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Nathan Goodyear

PLOS ONE: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Ther... - 0 views

  • For all TT prescription subjects combined, the post/pre prescription rate ratio for MI (RR)was 1.36
  • In men aged 65 years and older the RR was 2.19 (1.27, 3.77), while in men under age 65 years the RR was 1.17
  • increasing RR with increasing age.
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  • The RRs were 0.95 (0.54, 1.67) under 55 years
  • 1.35 (0.77, 2.38) at 55–59
  • 1.29 (0.71, 2.35) at 60–64,
  • 1.35 (0.44, 4.18) at 65–69, 1.62
  • 3.43 (1.54, 7.66) at 75 years and older
  • The adjusted post/pre RR for PDE5I across all ages was 1.08
  • For TT prescription, in men under age 65 years, the RR was 2.90 (1.49, 5.62) for those with a history of heart disease and 0.90 (0.61, 1.34) for those without
  • In men aged 65 year and older, the RR was 2.16 (0.92, 5.10) for those with a history of heart disease and 2.21 (1.09, 4.45) for those without.
  • Among men aged 65 years and older, we observed a two-fold increase in the risk of MI in the 90 days after filling an initial TT prescription
  • Among younger men with a history of heart disease, we observed a two to three-fold increased risk of MI in the 90 days following an initial TT prescription and no excess risk in younger men without such a history
  • Among older men, the two-fold increased risk was associated with TT prescription regardless of cardiovascular disease history
  • our own findings appear consistent with a higher frequency of thrombotic events following TT prescription among men with more extensive coronary vascular disease.
  • Our findings are consistent with a recent meta-analysis of placebo-controlled randomized trials of testosterone therapy lasting 12 or more weeks among mainly older men, which reported that testosterone therapy increased the risk of adverse cardiovascular-related events (OR = 1.54, 95%CI:1.09, 2.18), as well as serious adverse cardiovascular-related events (OR = 1.61, 95%CI:1.01, 2.56) which included myocardial infarction along with other conditions
  • This association appeared unrelated to average baseline testosterone level (p = 0.70) but varied by source of funding (p = 0.03), with a stronger summary effect in a meta-analysis of studies not funded by the pharmaceutical industry (OR = 2.06, 95%CI:1.34, 3.17) compared with studies funded by the pharmaceutical industry
    • Nathan Goodyear
       
      This supports prior analysis that studies done by pharmaceutical corps will be more favorable to their product(s) than those independently funded.  This is called bias.
  • the evidence supports an association between testosterone therapy and risk of serious, adverse cardiovascular-related events–including non-fatal myocardial infarction–in men
  • there is some evidence that low endogenous testosterone levels may also be positively associated with cardiovascular events
  • effects of endogenous and exogenous testosterone may differ. Exogenous testosterone (TT) is associated with physiologic changes that predispose to clotting and thrombotic disorders including increased blood pressure [18], polycythemia [19], reductions in HDL cholesterol [18], [20], and hyperviscosity of the blood and platelet aggregation. [20]–[23]; TT also increases circulating estrogens [24], [25] which may play a role in the observed excess of adverse cardiovascular-related events, given that estrogen therapy has been associated with this excess in both men and women
  • did not include information on the serologic or diagnostic indications for treatment.
  • no association between PDE5I prescriptions and the risk of MI
  • Recently TT has been increasing extraordinarily rapidly, including among younger men and among those without hormone measurement
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    New cohort study finds increased risk of Testosterone in men > 65 and those : these are based in marketing-based medicine not evidence based medicine.
Nathan Goodyear

An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Fa... - 0 views

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    Not only do PPIs increase risk of recurrent cardiovascular events in those with prior history, but they increase risk in those individuals with no preexisting history
Nathan Goodyear

The history of attention deficit hyperactivity disorder - 0 views

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    History of ADD/ADHD
umar111

