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Biomedical subjects

P Craig

Publications and source records attributed to P Craig.

At least 37 records · Page 2Linked to original sources

High-dose, double alkylating agent chemotherapy with DTIC, melphalan, or ifosfamide and marrow rescue for metastatic malignant melanoma.

Thirty-seven patients with widely metastatic malignant melanoma were treated with one of three chemotherapy regimens, incorporating high-dose dacarbazine (DTIC). The chemotherapy was followed by autologous bone marrow rescue which was harvested under local anesthesia in 25 of the patients. The three regimens comprised a 24-hour infusion of DTIC (Regimen A for patients less than 45 years of age, 4.3 to 10.5 g/m2; B, if greater than 45 years of age 2.7 to 4.0 g/m2; and later C, if greater than 45 years of age 7.0 to 8.0 g/m2). The second alkylating agent was given at +8 and +16 hours from the start of DTIC. The total doses of the melphalan ranged from 60 to 130 mg/m2 for Regimen A and 30 to 40 mg/m2 for Regimen B. Ifosfamide 5.0 to 8.0 g/m2 was given instead of melphalan in Regimen C. The response rates for the regimens were 81% (25% CR) for A, 27% (11% CR) for B, and 20% (with no complete responders) for Regimen C. There was no statistically significant difference between the three regimens for survival with a median value of 6 months. One of the 16 patients treated with the very high dose Regimen A died of septicemia and three of ten patients in Regimen C died within the first 2 weeks of treatment. There was statistically significant greater myelosuppression, stomatitis, and diarrhea in the very high dosage DTIC and melphalan (Regimen A) compared with the other two regimens. No significant difference in response rate or toxicity was observed for the different dosages escalated within each of the three regimens. Although hematologic and gastrointestinal toxicity were very severe, no unusual side effects were noted except for one episode of severe acute renal failure in the high-dose DTIC and melphalan, Regimen A. Responses occurred mainly in nonvisceral, nodal, and cutaneous sites and occasionally in pulmonary metastases. The Karnofsky performance improved 4 to 6 months after treatment notably with the high-dose DTIC and melphalan therapy. No survival benefit for the combination chemotherapy despite the high dosages was detected and such an approach currently cannot be recommended.

Adult↗

Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm.

Although wide surgical excision is the accepted treatment for thin malignant melanomas, there is reason to believe that narrower margins may be adequate. We conducted a randomized prospective study to assess the efficacy of narrow excision (excision with 1-cm margins) for primary melanomas no thicker than 2 mm. Narrow excision was performed in 305 patients, and wide excision (margins of 3 cm or more) was performed in 307 patients. The major prognostic criteria were well balanced in the two groups. The mean thickness of melanomas was 0.99 mm in the narrow-excision group and 1.02 mm in the wide-excision group. The subsequent development of metastatic disease involving regional nodes and distant organs was not different in the two groups (4.6 and 2.3 percent, respectively, in the narrow-excision group, as compared with 6.5 and 2.6 percent in the wide-excision group). Disease-free survival rates and overall survival rates (mean follow-up period, 55 months) were also similar in the two groups. Only three patients had a local recurrence as a first relapse. All had undergone narrow excision, and each had a primary melanoma with a thickness of 1 mm or more. The absence of local recurrence in the group of patients with a primary melanoma thinner than 1 mm and the very low rate of local recurrences indicate that narrow excision is a safe and effective procedure for such patients.

Adult↗

Resurfacing full thickness burns of scalp: 'the cross-word technique'. Practical note.

A technique for the closure of extensive scalp defects resulting from burns is described which is particularly suitable for elderly subjects not able to withstand extensive surgical treatment. This technique is safe, swift and effective for cases of extensive exposure of the bony outer table of the skull devoid of periosteum following trauma.

Aged↗

Veratridine-induced breakdown of cytosolic acetylcholine in rat hippocampal minces: an intraterminal form of acetylcholinesterase or choline O-acetyltransferase?

