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Biomedical subjects

M Rothenberg

Publications and source records attributed to M Rothenberg.

17 recordsLinked to original sources

Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer.

PURPOSE: To increase the taxol dose beyond the current standard dose intensity of 175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND METHODS: Fifteen patients who had platinum-refractory or recurrent advanced-stage ovarian cancer were treated with taxol in a phase I trial and were given granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of 170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily subcutaneous injection that started 24 hours after the completion of the taxol infusion. RESULTS: Four patients required either taxol dose reduction or delay. The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at 300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove sensory disturbance that primarily affected proprioception, and was associated with objective changes on nerve conduction studies in affected individuals. Mucositis was rarely observed. Substantial myelosuppression was observed, but was not dose-limiting. Five of 14 assessable patients experienced an objective response to therapy, with another five individuals who experienced a 30% to 45% reduction in tumor mass. CONCLUSION: Taxol can be safely administered in doses up to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose intensification.

Adult

Late recurrent Candida endocarditis.

Late recurrent Candida endocarditis (LRCE) developed on a prosthetic mitral valve 22 months after treatment for primary native mitral valve endocarditis. The LRCE was difficult to diagnose; results of two dimensional echocardiography and repeated blood cultures were negative. Only transesophageal echocardiography revealed a vegetation and only lysis centrifugation blood cultures demonstrated candidemia. Postmortem examination revealed a large Candida vegetation on the prosthetic valve and Candida in the mitral valve ring. This case and a review of the literature indicate that Candida endocarditis treated with amphotericin B and prosthetic valve replacement may recur months after treatment, and that LRCE, which is difficult to diagnose and treat, may be best prevented by lifelong antifungal suppressive therapy.

Adult

Oncology.

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Humans

Cisplatin-based combination chemotherapy in the treatment of advanced-stage testicular cancer: cost-benefit analysis.

A cost-benefit analysis of the impact of cisplatin-based combination chemotherapy for treatment of disseminated testicular cancer showed that the annual estimated economic value of this treatment innovation in the United States is approximately $150 million. The estimate was based on the human capital approach, which conservatively values a human life in terms of economic productivity. Because testicular cancer predominantly strikes young adult males, the savings reported were due to the future earning potential of the survivors. A comparison of relevant National Cancer Institute (NCI) costs for drug development and clinical trials versus annual savings realized indicated that the total costs over a 17-year period are recovered in less than 1 year. This report is an example of health care cost savings resulting from NCI support of biomedical research.

Antineoplastic Combined Chemotherapy Protocols

Structural characterization of a rice actin gene.

We have isolated and sequenced a full-length cDNA clone containing information for the rice actin gene RAc1. Transcript terminus mapping and sequence alignment between the RAc1 cDNA clone and a previously isolated RAc1 genomic clone were used to determine the structure of the RAc1 gene. This allowed us to make the first complete structural characterization of a plant actin gene. The analysis revealed the presence of a 5'-noncoding exon, separated by an intron, from the first translated exon of the RAc1 gene. This is one of the few reported cases of a plant gene containing such a 5'-noncoding exon. Sequence comparison between the previously isolated plant actin genes suggests that such an exon may be a common feature of plant actin gene structure. The present study also confirms that the rice actin gene family is composed of at least eight unique members.

Actins

Characterization of the rice (Oryza sativa) actin gene family.

Four rice (Oryza sativa) genomic actin genes have been characterized. The rice actin genes show a conservation of intron number and position that is characteristic of plant actins. Sequence comparisons revealed that the plant actins generally have a high degree of inter- and intraspecific sequence heterogeneity. However, one rice actin gene has a much higher degree of nucleotide sequence identity to a previously isolated actin sequence from Arabidopsis thaliana than to any other plant actin gene. This leads us to suggest that the two sequences may represent functionally homologous genes which arose from an ancient actin gene lineage that was separated by the divergence of the dicot and monocot plants. Genomic DNA blot analysis showed that the rice actin gene family contains at least eight unique members. RNA hybridization analysis revealed that individual rice actin genes can display different patterns of transcript accumulation. The observed differences in sequence and transcript accumulation patterns suggest that the individual rice actin genes may differ in their transcriptional regulation and/or cellular function.

Actins

Increased DNA repair as a mechanism of acquired resistance to cis-diamminedichloroplatinum (II) in human ovarian cancer cell lines.

A human ovarian cancer cell line, A2780, derived from an untreated ovarian cancer patient and relatively sensitive to cisplatin was treated by stepwise incubation with cisplatin to produce a cisplatin-resistant variant, 2780CP. The relative abilities of these cell lines to repair cisplatin-induced damage to cellular DNA then was examined by measure of [3H]thymidine incorporation into normal density DNA separated from bromodeoxyuridine-substituted DNA on alkaline cesium chloride gradients. These studies revealed that primary cisplatin resistance present in 2780CP was associated with a near twofold-increased ability to repair damage induced by the drug under conditions where 2780CP was approximately 5-fold resistant to cisplatin. Aphidicolin, a specific inhibitor of DNA polymerase alpha, showed a dose-dependent capacity to inhibit DNA repair in this system with maximum inhibition of 63% at 4 micrograms/ml. It was also found that inhibition of DNA repair during and shortly after cisplatin exposure resulted in an approximately threefold increase in the cytotoxicity of cisplatin as monitored by clonogenic cell survival in the resistant but not the sensitive parental cell line.

