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Hyperthermia

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Hyperthermia
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  Hyperthermia (heat shock)-induced protein denaturation in liver, muscle and lens tissue as determined by differential scanning calorimetry. Ritchie KP 1 , Keller BM, Syed KM, Lepock JR.    Author information Abstract Protein denaturation has been shown to occur in cells during heat shock and is closely correlated with the cellular responses to hyperthermia; however, little is known about protein denaturation in tissue. This study describes an analysis of endothermic transitions in the hyperthermic region using differential scanning calorimetry (DSC) in liver, white muscle, and lens tissue from Wistar rat, New Zealand white rabbit, and Rainbow trout. Complex DSC profiles consisting of several transitions were obtained for each tissue. Evidence is given that these transitions are due primarily to protein denaturation. Onset temperatures of denaturation (Tl) for rat liver, muscle, and lens are about 38, 39 and 48 degrees C, respectively. Thus, significant protein denaturation occurs in liver and muscle during mild hyperthermia (40-45 degrees C) with lens considerably more stable. The values of Tl for the same tissue from the different animals correlates well with body temperature (rabbit 39.4, rat 38.2, and trout grown at 11 degrees C); Tl increased in the same order as the body temperature for each tissue. Thus, there is correlation between the onset temperature for protein denaturation in these tissues and body temperature. Medical Hyperthermia   At the other end of the scale is medically-supervised hyperthermia - available in two forms: whole-body and localised  hyperthermia. Where the whole body is heated, this may not kill cancer cells or affect a tumour, but it makes the cancer cells much more sensitive to the effects of radiotherapy or drugs. Where heat is applied locally  directly to a tumour area, it is called ABLATHERM . And here it has been shown to kill cancer cells and even ´liquify´ tumours. Deep tissue tumours (for example, kidney, prostate) are already being treated using hyperthermia. 1) Localised hyperthermia  Elsewhere on this site you can read about Dr John Holt s pioneering work on Hyperthermia in Australia (CLICK HERE) which combines using radio waves to heat the tumours with glucose-blocking agents like glutathione and cysteine which the cancer cell absorbs. Glucose is essential to the energy systems of a cancer cell; without it the cancer cell dies. It´s a true double-whammy. The heat produced by the radio waves encourages their uptake and the cancer cell dies. As usual, Holt was dubbed a quack and a TV crew sent to rubbish his work. Unfortunately, they could only really find patients praising his work. Sadly, his work seems to have retired with him. The good news is that from China via Japan has come a variation of this Hyperthermia treatment, a localised hyperthermia called ablatherm, or ablation. This treatment has survived the vested interests and critics because it has been used to treat prostate cancer, a disease where the traditional treatment, surgery, causes so much harm and results in often dreadful side-effects according to one lead proponent at University College, London. Ablatherm applies High Intensity Focussed Ultrasound (HIFU) to localised and targeted prostate tumours (although it is also already used in some cases of confined kidney cancer). The treatment involves an endorectal probe which applies HIFU to the affected tissue heating them and liquefying the tumour cells, whilst leaving surrounding healthy cells unscathed. The treatment lasts about an hour and a half and only requires a brief hospital stay. You can read more about this ´breakthrough and the successful results obtained starting with an exclusive interview with Professor Mark Emberton of UCL by CLICKING HERE.  At CANCERactive, we have championed this low side-effect, cheap, non-invasive alternative to prostate surgery for over 8 years. We have commented that prostate cancer was potentially only the start. Right on cue comes a two year study from the Karolinska Institute on the use of Ablatherm with breast cancer  . Local anaesthetic, and a ten minute treatment involving probes into the tumour under local anaesthetic. The results of three studies? Excellent. No reoccurance after two years - now imagine the potential. Catch a cancer early, in a solid, confined state. Use hyperthermia. No surgery (so no risk of spreading the cancer), no need for radiotherapy or drugs. And the beauty of Ablatherm is that, in the rare case of the reappearance of another tumour, you can use the treatment again. Expect a major backlash against Ablatherm, driven by powerful vested interests. 