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Biomedical subjects

H Ball

Publications and source records attributed to H Ball.

At least 19 recordsLinked to original sources
PubMed1998

Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial.

OBJECTIVES: In an effort to critically examine the antitumor activity of altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the agent administered in this clinical setting. METHODS: Altretamine was administered at a dose of 260 mg/m2 orally for 14 days in a 28-day course. Treatment was continued until disease progression or unacceptable side effects prevented further therapy. A total of 36 patients (median age: 56.5) were treated on this trial, of whom 33 were evaluable for toxicity and 30 for response. All patients had previously received either cisplatin or carboplatin and paclitaxel. RESULTS: The major side effect was emesis (grade 3-4, 7/33, 21%). The objective response rate was 10% (one complete response, two partial responses). CONCLUSION: We conclude that altretamine has limited activity in platinum-refractory ovarian cancer.

Administration, Oral↗
PubMed1998

A phase II trial of amonafide in patients with mixed mesodermal tumors of the uterus: a Gynecologic Oncology Group study.

Amonafide demonstrated a poor response rate and substantial toxicity in patients who had measurable, advanced mixed mesodermal tumors of the uterus. Amonafide-a drug that acts through intercalation of tumor DNA-was used to treat 16 patients who had measurable, advanced mixed mesodermal tumors of the uterus as part of a Gynecologic Oncology Group (GOG) Phase II study. The starting dose was 300 mg/m2 intravenously over 1 hour for 5 consecutive days every 3 weeks. Severe or life-threatening hematologic toxicity occurred in 50% of the patients. Two patients experienced vomiting requiring hospitalization. Other toxicities were not severe. One patient had a partial response and one had stable disease, each lasting 4 months. This dose schedule was associated with poor response rate and substantial toxicity.

Adenine↗
PubMed1998

Offending pattern in a gerontophilic perpetrator.

Examples of sexual offences perpetrated against older female victims are infrequently found in the medical literature. The case of a gerontophilic offender is reported. The criminal career of the subject bears a strong resemblance to more typical sex offenders with the exception of the very specific nature of victim selection. The current lack of knowledge and understanding of such offences and perpetrators is emphasized.

Adult↗
PubMed1997

Molecular properties of complexes formed between the prion protein and synthetic peptides.

Complexes of the Syrian hamster cellular prion protein (PrPC) and synthetic Syrian hamster PrP peptides were found to mimic many of the characteristics of the scrapie PrP isoform (PrPSc). Either PrPC expressed in chinese hamster ovary (CHO) cells or a C-terminal fragment of 142 residues of recombinant PrP protein (rPrP) produced in Escherichia coli was mixed with an excess of a synthetic 56 amino acid peptide, denoted PrP(90-145). Complex formation required PrPC or rPrP to be destabilized by guanidine hydrochloride (GdnHCl) or urea and PrP(90-145) to be in a coil conformation; it was enhanced by an acidic environment, salt and detergent. If PrP(90-145) was in a beta-sheet conformation, then no complexes were formed. While complex formation was rapid, acquisition of protease resistance was a slow process. Amorphous aggregates with a PrPC/PrP(90-145) ratio of 1:1 were formed in phosphate buffer, whereas fibrils with a diameter of approximately 10 nm and a PrPC/PrP(90-145) ratio of 1:5 were formed in Tris buffer. The complexes were stable only in the presence of excess peptide in either the coil or beta-sheet conformation; they dissociated rapidly after centrifugation and resuspension in buffer without peptide. Neither a peptide having a similar hydrophobicity profile/charge distribution to PrP(90-145) nor a scrambled version, denoted hPrP(90-145) and sPrP(90-145), respectively, were able to induce complex formation. Although hPrP(90-145) could stabilize the PrPC/PrP(90-145) complexes, sPrP(90-145) could not. Studies of PrPC/peptide complexes may provide insights into how PrPC interacts with PrPSc during the formation of a nascent PrPSc molecule and into the process by which PrPC is converted into PrPSc.

Amino Acid Sequence↗
PubMed1997

Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and Y5 suggests coordinate transcriptional regulation.

