In vitro recordings of human neocortical oscillations.

Electrophysiological oscillations are thought to create temporal windows of communication between brain regions. We show here that human cortical slices maintained in vitro can generate oscillations similar to those observed in vivo. We have characterized these oscillations using local field potential and whole-cell recordings obtained from neocortical slices acquired during epilepsy surgery. We confirmed that such neocortical slices maintain the necessary cellular and circuitry components, and in particular inhibitory mechanisms, to manifest oscillatory activity when exposed to glutamatergic and cholinergic agonists. The generation of oscillations was dependent on intact synaptic activity and muscarinic receptors. Such oscillations differed in electrographic and pharmacological properties from epileptiform activity. Two types of activity, theta oscillations and high gamma activity, uniquely characterized this model-activity not typically observed in animal cortical slices. We observed theta oscillations to be synchronous across cortical laminae suggesting a novel role of theta as a substrate for interlaminar communication. As well, we observed cross-frequency coupling (CFC) between theta phase and high gamma amplitude similar to that observed in vivo. The high gamma "bursts" generated by such CFC varied in their frequency content, suggesting that this variability may underlie the broadband nature of high gamma activity.

Hypoglycemia-induced alterations in hippocampal intrinsic rhythms: Decreased inhibition, increased excitation, seizures and spreading depression.

UNLABELLED: Seizures are the most common clinical presentation of severe hypoglycemia, usually as a side effect of insulin treatment for juvenile onset type 1 diabetes mellitus and advanced type 2 diabetes. We used the mouse thick hippocampal slice preparation to study the pathophysiology of hypoglycemia-induced seizures and the effects of severe glucose depletion on the isolated hippocampal rhythms from the CA3 circuitry. METHODS AND RESULTS: Dropping the glucose perfusate concentration from the standard 10 mM to 1 mM produced epileptiform activity in 14/16 of the slices. Seizure-like events (SLEs) originated in the CA3 region and then spread into the CA1 region. Following the SLE, a spreading-depression (SD)-like event occurred (12/16 slices) with irreversible synaptic failure in the CA1 region (8/12 slices). CA3 SD-like events followed ~30 s after the SD-like event in the CA1 region. Less commonly, SD-like events originated in the CA3 region (4/12). Additionally, prior to the onset of the SLE in the CA3 area, there was decreased GABA correlated baseline SPW activity (bSPW), while there was increased large-amplitude sharp wave (LASW) activity, thought to originate from synchronous pyramidal cell firing. CA3 pyramidal cells displayed progressive tonic depolarization prior to the seizure which was resistant to synaptic transmission blockade. The initiation of hypoglycemic seizures and SD was prevented by AMPA/kainate or NMDA receptor blockade. CONCLUSIONS: Severe glucose depletion induces rapid changes initiated in the intrinsic CA3 rhythms of the hippocampus including depressed inhibition and enhanced excitation, which may underlie the mechanisms of seizure generation and delayed spreading depression.

Does type 1 diabetes alter post-exercise thermoregulatory and cardiovascular function in young adults?

Recent data demonstrated that individuals with type 1 diabetes mellitus (T1DM) exhibit impaired sweating and increased rectal temperature (i.e., heat storage) during exercise compared with healthy controls. Our purpose in this study was to investigate the consequences of T1DM on post-exercise thermal homeostasis. Sixteen participants (eight controls matched with eight T1DM) performed 90 min of cycling followed by 60 min of seated recovery. Esophageal and rectal temperatures, sweating (forearm, chest, and upper back), skin blood flow [forearm and upper back, presented as cutaneous vascular conductance (CVC)], and blood pressure [mean arterial pressure (MAP)] were measured at baseline and throughout recovery. Esophageal temperature was similar during baseline and recovery between groups (P = 0.88). However, rectal temperature was elevated in our T1DM group throughout recovery (P = 0.05). Sweating and CVC were similar between groups at all sites from 10-min post-exercise until the end of recovery (P ≥ 0.16). While absolute MAP was similar between groups (P = 0.43), the overall decrease in MAP post-exercise was greater in controls from 20 min (T1DM: - 8 ± 5 vs control: - 13 ± 6 mmHg, P = 0.03) until the end of recovery. We conclude that despite increased heat storage during exercise, individuals with T1DM exhibit a suppression in heat loss similar to their healthy counterparts during recovery.

