Postpandemic immunity debt of influenza in the USA and England: an interrupted time series study.

OBJECTIVES: The concept of "immunity debt" has gained attention in the public sphere, and some have argued that the recent out-of-season resurgence of respiratory syncytial virus demonstrates the presence of immunity debt. This study investigates the existence of immunity debt in the context of influenza. STUDY DESIGN: Interrupted time series analysis. METHODS: The positivity rate of influenza in the USA and England was gathered from the Centers for Disease Control and Prevention and the UK Health Security Agency. A time series model with an autoregressive approach was used to model the dynamics of positivity rate. Binary indicator variables were included in the model to account for the impact of non-pharmaceutical interventions (NPIs) and immunity debt. RESULTS: The impact of NPIs and immunity debt on the positivity rate of influenza was found to be statistically significant. CONCLUSIONS: This present work provides evidence supporting the existence of immunity debt in influenza in both the USA and England in the immediate month following the removal of NPIs such as lockdowns and facemask mandates.

The effect of superoxide dismutase in the myocardium during reperfusion in the dog.

The aim of the study was to investigate the pathological role of free radicals during myocardial reperfusion. Low (0.5 mg/kg body weight) and high doses (5 mg/kg) of superoxide dismutase (SOD) were infused into the left atrium of mongrel dogs for 4 min starting 29 min after ligation and 1 min before reperfusion of the left anterior descending coronary artery (LAD). Arterial blood pressure, heart rate, electrocardiogram, and the regional contractile force of the left ventricle were monitored throughout the ligation (30 min) and reperfusion periods (20 min). Concentrations of creatine kinase (CK) and malondialdehyde (MDA) in the coronary sinus blood were determined before (0 min) and during ligation (15 and 25 min) and during reperfusion of the LAD (2, 7, and 20 min). In other groups of dogs, the effect of the two doses of SOD on epicardial blood flow was investigated during ligation and reperfusion by the measurement of epicardial temperature using a thermocardiograph. Experimental subjects were mongrel dogs of either sex (n = 25), weight 10-35 kg. Compared to controls (mean +/- SEM, 43.1 +/- 1.2; n = 7), the number of ventricular extrasystoles during the first 5 min of reperfusion was significantly (p < .001) decreased in dogs treated with the high dose (15.01 +/- 2.14; n = 5), but not in those receiving the low dose of the drug (34.6 +/- 5.66; n = 5). The concentrations of CK increased gradually until the end of reperfusion without differences among the different groups. Plasma MDA was the highest in control dogs 7 min after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible therapeutic targets in cardiac myocyte apoptosis.

Since Kerr described programmed cell death (apoptosis) as a process distinct from necrosis, there have been many studies of apoptosis in disease, especially of immunological origin. Because cardiac myocytes are terminally differentiated cells, they have typically been assumed to die exclusively by necrosis. However, during the last decade this view has been challenged by several studies demonstrating that a significant number of cardiac myocytes undergo apoptosis in myocardial infarction, heart failure, myocarditis, arrhythmogenic right ventricular dysplasia, and immune rejection after cardiac transplantation, as well as in other conditions of stress. These are potentially relevant observations, because apoptosis--unlike necrosis--can be blocked or reversed at early stages. Specific inhibition of this process may confer a considerable degree of cardioprotection, but requires a thorough understanding of the underlying mechanisms. Recent progress includes a better understanding of the importance of mitochondria-initiated events in cardiac myocyte apoptosis, of factors inducing apoptosis in heart failure and during hypoxia, and of the dual pro-apoptotic and anti-apoptotic effects of hypertrophic stimuli such as beta-adrenoceptor agonists, angiotensin converting enzyme inhibitors, nitric oxide and calcineurin. The investigation of cytoprotective and apoptotic signal transduction pathways has revealed important new insights into the roles of the mitogen-activated protein kinases p38, extracellular signal regulated kinase and c-Jun N-terminal kinase in cardiac cell fate. Our present review focuses on the intracellular signal transduction pathways of cardiac myocyte apoptosis and the possibility of specific inhibition of the process.