The human y1 and y5 receptor genes are transcribed in opposite directions from a common promoter region on chromosome 4q31-q32. One of the alternately spliced 5' exons of the y1 receptor gene (1C) is also an integral part of the coding region of a novel neuropeptide Y receptor, Y5. Exon 1C of the y1 receptor gene, if translated from the opposite strand, encodes sequences corresponding to the large third intracellular loop of the Y5 receptor. The close proximity of the two neuropeptide Y receptor genes suggests that they have evolved from a gene duplication event with the small intron interrupting the coding sequence of the y1 gene being converted into a functional sequence within the y5 gene, while the reverse complementary sequence was utilized as an alternatively spliced 5' exon for the y1 gene. The transcription of both genes from opposite strands of the same DNA sequence suggests that transcriptional activation of one will have an effect on the regulation of gene expression of the other. As both Y1 and Y5 receptors are thought to play an important role in the regulation of food intake, coordinate expression of their specific genes may be important in the modulation of NPY activity.

Alternative Splicing↗
PubMed1997

Comparison of metabolic effects of vegetables and teas with colorectal proliferation and with tumour development in DMH-treated F344 rats.

The aim of this study was to screen potentially chemopreventive vegetables and teas for their effects as human dietary components for the colorectal epithelium and also to seek biomarkers of preventive efficacy. Groups of F344 rats were adapted to a human basal diet supplemented with vegetables or teas, having known contents of glucosinolates, polyphenols and anti-oxidants. Both inductions and suppressions were found for overall glutathione S-transferase (GST) and quinone reductase activities. The mitotic index (MI) showed a three-fold range between groups, with substantial reductions by black tea, spinach, petit pois and peppers. Changes to PCNA labelling index and proliferation zone were marginal. No correlation was found between colonic and hepatic enzyme activities, nor with glucosinolate intake. Colonic MI was associated with the activity ratio GST(hepatic)/GST(colonic) (r = 0.49, P < 0.002), possibly reflecting a need for direct induction rather than exposure to products of hepatic conjugation.

Animals↗
PubMed1996

Chemically synthesised human immunodeficiency virus P7 nucleocapsid protein can self-assemble into particles and binds to a specific site on the tRNA(Lys,3) primer.

The zinc-bound form of the human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein, p7, aggregates into particles visible by electron microscopy. The HIV primer tRNA(Lys,3) forms similar high molecular weight complexes with p7 that are also detected by gel mobility shift assays. RNA oligonucleotides of the three stem-loop structures in tRNA(Lys,3) were assayed for the competitive inhibition of p7-tRNA(Lys,3) binding by the intensities of free tRNA(Lys,3) bands on native gels. This reveals that the p7 binds specifically to the central domain of tRNA(Lys,3) where the D and T psi C loops come together, but not the anticodon stem-loop.

Base Sequence↗
PubMed1996

Sites of failure and times to failure in carcinoma of the vulva treated conservatively: a Gynecologic Oncology Group study.

OBJECTIVE: The objective of this review was to examine the patterns of failure after conservative therapy for vulvar carcinoma to establish a basis for the design of prospective cooperative trials in this disease. STUDY DESIGN: The records and characteristics of all patients in whom cancer recurred after conservative therapy in two prospective clinical trials were analyzed. RESULTS: Of 143 patients who received one or more modifications of therapy, 37 patients had recurrence of cancer and 20 died of the disease. The median intervals to recurrence were 35.9 months for vulvar cancer and 7.0 months for groin cancer (p = 0.0002). There were 12 groin recurrences; 11 (91.7%) of these patients have died of the disease. The median survival time after recurrence was 52.4 months for patients with vulvar cancer and 9.4 months for those with groin cancer (p = 0.0025). CONCLUSIONS: Groin cancer recurs earlier than vulvar cancer among patients treated conservatively. Future trials that evaluate modified therapy to the groin need to include early interim analyses. Follow-up for > 36 months after study entry may not be necessary to evaluate the impact of new treatments.

Adult↗
PubMed1995

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

Adult↗
PubMed1995

Primary chemotherapy with bleomycin, ifosfamide and cisplatinum (BIP) followed by radiotherapy in the treatment of advanced cervical cancer. A pilot study.

