A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma.

The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV). It is expressed in Reed-Sternberg cells of Hodgkin's disease (HD), tumor cells of nasopharyngeal carcinoma (NPC), and immunoblasts of angioimmunoblastic lymphadenopathy (AILD). A particular LMP1 deletion mutant was recently identified in NPC and clinically and histologically aggressive HD. We studied two patients with AILD that subsequently progressed into immunoblastic lymphoma (IBL) in order to investigate whether the LMP1 deletion mutant was implicated in progression of AILD into IBL. Immunohistology and in situ hybridization were performed on diagnostic biopsies. DNA extracted from fresh frozen material was used for rearrangement studies and polymerase chain reaction (PCR) based amplification and sequencing of portions of the LMP1 gene. Immunohistochemistry revealed B cell origin of both cases of IBL. In the first patient clonal rearrangement of the immunoglobulin heavy-chain gene was present in IBL but not in AILD. In this patient, scattered immunoblasts of AILD and numerous tumor cells of B-IBL were shown to contain EBV transcripts (EBER1) and to express LMP1. Sequence analysis of the LMP1 gene from AILD and IBL in the first, and from IBL in the second patient, revealed identical deletions and point mutations. This LMP1 deletion mutant is identical to those which have been reported in HD and NPC. Its association with evolution of AILD into B-IBL, aggressive HD and NPC, suggests that this particular mutant is more widespread than originally thought and is clinically relevant.

Diagnosis and treatment of intravascular lymphomatosis.

OBJECTIVE: To describe a patient with unusually good outcome of a rare, high-grade lymphoma that often involves the nervous system. DESIGN: Case report. SETTING: University hospital. CASE: A 70-year-old pharmacist first presented with meningoencephalitislike symptoms and 6 months later with acute confusional state followed by complex partial status epilepticus. Diagnosis of intravascular lymphomatosis was made using detection and biopsy of a bilateral adrenal tumor. MAIN OUTCOME AND RESULTS: Polychemotherapy consisting of CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) led to complete remission. The patient's survival time currently exceeds 21/2 years. CONCLUSIONS: The possibility of intravascular lymphomatosis should be considered in adult patients with unclear meningoencephalitic syndrome, acute confusional state, dementia, or other unexplained neurologic conditions with signs of a systemic disease. In intravascular lymphomatosis, as in other high-grade non-Hodgkin lymphomas, CHOP polychemotherapy should be the standard treatment.

Complex IgA gammopathy in Gaucher's disease.

A 55-year-old Jewish patient was simultaneously diagnosed as having Gaucher's disease and IgA multiple myeloma. Serum protein electrophoresis and immunoelectrophoresis showed two different IgA kappa type monoclonal spikes. After four years of observation, a rapid fatal course of disease developed together with expression of J chain protein and an additional IgA lambda paraprotein. Although dysproteinaemias and multiple myeloma have occasionally been reported in Gaucher's patients, such a complex gammopathy has to the best of our knowledge not yet been described.

Fatal vascular leak syndrome with extensive hemorrhage, peripheral neuropathy and reactive erythrophagocytosis: an unusual complication of recombinant IL-3 therapy.

A 39-year-old patient with severe aplastic anemia (AA), resistant to therapy, received recombinant human IL-3 (rhIL-3) on a phase I/II trial. During treatment she developed disseminated skin lesions, suggestive of vasculitis, and severe progressive peripheral neuropathy culminating in complete paralysis. She died 25 days after beginning treatment from profuse bleeding. On autopsy, evidence of vascular leaks with widespread bleeding and extensive hemorrhagic involvement of peripheral nerves was found. An additional feature was massive reactive erythrophagocytosis in lymph nodes, spleen and bone marrow. The coincidence between rhIL-3 administration and the dramatic events suggest a causal relation. As a possible pathogenic mechanism, an rhIL-3 induced excessive stimulation of macrophages and production of secondary cytokines such as tumor necrosis factor (TNF) is suggested. TNF is considered as a major factor in the development of both a vascular leak and reactive erythrophagocytosis. This case report can be regarded as an example of the possible unusual pathologic phenomena we may expect to see in the near future with increasing use of growth factors.

Progressive cutaneous herpes simplex infection in acute myeloblastic leukemia. Successful treatment with interferon and cytarabine.

