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Biomedical subjects

C Mahler

Publications and source records attributed to C Mahler.

At least 37 records · Page 2Linked to original sources
PubMed1995

Guanidino compounds in serum and urine of cirrhotic patients.

To investigate the metabolic relationship between urea and guanidinosuccinic acid (GSA), we determined the levels of the guanidino compounds, including GSA, and urea in serum and urine of cirrhotic patients. Linear correlation studies between serum urea and GSA levels were performed. Good positive linear correlation coefficients were found in the Child-Turcotte C subgroup (r = .847, P < .001) and in the total subgroup including B and C patients (r = .848; P < .0001). Serum guanidinoacetic acid levels were significantly increased in the Child-Turcotte C subgroup (P < .0001 for men and P < .001 for women). In contrast, GSA levels were significantly (P < .0001) decreased in the three studied subgroups. Similar results were found for urinary GSA excretion levels. Within each subgroup, serum and urinary GSA levels were significantly lower in patients with alcohol-induced cirrhosis than in nonalcoholic cirrhotic patients. Similar results were obtained for urea. The findings in cirrhotic patients clearly demonstrate a metabolic relationship between urea and GSA. They also show that urea and GSA biosynthesis is significantly lower in cirrhotic patients with an alcoholic origin than in cirrhotic patients with a nonalcoholic origin.

Adult↗
PubMed1995

Guanidino compound levels in brain regions of non-dialyzed uremic patients.

Guanidino compounds have been suggested to contribute to the complex neurological complications associated with uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of alpha-keto-delta-guanidinovaleric acid, alpha-N-acetylarginine and beta-guanidinopropionic acid remained below detection limits. Creatine, guanidinoacetic acid, argininic acid, gamma-guanidinobutyric acid, arginine and homoarginine were not increased in uremic patients. Argininic acid and homoarginine were detectable in some brain regions only. Creatine concentrations varied from 2500 +/- 2100 nmol/g tissue in hypophysis to 10500 +/- 1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for gamma-guanidinobutyric acid with the lowest concentration in the caudate nucleus (0.6 +/- 0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3 +/- 2.8 nmol/g tissue). The guanidinosuccinic acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of guanidinosuccinic acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of guanidinosuccinic acid increased with increasing degree of renal failure with levels up to 65 nmol/g tissue in the hypophysis. Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum urea levels. Guanidine and methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of guanidinosuccinic acid and creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable uremic toxins contributing to the neurological complications in uremia.

Aged↗
PubMed1995

Pituitary metastasis mimicking a pituitary adenoma. A description of two cases.

The cases of two elderly women treated for temporal hemianopsia due to a large pituitary mass with suprasellar extension are presented. In both cases, the clinical picture, without diabetes insipidus and cranial nerve paralysis, as well the neuroimaging and endocrinological investigation showing hypopituitarism, were suggestive of a non-secreting pituitary adenoma. In the first patient malignant tissue was unexpectedly encountered during transsphenoidal surgery. Anatomopathological investigation confirmed the presence of a metastasis of a breast carcinoma for which she had been treated 17 years earlier. In the second patient, a preoperative chest X-ray before transsphenoidal surgery revealed an asymptomatic bronchial tumour. Subsequently a squamous cell carcinoma with a metastasis in the pituitary was confirmed. These two cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary adenoma. Even in the absence of suggestive symptoms such as diabetes insipidus and/or cranial nerve paralysis the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.

Adenocarcinoma↗
PubMed1994

Phase I trial of high-dose fosfestrol in hormone-refractory adenocarcinoma of the prostate.

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

Acid Phosphatase↗
PubMed1994

Glucose metabolism in a patient with hyperthyroidism and an insulinoma.

A 67-year-old woman was admitted in hypoglycemic coma, with fever and signs of hyperthyroidism. Diagnosis was made of both an insulinoma and subacute ("De Quervain") thyroiditis. This rare coincidence of two diseases with opposite effects on serum glucose levels, offered a rare opportunity to study glucose metabolism in this peculiar physiopathological situation. During the day abnormally high postprandial blood glucose levels were seen, pointing to the glucose intolerance usually seen in the hyperthyroid state. During the night and after prolonged fasting, however, hypoglycemia predominated, consistent with the clinical picture typical of an insulinoma. After resection of the insulinoma and spontaneous healing of hyperthyroidism, glucose metabolism reverted to normal. As shown in this case, concurrent hyperthyroidism and an insulinoma may lead to consecutive episodes of glucose intolerance and hypoglycemia within the same 24-hour period.

