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S Killick

Publications and source records attributed to S Killick.

At least 19 recordsLinked to original sources
PubMed2004

A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function.

OBJECTIVES: To compare carbohydrate metabolism, adrenal and thyroid function during use of a combined contraceptive vaginal ring (NuvaRing, NV Organon, Oss, The Netherlands) with those of a combined oral contraceptive. METHODS: Healthy women aged 18-40 years used either the vaginal ring, delivering 15 microg ethinylestradiol and 120 microg of etonogestrel per day, or a combined oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, for six cycles. Each cycle comprised 3 weeks of use of the ring or the pill followed by 1 ring- or pill-free week. The following parameters were measured at baseline and at the end of cycles 3 and 6: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin); adrenal function (total cortisol, cortisol binding globulin, dehydroepiandrosterone sulfate); thyroid function (thyroid stimulating hormone, free thyroxine). RESULTS: Small and similar increases in insulin were seen in both groups. Concentrations of cortisol binding globulin and total cortisol rose significantly less during ring use than during combined oral contraceptive use (cycle 3, p= 0.0002; cycle 6, p < 0.0001). Levels of dehydroepiandrosterone sulfate did not change in either group. Thyroid stimulating hormone levels increased significantly more in the ring group at cycle 3 (p = 0.0016) but free thyroxine levels were unchanged in both groups. CONCLUSIONS: Both the vaginal ring and the oral contraceptive have no clinically relevant effects on carbohydrate metabolism, adrenal or thyroid function.

Adolescent↗
PubMed2002

Complete and robust ovulation inhibition with NuvaRing.

NuvaRing, a novel contraceptive vaginal ring, releases 15 microgram of ethinylestradiol (EE) and 120 microgram etonogestrel (ENG) per day. A randomized pharmacokinetic study compared NuvaRing with a combined oral contraceptive (COC) containing 30 microgram EE and 150 microgram desogestrel. Maximum levels of EE and ENG with NuvaRing were 30% and 40%, respectively, of those seen with the COC. Because ENG bioavailability was higher following vaginal administration, the systemic progestogen exposures were comparable with the two contraceptives. However, the EE bioavailabilities were similar with both routes and so EE exposure with NuvaRing was half that with the COC. Pharmacodynamic studies have examined ovarian function during recommended and altered NuvaRing use. The use of NuvaRing for the recommended 3-week period completely inhibited ovulation. During an additional 2 weeks of use, ovulation continued to be inhibited. Early NuvaRing removal after just 3 days had no effect on the time to ovulation compared with recommended use, thus indicating that 3 days of use seem to be sufficient to suppress ovarian activity. Finally, delayed ring insertion (when the follicles had developed to 13 mm) resulted in inhibition of ovulation in all women. In conclusion, NuvaRing effectively inhibits ovulation during recommended and altered use, showing that it is a robust contraceptive method.

Biological Availability↗
PubMed2000

A randomized comparison of the effects on vaginal and cervical epithelium of a placebo vaginal ring with non-use of a ring.

Little is known about the effects of contraceptive vaginal rings on the vaginal surface epithelium, although most studies have not demonstrated any significant deleterious effect. However, one study found that some medium-to-long-term levonorgestrel-releasing ring users developed chronic erythematous and ulcerative lesions in the posterior vaginal fornix. Subsequently, this ring was completely redesigned (IVR-2) with different dimensions and much greater flexibility. The first version of IVR-2 was designed as a placebo ring to explore effects on the vagina and cervix without addition of a progestogen. One-hundred-sixty-six healthy sexually active women volunteers were recruited in four centers and randomly assigned for 6 months to either placebo ring use or control (non-use) using a predetermined randomization code generated by WHO in a 2:1 ratio. Careful inspections of the vaginal and cervical epithelium were performed with a colposcope at admission and at 2-month intervals. No clinically significant lesions were detected in any center either among ring users or controls. However, a number of minor changes in appearance of the vaginal and cervical epithelium (erythema, petechiae, ecchymosis, and minor aceto-white changes) were described from the Sydney Center, some of which were present on admission and some of which were found on subsequent examination. Ten of eleven "red" changes on the cervix and vagina were noted in IVR-2 users, and only one in the controls, suggesting a contribution by the IVR-2 to minor epithelial surface changes. Five of ten resolved completely with continued ring use. There was no correlation in this study between epithelial changes and cigarette smoking or frequency of intercourse in the 14 days prior to colposcopic examination but a significant relationship between tampon use in the last 7 days and all epithelial changes (p = 0.05) and especially red changes (p = 0. 027) was noted. Red changes were significantly less likely to be found among condom users (p = 0.007). The IVR-2 placebo ring did not produce clinically significant changes in the vaginal epithelium and cervical mucosa and a carefully controlled and randomized study should be considered to compare the epithelial appearances in women using a placebo IVR-2 and one releasing 20 microg levonorgestrel.

