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Biomedical subjects

A Pont

Publications and source records attributed to A Pont.

At least 19 recordsLinked to original sources

Use of a new HemoCue system for measuring haemoglobin at low concentrations.

In many photometers and spectrometers used in routine practice Beer's law (relating absorbance to concentration) fails at low concentrations. A refinement of the HemoCue haemoglobin system (HemoCue AB, Sweden) provides a facility for accurate measurement of haemoglobin at the lower end of the scale. This study confirmed excellent linearity of the photometer response of the HemoCue Plasma/Low Hb photometer to haemoglobin concentration by direct measurement on whole blood samples, thus providing a reliable method when laboratory facilities are limited and where critical patient management may be dictated by the severity of anaemia. Furthermore, measurements on plasma and on samples of urine containing haemoglobin demonstrated the utility of the device for reliable quantification of plasma haemoglobin and haemoglobinuria, thus providing a useful method in investigating moderate or severe intravascular haemolysis. A study of plasma haemoglobin on stored samples of ethylenediamine tetraacetic acid (EDTA) blood showed that a small but measurable degree of lysis occurs after two days at room temperature and after four days when stored at 4 degrees C. This effect on the red cell count will reflect on the reliability of using such blood as a quality control preparation.

Hemoglobins↗

Cuba's national AIDS program. The first decade.

There is a high incidence of infection with the human immunodeficiency virus (HIV) in many Caribbean nations. But by 1993 Cuba, with a population of greater than 10 million people, had fewer than 1,000 seropositive persons and less than 200 cases of the acquired immunodeficiency syndrome (AIDS). To investigate Cuba's approach to the AIDS epidemic, we visited Cuba, reviewed published statistics, spoke with health care officials, interviewed HIV-positive patients, and toured medical facilities. Cuba established an extensive HIV surveillance program in 1983, and more than 15 million HIV antibody tests have been done. The sexual contacts of all infected persons are closely observed. A national education program is evolving. Since 1986, all known HIV-positive patients have been placed in sanitariums, which is the most controversial aspect of Cuba's program. We review available information on AIDS in Cuba and describe that nation's attempt to prevent the spread of disease. We discuss how the political system and Cuba's relative isolation have influenced this approach. Strategies have been developed that may be of limited efficacy and would not be acceptable in most Western nations.

AIDS Serodiagnosis↗

Unusual causes of hypercalcemia.

The unusual causes of hypercalcemia have been reviewed. These disorders are rarely derived as the cause of hypercalcemia from the usual tests that one obtains in working up hypercalcemic patients (such as PTH level, phosphorus, urinary calcium). These diagnoses (particularly drug-related hypercalcemia) can be determined only from a careful history. The vast majority of hypercalcemic patients have disease secondary to cancer, hyperparathyroidism, or disorders of vitamin D metabolism. It should be noted that some hypercalcemic patients may have more than one disease. Therefore, before assuming that a hypercalcemic patient with Paget's disease, thiazide ingestion, immobilization, or so forth has hypercalcemia secondary to the primary disorder, hyperparathyroidism and cancer should also be considered. Similarly, serum calcium levels can normalize in some patients with mild hyperparathyroidism or bony metastases with mobilization and/or cessation of thiazide therapy.

Diagnosis, Differential↗

Long-term experience with high dose ketoconazole therapy in patients with stage D2 prostatic carcinoma.

The antifungal drug ketoconazole has been shown to block testosterone synthesis. High dose ketoconazole therapy was given to 17 patients with previously untreated stage D2 prostatic cancer. Rapid relief of pain occurred in 15 patients with significant pain. Prostatic acid phosphatase levels normalized or decreased in all patients. Bone scan scores were stable or improved. Two patients remain on therapy for more than 30 months. The remainder have ceased treatment owing to subsequent progressive disease (5 patients), side effects (6) or noncompliance. Eleven patients who had relapse after previous endocrine ablative therapy were treated with ketoconazole. Subjective responses were frequent but long-term objective responses were rare. There was a high incidence of side effects, particularly nausea. Ketoconazole may have limited usefulness as initial therapy in patients with endocrine responsive advanced prostatic cancer. The drug can be palliative in some patients who have failed previous therapeutic modalities. Analogues of the drug should prove to have better efficacy and fewer side effects.

Aged↗

Inhibition of cholesterol synthesis by ketoconazole.

