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Clinical study of recombinant DNA-produced leukocyte interferon (clone A) in a intermittent schedule in cancer patients.

The effects of recombinant DNA-produced leukocyte interferon (IFLrA) were studied in 37 patients with metastatic cancer who received sequentially escalating doses of 9-86 million units (MU) of IFLrA by im injection twice weekly. The IFLrA was absorbed rapidly and reached a peak serum concentration 6-8 hours after injection. Serum concentration of IFLrA increased proportionately with the dose. The most common side effects included fever, chills, asthenia, anorexia, and weight loss, and leukopenia, granulocytopenia, and lymphopenia occurred frequently. Elevation of serum glutamic-oxaloacetic transaminase was frequent above doses of 50 MU. All side effects were reversible by discontinuation of the drug. Antibodies to IFLrA were detected in 3 patients while on treatment. The presence of antibodies coincided with drastic reduction in serum IFLrA concentration and, in 1 patient, with relapse of disease. Objective tumor responses were documented in patients with lymphomas but not in other groups of patients.

Adolescent↗

Amyloid goiter as the initial manifestation of systemic amyloidosis due to familial mediterranean fever with homozygous MEFV mutation.

We describe a case of amyloid goiter revealing a systemic amyloidosis secondary to familial Mediterranean fever (FMF) with homozygous MEFV mutation, and we review the literature. A 45-year-old euthyroid Sephardic man, known to suffer from FMF, developed a goiter with cold nodule, after which a subtotal thyroidectomy was performed. Histologic evaluation revealed diffuse AA amyloid deposition without any associated thyroid neoplasia. At that time, no other organ was found to be affected by amyloidosis. Colchicine and levothyroxine were prescribed. Eight years later, the patient presented with a rapidly growing neck enlargement. He reported that he had discontinued colchicine therapy 2 years earlier. The serum thyrotropin (TSH) and calcitonin levels were normal. Renal, digestive, and salivary gland biopsies confirmed the presence of systemic AA amyloidosis. Despite the reintroduction of colchicine, the onset of compressive symptoms led to the completion of the total thyroidectomy. The histopathology again demonstrated amyloid deposition, and excluded a malignant neoplasm. Nine cases of amyloid goiter associated with FMF have been reported in the literature; none of them had an amyloid goiter as the first manifestation of systemic amyloidosis. To our knowledge, this is the first case of FMF in which an amyloid goiter preceded the development of secondary systemic amyloidosis. The cessation of colchicine therapy may have played a role in local relapse and the secondary spread of amyloid deposits.

Amyloidosis↗

Chloramphenicol in the treatment of enteric fever.

Chloramphenicol is still very effective for acute enteric fever. A literature survey does not confirm the repeated claims of decreasing efficacy over the past 20 years (not taking into account the R factor mediated resistance noted since 1972/73). However, there have been regional variations in the time needed to achieve defervescence under chloramphenicol treatment since the early 1950s. When comparing alternative antimicrobials with chloramphenicol other criteria apart from clinical efficacy have to be considered, namely, influence on the rate of excretion of the organisms and the relapse rate, ease of administration parenterally, toxicity, cost, and the possible occurrence of resistance to Salmonella typhi or S. paratyphi A/B.

Chloramphenicol↗

Antibodies and the Aberdeen typhoid outbreak of 1964. I. The Widal reaction.

The outbreak of typhoid fever in Aberdeen during 1964 (Walker, 1965) presented an opportunity to study the antibody titres of typhoid fever patients and of TAB immunized individuals to obtain further knowledge concerning the behaviour of these titres with the passage of time.This paper gives an abbreviated version of part of a research programme which followed the Aberdeen typhoid outbreak of 1964.The antibody titres of patients were followed up for a period of 2 years after discharge from hospital and the findings have been compared with those in TAB immunized healthy individuals. The following points emerged:(1) The value of the Widal test as an aid to diagnosis was limited;(2) the flagellar antibody titre in patients' sera provided a more reliable aid towards diagnosis than did the somatic antibody titre;(3) the response of immunized and non-immunized patients to the somatic antigens was poor and often delayed well into the period following discharge from hospital;(4) titres of 1/40 and over for Vi agglutinins were present in immunized and non-immunized patients for at least 12 months after discharge without their being S. typhi excretors;(5) Vi agglutinin titres as high as 1/40 were present in TAB immunized healthy individuals and also in members of the general public;(6) the presence of S. typhi septicaemia need not result in a high antibody titre;(7) patients who relapse, may do so without enhancement of previous antibody titres and may relapse even in the presence of earlier appreciable titres.

