Ovarian neoplasia and subfertility treatments.
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Case-Control Studies↗
Biomedical subjects
D Nugent
Publications and source records attributed to D Nugent.
Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue.
OBJECTIVE: To develop an efficient isolation technique for human primordial follicles. DESIGN: Prospective, experimental study of ovarian biopsies collected from healthy women undergoing elective cesarean section. Ovarian blocks either were fixed for histology and follicle counting or partially disaggregated with type 1A collagenase before or after cryopreservation. After partial disaggregation, follicles were isolated by microdissection. SETTING: Leeds General Infirmary. MAIN OUTCOME MEASURE(S): Follicle viability was assessed with live-dead stains using 5-(and 6-) carboxyfluorescein diacetate, succinimidyl ester and propidium iodide, respectively, and using electron microscopy. The numbers recovered were expressed as a percentage of the numbers of primordial follicles in comparable blocks of tissue and the viability of the whole follicle and oocyte were scored separately. RESULT(S): On average, 18.0 +/- 3.8 and 15.9 +/- 2.2 (mean +/- SEM) follicles per block were recovered from fresh and cryopreserved ovarian tissue, respectively, corresponding to recovery rates of 57.9% +/- 8.8% and 56.2% +/- 16.7%. In the fresh group, the percent viability of whole follicles and oocytes were 71.6% +/- 2.4% and 91.3% +/- 2% compared with 71.5% +/- 4.7% and 95% +/- 4.3% in the frozen-thawed group. Electron microscopy confirmed that the majority of the cells lacked ultrastructural signs of damage after isolation and cryopreservation. CONCLUSION(S): Primordial follicles can be isolated from fresh and cryopreserved human ovarian tissue with similar high efficiency and viability rates.
Adult↗
Developing hypothermia: indicators.
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Humans↗
Platelet-associated factor XIII as a marker of platelet activation in patients with peripheral vascular disease.
In the past several years, monoclonal antibodies have been developed that distinguish between resting and activated platelets in vitro. These antibodies recognize epitopes expressed on membrane proteins or soluble proteins, such as factor XIIIa and thrombospondin, that bind only to activated platelets. We have used fluorescence flow cytometry to determine whether three such antibodies can detect platelet activation in patients with severe peripheral vascular disease (PVD). Using two activation-specific monoclonal antibodies and a polyclonal antiserum to factor XIII a-chain, we have examined the platelets from PVD patients, age-matched control subjects who were free of detectable PVD, and unmatched control subjects. Cells analyzed as platelets were identified by their light-scatter profile and their reactivity with monoclonal anti-glycoprotein Ib. The platelets of patients with PVD showed no increase in binding of activation-dependent 1B3 (directed against a 180-kD membrane protein) compared with age-matched control subjects (p = 0.780). Similarly, there was no difference between PVD patients and control subjects in activation-dependent CD63 expression. Conversely, the binding of anti-factor XIII a-chain was significantly higher than in the control groups (p < 0.001). These data suggest that the detection of soluble factors that bind to activated but not resting platelets may be of use in the detection of pathological in vivo platelet activation.
Adult↗
Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin or adriamycin. Results of long-term follow-up.
We evaluated 158 cases of patients with superficial bladder cancers (Stages Ta, T1, and Tis). These cases were treated with either intravesical bacillus Calmette-Guerin (BCG) (Tice strain) or Adriamycin (ADR), in a multicenter, nonrandomized study. One hundred thirty-one of these patients were followed up; the results continue to show a higher percentage of initial complete remissions with BCG (68%) than with ADR (57%). With additional therapy, both BCG and ADR achieved complete remission in 83 percent of the patients. When 7 failures with patients taking ADR were switched to BCG and the disease cleared, the rate of complete remission for BCG rose to 85 percent. The recurrence rate per 100 patient-months was only slightly different for BCG (0.9) and ADR (0.8). The percentage of progressions continued to be higher for BCG (8%) than for ADR (5%). Cystectomies were performed in 2.5 percent of the BCG patients. Using the Cox regression model with covariates, we found drug treatment, tumor grade, and sex to be statistically significant in determining failures throughout the protocol. Although both BCG and ADR were effective over the course of the study, BCG is the drug of choice for residual tumor (Stages T1 and Tis).
Administration, Intravesical↗
Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin.
