Cisplatin induces PKB/Akt activation and p38(MAPK) phosphorylation of the EGF receptor.

Cisplatin is an effective DNA-damaging antitumor agent employed for the treatment of various human cancers. In this study, we report that Cisplatin activates PKB/Akt in several cancer cell lines and that this activation is mediated by EGFR, Src and PI3-kinase. Inhibition of PI3-kinase activity decreases the survival of the cells exposed to Cisplatin, suggesting that Cisplatin-induced PKB/Akt activation may lead to Cisplatin resistance. While investigating the EGFR-dependent PKB/Akt activation in MDA-MB-468 cells, we found that the EGFR receptor undergoes a gel mobility shift upon Cisplatin treatment, which is mediated by p38(MAPK). An EGFR, in which threonine 669 was mutated to alanine (A669), is phosphorylated by p38(MAPK) to a much lesser extent, suggesting that threonine 669 is a p38 phosphorylation site. We found that Cisplatin induces EGFR internalization, which is mediated by p38(MAPK-)dependent phosphorylation of the receptor on threonine 669. Our results identify the EGFR as a new substrate of p38 and identify threonine 669 as a new phosphorylation site that regulates EGFR internalization. Together, these results suggest that Cisplatin has side effects, which may alter the signaling pattern of cancer cells and modulate the desired effects of Cisplatin treatment.

Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study.

PURPOSE: Somatostatin (SST) analogues have been used to treat proliferative diabetic retinopathy, pseudotumor cerebri, thyroid orbitopathy, and cystoid macular edema. There is a paucity of published data in regards to cell-specific distribution of SST receptors (SSTR) in normal human eye tissues. Gene expression for all five known SSTRs in normal human ciliary body/iris, retina, choroid, and cultured retinal pigment epithelial (RPE) cells were studied. METHODS: mRNA was isolated from human ocular tissues (iris/ciliary body, retina, and choroid) dissected from eight pairs of normal eyes (9-62 years) and from RPE cells grown in culture. RT-PCR was done for all five SSTRs in all analyzed tissues. Immunohistochemistry for SSTR1 and SSTR2 was performed on eight pairs of normal human eyes (28-74 years) imbedded in paraffin. RESULTS: SSTR1 to 5 genes are expressed in retina, SSTR1 and SSTR2 genes in cultured RPE cells, and SSTR1, 2, and 4 in ciliary body and choroid. SSTR1 and SSTR2 immunoreactivity (-ir) was observed on a variety of cells within all analyzed tissues including cornea, iris, trabecular meshwork, Schlemm's canal, ciliary processes, ciliary muscle, retina, choroid, cultured RPE cells, and optic nerve. CONCLUSIONS: SSTR genes are widely expressed in normal human eye tissues, with genes for SSTR1 and SSTR2 being the most widely expressed. Genes for all SSTRs are expressed in retina. SSTR1-ir and SSTR2-ir were observed in all analyzed ocular tissues. Detailed knowledge of SSTRs distribution and function in the human eye will result in a better understanding of their role in health and disease.

Chemical, physical, and environmental properties of pelleted newspaper compared to wheat straw and wood shavings as bedding for horses.

Two experiments were conducted comparing pelleted recycled newspaper (PN) to wheat straw (S) and kiln-dried pine wood shavings (WS) as an animal bedding material. Adult horses housed 20 to 21 h/d in boxstalls served as the animal model for comparisons. In Exp. 1 eight boxstalls, each housing one horse, were each bedded with two types of PN (0.32 and 0.64 x 2.54 cm), S, and WS over four 5-d periods (replicated 4 x 4 Latin square). Initial amounts of bedding materials surpassed most commercial conditions, but stalls were cleaned daily of feces only and additional clean bedding was added as needed to maintain animal cleanliness, thus challenging the bedding properties of each material. In Exp. 2 nine boxstalls were bedded with PN (0.32 x 2.54 cm), S, and WS over three 14-d periods (three 3 x 3 Latin squares) during summer and autumn. Feces and wet spots were removed daily and clean bedding was added to reestablish working volume and simulate commercial conditions. In Exp. 1 and 2 daily additions of clean bedding varied (P < 0.05) with material (S > WS > PN). The higher water-holding capacity of PN and WS contributed to fewer bedding replacements. Usage of each material was greater (P < 0.05) during the autumn; PN had the greatest increase. Type of material and season also influenced bedding environment. Bedding pH increased (P < 0.05) with use and was highest in PN and lowest in S. Higher concentrations of breathable NH3 N were present in stalls bedded with PN and during autumn. Higher pH of used PN and decreased ventilation due to closed doors and windows during autumn were contributing factors. Season, type of bedding, and duration of its use affected (P < 0.05) numbers as well as species of microorganisms present in the breathing zone, nasal cavity, and on the leg of the horse. Clean and used WS contained greater (P < 0.05) quantities of particle fines, but with 5 d of use, particle fines in PN also increased. Quantities of breathable dust during cleaning of stalls varied (P < 0.05) with material and duration of its use; dust peaked at d 7 with PN but continued to decrease with S and to increase with WS through d 14. These data indicate that management of bedding materials varies with type of material and season of year. Use of PN as a bedding material has high potential.