Agglutinins↗

[Mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria].

AIM OF THE STUDY: To evaluate mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria. MATERIAL AND METHODS: Prospective non randomized study in hospitalized children during one year. Acute falciparum malaria was defined by fever and a positive thin and/or thick smear. Malaria was presumed to have been contracted in Comoros archipelago and/or Madagascar 6 months previously. Patients were excluded, when quinine had to be used, according to World Health Organization's severity criteria. RESULTS: Forty-nine children were included: 29 were treated with halofantrine and 20 with mefloquine. Patients features in the two groups of treatment were identical, with exception for the mean time between first clinical signs and diagnosis (shorter in mefloquine group). Fever's and hospitalization's duration under treatment were similar. An increase in QTc interval was frequently observed in patients treated with halofantrine (56 versus 0%), although patients with mefloquine experienced vomiting (45 versus 0%). Relapses seemed to be more frequent with halofantrine (14 versus 0%). DISCUSSION: Halofantrine and mefloquine are efficient for falciparum malaria treatment in our pediatric series, despite a high rate of adverse events. Mefloquine's tolerance may probably be improved with changes in regimen and dose. Relapses are more frequent with a single first treatment of halofantrine, than with mefloquine. Unfortunately, features of a second halofantrine treatment are not defined.

Adolescent↗

A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation.

We initiated a randomized study of amifostine (the organic thiophosphate formerly known as WR-2721) given to patients during myeloablative conditioning therapy for allogeneic bone marrow transplantation. Amifostine was given at a dose of 1000 mg/day of conditioning and was well tolerated if attention was given to serum calcium levels, blood pressure and antiemetics. Since August 1998, 60 patients (30 on each arm) have completed the study. There was no significant difference in the days to neutrophil or platelet engraftment in either arm of the study. Significantly, the duration of grade I-IV mucositis was decreased in the group that received amifostine (P=0.02). Also grade III or IV infections (P=0.008), duration of antibiotic therapy (P=0.03) and duration of fever (P=0.04) were significantly reduced with amifostine. However, there were no differences in the incidence of grade III or IV mucositis, liver toxicity or renal toxicity. There were also no differences in early mortality, relapse and long-term survival. We conclude that amifostine, while reducing the duration of mucositis and infections (possibly through some preservation of gut mucosal integrity), has a modest effect in allogeneic bone marrow transplants given the multiplicity of factors influencing organ toxicity and survival in this setting.

Adolescent↗

Adjuvant high-dose chemotherapy supported by peripheral blood stem cell transplantation for high-risk cervical carcinoma.

Cervical carcinoma is a common disease for which the prognosis has not been substantially improved with standard locoregional treatments. Three stage IB patients with untreated cervical carcinoma were treated with high-dose chemotherapy and refrigerated peripheral blood stem cell support using the ICE program (Ifosfamide 10 g/m2 plus mesna at 100% of the ifosfamide dose; Carboplatin at 1.5 g/m2 and Etoposide 2.1 g/m2). Patients received the treatment in an adjuvant setting after radical hysterectomy with pelvic lymph-node dissection and postoperative cisplatin-based standard-dose chemotherapy. All patients underwent postoperative radiotherapy. The treatment was well-tolerated, all patients had rapid hematologic recovery, and the most frequent complications were grade 3 mucositis and neutropenic fever. The three patients are disease-free at 58, 60, and 63 months of follow-up. Our results show that adjuvant high-dose chemotherapy could be effective to reduce the likelihood of relapse in high-risk patients. High-dose chemotherapy deserves a formal evaluation in high-risk cervical cancer.

Journal Article↗

Parasitic sinusitis and otitis in patients infected with human immunodeficiency virus: report of five cases and review.

