KT/V and protein catabolic rate determination from serial urea measurement in the dialysate effluent stream

A bloodless technique of evaluating protein catabolic rate (PCR) and KT/V (K, clearance; T, dialysis time; V, urea distribution volume) in hemodialysis patients is presented based on serial measurement of urea in the dialysate effluent stream. PCR follows from equating urea generation and urea removal over a 7 day cycle, changes in body stores being comparatively negligible: PCR = 0.026 [U1 + U2 + U3]/BWdry + 0.17, where U1 is the amount of urea in mmol appearing in the dialysate for each session in the 7 day period. KT/V is obtained from the slope of the natural logarithm of spent dialysate urea concentration-time plot: KT/V = [- slope.T + 3.delta BW/BWdry]/[1 - 0.01786.T(hr], where delta BW = amount ultrafiltered in liters. The dialysate-based approach was validated and compared with conventional urea kinetic modeling (UKM) for 17 patients studied for three consecutive dialyses. The dialysate-based and UKM values of PCR agreed well when in vivo clearance values based on total dialysate collection were used for UKM. KT/V values agreed poorly on a session-by-session basis but were nearly equivalent when averaged for the three dialyses of the week. These findings lay the foundation for UKM automation with a urea sensor in the effluent dialysate stream.     

Detachable shape-memory sewing ring for heart valves

The novel sewing ring concept consists of a detachable ring snap connection between valve housing or stent and suture cuff. The suture cuff itself is a memory metal ring of nickel-titanium (NiTi) that is embedded within a textile fabric torus. After a special training program the ring can assume two geometric shapes when alternately cooled and heated. Due to this physical property, the sewing ring can be safely fixed within a groove of the housing or stent by changing between room and physiological temperature. This allows the surgeon first to implant the sewing ring followed by arbitrary positioning and final fixation of the valve by the shape-memory effect. Additional advantages are an increased stiffening of the valve base for minimizing potential leaflet dysfunction, and reduced time and risk of implantation, particularly when a reoperation is necessary.     

Recombinant human-type SOD attenuates circulatory disorders after reperfusion of splanchnic organs in rats

Oxygen free radicals (OFRs) have been reported to play pivotal roles in the pathogenesis of cell damage induced by ischemia and reperfusion. The efficacy of recombinant human superoxide dismutase (rh-SOD) in the treatment of circulatory disorders after reperfusion of the splanchnic area was investigated in rats. All rats died within 3 hours after release of 60-min superior mesenteric artery occlusion (SMAO) when no treatment was given. Animals which received rh-SOD, 2mg·100g^–1BW, at reperfusion followed by a continuous infusion of rh-SOD 0.67mg·100g^–1BW·hr^–1, exhibited prolonged survival times compared with no treatment rats (231 ± 35min and 149 ± 43min, respectively). Mean blood pressure in rats treated with rh-SOD was higher than in controls after reperfusion, and was concomitant with improvement in splanchnic perfusion. The results suggest excessive activity of OFRs in reperfused organs and a possible scavenging effect of rh-SOD as a means of eliminating them.(Bitoh H: Recombinant human-type SOD attenuates circulatory disorders after reperfusion of splanchnic organs in rats. J Anesth 6: 247–254, 1992)     

Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (^99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the^99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a pure blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03). Offprint requests to: A.M. Peters     

Photodynamic therapy in the bladder: Can the light dose be easily quantified?

The shape of the bladder and the optical characteristics of the tissue within the wall can be shown to play an important role in the amount of light actually received at the wall. The use of estimated doses even assuming spherical geometry, cannot therefore be relied upon. This paper describes some experimental work carried out on a glass model that was used to simulate the bladder. A specially constructed dual detector was used which consisted of an isotropic probe and semiconductor detector. This enabled measurements of irradiance and space irradiance (light energy fluence rate) to be made simultaneously. By changing the optical characteristics of the wall a four-fold increase in space irradiance was measured. Contamination of the water contained within the model by blood was also investigated and has shown that with concentrations as low as 0.5% the delivered light dose reaching the wall can be reduced by up to 50% at a wavelength of 510 nm. Some in vivo measurements are also presented together with some comments on the difficulties that have been encountered when transferring measurements from the model to the patient.     

Das Tumorrezidiv am Hals nach papillarem Schilddrüsenkarzinom Eine statistische Analyse zur Rezidivwahrscheinlichkeit nach Radikaloperation

