Procedural, clinical, and health status outcomes in chronic total coronary occlusion revascularization: Results from the PERSPECTIVE study.

BACKGROUND: Limited research has detailed the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) with independent core laboratory and event adjudication. This study examined procedural, clinical, and patient-reported health status outcomes among patients undergoing CTO PCI with specific focus on outcomes for those treated with zotarolimus-eluting stents (ZES). METHODS: Among 500 consecutive patients undergoing attempted CTO PCI, procedural and in-hospital clinical outcomes were examined in addition to the 1-year composite endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events, MACE). In a pre-specified cohort of 250 patients, health status measures were ascertained at baseline and 1 year. A powered secondary endpoint was 1-year MACE among patients treated with ZES compared with a performance goal. RESULTS: Demographic, lesion, and procedural characteristics for the overall population included prior bypass surgery, 29.8%; diabetes, 35.2%; occlusion length >20 mm, 71.3%; J-CTO score, 2.5 ± 1.1; and primary retrograde strategy, 30.8%. Overall guidewire crossing was 90.9%; clinical success following guidewire crossing, 94.3%; and 1-year MACE rate, 12.1%. One-year health status significantly improved from baseline with successful CTO-PCI (angina frequency, 72.7 ± 26.5 at baseline to 96.0 ± 10.8, p < .0001). Compared with a performance goal derived from prior CTO DES trials (1-year hierarchal MACE, 25.2%), treatment with ZES was associated with significantly lower MACE (18.2%, one-sided upper CI, 23.6%, p = .017). CONCLUSIONS: Favorable procedural success, health status improvements and late-term clinical outcomes inform the relative risks and benefits of CTO PCI when performed in a clinically indicated, complex patient population representative of those treated in clinical practice.

Temporal trends of fluoroscopy time and contrast utilization in coronary chronic total occlusion revascularization: insights from a multicenter United States registry.

BACKGROUND: The impact of operator experience on fluoroscopy time and contrast utilization during percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) has received limited study. METHODS: We evaluated temporal trends in fluoroscopy time and contrast utilization among 1,363 consecutive CTO PCIs performed at three US institutions between January 2006 and November 2011. RESULTS: Mean age was 65 ± 11 years, 85% of patients were men, 40% had diabetes, 37% had prior coronary artery bypass graft surgery, and 42% had prior PCI. The CTO target vessel was the right coronary artery (55%), circumflex (23%), left anterior descending artery (21%), and left main or bypass graft (1%). The retrograde approach was used in 34% of all procedures. The technical and procedural success rates were 85.5 and 84.2%, respectively. The mean procedural time, fluoroscopy time, and contrast utilization were 113 ± 61 min, 42 ± 29 min, and 294 ± 158 mL, respectively. Years since initiation of CTO PCI were independently associated with higher technical success rate (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.52-1.70, P < 0.001), lower fluoroscopy time (OR = 0.84, 95% CI = 0.75-0.95, P = 0.005), and contrast utilization (OR = 0.84, 95% CI = 0.62-0.79, P < 0.001) during the study period. CONCLUSIONS: Among selected US-based institutions performing CTO PCI, we observed a significant reduction in total fluoroscopy time and contrast utilization paralleled with an improved technical success rate over time.

Transradial approach for coronary chronic total occlusion interventions: Insights from a contemporary multicenter registry.