To determine if ketoconazole influences cholesterol metabolism in humans, plasma lipid levels were studied in seven men with advanced prostate cancer who were being treated with high-dose ketoconazole. Additionally, the effects of ketoconazole on cholesterol synthesis in cultured normal human fibroblasts were studied. High-dose ketoconazole therapy caused a 27 percent reduction in total serum cholesterol values without affecting serum triglyceride levels. The reduction in serum cholesterol levels was maintained for five months in six of seven patients. The fall in total cholesterol levels was due to a 38 percent reduction in low-density lipoprotein cholesterol levels without associated changes in high-density lipoprotein cholesterol levels. Serum lanosterol levels increased 46 percent during ketoconazole treatment. Studies in cultured normal human fibroblasts showed that ketoconazole inhibited cholesterol synthesis by blocking the conversion of lanosterol to cholesterol. These results establish that ketoconazole is a potent inhibitor of cholesterol production in vivo and in vitro.

Aged↗

Ketoconazole-induced increase in estradiol-testosterone ratio. Probable explanation for gynecomastia.

Ketoconazole, an antifungal drug, causes gynecomastia in some patients. It also inhibits androgen and glucocorticoid synthesis. In four volunteer male subjects, 600-mg doses of ketoconazole depressed serum testosterone concentrations markedly, but serum estradiol to a much lesser degree. The bound and free percentages of both hormones were not significantly altered. The net result was a significant elevation of the estradiol-testosterone ratio, expressed as either total circulating hormone or free hormone. In five male patients receiving long-term high-dose ketoconazole therapy, the testosterone concentrations fell, but the effect on estradiol was variable. In these patients the estradiol-testosterone ratio was persistently increased. Since gynecomastia appears to be the result of an elevated estradiol-testosterone ratio, the selective hormonal effect demonstrated may explain the side effect of gynecomastia after ketoconazole therapy.

Estradiol↗

Ketoconazole therapy for advanced prostate cancer.

Fifteen patients with biopsy-proven prostate cancer were treated with ketoconazole 400 mg every 8 h. Two patients withdrew from therapy, one for personal reasons and one because a paraspinal mass developed. The other thirteen patients completed at least 6 months of therapy. Ketoconazole greatly reduced the need for analgesics; serum prostatic acid phosphatase levels fell to normal, and testosterone levels were reduced. After 6 months thirteen of fourteen evaluable patients were in remission. The side-effects of ketoconazole therapy were limited.

Acid Phosphatase↗

Metastatic islet cell tumor in von Hippel-Lindau disease.

A 56-year-old woman with many unusual manifestations of von Hippel-Lindau syndrome is described. In addition to retinal hemangioblastomas, pheochromocytoma, renal cell carcinoma, and multiple organ cysts, she had a cerebellar astrocytoma, pancreatic exocrine insufficiency, diabetes mellitus, thyrotoxicosis, and a metastatic calcitonin-secreting islet cell carcinoma. This case report documents the first example of a metastatic islet cell tumor in a patient with von Hippel-Lindau disease. The possible relationship between this disorder, the other neurocutaneous syndromes, and the multiple endocrine neoplasia syndromes is discussed.

Adenoma, Islet Cell↗

Acromegaly and Zollinger-Ellison syndrome secondary to an islet cell tumor: characterization and quantification of plasma and tumor human growth hormone-releasing factor.

A young woman with acromegaly and Zollinger-Ellison syndrome associated with a GH-releasing factor (GRF)- and gastrin-secreting metastatic islet cell carcinoma was studied by means of specific antisera which recognize various regions of the GRF molecule. Using specific immunohistochemical techniques, the tumor cells were shown to contain GRF, gastrin, and gastrin-releasing peptide, but not GH. During a 4-h period, plasma GRF levels averaged 5.6 +/- 1.4 ng/ml (+/- SD), while GH levels averaged 148 +/- 71 ng/ml. GH secretion was pulsatile and increased after TRH administration. GRF RIAs may be useful in establishing the diagnosis of acromegaly secondary to the ectopic secretion of GRF.

Acromegaly↗

Conjugated estrogens in the treatment of postmenopausal women with hyperparathyroidism.

Fourteen postmenopausal women with mild hyperparathyroidism were given conjugated estrogens. Serum calcium levels became normal and urinary calcium excretion was reduced for up to 2 years in ten patients taking an average dose of 1.25 mg of estrogen daily. Hypercalcemia returned quickly when therapy was interrupted. Estrogen did not systematically alter serum immunoreactive parathyroid hormone or calcitriol levels or urinary excretion of cyclic adenosine monophosphate. Significant reductions in urinary hydroxyproline and serum alkaline phosphatase activity during estrogen therapy indicate that the major effect of therapy was to decrease bone turnover. Iliac crest biopsy specimens taken before estrogen therapy showed normal trabecular bone volume and excessive osteoid seams. Follow-up biopsy specimens were taken from six patients after 1 year on therapy. Bone volume remained stable, but hyperosteoidosis had improved in only one patient. Without understanding the long-term impact of untreated mild hyperparathyroidism on bone, the benefits of estrogen therapy on bone remain uncertain. However, therapy with conjugated estrogens provides sustained control of serum and urine calcium in most women with hyperparathyroidism and is a reasonable alternative in patients who are not surgical candidates.