A patient had acute myeloblastic leukemia and extensive progressive cutaneous herpes simplex virus infection. Complete and rapid healing of skin lesions with remission of the leukemia occurred during 15 days of therapy with human leukocyte interferon and minimal doses of cytarabine hydrochloride. Pharmacokinetic studies showed that the patient had a defective antiviral interferon response, which was effectively corrected by treatment with interferon alpha. This may help to explain the dramatic response of both conditions to therapy.

Enhanced urinary trypsin inhibitory activity in gentamicin-induced nephrotoxicity in rats.

We delineated in rats, the relationship between trypsin inhibitory activity in the urine and the nephrotoxic effects of gentamicin, eg, proteinuria and deterioration of glomerular filtration rate (GFR), measured by creatinine clearance. Gentamicin, 70 mg/kg per day, was injected intraperitoneally for 6-10 successive days. Serum and urine gentamicin levels were determined by a microbiological test. Trypsin inhibitory activity was assayed by the casein digestion method. The results showed a steady increase in urinary trypsin inhibitory activity starting from the fourth injection day. The increased levels of urinary trypsin inhibitory activity were associated with increased levels of urinary gentamicin excretion (r = 0.36, p less than 0.02, n = 50 after the fourth injection day), and were significantly higher than in control groups (p less than 0.001). The urinary trypsin inhibitory activity was inversely correlated with the GFR (r = -0.45, p less than 0.01, after the second injection day). The serum trypsin inhibitory activity remained unchanged throughout the study period in all groups. These data suggest that increased urinary trypsin inhibitory activity may be involved in the pathogenesis of gentamicin-induced nephrotoxicity.

Soft tissue response to textured silicone implants in an animal experiment.

In a study on rats to assess soft tissue response to textured silicone implants, ellipsoid 15 x 20 mm pieces from the bag of a Biocell breast prosthesis were implanted under the dorsal skin. Histological examinations including immunohistochemical detection of myofibroblasts were made 2 weeks and 1, 3, 6, and 8 months after implantation (12 specimens for each time interval). On the smooth side of the implant, which served as a control, the thin connective tissue capsule characteristically seen with silicone elastomer implants developed within a month. Myofibroblasts were present after the first month and appeared to reach a peak 3 months after implantation, after which they showed marked regression. On the textured side of the implant, villous processes were a characteristic feature of the capsules; originating in a common basal layer, they penetrated into the cavities of the implant. Collagen deposits and myofibroblasts only became more evident during the third month after implantation; they were limited to the common basal layer of the capsule, though foreign body reaction persisted in the villous processes until the end of the experiment. The experimental study, limited to an 8-month period after implantation, showed that texturing of the implant surface prevents compact capsule development and considerably delays or inhibits the maturation process.

Massive atheromatous emboli to both kidneys: a fatal complication following aortic surgery.

A patient with severe and diffuse ulcerative atherosclerotic arterial disease developed acute renal failure and anuria during insertion of an aortobifemoral graft. Postoperative septicemia, with Pseudomonas aeruginosa and Streptococcus fecalis, led to a deterioration in his condition and death. At autopsy the Dacron bifurcation graft showed no sign of infection, but massive atheromatous emboli of recent origin were found in both kidneys. We suggest using an extra-anatomic approach in reconstructive surgery for occlusive disease of the abdominal aorta in patients with ulcerative atheroma.

Cytomegalovirus-infected cells in a pleural effusion from an acquired immunodeficiency syndrome patient. A case report.

Cells with typical cytomegalovirus (CMV) inclusion bodies were found in smears of a pleural effusion from a 51-year-old acquired immunodeficiency syndrome patient. He suffered from severe, generalized CMV infection and Pneumocystis carinii pneumonia complicated by recurrent pneumothorax. CMV infection was proven by a positive immunohistochemical reaction. Cytologic demonstration of CMV-infected cells in a pleural effusion has not been reported before to the best of our knowledge.

Carcinocythemia. Report of two cases, one simulating a Burkitt lymphoma.

Carcinocythemia is a rare complication of metastatic carcinoma, characterized by the presence of carcinoma cells in the peripheral blood, which may mimic acute leukemia. Two cases are reported in which the patients developed carcinocythemia several years after being treated for carcinoma of the breast. Cytologic examination of peripheral blood smears in both cases showed the presence of numerous large abnormal cells; in one case the cells simulated those of a Burkitt lymphoma. Cytochemical and/or immunologic marker studies ruled out a hematopoietic origin of the malignant cells in both cases and confirmed a diagnosis of carcinocythemia. The rapidly fatal outcome observed in these two cases was in accordance with the poor prognosis usually encountered with this rare phenomenon.

