A. J. van der Kleij

Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV

The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [131I]MIBG and hyperbaric oxygen compared to 12% for [131I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain.

Immunomodulatory effect of oxygen and pressure

The immunomodulatory effect of hyperbaric oxygen, involving altered cytokine release by macrophages, is well described. Importantly, however, it is not known what the relative contribution is of the hyperbaric environment of the cells vs. increased oxygen tension on these hyperbaric oxygen-dependent effects. We compared, therefore, cytokine release by murine macrophages under hyperbaric oxygen, hyperpressure of normal air and normobaric conditions. We observed that hyperbaric oxygen enhanced cytokine release of both unstimulated as well as lipopolysaccharide (LPS)-challenged macrophages. Hyperpressure of normal air, however, enhanced LPS-induced cytokine production but did not elicit cytokine release in unstimulated macrophages. To further investigate the molecular details underlying the effects of hyperbaric oxygen, we investigated the effect of the p42/p44 mitogen-activated protein (MAP) kinase inhibitor PD98059 and the p38 MAP kinase inhibitor SB203580. Neither inhibitor, however, had a significant effect on the modulatory effects of hyperbaric oxygen on cytokine release. We concluded that the immunomodulatory effect of hyperbaric oxygen contains a component for which hyperpressure is sufficient and a component that apart from hyperpressure also requires hyperoxygenation.

Soft Tissue Infections Including Clostridial Myonecrosis: Diagnosis and Treatment

Necrotizing soft tissue infections caused by mixed aerobic and anaerobic bacterial floras are a continuing challenge in surgical and medical practice. They occur with increasing frequency and seriousness especially in immune-compromised patients. They vary from simple pyodermas to life-threatening infections.

Continuous Tissue Oxygenation Assessment During Bloodflow Alterations in an Isolated Hindlimb Model of the Pig

A continuous intramuscular oxygen tension sensor was compared, with transcutaneous oximetry and laser Doppler flowmetry, during periods of arterial flow alterations in an isolated hindlimb model in the pig. The intramuscular oxygen tension sensor correlated well with bloodflow and was superior to the other two methods.

Laser-Assisted Optical Rotational Red Cell Analyzer (LORCA) in Clinical Practice

Relevant hemodynamic changes in arterial hypertension (i.e. vasoconstriction induced by an organic arterial wall thickening or a functionally induced vasospasm) can lead to increased peripheral resistance. In the microvasculature of hypertensive subjects it is often possible to detect decreased peripheral perfusion together with hemorheological alterations (such as the presence of red blood cell aggregates, decreased erythrocyte deformability). These hemorheological changes can raise blood pressure (increasing the resistance of the blood flow in the microvasculature) and may finally induce a reduction in peripheral tissue oxygenation. These conditions are negatively influenced by lipoido-proteinosis, diabetes and smoking, which very important risk factors in hypertensives for acute myocardial infarction, transient ischemic attack, ictus, and peripheral occlusive arterial disease (Cesarone, 1992; Cicco, 1993, 1998). It has been shown that a good pharmacological control of the blood pressure and the lipoidoproteinosis influence the hemorheological patterns in the microvasculature, improving peripheral perfusion and tissue oxygenation (Cicco, 1994, 1995, 1997).

Red Blood Cell Velocity in Nailfold Capillaries during Hyperbaric Oxygenation

Microcirculatory hemodynamics of the skin during hyperbaric oxygenation were assessed by determination of nailfold capillary red blood cell velocity (Vrbc). Under hyperbaric conditions a continuous increase in Vrbc was found. Control values, 0.43 +/- 0.12 mm. sec-1 (mean +/- sem), were significantly (P < 0.05) lower compared with Vrbc at the end of hyperbaric oxygenation (0.62 +/- 0.16 mm.sec-1).

Clinical value of transcutaneous PO2 assessment during hyperbaric oxygen therapy.

The reason that transcutaneous PO2 electrodes (TcPO2) are more frequently used during clinical normobaric conditions to assess tissue oxygenation is because the method is non-invasive and relatively simple. Also in hyperbaric medicine TcPO2 measurements are more frequently used e.g. to predict the final outcome of woundhealing enhancement 10,16 or to adjust the administered oxygen in order to keep the TcPO2 values within or above certain limits 21. During normobaric conditions TcPO2 values are age related according to the linear regression line TcPO2 = 96.6 — 0.47 × age (in years)4. However, it has been reported that TcPO2 values during normobaric conditions may differ 4 or not17 between age groups. Variations and differences between the measurement site, shoulder 20, forearm 7, anterior chest6 has also been investigated. During normobaric conditions only TcPO2 values at the forehead, cheek, medial site of the leg and the scapular region are sites differing from other sites of the body17.

The Effect of Losartan on Red Blood Cell Deformability and Tissue Oxygenation in Patients with Arterial Hypertension

Norepinephrine (NE) plays an important vasoconstrictive role (via postsynaptic alpha-receptors). Parasympathetic cholinergic stimulation induces the release of acetylcholine (Ach) which stimulates the muscarine receptors to inhibit the release of NE modulating vasodilatation in the microvasculature. It is known that Angiotensin II formed following renin stimulation from the kidneys or locally formed is an extremely important vasoconstrictive agent. In fact Angiotensin II induces the release of norepinephrine (NE) from the terminal neurones, it acts directly on Angiotensin II receptors (AT,), and enhances calcium current influx and releases endothelin (ET) from the endothelium (1). These systems influence the peripheral vascular system, inducing a predominantly vasoconstrictive action that can increase blood pressure. Therefore increased peripheral vascular resistance is almost always observed in hypertensive patients.

New Frontiers: Hyperbaric Oxygen Therapy (HBO) in Open Heart Surgery’s Complications

Modern open heart surgery has been made possible by development of cardiopulmonary bypass (CPB). It is almost impossible to know who first had the idea of diverting the blood circulation to an oxygenator outside the body and pumping it back to the patient in order to allow surgery within the heart, but surely the first successful operation in which the patient was totally supported by CPB was done by Gibbon in 1953. Afterwards the field of cardiac surgery using CPB began to expand and is presently safely and widely practiced.

Clinical Hyperbaric Medicine and the WWW Question

There is a revival of interest in the literature for clinical hyperbaric medicine1,2,3,4 and even new horizons are recognized.5,6 This phenomenon may be a new development, or could it be a matter of history repeating itself? In 1885, E.T. Williams from the Brompton Hospital at London wrote in the British Medical Journal: “The use of atmospheric air under different degrees of atmospheric pressure, in the treatment of disease is one of the most important advances in modern medicine, and when we consider the simplicity of the agent, the exact methods by which it may be applied, and the precision with which it can be regulated to the requirements of each individual, we are astonished that in England this method of treatment has been so little used”. In that period doctors practised modern medicine and nowadays doctors do claim to do the same. However, there is a difference. Today we know that oxygen is not a simple agent. Furthermore, expected linearity effects of increased ambient pressure and/or FiO2 are attenuated by regulatory networks within the vascular bed and heterogeneity of perfusion. In fact to unravel the complicated path-way of oxygen from the ambient air to the mitochondrium is one of the fundamental drives for the ISOTT.