Multiple myeloma.

Multiple myeloma occurs in over 2000 new patients in England and Wales each year. It presents most frequently as bone pain and patients tend to become dehydrated and may develop renal failure. No available treatment is curative, but about two thirds of patients achieve a stable response with low dose combination chemotherapy. Combination chemotherapy including doxorubicin and carmustine with the alkylating agents cyclophosphamide and melphalan achieve a higher stable response rate than conventional treatment with melphalan and prednisone without additional haematological toxicity. These responses are associated with loss of bone pain and patients remain symptom free for months without further treatment. Relapse occurs on average in a little under two years and, though second responses are frequently obtained, the disease eventually becomes refractory. This paper looks at who should be treated and the benefits that may be expected from the treatments available.     

Multiple myeloma/hypercalcemia

Multiple myeloma, a cancer of plasma cells, is associated with excessive tumor-induced, osteoclast-mediated bone destruction. Hypercalcemia remains the most frequent metabolic complication of myeloma in patients, and excessive osteolysis plays a major contributory role in its pathogenesis. The clinical presentation of hypercalcemia in patients varies depending on the level of ionized calcium; it can be life threatening, as in the case of hypercalcemic crisis, requiring immediate medical treatment to prevent death. During the past few years there have been exciting developments in our understanding of the pathogenesis of myeloma bone disease; in particular, key mediators of the osteoclastic bone resorption in myeloma have been identified, including receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage inflammatory protein-1alpha. There is also increasing evidence that Dickkopf 1, which has been shown to be over-expressed in myeloma patients, is also a potent stimulator of osteoclast formation and activity. Importantly, the available data suggest that RANKL is the final common mediator of osteoclastic bone resorption, irrespective of the upstream initiator molecule. This brief review presents an overview of the roles played by these mediators in inducing osteolysis in myeloma bone disease, and it discusses targeting RANKL as a potential new treatment strategy in myeloma bone disease and myeloma-associated hypercalcemia.     

Transurethral prostatectomies; a review of 560 cases

Spontaneous pneumoperitoneum most often occurs following ruptured peptic ulcer. In 80 to 85 per cent of cases of perforated ulcers, free intraperitoneal air is demonstrable. There have been reported three cases in which air was present without demonstrable cause, without peritoneal irritation or peritonitis. This presentation adds a fourth. Examination of a patient with acute disease of the abdomen should include not only a roentgenogram with the patient supine but films made in the left lateral decubitus position and/or upright position to demonstrate free air. The radiologist should be ready and willing to consult with the surgeon at the time of examination. Attention is called to a sign described recently by Rigler in supine films, namely, the visibility of both the inside and the outside of the intestinal lumen. Another sign in the supine film, namely the contrast of air against the peritoneal reflections, is described.     

多发性骨髓瘤与白细胞介素-6

白细胞介素-6是多发性骨髓瘤(multiple myeloma,MM)瘤细胞生长和生存的关键因子,也是MM患者发病的主要因子。IL-6/IL-6R系统通过不同通路影响多发性骨髓瘤瘤细胞生长并导致患者骨损害、类风湿性关节炎等一系列并发症。针对IL-6/IL-6R系统的治疗方法将给MM的治疗带来重大的进展。     

Hodgkin's disease; a clinical-pathological review of 150 cases

One hundred and fifty cases of Hodgkin's disease were analyzed in an effort to detect significant clinical-pathological correlations and to elucidate any possible factors of prognostic or etiological importance.A relatively long survival for patients with Hodgkin's paragranuloma was not noted in this series. Instead the survival rate among them was closely parallel to that of patients with classical granuloma. Hodgkin's sarcoma is a more malignant disease with a patient survival rate not more than half that of patients with the granuloma variety. It is not necessarily a disease of older age groups. Great caution must be exercised to avoid including non-Hodgkin's disease tumors under the heading of Hodgkin's sarcoma or paragranuloma. The series reported corresponds with many other reported series of Hodgkin's disease as regards greater incidence in males and longer survival in females. In this series the cases in patients under the age of 15 were all in males. The predominance of initial enlargement of the cervical nodes was again noted in this series, as was the high proportion of negative reaction to tuberculin tests. The incidence of tuberculous lesions in patients who died of Hodgkin's disease was only slightly greater than in those who died of other lymphoma. Site of origin of the disease apparently affects survival time. There was statistical evidence that gonadal activity might influence the equilibrium of the disease. Lymph node bacteriological cultures were not remarkable. Brucella organisms were absent. Fertile egg passages for detecting possible viral agents revealed increased egg mortality and cutaneous sensitivity reactions to the harvested amniotic fluid.     