Intraorbital rupture of a cavernous internal carotid artery aneurysm: therapeutic options.

PURPOSE: To describe the use of an endovascular therapeutic technique in the management of a giant carotid cavernous aneurysm. METHODS: We reviewed the clinical and neuroradiologic findings of a patient with an unusual case of carotid cavernous aneurysm and intraorbital rupture. The medical literature was searched for similar cases and to review the use of endovascular techniques. RESULTS: The patient was treated by balloon occlusion of the left internal carotid artery. CONCLUSIONS: Endovascular techniques can be used to treat complex giant cranioorbital cavernous aneurysms.

Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats.

Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat.

Echocardiographic assessment of cardiac morphology and function in mutant dwarf rats.

Although the mutant dwarf rat has been proposed as a model of growth hormone (GH) deficiency, few studies have addressed its cardiovascular abnormalities. Therefore, the aim of the present study was to investigate cardiac structure and function in mutant dwarf rats in vivo before and after chronic GH administration, by means of transthoracic Doppler echocardiography. To this purpose, forty 90-day-old female dwarf rats were randomized to receive either GH treatment or placebo. Twenty age-and sex-matched Lewis rats (200-250 g) served as the control group. All rats underwent echocardiograms before receiving any drug and after 3 weeks of therapy. Echocardiographically detected left ventricular mass indexed to tibial length was reduced by 41% in dwarf rats compared to the control group. Such relative cardiac atrophy was also evident at the myocyte level, and was fully reversible after GH therapy. In contrast to the control group, dwarf rats also showed a reduction of left ventricular diastolic volumes normalized to tibial length and impaired cardiac performance as suggested by the reduction of cardiac index, abnormal stress-shortening relations, and a significant elevation of total peripheral vascular resistance. All these abnormalities were reversible upon GH therapy for 3 weeks. In conclusion, GH plays an important role in maintaining a normal cardiac structure and function. Since the observed changes are similar to those seen in GH-deficient men, the mutant dwarf rat represents a faithful animal model of GH deficiency.

Intersession repeatability of macular thickness measurements with the Humphrey 2000 OCT.

PURPOSE: This study was designed to determine intersession repeatability of measurements of macular thickness made with a commercially available optical coherence tomography (OCT) system. The images that can be routinely acquired with the commercial instrument differ significantly in quality from the images in the literature, which have mostly been acquired on prototype systems. METHODS: Multiple OCT images of the nasal macula were obtained from the right eye during three independent measuring sessions, using the Humphrey 2000 OCT system (Humphrey, San Leandro, CA). Twenty-six volunteers with no history of ocular disease participated in this investigation. Eyes in all subjects were undilated during scan acquisition. Scans were horizontal, 3 mm long, and through the fovea. Five scans were used from each session, for a total of 15 scans per subject. Retinal boundaries were automatically detected using custom software. Statistical software was used to calculate intersession and intrasession repeatability. Manual correction was performed on the automatically detected boundaries, and a second analysis was performed using these boundaries. RESULTS: When no manual correction of boundaries was performed, there were no significant effects between different sessions (P = 0.529) or between different scans within the same session (P = 0.509). Average retinal thickness was found to be 274 +/- 17 microm for a 1-mm long region 0.75 mm from the fovea. Individual scan averages differed from overall patient averages by 0 +/- 4.3 microm (99% confidence interval, 11.2 microm). CONCLUSIONS: OCT measurements of macular thickness made with the Humphrey 2000 OCT system are repeatable over different sessions with an expected variation of less than 11 microm (99% confidence interval).