Reduced left ventricular systolic pump performance and depressed myocardial contractile function in patients > 65 years of age with normal ejection fraction and a high relative wall thickness.

We studied the relation between relative wall thickness, left ventricular systolic pump performance, and myocardial contractile function in 77 older patients with normal ejection fraction who were free of valvular and myocardial ischemic disease. Group 1 comprised 49 patients with relative wall thickness > or = 0.45; group 2 (n = 28) had normal relative wall thickness. Pump performance was characterized by stroke volume index, cardiac index, and stroke work; myocardial function was characterized by midwall shortening and circumferential stress versus shortening relations. Group 1 patients had lower end-diastolic volume (83 +/- 3 vs 124 +/- 5 ml, p < 0.05), cardiac index (2.6 +/- 0.2 vs 3.5 +/- 0.1 L/min/m2, p < 0.05), and stroke work/100 g left ventricular mass (43 +/- 2 vs 53 +/- 3 g-m/100 g, p < 0.005). Although there was no significant difference with regard to ejection fraction or fractional shortening at the endocardium, fractional shortening at the midwall was significantly lower in group 1 than in group 2 (16 +/- 1% vs 19 +/- 1%, p < 0.005). This lower value for midwall shortening was observed despite lower values for endsystolic stress, implying decreased myocardial contractile function. Lower stroke volume index in group 1 patients, likely due to small chamber size, was not offset by increased heart rate, resulting in a low-normal cardiac index; in 33% of group 1 patients, cardiac index was < 2.2 L/min/m2, indicating reduced pump performance. Our data indicate an abnormality in pump performance and myocardial function in patients who have high relative wall thickness and normal ejection fraction.

Pulmonary embolization of trophoblastic tissue in molar pregnancy.

A case of pulmonary embolization of trophoblastic tissue is described. The signs and symptoms of this syndrome are discussed, and its optimal management is outlined.

Epidemiology of benign prostatic hyperplasia: present knowledge and studies needed.

Despite being such a common condition, morphologically prevalent in 88% of autopsies of old (greater than 80 years) men, little epidemiologic research has been undertaken on benign prostatic hyperplasia (BPH). The prevalence of BPH, and probably the incidence, increases with age although the belief that BPH is a direct consequence of aging per se still awaits proof. Many observers have concluded that the age association reflects age-related hormonal changes, although this also requires proof. BPH is a very common condition in aging men: 3 in every 10 may ultimately require surgery for this condition if current estimates of prevalence are correct. Despite its common occurrence, little is known with any degree of certainty about risk factors for BPH apart from being male, being old, and having had a pair of functioning testicles since puberty. There are good reasons why the epidemiology of BPH has remained poorly understood although the application of more epidemiologic thought could pay great dividends, particularly if prostate screening programs could be exploited maximally.

Adenosine A1 receptor-mediated antiadrenergic effects are modulated by A2a receptor activation in rat heart.

Presently, the physiological significance of myocardial adenosine A2a receptor stimulation is unclear. In this study, the influence of adenosine A2a receptor activation on A1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat hearts and isolated rat ventricular myocytes. In isolated perfused hearts, the selective A2a receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2, 4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10(-8) M)-elicited contractile responses (+dP/dtmax) in a dose-dependent manner. The effect of ZM-241385 on adenosine-induced antiadrenergic actions was abolished by the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10(-7) M), but not the selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10(-7) M). The A2a receptor agonist carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at 10(-5) M attenuated the antiadrenergic effect of the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), whereas CSC did not influence the antiadrenergic action of this agonist. In isolated ventricular myocytes, CSC potentiated the inhibitory action of adenosine on Iso (2 x 10(-7) M)-elicited increases in intracellular Ca2+ concentration ([Ca2+]i) transients but did not influence Iso-induced changes in [Ca2+]i transients in the absence of exogenous adenosine. These results indicate that adenosine A2a receptor antagonists enhance A1-receptor-induced antiadrenergic responses and that A2a receptor agonists attenuate (albeit to a modest degree) the antiadrenergic actions of A1 receptor activation. In conclusion, the data in this study support the notion that an important physiological role of A2a receptors in the normal mammalian myocardium is to reduce A1 receptor-mediated antiadrenergic actions.