Aged↗
PubMed1994

Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer.

OBJECTIVE: Casodex (Zeneca) is a new potent, long-acting non-steroidal anti-androgen, which produces androgen deprivation by blocking the androgen receptor. We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer. DESIGN: As part of a large, multicentre study comparing the therapeutic effects of surgical castration with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a subgroup of 23 patients on Casodex were studied in detail for changes in endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol, prolactin, sex hormone binding globulin and free testosterone were measured at the start of therapy and after 1, 4, 8, 12 and 24 weeks. Effects on libido, sexual activity and the appearance of hot flushes, breast pain and gynaecomastia were recorded. RESULTS: Administration of Casodex resulted in a rise in LH levels in all patients with a mean increase after 24 weeks of 102% (P < 0.001). Mean FSH levels showed a limited increase (7%) after 24 weeks, which was significant only after 1 week (P < 0.001). As a result of the high LH levels, total testosterone levels increased after 24 weeks by 66% (P < 0.001), free testosterone by 57% (P < 0.001) and dihydrotestosterone by 24% (P = 0.0112). Parallel to testosterone, oestradiol levels rose by a mean of 66% (P < 0.001). Mean sex hormone binding globulin and prolactin levels rose by respectively 8% (P = NS) and 65% (P < 0.01). Despite an increase in testosterone levels, excellent androgen blockade was obtained, as shown by a decrease in prostate specific antigen levels in 22/23 patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No patient complained of hot flushes. However, mild gynaecomastia and/or breast tenderness were seen in 48 and 30% of cases respectively. CONCLUSION: Casodex 150 mg/day monotherapy resembles surgical castration in achieving androgen deprivation, despite an increase in LH and testosterone levels. In contrast to castration, libido and sexual activity are usually maintained and hot flushes are rare. However, mild gynaecomastia and/or breast tenderness were noted in 48 and 30% of patients.

Aged↗
PubMed1994

Octreotide in advanced prostatic cancer relapsing under hormonal treatment.

Since somatostatin analogues have been shown to possess inhibitory activity on prostatic cancer cells in animal models, we studied the clinical effects of the long-acting somatostatin analogue octreotide in the treatment of advanced prostatic cancer. Five patients with metastatic prostatic cancer in relapse under hormonal treatment and with rapidly increasing levels of prostate specific antigen (PSA) received a subcutaneous infusion of octreotide in a dose of 400 to 1,000 micrograms/day for a period of 2 to 6 months. Patients were followed clinically and by monthly measurement of PSA levels. During treatment 3/5 patients showed a temporary halt in rising PSA levels, while another patient had a small decrease. This inhibitory effect however was lost after 1 to 3 months of therapy in 3 patients. The remaining patient died after 4 months before an escape of PSA levels was seen. Side effects consisted of mild diarrhoea in three patients. From this very preliminary data, it appears that octreotide in a dose of 400 to 1,000 micrograms/day may give only a moderate and temporary inhibition of tumor growth in patients with advanced prostatic cancer. Because of the limited effects the study was interrupted prematurely. Since higher doses, other somatostatin-analogues or the combination of LHRH analogues may give better results, further studies are needed to determine the potential therapeutic role of somatostatin-analogues in this group of patients.

Aged↗
PubMed1993

Is disease flare a problem?

When given for the first time to previously untreated patients with advanced prostate cancer, luteinizing hormone-releasing hormone (LHRH) analogs induce a transient rise in pituitary luteinizing hormone levels. As a consequence of this increase of LH, there is, within the first 2 to 3 days, a surge of testosterone, which can cause an exacerbation of the symptoms. First reports concerning this flare have been anecdotal, and in most studies, flare is reported with an incidence of 4-33%. This variance is due mainly to the confusion about the definition of the flare phenomenon. No distinctions have been made between clinical flare, with its manifestations of subjective or objective aggravation of cancer related symptoms, and the biochemical flare that results of the LHRH analog administration and that occurs in a majority of patients and is characterized by increases in testosterone, prostatic acid phosphatase, and prostate specific antigen. As the possible interference of the flare phenomenon on the ultimate aftermath of the patient's response to therapy is not yet known, it seems mandatory that flare prevention should be carried out whenever LHRH analogs are prescribed in monotherapy.

