Respiratory pattern and rebreathing in the Mapleson A, C and D breathing systems with spontaneous ventilation. A theory

A theoretical analysis is presented of the Mapleson A, C and D breathing systems when used in spontaneous respiration. The influence of the respiratory pattern is explained diagrammatically. Simple equations are derived, predicting the fresh gas flow required to prevent rebreathing with different respiratory patterns. Further equations allow the degree of rebreathing caused by inadequate fresh gas flow to be quantified. These are used to examine the effects of different respiratory patterns on the efficiency of the three systems. It is demonstrated that the single most important determinant of efficiency is the duration of the expiratory pause. The nature of the inspiratory and expiratory waveforms is less important and the I:E ratio far less important. The analysis suggests that the Mapleson A system will always be the most efficient of the three systems. The Mapleson C system will be efficient if inspiration is long and the expiratory pause is minimal. The Mapleson D system will be efficient if the expiratory pause is sufficiently long.     

Limb reduction defects in the A/J mouse strain associated with maternal blood loss

We previously described a high incidence of digit/limb anomalies in the offspring of A/J mice subjected to surgery on day 12.5 postconception (p.c.), but not in the offspring of untreated control mice. To investigate the cause of these defects, we compared the offspring of mice in experimental groups involving adrenalectomy, sham adrenalectomy, blood sampling, and anesthesia with the offspring of control mice. All treatments significantly reduced fetal weight and increased resorptions as compared with the controls. The highest incidence of digit anomalies occurred in the offspring of dams from which blood samples had been drawn on days 12.5, 14.5, and 15.5 p.c. The incidence of isolated cleft palate was also increased in the offspring of mice that had been subjected to blood sampling. We conclude that digit anomalies in the offspring of A/J mice result from fetal vascular disruptive phenomena subsequent to maternal blood loss induced hypovolemia and hypoperfusion to the uterus and placenta as has been suggested for uterine vascular clamping, misoprostol, chorionic villus sampling, and cocaine teratogenesis. The etiology for cleft lip in these mice may involve mechanisms unrelated to uterine/placental hypoperfusion.     

Voltage imaging of epileptiform activity in slices from rat piriform cortex: onset and propagation

The piriform cortex is a temporal lobe structure with a very high seizure susceptibility. To investigate the spatiotemporal characteristics of epileptiform activity, slices of piriform cortex were examined by imaging electrical activity with a voltage-sensitive fluorescent dye. Discharge activity was studied for different sites of stimulation and different planes of slicing along the anterior-posterior axis. Epileptiform behavior was elicited either by disinhibition with a gamma-aminobutyric acid-A receptor antagonist or by induction with a transient period of spontaneous bursting in low-chloride medium. Control activity recorded with fluorescent dye had the same pharmacological and temporal characteristics as control activity reported previously with microelectrodes. Simultaneous optical and extracellular microelectrode recordings of epileptiform discharges showed the same duration, latency, and all-or-none character as described previously with microelectrodes. Under all conditions examined, threshold electrical stimulation applied throughout the piriform cortex evoked all-or-none epileptiform discharges originating in a site that included the endopiriform nucleus, a previously identified site of discharge onset. In induced slices, but not disinhibited slices, the site of onset also included layer VI of the adjoining agranular insular cortex and perirhinal cortex, in slices from anterior and posterior piriform cortex, respectively. These locations had not been identified previously as sites of discharge onset. Thus like the endopiriform nucleus, the deep agranular insular cortex and perirhinal cortex have a very low seizure threshold. Additional subtle differences were noted between the induced and disinhibited models of epileptogenesis. Velocity was determined for discharges after onset, as they propagated outward to the overlying piriform cortex. Propagation in other directions was examined as well. In most cases, velocities were below that for action potential conduction, suggesting that recurrent excitation and/or ephaptic interactions play a role in discharge propagation. Future investigations of the cellular and organizational properties of regions identified in this study should help clarify the neurobiological basis of high seizure susceptibility.     

Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop

High doses of morphine produce a state of behavioural inactivity and muscular rigidity. This type of 'catalepsy' is clearly different from the state which is produced by the administration of neuroleptics, e.g. haloperidol. While haloperidol-induced catalepsy can easily be antagonised by NMDA receptor antagonists, there has been a report that the non-competitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801) potentiates morphine-induced catalepsy. The aim of this study was to further examine the role of glutamate receptors in the mediation of morphine-induced catalepsy. To this end we coadministered morphine (20, 40, 60 mg/kg i.p.) with MK-801 (0.1 and 0.3 mg/kg i.p.), the competitive NMDA receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentoic acid (CGP 37849) (2 and 6 mg/kg i.p.), or 1-(4-aminophenyl)-4-methyl-7,8-methylen-dioxy-5H-2,3- benzodiazepine (GYKI 52466) (2 and 4 mg/kg), an antagonist of the AMPA type of glutamate receptors, respectively. The degree of catalepsy was assessed using two different methods, the 'bar/podium/grid' test which is commonly used to measure neuroleptic-induced catalepsy, and a test for the presence or absence of righting reflexes after turning the animals into a supine position. It was found that in the 'bar/podium/grid' test coadministration of both NMDA receptor antagonists significantly and dose-dependently augmented morphine-induced catalepsy. The results using the AMPA receptor antagonist were less clear since the lower dose of GYKI 52466 tended to attenuate the morphine effect whereas the higher dose augmented morphine-induced catalepsy in some cases. While placing the animals on the bar and on the podium produced essentially the same results, the grid was found to be inapplicable for the measurement of morphine-induced catalepsy since the animals did not cling to the grid and fell off almost immediately after being released from the experimenter's hand. With respect to the righting reflexes it was found that the number of animals not showing these responses increased when MK-801 or CGP 37849 was coadministered with morphine. In contrast, most of the animals treated with GYKI 52466 and morphine displayed intact righting reflexes. It is concluded that glutamatergic transmission plays an important role in the mediation of morphine-induced catalepsy, though different to that of haloperidol-induced catalepsy, and that NMDA and AMPA receptors are differentially involved in different aspects of the associated behavioural state.     

Hepatocellular carcinoma presenting as pyogenic liver abscess: characteristics, diagnosis, and management

We performed a 17-year retrospective analysis of 10 cases of hepatocellular carcinoma presenting as pyogenic liver abscess. Spontaneous tumor necrosis and biliary obstruction caused by tumor thrombi, superimposed with bacterial infection, were the two major pathogeneses. Exact diagnosis of the underlying hepatocellular carcinoma was made for five of the 10 patients before management was attempted. Main clinical manifestations included fever, chills, right-upper-quadrant pain, malaise, anorexia, jaundice, and hepatomegaly. Characteristics such as middle age and male sex, seropositivity for hepatitis B and/or hepatitis C, chronic liver disease, unexplained anemia, marked weight loss, and a severely inversed albumin/globulin ratio raise suspicions about the underlying hepatocellular carcinoma. Management strategies included percutaneous drainage (n = 3), surgical drainage (n = 4), and hepatectomy (n = 3) in addition to administration of parenteral antibiotics in all cases. The prognosis was dismal, with a mean survival of 3.5 months (range, 8 days to 6 months).     

Evidence for involvement of ventral tegmental area cyclic AMP systems in behavioral sensitization to psychostimulants

The present study investigated the role of ventral tegmental area (VTA) cyclic AMP (cAMP) systems in the behavioral sensitivity to psychostimulants in male Sprague-Dawley rats. Bilateral microinjections of cholera toxin (CTX) into the VTA (50-500 ng/500 nl/side) dose-dependently sensitized animals to the locomotor stimulant effects of systemic d-amphetamine, cocaine and apomorphine, but were without effects on morphine-induced locomotion 24 hr after microinjection. The CTX-induced behavioral sensitization to amphetamine was even greater 72 hr after microinjection, but was no longer present 14 days after intra-VTA CTX pretreatment. Coadministration of the cAMP-dependent protein kinase inhibitor H8 into the VTA blocked CTX-induced sensitization to amphetamine, suggesting that the sensitization is dependent on phosphorylation events in the VTA mediated by cAMP-dependent protein kinase. Pretreatment with CTX did not enhance amphetamine-induced dopamine release in the nucleus accumbens relative to saline controls 24 hr after microinjection. A single bilateral injection of d-amphetamine into the VTA (5 micrograms/side) produced a significant sensitization to systemic amphetamine challenge 72 hr later, and this effect was also blocked by coadministration of H8 into the VTA. These results extend previous studies which have established the importance of the VTA in the development of behavioral sensitization and suggest that cAMP systems may play a crucial role in this neuroadaptive process.     