Zusammenfassung 308 Patienten mit papillärem Schilddrüsenkarzinom (82,6% des Gesamtkrankengutes, Operation 19522–1987), die postoperativ als tumorfrei eingestuft worden waren, wurden retrospektiv analysiert. Die Beobachtungszeit reicht von 1 Monat bis zu 29,4 Jahren (mediane Beobachtungszeit 4,58 Jahre). Bei 32 Patienten (10,4%) wurde ein Tumorrezidiv am Hals diagnostiziert (lokal und/oder regionär). 8 davon sind am Ende der Beobachtungszeit nicht tumorfrei, 6 sind am Tumor verstorben (tumorbedingte Todesrate 18,8%, relative Mortalität 66,7%, im Gesamtmaterial 2,9% bzw. 29,0%). Die kumulative Rezidivwahrscheinlichkeit beträgt 9,98% nach 5 und 16,98% nach 10 Jahren. Die statistische Analyse der Rezidivwahrscheinlichkeit erfolgte nur an Patienten, die mindestens 5 Jahre beobachtet wurden oder innerhalb dieses Zeitraumes verstarben. Als Einflußgrößen wurden neben Alter and Geschlecht, tumorstadium und histologische Kriterien des Tumors berücksichtigt. Als bestimmend für das Auftreten eines Rezidivs nach 5 Jahren Beobachtungszeit erweisen sich der Status der regiondren Lymphknoten, der Differenzierungsgrad des Tumors und das Geschlecht der Patienten. Zur Verbesserung der Rezidivrate wird eine abgestufte therapeutische Radikalität in Abhängigkeit von den Einflußgrößen empfohlen.

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Cervical tumour recurrence after papillary thyroid carcinoma. A statistical analysis on the recurrence after potentially curative surgery

Summary 308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended.

     

Benzodiazepine effects upon Geller-Seifter conflict test in rats: analysis of individual variability

The aim of the present study was to investigate in a large group of "drug sophisticated" animals the effect of several doses of oxazepam upon conflict behavior. To this end 43 rats, trained according to the original Geller-Seifter paradigm, were tested with 5 doses (6.25, 12.5, 20.9, 25, and 50 mg/kg IP) of oxazepam. In addition the influence of prior drug experience on the effects of benzodiazepines on punished and unpunished responding was investigated comparing data from the same animals relative to a single oxazepam treatment before and after "drug sophistication." It was found that: (1) after "drug sophistication" oxazepam effect upon the unpunished schedule is decreased, while the disinhibitory action upon punished behavior is increased, unchanged or even decreased; (2) sedative and anticonflict activities of the drug cannot be explained in terms of rate dependency and are independently assessable since, even when unpunished responding is lowered by high doses, the anxiolytic effect is masked in only 27% of the cases; (3) about 20% of the animals appear to be insensitive to the anticonflict effect of oxazepam; (4) the responsiveness to the anxiolytic effect of the drug is related to the shock intensities given during training and to the animal variability under control conditions.     

A method for estimating within-individual variability in clearance and in volume of distribution from standard bioavailability studies

Bioavailability studies are commonly undertaken, and most, because they involve subjects taking repeated doses of a drug, contain information on intraindividual variability in pharmacokinetics. However, because in such studies bioavailability itself is unknown, it is difficult to resolve which pharmacokinetic parameters vary within individuals. A mathematical model is presented which permits estimation of variability in clearance and in volume of distribution. When applied to pooled data arising from five theophylline bioavailability studies, this model has given statistical evidence that clearance of theophylline is inherently more variable within individuals (coefficient of variation, 13%) than volume of distribution (8%). As a result, use of the measurement AUC · rather than AUCas a more precise index of bioavailability is justified in studies where is measured with reasonable precision. The model could be applied to estimation of withinbatch within-person variability in bioavailability.Deceased, April 4th, 1981.     

对《药物吸收速率常数的一种简便计算法》一文的几点看法

本文对药物吸收速率常数(K_α)的简便计算法的可靠性进行了讨论并对应用中的具体措施提出了不同看法。无论是在特征值左右多取几个血样或是用“二次抛物线拟合”都不能肯定地提高计算精度。对于K_α精度要求较高的药代动力学实验研究,该法还有待进一步改进。     

Chronic Δ9-Tetrahydrocannabinol in rats: Effect on social interactions,mouse killing,motor activity,consummatory behavior,and body temperature

Behavioral and physiologic effects of daily administration of ⁹-tetrahydrocannabinol (THC) were assessed over a 60-day period, investigating different dose levels (10, 20, 50 mg/kg), routes of administration (i.p., p.o.), drug vehicles [5%–18% propylene glycol(PG)/1% Tween 80-saline; sesame oil], and rat strains (Sprague-Dawley, Wistar, Long-Evans, Fischer). All THC-treated rats showed compulsive motor routines (i.e., forepaw treading, rhythmic jaw movements, prolonged head grooming, and biting of cage wires) after 3–4 weeks. Whether maintained on a restricted feeding regimen or not, three was no evidence for increased aggressive behavior between cagemates in any of the treatment groups. Mouse killing was induced in 70%–75% of all Sprague-Dawley (i.p., PG/Tween 80-saline vehicle) and Fischer rats (p.o., sesame oil vehicle), but not in the other THC-treated groups. Rearing activity was greatly decreased in all THC-treated groups throughout the treatment period. Food and water intake decreased by approximately 40% during the first 2–6 days of THC administration. Growth rate was reduced for the entire treatment period in THC-treated rats. THC decreased rectal temperature on the 1st day, and also on the 2nd day in Fischer rats receiving the drug in sesame oil, but not thereafter. This pattern of effects shows that tolerance develops rapidly to THC's effects on body temperature and consummatory behavior, but not to changes of certain motor activities.