Biomedical subjects
R M Chapman
Publications and source records attributed to R M Chapman.
Gonadal injury resulting from chemotherapy.
Radiation, alkylating agents and the vinca alkaloids produce variable degrees of gonadal dysfunction in humans; additional drugs have been linked to gonadal damage in males only. Age at time of exposure and total dose of drug administered are associated with the degree of gonadal injury. Irreversible sterility develops at lower doses in men than in women. The infertile men usually retain sexual function, whereas the infertile women experience premature menopause and sexual dysfunction. Subfertility with normal sexual function is the sequela of lesser degrees of gonadal injury in men and women. For a given drug dose, children apparently sustain less gonadal damage than their adult counterparts. Rigorous reporting of basic essential data will enhance our understanding of drug-induced gonadal damage; incomplete reports only cloud the issue.
Testicular dysfunction in untreated Hodgkin's disease.
Gonadal function was examined in 19 young men with Hodgkin's disease before therapy and compared with that of 11 men with other malignancies, 13 men with primary testicular failure, and 19 normal men of similar age. Total (p less than 0.01) and free (p less than 0.05) testosterone levels were decreased in Hodgkin's disease. In those with advanced (stage III + IV) and symptomatic (B), Hodgkin's disease serum testosterone levels were indistinguishable from those in primary testicular failure, yet serum levels of luteinizing hormone were normal. Moreover, the acute response of serum testosterone to exogenous human chorionic gonadotropin (HCG) was significantly greater in Hodgkin's disease than in primary testicular failure (p less than 0.03). These data and the finding that basal serum follicle-stimulating hormone levels are significantly lower than normal in Hodgkin's disease (p less than 0.05) suggest that the cause of pretreatment hypogonadism in Hodgkin's disease is not simple primary testicular failure. Total sperm count was decreased in 40 percent of men with Hodgkin's disease but in none of the men with other malignancies (p less than 0.05), suggesting specific seminiferous tubular dysfunction in Hodgkin's disease. However, motility was abnormal in 69 percent of men with Hodgkin's disease and 60 percent of those with other malignancies, suggesting that this is a nonspecific effect of cancer. Serum prolactin levels were significantly higher than normal in Hodgkin's disease (p less than 0.05) but not in other malignancies. Our findings suggests that the cause of testicular dysfunction that is present before treatment of Hodgkin's disease is complex, perhaps involving both pituitary and gonadal abnormalities.
Hodgkin's disease and the pregnant patient.
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Effect of cytotoxic therapy on sexuality and gonadal function.
Many chemotherapeutic agents have been shown to cause variable degrees of gonadal dysfunction in both sexes and in all age groups. The severity of the dysfunction depends on the total drug dose and the age at time of therapy. In general, cytotoxic agents produce gonadal dysfunction in men while they produce premature gonadal failure in women. Men develop azoospermia and compensated Leydig-cell function; women sustain ovarian damage causing impaired fertility in the short term and early ovarian failure later. This dysfunction is associated with sexual and emotional difficulties in many patients. In order to discover these problems the physician must sympathetically ask patients and families about their sexual and emotional health. Endocrine and psychologic evaluation help the physician identify the problem. Appropriate counseling and hormone replacement therapy may ameliorate most symptoms and help the patient emotionally adjust to illness and infertility. Prevention of gonadal damage during cytotoxic therapy may be possible in the future. For those young people who retain fertility after cytotoxic therapy, prognosis should be taken into account when counseling about parenthood is given. There is no evidence of genetic abnormalities in the offspring of people previously treated with chemotherapy or irradiation.
Male gonadal dysfunction in Hodgkin's disease. A prospective study.
Forty-seven men (median age, 31.5 years) were studied prospectively to assess the effect of Hodgkin's disease and subsequent chemotherapy on gonadal function. Before therapy, 16 (43%) of 37 men were functionally subfertile, as assessed by impotence (four of 37) and "inadequate" sperm counts (12 of 37). Histological abnormalities were noted in eight of nine pretreatment testicular biopsy specimens. Additionally, changes were noted in blood hormone levels and libido. After completion of only two cycles of chemotherapy, 14 of 14 men became persistently azoospermic, with blood follicle-stimulating hormone levels four to five times normal. Posttreatment testicular biopsy specimens confirmed germ cell aplasia. During therapy 17 (81%) of 21 men had mild or no libido; irritability in 16 (84%) of 19 and violence in four (18%) of 22 caused additional family distress. While it is clear that cytotoxic therapy induces infertility, these data further indicate that a proportion of men have gonadal dysfunction prior to treatment.
Principal components analysis of sources of variability in retinal ganglion cell responses.
An approach to the functional organization of retinal ganglion cell processing in terms of correlation matrices (Levine and Shefner, 1975; 1977a, b; Shefner and Levine, 1979) is extended by applying Principal Components Analysis. This analysis reduces each correlation matrix to a few components which are implicit in the data. The component loadings describe properties of the system in terms of loadings (correlations) of time bins on the underlying components. Each component is identified by the experimental conditions associated with the highest loadings. Mixed conditions are quantitatively interpreted as weighted contributions from the various identified components. This has led to new interpretations of existing data. Several properties of ganglion cell inputs are analyzed in this manner, including ON and OFF processes, center and surround mechanisms, rod and cone inputs, and spatially distinct areas within the receptive field center. Although the details vary, generally one of the components is highly associated with ON processes and the other with OFF and/or MAINTAINED processes. several advantages may be realized through the use of Principal Components Analysis: (1) all of the data contribute to the analysis, (2) the number and relative importance of contributing processes may be assessed, (3) the relative contribution of underlying processes to mixed responses may be assessed, and (4) the most parsimonious representation of the data is obtained.