Therapeutic donor insemination; a review of 440 cases

Of 399 patients inseminated therapeutically with the semen of a donor, 303 became pregnant, the great majority of them within six months of the time inseminations were begun. The average number of inseminations was 6.2 and the average number of menstrual cycles over which they were carried out was 3.55. The greatest number of pregnancies occurred between the twelfth and the fifteenth day of the menstrual cycle. Seven patients had four pregnancies by this method, 17 had three and 59 had two. Emotional problems related to children of artificial insemination were far fewer than those associated with adoption.     

Carcinoma of the thyroid gland; a review of 106 cases

In a review of 106 cases of carcinoma of the thyroid gland, it was noted that a solitary thyroid nodule is the most outstanding single physical sign in this disease. It should be investigated by biopsy of a specimen removed at operation. Patients and physicians were sometimes guilty of delay in this regard. Papillary carcinoma involved multiple foci within the gland in at least half of the cases and there was a high incidence of regional lymph node metastasis associated with this type. Doubt was cast on conclusions by other investigators that carcinoma of the thyroid rarely is lethal in patients less than 40 years of age.     

Decidual reaction of the cervix; a review of 27 cases

Decidual reaction of the cervix is a benign growth produced by the hormones of pregnancy. These reactions or changes in the cervix are present in about 20 per cent of normal pregnant women. They may look like cancer but are not cancer. They are benign lesions. Bleeding is a common symptom and may occur at any stage of pregnancy. The presence of decidual reaction does not predispose to spontaneous miscarriage. In most cases no treatment is required; in a few light cauterization may be needed to control bleeding. Any suspicious lesion should be biopsied to rule out malignancy. By microscopic examination any experienced pathologist can differentiate a decidual reaction from cancer. The consensus of opinion is to let the pregnant woman deliver, normally, with this benign lesion, for it disappears after the baby is born. If cancer is found during pregnancy, it should be actively treated.     

Tetanus in California; epidemiology and a review of 232 cases

A study was made of records of the 232 reported cases of tetanus in California, from 1953 through 1958. Cases occurred in 30 of California's 58 counties. Two-thirds of the patients lived in suburban and urban areas. Two-thirds of the cases occurred in persons over the age of 20 years. The incidence was twice as high in males as in females. Forty-seven per cent of the patients died, with the highest death rates being in persons over the age of 40 years.Sixty-three per cent of the injuries associated with these 232 cases occurred in the home environment and 17 per cent at the place of employment.Ninety-one per cent of the patients had never been immunized with tetanus toxoid, or if they had been immunized, had not received the booster injections necessary to maintain effective immunity. Nine per cent gave a history of having had one or more injections of tetanus toxoid within five years.     

Multiple myeloma superimposed on chronic myelocytic leukemia

A 65-year-old woman with chronic myelocytic leukemia and multiple myeloma is described. Cases of acute leukemia complicating multiple myeloma have been reported in recent years, but to our knowledge this is the first case where multiple myeloma developed in a patient who had pre-existing chronic myelocytic leukemia.     

Translocation (3;21)(q26;q22) in secondary leukemia. Report of two cases and literature review.

The authors report two cases of secondary myelodysplasia and acute myeloid leukemia with t(3;21)(q26.3;q22) as the only cytogenetic abnormality in neoplastic bone marrow. This translocation was identified as a rare, recurring, non-random aberration in chronic myeloid leukemia less than five years ago and in secondary acute myeloid leukemia and myelodysplasia in 1990. The known and suspected cases in the literature are reviewed.     

Mumps meningoencephalitis; a clinical review of 119 cases with one death

Mumps is one of the most common viruses to affect the central nervous system and should be given primary consideration in the differential diagnosis of aseptic meningitis. Many cases of numps infection do not involve the salivary glands. The course of numps meningoencephalitis is usually benign, with fever and signs of meningeal irritation lasting less than five days. The findings in the cerebrospinal fluid are usually distinctive, with leukocyte content greater than 200 per milliliter, of which 80 per cent or more are lymphocytes. Sequelae, even of a minor nature, are rare. Death is extremely rare in recorded literature. A fatal case of numps meningoencephalitis is described herein.     

Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.