Biomedical subjects
Publications and source records attributed to R J Mark.
We report a case of primary urethral lymphoma successfully managed by external beam radiation therapy. Long-term freedom from recurrence in this case suggests irradiation is a viable treatment option for this rare malignancy.
Chondrosarcoma of the head and neck is a rare tumor. In an attempt to clarify optimal treatment of these lesions, we reviewed the records and pathologic material of 18 consecutive cases of head and neck chondrosarcoma seen at our institution between 1955 and 1988. Follow-up ranged from 3 to 168 months with a median of 72. Absolute 5-year survival was 68% (11/16), with 9/16 (56%) patients surviving disease-free. Grade was the most important prognostic factor. Only one of 7 (14%) patients known to have high grade histology was rendered disease-free, as opposed to 9/10 (90%) with low-grade lesions. Tumor size and completeness of surgical resection were also important prognostic factors. Four of 10 patients managed initially with surgery alone achieved local control with greater than 5-year survival. All four had low-grade lesions. Five patients received surgery and radiation as primary treatment, and three are disease-free with greater than 5-year follow-up. Two of these were irradiated because of positive margins. One patient received radiation alone and has persistent disease. Two patients received combined chemotherapy and surgery because of high-grade lesions, and one is free of disease with greater than 5-year follow-up. Patients with incomplete resections should receive further surgery or postoperative radiation therapy. High-grade lesions should be treated aggressively.
To define optimum treatment and delineate recurrence patterns and prognostic factors in oligodendrogliomas, the authors reviewed the records of 49 patients who received treatment for these rare tumors between 1957 and 1990; 41 patients had at least 5 years follow-up. Age, race, gender, performance of computed tomography (CT), tumor location and grade, histologic findings, calcifications, surgery with or without postoperative radiation therapy, and the doses and fields used in radiation therapy were evaluate for prognostic relevance by means of chi 2 and Wilcoxon log-rank tests. Metaanalysis of relevant literature was also performed. Actuarial survival at 5, 10, and 15 years was 61%, 41%, and 24%, respectively. The pattern of recurrence was predominantly local alone (30 of 31 patients [97%] with recurrence). Age younger than 40 years, low-grade tumor, calcifications, and performance of CT were statistically significant prognostic factors. A trend existed toward improved 5-year survival in patients who underwent postoperative radiation therapy (P = .067); at stratification for subtotal resection, this improvement became significant (74% vs 25%, P = .019). Metaanalysis demonstrated a survival advantage for surgery with radiation therapy versus surgery only (56% vs 42%, P < .01).
Randomized studies of stage I and II breast cancer have shown that breast conservation treatment is equivalent to modified radical mastectomy in regard to local-regional control and survival. Little has been published on breast conservation for patients with large tumors. We analyzed 68 patients with tumors measuring 4 cm or larger (range, 4 to 12 cm) treated with breast-conserving surgery and radiation therapy. The median follow-up was 46 months; the mean tumor size was 5 cm. The 5-year actuarial local-regional recurrence rate was 8.5%, and the overall survival and disease-free survival rates were 76% and 68%, respectively. We conclude that breast conservation treatment may be a reasonable alternative to mastectomy in patients with tumors 4 cm or larger without compromise in local-regional control or survival, while achieving acceptable cosmesis.
Most mitochondrial proteins destined for the intermembrane space (IMS) carry in their presequence information for localization to the IMS in addition to information for their import. By selecting for mutants in the yeast Saccharomyces cerevisiae that mislocalize an IMS-targeted fusion protein, we identified mutations in the IMS sorting signal of the cytochrome c1 protein. Amino acid substitutions or deletions in a stretch of 19 hydrophobic amino acids of the cytochrome c1 presequence resulted in accumulation of the intermediate form of the cytochrome c1 protein in the matrix. In some cases, the accumulated intermediate appeared to be slowly exported from the matrix, across the inner membrane to the IMS. Our results support the hypothesis that the cytochrome c1 precursor is normally imported completely into the matrix and then exported to the IMS.
One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease-free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5- and 10-year actuarial survival rates for all patients were 58% and 47%, respectively. Disease-free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty-four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy-nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long-term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.
Between 1955 and 1987, twenty-nine patients with the diagnosis of fibrosarcoma of the head and neck were seen at the UCLA Medical Center. Follow-up ranged from 15 to 192 months, with a median of 66 months. Absolute 5-year survival was 62% (13/21). Five of 17 patients treated initially with surgery alone achieved local control and long-term survival. All five had low-grade lesions. Five patients received postoperative radiation therapy because of positive surgical margins. Three were rendered disease free, and all had low-grade lesions. Radiation therapy was used as primary treatment in six patients, four of whom received additional chemotherapy. Of these six, two are disease free with longer than 5-year follow-up. Surgery with and without adjuvant therapy successfully salvaged 42% (5/12) of the patients with local recurrence. Eighty percent (12/15) of the patients with low-grade lesions were ultimately rendered disease free vs only 8% (1/12) of the patients with high-grade histologic features. Seventy-two percent (13/18) of the patients with local recurrence were known to have positive surgical margins. Sixty-eight percent (13/19) of the patients with recurrent disease had high-grade lesions and/or tumor size larger than 5 cm. Tumor grade is the most important prognostic factor followed by tumor size and surgical margin status. Patients with low-grade lesions and adequate surgical margins are treated well with surgery alone. Patients with high-grade lesions or positive surgical margins should receive adjuvant treatment.
