Life Span of Reticulocytes in Paroxysmal Nocturnal Hemoglobinuria

Two patients with PNH were transfused with young and old Cr⁵¹-labeledred cells. The young red cells (reticulocytes) were destroyed more rapidlythan the older red cells. In vitro studies also revealed that the reticulocytewas more susceptible to acid hemolysis in acidified serum.

In contrast the Cr⁵¹-labeled reticulocytes in 3 patients with perniciousanemia responding to cyanocobalamin showed a normal life span.

In the patients with PNH and pernicious anemia, no sequestration of Cr⁵¹-labeled reticulocytes was noted in the liver or spleen by surface scanning.

Submitted on June 2, 1964 Accepted on September 18, 1964     

Interferon-γ signal transduction during parasite infection: modulation of MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii

We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii . In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii . The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-γ. However, IFN-γ treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-γ altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-γ directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-γ may be involved in mediating their protective signals .     

Comparison of Fixed Tilt and Tuned Defibrillation Waveforms: The PROMISE Study

Comparison of Defibrillation Waveforms . Background: All modern defibrillation systems use biphasic shock waveforms. Typically a fixed tilt waveform is used for implantable defibrillators (ICDs), but a tuned waveform with duration based on shock impedance may be superior based on theoretical calculations. Objective: The objective of this study was to compare defibrillation efficacy of fixed tilt and tuned waveforms. Methods: PROMISE was designed as a prospective, within‐patient, randomized study of defibrillation thresholds (DFTs) comparing a tuned (assuming a 3.5 milliseconds membrane time constant) versus a 50/50% tilt waveform. All patients had a left pectoral implant (active can) and testing was performed with a single coil shocking configuration (“SVC coil OFF”). DFTs were measured in random order with a binary search method in 52 patients, using the high‐voltage lead impedance to select the pulse widths for both waveforms. Results: At the DFT, the tuned waveform had similar delivered energy (10.5 ± 6.3 vs 9.5 ± 5.5 J, P = 0.47), stored energy (13.6 ± 7.9 vs 11.3 ± 6.3 J, P = 0.06), peak current (7.5 ± 3.0 vs 6.8 ± 2.2 A, P = 0.09), and delivered voltage (451.0 ± 134.5 vs 411.5 ± 120.7 V, P = 0.05) compared with the 50/50% tilt waveform. Conclusion: The DFTs for 3.5‐millisecond time constant based tuned and 50/50% tilt waveforms are similar using a single coil, left pectoral active can. (J Cardiovasc Electrophysiol, Vol. 24, pp. 323‐327, March 2013)     

DERMIS-FAT GRAFT: EVOLUTION OF A LIVING PROSTHESIS

Over the past two years 15 dermis-fat grafts were performed Ten were primary grafts, two were implanted because of migrated implants, two for extruding implants and one to correct deep superior sulcus recession.
Our experience showed dermis-tat grafts to be an effective method of correcting orbital volume deficit, of maintaining satisfactory prosthetic motility and of preventing the development of conjunctival deficiency.
In primary dermis-tat grafts fat atrophy was less than 70%, whilst in secondary implants fat atrophy was less than 30% Complications were minimal in our small series     

Fractional Flow Reserve: The Ideal Parameter for Evaluation of Coronary, Myocardial, and Collateral Blood Flow by Pressure Measurements at PTCA

To overcome the fundamental limitations of coronary arteriography to assess the functional significance of coronary artery disease, it is necessary to obtain direct information about coronary blood flow. Recently we validated three pressure flow equations, which enable calculation of maximum coronary, myocardial, and collateral flow by merely measuring aortic, central venous, and distal coronary pressures under the condition of maximum vasodilation and using an ultra thin pressure monitoring guide wire for distal coronary pressure recording. In this paper, the first clinical experiences of this method are described. For that purpose, the concept of fractional flow reserve (FFR) is important. Fractional coronary flow reserve (FFR_cor) is defined as the maximum achievable blood flow in a stenotic artery, divided by normal maximum flow in that same artery, i.e. maximum flow in that artery in the case that it would be completely normal. Fractional myocardial flow reserve (FFR_myo) is defined in a similar way, and recruitable collateral blood flow is expressed as a fraction of normal maximum myocardial flow. Fractional flow reserve, defined in this way, is easy to obtain at percutaneous transluminal coronary angioplasty (PTCA) by the pressure-flow equations, is independent of pressure changes, applicable to three vessel disease, and enables calculation of the separate contribution of coronary and collateral flow to total myocardial perfusion. In 18 patients a very close correlation was demonstrated between FFR_myo, calculated by pressure recordings at PTCA by the first pressure flow equation, and FFR_myo obtained by positron emission tomography, which is considered the gold standard for myocardial perfusion. In 60 other patients, maximum recruitable collateral blood flow at balloon inflation (Q_c/Q^N) was calculated according to the third pressure-flow equation and correlated to the presence or absence of ischemia. It could be demonstrated that Q_C/Q^N exceeds 22% in all 23 patients without ischemia, whereas Q_c/Q^N was less than 22% in 34 out of 37 patients who experienced ischemia during balloon inflation. This margin value of 22% is very close to the theoretically expected value of 20%. based upon a coronary flow reserve of 5 under standard physiologic conditions. It can be concluded that the concept of fractional flow reserve provides a rapid, accurate, and elegant way for quantitative assessment of maximum coronary and myocardial blood flow before and after PTCA. Moreover, this is the first method that enables quantitative calculation of collateral blood flow in clinical practice. (J Interven Cardiol 1993; 6:331–344)     

Testosterone and other gonadal factor(s) restrict the efficacy of genes controlling resistance to Plasmodium chabaudi malaria

The effect of circulating concentrations of testosterone (Te) on resistance to Plasmodium chabaudi malaria was investigated in the H-2 congenic mouse strains C57BL/10, B10.A, B10.A(3R), B10.A(4R), and B10.D2. Te-levels were determined by radioimmunoassay and resistance was expressed in terms of percent self-healers after challenge with 10(6) P. chabaudi-infected erythrocytes. Our data indicate: (i) Females and castrated males reveal very similar interstrain variations of resistance. These do not correlate with the interstrain variations of the Te-levels. This is consistent with the view that resistance to P. chaubaudi is controlled by genes of the H-2 complex and genes of the non-H-2 B10-background, (ii) The polygenic control of resistance is inefficacious at high Te-levels. This is evident as high susceptibilities of males, Te-treated females and Te-treated castrated males. Moreover, high Te-levels correlate with susceptibilities to P. chabaudi within mice of the same sex of a given strain, (iii) B10-males chemically castrated using buserelin display the same low Te-level as those surgically castrated. The latter become resistant, while the former remain as highly susceptible to P. chabaudi as untreated B10-males. Obviously, other gonadal factor(s), besides Te, impose restrictions on genes controlling resistance to P. chabaudi malaria.