Influence of Age on the Disposition and Renal Handling of Enprofylline in Rats

Abstract— The effects of ageing on the pharmacokinetics, renal handling and protein binding of enprofylline were investigated in 6-, 13- and 18-month-old male Fischer 344 rats. Concentrations of enprofylline in plasma and urine were determined by HPLC, and pharmacokinetic parameters were estimated by model-independent methods. No significant differences in the volume of distribution, systemic clearance of enprofylline or urinary recovery of unchanged enprofylline (> 85%) were observed among any of the groups of rats. The dissociation constant and free fatty acid concentration in plasma increased with age. Age-dependent decreases in the systemic clearance for unbound drug were observed, and the volume of distribution for unbound drug tended to decrease with age. The ratio of systemic clearance for unbound drug to the glomerular filtration rate (GFR) decreased with ageing. Ageing was associated with decreases in the apparent maximum capacity of transport (V_max) (223·33,160·24 and 142·98 μg min^?1 kg^?1 for 6-, 13- and 18-month-old rats, respectively) and in the tubular secretory intrinsic clearance (V_max/K_m) of enprofylline (75·45, 51·03 and 44·13 mL min^?1 kg^?1, respectively), while a slight change in the Michaelis-Menten constant (K_m) was observed. These results indicate that the mechanism responsible for age-related changes in the disposition and renal handling of enprofylline may be responsible for a decrease in the ability of the tubular anion transport system.     

Effects of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion: Preliminary results

BACKGROUND: The present study was designed to reveal the usefulness of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion as evaluated by symptom scores, transrectal ultrasonography (TRUS) and magnetic resonance (MR) venography. METHODS: Ten male patients suffering from non-inflammatory chronic pelvic pain syndrome (NIH category IIIB) with intrapelvic venous congestion were treated using acupuncture. Eight patients had previously received pharmacotherapy, which was unsuccessful. Acupuncture was performed using disposable stainless steel needles, which were inserted into the bilateral BL-33 points and rotated manually for 10 min. The treatment was repeated every week for 5 weeks without other therapeutic maneuvers. Results from TRUS and MR venography, as well as clinical symptoms based on the NIH chronic prostatitis symptom index (NIH-CPSI) and the international prostate symptom score (IPSS), were compared before and after the treatment. RESULTS: No side-effects were recognized throughout the treatment period. The average pain and QOL scores of the NIH-CPSI 1 week after the 5th acupuncture treatment decreased significantly (P < 0.05 and P < 0.01, respectively) compared with the baseline. The maximum width of the sonolucent zone 1 week after the 5th treatment also decreased significantly (P < 0.01, compared with the baseline). Intrapelvic venous congestion demonstrated by MR venography was significantly improved in four patients. CONCLUSION: This study provided novel information concerning the therapeutic effects of acupuncture on non-inflammatory chronic pelvic pain syndrome.     

Oral Sustained-release Cisplatin Preparation for Rats and Mice

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin–ethylcellulose–stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg^?1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg^?1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 ± 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 ± 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL^?1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10–16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL^?1 in mice serum in which the total cisplatin concentration was 0.30 mg mL^?1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.     

Epidemiology of poliomyelitis in Karachi,Pakistan: Prospective studies during 1990–93

Between October 1989 and September 1993, 245 cases of poliomyelitis visited the Department of Pediatrics, Civil Hospital Karachi, Pakistan. The majority of them were between 6 months and 2 years of age and the epidemic occurred during the hot season. The dominant serotype was polio type 1. All of the polioviruses isolated from the patients were wild type. Virological studies also disclosed that enteroviruses other than polioviruses were prevalent among healthy children as well as diarrheal and polio patients. Serodiagnosis by poliovirus-specific immunoglobulin M antibody tests using the capture enzyme-linked immunosorbent assay method were in good agreement with the results of virus isolation. The present study demonstrated that Pakistan is a region endemic for wild poliovirus and more aggressive preventive measures are needed to eradicate poliomyelitis from the region.     

The effect of coping on the caregiver of elderly patients with dementia

Abstract Ninety-eight caregivers of elderly patients with cognitive impairment were surveyed by questionnaires in order to examine the relationship between their coping strategies and subjective burden. Confrontative coping and avoidance coping were significantly associated with their burden. The severity of cognitive impairment and the behavioral problems of the patients were also significantly associated with the caregivers' burden. However, a multiple regression analysis suggested that the caregivers' coping strategies may be more important than the patients' condition in terms of the effects on the burden.     

A case of sub wakefulness syndrome

Abstract We report a patient, a 30-year-old male Japanese-Brazilian migrant construction worker, suffering from excessive daytime sleepiness for at least 6 months. Electroencephalogram recordings during his waking states showed that 10-Hz and 60-µV alpha activity was present prominently in the occipital regions. From the multiple sleep latency test, it was found that stages 1–2 NREM sleep episodes appeared repetitively without any REM episodes, and that the mean sleep latency was 10.2 min. These findings support the diagnosis that this patient suffers from subwakefulness syndrome.     

