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Biomedical subjects

R Vollmer

Publications and source records attributed to R Vollmer.

At least 37 records · Page 2Linked to original sources

Juvenile malignant melanoma.

Malignant melanoma in children and adolescents is a rare phenomenon. During a retrospective computer-aided chart review, 78 patients less than 20 years of age were identified who had the diagnosis of malignant melanoma. This accounted for 1.8 per cent of all the melanomas registered at the University Melanoma Clinic. Fifty-one per cent were females, and all the patients were white. Most of the lesions were found on the primary areas of the trunk and extremities. Sixty-seven per cent of the melanomas were of the superficial spreading type, and 82 per cent were invasive to Clark level III and IV. The range of tumor thickness was 0.32 to 5.22 millimeters, with a mean of 1.76 millimeters. Similar population characteristics were noted in the adult and juvenile populations. Controlling for the two most powerful prognostic factors for Stage I melanoma, that is, ulceration and tumor thickness, the actuarial survival times between the two population groups were similar. The median survival times in the adult and juvenile population were 12.9 and 11.9 years, respectively (p = 0.54). There was a trend toward a shorter disease-free interval in the juvenile population. The five year disease-free interval was 65 per cent for adults with melanoma compared with 57 per cent for juveniles with malignant melanoma (p = 0.16). Multiple regression analysis failed to reveal age less than 20 years to be an independent prognostic factor for the development of metastases or over-all survival time. Recurrent disease was observed in 46.2 per cent of juveniles with melanoma who were initially Stage I at diagnosis. Eighty per cent of the relapses occurred in either the local skin or regional lymph nodes. Although malignant melanoma is rare in populations of patients younger than 20 years of age, clinicians should be aware that melanoma does occur in juveniles. With an aggressive approach to surgical therapy, survival rate is comparable with that of the adult population.

Adolescent↗

Stage II malignant melanoma: presentation of a prognostic model and an assessment of specific active immunotherapy in 1,273 patients.

The ability to redefine risk factors and to predict prognosis in patients with malignant melanoma at the time they manifest nodal metastasis can be a benefit to the patient emotionally and to the physician therapeutically. A retrospective review of 1,273 patients with stage II malignant melanoma was performed at our institution. The most significant prognostic factors in a simultaneous hazard Cox multivariate analysis, predicting melanoma-related mortality among stage II patients, were the number of positive nodes (P less than 0.0001), age (P = 0.0004), site of the primary lesion (P = 0.0036), disease-free interval (P = 0.016), thickness of the primary lesion (P = 0.017), and sex of the patient (P = 0.0616). We have developed a model for predicting survival of stage II patients, designed for use in the clinic setting. Its application in a computer system makes it accessible and understandable. The most favorable risk group (18% of the population) has actuarial 5- and 10-year survival rates of 58% and 49%, respectively, from the time of the nodal metastasis. The least favorable risk group (7% of the population) has 5- and 10-year survival rates of 15% and 10%, respectively. There are three intermediate risk groups. All groups differ prognostically (P less than 0.04). The principal adjuvant therapy offered to these patients was specific active immunotherapy, which appears to have a 10-20% survival benefit in stage II patients with greater than one positive node, when compared with institutional controls. The apparent survival benefit of the immunotherapy supports continued clinical investigation of its therapeutic potential.

Actuarial Analysis↗

Prognosis for recurrent stage I malignant melanoma.

The outcome of patients with stage I malignant melanoma has been well assessed in terms of prognostic factors and their effect on survival; however, little is known of the recurrence patterns of cutaneous melanoma or the survival of these patients subsequent to recurrence. A retrospective, computer-aided chart review identified 4185 patients with melanoma who had stage I disease clinically. During a follow-up period of one to 14 years, 35.9% suffered a recurrence. Melanoma of the trunk (37.8%) and head and neck area (46.1%) had an increased incidence of recurrent metastases compared with melanoma of the extremities (29.8%). Local regional metastases accounted for 62.5%, 77.3%, and 85.6% of the recurrences in the head and neck, trunk, and extremity primary sites, respectively, with 65% of the relapses occurring within the first three years. Actuarial five-year survival rates of patients who had recurrent disease were significantly decreased compared with those of patients who had no evidence of metastases during their clinical course. A multivariate analysis was performed to estimate the survival of patients after recurrence. One may use this mathematical model to predict the outcome of individual patients after recurrence and provide a more rationally based prognosis for them and their families.

Adult↗

Segmentation of the EEG by minimization of the total gain in information.

A new procedure for detecting departures from constancy of the parameters of a probabilistic model over a period of time is proposed. It basically consists of specification of a joint probability distribution for data and models and minimization of the total gain in information. In contrast to conventional techniques, this procedure can be used to determine both the number of different models and the positions of the points at which the switches from one model to another occur. It is demonstrated how this new method can be applied to the problem of identification of different stages of EEG background activity. The lengths of these stages might serve as indicators for drug effects in the EEG.

Cerebral Cortex↗

A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.

