Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle.

Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I(CCh)), especially the steady-state I-V relationship of I(CCh) showed a chracteristic U-shaped curve; reversal potential of around 0 mV and inward rectification at around +15 mV and a negative slope conductance at negative potential range. Under physiological conditions, the measured single channel conductance of NSCC was approximately 25 pS. The single channel conductance was modulated by external monovalent and divalent cations including Na+, Cs+, Li+, and Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of I(CCh) (f(Ca)) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, f(Ca) was 2.3%. Quinidine blocked I(CCh) potently in a reversible manner; IC50 was 0.25 microM. There were two kinds of I(CCh) modulations through Ca(2+)-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of I(CCh) via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of I(CCh) via Ca(2+)-dependent PKC pathway. In the mouse stomach, all seven types of TRPC mRNA were detected with RT-PCR. On the basis of electrophysiological, pharmacological, and molecular biological experiments, we reported the mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.     

Features of head injury in a developing country--Taiwan (1977-1987)

Certain features of head-injured patients admitted to the Chang Gung Memorial Hospital in Taiwan during the period 1977 to 1987 were reviewed. The most common causes of injury were motorcycle accidents (56.3%) and street accidents with pedestrian injury (29.47%). The age groups with the greatest incidence of injury were aged 16-20 years, 21-25 years, and 25-30 years. The pedestrian group involving the highest incidence of injury was less than 10 years of age. Overall mortality was 17.26%. The injured pedestrian group had the highest mortality (19.1%). Initial clinical assessment was recorded using the Glasgow Coma Scale. Head-injured patients with a GCS less than 8 had a mortality in the injured pedestrian group of 46%, whereas the mortality rate in the motorcycle accident group was 41%. Additional features studied were time of occurrence of injury and pattern of injury. Information gathered from this study would suggest the need to establish a Head Injury Prevention Program in Taiwan. This of course implies major cooperation among the providers of health care delivery, the medical profession, legislators, and the government at all levels.     

Pulsion hernias of the tympanic membrane

A pulsion hernia of the tympanic membrane is an outwardly bulging, thin, atrophic area of the tympanic membrane. Those patients who develop pulsion hernias repeatedly autoinflate the middle ear and consequently maintain a positive middle ear pressure, which pushes the thin atrophic portion of the tympanic membrane laterally beyond the normal plane of the tympanic membrane. The thinness of the tympanic membrane over the pulsion hernia suggests that the herniation has developed through a pre-existing area of weakness where the fibrous middle layer has disappeared.     

Effect of tissue inhomogeneity on beta dose distribution of 32P

In a homogeneous medium of soft tissue the radiation dose distribution due to a nonuniformly distributed beta source can be calculated by convolution of the beta dose point kernel of the nuclide with the source distribution. A possible extension of the technique to the calculation of the dose distribution in heterogeneous media involving relatively simple geometric interfaces requires the knowledge of the resulting perturbation to the beta point kernels in individual media. We simulated a soft-tissue-bone planar interface by a polystyrene (PST)-aluminum junction and measured the change in beta dose from the dose value in homogeneous PST due to a point source of 32P using 7LiF thermoluminescent dosimeters. With the point source at the interface, the dose rates at 0-31, 125-156, and 283-314 mg/cm2 separations from the interface were increased by (12 +/- 3)%, (8 +/- 2)%, and (3 +/- 2)%, respectively, compared with homogeneous PST. With the point source at a PST-air planar interface to simulate a soft-tissue-air junction, the dose rates at 0-31, 139-170, and 283-314 mg/cm2 from the interface were decreased by (25 +/- 4)%, (11 +/- 7)%, and (5 +/- 2)%, respectively. The changes in dose rates for these two interfaces have also been measured with degraded spectra of 32P. Comparison of the experimental data with Monte Carlo calculation for a point source and the two-group method of calculation for a plane source is also presented.     

Aspiration cytology in the management of breast lesions

In a group of patients with breast lumps, diagnosis made by pre-operative aspiration cytology was compared with that obtained by histological section of excised specimens. Results showed that aspiration cytology correctly diagnosed 89% of malignant lesions and 92.6% of benign lesions based upon histological diagnosis. Cytological diagnosis of benign disease had a false negative rate of 6% while cytological diagnosis of malignant disease had a 2.7% false positive rate. Only 3.5% of cytologies returned an inadequate diagnosis. This study shows that aspiration cytology should be useful in allowing a better psychological preparation of patients before surgery as well as better utilization of operation theatre facilities.     

Conformational State-dependent Effects of Halothane on Cardiac Na sup + Current

Background: The Na sup + channel is voltage gated and characterized by three distinct states: closed, open, and inactivated. To identify the effects of halothane on the cardiac Na sup + current (INa) at various membrane potentials, the effects of 1.2 mm halothane at different holding potentials (VH) on INa were examined in single, enzymatically isolated guinea pig ventricular myocytes.

Methods: The INa was recorded using the whole-cell configuration of the patch-clamp technique. Currents were generated from resting VH s of -110, -80, or -65 mV. State-dependent block was characterized by monitoring frequency dependence, tonic block, and removal of inactivation by veratridine.

Results: Halothane produced significant (P < 0.05) VH -dependent depressions of peak INa (mean +/- SEM): 24.4 +/- 4.1% (VH = -110 mV), 42.1 +/- 3.4% (VH = -80 mV), and 75.2 +/- 1.5% (VH = -65 mV). Recovery from inactivation was significantly increased when cells were held at -80 mV (control, tau = 6.0 +/- 0.3 ms; halothane, tau = 7.1 +/- 0.4 ms), but not at -110 mV. When using a VH of -80 mV, halothane exhibited a use-dependent block, with block of INa increasing from 8.6 +/- 1.4% to 30.7 +/- 3.5% at test pulse rates of 2 and 11 Hz, respectively. Use-dependent inhibition was not apparent at VH of -110 mV. When inactivation of INa was removed by exposure to 100 micro Meter veratridine, no significant difference was observed in the depressant effect of halothane at both VH s: 26.6 +/- 4.5% (VH = -80 mV) and 26.4 +/- 5.6% (VH = -110 mV).     

Loss of T-type Calcium Current in Sensory Neurons of Rats with Neuropathic Pain

Background: Pathophysiology in the primary sensory neuron may contribute to chronic neuropathic pain. Ca channels play a central role in neuronal processes, and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs). However, the physiologic function of these channels is unknown. Their possible role in rebound burst firing makes them a candidate for increased excitability after neuropathic injury.

Methods: This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.

Results: After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability.