Identification of a novel c-DNA overexpressed in Fanconi''s anemia fibroblasts partially homologous to a putative L-3-phosphoserine-phosphatase

Glycoprotein (G) of viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV) contains several neutralizing epitopes. However, recombinant G protein never matches intact viral particles for immunogenicity. DNA immunization offers the possibility to deliver the antigen through the cellular machinery, thus mimicking natural infection. We constructed pCDNA gVHS and pCDNA gIHN plasmids with the G gene of VHSV and IHNV under the control of the CMV promoter, and we tested the plasmids for the accurate G protein expression prior to their use in fish immunization. Following intramuscular injection to adult rainbow trout, plasmid DNA was found inside the muscle cells shortly after injection and was still present 45 days later. mRNA of the G protein was detected in muscle tissue extracts, and the G protein was found within muscle cells at the site of injection. This resulted in the synthesis of high levels of specific neutralizing and protective antibodies. Fish injected with pCDNA gVHS and pCDNA gIHN in combination responded similarly to fish receiving one recombinant plasmid. In addition to the elicitation of a strong humoral response, DNA immunization was able to activate specialized cells of the immune system as well as nonspecific defense mechanisms, since mRNAs of MHC class II and Mx were strongly activated at the site of injection.     

Cytogenetic abnormalities in patients with severe aplastic anemia

BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.     

Brain tumors with symptomatic onset in the first two years of life

Eighty children who in the first 2 years of life had signs and symptoms relating to a cerebral neoplasm were studied over an 18-year period (1970-1987), the mean follow-up being 8.2 years. In each case age at onset, clinical presentation, tumor location and pathological diagnosis, extent of surgical resection, postoperative mortality, adjuvant therapy length of survival and quality of life were assessed. Supratentorial tumors (59%) were more common than infratentorial. The most frequent clinical presenting feature (70%) was increased intracranial pressure. Sixty-three patients (79%) were operated on and in all of these cases a histological diagnosis was obtained. Astrocytomas (41%) and medulloblastomas (20%) were the most common oncotypes. Surgical mortality was 17.4% and the 5-year survival rate was 54%. Quality of life was assessed for all long-term surviving patients using a specifically designed protocol. Normal physical and intellectual performances were found in 46% of cases, and all together 75% of the patients had sufficient autonomy in daily life. The prognosis is more closely related to tumor location and type of treatment than to histological diagnosis or age at onset.     

Pituitary tumors in patients with secondary amenorrhea

A new semisynthesis of human insulin starting from porcine insulin is described. NalphaA1, NalphaB1-di-Boc-desoctapeptide-(B23-30)-insulin bearing 6 free carboxyl groups is coupled with the suitably protected human insulin-(B23-30)-octapeptide. The preferred reaction site is the carboxyl group of ArgB22. Side products are eliminated by extensive chromatographic purification.     

Blast-transformation reaction in patients with bone tumors

The authors have studied phytohemagglutinin stimulation of DNA synthesis in leucocytes cultures of the peripheral blood in patients with some malignant osteoplasms and benign tumors, and the influence of plasma factors on this process, as well. In most cases, lymphocytes of patients with malignant tumors were shown to have a considerably decreased, as compared with the control, level of blasttransformation. No such difference was found for leucocytes cultures of patients with benign tumors.     

Brain scanning in patients with recurrent breast cancer

Brain scans were performed on 116 patients with recurrent breast cancer. Seventy-eight of 79 (98%) asymptomatic patients with recurrent disease had negative brain scans. Eleven of 37 (30%) patients with central nervous system (CNS) symptoms had scans indicative of intracranial metastases. There was no difference in the distribution of extracranial metastaic disease in patients who had positive brain scans when compared with those who did not. Brain scaning is of value in detecting intracranial metastases in patients with CNS symptoms. Brain scanning seems unnecessary, however, in the staging of patients with recurrent breast cancer who have no CNS symptoms.     

