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Biomedical subjects

M A Ferro

Publications and source records attributed to M A Ferro.

At least 19 recordsLinked to original sources

Glutamate dehydrogenase deficiency in Machado-Joseph disease.

We studied the activity of glutamate dehydrogenase (GDH) in leukocytes from 23 patients with dominantly inherited ataxia. All the patients were assessed with a rating scale for ataxias and met the clinical criteria for the diagnosis of Machado-Joseph disease. The mean age of onset of symptoms was 37.8, SD 13.4 years and the duration of the disease was 7.4, SD 4.9. Leukocyte GDH activity was significantly decreased (p < 0.001) when compared to 20 normal controls. These data extend previous reports indicating that a GDH deficiency is present in peripheral tissues from some patients with spinocerebellar degenerations. Furthermore, this study suggests that a genetic deficiency of GDH may underlie some forms of dominant ataxias; this deficiency may be marked in patients with Machado-Joseph disease and is not specific for any type of multiple system atrophy.

Adolescent

Does transurethral thermotherapy induce a long-term alpha blockade? An immunohistochemical study.

10 patients underwent transurethral thermotherapy and after few days were submitted to open prostatectomy. The surgical specimens were compared to those of 2 other patients used as controls. Pathological specimens were evaluated using histological and immunohistochemical stains. Microscopic examination showed a well-preserved urethra and microabscesses, epithelial necrosis and vasculitis in the prostatic tissue at a depth of 0.5-2 cm from the urethral lumen. Immunohistochemical stains showed the damage and disappearance of nervous fibers.

Aged

Tumor markers in prostate cancer.

Prostatic specific antigen (PSA) is a tissue specific marker that is now the most widely used biochemical test for the assessment and follow-up of prostate cancer. The levels of PSA rise with tumor stage, but there is considerable overlap of their distribution between stages. PSA measurement now forms a part of the workup of a suspected carcinoma of the prostate, with a level of more than 4 ng/ml being an indication for further investigation. The sensitivity of PSA makes it an essential test for the postoperative assessment of radical prostatectomy and curative radiation therapy. The rates of change of PSA levels in locally advanced and metastatic disease treated by hormone manipulation can provide prognostic information. Low levels of PSA (less than 10 ng/ml) 6 months after treatment are a sign that the response will be prolonged. However, the sensitivity of PSA often results in a rising level preceding clinical evidence of progression by several months and is not necessarily an indication to change treatment. Alkaline phosphatase and prostatic acid phosphatase provide a less sensitive test for the bone response to skeletal metastases and tumor activity in advanced disease, respectively.

Acid Phosphatase

Use of intravenous stilbestrol diphosphate in patients with prostatic carcinoma refractory to conventional hormonal manipulation.

The patient presenting with severe bone pain after primary hormonal therapy, with vertebral collapse, or with uremia resulting from ureteric obstruction should be considered for intravenous stilbestrol diphosphate therapy. The urologist can expect early marked improvement in the patients' mobility and pain, with a reduction in analgesic requirements, from a single 7-day course of treatment. In addition, the drug is inexpensive and free of the side effects commonly associated with cytotoxic therapy. Accurate monitoring of the response is possible with serum prostate-specific antigen measurements, which also enable further therapy to be planned efficiently.

Diethylstilbestrol

Quantification of prostatic cancer metastatic disease using prostate-specific antigen.

The serum prostate-specific antigen (PSA) of 58 men with benign prostatic hypertrophy (BPH) and 17 men with carcinoma of the prostate (CaP) was correlated with the weight of prostatic tissue resected at transurethral prostatectomy (TURP). A significant correlation was identified between the weight of resected BPH tissue and the serum PSA (p less than or equal to 0.001; r = 0.54). No such correlation was seen in the CaP patients. By arbitrarily dividing the serum PSA by the prostate weight, it was possible to devise an index. This index corrected PSA in relation to prostatic size and unlike PSA in isolation did not differ significantly between normal controls and those with BPH. The index in CaP was significantly greater than that of either controls or BPH (p less than or equal to 0.001). Furthermore the index of metastatic CaP (M1) was significantly higher than that of nonmetastatic disease (MO) (p = 0.05). The higher index found in CaP would seem to be related to the bulk metastatic tumor, either manifest or occult. Comparing the index of CaPs to that found in normal and benign disease (a constant) offers a possible means of estimating the extent of local and metastatic tumor mass.

Antigens, Neoplasm

Parental age and the origin of trisomy 21. A study of 302 families.

Several studies have attempted to define the role of parental age in determining the prevalence of 47, +21 according to the origin of nondisjunction. This report analyzes the original data of 197 informative families from Italy and reviews the available literature (96 families from Denmark and 201 from other countries). Mothers whose gametes showed nondisjunction are treated as cases, and those with normal meiosis as controls within each study. To utilize the data fully, maternal age at birth of a 47, +21 individual is treated as a continuous variable in a nonparametric comparison. The combined evidence indicates that nondisjunction in the female is associated with a significant age difference between cases and controls which is mostly due to errors in the second meiotic division. It may be inferred that in the general population, aging enhances nondisjunction at both first and second division in the female, while aging in the male is presumably associated mostly (or only) with first division errors. Implications and alternative models are discussed.

Abortion, Spontaneous

High-dose intravenous estrogen therapy in advanced prostatic carcinoma. Use of serum prostate-specific antigen to monitor response.

