Anticonvulsants for poisoning by the organophosphorus compound soman: pharmacological mechanisms.

Exposure to high doses of organophosphorus nerve agents such as soman, even with carbamate pretreatment, produces a variety of toxic cholinergic signs, including secretions, convulsions and death. Evidence suggests that soman-induced convulsions may be associated with postexposure brain neuropathology. The purpose of this study was to investigate the pharmacologic mechanism of action of soman-induced convulsions and of anticonvulsant drugs. Various classes of compounds were evaluated for their efficacy in preventing soman-induced convulsions in rats pretreated with the oxime HI-6 to increase survival time, along with various doses of the test compounds (IM) either in the absence or presence of atropine sulfate (16 mg/kg, IM) 30 minutes prior to a soman challenge dose (180 micrograms/kg, SC; equivalent to 1.6 x LD50) that produced 100% convulsions. Without atropine sulfate, only tertiary anticholinergics (scopolamine, trihexyphenidyl, biperiden, benactyzine, benztropine, azaprophen and aprophen), caramiphen, carbetapentane and MK-801 were effective anticonvulsants. In the presence of atropine sulfate, the benzodiazepines (diazepam, midazolam, clonazepam, loprazolam and alprazolam), mecamylamine, flunarizine, diphenylhydantoin, clonidine, CGS 19755 and Organon 6370 studied were effective. We have examined the possibility that diazepam may exert some of its anticonvulsant effects through cholinergic mechanisms and found that a reduced release of ACh into synapses after diazepam and atropine treatment may account for diazepam's anticonvulsant activity against soman. We also found that at anticonvulsant doses biperiden and trihexyphenidyl each significantly reversed the effects of soman on striatal levels of DOPAC and HVA, the metabolites of dopamine, and have concluded that in addition to actions on muscarinic receptors, the anticonvulsant effects of these anticholinergics in soman poisoning may be partially related to their actions on the striatal dopaminergic system. These findings allow us to postulate that central muscarinic cholinergic mechanisms are primarily involved in eliciting the convulsions following exposure to soman and that subsequent recruitment of other excitatory neurotransmitter systems and loss of inhibitory control may be responsible for sustaining the convulsions and for producing the subsequent brain damage. Future studies to confirm these neuropharmacological mechanisms are proposed.     

Cholescintigraphy in the detection of cholelithiasis: a review of 23 cases and a case report demonstrating the sequential evolution of the appearance of the gallbladder defect

Cholescintigraphy of cholelithiasis has been reported as a defect or photon deficient area in the gallbladder. We present the case of a patient with gallstones whose cholescintigraphic study showed a sequential evaluation of the scan appearance from a defect, to a septation, a hole, and finally a filled-in appearance. Cholescintigrams and histopathologic findings after cholecystectomy of another 22 patients with cholelithiasis were also retrospectively reviewed. The results of the study concluded that: cholelithiasis is rarely demonstrated by cholescintigraphy and nonvisualization of the gallbladder may be due to acute or chronic cholecystitis associated with cholelithiasis.     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

Conservative treatment of neonatal hydronephrosis.

From February 1990 to January 1991, 19 cases of hydronephrosis in children of less than one year of age were managed at Mackay Memorial Hospital. In the majority of these patients, there were evident causes such as ureteropelvic junction stenosis, ureterovesical reflux or a posterior urethral valve for which definite therapeutic measures were performed. However, some cases had no obvious origins and the hydronephrosis was speculated to be from nonobstructive or physiologic dilatation of the kidneys. The conventional tools, such as intravenous pyelogram or renal ultrasound, which comprise the mainstay of diagnosis, provide limited information on renal functional status. Recent introduction of the Tc-99m diethylene triamine penta-acetic acid (DTPA) diuretic renal scan has enabled us to distinguish between obstructive and nonobstructive hydronephrosis and helps us to determine whether or not surgery is necessary. In the past year, eight patients with hydronephrosis of less than one year of age were diagnosed as nonobstructive after a series of evaluations using renal ultrasound, voiding cystourethrography (VCUG) and Tc-99m DTPA diuretic renal scan. Follow-up studies by echography or DTPA renal scan revealed spontaneous resolution of the dilated collecting systems in these cases and confirms our belief that some hydronephrosis in neonates and infants may resolve spontaneously and may just be a manifestation of physiologic change during development. The value of the Tc-99m DTPA diuretic renal scan in the diagnosis of obstructive uropathy is discussed.     