We describe five cases of parasitic sinusitis and otitis in patients infected with human immunodeficiency virus (HIV) and review 14 reported cases. The pathogens identified in our group of patients included agents such as Microsporidium, Cryptosporidium, and Acanthamoeba species. The clinical features common to these patients included a long history of HIV seropositivity associated with advanced immunosuppression and multiple opportunistic infections as well as long-standing local symptoms refractory to multiple courses of antibacterial agents. Symptoms often included fever and chills in addition to local tenderness and discharge. Invasive diagnostic procedures were necessary to obtain the final diagnosis and to initiate appropriate therapy. Although most patients responded at least partially to specific therapy, relapses and recurrences were frequent in patients who did not receive long-term suppressive therapy. The general outcome for HIV-infected patients with parasitic sinusitis and otitis was poor; however, deaths were generally associated with other complications of the underlying HIV infection.

AIDS-Related Opportunistic Infections↗

Childhood brucellosis in Israel.

BACKGROUND: Brucellosis has become a major medical problem in Israel particularly in the Muslim Arab population. METHODS: Eighty-eight children with acute brucellosis are described. Sixty-seven were studied retrospectively during 1987 through 1988, and 21 children were studied prospectively during 1989 through 1992. Epidemiologic, clinical and laboratory features were evaluated, and the outcome of 4 antimicrobial regimens are compared. RESULTS: Although the clinical manifestation varied, the classical triad of fever (91%), arthralgia or arthritis (83%) and hepato- and/or splenomegaly (63%) characterized most patients. Sixty-one percent of the children had elevated liver enzymes. Brucella melitensis was isolated from 61% of blood cultures. The relapse rate in patients who were treated with monotherapy (doxycycline) was 43% compared with 14% with regimens of combined therapy with rifampin and doxycycline, streptomycin and doxycycline or rifampin and trimethoprim-sulfamethoxazole (P < 0.049). Eleven children (33%) who were treated for 3 weeks had relapse compared with 1 patient (3.5%) treated for 4 weeks or longer. The total relapse or reinfection rate was 20%. All patients with relapse recovered after a second course of antibiotic therapy. During the 2 years of follow-up one child progressed to chronic osteomyelitis. CONCLUSIONS: Combination therapy and extending treatment for 4 weeks or longer gave significantly better results than monotherapy or shorter courses of therapy and resulted in fewer relapses.

Adolescent↗

Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma.

BACKGROUND: Immunotherapy given post-autologous stem cell transplantation may eliminate residual tumor cells escaping the conditioning protocol. METHODS: Five children suffering from stage IV neuroblastoma were treated by recombinant interleukin-2 (IL-2) post-autologous peripheral blood stem cell transplantation. The patients' peripheral mononuclear cells were monitored for CD3+ and CD56+ levels, their proliferative response and killing of various cell lines targets. RESULTS: An increase in the level of total lymphocytes, mainly due to expansion of T cells, and enhanced proliferative response to phytohemaglutinin were observed. Elevated cytotoxicity against K562 and neuroblastoma target cells was detected in four patients and against K562 targets in one patient. Toxicity included mild thrombocytopenia, and fever in four patients and mild to moderate encephalopathy which necessitated withdrawing one patient from the protocol. Three of five patients studied are alive today, one of them whose IL-2 was stopped, is in relapse. Two patients have died. CONCLUSIONS: Immunotherapy with s.c. intermediate-high dose IL-2 is feasible and results in expansion of T cells and in stimulation of killing activity against several targets including in some cases, neuroblastoma tumor cells.

Child, Preschool↗

[Inflammatory syndrome after thoracic aortic endoprosthesis implantation associated with cortico-suprarenal adenoma].

We report a case of a 68-year-old patient, admitted with diagnosis of aneurysm of the descending thoracic aorta to the Department of Cardiac Surgery, where he underwent percutaneous endovascular application of 4 endoprostheses in the descending thoracic aorta. After antibiotic prophylaxis and hemodynamic stabilization, the patient was admitted to the Cardiac Rehabilitation Unit for the management of the of postoperative course and undergo a program of cardiac rehabilitation. Five days following admission and before starting physical training, the patient developed fever associated with neutrophil leukocytosis, strong activation of inflammatory markers and sideropenic anemia, compatible with post-implantation inflammatory syndrome. Significant hypokalemia also occurred. Further investigations showed left cortical-suprarenal adenoma. The inflammatory state relapsed spontaneously and the patient was discharged with indication to undergo an endocrinologic consultation.

Adenoma↗

[Childhood t(8;21) acute myelocytic leukemia: a comparison of clinical features and risk factors with adult cases].