High-dose intravenous estrogen therapy was shown to be effective in relieving bone pain due to metastatic disease in 22 of 29 (75.9%) men with advanced hormone-resistant prostate cancer. This clinical response was accompanied by significant falls in serum prostate-specific antigen (PSA) levels in 13 (44.8%) patients. It is suggested that this clinical benefit is due to a direct inhibitory effect of estrogen on prostate cancer cells.

Antigens, Neoplasm

Testing the chemosensitivity of renal carcinoma in vitro.

Tumour cells from 23 renal carcinomas were exposed in vitro to increasing concentrations of medroxyprogesterone acetate (MPA) or one of several cytotoxic agents. Thereafter the uptake of 75Selenomethionine (75SeM) was compared to that of tumour cells not exposed to the drug. Using drug concentrations similar to those seen following in vivo administration in patients, MPA produced greater than or equal to 50% inhibition of 75SeM uptake in 5 of 23 cases. The comparable proportion for doxorubicin was 4 of 5 and for mitozantrone 7 of 12. Methotrexate and Vinblastine were much less effective. In all cases where greater than or equal to 50% inhibition was obtained with doxorubicin and mitozantrone the carcinoma had spread beyond the kidney. Thus drug sensitivity may be associated with a high mitotic rate.

Aged

Effect of stilboestrol and testosterone on the incorporation of 75selenomethionine by prostatic carcinoma cells.

Controversy still exists as to whether oestrogens exert a direct effect on the prostatic cell. Incorporation of 75Selenomethionine (SeM) was used as a measure of protein synthesis by prostatic carcinoma cells in vitro to investigate the action of hormones on prostatic carcinoma cells in tissue culture. Stilboestrol (DES) and stilboestrol diphosphate (Honvan) inhibited protein synthesis in a proportion of patients, while testosterone was stimulatory. A similar effect was noted in cells from patients with benign hyperplasia (BPH). This work confirms that oestrogens have a direct inhibitory effect on prostatic cells at high concentrations which can be attained in patients given intravenous stilboestrol diphosphate.

Cyproterone

Tumour markers in prostatic carcinoma. A comparison of prostate-specific antigen with acid phosphatase.

A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (MO) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with MO disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the MO group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy.

Acid Phosphatase

Intranuclear androgen receptor deployment and protooncogene expression in human diseased prostate.

Androgen receptors were quantified in nuclei from human prostate tissue and in nuclear fractions derived by exhaustive digestion with micrococcal nuclease. In nuclei from benign hypertrophic prostate (BPH), the population of androgen receptors solubilized during nucleolysis predominated whereas in carcinoma nuclei the nuclease-resistant population was in excess. This phenomenon was restricted to intranuclear deployment and could not be attributed to recompartmentalization within the cell. Receptor content could not be correlated to the expression of the cellular protooncogenes myc, H-ras, K-ras or sis, in either BPH or carcinoma. However, in both BPH and carcinoma, significant correlation was observed between nuclear androgen receptor content and expression of c-fos. Expression of c-fos was not elevated in carcinoma compared to BPH, whereas expression of c-myc was elevated in carcinoma specimens of all grades of glandular differentiation, and expression of H-ras became increasingly elevated as differentiation was lost.

Cell Nucleus

The use of CA-50 radioimmunoassay test in diagnosis of urologic malignancy. Tie for second place Jobst award.

Circulating levels of the oncofetal antigen, CA-50, have been used to differentiate benign and malignant disease of the prostate, bladder, and kidney, taking 17 units/ml as the upper limit of normal. All 60 normal subjects and 59 of 61 (97%) patients with benign prostatic hypertrophy had levels below 17 units/ml. The test was positive in 29 of 68 (43%) patients with prostatic carcinoma, including 24 of 34 (75%) with metastases, but only five of 34 (15%) patients without metastases (P less than 0.01). Positivity also correlated with histologic grade: 0 per cent with well-differentiated tumors (n = 8), 33 per cent with moderately differentiated (n = 11), and 66 per cent with poorly differentiated tumors (n = 27). All 14 patients with benign bladder disease had negative values, whereas 13 of 21 (62%) patients with bladder carcinoma had positive. Noninvasive tumors were less likely to give a positive value than invasive tumors (42 vs 89%; P less than 0.05). One of 11 (9%) patients with benign renal conditions was positive as opposed to seven of 15 (47%) patients with renal carcinoma. The overall sensitivity of the CA-50 test for urologic malignancy was 47 per cent and specificity was 97 per cent; moreover, serum levels correlated with stage and grade of disease.

Antigens, Neoplasm

Double J stents. A review of 100 patients.

Double J stents have been advocated for drainage or splintage of the ureter. One hundred and thirty-eight attempts at stent insertion were made in 100 patients. In 78% of attempts the stent was satisfactorily placed. Their use in retroperitoneal fibrosis, ureteric trauma and acute hydronephrosis of pregnancy has been encouraging. Poor results have been obtained in patients with malignant obstruction or tuberculous stricture.

Adolescent

Cause of death and accuracy of certification of colorectal cancer.

Of 160 patients who died of colorectal cancer in the Exeter district in 1979 and 1980, 15 had not been correctly certified as such and of these 10 had died postoperatively. A further 2 had not died of colorectal cancer and in 9 the diagnosis was unsubstantiated. When those not proven to have cancer are considered, colorectal cancer as a cause of death was underestimated by about 5%, which is much more accurate than for other diseases. A total of 35 patients (21.8%) had no operative treatment due to advanced disease, old age or rapid death. The mean inpatient stay was 32.3 days, and 184 operations were performed on 125 patients. Only 20 patients were admitted to the district hospital for terminal care.

Adult