Visual loss and central venous catheterization: cortical blindness and hemianopsia after inadvertent subclavian artery entry.

A case of presumed embolic transient ischemic episodes and multifocal infarcts to the occipital and parietal cortices and the cerebellum of a young woman with ulcerative colitis is reported. These episodes were manifested by multifocal neurologic deficits including cortical blindness, visual hallucinations, and homonymous hemianopsia. They correlated with parenteral nutrition via a central line, presumed venous, but found to be in the subclavian artery. The complications of central venous lines are reviewed. The need for attention to neighborhood structures and unexpected symptoms, in view of the less well-recognized arterial embolic complications is emphasized.

Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy.

BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

Abnormal cardiac function in the streptozotocin-induced non-insulin-dependent diabetic rat: noninvasive assessment with doppler echocardiography and contribution of the nitric oxide pathway.

OBJECTIVES: We sought to evaluate in vivo and in vitro left ventricular (LV) geometry and function in streptozotocin-induced diabetic rats and the possible role of the nitric oxide (NO) pathway. BACKGROUND: Diabetes results in cardiac dysfunction; however, the specific abnormalities are unknown. Because decreased NO contributes to abnormal vascular function in diabetics, we hypothesized that NO pathway abnormalities may contribute to diabetic cardiomyopathy. METHODS: Control rats and those with non-insulin-dependent diabetes mellitus (NIDDM) underwent echocardiography, hemodynamic assessment, isolated heart perfusion and measurement of exhaled NO and LV endothelial constitutive nitric oxide synthase (ecNOS). RESULTS: Diabetic rats had increased LV mass (3.3 +/- 0.6 vs. 2.6 +/- 0.3 g/g body weight [BW], p < 0.001) and cavity dimensions (diastolic 2.0 +/- 0.1 vs. 1.8 +/- 0.2 cm/cm tibial length [TL], p < 0.05). Diabetic rats had prolonged isovolumic relaxation time (IVRT) (40 +/- 8 vs. 26 +/- 6 ms, p < 0.0001), increased atrial contribution to diastolic filling (0.47 +/- 0.09 vs. 0.30 +/- 0.08 m/s, p < 0.0001), and elevated in vivo LV end-diastolic pressure (7 +/- 6 vs. 2 +/- 1 mm Hg, p = 0.04). Diabetic rats had increased chamber stiffness. Shortening was similar in both groups, despite reduced meridional wall stress in diabetics, suggesting impaired systolic contractility. Exhaled NO was lower in diabetic rats (1.8 +/- 0.2 vs. 3.3 +/- 0.3 parts per billion, p < 0.01) and correlated with Doppler LV filling. The ecNOS was similar between the groups. CONCLUSIONS: Diabetic cardiomyopathy is characterized by LV systolic and diastolic dysfunction, the latter correlating with decreased exhaled NO. The NO pathway is intact, suggesting impaired availability of NO as contributor to cardiomyopathy.

Cardiovascular abnormalities in transgenic mice with reduced brown fat: an animal model of human obesity.

BACKGROUND: A new model of murine obesity has recently been developed through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined. METHODS AND RESULTS: Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85+/-1 versus 66+/-2 mm Hg; P<0.01), left ventricular dilation and hypertrophy (mass/body weight 4.0+/-0.2 versus 2.7+/-0.3 mg/g; P<0.01), and high cardiac output (cardiac index 3.2+/-0.4 versus 2.4+/-0.1 mL x kg(-1) x min(-1); P<0.01). Baseline functional parameters assessed in vitro were not different, but after imposition of zero-flow ischemia, significant relaxation impairment developed in obese mice. Although morphometrically determined myocyte diameters were similar, the percentage of interstitial fibrosis was significantly increased in transgenic mice compared with wild-type controls (7.5+/-2% versus 4. 2+/-0.2%; P<0.01). CONCLUSIONS: Transgenic ablation of brown adipose tissue is associated not only with obesity but also with systemic hypertension, left ventricular hypertrophy with eccentric remodeling and fibrosis, and high cardiac output, a unique constellation of findings strikingly similar to that seen in human obesity. Mice with reduced brown fat may serve as a new model for the cardiovascular morbid complications associated with obesity in humans.

Left atrial appendage anatomy and function: short term response to sustained atrial fibrillation.

