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Biomedical subjects

P G Cohen

Publications and source records attributed to P G Cohen.

At least 19 recordsLinked to original sources
PubMed2001

Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection.

In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time.

Adipose Tissue↗
PubMed1999

The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt--a major factor in the genesis of morbid obesity.

Massive obesity in males is associated with decreased total and free testosterone levels as well as elevated estradiol levels. The decrease in testosterone occurs without the compensatory increases in gonadotropin and a progressive hypogonadotropic hypogonadal cycle develops. During the hypogonadal state, there is a preferential deposition of abdominal adipose tissue. With the increasing fatty-tissue accumulation, there is an increase of aromatase activity that is associated with a greater conversion of testosterone to estradiol (testosterone-estradiol shunt). This results in further depression of testosterone concentrations and leads to the increased preferential deposition of abdominal fat that, in turn, leads to a progressive hypogonadal state. Testalactone, an aromatase inhibitor, interrupts this cycle and repairs the depressed testosterone concentrations and decreases estradiol levels. This increases the testosterone levels and reverses the preferential deposition of abdominal fat, while increasing muscle protein and fat-free mass.

Aromatase↗
PubMed1999

Effects of fenfluramine on ejaculatory function, luteinizing hormone and testosterone levels in men with hypogonadotropic hypogonadism and premature ejaculation.

Serotonergic neurotransmission is associated with the regulation of aggressive behaviour, anxiety and affect. Serotonin (5-HT) reuptake inhibitors (SRIs) have been extensively utilized in the treatment of affective disorders; however, their use often results in ejaculatory inhibition. Serotonin appears to modulate male sexual function through its influence on luteinizing hormone (LH) secretion but only when the steady state is altered. Premature ejaculation (PME) is defined as persistent or recurrent ejaculation with minimal sexual stimulation (DMS-III-R). While the aetiology of PME remains unclear, an underlying anxiety disorder may be a major contributing factor. It has been recently suggested that patients with premature ejaculation (PME) have an associated hypogonadotropic hypogonadism. This study was undertaken to determine whether the administration of the SRI fenfluramine would result in changes in PME (inhibitory effect) and release of LH which could be indirectly measured through an increase in the production of testosterone (disinhibitory effect). Six patients with PME and hypogonadotropic hypogonadism were treated with fenfluramine (20 mg). Both inhibition of PME (based on graded couple's responses) and increased plasma LH and testosterone levels occurred following treatment. These observations strongly suggest a role for serotonergic modulation in the occurrence of PME.

Adult↗
PubMed1998

The role of estradiol in the maintenance of secondary hypogonadism in males in erectile dysfunction.

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.

Aging↗
PubMed1997

The association of premature ejaculation and hypogonadotropic hypogonadism.

Twelve patients with premature ejaculation were evaluated and the hypothalamic anterior pituitary-testicular axis studied to determine whether hormonal abnormalities occurred. Plasma testosterone and free testosterone levels were found to be diminished, as were LH and FSH levels. Four of 12 patients with premature ejaculation had increased prolactin levels. The findings of decreased testosterone without the expected increases in gonadotropin in male patients between 24 and 25 years old points to hypothalamic pituitary dysfunction as a factor in the genesis of the hypogonadal state. Further studies are needed to document the association of premature ejaculation and hypogonadotropic hypogonadism, along with other possible clinical correlations that remain to be described.

Adult↗
PubMed1986

The pathogenesis of vascular headaches in patients with hypertension; the role of the ammonia-potassium axis.

Headaches may occur in as many as 25% of hypertensive patients and generally bears little relationship to level of diastolic blood pressure. Previous observations, in normotensive patients, suggested that abnormalities in both potassium and ammonia metabolism might be related to the pathogenesis of these headaches. The present study was undertaken to see whether these factors also occurred in hypertensive patients with headaches. The present observations were made in thirteen hypertensive patients with vascular headaches. The major findings include potassium levels of 3.45 +/- 0.25 mEq/L; CO2, 29.85 +/- 1.21 mEq/L; blood ammonia, 41 +/- 8.40 U mol/L and an alkaline pH of the urine. The blood ammonia levels, when factored by the BUN, yielded elevated ammonia to BUN ratios (3.81 +/- 1.82). These findings are similar to those previously observed in normotensive patients with vascular headaches. The profile of hypokalemia and/or alkalosis, increased blood ammonia to BUN ratios and a relatively alkaline urine appears to be a commonly observed pattern in patients with vascular headaches. These data suggest that a biochemical basis exists for the genesis of vascular headaches in patients with hypertension.

Ammonia↗
PubMed1984

Nontropical chyluria secondary to massive mesenteric adenitis. Case report with metabolic and immunologic studies.