Quantitative Analysis of Concealed Conduction into Accessory Atrioventricular Pathways in Wolff-Parkinson-White Syndrome

Concealed conduction is demonstrated to occur in an accessory AV pathway (AP). To test the hypothesis that anterograde and retrograde concealed conduction in the AP would have different characteristics, 35 consecutive patients with single APs were studied. The anterograde or retrograde ERP of the AP could be determined in 23 of those patients. Anterograde concealed conduction in the AP was assessed in the first 13 patients with retrograde AP conduction (8 APs with retrograde conduction only and 5 with both directions) (group A). Retrograde concealed conduction in the AP was evaluated in the remaining 10 patients with anterograde AP conduction (6 APs with anterograde conduction only and 4 with both directions) (group B). The concealed conduction in the AP was quantified by determining the ERP of the AP using a “probe” extrastimulus (S_p) introduced in the opposite chamber. The ERP was determined both during conventional extrastimulus (S₁S₂ method; ERP_c) and during that with an S_p (S₁S_pS₂ method; ERP_p). The S_p was delivered before or after the last S₁ with various S₁S_p intervals. The ERP_p was determined at each S₁S_p interval. Three distinct patterns in concealed conduction in the AP were noted. In the first pattern, the ERP_p was always shorter than the ERP_c, whereas the reverse relation was noted in the second pattern. The third pattern showed a combination of the two. In group A, only the first pattern was noted. In group B, the first, second, and third patterns were noted in 4, 2, and 4 patients, respectively. The first pattern was noted only in septal APs and the second and third were seen only in left free-wall APs. The second pattern was seen in patients with retrograde AP conduction, whereas the third one was mainly noted in patients without retrograde AP conduction. These observations indicate that anterograde and retrograde concealed conduction in the AP have different characteristics. Shortening of the ERP_p might be due to the “peeling back” phenomenon, and its lengthening might be caused by the presence of the inhomogeneous refractory periods of the AP. (PACE 1997; 20[Pt. I]:1342-1353)     

Endoscopy-Assisted Radiofrequency Ablation Around the Coronary Sinus Ostium in Dogs:

Endoscopy for Ablation Around the CS Ostium. Introduction : Radiofrequency ablation of the slow pathway can prolong atrioventricular (AV) nodal properties and RR intervals during atrial fibrillation (AF) in many patients with AV nodal reentrant tachycardia. However, it is not well elucidated whether these changes are related to the presence of dual AV nodal pathway physiology. The aim of this study was to evaluate changes of AV nodal properties and RR intervals during AF caused by ablation of two specific areas in dogs.
Methods and Results : Assisted by fiberoptic endoscopy, linear lesions were created between the coronary sinus ostium and tricuspid valve annulus (area 1) or posterior to the ostium (area 2) in 15 dogs. Three additional dogs served as controls. The measurements were made under autonomic blockade. Catheter ablation could be assisted in all dogs by means of endoscopy. Linear lesions were confirmed at autopsy. AV nodal parameters and RR intervals showed no overall changes. Individual data showed that ablation of area I resulted in modification of AV nodal properties in 54.5% (facilitation in 363% and inhibition in 18.2%), whereas ablation of area 2 induced changes in 50% (facilitation in 10% and inhibition in 40%). The RR intervals were shortened in 33.3% and 20% and prolonged in 44.5% and 40% after ablation of areas 1 and 2, respectively. The RR intervals during AF correlated well with the Wenckebach cycle length and the AV node functional refractory period before and after ablation (r = 0.78 to 0.94, P < 0.01 for each).
Conclusions : Ablation of the two specific areas around the coronary sinus ostium was equally effective in modifying AV nodal properties and the ventricular response during AF without dual AV nodal pathway physiology. The ventricular rate to AF after ablation correlated well with the residual AV nodal properties.     

Juvenile Secretory Carcinoma and Juvenile Papillomatosis

Two cases of juvenile secretory carcinoma associated with juvenilepapillomatosis are reported. One patient's disease was initiallydiagnosed at the age of 13 and she died 12 years later withextensive metastases. The contralateral breast at autopsy showedfindings indicative of juvenile papillomatosis. The second caseis that of an 18-year-old girl who had multiple juvenile secretorycarcinomas in the left breast associated with juvenile papillomatosis.     

Prediction of Optimal Atrioventricular Delay in Patients with Implanted DDD Pacemakers

In patients with an implanted DDD pacemaker (PM), the atrial contribution may be interrupted by too short an atrioventricular (AV) delay, and filling time may be shortened by too long an AV delay. The AV delay at which the end of the A wave on transmitral flow coincides with complete closure of the mitral valve may be optimal. The subjects were 15 patients [70.3+/-12.3 (SD) years old] with an implanted DDD PM. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter. Transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 msc. When the AV delay was set at 155+/-26 ms, the end of the A wave coincided with complete closure of the mitral valve. When the AV delay was prolonged 25, 50, 75, and 100 ms from this AV delay, the interval between the end of the A wave and complete closure of mitral the valve was prolonged 16+/-5, 39+/-6, 65+/-4 and 88+/-5 ms, respectively (r = 0.97, P<0.0001) and diastolic mitral regurgitation was observed during this period. Thus, the optimal AV delay may be predicted as follows: the slightly prolonged AV delay minus the interval between the end of the A wave and complete closure of the mitral valve. When the AV delay was set at 215 ms, there was a significant positive correlation between the predicted optimal AV delay (166+/-23 ms) and the optimal AV delay (CO: 161+/-26 msec, r = 0.93, P<0.0001, PCWP: 161+/-28 msec, r = 0.95, P<0.0001). In conclusion, optimal AV delay can be predicted by this simple formula: slightly prolonged AV delay minus the interval between end of A wave and complete closure of mitral valve at the AV delay setting.