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Biomedical subjects

H Scher

Publications and source records attributed to H Scher.

At least 19 recordsLinked to original sources

T-wave amplitude utility revisited: some physiological and psychophysiological considerations.

The last decade has seen some quite polemicized discussions concerning the utility of T-wave amplitude as a psychophysiological measure, but more recent reports indicate that we are now moving into a more empirically oriented and analytic examination of this topic. Such a report is one by Contrada et al. (1989), who manipulated sympathetic (beta-adrenergic) influences both pharmacologically and behaviorally, and whose main conclusion was that their results "support the hypothesis that T-wave is significantly affected by beta-sympathetic influence on the heart". However, we question their other conclusion that "a nonspecific effect of heart rate change on T-wave amplitude would also account for these results", and also suggest that their discussion of the "implications for the utility of T-wave amplitude in psychophysiological research" bears further consideration. In particular, for psychophysiologists, of fundamental importance is the distinction between T-wave amplitude's utility as a physiological index and its utility as a psychophysiological index. Concerning the former issue, we consider: (a) the alpha/beta adrenergic distinction, (b) inappropriate T-wave amplitude augmentation effects to sympathomimetic stimulation, (c) the nonspecific-response-to-tachycardia argument, and (d) the view of pulse transit time as a criterial standard, rather than as a candidate index. Regarding the issue of psychophysiological index utility, we consider: (a) dependent-variable sensitivity, drawing a further distinction between reactive and specific sensitivity, and (b) independent-variable-manipulation effectiveness.

Autonomic Nervous System

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.

Brain

Prognostic factors for survival of patients with advanced urothelial tumors treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy.

Between February 1983 and February 1986, 132 patients with advanced urothelial tract tumors were treated with methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Analysis of prognostic factors for survival of the first 92 patients was undertaken using the Cox proportional hazards model. Normal alkaline phosphatase and high Karnofsky performance status (KPS) were predominant for long survival. Patients 60 years or older at initiation of therapy were likely to survive longer than younger patients, perhaps indicating physician selectivity of older patients for this therapy, and those with initial hemoglobin in the normal range were also likely to survive longer. The additional 40 patients' data were used to validate the model. Clinical implications of the prognostic factors are discussed.

Adult

Limited small-cell lung cancer: do favorable short-term results predict ultimate outcome?

Advances in the treatment of limited small-cell lung cancer (L-SCLC) have led to improved short-term outcome. However, it is not clear how well this predicts the ultimate fate of the patients. This may be affected by late relapse of SCLC, the development of second malignancies, and the long-term toxicity of therapy. To address this issue we report follow-up in excess of 5 years on a cohort of 36 patients who had high short-term survival resulting from treatment with chemotherapy combined with cranial and thoracic irradiation. All patients were followed until death or the time of analysis. The initially promising result of 31% survival at 3 years, was reflected in survival from SCLC of 27% at 5 years, and 23% at 9 years. However, when death from all causes was analyzed, survival was only 19% at 5 years and 7% at 9 years. There were 2 survivors disease-free at 7 and 8 years; 7 patients died of other causes without any evidence of SCLC. Among those not dying of SCLC, 4 patients developed second malignancies with a risk of 22% at 3.2 years and 50% at 8 years. Clinical neurotoxicity developed in 3 patients. These data suggest that cure of SCLC is possible in a modest proportion of patients with limited disease, but that the survivors are at significant risk of developing second malignancies which emerge as the most common cause of death during prolonged follow-up. Successful outcome of treatment is further hampered by the occurrence of neurotoxicity. Clinical strategies to prevent these sequelae of therapy are discussed.

Adult

Prostatic cancer: where do we go from here?

This paper focuses on advances in prostatic cancer that occurred during the past year. Specific areas reviewed here are screening, radical surgery, locoregional disease, the no-therapy option, androgen-ablative therapy, prognostic factors, bone-specific therapy, hormone refractory disease, and prostate cancer biology.

Humans

Phase II trial of Didemnin B in patients with advanced renal cell carcinoma.