2) Whole Body hyperthermia  The principle of hyperthermia is that cancer cells are much more sensitive to and intolerant of the effects of excessive heat than normal cells. Also, tumours have an impaired ability to adapt their blood circulation to the effects of high temperatures and thus hyperthermia can cause a reduction of blood flow to a tumour. In addition, heat at this level pushes cancer cells toward acidosis (decreased cellular pH) which decreases the cells viability and ability to spread. It also activates the immune system, causing both increased production of interferon alpha, and increased immune surveillance. German expert, Professor Rolf Issels , believes that hyperthermia increases ´heat shock´ proteins on the surface of the cancer cells making them more prone to attack by the immune system. 3) Combination Therapies  The success of the treatment on its own is not significant, but it has been used most successfully in conjunction with other treatments. For example, tumour masses tend to have oxygen-deprived (hypoxic) cells within the inner part of the tumour. These cells are resistant to radiation, but they are very sensitive to heat. This makes hyperthermia is an ideal companion treatment to radiation. Radiation kills the oxygenated outer cells, while hyperthermia acts on the inner low oxygen cells making them more susceptible to radiation damage. Hyperthermia overcomes tumour resistance to chemo and radiation In March 2000, the respected medical journal, The Lancet published the results of a six year cancer study comparing the effectiveness of hyperthermia and radiation with radiation treatments alone. The trials reported are a randomised, Phase III study performed on 358 patients with cancer. Although the study showed promise for the treatment of advanced cervical, bladder and colorectal cancer, the most remarkable results were obtained with advanced cervical cancer. Complete disappearance of the tumour was obtained in 83% of those who received the combined treatment, compared to 57% who were treated with radiation alone. In addition, the three-year survival rate for those who received the combined treatments nearly doubled (improved 89%), compared with those who just received radiation. The study was well-received in the Netherlands, where it was conducted and the treatment has received government approval. The other advantage noted in the report was the fact that there was none of the nausea often experienced with radiation, and hospitalisation was not required. In a 2001 article by Issels, a 5-year trial on sarcoma patients using such combination therapies produced remarkable improvements. With 59 patients the 5-year survival doubled from the conventional treatment norm of around 25 per cent to 49 per cent with 36 patients being completely disease-free after 5 years. In the 2009 Berlin European Society of Medical Oncology a presentation on Sarcoma using chemotherapy alone, or chemotherapy plus hyperthermia showed that in a randomised trial, the group also using hyperthermia doubled their survival times from a mean of 18 months to over 32 months ( Journal of the National Cancer Institute 2010: Twombley  ) Hyperthermia allows very high doses of chemotherapy to be administered more successfully and sometimes without significant side-effects There are a number of German clinics, such as those operated by Dr Wolf in Hanover or by Drs Herzog and Douwes, that practice the use of hyperthermia in combination with more ´orthodox´ therapies. The use of hyperthermia with chemotherapy, according to one report in the Lancet, seems to significantly increase 5-year survival rates and chemotherapy success. Another report in the Lancet reviewed various studies in USA and Europe and reported that response rates for chemo and hyperthermia combined are 70%, whilst hyperthermia alone gives a response rate of 15%, chemotherapy can give results of 5 - 60 per cent depending upon the drug, and radiotherapy alone about 35%. Hyperthermia also appears to allow very high doses of chemotherapy to be administered more successfully and sometimes without significant side-effects. What seems to be the case is that hyperthermia overcomes tumour resistance to chemo and radiation; that it can help the performance of some chemo agents and that it helps destroy cancer cells in especially resistant phases of cell division. How can you improve your personal odds of survival using hyperthermia?   