Computer Science: Computer hardware - 0 views

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    Computer Science Tuesday, April 25, 2023 Computer hardware Computer hardware is the physical components that make up a computer system. It includes everything from the central processing unit (CPU) to the monitor, keyboard, and mouse. Understanding the different types of hardware and how they work together is essential for anyone who works with computers. In this article, we will explore the various components of computer hardware, including internal and external components, and the peripherals that connect to them. We will also discuss the importance of hardware maintenance, the latest advancements in computer technology, and factors to consider when choosing the right hardware for your needs. Whether you are a computer technician, a gamer, or simply someone who uses a computer for everyday tasks, this article will help you better understand the world of computer hardware. Introduction to Computer Hardware Computer hardware refers to the physical components that make up a computer system. It includes everything from the processor and memory to input/output devices such as the keyboard and monitor. In this article, we will explore the different types of computer hardware and their functions. What is Computer Hardware Computer hardware refers to the physical components of a computer system. It includes all the components that can be touched, seen, and used to interact with a computer, such as the monitor, keyboard, and mouse. Hardware is different from computer software, which refers to the programs and applications that run on a computer system. History of Computer Hardware The history of computer hardware dates back to the 1820s when Charles Babbage, an English mathematician, and inventor, designed the first analytical engine, which was considered to be the first mechanical computer. With time, more complex electronic computers were developed, including the first Intel microprocessor in 1971. Since then, computer hardware has continued to evolve, becoming
Nathan Goodyear

The orgasmic history of oxytocin: Love, lust, and labor - 0 views

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    review of the history of knowledge on oxytocin.
Nathan Goodyear

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead - 0 views

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    great review of the history of immunotherapy in cancer treatment
Nathan Goodyear

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture - 0 views

  • Achilles tendinitis or rupture is among the most serious side effects associated with FQ use
  • The large body of data provided by clinical reports, histopathological examination, and experimental studies provides cogent evidence supporting a direct link between FQ use and tendonitis/tendon rupture
  • Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders
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  • The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement
  • Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff
  • FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture
  • a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)
  • patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition
  • Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics
  • Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months
  • Approximately 85 percent of patients present in less than one month
  • The exact pathophysiology of FQ-induced tendinopathy remains elusive
  • it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue
  • It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)
  • histopathological findings are similar to those observed in overuse conditions in athletes
  • Treatment with a FQ should be discontinued and physical therapy initiated
  • treatment should include rest and decreasing the physical load on the tendon.
  • The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days
  • Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop
  • FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction
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    Great review of the link between flouroquinolones and Tendinitis and Tendon rupture.  Yes, there is a direct link.
Nathan Goodyear

Co-occurrence of Cardiovascular and Prothrombotic Risk Facto... : Obstetrics & Gynecology - 0 views

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    preeclampsia should be a history marker that reveals increased cardiovascular disease (CVD).  
Nathan Goodyear

Improved coronary risk assessment among intermediate risk patients using a clinical and... - 0 views

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    study suggests biomarkers, CHDRA, with history provides good 5 year CHD risk assessment among those with intermediate risk.
Nathan Goodyear

Testosterone replacement therapy after primary treatm... [J Urol. 2005] - PubMed - NCBI - 0 views

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    Testosterone therapy in men with history of prostate cancer not found to increase risk of recurrence.
Nathan Goodyear

The benefits and risks of testosterone replacement therapy: a review - 0 views

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    Benefits and risks of testosterone therapy discussed.  This study gives a brief history of hypogonadism,  highlights the different therapeutic techniques.  Most important, is the evidence based positive effects and side effects. The majority of the side effects occurs through overdosing and the physiologic dysfunction that occurs in these men's micronenvironments.
Nathan Goodyear

Current treatment options for Dientamoeba fragilis infections - 0 views

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    Nice historical history and current recommendations on Dientamoeba fragilis.
Nathan Goodyear

The relationship between total testosterone levels an... [J Urol. 2014] - PubMed - NCBI - 0 views

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    meta-analysis finds risk of Testosterone replacement in those with a history of prostate cancer is small.  The problem, as the authors state, is that the studies are very heterogeneous in their design, methods...This study only looked at Total Testosterone.
Nathan Goodyear