Memory processes and evoked potentials.
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Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease.
It has been reported by us and by others that after chemotherapy for Hodgkin's disease the ovary contains fewer than 5 primordial and primary follicles per 5 x 5 mm biopsy section. In young women this is associated with premature menopause. We report here that before treatment the tissue contains 18--55 such follicles per biopsy section. When women took combination oral contraceptives throughout the course of MVPP therapy, the posttreatment ovarian biopsy tissue had more than 20 follicles per histologic section. Normal menses were established in the five women who discontinued oral contraceptives at the end of MVPP therapy, and one of them is now pregnant.
Behavioral and neural analyses of connotative meaning: word classes and rating scales.
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Cytotoxic-induced ovarian failure in women with Hodgkin's disease. I. Hormone function.
Forty-one women with advanced Hodgkin's disease were studied to determine the effect of combination chemotherapy on fertility and ovarian function. Histories and pretreatment ovarian biopsy specimens indicated normal fertility before therapy, thus implying no adverse effect of Hodgkin's diseases on female gonadal function. Ovarian activity was assessed after therapy by menstrual history, serial basal body temperatures, and hormonal levels. Each case was assigned to one of three categories: primary ovarian failure (failed ovary), irregular ovarian activity (failing ovary), and normal cyclic ovarian activity (functioning ovary). After therapy, 20 of 41 patients (49%) were categorized as failed, 14 (34%) as failing, and only 7 (17%) as functioning. In 16 months of further observation, progressive loss of ovarian function occurred that was clearly age related but not statistically dose related. Induction of premature, irreversible menopause presents a need for effective hormonal replacement and patient counseling.
Cytotoxic-induced ovarian failure in Hodgkin's disease. II. Effects on sexual function.
Chemotheraphy for Hodgkin's disease produces ovarian failure in young women. The consequences of this are emotional distress, sexual dysfunction, and the disruption of families and friendships. These previously unappreciated side effects of cytotoxic therapy had developed in 25 of 41 patients, among whom we conducted a retrospective study.
Cyclical combination chemotherapy and gonadal function. Retrospective study in males.
The effect of cyclical chemotherapy on fertility and gonadal function was investigated in seventy-four male patients who had been treated for advanced Hodgkin's disease. All patients were azoospermic after therapy, and, with a median follow-up period of 27 months (range 1--62 months), only four patients have regained spermatogenesis. Testicular biopsy showed an absence of germinal epithelium without other gross architectural changes. Despite this high degree of infertility, 60% of patients were practising contraception. A decline in libido and sexual performance with frequent long periods of sexual inactivity was noted by most men during therapy. Although some recovery was apparent once therapy was stopped, this was incomplete in approximately half of the patients. Follicle-stimulating-hormone levels were consistently raised after therapy at all periods of study. Median luteinising-hormone levels were at, or just above, the upper limit of normal, and median testosterone levels were normal. Increased prolactin levels were noted in 42% of patients, of whom about a half had an identifiable cause for hyperprolactinaemia. Return of spermatogenesis could not be predicted by serial hormone assessment. Because of the guaranteed infertility and the low frequency and unpredictability of recovery of spermatogenesis, sperm storage should be available for male patients undergoing cytotoxic therapy, since most of these patients may enjoy prolonged survival. Hormone-replacement therapy will usually be unnecessary. However, the probability of major changes in libido and sexual performance should be discussed with patients so that additional stress can be avoided. Contraceptive advice should be available to those who require it.
Short-term memory: the "storage" component of human brain responses predicts recall.
An evoked potential component with a poststimulus peak at about 250 milliseconds is related to the storage of information in short-term memory. This storage component was found in an investigation of brain potentials in relation to a number and letter comparison task. In replications of this experiment at three different light intensities spaced 1.0 log unit apart, the component had essentially the same waveform and pattern of scores. The memory storage interpretation was confirmed in a behavioral experiment that probed short-term memory. Recall was predicted by the magnitude of the storage component.
Brain responses related to semantic meaning.
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Immune neutropenia.
A patient with hyperthyroidism and severe neutropenia had a clinical course and family history that suggested an immune cause. Neutrophil-binding IgG was demonstrated in serum using the Fab-anti Fab assay. The antineutrophil factor bound specifically to either homologous or autologous neutrophils and could be adsorbed by the target neutrophils. The quantity of IgG required to saturate the neutrophil-binding sites (175 000 molecules per neutrophil) and the serum concentration (1.3 mug/ml) were determined. It was estimated that at the time that blood and marrow neutrophils were markedly reduced, serum contained sufficient neutrophil-binding IgG to saturate the binding sites of 1.2 times the total blood neutrophil pool.
Letter: Elective dental extraction in leukemia.
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