Hyperthermia is the only agent to treat cancer that does not itself appear to be oncogenic (cancer-inducing). Firstly, what does treatment consist of? Generally speaking, whole-body hyperthermia induces a fever. Patients lie naked in a structure that is like a small tent, where they are closely monitored. The idea is that the body is heated to extremely high temperatures - between  107 and 113 degrees F - not exactly a pleasant sensation, so patients are generally sedated so they can tolerate the heat. But if you want treatment using hyperthermia you may well need to look abroad. Cancer patients in Britain encouraged by the above account may be disappointed to hear that hyperthermia isnt readily available at their local hospital. Sadly, the one private specialist, Dr Fritz Schellander of the Liongate Clinic in Tunbridge Wells, has retired too! One of his patients was featured in the Living Proof section of icon . Hazel Scade abandoned conventional treatment for breast cancer in favour of a less-invasive route. In addition to many nutritional therapies she used some localised hyperthermia, and wrote about her experience in the July 2003 issue. She quoted a Dr TK Hei of the Columbia University College of Physicians who stated, Hyperthermia is the only agent to treat cancer that does not itself appear to be oncogenic (cancer-inducing). Sadly, although Hazel beat the 5-year milestone successfully, she passed away in 2008. Fortunately, the new Raphael Centre , in Hildenborough, Tonbridge, Kent provides an option. It uses the latest generation Heckl machine that has water cooled lamps allowing the body to move to internal fever temperature levels (around 104 degrees) without the skin being damaged. No sedation is required therefore.  Dr Maurice Orange of the centre adds, Dose is decided according to tolerance. If used in conjunction with chemotherapy, a patient might have a session once a week or fortnightly, whilst having hyperthermia treatment usually around two or three days away from the chemotherapy Hyperthermia can be effective even when other treatments have failed Urinary casts Share on facebookShare on twitterBookmark & SharePrinter-friendly version    Urinary casts are tiny tube-shaped particles that can be found when urine is examined under the microscope during a test called urinalysis.    Urinary casts may be made up of white blood cells, red blood cells, kidney cells, or substances such as protein or fat. The content of a cast can tell your health care provider whether your urine is healthy or abnormal. Casts Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). The proximal convoluted tubule (PCT) and loop of Henle are not locations for cast formation. Hyaline casts are composed primarily of a mucoprotein (Tamm-Horsfall protein) secreted by tubule cells. The Tamm-Horsfall protein secretion (green dots) is illustrated in the diagram below, forming a hyaline cast in the collecting duct: Even with glomerular injury causing increased glomerular permeability to plasma proteins with resulting proteinuria, most matrix or glue that cements urinary casts together is Tamm-Horsfall mucoprotein, although albumin and some globulins are also incorporated. An example of glomerular inflammation with leakage of RBC's to produce a red blood cell cast is shown in the diagram below: The factors which favor protein cast formation are low flow rate, high salt concentration, and low pH, all of which favor protein denaturation and precipitation, particularly that of the Tamm-Horsfall protein. Protein casts with long, thin tails formed at the  junction of Henle's loop and the distal convoluted tubule are called cylindroids. Hyaline casts can be seen even in healthy patients. Red blood cells may stick together and form red blood cell casts. Such casts are indicative of glomerulonephritis, with leakage of RBC's from glomeruli, or severe tubular damage. White blood cell casts are most typical for acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates inflammation of the kidney, because such casts will not form except in the kidney. When cellular casts remain in the nephron for some time before they are flushed into the bladder urine, the cells may degenerate to become a coarsely granular cast, later a finely granular cast, and ultimately, a waxy cast. Granular and waxy casts are be believed to derive from renal tubular cell casts. Broad casts are believed to emanate from damaged and dilated tubules and are therefore seen in end-stage chronic renal disease.   The so-called telescoped urinary sediment is one in which red cells, white cells, oval fat bodies, and all types of casts are found in more or less equal profusion. The conditions which may lead to a telescoped sediment are: 1) lupus nephritis 2) malignant hypertension 3) diabetic glomerulosclerosis, and 4) rapidly progressive glomerulonephritis. In end-stage kidney disease of any cause, the urinary sediment often becomes very scant because few remaining nephrons produce dilute urine. LEUKOCYTOSIS AND EXERCISE Hard muscular work is accompanied by a leucocytosis in normal individuals and trained athletes, the leucocytosis in football players often showing an increase of between 200% and 300%. The magnitude of leucocytosis is related to both the duration and the intensity of work. Excitement alone will not cause a leucocytosis. Intense exertion of short duration produces a lymphocytosis which is followed by a polynuclear stage if the work is continued for a long enough time. The average recovery curve exhibits no appreciable drop in leucocyte count during the two hours following a football game unless the player