Rat hippocampal minces were loaded with N-methyl-[3H]acetylcholine ([3H]ACh) in the presence of the 'poorly penetrating' acetylcholinesterase (EC 3.1.1.7, AChE) inhibitor echothiophate and the effect of the depolarizing agent veratridine determined on the subcellular storage and release of [3H]ACh and [3H]choline. Results indicated that veratridine stimulated the release of [3H]ACh from a crude vesicular fraction (P3) by a Ca2+-dependent process, while simultaneously accelerating the breakdown of cytosolic (S3) [3H]ACh. A portion of the [3H]choline derived from the hydrolyzed S3 [3H]ACh was donated to the P3 fraction for [3H]ACh formation and release. When the identical experiment was done using hippocampal minces from septal lesioned rats, veratridine did not stimulate either the Ca2+-dependent release of [3H]ACh or the hydrolysis of cytosolic [3H]ACh. Incubation of control hippocampal minces with paraoxon, an AChE inhibitor which can penetrate cholinergic nerve terminals more rapidly than echothiophate, prevented veratridine from stimulating the Ca2+-dependent release of [3H]ACh from the P3 fraction. Instead, it then stimulated the Ca2+-independent release of [3H]ACh from the S3 fraction. When minces were incubated with the choline O-acetyltransferase (EC 2.3.1.6, ChAT) inhibitor 4-(1-naphthyl)vinyl pyridine (NVP), veratridine was no longer able to stimulate the Ca2+-dependent release of labelled ACh either. Instead, veratridine stimulated the Ca2+-independent release of labelled ACh from the S3 fraction. NVP also abolished the veratridine-induced, Ca2+-dependent release of total ACh. Both paraoxon and NVP inhibited the reversible reaction of ionically bound ChAT prepared from rat brain when tested in vitro, yet paraoxon was much less potent than NVP, and was unable to inhibit this reaction at the low concentration which prevented the veratridine induced breakdown of S3 [3H]ACh during mince incubation. Veratridine depolarization of hippocampal minces stimulated the activity of a membrane-bound fraction of ChAT associated with the P3 fraction, but this fraction of ChAT did not become more sensitive to inhibition by paraoxon during tissue incubation. Veratridine depolarization of minces also increased the activity of membrane-bound AChE, but this enzyme was not inhibited by the low NVP concentration which prevented the veratridine-induced breakdown of S3 [3H]ACh. The veratridine-induced increase in membrane-bound ChAT activity was dependent on the presence of extracellular Ca2+ in the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Treatment of metastatic melanoma by 24-hour DTIC infusions and hemibody irradiation.

Forty-three patients with widely metastatic melanoma were studied. Visceral metastases were present in 79% of the patient group, including five patients with brain metastases. No patients were excluded because of "early death," etc., from analysis. All 43 patients received 24-hour DTIC infusions. Dosages for individual patients ranged from 350 mg/M2 to 2.5 g/M2, a maximum of 6 courses being given. A total of 155 courses was administered. Hemibody irradiation (HBI) was delivered after 1 or 3 courses of DTIC to the area of maximum disease in 23 patients. Fourteen of the 43 patients responded to DTIC chemotherapy (with one complete response), a response rate of 33%. Seven of the chemotherapy responders also responded in other sites to subsequent HBI, a response rate of 30% (7/23). No patient responded to HBI and not to DTIC. Median survival was 4 months (range, 1-15), and nine patients are still alive at 3 to 15 months. Toxicity was generally mild, although there was one possible treatment-related death. Further exploration of DTIC infusion chemotherapy and HBI would be of interest.

Adult↗

Randomized study of Corynebacterium parvum adjuvant therapy following surgery for (stage II) malignant melanoma.

One hundred and fifteen patients with histologically proven primary cutaneous melanoma were entered into a randomized prospective study following surgical removal of clinically obvious regional metastases. The study started in 1977 and was completed in June 1982. Fifty-eight patients (10 with regional skin metastases and 48 with regional node metastases) were in the control group and 57 (15 regional skin, and 42 regional node metastases) received adjuvant C. parvum. Other clinical features were well balanced for each group. C. parvum, 2 mg/m2 IV was repeated eight times at three weekly intervals. The schedule was based on previous work which indicated significant increase in killer cell activity. There was no serious toxicity and 22 patients exhibited tachyphylaxis. Seventeen patients in the control group (11 tumour free) are alive at 24-80 months, and 20 patients in the C. parvum group (12 tumour free) are alive 24-76 months from randomization. No statistically significant difference (P greater than 0.05) was observed between the two patient groups for overall survival (median 26 months) or relapse free survival (median 8 months) from the date of randomization. Nor was the overall survival from the date of primary surgery (median 52 months, range 4-237) or the relapse free survival, median 28 months, range 2-225, significantly different between the two groups of patients. The relapse pattern in the two groups, and survival after relapse were no different though the response rate to actinomycin D and DTIC chemotherapy was significantly higher in the control (48 per cent) than in the C. parvum (23 per cent) group. Toxicity to chemotherapy was not significantly affected by previous C. parvum treatment. Although there were trends for better survival, in the C. parvum patient group, statistically significant activity has not been noted in this study.