We evaluated 155 patients with superficial bladder cancers (Stages Ta, T1, and TIS) and treated them with either intravesical bacillus Calmette-Guérin (Tice strain) (BCG) or doxorubicin hydrochloride (Adriamycin), in a multicenter nonrandomized study. At present 140 of these patients in treatment Groups I and II are being followed up. With additional follow-up, BCG continued to produce a higher percentage of complete remissions (71%) than doxorubicin (54%). The percentage of incomplete remission with BCG (7%) was half that with doxorubicin (14%). Half of the patients whose initial therapy failed had complete remission after additional therapy. However, for patients with recurrence, additional follow-up shows a recurrence rate per 100 patient-months for BCG (1.0) only slightly lower than that for doxorubicin (1.1). The percentage of progressions continued to be higher with BCG (8.5%) than with doxorubicin (5%), but the difference between these results for the two drugs proved slightly less than we reported previously. Of the patients in this study, 2.5 percent (all treated with BCG) required cystectomy. A comparison of the results of our study with those of 13 other studies using BCG to treat bladder cancer indicates that therapy beyond an initial course of 6 weekly treatments increases the percentage of complete response. All of the studies showed that the greatest improvement in percentage of complete response occurred with the second course of treatment. The value of maintenance therapy cannot yet be determined, since few studies have used that protocol. The percentage of patients requiring cystectomy in studies with fewer than 20 treatments was 2.2 times higher than in studies with more than 20 treatments.
Administration, Intravesical↗
Characterization of an antigen expressed on activated human T cells and platelets.
We have identified a protein complex on the surface of activated human T cells and platelets. This Ag, detected by the murine mAb 1B3, is not expressed on resting human T cells or platelets or on other hematopoeitic cells. The majority of T cells express the Ag after stimulation with PHA, Con A, or allogeneic cells. Platelets express the Ag after activation with 1 U/ml thrombin. Immunoprecipitation of 125I-labeled activated T cells with antibody 1B3 shows a heterodimer of 180,000 and 155,000 Mr. An additional protein of 130,000 Mr is very faintly seen depending on the cell type. On platelets, the 180,000 Mr protein is the predominant protein immunoprecipitated under both nonreducing and reducing conditions. Antibody 1B3 may prove useful in identification of activated T cells and platelets as well as definition of specific mechanisms of T cell and platelet activation.
Animals↗
Superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin: follow-up report.
We evaluated 139 patients with superficial bladder cancer (Stages Ta, Tl, and TIS) and treated them with either intravesical bacillus Calmette-Guérin, Tice strain (BCG), or doxorubicin hydrochloride (Adriamycin [ADR]) in a nonrandomized, multicenter study. Our follow-up study comprises 135 of these patients. Of these patients, 78 tumors were completely resected, and 61 were incompletely resected. When a proportional-hazards model (Cox) was applied, there was a statistically significant difference between the recurrence rates for the two drugs. On the basis of recurrence rates per 100 patient-months, both BCG (1.2) and ADR (0.9) worked well with completely resected tumors. However, for incomplete resections, the recurrence rate for BCG (0.9) was less than half that for ADR (1.9). The overall recurrence rates were 1.1 and 1.3 for BCG and ADR, respectively. There have been 42 failures of treatment with either BCG or ADR. We defined failure as any recurrence of tumor; progression of the cancer in stage, grade, tumor number or size; or any residual tumor after 18 treatments (14 months of therapy). As to the failures in patients whom we followed up, and whose treatment was either switched from ADR to BCG or continued on further BCG treatment, 53 per cent have achieved complete remission. Complete remission for BCG and ADR were 76 per cent and 52 per cent, respectively. Of the various factors considered in the study, only tumor grade and treatment drug were statistically significant. The cystectomy rate was 1 per cent for BCG-treated patients and 0 for ADR-treated patients.
Administration, Intravesical↗
Glycoprotein IIb-IIIa as an immunologic target.
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Antigens, Human Platelet↗
Isolation and characterization of the alpha and beta chains of human platelet glycoprotein Ib.
Human platelet glycoprotein Ib has been purified in milligram amounts from platelets obtained by pheresis of thrombocytotic donors. Purification steps included lectin (wheat germ agglutinin) and immuno (murine monoclonal anti-glycoprotein Ib antibody)-affinity chromatography. The disulfide-linked individual alpha and beta chains of GPIb were separated and the amino-terminal amino acid sequence of each chain was determined. Rabbit polyclonal antibody directed against each individual chain was prepared by affinity chromatography and shown to be monospecific by western blot analysis using whole platelet lysate as antigen. These studies outline a useful approach to isolate and characterize the individual chains of GPIb.