Biopsy↗
PubMed2000

Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.

Adolescent↗
PubMed2000

Errors in the measurement of endometrial depth using transvaginal sonography in postmenopausal women on tamoxifen: random error is reduced using saline instillation sonography.

OBJECTIVE: The endometrium in women on tamoxifen is often made irregular by small cysts. The aim of this study was to assess the accuracy and precision of the measurement of endometrial depth by transvaginal sonography. METHODS: The endometrial depth from endometrial biopsies obtained with the resectoscope in 15 women receiving tamoxifen was compared to the endometrial depth measured by TVS. The inter-observer variability was measured in 58 women. RESULTS: In those biopsies of sufficient quality to allow a measurement, the corresponding depth measurement obtained by ultrasound was up to 3 mm greater than the histological measurement. The interobserver variability for the measurement of endometrial depth using TVS was assessed in 58 postmenopausal women on tamoxifen. The interobserver variability deteriorated as the mean endometrial depth increased, probably because the increase in depth resulted from greater morphological changes within the endometrium such as cyst formation which resulted in an irregular endometrial/myometrial boundary. This may, however, be improved by performing saline instillation sonography. In a prospective study of 10 postmenopausal women, the interobserver variability was significantly greater during tamoxifen treatment compared to pretreatment. CONCLUSIONS: On the basis of the above, if uterine surveillance using TVS were to be offered to postmenopausal women on tamoxifen, then the procedure should be augmented by saline instillation sonography if the endometrial depth is > 4 mm, as this will improve the measurement precision and also identify intrauterine pathology.

Antineoplastic Agents, Hormonal↗
PubMed1999

Impact of previous high-dose therapy on outcome after allografting for multiple myeloma.

We describe a single centre experience of 33 patients allografted for multiple myeloma, of which 28 received matched sibling marrow, one haploidentical family donor marrow and four matched but unrelated donor marrow. Median follow-up after transplant is 27 months, and 13 patients are currently alive. One out of four patients with an unrelated donor survives and 12 out of 28 (42.8%) with matched sibling donors. Four patients were unevaluable because of early death (<day 21), and one patient experienced graft failure. The probability of overall survival is 35.7 % at 3 years. The probability of disease-free survival is 39% at 3 years, and the probability of treatment-related mortality is 54% at 1 year. Acute GVHD developed in 26 (78.8%) patients and was responsible for six deaths. Twenty-four patients (72.7%) developed renal dysfunction and 22 (66.7%) developed hepatic dysfunction. Seventeen patients (51.5%) died of transplant-related problems in the first 150 days, and one at 6 months. Among the 13 survivors, none has experienced disease progression at a median follow-up of 27 months (range 3-65 months). We conclude that since allogeneic bone marrow transplantation is the only potentially curative option in myeloma, it should be offered to younger patients early in the course of their disease, when procedure-related morbidity and mortality are likely to be at their lowest.

Adult↗
PubMed1999

Acute erythroid leukemia (M6): outcome of bone marrow transplantation.