Absence of chronic traumatic encephalopat... [Front Hum Neurosci. 2013] - PubMed - NCBI - 0 views

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    Study finds that not all football players with a history of multiple concussions and neurologic symptoms have CTE.
Nathan Goodyear

Serum oestradiol and ischaemic heart disease--relati... [Q J Med. 1985] - PubMed - NCBI - 0 views

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    Significantly higher estradiol levels found in men with a history of MI.  These men would likely have an increase in adverse effects associated with Testosterone therapy.
Nathan Goodyear

Normalization of testosterone level is associated with reduced incidence of myocardial ... - 0 views

  • Normalized-TRT group had significantly fewer deaths than no-TRT
  • Mortality was also significantly lower in the non-normalized-TRT group compared with those in no-TRT group
  • the normalized-TRT group was associated with significantly increased all-cause mortality-free survival (log-rank, P < 0.05) compared with the non-normalized-TRT or no-TRT groups
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  • normalized-TRT group showed lower risk of MI than non-normalized-TRT (HR: 0.82, CI 0.71–0.95, P = 0.008) and no-TRT
  • normalized-TRT group had significantly lower stroke events compared with non-normalized-TRT (HR: 0.70, CI 0.51–0.96, P = 0.028) and no-TRT
  • study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes
  • retrospective study
  • the first study to demonstrate that significant benefit is observed only if the dose is adequate to normalize the TT levels
  • Patients who failed to achieve the therapeutic range after TRT did not see a reduction in MI or stroke and had significantly less benefit on mortality
  • selected patients without any previous history of MI or stroke prior to initiation of TRT to reduce bias related to CV outcomes
  • currently only half of the men on TRT had been diagnosed with hypogonadism.
  • 25% of users did not have their T concentrations tested prior to initiating therapy, and 21% of those prescribed TRT did not have their levels tested at any time during treatment.
  • men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
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    Testosterone therapy in men with low T found to reduce all cause mortality, stroke and MI.
Richard  Joseph

Importance of Eye exams in St. Louis | Overland Optical Family Eyecare - 0 views

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    Eye exams are important for patients of all ages to get regular eye exams whether they are having problems or not. Eye exams can detect a problem before you even know you have one. This is particularly important if you have a family history of eye problems.
Nathan Goodyear

The reversibility of anabolic steroid-induced azoospe... [J Urol. 1995] - PubMed - NCBI - 0 views

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    Case study of 1 of a man with remote history of anabolic steroid use and current azoospermia.  HCG therapy for 3 months led to resolution of infertility.
Nathan Goodyear

Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views

  • defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
  • the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
  • most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
    • Nathan Goodyear
       
      this equals 251 to 366 in serum Total Testosterone
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  • Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
  • −0.124 nmol/L/year in serum total testosterone
    • Nathan Goodyear
       
      this equates to a 4 ng/dl decline annually in total Testosterone.
  • In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
  • In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
  • testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
  • by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
  • testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
  • In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
  • independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
  • In short, androgen improves insulin resistance by changing body composition and reducing body fat.
  • Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
  • In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
  • leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
  • Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
    • Nathan Goodyear
       
      So what is "unequivocal"?
  • Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
  • 30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
  • As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
  • Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
  • alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
  • listed in Table​T
  • A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
  • Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
  • subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
  • In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
  • Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
  • Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
  • The reduction of total testosterone was 0.4% per year in both groups
  • HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
  • pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
  • In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
  • Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
  • Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
  • The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
  • In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
  • a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
  • In India, men with CAG ≤19 had increased risk of prostate cancer
  • the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
  • assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
  • In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
  • a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
  • A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
  • Low testosterone is commonly associated with a high prevalence of MES
  • most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
  • MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
  • Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
  • In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
  • weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
  • To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
  • In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
  • low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
  • Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
  • low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
  • low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
  • European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
  • Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
  • serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
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    Nice review of Testosterone levels and some of the evidence linking Diabetes with low T.  However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling.  The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
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