Amino Acid Sequence↗
Superficial bladder cancer treated by intravesical bacillus Calmette-Guerin or adriamycin: multicenter study interim report.
One hundred sixteen patients with superficial bladder cancers (Stages Ta, T1, and TIS) were evaluated and treated with either intravesical bacillus Calmette-Guerin [Tice strain] (BCG) or doxorubicin hydrochloride (Adriamycin [ADR]), in a multicenter study. One hundred nine of these patients currently have follow-up. Of these, 54 were completely resected and 55 incompletely resected. For complete resections, based on recurrence rates per 100 patient months, both BCG (0.22) and ADR (0.91) worked well, although BCG had a slightly lower recurrence rate. However, for incomplete resections, BCG (0.20) had a markedly lower recurrence rate than ADR (2.52). Eighteen patients failed initial treatment, with either BCG or ADR. All have been placed on long-term therapy schedules. Of the 12 failures who currently have follow-up, 11 (92%) have either partially or completely responded with additional intravesical therapy. No patients in this study have yet required cystectomies.
Administration, Intravesical↗
Infantile hemorrhagic angiodysplasia.
We report a female infant who presented at birth with an unusual syndrome of disseminated cutaneous and gastrointestinal vascular malformations associated with severe thrombocytopenia and chronic gastrointestinal hemorrhage. The infant required extensive blood-product support and expired at 7 months of age. Postmortem examination confirmed the presence of numerous flat vascular lesions, descriptively classified as angiodysplastic, and composed of congeries of dilated capillaries, arterioles, and postcapillary venules. No visceral space-occupying hemangiomas were found. The case is discussed in relation to a spectrum of congenital vascular malformation syndromes including disseminated neonatal hemangiomatosis and hereditary hemorrhagic telangiectasia (HHT). Some pathologic characteristics appear to link it to the latter entity. However, other clinical and pathologic features distinguish it from the reported spectrum of congenital HHT, prompting its essentially descriptive designation.
Blood Vessels↗
Hemorrhage involving the upper airway in hemophilia.
Bleeding involving the upper airway is a rare, highly emergent complication of hemophilia. This report describes the occurrence of two distinct episodes in a patient with severe factor IX deficiency. Clinical data from other cases described in the literature is summarized with regard to predisposing factors, age of incidence, presenting symptomatology, diagnosis, and management. Pertinent features of this bleeding complication include: high prevalence involving the pediatric population, presentation with non-specific symptoms (e.g., sore throat, dysphagia) early in the course of the bleeding episode, progression to complete upper respiratory obstruction if not recognized and treated, and the need for relatively high levels of the deficient coagulation factor for a period of at least 7 days to ensure resolution of the hematoma. The diagnosis is confirmed by observing retropharyngeal soft-tissue widening on lateral neck x-ray or alternatively, via cervical computed tomography.
Child, Preschool↗
Transplantation in reproductive medicine: previous experience, present knowledge and future prospects.
The use of transplantation in reproductive medicine has been considered by physicians and scientists alike for many years. Despite being side-tracked into futile pursuits of rejuvenation in the early days, the possibility of usefulness remains, particularly for preserving fertility in patients undergoing ablative chemo- or radiotherapy. These aims have been enhanced by advances in tissue cryopreservation. When isolated primordial follicles are transferred in the mouse, or ovarian tissue slices are grafted into sheep, it is possible to obtain follicular survival with subsequent maturation and oestrogen secretion and even restore fertility to sterilized hosts. For preservation of fertility, autografts avoid both the immunological problems of allografts and the ethical dilemmas when using donor tissue. In the male, the concept of spermatogonial cell transfer after isolation and frozen storage of cells recovered from a testicular biopsy is most attractive, since it may provide another option for rescuing fertility in cancer patients, and provide a much needed one in children. Recent results demonstrate that gonocytes from immature mice injected into the tubules of sterilized hosts restore spermatogenesis and produce fertile spermatozoa. Furthermore, the gonocytes can be stored frozen prior to transfer and still produce fertile tubules. This review presents a broad history of transplantation in the male and female genital tracts as well as attempts to anticipate possible future developments.
Animals↗