Antineoplastic Agents↗
PubMed1993

Orchidectomy versus goserelin plus flutamide in patients with metastatic prostate cancer (EORTC 30853). European Organization for Research and Treatment of Cancer--Genitourinary Group.

A total of 327 patients with metastatic prostate cancer were randomized to receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial aimed to evaluate subjective and objective time to progression, survival, and incidence and duration of response. Strict quality control and evaluation by independent ad hoc committees were organized. Progression was assessed for each of 13 parameters. The time to subjective and objective progression was in favor of the combination treatment, with statistical significances of P = 0.009 and P = 0.008, respectively. This delay in objective progression resulted in increased survival in favor of the combination treatment for death by cancer (P = 0.02) or overall survival (P = 0.05). Survival differences were more marked in the patients with better prognostic factors. The clinical significance of these differences for the individual patient requires detailed assessment.

Adult↗
PubMed1993

[Angio-immunoblastic lymphadenopathy].

Angioimmunoblastic lymphadenopathy is a rare lymphoproliferative disease with a poor prognosis. We saw a 24-year-old female patient with a fulminant evolution of an angioimmunoblastic lymphadenopathy, possibly a recurrence after a 10 years remission.

Adult↗
PubMed1993

Ketoconazole and liarozole in the treatment of advanced prostatic cancer.

BACKGROUND: Ketoconazole, an imidazole derivative, is an orally active antifungal agent. In high doses (400 mg three times a day), it inhibits the biosynthesis of testicular and adrenal androgens and may therefore be useful for the treatment of hormone dependent diseases such as advanced prostatic cancer. Similarly, a new imidazole derivative, liarozole, was recently found to interfere with testicular and adrenal steroid biosynthesis in animals and healthy volunteers. METHODS: The therapeutic and endocrine effects of ketoconazole and liarozole in patients with disseminated prostatic cancer are discussed, including data from the literature and personal experience. RESULTS: Using high-dose ketoconazole, medical castration with the expected clinical response was achieved easily in previously untreated patients in all clinical series (personal data include seven patients). In patients with prostatic cancer who had relapses after castration, few objective remissions were achieved. By contrast, long-lasting subjective remissions, especially pain relief, were seen in more than half of the patients (personal data include 20 patients). Gastrointestinal intolerance, which was the main side effect, severely limits the routine use of the drug. Recently, the authors studied the effect of liarozole on adrenal steroid production in castrated patients whose disease was progressive after first-line treatment. Unlike ketoconazole therapy, adrenal androgen and cortisol levels were not modified. A Phase I-II trial was then done in 44 patients with metastatic prostatic cancer in clinical relapse. In patients with measurable disease, objective responses, including tumoral volume reduction, occurred in approximatively 30%. A prostate specific antigen reduction of 50% or more was noted in approximatively 50% of patients. Pain relief occurred in most patients. Mucocutaneous side effects were observed in most patients--dryness of the skin and onychomalacia. Raised tissue retinoic acid levels suggested a possible pathway by which this drug might exert its cytotoxic effects. CONCLUSIONS: Ketoconazole in high doses is effective in first-line and second-line therapy for advanced prostatic cancer, but gastrointestinal side effects limit its routine use. Liarozole is a new imidazole that is also effective in second-line therapy for prostatic cancer and has fewer side effects. Unlike ketoconazole, its effect is not mediated by inhibition of steroid biosynthesis.

Aged↗
PubMed1993

Wolfram syndrome: a clinical study of two cases.

Two unrelated patients with two different images of Wolfram (or 'DIDMOAD') syndrome are presented: a 19-year old woman suffering from all the important features of this syndrome, and a 38-year old man showing two major characteristics but several minor abnormalities. This syndrome should be considered in young diabetic patients with unexplained visual loss or with polyuria and polydipsia in the presence of adequate blood sugar control. An early diagnosis is important to prevent unnecessary diagnostic investigations.

Adult↗
PubMed1993

The association of meningioma and pituitary adenoma: report of seven cases and review of the literature.