Adult↗

The diagnostic distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung as defined by a monoclonal antibody (B72.3).

The correct distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung has become increasingly complex, with a variety of histochemical, immunohistochemical, and ultrastructural studies to be performed on biopsy material. The reliability of immunohistochemical studies has been hampered by the use of polyclonal antisera to "carcinoembryonic antigen (CEA)" and keratin. Hybridoma technology now offers monoclonal antibodies (MAbs) in unlimited quantity and standardized quality to selective ranges of specific antigenic determinants. MAb B72.3, generated against a membrane-enriched fraction of human metastatic breast carcinoma, was used to distinguish malignant mesothelioma of the pleura from adenocarcinoma of the lung in tissue sections and was compared in terms of diagnostic utility with polyclonal anti-keratin and anti-CEA to make the same distinction. Reactivity with MAb B72.3 in at least 10% of tumor cells or more was noted in 19 of 22 adenocarcinomas of the lung (P greater than 0.0001), whereas none of the 20 cases of malignant mesothelioma demonstrated comparable reactivity. Furthermore, MAb B72.3 showed no reactivity with benign mesothelial proliferations. MAb B72.3 thus appears to be an appropriate diagnostic adjunct capable of discriminating between these malignancies.

Adenocarcinoma↗

[Analysis of the extension of epileptic discharges in the animal model].

The study was aimed at the enlightenment of intracortical spreading mechanisms in focal epileptic seizures produced by local application of Acetylcholine. Experiments were made in rabbits. Epi- and intracortical seizure potentials were recorded simultaneously with special electrodes. The recorded signals were analysed using computer aided methods. The results show, that the spreading of the pathological events does not take place continuously but by successive generation of "active zones" independent of the original focus produced by Acetylcholine. In the epicortical recordings, the development of a new focus is indicated by a functional uncoupling between the superficial layers of the cortical area to be involved and the momentary active focus. This functional uncoupling is due to an activation of the middle cortical layers of this area by the focus. As a first sign, high frequent potentials can be observed in the middle cortical layers accompanied by an amplitude decrease in the superficial layers. In the further development high negative discharges appear in the middle cortical layers which lead to characteristic surface positive potentials. This phase indicates that a new focus has developed, i.e. the discharges are no longer triggered by the previous focus. These processes continue as long as inactive cortical areas are available. From the obtained results it can be assumed with high probability that in contrast to previous assumptions the generation of a new epileptic focus is not initiated via superficial axon collaterals but that other cortical connections must be responsible. Additionally, it has to be taken into account that extra- and/or intracellular changes of ion concentrations as a consequence of the massive synaptic bombardment may be responsible for the independent discharges in the focus.

Acetylcholine↗

Malignant melanoma and pregnancy.

Confusion exists concerning the influence of pregnancy on survival in patients with malignant melanoma. To evaluate this problem a retrospective computer-aided study was performed of women in the child-bearing years treated for Stage I cutaneous melanoma at the Duke University Comprehensive Cancer Center. Fifty-eight women were identified who had melanoma arise during pregnancy (Group 1) and 43 patients were noted who became pregnant within 5 years of diagnosis of their melanoma (Group 2). Appropriate control groups matched for the clinical variables of age, primary site, and stage of disease and the pathologic variables of Clark's Level, tumor thickness, ulceration, and histologic type were selected from the cohort of 2938 melanoma patients seen at Duke. Actuarial survivals for Group 1 and 2 patients did not differ from their respective controls, although the small number of deaths in each group resulted in wide confidence intervals. When actuarial disease-free intervals were plotted, there was a significant difference between women who had melanoma develop during pregnancy when compared to their controls (P = 0.04). In a multivariate regression analysis, after adjustment for the influence of the more significant prognostic factors for Stage 1 melanoma, including Clark's Level, ulceration and tumor thickness, the effect of pregnancy on disease-free interval became more apparent (P = 0.02). No difference in actuarial disease-free interval was noted in the melanoma patients who elected to become pregnant within 5 years of diagnosis (P = 0.31). A multivariate regression analysis confirmed this finding. These data indicate that although an intercurrent melanoma during pregnancy has a worse prognosis than the control groups, once a woman has been diagnosed as having a cutaneous melanoma, a subsequent pregnancy has no effect on recurrence rate or survival.

Actuarial Analysis↗

Combination chemotherapy in small cell lung carcinoma. A randomized study of two intensive regimens.