Adult↗

High-dose ketoconazole therapy and adrenal and testicular function in humans.

Ketoconazole, an oral antifungal, when given in conventional doses, transiently blocks testosterone synthesis and adrenal response to corticotropin. Higher therapeutic doses (ie, 800 to 1,200 mg/day), even once daily, caused more prolonged blockade. In some men, the serum testosterone concentrations were always subnormal. Bound and free testosterone values were equally diminished. Oligospermia and azospermia after prolonged therapy were noted. Impotence and decreased libido were found. Gynecomastia appeared more common than with lower doses. Depressed response to corticotropin was pronounced. Urine cortisol excretion was depressed. The blockade appeared related to the serum ketoconazole concentration. Instances of normal hormone levels or responsiveness were associated with low ketoconazole concentrations. The hormonal effects were generally unrelated to duration of therapy, although there may have been partial reversal with continued therapy. These effects appeared reversible with discontinuation of therapy. Patients receiving ketoconazole should be considered potentially unable to mount an adrenal stress response and may require testosterone supplementation.

Adrenal Glands↗

Ketoconazole: a novel and rapid treatment for advanced prostatic cancer.

Ketoconazole is an orally administered broad-spectrum antifungal agent that acts through the inhibition of the steroid synthetic pathways. At high doses in humans ketoconazole can lower rapidly serum testosterone and maintain it in the castrate range with frequent administration. This property suggested that ketoconazole might be useful in the treatment of prostatic cancer. We report a case of prostatic cancer in which ketoconazole resulted in rapid and sustained reduction in serum androgens as well as rapid induction of a clinical remission. Ketoconazole may be a valuable agent in the treatment of prostatic cancer.

Aged↗

Hyperthyroxinemia in patients with acute psychiatric disorders.

Thyroid function tests were measured in 645 patients admitted to an acute psychiatric disorders unit. Thirty-three percent had elevated serum thyroxine (T4), and 18 percent had an elevated free T4 index (FTI). Serum triiodothyronine (T3) was low, normal, or minimally elevated in 77 patients, with a high initial free T4 index. Twenty-two patients with an initial elevation of their free T4 index were serially followed (study group). Serum T4, free T4 index, and free T4 fell in every patient: serum T4 from 13.95 +/- 1.93 micrograms/dl (mean +/- standard deviation: SD) to 9.33 +/- 2.4 micrograms/dl (p less than 0.001); free T4 index, from 6.15 +/- 0.83 to 3.79 +/- 1.1 (p less than 0.001); free T4, from 2.43 +/- 0.65 mg/dl to 1.38 +/- 0.35 ng/dl (p less than 0.001). Serum T3 was initially normal or low, and then fell in 17 patients, and rose in five. Serial testing of thyrotropin-releasing hormone (TRH) demonstrated both flat and normal responses in patients with a variety of psychiatric diagnoses and at varying stages of thyroid disease activity.

Acute Disease↗

Thyroid steal syndrome?

A 57-year-old woman with hyperthyroidism had a loud to-and-fro bruit which persisted when the patient was inadvertently rendered hypothyroid with antithyroid drugs. Symptoms suggestive of transient cerebral ischemia prompted an angiographic study which demonstrated both normal cerebral circulation and an enormous increase in the size of thyroid vasculature. The possibility that the enhanced blood supply to the thyroid had compromised cerebral circulation (thyroid steal syndrome) was considered. The angiographic presentation of hyperthyroidism is reviewed, and the lack of specificity of thyroid bruits as a marker of hyperthyroidism in patients on antithyroid drugs is stressed.

Carotid Arteries↗

Ketoconazole blocks adrenal steroid synthesis.

Ketoconazole, a broad-spectrum, antifungal drug that is administered orally, has been shown to inhibit sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats. In healthy humans, the cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose. The inhibition persisted for up to 8 hours and was absent by 16 hours. This finding indicated that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketoconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may prove useful as an agent to block steroid synthesis.

Adrenal Cortex↗