Adjuvants, Immunologic↗

Corynebacterium parvum followed by chemotherapy (actinomycin D and DTIC) compared with chemotherapy alone for metastatic malignant melanoma.

Seventy-nine patients with Stage III widely metastatic melanoma were prospectively randomised to a 'no treatment' control group who received on tumour progression DTIC (250 mg/m2 i.v. daily X 5) and Actinomycin D 1.5 mg/m2 on Day 1. A total of six courses at 3-week intervals was given. Chemotherapy was only given on progression of disease. The other group received initially Corynebacterium parvum (2 mg/m2) every 3 weeks for a maximum of eight courses and then the same chemotherapy on evidence of progressive disease. Minimum follow up time is 3 yr. The chemotherapy response rate (control 37%, C. parvum 24%) was not statistically different nor was the effect of chemotherapy on the site of individual metastases. Radiotherapy responses for irradiated soft tissue disease again were not significantly different, between the two patient groups. No significant differences in survival (control group median, 4 months, range 1-46; C. parvum median 3 months range 1-35) were observed and only one patient is alive at 35 months. The pattern of relapse was also similar in both groups. Reduction in haematological toxicity consequent on chemotherapy was not observed in the C. parvum-treated patients. No additional benefit was observed when C. parvum was followed by DTIC and Actinomycin D chemotherapy compared with the results from the chemotherapy given alone, although C. parvum on this schedule had minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

The organization and management of medical education in Australia.

The review highlights the interdependence among the various subsystems involved in medical education and hence the need for coordination. Observations and perceptions derived from interviews and the review of the literature were reported to underline the existing difficulties and factors which impede the integration of efforts of the various subsystems. Problems of coordination seem to relate to the functioning of the existing mechanisms rather than to the absence of structural arrangements. Hence, it seems necessary to improve the skill of committees and other coordinating bodies in the processes of mutual adjustment and responsiveness to changing conditions.

Academic Medical Centers↗

In search of criteria for the assessment of medical education.

This paper describes results of a study to assess whether an undergraduate educational curriculum is 'relevant'. The people surveyed comprised 290 individuals involved in medical education or health service administration. They were asked to suggest five major criteria for judging whether a medical undergraduate programme is relevant or not and to say whether they felt current curricula meet these criteria. Of those sampled, 40% replied. An analysis of the data from respondents showed that medical school professors and senior administrators of health services in Australia have roughly similar expectations of the outcome of medical education. Both groups were concerned that graduates be conscious of health care requirements and costs, that they have adequate clinical skills, knowledge in medical school subjects and skill in interacting with patients and managing their continuing education. On the various dimensions examined there were frequently strong expressions of dissatisfaction with current achievements.

Achievement↗

Intern training in New South Wales.

The process of intern training in New South Wales is at present undergoing critical examination. This article is a brief review of the status of intern training in Australia and New Zealand as revealed by a survey of accredited hospitals and the medical boards. Also reported are the results of a questionnaire widely distributed to the medical profession in New South Wales which sought its views on the nature of, and problems with, the internship.

Attitude of Health Personnel↗

Home dialysis: its costs and problems.

A short description is given of the starting and the running of a home dialysis unit for chronic renal failure. The cost of training and treating 22 home dialysis patients, over an 18-month period is recorded. The annual maintenance costs of patients on home hemodialysis are found to be no more, and often less, than those of the institutional care of any other chronic malady. Furthermore, the prospects for full rehabilitation are good. This being so, home dialysis cannot be regarded as a costly luxury but a treatment which every suitable candidate may reasonably expect.

Adult↗