OBJECTIVES: To examine the impact of transradial access on the procedural outcomes of chronic total occlusion (CTO) percutaneous coronary interventions (PCI). BACKGROUND: The efficacy and safety of transradial access in CTO PCI has received limited study. METHODS: We compared the technique and outcomes of transradial vs. transfemoral access among 650 CTO PCI cases performed between January 2012 and March 2014 at 6 US centers. RESULTS: Most patients were men (87%) with high frequency of diabetes mellitus (42%) and prior coronary artery bypass graft surgery (36%). The CTO target vessel was the right coronary (59%), left anterior descending (20%), or circumflex (17%) artery. TR access was used in 110 (17%) of the 650 cases, as follows: bilateral radial access (63%); bilateral radial access plus unilateral or bilateral femoral access (7%); unilateral radial access plus unilateral or bilateral femoral access (26%); and unilateral radial access (4%). Six and eight French guide catheters were used through the radial and femoral artery, respectively. Compared to transfemoral, transradial cases had similar technical (92.6% vs. 93.0%, P = 0.87) and procedural (91.1% vs. 90.0%, P = 0.95) success and major complication rates (1.7% vs 1.8%, P = 0.99). However, transradial access was associated with higher mean procedure (142 ± 83 vs. 120 ± 60 min, P = 0.008) and fluoroscopy (58 ± 40 vs. 49 ± 31 min, P <0.026) time, and number of crossing approach changes (0.7 ± 1.0 vs. 0.5 ± 0.7, P = 0.008). CONCLUSION: Transradial CTO PCI can be performed with similar success and complication rates with transfemoral CTO PCI, but is associated with longer procedural and fluoroscopy times. © 2015 Wiley Periodicals, Inc.

The efficacy of "hybrid" percutaneous coronary intervention in chronic total occlusions caused by in-stent restenosis: insights from a US multicenter registry.

OBJECTIVES: To examine the success and complication rates in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) caused by in-stent restenosis (ISR). BACKGROUND: PCI for in-stent total occlusive disease has traditionally been associated with low success rates. We sought to examine angiographic and procedural outcomes of patients who underwent CTO PCI due to ISR using the novel "hybrid" algorithm, and compare them with patients with de novo CTOs. METHODS: We examined 521 consecutive patients who underwent CTO PCI at five high-volume PCI centers in the United States using the "hybrid" approach. Clinical, angiographic, and procedural outcomes were compared between CTOs due to ISR and de novo CTOs. RESULTS: The target CTO was due to ISR in 57 of 521 patients (10.9%). Compared to patients with de novo CTOs, those with CTO due to ISR had higher frequency of diabetes (56.1% vs. 39.6%, P = 0.02) and less calcification (5.3% vs. 16.2%, P <0.001), but longer occlusion length [38 (29-55) vs. 30 (20-51), P = 0.04]. Technical success in the ISR and de novo group was 89.4% and 92.5% (P = 0.43), respectively; procedural success was 86.0% and 90.3% (P = 0.31), respectively; and the incidence of major adverse cardiac events was 3.5% and 2.2% (P = 0.63), respectively. CONCLUSIONS: Use of the "hybrid" approach to CTO PCI was associated with similarly high procedural success and similarly low major complication rates in patients with de novo and ISR CTOs.

Development of a high-volume, multiple-operator program for percutaneous chronic total coronary occlusion revascularization: procedural, clinical, and cost-utilization outcomes.

BACKGROUND: Development of a specialized chronic total coronary occlusion (CTO) revascularization program attentive to procedural guidelines, quality oversight, and cost/resource utilization has not been described. METHODS: A single-center CTO interventional program was initiated with requirements including: extensive didactic training, on-site proctorship, routine determination of case appropriateness, adherence to procedural safety guidelines, and a 2-operator/case approach. Clinical and angiographic characteristics, procedural outcomes, in-hospital clinical events, and cost/resource utilization were examined. RESULTS: Among 145 patients, 160 consecutive CTO revascularization procedures were attempted between October 2009 and December 2010. Selected procedural and technical characteristics included: bilateral femoral access, 90.0%; planned retrograde guidewire placement, 37.5%; re-entry catheter, 10.0%; reattempt, 10.6%; fluoroscopic time, 67.4 ± 45.5 min; contrast volume, 403 ± 215 mL. Average stent number and total stent length per CTO vessel were 2.6 ± 1.1 and 64.7 ± 30.7 mm, respectively. Overall CTO success rate was 85.6% (137/160). In-hospital adverse outcomes included: death 0.6%; emergency bypass surgery, 0.6%; tamponade, 0.6%; myocardial infarction, 1.9%; transient nephropathy, 1.2%. Compared with patients undergoing non-CTO PCI, procedural and total cost per patient were significantly higher among the CTO cohort despite overall similar contribution margins ($5,173 ± 12,052 versus $5,730 ± 8,958, P = 0.58). CONCLUSIONS: Following initiation of a dedicated program with implementation of quality and performance guidelines, complex CTO revascularization may be safely performed with outcomes comparable with reports from established centers. Despite higher resource utilization, CTO revascularization is associated with a positive contribution margin. Requirement of educational and performance standards, mentorship from experts, consensus review for appropriateness and provision of catheterization laboratory policies may represent a model for program development.