OBJECTIVE: To determine whether there is significant atrial or atrial appendage enlargement or functional remodelling as a result of one to two months of sustained atrial fibrillation, a duration similar to that experienced by patients undergoing warfarin anticoagulation before elective cardioversion. METHODS: To test the hypothesis that left atrial and left atrial appendage enlargement develop as a result of short term atrial fibrillation, serial anatomical and functional indices were measured using transoesophageal echocardiography (TOE) in 20 patients with recent onset atrial fibrillation (14 men, six women; mean (SEM) age 67 (2) years). Serial TOE was performed 2.5 months apart in patients with sustained atrial fibrillation. RESULTS: There was no significant change in left atrial area (23.7 cm(2) to 24.1 cm(2), p = 0.98); length (5.7 cm to 5.7 cm, p = 0.48); width (5.2 cm to 5.2 cm, p = 0. 65); volume (83 cm(3) to 87 cm(3), p = 0.51) or left atrial appendage area (7.9 cm(2) to 8.1 cm(2), p = 0.89); length (4.6 cm to 4.5 cm, p = 0.8); or width (2.5 to 2.4 cm, p = 0.87). Peak left atrial appendage velocity ejection (0.2 m/s to 0.2 m/s, p = 0.57), and presence of severe spontaneous echo contrast in the left atrial appendage (n = 15 (75%) to n = 13 (72%)) were also not significantly different. There was no correlation between changes in left atrial or left atrial appendage dimensions. CONCLUSIONS: In the setting of sustained atrial fibrillation, significant left atrial and left atrial appendage functional and anatomical remodelling do not occur with atrial fibrillation of a duration similar to that used for conservative anticoagulation in preparation for cardioversion.

Gender differences in postinfarction left ventricular remodeling.

OBJECTIVE: Previous studies suggest that gender affects the adaptive responses of the heart to some forms of cardiac overload. It is unknown whether gender influences left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in age-matched male (n = 17) and female (n = 16) rats before, and 1 and 6 weeks after transmural MI or sham surgery. RESULTS: Following large MI (male = 45 +/- 1% LV circumference vs. female = 48 +/- 4%, p = NS), both male and female rats developed progressive LV dilatation. Infarctions caused a similar degree of global and regional LV systolic dysfunction in males and females. Male rats had significant increases in the thickness of the noninfarcted posterior wall by 6 weeks after MI. However, posterior wall thickness did not change in the infarcted female rats. Average myocyte diameter in the noninfarcted region of the heart was also greater in male than female MI rats. The combination of increased cavity size with little change in wall thickness resulted in a greater decline in relative wall thickness in the female rats compared to the males. Male rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. Female rats had less of an increase in the ratio of early to late transmitral velocities and less of an increase in the E wave deceleration rate after MI. CONCLUSIONS: Female rats showed a different pattern of LV remodeling than males with less of an increase in thickness of the noninfarcted portions of the left ventricle than males, but comparable LV cavity enlargement and systolic dysfunction. Despite similar infarct size, females developed less pronounced abnormalities of LV diastolic filling. We hypothesize that the gender-related differences in postinfarction LV remodeling may contribute to the different LV filling patterns, and might ultimately relate to differences in clinical outcome.

Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure.

1. Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved. 2. We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles. 3. Untreated MI rats had significant LV dilatation (10.6+/-0.4* vs 8.9+/(-0.3) mm, MI vs control), impaired systolic function (fractional shortening=11+/-2* vs 38+/-2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6+/(-0.5) mm) and systolic function (13+/(-2%). The propranolol treated animals had higher LV end-diastolic pressures (27+/-2* vs 20+/(-3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6+/(-0.3) vs 2.4+/(0.5 g mm(-2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6+/(-0.3 g mm(-2) or the duration of Ca transients during isoproterenol stimulation. 4. Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium.

Gender differences in molecular remodeling in pressure overload hypertrophy.