Botulism in China

During the period 1958-1983, 986 outbreaks of botulism occurred in China, affecting 4,377 individuals and resulting in 548 deaths. The initial cases of botulism were found in Xinjiang province, where the incidence was highest. Outbreaks have occurred in all of the northern provinces and in some of the southern provinces of China. The toxin found most frequently in the northwest region of China was type A; in north China, type B; and in the northeast, type E. The most frequently offending food was home-made strong-smelling preserved bean curd, which was implicated in 74% of the outbreaks. The complex clinical manifestations of botulism can be grouped into those affecting the eyes, the mouth, the pharynx, and the skeletal muscles. Following the institution of effective methods of prevention and treatment, epidemics of botulism in China have been controlled and the mortality rate reduced from 41% (1950s) to 7.6% (1983).     

Amorphous oxide--a platform for drug delivery.

Usually, a drug is loaded onto the metallic surface of a medical device by applying a polymer layer containing the drug. Unfortunately, polymer coatings on the metallic surface may exhibit numerous problems after implantation, such as late thrombosis, inflammation, and restenosis. Current research was conducted to investigate whether a suitable oxide layer can be used as a polymer-free platform for drug loading, especially for cardiovascular stents. The loading of heparin onto, as well as eluting of heparin from, the amorphous oxide film on the 316LVM stainless steel wire was confirmed by experimental studies using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), electron spectroscopy for chemical analysis (ESCA), high-performance liquid chromatography (HPLC), and activated clotting time (ACT). Evidence shows that amorphous oxide can be an ideal substitute for the polymer coating of drug-loaded stents to minimize metallic corrosion, inflammation, late-thrombosis, and restenosis.     

Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism.

BACKGROUND: This study investigated the utility of the alveolar - arterial oxygen pressure difference (AaDO (2)) in predicting the short-term prognosis of acute pulmonary embolism (PE). METHODS AND RESULTS: This study retrospectively enrolled 114 consecutive patients with acute PE, diagnosed by either spiral computed tomography or high probability ventilation - perfusion lung scans. During the first 24 h of admission, all patients had initial artery blood gas collected under room air. Patient exclusion criteria were chronic lung disease, septic emboli, and moderate and low probability lung scans. Patients were assigned to 2 groups based on either 30-day death or a 30-day composite event. Receiver operating characteristic analyses was used to determine the AaDO(2) cut-off value for predicting primary and composite endpoints. Statistical analysis demonstrated significant differences in AaDO(2) between the 30-day composite endpoint group and the 30-day composite event-free survival group (p=0.012). The AaDO(2) had a strong trend between the 30-day death group and the survival group (p=0.062). The best cut-off value for AaDO(2) was 53 mmHg and using this, the positive predictive value for 30-day death was 25% and the negative predictive value was 92%. For the 30-day composite endpoint, the positive predictive value for AaDO(2) was 35%, and the negative predictive value was 84%. In this study, thrombocytopenia was also an indicator of poor prognosis for patients with acute PE. CONCLUSION: The AaDO(2) measurement is a highly useful and simple measurement for predicting short-term prognosis in patients with acute PE. It has high negative predictive value and moderate positive predictive value for 30-day death and 30-day composite event. Aggressive thrombolytic treatment strategies should be considered for patients with an initial poor prognostic parameter (ie, AaDO(2) >or=53 mmHg).     

Treatment of 84 cases of femoral nonunion.

Eighty-four femoral nonunions were treated with Küntscher nailing, Grosse-Kempf locked nailing, plating, and Huckstep nailing, and were followed-up for a median of 34 months. Küntscher nailing and locked nailing were superior, with fewer complications, less operation time, and less blood loss. A Küntscher nail was preferred for the isthmic region when there was no shortening of the bone, and a locked nail was preferred above or below this region or when lengthening was indicated.     

