Malignant bone pain: pathophysiology and treatment

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carcinoma, including hepatomegaly with variable-sized foci and neoplastic nodules. Severe damage was observed in the rats treated with AAF and NaNO2. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c-Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO2. These data confirmed that the strengthening of AAF-induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc.     

Malignant pleural mesothelioma in general practice; complex pain problems

In three patients, men aged 67, 57 and 69 years, malignant pleural mesothelioma was diagnosed. All three had worked as coal miners and were presented with thoracic pain. They were among seven cases of malignant pleural mesothelioma diagnosed in a period of five years in one suburban general practice (adherence: 5600 patients) in the former mining area in the province of Limburg. The terminal phase of the disease was characterized by intractable pain. High doses of opioids and adjuvants were necessary to achieve acceptable pain relief. It is suggested that step one of the 'analgesic ladder for cancer pain management' of the WHO (non-opioids) should be followed soon by step three (strong opioids). Because the incidence of pleural mesothelioma is not yet decreasing, it is important to know that pain management remains a serious problem.     

Overview of nuclides for bone pain palliation

Currently, six distinct types of hepatitis virus have been identified: A, B, C, D, E, and G. Hepatitis A virus infection does not cause a chronic carrier state, and perinatal transmission is extremely uncommon. Hepatitis B can be transmitted perinatally, but immunization of the newborn with hepatitis B immune globulin and hepatitis B vaccine markedly reduces the risk of neonatal infection. Hepatitis D virus is dependent on coinfection with the hepatitis B virus for replication. Immunoprophylaxis against hepatitis B also is effective against hepatitis D. Hepatitis C virus is primarily transmitted by the parenteral route and is particularly likely to cause chronic liver disease. Perinatal transmission of hepatitis C principally occurs in women who have high titers of HCV-RNA or who are coinfected with human immunodeficiency virus. At this time, no immunoprophylaxis for hepatitis C is available. Hepatitis G, a recently described organism, is related to hepatitis C. Its clinical significance remains undetermined. Hepatitis E is transmitted in a manner similar to hepatitis A. Perinatal transmission is unusual, but maternal disease is often severe.     

Use of calcitonin in treatment of bone pain

The studies were carried out assessing the effect of calcitonin in the treatment of bone pain. In the years 1990-1992 43 patients were studied. Pain intensity scale was used with evaluation by doctor and patient.     

Bisphosphonates for controlling pain from metastatic bone disease

The rationale for and efficacy of bisphosphonates for pain due to cancer that has metastasized to bone are reviewed. Typical strategies for controlling metastatic bone pain have consisted of opioids, nonsteroidal anti-inflammatory drugs, surgery to stabilize bone, cancer chemotherapy, radiation therapy, and radiopharmaceuticals. Cancer metastasis to bone can produce pain through the release of prostaglandins, bradykinin, substance P, and histamine; growth of tumor into surrounding tissue; stretching of the periosteum; and pathological fractures. It has been suggested that bisphosphonates can benefit these patients by decreasing the amount of pain or decreasing analgesic requirements. Bisphosphonates bind to hydroxyapatite crystals, making it more difficult for osteoclasts to recognize exposed unmineralized bone surfaces, and are directly toxic to osteoclasts. Etidronate disodium, pamidronate disodium, clodronate disodium, and alendronate sodium are bisphosphonates that have been studied in patients with painful bone metastases. Although each of these has shown at least some benefit, the most promising agent appears to be pamidronate, especially the i.v. formulation given monthly. Although oral formulations of this agent have been studied, poor bioavailability and adverse effects limit their usefulness. Adverse effects of bisphosphonates include GI reactions, impairment of renal function, anemia, and electrolyte abnormalities. Bisphosphonates are of some benefit in relieving metastatic bone pain, but the exact role, agent, route, and duration are issues that need further study.     