Brain metastases in patients with differentiated thyroid carcinoma

We present a retrospective review of six patients who developed brain metastases in our series of 649 with differentiated thyroid carcinoma seen at the Royal Marsden Hospital between 1936 and 1991. Prognosis was poor, with survival 1-19 months from the diagnosis of brain metastases in five patients. One patient remains alive at 18 months. A dosimetric approach may help to individualize and optimize treatment.     

Percutaneous endoscopic gastrostomy in patients with ENT tumors

Oral food intake in patients with obstructing pharyngeal and esophageal carcinomas is commonly insufficient because of tumor-induced dysphagia which gives rise to cachexia unless treated. While entailing an unfavorable prognosis, malnutrition is often a therapy-limiting factor. Tube feeding with liquid formula diets currently offers the most efficient and least-risky approach to long-term use and is best adopted even at a pretreatment stage irrespective of the tumor therapy intended. A feeding tube placed by a percutaneous endoscopically controlled gastrostomy (PEG) increasingly offers an alternative to a nasogastric tube. After using diaphanoscopy, the stomach is punctured from outside under local anesthesia and a feeding tube inserted by means of a retrograde thread or a direct puncture method. A modification of the direct puncture method has been preferred at the Magdeburg University E.N.T. Department. The tube is held in place by thermally activated helical winding of a gastric tube end (using a memory-retaining helix). During the 1991-1996 period 415 patients with obstructing carcinomas of the upper digestive tract were treated with a feeding tube. No fatal complications were observed. Severe complications (peritonitis) occurred in three patients. In 160 patients with PEG the following parameters were recorded: weight-to-size index, body mass index, degree of dysphagia, nutrition status, lymphocyte count, total serum protein and patients' compliance to PEG. The enteral nutrition therapy used was indicated in all of the patients treated with advanced carcinomas of the head and neck. In 81% of the patients the compliance to PEG was positive. Findings demonstrated that long-term intestinal nutrition via PEG was a safe and effective form of treatment. Inserting the tube by the direct puncture method was advantageous for patients with carcinomas in the upper digestive tract as only few mechanical alterations take place along tumorous tissues following PEG while contamination with bacteria and neoplastic cells from the tumor region into the abdomen are precluded.     

Prevalence of monosymptomatic celiac disease in patients with iron deficiency anemia

A prospective study of the prevalence of monosymptomatic celiac disease presented as ferropenic anemia in patients admitted for study such complication of was carried out. All the patients were evaluated by gastroscopy and biopsy of the distal duodenal segment, regardless of endoscopic appearance. Patients presenting an endoscopic lesion clearly suggestive as the origin of the chronic bleeding were excluded from the study. The prevalence of celiac disease, the only manifestation of which was ferropenic anemia, was 3.3% in this series. What is important to note in this study is the importance of duodenal biopsy in the study of ferropenic anemia, with the aim of avoiding diagnostic delay of a possible monosymptomatic celiac disease as the cause of the anemia.     

Treatment of anemia in patients with chronic renal insufficiency with recombinant human erythropoietin

The discovery of recombinant human erythropoietin has enabled treatment of anaemia in patients whose anaemia was primarily caused by the lack of erythropoietin. This agent was most widely used in the treatment of anaemia in chronic renal failure patients. Non-regulated hypertension is considered to be the only absolute contraindication for recombinant human erythropoietin application, but thrombocytosis, predisposition to thromboses of arterio-venous fistulae, and convulsions are regarded as relative contraindications. Recombinant human erythropoietin may be administered intravenously, but the subcutaneous route is considered more rational. The treatment is initiated by low doses with gradual dose increase, what enables gradual anaemia correction and prevents the appearance of adverse effects. Haemoglobin level of around 100 g/l is considered the target haemoglobin level. The majority of patients respond well to treatment by human recombinant erythropoietin and the absence of anaemia improvement may be the result of iron deficiency, occult haemorrhages, chronic infection, inadequate dialysis, secondary hyperparathyroidism, aluminium intoxication. Anaemia improvement during the treatment with recombinant erythropoietin leads to the improvement of function of most organs and the quality of life in general as well as avoidance of blood transfusions and their adverse effects. The most frequent adverse effect of recombinant erythropoietin is the development of iron deficiency or hypertension aggravation.     