Complete Genome Sequence of Roseibium sp. Strain Sym1, a Bacterial Associate of Symbiodinium linucheae, the Microalgal Symbiont of the Anemone Aiptasia.

We sequenced the genome of Roseibium sp. strain Sym1, a strain isolated from a monoculture of a Symbiodiniaceae marine dinoflagellate, Symbiodinium linucheae, a microalgal symbiont of cnidarians. The completed genome consists of one circular chromosome of 6,694,563 bp and four plasmids of 192,102 bp, 160,136 bp, 120,881 bp, and 89,413 bp.

Metagenome-Assembled Genome HetDA_MAG_MH13 of the Family Devosiaceae, from a Marine N2-fixing Cyanobacterial Enrichment Culture.

Here, we present a draft genome in the order Rhizobiales and family Devosiaceae. This draft genome comes from an enrichment of a heterocystous, cyanobacterial diazotroph (HetDA) that was originally living in association with Trichodesmium species. This Rhizobiales organism is proposed to be an anoxygenic phototroph capable of dissimilatory nitrate reduction to ammonia (DNRA).

Antipsychotic-Related Prolactin Levels and Sexual Dysfunction in Mentally Ill Youth: A 3-Month Cohort Study.

OBJECTIVE: Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce. METHOD: Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician's-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly. RESULTS: Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61), galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001). CONCLUSION: Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related galactorrhea, SeAEs did not differ significantly across SDAs, and only galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.

The Energetic Potential for Undiscovered Manganese Metabolisms in Nature.

Microorganisms are found in nearly every surface and near-surface environment, where they gain energy by catalyzing reactions among a wide variety of chemical compounds. The discovery of new catabolic strategies and microbial habitats can therefore be guided by determining which redox reactions can supply energy under environmentally-relevant conditions. In this study, we have explored the thermodynamic potential of redox reactions involving manganese, one of the most abundant transition metals in the Earth's crust. In particular, we have assessed the Gibbs energies of comproportionation and disproportionation reactions involving Mn2+ and several Mn-bearing oxide and oxyhydroxide minerals containing Mn in the +II, +III, and +IV oxidation states as a function of temperature (0-100°C) and pH (1-13). In addition, we also calculated the energetic potential of Mn2+ oxidation coupled to O2, NO2 -, NO3 -, and FeOOH. Results show that these reactions-none of which, except O2 + Mn2+, are known catabolisms-can provide energy to microorganisms, particularly at higher pH values and temperatures. Comproportionation between Mn2+ and pyrolusite, for example, can yield 10 s of kJ (mol Mn)-1. Disproportionation of Mn3+ can yield more than 100 kJ (mol Mn)-1 at conditions relevant to natural settings such as sediments, ferromanganese nodules and crusts, bioreactors and suboxic portions of the water column. Of the Mn2+ oxidation reactions, the one with nitrite as the electron acceptor is most energy yielding under most combinations of pH and temperature. We posit that several Mn redox reactions represent heretofore unknown microbial metabolisms.

Polycystic ovary syndrome: epidemiologic assessment of prevalence of systemic rheumatic and autoimmune diseases.

BACKGROUND: Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases. OBJECTIVE: To examine the frequency of certain rheumatic diseases in PCOS. METHODS: This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data. RESULTS: The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p < 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955). CONCLUSION: We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome.

Subjective health legacy of the Chornobyl accident: a comparative study of 19-year olds in Kyiv.