This report describes metabolic and immunologic studies in a 17-year-old white man with nontropical chyluria secondary to massive mesenteric adenitis. Numerous red cells and mature lymphocytes were observed in the urine, and cystoscopic examination demonstrated chyle emanating from both ureteral orifices. Retrograde studies demonstrated pyelolymphatic backflow, and lymphangiography revealed prominent lymphaticocaliceal communications. Twenty-four-hour urinary studies showed proteinuria and lipiduria, which decreased after lymphangiography and a low-fat diet. Skin tests for delayed hypersensitivity were nonreactive, the lymphocyte count was decreased, and lymphocyte responses to phytohemagglutinin and pokeweed mitogen were normal. Chyluria ceased after interruption and ligation of the renal and mesenteric lymphatics.

Adolescent↗
PubMed1984

The metabolic basis for the genesis of seizures: the role of the potassium-ammonia axis.

A conceptual approach to the understanding of the pathogenesis of idiopathic seizures is presented. Hypokalemia and/or alkalosis promotes the elaboration of an alkaline urine, which increases the renal return of ammonia and exposes the brain to chronically higher concentrations of ammonia. In the brain, ammonia is preferentially detoxified to glutamine and therefore depletes the available glutamic acid, which is also a precursor of GABA, the major mediator of central inhibition. Mild chronic elevations of ammonia may also result in long-term nutritional alterations of amino-acid precursors of other brain neurotransmitters. A linkage thus exists for the metabolic basis of seizures: the role of the potassium-ammonia axis may be important in the selective depletion of GABA, the major mediator of central inhibition.

Alkalosis↗
PubMed1984

The hypokalemic, bowel, bladder, headache relationship; a new syndrome. The role of the potassium ammonia axis.

A conceptual approach that relates vascular headaches, bowel and bladder dysfunction to abnormalities of the "ammonia potassium axis" is presented. Hypokalemia alters smooth muscle function of both the bowel and bladder and results in the elaboration of an alkaline urine. The occurrence of an alkaline urine, along with bladder dysfunction and urinary stasis, predisposes to recurrent urinary tract infections. Hypokalemia and/or alkalosis increases the renal return of ammonia, exposes the brain to chronically higher concentration of ammonia and facilitates its passage into the central nervous system. Increased levels of blood ammonia predispose to hyperventilation which results in a superimposed respiratory alkalosis on a pre-existing hypokalemia and/or alkalosis therefore causing intense cerebral vasoconstriction. Varying degrees of cerebral ischemia and hypoxia occur and give rise to higher brain concentrations of ammonia. Vasodilatation occurs during the headache phase and may be a consequence of the sudden increase of brain ammonia and/or due to the release of other vasoactive mediators. As a consequence of increased blood ammonia, a reduction of protein intake may result in the alterations of amino acid precursors for brain uptake and therefore further interferes with the modulation of cerebral blood flow and brain function.

Adult↗
PubMed1984

The metabolic basis for the genesis of seizures: the role of the potassium-ammonia axis.

A conceptual approach to the understanding of the pathogenesis of idiopathic seizures is presented. Hypokalemia and/or alkalosis promotes the elaboration of an alkaline urine, which increases the renal return of ammonia and exposes the brain to chronically higher concentrations of ammonia. In the brain, ammonia is preferentially detoxified to glutamine and therefore depletes the available glutamic acid, which is also a precursor of GABA, the major mediator of central inhibition. Mild chronic elevations of ammonia may also result in long-term nutritional alterations of amino-acid precursors of other brain neurotransmitters. A linkage thus exists for the metabolic basis of seizures: the role of the potassium-ammonia axis may be important in the selective depletion of GABA, the major mediator of central inhibition.

Alkalosis↗
PubMed1984

Acute anuria and hypertension after left renal vein ligation: reversal after decompression of renal venous system.

Ligation of the renal vein in a patient with a solitary left kidney resulted in acute anuria and hypertension. These conditions were reversed by decompressing the renal venous system through anastomosis of the end of the left renal vein to the side of the splenic vein. After the anastomosis there was a decrease in renal size, a prompt diuresis, and a return of blood pressure to normal. Four months later, computerized tomography of the abdomen showed dilated renal and splenic veins and a slightly enlarged kidney; renal function was stable and the blood pressure was within normal limits.

Acute Disease↗
PubMed1983

The pathogenesis of recurrent urinary tract infection: the bowel, bladder hypokalemia connection.

A conceptual approach to the understanding of the pathogenesis of recurrent nonobstructive urinary tract infections is presented. Abnormal colonic function is associated with potassium wastage which alters smooth muscle function of both the bowel and bladder. Hypokalemia additionally results in the elaboration of an alkaline urine and bladder dysfunction leads to urinary stasis. Vaginal and perineal contamination from the bowel flora are etiologically important in the genesis of such infections. Thus, a linkage exists between bowel dysfunction, potassium wastage and recurrent urinary tract infection.

Adult↗