Bleomycin, Ifosfamide and Cisplatinum were combined in a 3 cycle regime of neoadjuvant chemotherapy given prior to radiotherapy in the treatment of 26 patients with late Stage (FIGO IIB-IIIB) cervical cancer. Seven patients were withdrawn for reasons of compliance and 1 patient due to toxicity. The response rate to chemotherapy in the remainder (18 patients) was 44.4%. Sixtyfour per cent of 17 patients who completed chemoradiotherapy responded completely. This regime was generally well tolerated and neurotoxicity was less problematic than in other reports, although fatal pneumotoxicity occurred in one patient. It is too early to comment on survival; this is an interim report of responses and toxicities. The results are less impressive than in other reported studies and cast doubt on the role of neoadjuvant chemotherapy in the management of advanced cervical cancer in developing countries.

Adult↗
PubMed1994

Salvage therapy for recurrent and refractory ovarian cancer with high-dose chemotherapy and autologous bone marrow support: a Gynecologic Oncology Group pilot study.

Nine patients with recurrent or refractory epithelial ovarian carcinoma following previous chemotherapy were treated with high-dose carboplatin (300 mg/m2) and ifosfamide according to a dose escalation schedule (1.50, 1.75, 2.00 g/m2), each given intravenously daily for 5 days with autologous bone marrow support. Eight of the nine patients were evaluable for response. Five achieved complete response (CR), all of whom relapsed at 4, 5, 6, 8, and 23 months following treatment. Two partial responses persisted for 6 months, and one patient with stable disease progressed after 2 months and has since died of disease. The median duration of remission was 6 months. The treatment was well tolerated across the doses of ifosfamide with the exception of one treatment-related death which was due to acute renal failure and central nervous system toxicity from ifosfamide. It appears that the use of high-dose chemotherapy with autologous bone marrow support in the treatment of ovarian cancer produced a high rate of response of short duration in this small group of heavily pretreated women.

Adult↗
PubMed1994

The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer, in which the maximum diameter of residual is < or = 1 cm, and suboptimal residual cancer, in which the residual disease is > 1 cm. Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed. This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a randomized trial of intense versus standard chemotherapy. STUDY DESIGN: Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses, respectively. There was no difference in progression-free interval or survival between the two arms. Of the 458 stage III (with residual disease > 1 cm) and stage IV patients entered in this study, 294 stage III patients comprise the current analysis. Surgical reporting forms, operation reports, and pathology reports were reviewed to determine initial greatest tumor diameter and residual tumor diameter. Patients were grouped by residual diameter. Multivariate analysis considered residual diameter of disease, age, histologic characteristics, performance status, and ascites. An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group. RESULTS: Patients ranged in age from 20 to 80 years, with a median of 60 years. All patients were Gynecologic Oncology Group performance status 0 to 2. Fifty-two percent had grade 3 tumors, and 39% and 9%, respectively, had grade 2 or 1 tumors. All patients had stage III disease. Ninety percent had serous, endometrioid, or mixed epithelial cell type tumors. Multivariate analysis revealed a relative risk of dying as follows: residual disease < 2 cm, relative risk 1.00; 2 to 2.9 cm, relative risk 1.90; 3 to 3.9 cm, relative risk 1.91; 4 to 5.9 cm, relative risk 1.74; 6 to 7.9 cm, relative risk 1.85; 8 to 9.9 cm, relative risk 2.16; > or = 10 cm, relative risk 1.82. The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant (p < 0.01). There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm. CONCLUSIONS: Among patients with suboptimal (> 1 cm residual disease) epithelial ovarian cancer, those who have small diameter residual disease (< 2 cm) tend to survive longer than those who have larger residual disease. Among those with larger residual disease, size does not affect prognosis appreciably.

Adult↗
PubMed1994

Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.