Twenty-three patients with advanced renal cell cancer were treated with Didemnin B. One partial response was achieved (5%) in 21 evaluable patients. An allergic reaction was noted in four patients including one patient with anaphylaxis. Didemnin B is not recommended in the treatment of renal cell carcinoma.

Adult

The staging of M+ disease.

Patients with newly diagnosed prostatic cancer should be investigated with regard to the presence or absence of distant metastases by: (1) Clinical history especially of weight loss, recent pain, or analgesics intake. (2) Physical examination, looking especially for hepatic enlargement, peripheral lymph nodes, local bone tenderness. (3) Performance status. (4) Hemoglobin, creatinine, PSA and/or PAP, alkaline phosphatases, liver tests, testosterone. (5) Bone scan with X-ray of doubtful hot spots. (6) Chest X-ray. (7) Ultrasound scans (liver, kidney, lymph nodes) or CT scan may be indicated if abnormal blood parameters or in specific situations. (8) Other investigations are only indicated in special circumstances. Follow-up should include: (1), (2), (3), (4) every 3 months. For patients in clinical trials, depending on the end point, bone scan should be repeated every 6 months or possibly depending on the prognostic group (good: every 12 months; bad: 3 to 6 months). For routine clinical management, it could be repeated only when markers (PAP, PSA, alkaline phosphatase) show significant (25-50%) increase and provided the result will influence treatment. Other investigations should only be repeated or performed if abnormal at the start of if clinical data require them.

Biomarkers, Tumor

Sex differences in small-magnitude heart-rate responses to sexual and infant-related stimuli: a psychophysiological approach.

Small-magnitude (2-3 beats per minute) heart-rate responses can show sex differences if assessed with a psychophysiological approach in which temporally fine-grained methods are used to determine topographical differences. Such differences emerged when 15 males and 37 females were shown videosegments depicting emotional scenes. Specifically, males accelerated to erotic segments (couples making love), while females accelerated to segments showing babies crying. In addition, the peak development of baby-cry-elicited accelerations occurred about 1 second before that of erotic segment-elicited accelerations. The results are consistent with a preparatory-response interpretation, but more research is needed both to investigate the generality of these sex differences in heart-rate responses, and to determine the role of experiential and psychosocial factors.

Adult

Neo-adjuvant chemotherapy for invasive bladder cancer. Experience with the M-VAC regimen.

A series of 71 patients with muscle invasive bladder cancer received a median of 3 cycles (range 1-6) of methotrexate, vinblastine, Adriamycin and cisplatin (M-VAC). Efficacy assessed by transurethral resection alone showed that 48% of patients were TO, 13% Tis and 54% had normalisation of initially positive urinary cytology after treatment. However, when considering transurethral resection of the bladder (TURB), cytology and non-invasive procedures (CT scan and/or ultrasound), only 21% had a clinical complete remission (cCR); 48 patients (68%) had pathological evaluation and 13 (27%) were PO after treatment. Non-responding patients had a poor prognosis: 14/30 (47%) developed metastatic disease and 13 died. In assessing the primary lesions, clinical understaging was significant. Of 15 patients who were TO cystoscopically prior to surgery, 6 (40%) had residual disease in the pathological specimen, including 4 with muscle infiltration; 23 patients (32%) remained clinically staged, only 8 of whom remain disease-free. With a median follow-up of 24 months (range 2-42+), 41 patients are alive and disease-free, including 20 with a functional bladder. The large staging error raises questions concerning studies using clinical rather than pathological endpoints as the sole criteria of efficacy.

Adult

Brief assessment of cognitive impairment in patients with stroke.

The Stroke Unit Mental Status Examination (SUMSE) has been developed to provide a reliable poststroke test of cognitive functioning that may be administered at bedside. SUMSE was designed to assess major cognitive disorders caused by stroke (eg, language disorders, visuoperceptual deficits, and memory disorders) while avoiding, as much as possible, reliance on patients' English language skills and motor movements. SUMSE's reliability and validity were evaluated by administering it to patients on a stroke rehabilitation unit in conjunction with already validated tests. The results indicated that SUMSE has the potential to become a useful tool for the bedside assessment of mental impairment in stroke patients.

Aged

Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium.

We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.

Adult

Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.

Adult