The utilization of traditional Chinese medicine and associated factors in Taiwan in 2002

Background Previous studies have noted that there is a high utilization rate of traditional Chinese medicine (TCM) services in Taiwan, China and in western countries, but few studies investigated factors associated with the utilization of TCM in Taiwan. This study analyzes the utilization rate and the factors associated with the utilization of TGM in Taiwan. Methods Data for this study were from the 2002 HPKAP Survey that conducted the face-to-face questionnaire interviews of people aged 15 years and over from October 2002 to March 2003 in Taiwan. This study analyzed the utilization of TCM outpatient services, including admission to the hospital and clinic visits. Results A total of 26 755 participants completed the survey in the six-month period. The data revealed that 10.4% of participants had utilized TCM services in the past one month while 4.2% of participants utilized TCM only (without using Western medicine outpatient services (WM) or Folk therapy (F'I')). The average visits of TCM services per patient was higher among people who had utilized TCM and FT services (2.68 visits) than among those who had utilized WM and FT services (2.15 visits) or TCM services alone (2.15 visits) during the previous one month. Younger people (odds ratio OR= 1.78, 95%C/= 1.47-2.16), women (compared with men), and people with higher education levels (OR = 1.58, 95%CI =1.25-1.98) were more likely to visit TCM than compared groups. People with self-reported poor health status (OR = 2.07,95%CI = 1.76-2.44) and people who exercise regularly (OR = 1.17, 95%CI = 1.07-1.27) had higher ORs to visit TCM service than comparison group.Conclusions There is a high utilization of TCM in Taiwan. Further studies are needed to investigate the related factors and determinants between the utilization of TCM and the utilization of FT in Taiwan.     

The adverse effect of treatment prolongation in cervical cancer by high-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: The potential risk of prolongation of treatment time in cervical cancer has been reported for many low-dose rate (LDR) studies, with an estimated loss of local control ranging from 0.3 to 1.6% per day of treatment prolongation. Since the treatment schedule for fractionated high-dose rate intracavitary brachytherapy (HDRICB) is not directly comparable with that for low-dose rate studies, this report aims to evaluate the adverse effect of treatment prolongation specifically for cervical cancer treated with HDRICB. MATERIAL AND METHODS: From September 1992 to December 1997, 257 patients diagnosed with uterine cervical cancer (35 Ib, 26 IIa, 122 IIb, 10 IIIa, 57 IIIb, 7 IVa), who underwent external radiotherapy combined with between two and four courses of HDRICB and a minimum of 3 years of follow-up (median 57 months), were analyzed. Treatment consisted of irradiation of the whole pelvis with 44-45 Gy consisting of 22-25 fractions by 5 weeks, with the dose boosted to 54-58 Gy (with central shielding) for patients diagnosed as FIGO stage IIb-IVa bilateral parametrial disease. HDRICB was performed using an Ir-192 remote afterloading technique at 1-week intervals. The standard prescribed dose for each course of HDRICB was 7.2 Gy to point A for three insertions (before July 1995), or 6.0 Gy to point A for four insertions (after July 1995). Total prescribed point A doses (external beam radiotherapy+HDRICB) ranged from 58 to 71.6 Gy (median, 65.6 Gy) for stage IB-IIA, while analogous dosage for larger lesions (stage IIb-IVa) ranged from 59 to 75.6 Gy (median, 65.6 Gy). Kaplan-Meier and multivariate analyses were used to test the effect of treatment time on pelvic control rate (PCR) and cause-specific survival (CSS) at 5 years. RESULTS: Median treatment time was 63 days. For all stages of disease, the 5-year CSS and PCR were significantly different comparing treatment times of less than and greater than or equal to 63 days [83% and 65% (P=0.004], 93% and 83% (P=0.02), respectively]. These associations were also significant for stage Ib/IIa [97% and 79% (P=0.01), and 100% and 87% (P=0.02), respectively), but not for stage IIb [75% and 72% (P=0.79), and 93% and 87% (P=0.83), respectively] or stage III [66% and 49% (P=0.2), and 83% and 72% (P=0.21), respectively]. Multivariate analysis identified three prognostic factors for CSS, stage (P<0.001), tumor response to external RT (P=0.001), and overall treatment time (OTT; P=0.006). Prognostic factors for pelvic failure were stage (P<0.001), tumor response to external RT (P=0.001), and OTT (P=0.03). Prolongation of treatment time resulted in a daily decrease in pelvic control rate of 0.67% overall, and 0.43% for stage Ib-IIa, 0.57% for stage IIb, and 0.73% for stage III patients. CONCLUSION: Analysis of the data from the current study demonstrates that the adverse effect of treatment prolongation was observed later in the treatment course for the high-dose rate (HDR) series compared to the LDR analog, however, treatment-time prolongation still negatively influenced the cause-specific survival and pelvic control rate for both dosage groups.