Seven patients with the co-occurrence of meningioma and pituitary adenoma are reported. Diagnosis was based on histological examination and if not available on MR imaging. Extensive review of the literature reveals only 18 other cases with this association if meningiomas appearing after radiation therapy for pituitary tumors are excluded. As in isolated meningiomas, the female-to-male ratio is high. A preponderance of perisellar meningiomas is apparent. Another distinct characteristic of this combination is not revealed, since no specific typing of the meningioma and no specific endocrine syndrome is uncovered. Two patients presented with multiple meningiomas, of which one showed two histologically different tumor types. The presence of other tumors in association with pituitary adenomas and meningiomas in our series is striking and could suggest a genetic dysregulation leading to the development of these tumors.

Adenoma↗
PubMed1993

Hyperfunctioning unilateral adrenal macronodule in three patients with Cushing's disease: hormonal and imaging characterization.

We aimed to investigate the dynamics of adrenocorticotropin (ACTH) and cortisol secretion in pituitary-dependent Cushing's syndrome with bilateral macronodular adrenal hyperplasia presenting as a single adrenal macronodule, and to determine the imaging characteristics of this syndrome. Three female patients were studied. Plasma ACTH and serum cortisol secretion were studied by determining their rhythmicity and pulsatility and their responses to the administration of ovine corticotropin-releasing factor, thyrotropin-releasing hormone, metyrapone, tetracosactrin, insulin and dexamethasone. Techniques used to localize the anatomical lesion were bilateral simultaneous inferior petrosal sinus sampling, magnetic resonance examination of the pituitary, computed tomography (CT) scanning and [75Se]cholesterol scintigraphy of the adrenal glands. Plasma ACTH and serum cortisol levels were measured using a commercial radioimmunoassay and an immunoradiometric assay. The ACTH and cortisol pulse number and amplitude were calculated using established computer software. In all three patients ACTH and cortisol secretory dynamics fulfilled the requirements for diagnosis of pituitary-dependent Cushing's syndrome. A close relationship between ACTH and cortisol pulses also favored a pituitary dependency. Study of the amplitude of cortisol pulses classified two patients in the group of hypopulsatile Cushing's disease. Adrenal CT scanning demonstrated the presence of a large single nodule. [75Se]Cholesterol scintigraphy showed bilateral radionuclide uptake, although mostly localized over the adrenal nodule. All patients underwent successful trans-sphenoidal hypophysectomy. Over a period of 1 year, a slow shrinkage of the adrenal nodule was observed in two patients, while no change in volume was observed in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1993

Clinical and endocrine effects of laser vaporization in patients with polycystic ovarian disease.

Responses to laparoscopic ovarian laser vaporization were studied in 17 anovulatory patients with clomiphene citrate-resistant polycystic ovarian disease (PCOD). Ovulatory cycles were obtained in 14 patients (82%). A total of 11 patients (65%) conceived within 1-8 months. Measurements of basal serum hormone levels before and after the procedure in 12 patients revealed a significant decline in testosterone, dihydrotestosterone and androstenedione. In addition, luteinizing hormone (LH) levels decreased, but not significantly. On the other hand estradiol levels slightly increased and a surge in luteal progesterone levels was noted. Serum levels of sex hormone binding globulin, prolactin, dehydroepiandrosterone (DHEA) sulfate, 17-OH-progesterone and follicle stimulating hormone (FSH) remained unchanged. These results suggest that ovarian laser vaporization is very useful when clomiphene citrate fails in PCOD, and has no risk of ovarian hyperstimulation syndrome or multiple gestation, which is frequently observed in ovulation induction with drugs. Most of the endocrine abnormalities associated with PCOD are corrected by the laser procedure.

Adult↗
PubMed1992

Management of relapsing disease in prostate cancer.

Almost all patients with prostatic cancer will eventually escape the control of the first-line endocrine therapy and relapse. This escape is attributed to selecting and/or cloning preexisting or de novo appearing hormone-independent or resistant cell lines and occurs in most patients after a median time of 12 to 18 months. Currently, there are no generally accepted rules for second-line management, either endocrine or by other means. It seems reasonable to consider length of survival as the only objective response criterion and not to rely on other response criteria. Available second-line therapeutic modalities in relapsed prostatic cancer are alternative endocrine manipulations, chemotherapy, combined endocrine and cytotoxic therapy, new drugs, radiation therapy, and general antitumoral and supportive care. Second-line therapy in relapsed disease makes sense if life can be prolonged while relieving symptoms and maintaining or improving the quality of survival. The capacity to prolong survival is limited. As a result, second-line therapy should aim more at improving the quality rather than the length of survival while considering the specific expectations and wishes of the patient.

Aminoglutethimide↗