Erythroid leukemia is an uncommon form of acute myeloid leukemia (AML) which has previously been associated with a poor prognosis. We present the outcome of 27 patients with AML-M6 (19 de novo and 8 secondary) treated with intensive regimens including bone marrow transplantation (BMT). In the de novo group, median age was 30 years (2-72); 5 cases were under 15 years. Remission rate after induction chemotherapy was 95%. Consolidation in those achieving remission with BMT was 82%. Transplant related mortality was 36%. Median survival for de novo M6 was 2.9 years which was not significantly different to matched controls with AML (non M6). Overall relapse rate was 35%. In contrast, patients with secondary disease had a poor prognosis with lower remission rates (57%) and higher relapse rates (75% of those achieving remission after induction chemotherapy). In our series, the prognosis of patients with AML-M6 was most closely related to age and disease status at presentation (de novo or secondary). The disease is sensitive to AML induction regimens and long-term survival can be achieved with BMT in first complete remission.

Adolescent↗
PubMed1999

Monosomy X as the sole cytogenetic abnormality in acute lymphoblastic leukemia: a report of two new patients.

Monosomy X as the sole acquired cytogenetic abnormality is usually found in myeloid hematological malignancies, especially those with myelodysplastic features. Only three cases of acute lymphoblastic leukemia (ALL) with this abnormality have been previously reported. We add two cases to this series and comment on the likelihood of a tumor suppressor gene being located on the X chromosome.

Adolescent↗
PubMed1999

Outcome of biphenotypic acute leukemia.

BACKGROUND AND OBJECTIVE: Although biphenotypic leukemia is now a defined entity, outcome of this rare form of acute leukemia has not been well documented. We present the first comprehensive study analyzing induction and consolidation therapy of biphenotypic leukemia and correlate outcome to prognostic factors. DESIGN AND METHODS: In this retrospective study, the incidence of biphenotypic leukemia was found to be 3.6% from 693 adult and pediatric acute leukemias referred to our center for treatment over the last 8 years. Of these, 15 were B-lymphoid/myeloid, 8 were T-lymphoid/myeloid, one was T/B lymphoid and one had trilineage differentiation. RESULTS: Induction of remission in de novo cases was achieved in 70% of patients and relapse of disease occurred in 15%. The use of combined lymphoid and myeloid drugs for induction resulted in a high incidence of early deaths (25%). The overall probability of survival at 2 years was 39.4%. Patients with secondary disease had a uniformly poor outcome with low remission rates and high relapse rates. INTERPRETATION AND CONCLUSIONS: Prognosis was most strongly related to the presence of the Philadelphia chromosome (p=0.03) and age under 15 years (p=0.01). We conclude that patients with biphenotypic leukemia should have risk stratification with treatment tailored to their prognostic factors.

Acute Disease↗
PubMed1998

Prolonged disease-free survival in relapsed/refractory low-grade lymphoma treated with fludarabine: a report of four cases.

We report four patients with relapsed or refractory follicular (three) and lymphoplasmacytic (one) lymphoma who achieved complete remission (CR) with fludarabine (FDR) lasting from 3.2 to 6 years. One had stage III and three stage IV and were resistant to chlorambucil and/or anthracycline. FDR was well tolerated, the only complication being herpes zoster infection in three patients, which was controlled with aciclovir. One patient developed a gastric MALT lymphoma from a different clone than the follicular lymphoma. In conclusion, some patients with refractory low-grade lymphoma achieve long-term CR with FDR: therefore this agent may be considered as alternative to stem-cell transplantation.

Adult↗
PubMed1996

Ovarian activity and vaginal bleeding patterns with a desogestrel-only preparation at three different doses.

A randomized, double-blind, group-comparative study was performed over a 6 month period to compare ovarian suppression and vaginal bleeding during the use of three oral contraceptives containing doses of 30, 50 or 75 micrograms desogestrel. A total of 44 female volunteers with regular cycles and established ovulation by ultrasonography were recruited from an out-patient clinic in a university hospital and asked to participate in the study. Ultrasonography and serum oestradiol and progesterone measurements were performed during two assessment periods. The 75 microgram dose showed complete suppression of ovulation and a more acceptable bleeding pattern than the lower doses. The 75 microgram dose of desogestrel is the most promising dose for the development of a new progestogen-only oral contraceptive agent.

Adult↗