Despite the abundance of reports describing adult cases of t(8;21) acute myelocytic leukemia (AML), childhood cases have received little attention. We retrospectively investigated 14 childhood cases of t(8;21) AML, and compared their clinical characteristics with those of adult cases, focusing on the risk factors for poor prognosis. Seventy-one percent of the patients had fever. Their mean leukocyte count was 12,700/microliter, and they showed decreased NAP activity. The cell surface showed positivity for CD13, 33, 19, 34, and HLA-DR. The complete remission rate was 100%, and relapse was observed in three of the patients. Bone marrow eosinophilia was present in a smaller proportion of the childhood cases than in the adult cases. Although an increased leukocyte count, tumor formation, and other risk factors have been reported in adults, there was no correlation between these factors and prognosis in our childhood cases. As children who showed AML relapse had TdT-positive blasts, detectable blast TdT activity may be a risk factor for relapse in childhood cases of t(8;21) AML. However, to confirm this, a study with a larger subject base should be conducted.

Adolescent↗

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation.

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.

Autopsy↗

Ofloxacin versus co-trimoxazole in the treatment of typhoid fever in children.

Ofloxacin has been successfully used in the treatment of typhoid fever and Salmonella infectious of adults for many years. However, it has rarely been tried for the typhoid fever of children. In the present study, the therapeutic efficacy of ofloxacin in the treatment of typhoid fever in children was compared to that of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared according to the clinical variables (apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms) and the time when cultures became negative. All patients in both groups were cured without relapse. Apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms were obtained in a significantly shorter time with ofloxacin than with co-trimoxazole (P < 0.05). The interval between onset of therapy and the time when cultures became negative was significantly shorter in the ofloxacin group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good alternative in the treatment of typhoid fever caused by co-trimoxazole resistant salmonellae in children aged less than 16 years. It is well tolerated by the patients and it causes no side effects with short-term usage.

Anti-Bacterial Agents↗

Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: This multicenter phase II study evaluated the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients received a dosimetric dose that consisted of 450 mg of anti-B1 antibody followed by 35 mg (5 mCi) of iodine-131 tositumomab. Serial total-body gamma counts were then obtained to calculate the patient-specific millicurie activity required to deliver the therapeutic dose. A therapeutic dose of 75 cGy total-body dose (attenuated to 65 cGy in patients with platelet counts of 101,000 to 149,000 cells/mm(3)) was given 7 to 14 days after the dosimetric dose. RESULTS: Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies. CONCLUSION: Iodine-131 tositumomab produced a high overall response rate, and approximately one third of patients had a CR despite having chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL.

Adult↗

[Granulopenia of infectious origin].

Among the various infectious and parasitic disease liable to produce granulopenia, the authors selected certain diseases which represented their personal experience. Classically, leukopenia may occur during typhoid fever, but was not present in all of the series of 114 adults they observed with this disease. It only occurs after antibiotic treatment (Thiamphenicol in the majority of cases). During acute brucellosis (188 cases studied) granulopenia was constant. It occurs early and is lasting. It reappears during septicemic relapse. Leukopenia is corrected during treatment by tetracycline antibiotics. Neutropenia during disease is frequent but usually labile. This characteristic explains why there was no granulopenia in 90 cases of mumps and 64 cases of chickenpox. Finally, during Kala Azar, 8 cases confirmed certain already well known data: the considerable reduction in granulocytes but also anemia and thrombocytopenia.

Acute Disease↗

Ceftriaxone versus chloramphenicol in the treatment of enteric fever.

Fifty-five patients with culture-proven Salmonella typhi and paratyphi enteric fever were assigned to one of two therapeutic regimens. Group I received ceftriaxone 60-80 mg/kg/day intramuscularly for 5-7 days, those in group II received chloramphenicol 50-80 mg/kg/day orally in 4 divided doses for 12-14 days. both groups were comparable as regards age, sex, severity and duration of symptoms prior to admission. A significant reduction in the mean number of days taken for patients to become afebrile, disappearance of clinical signs and symptoms, duration of therapy and hospital stay were observed in patients receiving ceftriaxone as compared to those receiving chloramphenicol. None of the patients receiving ceftriaxone relapsed, while three patients receiving chloramphenicol relapsed. No major reactions were seen with either drug.

Adolescent↗

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