Enucleation procedures in patients with multiple hereditary renal tumors

Parenchymal sparing surgery is frequently appropriate in patients with familial renal tumors detected through the screening of affected kindreds. An enucleation technique for the rapid removal and hemostasis of multiple small renal tumors in patients with hereditary renal cancers is described herein. This technique facilitates the removal of multiple small superficial renal tumors, usually without hypothermia.     

Treatment of febrile neutropenia in patients with solid tumors

BACKGROUND: Febrile neutropenia (FN) is one of the most serious complications of anti-tumourous treatment calling for early diagnosis and intensive treatment. The objective of the trial was to recommend a standard procedure for the treatment of febrile neutropenia at their Oncological Clinic, based on analyses of attacks of febrile neutropenia and the current microbial situation. METHODS AND RESULTS: In 1995-1997 in 30 patients (24 women, 6 men) 39 attacks of febrile neutropenia were treated. The age distribution of patients was within the range of 20-68 years, the mean age being 50 years. In the group patients with breast cancer predominated (14), soft tissue sarcomas (4), colorectal carcinoma (3), other diagnoses participated with 9 episodes. The analysis of the microbial situation was based on cultivation findings made in patients with attacks of FN. For empirical treatment of FN the authors use at combined treatment piperacillin-gentamicin or sultamicillin-cefpodoxim/or ciprofloxacin. If empirical treatment fails, therapy is based on the results of cultivation and the patient's clinical condition. Growth factors are indicated for treatment only in FN complicated by mycotic infection, inflammatory pulmonary infiltrates or cardiopulmonary failure. CONCLUSIONS: The standard procedure in the treatment of FN should be broad spectrum bactericidial antibiotics. The use of growth factors is reserved for complicated episodes of FN.     

De novo tumors in adult patients with hepatic transplant

The incidence of de novo neoplasms was analyzed in 340 patients with liver transplantation who survived more than 2 months post transplantation. Sixteen (4.7%) patients developed a new tumor following transplantation. The most frequent tumor observed was a lymphoma which was detected in four patients (1.2%). In three of the four lymphomas histologic diagnosis of non Hodgkin phenotype B lymphoma was confirmed and in three patients the central nervous system was involved. The remaining tumors consisted of two cases of adenocarcinoma of the colon, papillary carcinoma of the urinary bladder and ductal breast cancer (0.6%) for each of these tumors and one case of cervical cancer, adenocarcinoma of the small intestine, Kaposi sarcoma, laryngeal carcinoma, pharyngeal carcinoma and malignant melanoma (0.3% for each tumor). None of the patients developed more than one tumor. The mean time to the appearance of the tumors was 28 months (range: 3-52 months). These results suggest that de novo neoplasms in patients with liver transplantation are relatively frequent, particularly lymphoma.     

The effect of transfusion on cardiac function in patients with chronic anemia

BACKGROUND: The deteriorating cardiac function of patients with chronic anemia may be improved with transfusion. The effect of transfusion on cardiac function was evaluated in patients with chronic anemia. STUDY DESIGN AND METHODS: In a prospective study, ejection fraction (EF) was determined before and after transfusion in 41 patients with chronic anemia. The results were compared and analyzed. RESULTS: The volume of red cells transfused and the levels of pretransfusion hemoglobin, hematocrit, and red cell, white cell, and platelet counts did not affect the posttransfusion EF, whereas the pretransfusion EF of the right or left ventricle inversely affected the posttransfusion change in EF in the respective ventricle (p < 0.001 and r = -0.5022; p = 0.01 and -0.3917, respectively). There was no significant difference in the change in EF in the right and left ventricles. CONCLUSION: Transfusion produced little immediate effect on cardiac function, but did change the EF to an extent that aided cardiac function in chronic anemia patients. The pretransfusion EF itself, but not the degree of anemia or volume of red cells transfused, affected the posttransfusion change in EF.