lies down immediately after leaving the field. The absolute lymphocyte count falls rapidly for an hour or more after the player leaves the game. The rapidity of the leucocyte changes, the evidence against leucocytolysis and the absence of an appreciable increase in the Schilling  - Torgau “band - form” cells all point toward a storage phenomenon. The bone marrow, spleen, liver, lungs, and organs of internal secretion must  be considered as possible reservoirs, although no definite statement can yet be made as to the relative importance of each. The fact that lactic acid, blood sugar, blood pressure, body temperature, and capillary dilation can be ruled out as separate variables directly related to leucocytosis in exercise points toward a stimulus perhaps more complicated than has yet been studied. Any explanation of leucocytosis in exercise involving only a simple physical mechanism cannot at present be considered adequate. The authors are indebted toL. J. Henderson, D. B. Dill, andT. K.  Richards for their cooperation and assistance in this work. INTRODUCTION  Exercise is the one of the many causes of hematuria (increased red blood cells excretion in the urine) (figure 1).   Exercise-induced hematuria can be defined as gross or microscopic hematuria that occurs after strenuous exercise and resolves with rest in individuals with no apparent underlying kidney or urinary tract pathology [1]. Issues related to exercise-induced hematuria in otherwise healthy individuals will be reviewed here. Exercise may also worsen hematuria in patients with underlying glomerular disease, such as IgA nephropathy [2,3]. The general evaluation of adults or children with hematuria is discussed separately. (See  Etiology and evaluation of   hematuria in adults  and  Evaluation of microscopic   hematuria in children  and  Evaluation of gross hematuria in   children .) ETIOLOGY AND PATHOGENESIS  Hematuria has been described after a variety of forms of exercise [1,4,5]. These include contact sports, such as football and boxing, and noncontact sports, such as long-distance (marathon or endurance) running [6-8], rowing, and swimming. Hematuria appears to be rare with cycling but has been described, even with stationary bike riding (eg, spinning) [9,10].   The frequency with which hematuria occurs with long-distance running was evaluated in a study of 45 male and female participants who competed in an ultra long-distance marathon [6]. After the race, 11 (24 percent) had hematuria. The hematuria disappeared within seven days. A similar incidence (18 percent) was noted in a report of 50 marathon runners who did not have hematuria on prerace samples obtained daily for three days Prevention   To prevent hematuria related to strenuous exercise, switch to a less-intense exercise program. In general, you can help to prevent other forms of hematuria by following a lifestyle that fosters a healthy urinary tract:    Stay well hydrated. Drink about eight glasses of fluid daily (more during hot weather).    Avoid smoking cigarettes, which are linked to urinary tract cancers. Sports hematuria.  Abarbanel J 1 , Benet AE, Lask D, Kimche D.  Author information Abstract Strenuous exercise makes extraordinary demands. The transition from rest to intensive physical activity can cause pathological changes in various organs, particularly in the urinary tract. Hematuria (microscopic or macroscopic) is one of the abnormalities commonly found after sports activity. This phenomenon can occur in noncontact sports (such as rowing, running and swimming) as well as in contact sports (boxing, football and so forth). The pathophysiology can be either traumatic or nontraumatic. Renal trauma and/or bladder injury due to repeated impact of the posterior bladder wall against the bladder base can cause vascular lesions and consequently hematuria. There are 2 mechanisms of nontraumatic injury. 1) Vasoconstriction of the splanchnic and renal vessels occurs during exercise in order that blood can be redistributed to the contracting skeletal muscles, thus causing hypoxic damage to the nephron. This results in increased glomerular permeability which would favor increased excretion of erythrocytes and protein into the urine. 2) A relatively more marked constriction of the efferent glomerular arterioli results in an increased filtration pressure, which favors increased excretion of protein and red blood cells into the urine. It must be noted that sports hematuria differs from other conditions that may cause reddish discoloration of the urine due to physical exercise, such as march hemoglobinuria and exercise myoglobinuria. In the latter 2 abnormalities there is excretion of hemoglobin and myoglobin molecules in the urine and not whole blood or intact red blood cells. Sports hematuria usually has a benign self-limited course. However, coexisting urinary tract pathological conditions should be excluded carefully.
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