From April, 1979 to November, 1981, 293 patients with small cell lung carcinoma (SCLC) were entered on a randomized, controlled study comparing the two induction regimens of high-dose CAV (HD-CAV) (cyclophosphamide [CTX] 1200 mg/m2, doxorubicin [ADR] 70 mg/m2 and vincristine [VCR] 1 mg/m2 intravenously (IV) on days 1 and 21) versus, conventional-dose CAV + VP-16 (etoposide) (CAV-VP) (CTX 1000 mg/m2, ADR 40 mg/m2, VCR 1 mg/m2 IV on days 1 and 21 with VP-16 100 mg/m2 on days 1-3, and 21-23). Responding and stable patients were continued on conventional-dose CAV for 5 consolidation courses. Prophylactic brain irradiation delivered after the first consolidation course in responders was optional. Patients were included in the study if they had extensive disease (i.e., beyond one hemithorax), no prior chemotherapy, or radiotherapy and performance status of 50 or above. After 2 induction courses, 215 cases are evaluable. Of these, 76 of 106 (72%) patients treated with HD-CAV have responded (greater than 50% regression), including 13 complete responders (CRs) versus 80 of 108 (74%) patients on CAV-VP, including 15 CRs. Of the 130 evaluable patients who have completed consolidation (HD-CAV, 65; CAV-VP, 65), an additional 22 patients achieved CR (HD-CAV, 12; CAV-VP, 10) for an overall CR rate of 24%. Median duration of remission was 33.6 weeks for HD-CAV and 35.6 weeks for CAV-VP (P = 0.61). Median duration of complete response for HD-CAV was 33.8 weeks and for CAV-VP 36.7 weeks (P = 0.81). Survival curves were similar for the two regimens, with medians of 42.1 weeks for HD-CAV and 42.3 weeks for CAV-VP (P = 0.35). Survival correlated with performance status and quality of response. As anticipated, the major toxicity for both induction regimens was leukopenia. During induction, granulocyte nadirs of less than 500/mm3 occurred in 81% of patients on HD-CAV and 77% of patients on CAV-VP. Thus, dose intensification appears to produce high response rates and modest complete response rates in extensive SCLC, but it does not appear to improve materially survival compared to prior reports of conventional-dose therapy.

Adult↗

[Combined treatment of malignant gliomas].

A controlled study of 226 age-matched patients with histologically proven grade 3 and 4 supratentorial gliomas with maximum feasible tumour resection, postoperative Karnofsky performance over 50 and minimum survival of 8 weeks compares the results of supportive care (45 cases), high-dose irradiation of 40 to 66 Gy (59 cases), COMP protocol (CCNU, procarbazine, vincristine, methotrexate, prednisone in 15 day cycles-42 cases) and simultaneous irradiation and COMP chemotherapy (80 cases including 30 survivors). Median recurrent-free intervals in the treatment groups (7 to 11.7 months) were significantly longer than after supportive care (4.4 months). Median survival with supportive care (6.7 months) was significantly shorter than after radiation or COMP treatment (11.7 and 12.3 months) and 14.9 to over 19.9 months with combined treatment, where the two-year survival rates were 33 and 67% (for survivors), and the 3-year survival rates 13 to 30%. Toxic side effects of multimodality treatment were more frequent than after chemotherapy. In addition to space-occupying intracranial cysts often simulating tumour recurrence (12%) and rare radiation necrosis, about 15% of long-term survivors developed progressive intellectual dysfunction with brain atrophy, in the absence of tumour regrowth. Despite some promising results of multimodality approaches towards the management of malignant supratentorial gliomas, the overall results are unsatisfactory and need further optimization.

Adult↗

Histiocytoid hemangioma of the skin and scapula. A case report with electron microscopy and immunohistochemistry.

This report presents the interesting case of a 50-year-old white man with an unusual benign tumor composed predominantly of a proliferation of atypical endothelial cells combined with a variable inflammatory response. This case represents an instance of the recently renamed entity "histiocytoid hemangioma" in which two organ systems are involved. Both skin and bone showed typical lesions. No physical connection jointed the separate lesions. The results of examination by light microscopy, electron microscopy, and immunoperoxidase examination for lysozyme and Factor VIII are reported. The significance of this case is that it supports the concept of classifying similar vascular lesions, despite varied organ system origin, into a single entity, the histiocytoid hemangioma.

Bone Neoplasms↗

Correlation between EEG changes indicative of sedation and subjective responses.

The central activity of ketotifen ( Zaditen ), a benzocycloheptathiophene derivative for use in the prophylaxis of asthma, was determined by quantitative pharmaco-EEG in 7 healthy volunteers in a single-blind trial. During the 1st week of the trial, placebo was given twice daily followed by ketotifen 1 mg twice daily for 3 weeks. Placebo was again given for a further week. 15-min resting EEGs were taken immediately before and 3 and 6 h after medication on 8 defined days during the study, and the subjects were asked for side effects. Lead O2-Cz was analyzed by spectral analysis, and the relative power of the delta, theta, and fast and slow alpha bands as well as the dominant alpha frequency were calculated. The mean of each of these parameters was calculated per subject for each of the three measurements on each study day and compared with the baseline by means of one-way analysis of variance. A statistically significant slowing of the dominant alpha frequency, a decrease of the relative power of the fast alpha activity, and an increase of the relative power of the theta rhythm were found. These effects, indicative of a mild sedation, were highest during the 1st week of treatment with ketotifen, with a peak at the 3rd day, and gradually decreased thereafter. In contrast to the sensitive pharmaco-EEG method, none of the subjects complained of sedation or tiredness while taking ketotifen.

Adult↗