[Malignant histiocytosis associated with chronic hepatitis]. / Krónikus hepatitissel szövödött malignus histiocytosis.

A case of malignant histiocytosis successfully treated with splenectomy and chemotherapy is presented. 33 months after surgery the patient's overall condition is satisfactory. The result is attributed to the fact, that in the time of the operation there was no systemic proliferation. The concomitantly present chronic viral hepatitis was worsened by the treatment.

[Diffuse intestinal malignant lymphoma]. / Diffuz intestinalis malignus lymphoma.

The authors describe a patient with malignant lymphoma presenting with clinically severe malabsorption due to diffuse involvement of the small intestine and with intestinal obstruction. The histologic diagnosis was based on the association of (1) diffuse involvement of the small intestine showing lymphoid tissue expansion and (2) a non-classified form of highly malignant lymphoma. After surgical resection of a stenotic part of the small intestine, abdominal irradiation therapy was done, and the patient improved.

[The role of oxidative stress, caused by amiodarone, in the side effects of the drug]. / Az amiodaron által elöidézett oxidativ stresszállapot szerepe a gyógyszer mellékhatásaiban.

It was supposed that free radicals are produced during the metabolism of amiodarone and involved in the mechanism of the drug's side effects. In vitro and in vivo experiments were performed in rats to check this hypothesis. We verified that amiodarone generated free radicals in vitro by chemiluminometric method. The light emission induced by amiodarone was inhibited by dihydroquinoline type antioxidants CH 402 and MTDQ--DA in a dose dependent manner. The malondialdehyde content, --one of the end products of lipid peroxidation--was increased by in vivo amiodarone administration in the serum and liver homogenate of rats. Amiodarone treatment increased significantly the NADPH and Fe3+ induced lipid peroxidation in rat liver microsomal fractions. The protective effect of antioxidants, MTDQ--DA and silibinin were ambiguous in these in vivo "short term" experiments.

[Thoracic injury and fat embolism]. / Mellkassérülés és zsírembólia.

The authors state that fat embolism occurs rather frequently following thoracic injuries. It is difficult to make a diagnosis because of the complexity of the symptoms. The correct evaluation of the characteristic clinical and laboratory signs arising after a period free of symptoms is essential. The authors outline the brief case history of a successfully treated patient, who recovered, owing to the use of the respirator in the intensive care unit.

The effect of adenosine diphosphate on the interaction of actin-myosin-adenosine triphosphate.

It was shown in experiments made on natural actomyosin of rabbit skeletal muscle that ADP possesses direct and indirect effects on superprecipitation. The presence of ADP increases the turbidity of the actomyosin suspension. An optimal ATP/ADP ratio may help the development and existence of a PC conformer of actomyosin corresponding to a myosin-ADP-actin-myosin-ATP complex. In this complex the extent of actin-activation is controlled by the cooperativity between the two myosin heads which, on the other side, may regulate in vivo the optimal transformation of the chemical energy of ATP for mechanical work.

Idiopathic dilatation of the right atrium. A case report.

Idiopathic dilatation of the right atrium in a young woman is reported. Thoracotomy was performed for suspected pericardial cyst. Intraoperative findings suggested idiopathic right atrial dilatation, which was histologically confirmed. Two years after partial resection of the dilated right atrial wall the patient is doing well. Management of asymptomatic idiopathic dilatation of the right atrium should be medical, surgery being reserved for patients with symptoms.

Effect of primycin on some electric properties of the frog skeletal muscle.