BACKGROUND: Since the Chornobyl accident in 1986, the physical health of exposed children in Ukraine has been monitored, but their perceived health has not been studied. This study examines health perceptions of Ukrainian adolescents exposed to radioactive fallout in utero or as infants, and the epidemiologic and Chornobyl-related influences on self-reported health. METHOD: We assessed three groups of 19-year olds in Kyiv: 262 evacuees from contaminated areas near the plant; 261 classmate controls; and 325 population-based controls. The evacuees and classmates were previously assessed at age 11. Structured interviews were conducted with the adolescents and their mothers (N = 766), followed by general physical examinations (N = 722) and blood tests (N = 707). Proportional odds logistic regression and multi-group path analysis were the major statistical tests. RESULTS: The examination and blood test results were similar across groups except for a significantly elevated rate of thyroid enlargement found by palpation in evacuees (17.8%) compared former classmates (8.7%) and population-based controls (8.0%). In addition, four evacuees and one population control had had a thyroidectomy. Compared to controls, the evacuees rated their health the least positively and reported more medically diagnosed illnesses during the 5 years preceding the interview, particularly thyroid disease, migraine headache, and vascular dystony. The consistent risk factors (p < 0.001) for these subjective health reports were evacuee status, female gender, multiple hospitalizations, and health risk perception regarding Chornobyl. All three groups of mothers rated their children's health more negatively than the adolescents themselves, and maternal ratings were uniquely associated with the adolescents' health reports in the adjusted models. In the longitudinal evacuee and classmate subsamples, path analysis showed that mothers' health ratings when the children were age 11 predicted their later evaluations which in turn were associated with the adolescent self-reports. CONCLUSION: The more negative self-evaluations of the evacuees were linked to a number of risk factors, including multiple hospitalizations, health risk perceptions, and epidemiologic risk factors. The increased rate of thyroid cancer and other diagnoses no doubt contributed to the evacuees' less positive subjective health. The strong effect of the mothers' perceptions argues in favor of developing risk communication programs for families rather than for mothers or adolescents as separate target groups.

Gynecomastia.

Gynecomastia is common and may be asymptomatic. In most cases, a thorough history and physical examination, along with limited laboratory investigations, can help to exclude breast malignancy and serious underlying endocrine or systemic disease. Careful clinical observation may be all that is required in many cases, because gynecomastia often resolves spontaneously. Because gynecomastia is usually caused by an imbalance of androgenic and estrogenic effects on the breast, medical therapy may include antiestrogens, androgens, or aromatase inhibitors. Surgery is useful in the management of patients with long-standing symptomatic gynecomastia or when medical therapy is not successful.

Human adrenal cortex hyperfunction due to LH/hCG.

Adrenal cortex hyperfunction may occasionally be due to stimulation of steroid hormone production by LH/hCG. The recent demonstration of the LH/hCG receptor in a variety of normal and abnormal human adrenal tissues has provided a novel explanation for these clinical observations and offers the possibility of spontaneous remission (as in pregnancy-related hyperfunction) or effective treatment with GnRH-agonists (to down-regulate LH secretion in menopausal patients). Involvement of adrenal LH/hCG receptors should be considered in pregnant or post-menopausal patients with ACTH-independent Cushing's syndrome or androgen excess. Additional investigations are needed to better define the role of the LH/hCG receptor in the normal adult and fetal human adrenal and to understand how this system is excessively activated in rare cases of human disease.

New medications which decrease levothyroxine absorption.

OBJECTIVE: Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. DESIGN: We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. MAIN OUTCOME: Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. CONCLUSION: Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.

Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents.

OBJECTIVE: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. METHOD: Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies. RESULTS: Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern. CONCLUSIONS: Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Pheochromocytoma in a pregnant woman with a history of intracerebral aneurysms.

Pheochromocytoma in pregnancy is rare; if unrecognized, potentially fatal hypertensive crises may occur. We report a case of a 35-year-old woman with a history of two intracerebral aneurysms who presented at 26 weeks' gestation with tachycardia, hypertension, and pulmonary edema. Laboratory data revealed elevated 24-hour urinary catecholamine and metanephrine levels, and abdominal sonography showed a 10-cm right adrenal mass. After stabilization with phenoxybenzamine and metoprolol, cesarean section was successfully performed at 36 weeks' gestation. Postpartum abdominal computed tomography scanning confirmed a 10-cm right adrenal mass. A benign pheochromocytoma was removed without incident. This case illustrates the importance of early diagnosis and management of pheochromocytoma in pregnancy and is also an example of the rare association of pheochromocytoma with intracerebral aneurysms.