Eighteen cases of osteogenic sarcoma of the head and neck were treated at our institution between 1955 and 1987. The patients' ages ranged from 5 to 73 years, with a median age of 28 years. The sex distribution was equal. Follow-up ranged from 1 to 276 months, with a median of 79 months. The primary site of the tumor was the mandible in nine cases, maxilla and paranasal sinuses in six, skull in two, and orbit in one. Six of 18 patients were free of disease with greater than 5 years of follow-up. Four of the six received combined surgery, radiation therapy, and chemotherapy as their primary treatment. Of the five patients treated with surgery alone, four suffered recurrences, one of whom was salvaged with further surgery and chemotherapy. Five patients were treated initially without surgery. They received radiation therapy with or without chemotherapy; all five developed local recurrence. We conclude that osteogenic sarcoma of the head and neck is an aggressive tumor, prone to both local and distant failure. Based on our series and from published experience involving the extremities, osteogenic sarcoma of the head and neck should be managed with multimodality therapy.
Four offspring of three different Huntington disease (HD) affected x affected matings were assessed by genetic linkage analysis for possible homozygosity. One individual was found to have a 95% likelihood of being an HD homozygote. The homozygote individual had an age at onset and symptoms which were similar to those of affected HD heterozygote relatives, including some with younger onset. This confirms the observation of Wexler et al. that in HD the homozygote is not more severely afflicted than the heterozygote.
Of 19 studies on 15 patients with morbid obesity and fatty infiltration of the liver, 16 had increased uptake and retention of 133Xe in the liver following 5-minute rebreathing of 133Xe and oxygen. This observation shows a high correlation with the histologically proven presence of fat in the hepatocytes, and offers a simple, accurate and precise indication of the excess fat in the liver.
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The General Electric-Elscint system for telephone line transmission of rectillinear scans has been tested and with certain limitations found to be acceptable in terms of diagnostic accuracy for many scan procedures. The system tested had some logistic disadvantage requiring batch processing of the scans, and making quality control of the scans difficult with the one video data processor available at the reference centre.
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INTRODUCTION: The treatment of children with rhabdomyosarcoma (RMS) has been established in multicenter protocols. There are few data available regarding the treatment of other sarcomas in pediatric patients. METHODS: From 1955 to 1988, a retrospective review of 33 children with sarcomas other than RMS of the head and neck was performed to identify prognostic factors and to determine optimal treatment. Grade, tumor size, and RMS grouping of the tumors were found to be of prognostic value. RESULTS: Eighteen of 33 (54%) patients are currently disease free. Only 3 of 16 (19%) patients treated initially with surgery alone were rendered disease free. However, 6 patients were salvaged with an additional surgical procedure, yielding 9 of 16 (56%) patients disease free treated with surgery alone. Of patients receiving surgery plus radiation therapy, with or without chemotherapy, 7 of 14 (50%) have no evidence of disease. CONCLUSION: After salvage therapy, 5-year disease-free survival was 56% (15 of 27). Unlike rhabdomyosarcoma, complete surgical extirpation is the mainstay of treatment in pediatric sarcomas other than RMS of the head and neck. Adjuvant radiation with or without chemotherapy should be administered when complete resection is not possible.
Increasing evidence supports the involvement of amyloid beta-peptide (A beta) and an excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. However, approaches aimed at preventing A beta toxicity and neurofibrillary degeneration are undeveloped. We now report that anticonvulsants (carbamazepine, phenytoin, and valproic acid) can protect cultured rat hippocampal neurons against A beta- and glutamate-induced injury. Each of the anticonvulsants attenuated the elevation of intracellular free calcium levels [(Ca2+)i] elicited by A beta or glutamate suggesting that their neuroprotective mechanism of action involved stabilization of [Ca2+]i. These compounds were effective at clinically relevant concentrations (carbamazepine, 100 nM-10 microM; phenytoin, 100 nM-1 microM; valproic acid, 100 nM-100 microM). The anticonvulsants suppressed glutamate-induced alterations in tau and buiquitin immunoreactivities. Compounds that stabilize [Ca2+]i may afford protection against the kinds of insults believed to underlie neuronal injury in Alzheimer's disease.
Patients with the acquired immunodeficiency syndrome (AIDS) are characterized by a decrease in the number of T helper cells, a defect that is linked to the impaired immunologic competence. Vitamin A and its dietary precursor, beta-carotene, increase absolute T helper cell counts as well as indices of T cell function in both human and animal models. To determine if short-term beta-carotene treatment affects T lymphocyte subsets in patients with AIDS, a single-blind, non-randomized clinical trial of beta-carotene was performed in seven patients with AIDS. Enrollment criteria included no evidence of: a) active opportunistic infection: b) greater than 1 kilogram change in weight in the month preceding enrollment; c) chronic diarrhea or malabsorption; and d) hepatic disease or significant anemia. Beta-carotene was given with meals in two divided doses of 60 mg/day for four weeks; this was followed by no therapy for six weeks. Samples for total white blood cell, lymphocyte and T lymphocyte subset counts were measured at baseline, at the end of four weeks of treatment and another six weeks after treatment had stopped. P24 antigen, beta-2 microglobulin and liver function tests were also measured. All subjects tolerated the treatment well without evidence of toxicity. In response to beta-carotene, total lymphocyte counts rose by 66 percent (.05 < p < .10), and CD4+ cells rose slightly, but insignificantly, in the entire group. In all three of the patients who had baseline CD4+ cells greater than 10/microliters, however, the mean absolute increase in CD4+ cells in response to beta-carotene was 53 +/- 10 cells/microliters (p < .01). Six weeks off beta-carotene treatment, the absolute CD4+ cell count returned to pretreatment levels (p < .01). No change was observed in CD8+ cells. P24 antigen and beta-2 microglobulin did not change during treatment. These preliminary observations suggest that short-term treatment with beta-carotene may increase CD4+ cell counts in patients with AIDS who have greater than 10 cells/microliters.