The effect of primycin, a guanidine-type antibiotic was studied on the electric properties and 42K+ uptake of the frog sartorius and semitendinosus muscle. Both in normal and choline chloride Ringer solution, primycin evoked a concentration and time dependent depolarization of the surface membrane of the muscle. This depolarization was significantly increased by Na ions. Primycin treatment was shown to evoke a dose-dependent decrease of the depolarization induced by 20 mM K+-Ringer. When the muscles were incubated in a Ringer solution containing choline chloride, during an incubation period of 30 min the uptake of 42K+ was decreased to 12% upon the exposure to 5 x 10(-6) mol primycin as compared to the control value. As the primycin-induced depolarization increased, the shape and amplitude of the action potentials elicited by square-wave electric impulses were altered and decreased, respectively. In sodium isaethionate Ringer 1--2 x 10(-6) M primycin induced a slow depolarization resulting in firing potentials. The results suggest that primycin depolarizes the surface membrane exclusively through the blockade of the resting K+ channels, the other phenomena being the results of this depolarizing effect.

Study of the effect of superoxide dismutase on acute renal failure in dogs.

Warm ischaemia was provoked by occlusion of the left renal artery in dogs narcotized with Nembutal and it was studied whether a small (0.5 mg/kg body weight /n = 6/) or a large dose (5 mg/kg body weight /n = 7/) of superoxide dismutase (SOD) improves renal function during 90 min reperfusion, compared to the control group (n = 6). In the first period after release of occlusion (min 0-15) the GFR and cPAH values reached 10-20% of those in the contra lateral kidney with normal circulation. The GFR and cPAH values as well as urine flow, sodium and potassium excretion were not different in the three groups. Renal function significantly improved in all groups during reperfusion. At the early stage of reperfusion the malondialdehyde (MDA) concentration exceeded that before occlusion. Such an increase could not be seen when superoxide dismutase (SOD) treatment was applied. Our results show that SOD treatment does not improve renal function at the early stage of acuterly stage of acute renal failure of ischaemic origin.

Exogenous superoxide dismutase uptake by the myocardium and kidney in an ischaemic reperfusion model in dogs.

The renal and cardiac tissues of dogs were examined with autoradiographic method in ischaemic reperfusion trials with the aim of studying the access of exogenous superoxide dismutase (SOD) enzyme to the cells. Penetration of SOD into the cells was demonstrated. The enzyme showed special affinity to the mitochondira and myofilaments in the myocardium and it was seen both in the glomeruli and the tubules in the kidney. In both organs the uptake of the enzyme was most abundant in the ischaemic regions than in tissues with intact circulation.

The importance of changes in ATP and ADP concentrations in the development of the phasic superprecipitation of actomyosin.

It has been shown previously that at physiological K+-concentrations the development of superprecipitation has a phasic character. Studying the reason of this effect, by the use of beta-32P-ADP ATP-regeneration from ADP was detected during the first phase of superprecipitation. Myokinase activity of actomyosin may be responsible for the appearance of this first phase of turbidity change of actomyosin suspension. Myokinase contributes to the stabilization of an ATP/ADP ratio within narrow limits. During the first phase of superprecipitation the ATP/ADP ratio is between these limits, while during the second phase the ratio has a low value. This phasic evolution of superprecipitation is, probably connected with the physiological functional state of the muscle (contraction or rigour).

Effect of antioxidant treatment on the myocardium during reperfusion in dogs.

Open chest dogs undergoing 30-min occlusion of the left anterior descending coronary artery (LAD), followed by 20-min reperfusion, received silibinin (2 mg/kg body weight), allopurinol (100 mg for two days as pretreatment, 20 mg/kg body weight during ischemia and reperfusion), superoxide dismutase (SOD, 5 and 0.5 mg/kg body weight, starting from the last minute of ischemia over 6 min). Control and treated dogs were comparable with respect to myocardial regional contractile force (strain gauge), malondialdehyde (MDA) and creatinine kinase (CK) levels of sinus coronarius blood samples, heart rate, and blood pressure. Allopurinol and large doses of SOD produced significant improvement in contractility and decreased MDA levels, which might suggest free radical mediated reactions during reperfusion.