Malignant peripheral nerve sheath tumor of bone in children and adolescents

In situ vascular endothelium is characterized by many cytoplasmic vesicles (caveolae) and vacuoles. In venules these are organized into prominent clusters called vesiculo-vacuolar organelles or VVOs. VVOs provide an important pathway for plasma protein extravasation in response to vasoactive mediators. In contrast, cultured endothelial cells isolated from many sources lack VVOs and generally have few caveolae. Our goal was to preserve VVOs in cultured endothelium. Bovine adrenal microvascular endothelial cells (BCEs) cultured on floating Matrigel-collagen Type I gels with vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) exhibited typical VVOs by electron microscopy. Both in vivo and in culture VVOs were caveolin-positive by immunoelectron microscopy. On the basis of caveolin immunostaining, VVOs could also be detected by light (confocal) microscopy. When BCEs were cultured without VPF/VEGF, caveolin staining was finely punctate and electron microscopy confirmed the near absence of VVOs. BCE VVOs were sensitive to N-ethylmaleimide. Other types of endothelium cultured on Matrigel-collagen gels with or without VPF/VEGF exhibited few caveolae and no VVOs. Therefore, preservation of VVOs in cultured endothelium required a specific combination of endothelial cells (BCEs), surface matrix (Matrigel-collagen), and growth factor (VPF/VEGF). These endothelial cells should be useful for in vitro studies of trans-endothelial transport.     

Causes and treatment of bone pain of malignant origin

Pain relief has been one of the oldest and most important duties of the physician. There has been little change with regard to this obligation of all caregivers. One-third of patients with advanced cancer will develop clinically relevant skeletal metastases and chronic pain during the course of their disease. All physicians involved in the treatment of cancer patients should know the basic principles of pain treatment. These are described in the following article with special regard to bone pain of malignant origin. Correct assessment of pain intensity and frequency, as well as of the probable causes of pain, and the administration of adequate analgesic treatment should achieve satisfactory results in the vast majority of patients. Every physician should obtain detailed knowledge of the indications and adequate administration of pain-killing therapy as well as possible adverse effects and their successful treatment. It is important in particular to concentrate on a few nonsteroidal anti-inflammatory drugs (NSAIDs) as well as opiates. Knowledge of adequate doses, maximal recommended daily doses, pharmacological properties, important adverse effects and interactions is essential for success in the daily routine. Only by selecting 2 or 3 drugs from each step in the analgesic ladder (WHO) will the nonspecialised physician obtain sufficient experience for optimal analgesia. Physicians should also not hesitate to contact other specialists (medical oncologists, radiotherapists, neurosurgeons, anaesthesiologists and others) in order to maximise benefit for an individual patient.     

The effect of bone drilling on pain in gonarthrosis

Problem doctors are a heterogeneous group, and it is sometimes difficult to determine whether a doctor is incompetent or simply makes repeated mistakes hard to avoid completely under pressure of the clinical work-load. The profession has a small repertoire of informal methods for dealing with situations where a colleague has become a problem. An interview study, carried out in Britain and Sweden, revealed the approaches most commonly used. It also showed that the problem doctor's colleagues often hesitate too long in taking the informal approach that the problem is much more difficult to resolve by the time department heads and administrators become involved.     

Leg bone pain syndrome due to cyclosporine in a renal transplant patient

A leg bone pain syndrome of unclear etiology has been recently described in renal transplant patients receiving cyclosporine A. Herein we report a 54-year-old woman treated with cyclosporine A (CsA), corticosteroids and azathioprine who developed two months after renal transplantation severe symmetric pain with periarticular soft tissue swelling in the knees and metatarsophalangeal joints. Scintigraphy showed periarticular radionuclide activity. Clinical onset was associated with both the high dosage and with the plasma levels of CsA. Symptoms improved when the dosage of CsA was reduced and the plasma levels declined to less than 150 ng/ml.     

Malignant melanoma

Family physicians should be aware of the early signs of malignant melanoma, as well as measures that can be taken to prevent the disease. Etiologic factors for melanoma include sunburns, particularly those occurring early in life, giant congenital nevi, dysplastic nevi and the presence of numerous nevi. The four major subtypes of melanoma are lentigo maligna, superficial spreading melanoma, acral lentiginous melanoma and nodular melanoma. Diagnosis is based on excisional, incisional or punch biopsy. The crude five-year survival rate for malignant melanoma is 81 percent, but survival depends on stage of disease, anatomic site, the patient's age and sex, histologic factors and clinical subtype. Surgical excision is the usual treatment for primary melanoma. Surgery, radiation therapy and chemotherapy are used in the management of metastatic disease, but the prognosis following the development of metastases remains poor. Family physicians can affect survival rates by improving early detection, promoting patient awareness and self-examination, and encouraging regular physical examination of patients who are at increased risk of melanoma.     

Malignant endometriosis

Presentation of two case reports of severe and multiple urinary tract involvement by endometriosis due to the low frequency of this disorder. Although this is a benign condition, the term "malignant" endometriosis has been used because of the significant consequences it may have for the urinary tract, since it may compromise both excretory systems with a likely vital risk.