Regulation of classic and alternative bile acid synthesis in hypercholesterolemic rabbits: effects of cholesterol feeding and bile acid depletion

The effect of cholesterol feeding (3 g/day) on bile acid synthesis was examined in 10 New Zealand white rabbits (NZW), 8 Watanabe heterozygous and 10 homozygous rabbits with partial and complete deficiencies of LDL receptors. After 10 days of cholesterol feeding, bile fistulas were constructed and bile acid pool sizes were measured. Cholesterol feeding increased plasma and hepatic cholesterol levels in all rabbit groups. Baseline bile acid pool sizes were smaller (P < 0.01) in heterozygotes (139 +/- 3 mg) and homozygotes (124 +/- 30 mg) than NZW rabbits (254 +/- 44 mg). After feeding cholesterol, bile acid pool sizes doubled with increased cholic acid synthesis in NZW and, to a lesser extent, in Watanabe heterozygous rabbits but not in homozygotes. Baseline cholesterol 7alpha-hydroxylase activity in NZW and heterozygotes declined 69% and 53% (P < 0.001), respectively, after cholesterol feeding. Sterol 27-hydroxylase activity reflecting alternative bile acid synthesis increased 66% (P < 0.01) in NZW and 37% in Watanabe heterozygotes but not in homozygotes after feeding cholesterol. Bile fistula drainage stimulated cholesterol 7alpha-hydroxylase activity but not sterol 27-hydroxylase activity in all three rabbit groups. These results demonstrated that dietary cholesterol increased hepatic sterol 27-hydroxylase activity and alternative bile acid synthesis to expand the bile acid pool and inhibited cholesterol 7alpha-hydroxylase in NZW and in Watanabe heterozygous rabbits but not in homozygotes with absent hepatic LDL receptor function. Thus, in rabbits, sterol 27-hydroxylase is up-regulated by the increased hepatic cholesterol that enters the liver via LDL receptors whereas cholesterol 7alpha-hydroxylase is controlled by the circulating hepatic bile acid flux.     

Renal resistive index in experimental partial and complete ureteral obstruction

RATIONALE AND OBJECTIVES: Recent clinical work suggests that the Doppler resistive index (RI) may be useful in distinguishing obstructive from nonobstructive hydronephrosis. We evaluated the usefulness of the RI in a rabbit model of hydronephrosis. METHODS: Unilateral partial ureteral obstruction was produced in nine rabbits and complete obstruction in another nine. Three sham operations were performed, and these animals served as control subjects. The RI was measured in all kidneys before and 6 hr after surgery and on days 1, 4, and 7 postoperatively. The RI and the difference in RI (delta RI) between the obstructed and normal kidney were evaluated over time using a two-way analysis of variance. The intravenous urography and Whitaker tests served as gold standards. RESULTS: Hydronephrosis was observed on sonograms in all obstructed kidneys. Comparing groups, there was no significant difference in mean RI or delta RI between the three groups at any time point. Looking at individual groups over time, there was no significant change in mean delta RI, whereas the change in mean RI was significantly elevated above baseline only in the complete obstruction group at 6 hr (p = .002) and on days 4 (p = .008) and 7 (p = .006). In evaluating varying thresholds of RI and delta RI, we could not consistently discriminate between normal and obstructed kidneys. CONCLUSION: Although complete obstruction caused a significant increase in RI, partial obstruction failed to do so. RI and delta RI values proved to be insensitive predictors of obstruction in this rabbit model.