Telepathology on the Solomon Islands--two years' experience with a hybrid Web- and email-based telepathology system.

The National Referral Hospital in Honiara, Solomon Islands, has used an Internet-based system in Switzerland for telepathology consultations since September 2001. Due to the limited bandwidth of Internet connections on the Solomon Islands, an email interface was developed that allows users in Honiara to submit cases and receive reports by email. At the other end, consultants can use a more sophisticated Web-based interface that allows discussion of cases among an expert panel. The result is a hybrid email- and Web-based telepathology system. Over two years, 333 consultations were performed, in which 94% of cases could be diagnosed by a remote pathologist. A computer-assisted 'virtual institute' of pathologists was established. This form of organization helped to reduce the median time from submission of the request to a report from 28 h to 8.5 h for a preliminary diagnosis and 13 h for a final report. A final report was possible in 77% of all submitted cases.

Decreased Cellularity and Hemosiderin of the Bone Marrow in Healthy and Overtrained Competitive Distance Runners.

In brief: Fourteen healthy and seven overtrained competitive distance runners were studied to investigate the frequency and significance of decreased bone marrow cellularity (BMC) and bone marrow hemosiderin (BMH) and the relationship between BMC, BMH, hemoglobin, and serum ferritin levels. Bone marrow hypocellularity or mild hypocellularity was found in 54% of the healthy male runners. Hypocellular marrow was found in 66% of the overtrained male runners. Absence or severe reduction of BMH granules was found in all runners. The mean hemoglobin and serum ferritin values were normal but somewhat lower than those of a control group. There may be a direct relationship between decreased BMC and years of running.

[T-cell lymphoma].

8 patients with lymphoproliferative disorders of T-cell origin were diagnosed during the years 1985-1987. They included 2 cases of so-called Lennert's lymphoma, 1 case of T-cell lymphoma simulating malignant histiocytosis and 1 case of T-cell lymphatic lymphoma with splenic T-cell lymphoma which survived 10 years. The other cases presented with peripheral T-cell lymphomas. Immunologic typing of malignant lymphomas with cell suspensions is of diagnostic value.

Bone marrow examination for primary diagnosis and follow-up in patients with lymphoproliferative disorders. An overview with emphasize on bone marrow histology.

The aim of his overview is to provide some insight into the manifold applications of bone marrow examination in lymphoproliferative disease. Having a large selection of methods any clinician working in this field should be familiar with the diagnostic relevance of each method for a given diagnostic problem. The choice of the appropriate investigations will warrant a correct diagnosis and helps to lower health expenses. Because of the multiplicity of the methods, often performed at different institutions, a lot of confusion can be caused by conflicting interpretation of isolated results. A diagnosis should never be based on isolated findings such as immunophenotyping or demonstration of a clonal population. Results of various investigations are to be integrated into a final diagnostic concept, which will be the basis for therapeutic decisions.

Predisposing factors in adverse reactions to drugs.

Predisposing factors were sought in 118 patients who developed adverse drug reactions in hospital. Significantly more patients of 60 years and over, and more women than men, developed adverse drug reactions. Patients with reactions had more drugs before the development of the reaction than patients who did not develop reactions. A previous adverse drug reaction and a history of allergic disease were significant factors, while a history of jaundice or the presence of diabetes mellitus and renal disease was not.

Admissions to hospital due to drugs.

In a survey of adverse drug reactions in wards of two Belfast hospitals for 52 weeks in 1965-6, 2.9% of 1,268 patients seen were admitted to hospital because of adverse reactions to drugs taken for therapeutic reasons and 2.1% were admitted because of self-poisoning. Patients admitted because of adverse drug reactions were older than those admitted because of self-poisoning and stayed in hospital longer. Among the drugs which caused the adverse reactions were digitalis preparations, antibiotics, corticosteroids, anticoagulants, analgesics, and tranquillizers. Hypersensitivity and side-effect types of reactions were the most common. Barbiturates were the most frequently used drugs in suicidal attempts.