringer lactate IL were given intravenously and the patient regained consciousness 1 h later. Levels of serum myoglobin, urinary myoglobin and creatine kinase were followed until they returned to normal. Despite a peak serum myoglobin of 58.000 micrograms.l-1 and peak urinary level of 446,000 micrograms.l-1, no renal impairment occurred. Subsequent testing for susceptibility to malignant hyperthermia proved positive for the patient and four other members of the family.

Adolescent↗
PubMed1995

Luteinized unruptured follicle: morphology, endocrine function and blood flow changes during the menstrual cycle.

A case of spontaneous luteinized unruptured follicle syndrome is presented with full documentation of hormonal, morphological and haemodynamic changes. Changes in uterine blood flow were also noted. Growth of the leading follicle was slow during the follicular phase of the cycle. After the luteinizing hormone (LH) surge, growth of the follicle was more rapid. Concurrently, the follicle developed internal echogenicity with ultrasonic evidence of separation of the granulosa cell layer. The follicle was no longer visible 144 and 132 h after the LH rise and peak respectively. There was no primary progesterone rise associated with either the LH rise or peak, but a secondary progesterone rise occurred 42 h after the onset of the LH surge. Peri-follicular blood flow velocity was detected for the first time on cycle day 5 and appeared to rise after the onset of the LH surge. Peri-follicular blood flow velocity appeared to reduce after the LH surge to values associated with the follicular phase. These observations are consistent with an association of a primary granulosa cell defect with luteinized unruptured follicle syndrome which would account for the initial slow follicular growth, absent primary progesterone rise and reduction in blood flow in the wall of the follicle after the LH surge.

Adult↗
PubMed1993

Psychological impact of screening for familial ovarian cancer.

BACKGROUND: Psychological distress following false-positive results could constitute a substantial disadvantage of cancer screening. PURPOSE: The purpose of this prospective study was to evaluate the psychological impact of true-negative and false-positive results in a high-risk group of women in a screening program to detect early familial ovarian cancer by ovarian ultrasound scan. The influence of coping style was also assessed. METHODS: Of 500 women who contacted the nationally advertised screening program, 302 received the scan and participated in the study. Before the screening, they were mailed a questionnaire concerning psychological state, coping style, and anxiety about risk of cancer. Transabdominal ultrasonography and transvaginal ultrasonography with color Doppler imaging were used to detect persistent ovarian lesions and changes in volume. Women were informed of any abnormality immediately and asked to return for another scan after 6 weeks. Those with a persistent ovarian mass were referred for hysterectomy and bilateral oophorectomy. The questionnaire was used to reassess psychological distress after the first ultrasound scan, after re-scanning, and after surgery. RESULTS: The first scan showed negative results for 233 of the 302 women; 69 (23%) had abnormalities in ovarian morphology. Sixty-four of the 69 had a second scan, with negative results for 32 and equivocal results for 12; 20 had surgery because the results of both scans were positive. None of the patients in the screening program were found to have ovarian cancer. After the first scan, psychological distress and worries about cancer were significantly reduced (P < .001) in the women who had negative results. Responses to positive results depended on the baseline coping style and the clinician's appraisal of malignancy potential at the time of the scan. Women who had information-seeking coping styles and those who were referred for surgery had higher levels of distress than other women. At follow-up, the anxiety scores of women who had positive results on both scans but negative results at surgery had returned to baseline levels. CONCLUSIONS: The findings suggest that false-positive results in screening are associated with increased distress in the short term, but these adverse effects do not appear to be severe or persistent. Women who had surgery appeared to welcome the certainty that they could never develop ovarian cancer. IMPLICATIONS: The issue of continued surveillance needs to be addressed, since many women expressed the desire to have the scan repeated regularly.

Adult↗
PubMed1991

Ovarian morphology, endocrine function and intra-follicular blood flow during the peri-ovulatory period.

Transvaginal ultrasonography with colour flow mapping has been used to study changes in intra-follicular morphology and blood flow during a peri-ovulatory period in one volunteer. Aspects of uterine morphology and blood flow were also recorded. The intervals from a defined luteinizing hormone (LH) rise and peak to the mean time of follicular rupture were 37.5 and 17.5 h, respectively. Blood flow velocity waveforms were observed clearly at the time of the LH rise and blood vessels were visible when the hormone level reached a peak. Concurrently, the wall of the follicle became less clear, crenated, thicker and more echogenic. A structure resembling the detached cumulus and oocyte was seen before the follicle had ruptured. Peak systolic blood velocity was highest immediately after ovulation had occurred. Blood flow impedance in the uterine arteries suggested the presence of a circadian rhythm, but no pronounced daily changes were observed over the study period. In contrast, flow velocity waveforms were clearly visible in the endometrium around the time of ovulation. These preliminary data suggest that intra-follicular vascularization or angiogenesis may be critical processes that might be used to predict ovulation and could possibly be modified to help achieve or avoid a pregnancy.

Adult↗
PubMed1990

Influence of superovulation on endometrial and embryonic development.

The authors have studied the temporal relationship between follicular rupture and endometrial development in 13 women during a natural ovarian cycle (length 25 to 35 days), and subsequently after standard treatment with clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin (hCG) to induce multiple folliculogenesis for oocyte recovery, in vitro fertilization, and embryo freezing (cycle length 23 to 27 days). An endometrial biopsy was taken during both cycles 1.5 to 2.0 days after the oocytes had been released or removed. The samples were examined by light and transmission electron microscopy. Samples of peripheral blood were taken at defined times for hormone analysis. After treatment 11 subjects (85%) had advanced morphological development of the endometrium (8 women by 3 to 4 days, 3 women by 1 to 2 days). The concentrations of plasma estradiol (E2) and progesterone (P) on the days of follicular rupture and endometrial biopsy were significantly raised in the treatment cycles. The concentration of total urinary estrogens on the day of hCG administration and the mean change in the concentration of plasma E2 (treatment/control) on the days of endometrial biopsy were positively correlated with the extent of endometrial advancement. In addition, the mean change in the concentration of plasma P (treatment/control) was markedly increased on the days of follicular rupture and endometrial biopsy in those subjects with an advanced endometrium. Embryonic development was not so obviously related to the extent of superovulation. Asynchronous endometrial and embryonic development may therefore contribute to the low pregnancy rate in these patients.

Adult↗