Aphidicolin

Breast cancer screening in an urban black population. A preliminary report.

Breast cancer is a major cause of death among black women. At Cook County Hospital in Chicago, a hospital serving a predominantly black population, only 31% of breast cancers were localized at the time of diagnosis in the years 1980-1983. A survey of patient records in the largest primary care clinic in the hospital revealed that only 2% of eligible patients had received mammograms in 1982. A nurse-run breast cancer detection program was begun in mid-1983. Since that time the proportion of women who have received periodic breast examinations has increased from 26% to 46% (P less than 0.001) and periodic mammograms have increased from 2% to 41% (P less than 0.001). The proportion of women having received breast self-examination teaching increased from 10% to 58% (P less than 0.001). The proportion of localized breast cancer was significantly greater for those women whose cancer was diagnosed through the screening program (44 of 72, 61%) compared to other clinical areas (71 of 213, 33%) in the years 1984 through 1986 (P less than 0.001). There has been a significant increase in the percentage of localized breast cancer at Cook County Hospital comparing 1980-1983 statistics (31%), before the Breast Cancer Detection Program was fully established, with 1984-1986 statistics (40%) (P less than 0.02).

Black or African American

Monitoring vocal fold abduction through vocal fold contact area.

A number of commercial devices for measuring the transverse electrical conductance of the thyroid cartilage produce waveforms that can be useful for monitoring movements within the larynx during voice production, especially movements that are closely related to the time-variation of the contact between the vocal folds as they vibrate. This paper compares the various approaches that can be used to apply such a device, usually referred to as an electroglottograph, to the problem of monitoring the time-variation of vocal fold abduction and adduction during voiced speech. One method, in which a measure of relative vocal fold abduction is derived from the duty cycle of the linear-phase high pass filtered electroglottograph waveform, is developed in detail.

Electric Conductivity

Electroglottographic observations of young stutterers' fluency.

The purpose of this study was to compare the laryngeal behavior associated with the perceptually fluent speech of young stutterers (n = 8) to that of their normally fluent peers (n = 8). Laryngeal behavior during fluent productions of the initial and final consonants and medial vowels in each of the words Pete, bake, face, and veal was observed by means of an electroglottograph (EGG). The recorded EGG signal was electrically processed to obtain a measure of vocal fold abduction from the "open quotient" (glottal open time divided by glottal period) during consonant-vowel (CV) and vowel-consonant (VC) transitions, as well as during the central portion of the vowel. In each case, a Typical pattern for the abduction measure that was consistent with the underlying production mechanism for the sound sequence was found for the normally fluent subjects. The normally fluent children exhibited significantly more Typical patterns during the CV/CV transitions than did the stuttering youngsters, with 72% of the total transition samples from normally fluent youngsters being Typical versus 42% for the young stutterers. Though some Atypical patterns for the vowels were noted, most of the normally fluent (94%) and stuttering (84%) youngsters' total vowel samples were Typical. These findings suggest that some young stutterers tend to have difficulty stabilizing and controlling laryngeal gestures even during speech judged fluent by trained listeners, particularly at those points in the utterance where these youngsters must move between sound segments.

Child, Preschool

Encoding voice fundamental frequency into vibrotactile frequency.

Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency.

Adult

Measurement of airflow in speech.

It has been shown previously that a mask-type wire screen pneumotachograph can be constructed with a time resolution of 1/2 msec. In this paper it is shown that with careful design a resolution of about 1/4 msec can be achieved. The various factors involved in optimizing such a mask are described. A major practical limitation in the design has been the need for a fast-responding differential pressure transducer to measure mask pressure; however, a simple electrical compensating network is described that allows the use of a nondifferential transducer. Also determined are the conditions under which breath moisture condensing on the wire screen affects the performance of the mask. An example is given of how a high-speed pneumotachograph can be used, with a measure of the pressure across a constriction in the vocal tract, to derive the time variation of the flow conductance and resistance at that constriction. The advantages of a high-speed pneumotachograph in laryngeal frequency extraction are also considered.

Adult

Vibrotactile frequency for encoding a speech parameter.

Frequency of vibration has not been widely used as a parameter for encoding speech-derived information on the skin. Where it has been used, the frequencies employed have not necessarily been compatible with the capabilities of the tactile channel, and no determination was made of the information transmitted by the frequency variable, as differentiated from other parameters used simultaneously, such as duration, amplitude, and location. However, several investigators have shown that difference limens for vibration frequency may be small enough to make stimulus frequency useful in encoding a speech-derived parameter such as the fundamental frequency of voiced speech. In the studies reported here, measurements have been made of the frequency discrimination ability of the volar forearm, using both sinusoidal and pulse waveforms. Stimulus configurations included the constant-frequency vibrations used by other laboratories as well as frequency-modulated (warbled) stimulus patterns. The frequency of a warbled stimulus was designed to have temporal variations analogous to those found in speech. The results suggest that it may be profitable to display the fundamental frequency of voiced speech on the skin as vibratory frequency, thought it might be desirable to recode fundamental frequency into a frequency range more closely matched to the skin's capability.

Acoustics