Effect of combination glipizide GITS/metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects.

OBJECTIVE: Epidemiological studies have implicated increased plasminogen-activated inhibitor 1 (PAI-1) as a marker or predictor of accelerated coronary atherosclerotic disease in type 2 diabetes. We sought to determine whether metabolic control, independent of its oral mode of implementation, affects PAI-1 in patients with marked hyperglycemia. RESEARCH DESIGN AND METHODS: A total of 91 subjects were screened, subjected to a 4-week drug washout, and randomized to daily treatment with glipizide GITS (maximum 20 mg, n = 46) or metformin (maximum 2,550 mg, n = 45) as monotherapy. After monotherapy, combination therapy was initiated by adding the second agent to the regimen. Plasma glucose (fasting and postprandial), HbA(1c), fructosamine, and PAI-1 were assayed before and after randomization and sequentially thereafter in all subjects; hepatic glucose output (HGO) and abdominal fat distribution were each measured in a subset of subjects. RESULTS: Glycemic control was markedly impaired at baseline (mean HbA(1c) 10.4 +/- 0.2% glipizide GITS; 10.0 +/- 0.2% metformin) but improved comparably with each agent as monotherapy and in combination (P < 0.0001 vs. baseline), as assessed with meal tolerance studies, fructosamine values, and HGO. Body weight and abdominal fat distribution did not change significantly in either group. PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 +/- 12 ng/ml glipizide GITS; 201 +/- 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy. CONCLUSIONS: When hyperglycemia is profound, increases in PAI-1 are also profound. Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.

Presence of luteinizing hormone/human chorionic gonadotropin receptors in male breast tissues.

Receptors for LH/human chorionic gonadotropin (hCG) have been found in a variety of nongonadal tissues including the female breast. Using in situ hybridization and immunohistochemistry, we demonstrated the presence of LH/hCG receptor mRNA and protein in normal male breast tissue obtained at autopsy (n = 4) and archival samples of benign gynecomastia (n = 14) and male breast carcinoma (n = 5). Although the function of these receptors remains to be determined, the findings suggest the possibility that LH and hCG may play a role in the pathogenesis of male breast disorders.

Gynecomastia: its features, and when and how to treat it.

Gynecomastia is common, being present in 30% to 50% of healthy men. A general medical history and careful physical examination with particular attention to features suggestive of breast cancer often suffice for evaluation in patients without symptoms or those with incidentally discovered breast enlargement. Men with recent-onset gynecomastia or mastodynia need a more detailed evaluation, including selected laboratory tests to search for an underlying cause. Treatment depends on the cause and may include observation, withdrawal of an offending drug, therapy of an underlying disease, giving androgen or antiestrogen drugs, or plastic surgery.

Gynaecomastia--pathophysiology, diagnosis and treatment.

Gynaecomastia (enlargement of the male breast tissue) is a common finding in the general population. Most cases of gynaecomastia are benign and of cosmetic, rather than clinical, importance. However, the condition might cause local pain and tenderness, could occasionally be the result of a serious underlying illness or a medication, or be inherited. Breast cancer in men is much less common than benign gynaecomastia, and the two conditions can usually be distinguished by a careful physical examination. Estrogens are known to stimulate the growth of breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result from deficient androgen action or excessive estrogen action in the breast tissue. In some cases, such as pubertal gynaecomastia, the breast enlargement resolves spontaneously. In other situations, more active treatment might be required to correct an underlying condition (such as hyperthyroidism or a benign Leydig cell tumour of the testis) or medications that could cause breast enlargement (such as spironolactone) might need to be discontinued. For men with hypogonadism, administration of androgens might be helpful, as might antiestrogen therapy in men with endogenous overproduction of estrogens. Surgery to remove the enlarged breast tissue might be necessary when gynaecomastia does not resolve spontaneously or with medical therapy.