OBJECTIVES: The objective of this study was to examine gender differences in left ventricular (LV) function and expression of cardiac genes in response to LV pressure overload due to ascending aortic stenosis in rats. BACKGROUND: Clinical studies have documented gender differences in the pattern of adaptive LV hypertrophy. Whether these differences result from intrinsic differences in molecular adaptation to pressure overload between men and women, or are related to other factors is not known. METHODS: Male (n = 8) and female (n = 8) Wistar rats underwent ascending aortic stenosis and were studied 6 weeks after banding with gender-matched control rats (male n = 7; female n = 7). The LV contractile reserve was examined in isolated hearts from each group. We compared LV messenger ribonucleic acid (mRNA) levels of atrial natriuretic factor (ANF), beta-myosin heavy chain, sarcoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) and Na+-Ca2+ exchanger. Reverse transcriptase polymerase chain reaction was used to identify estrogen receptor transcript in cardiac myocytes and LV tissue. RESULTS: The magnitude of LV hypertrophy (LVH) and systolic wall stress were similar in male and female animals with LVH. Male LVH hearts demonstrated a depressed contractile reserve; in contrast, contractile reserve was preserved in female LVH hearts. The expression of beta-myosin heavy chain and ANF mRNA was greater in male versus female LVH hearts. Sarcoplasmic reticulum Ca2+-ATPase mRNA levels were depressed in male LVH but not in female LVH compared with control rats, and Na+-Ca2+ exchanger mRNA levels were increased similarly in both male and female LVH hearts. Estrogen receptor transcript was detected in both adult male and female cardiac myocytes and LV tissue. CONCLUSIONS: There are significant gender differences in the LV adaptation to pressure overload despite a similar degree of LVH and systolic wall stress in male and female rats. There is the potential for estrogen signaling through the adult myocyte estrogen receptor in both male and female rats to contribute to gender differences in gene expression in pathologic hypertrophy.

Suck and spit, don't blow: orbital emphysema after decompression surgery.

PURPOSE: To describe the occurrence of vision-threatening orbital emphysema in patients awakening from orbital decompression surgery and to assess risk factors and preventive measures. DESIGN: Small noncomparative case series. PARTICIPANTS: Three patients undergoing bilateral orbital two-wall decompression experienced significant orbital emphysema associated with persistent coughing and Valsalva at the time of extubation. INTERVENTION: In two patients, symptoms resolved with simple observation, whereas one patient required sedation, topical anesthesia around the endotracheal tube, and needle decompression of trapped air. MAIN OUTCOME MEASURES: Visual acuity, pupils, visual fields, and sensorimotor examination. RESULTS: No patient experienced a permanent deficit of visual or sensorimotor function. CONCLUSIONS: Acute orbital emphysema can occur after orbital decompression surgery despite the large bony opening created. Violent coughing spells at the time of extubation are more common in patients with a history of heavy tobacco use and may be causative. Opening the periorbita may be another specific predisposing risk factor. Knowledge of this dangerous phenomenon, along with appropriate perioperative management, may prevent this complication from occurring.

Diagnosis of polycystic ovary syndrome.

The clinical features of polycystic ovary syndrome (PCOS) include hirsutism and irregular menses, which are the results of ovarian hyperandrogenism and chronic, unopposed estrogen secretion. The discovery that most women with PCOS are insulin-resistant and have compensatory hyperinsulinemia, with increased risk for type 2 diabetes mellitus, designates this condition as a reproductive-metabolic disorder. That the symptoms of PCOS may be mimicked by other endocrine disorders of the ovary and adrenal glands warrants careful evaluation to exclude these associated conditions.

Prolonged exercise alters cardiac chronotropic responsiveness in endurance athletes.

OBJECTIVE: To determine whether exhaustive exercise alters cardiac adrenergic chronotropic responsiveness in endurance-trained athletes. METHODS: Fifteen athletes were studied prospectively 2-4 days before and within 3.3 hours after completing the Hawaii Ironman Triathlon (3.9 km swim, 180.2 km bike, 24.2 km run). Increasing intravenous boluses of isoproterenol were given until the rise in heart rate was > 30 bpm (n = 3-6 doses). A log dose heart rate response curve was constructed, and the dose required to increase heart rate by 15 and 25 bpm estimated. Left ventricular size and function were also assessed by echocardiography. RESULTS: After race finish, left ventricular volume (98 vs 83 cc), ejection fraction (56 vs 46%) and diastolic filling (3.86 vs 3.12 edv/sec) were reduced (all p < 0.01). Resting heart rate rose from 54 +/- 7 bpm to 70 +/- 10 bpm. The isoproterenol dose required to increase heart rate by 15 bpm rose from 0.6 to 1.7 micrograms by 25 bpm rose from 1.8 to 4.0 micrograms, both p < 0.01. The linear relationship between change in heart rate and log isoproterenol dose was preserved. CONCLUSIONS: Cardiac chronotropic responsiveness is reduced following an Ironman triathlon.