PURPOSE: This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors. PATIENTS AND METHODS: After tumor removal and thorough surgical staging, patients were enrolled on this study and treated with three courses of cisplatin, etoposide, and bleomycin (BEP). Reassessment laparotomy was required of consenting, appropriate patients initially, but became an optional procedure in 1989. RESULTS: Of 93 patients assessable on this trial, 89 are continuously free of germ cell cancer. At second-look laparotomy, two other patients were found to have small foci of immature teratoma; both remain clinically free of recurrence. One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93 patients are currently free of germ cell cancer. Follow-up duration ranges from 4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute toxicity was moderate. One patient developed acute myelomonocytic leukemia 22 months after diagnosis. Another patient was noted to have a malignant lymphoma 69 months after protocol treatment. CONCLUSION: Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients. The development of acute leukemia as a complication of treatment is disturbing and mandates careful long-term follow-up, but is unusual and does not alter the risk-to-benefit ratio of treatment.

Adolescent↗
PubMed1994

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.

PURPOSE: This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS: Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS: Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION: Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.

Adult↗
PubMed1994

Chromic phosphate therapy in carcinoma of the ovary.

BACKGROUND: Adjuvant therapy with intraperitoneal (IP) chromic phosphate (P-32) instillation in both early and advanced carcinoma of the ovary requires adequate intra-abdominal distribution for maximum therapeutic benefit. Abdominal-pelvic computed tomographic (CT) scanning with water-soluble IP contrast to establish the absence of intra-abdominal adhesions prior to P-32 instillation has not been previously reported. STUDY DESIGN: Sixteen patients with carcinoma of the ovary who were offered IP P-32 therapy between January 1988 and December 1992 were retrospectively reviewed. Computed tomographic scans on 13 patients were reevaluated using a modification of Muggia and associates' distribution scoring system. RESULTS: Of the 16 patients, one had a negative second look operation for stage IIIc carcinoma of the ovary. The remaining 15 with stage I and II disease underwent at least a staging laparotomy, bilateral salpingo-oophorectomy, and omentectomy. The mean time from operation to IP P-32 attempt was 28 days with a range of 17 to 90 days. Adequate distribution was considered present in two of the three cases evaluated by technetium scanning and in four of the 13 cases studied by CT scanning. On review, 12 of 13 cases studied by CT scans revealed some areas of IP contrast exclusion and loculation. CONCLUSIONS: We suspect that uneven postoperative IP P-32 distribution is common and may be missed by two-dimensional imaging techniques such as technetium scanning or fluoroscopy.

Adult↗
PubMed1991

Chemical synthesis of 10 kDa chaperonin. Biological activity suggests chaperonins do not require other molecular chaperones.

Molecular chaperones are required for the correct folding and assembly of certain other polypeptides. It is not known whether molecular chaperones themselves require other chaperones to become functional. A 97-amino acid chaperone, the chaperonin 10 protein was chemically synthesised so that during synthesis and purification there was no contact of the chaperone with any other protein. The purified, synthetic chaperonin 10 protein formed oligomeric structures spontaneously and was biologically active as a chaperonin. This is the first description of a chemically synthesised chaperonin, and suggests that no other chaperones are required for correct folding, polymerisation and biological activity of this chaperone.

Bacterial Proteins↗
PubMed1990

Stage II carcinoma of the cervix: analysis of the value of pretreatment extraperitoneal lymph node sampling and adjunctive surgery following irradiation.

This is a retrospective analysis of the results of treatment of 24 patients with bulky stage II carcinoma of the cervix treated with full course irradiation followed by adjunctive surgery between 1975 and 1980. A review of the surgical specimens following irradiation showed that 12 patients had no residual cancer, five had only microscopic foci of cancer, and five had extensive residual cancer. Two patients had unresectable persistent cancer. Six patients had histological evidence of lymph node metastases prior to irradiation. The surgical-pathological findings following irradiation had important prognostic implications. All five patients with extensive residual cancer in the surgical specimen recurred, 2 of 5 patients with only microscopic foci of residual cancer and, none of the 12 patients with no residual cancer in the resected specimens developed a recurrence. Lymph node involvement was not associated with an increased incidence of recurrence. Most patients with residual cancer following full course irradiation recurred locally. Thus the addition of adjunctive surgery following full course irradiation did not significantly improve the treatment results of patients with bulky stage II carcinoma of the cervix.

Brachytherapy↗