LOPH and D-MHC in the Treatment of FeLV Associated Acute Leukemia in a Cat

Background: Bone marrow primary malignancies are denominated leukemias, classified as myeloid or lymphoid, according to the cell lineage, and acute or chronic, according to the cell´s state of maturation. In cats, acute lymphoid leukemia is the most common form, especially in regions endemic for feline leukemia virus and / or feline immunodeficiency virus. A new treatment protocol for lymphomas, called LOPH, has been described for animals with FeLV persistent viremia. This study aimed to report a case of a cat presenting with FeLV associated acute leukemia and treated with the LOPH protocol, and, in the rescue phase, a modification of the D-MAC protocol, denominated D-MHC.Case: A 4-year-old mixed breed intact queen was attended due to lethargy and inappetence. The patient did not present any relevant abnormalities in the clinical exam and complementary exams were performed including complete blood count, biochemical profile, SNAP Feline Triple Test, chest radiographs and abdominal ultrasound. Imaging tests and biochemical values were unremarkable, but the patient presented a reagent result for FeLV and severe leukocytosis due to lymphocytosis. The morphological evaluation of the blood smear revealed the presence of blasts, in a concentration greater than 20% of the nucleated cells, which allowed the characterization of a leukemic state, probably lymphoid. First-line treatment was based on the LOPH protocol, including Lomustine, Vincristine, Prednisoloneand Doxorubicin, in four-week cycles. Nevertheless, during the third cycle, 66 days after the institution of this protocol, the patient presented a febrile condition along with marked leukocytosis due to lymphocytosis, confirming leukemia recurrence. A rescue attempt was performed with a modification of the D-MAC protocol, originally consisting of the combination of dexamethasone, melphalan, actinomycin-D and cytarabine, but with replacement of actinomycin-D by doxorubicin, and therefore nominated D-MHC. After the three cycles there was a return of the febrile condition associated with severe pancytopenia and euthanasia was elected due to poor clinical condition, resulting in a survival time of 124 days. The hematological toxicity of the induction protocol included anemia and neutropenia, with mainly grade I events, but with the occurrence of a grade IV event. The adverse effects of the rescue protocol were similar, but with a greater number of grade IV events.Discussion: FeLV is considered the most lethal retrovirus of the domestic cat, with a major impact on health and life expectancy. Persistent FeLV antigenemia increases the risk of hematopoietic neoplasms in 62.1 times due to a direct insertional mutagenesis. In endemic regions, approximately 70% of cats with acute leukemia have persistent FeLV antigenemia, as the patient in this report. The diagnosis was made through association of retroviral status and the identification of more than 20% of blasts, possibly lymphoblasts, in the blood stream, sparing the need for a myelogram. Considering the poor prognosis for acute lymphoid leukemias and the patient's retroviral status, treatment was initiated with the LOPH protocol, including lomustine, as a potent agent to induce remission, and doxorubicin, which can result in longer remission intervals. After 66 days free of the disease, the patient presented recurrence of the leukemic condition, starting the rescue protocol D-MHC. Remission was again obtained with duration similar to the first protocol, however, on the occasion of a new leukemia recurrence, euthanasia was elected. The treatment adopted for the patient in this report resulted in a longer survival time than reported in other studies. Despite the aggressiveness of the protocols, especially the D-MHC, it was possible to perform it using the monocyte and granulocyte stimulation factor to reverse neutropenia.

Long-term fever in a child: what is the reason, how to examine, treat or not treat?

Long unclear fever in children of different ages remains one of the difficult and topical issues in the paediatric practice. Despite up-to-date techniques of laboratory and instrumental examination, verification of prolonged fever causes remains difficult; it cannot be deciphered in 10% of cases. It is especially important to differentiate fever from hyperthermia in paediatric practice. The article provides an overview of the status update on the issue. The mechanisms of fever and hyperthermia are described, criteria for fever of unknown origin are given. It is stated that infectious diseases under the guise of fever of unknown origin develop in 60–70% of children. Systemic connective tissue disease and vasculitis are detected in 20% of cases, hemato-oncological – in 5%, auto-inflammatory – in 5%, the cause of fever remains unknown in 10% of cases. The article provides clinical observations of children with diseases debuting as fever of unknown origin with the following diagnoses: juvenile rheumatoid arthritis (JRA), a systemic variant with high activity (DAS index 28 = 5.1 at the rate of < 2.6); mucocutaneous lymphonodular syndrome (Kawasaki syndrome), damages of cardiovascular system (small coronary artery aneurysms), bacterial-viral infection; auto-inflammatory syndrome – mevalonate kinase deficiency syndrome (hyper-IgD syndrome). Diagnostic approaches to the verification of febrile condition are outlined. It is noted that treatment should not be started in a stable condition of the patient without establishing the cause of the fever, and it is advisable to use only an antipyretic agent with central and peripheral effects, pronounced antipyretic effect, analgesic and anti-inflammatory effects.

Clinical course of coxsackievirus B (1-6) infection

Objective. Coxsackievirus B (1-6) infections are the common infections of children and adults. Clinical manifestations include fever, aseptic meningitis, pleurodinia, myocarditis, gastroenterocolitis, maculous exanthem. The clinical course of the infection is influenced by the characteristics of the host, as well as the virus serotype. The pathogenesis of the diseases is explained by the immune mediated mechanism and the direct cytotoxic effect of the virus. Methods. Retrospectively analyzed virus serotype, clinical and biochemical data in patients with coxsackievirus B (1-6) infection. Patients who had an unclear febrile condition for more than six months were tested for autoantibodies. Results. We examined a total of 378 patients with coxsackievirus B (1-6) infection (302 women, 76 men), age 19 to 79 years. The dominant symptoms were weakness, elevated body temperature, fatigue and muscle aches. In 55% the clinical course was fever of unknown origin, in 13% myalgia/pleurodinia, 9% acute gastroenterocolitis and acute myocarditis/ pericarditis, 2% aseptic meningitis, 2.4% respiratory disease, 3% acute pancreatitis and 1% diabetes mellitus. Autoantibodies were detected in 69% of patients with fever of unknown origin. Antinuclear antibodies were most common, in 67%. Serotype B2 had 36% of these patients. Serotype B2 had 36% of these patients and serotype B4 had 14%. Conclusion. The most common clinical form of coxsackievirus B (1-6) infection is an fever of unknown origin caused by a B2 serotype of the virus. In most of these patients, an elevated titre of antinuclear antibodies can be detected.

CORRELATION OF TOTAL COUNT (WBC), NEUTROPHIL COUNT AND CRP TEST AMONG FEBRILE PATIENTS IN NAVIMUMBAI.

150 febrile patients included children (50), adult (50) and neonates (50) from outpatient departments and inpatients of private clinics and hospitals. Patients presented with fever and chills for more than 1 day to 3 days, throat infection, ear infection and cold and fever and only fever as the principal symptoms. After clinical examination all the patients were prescribed for Complete Blood Count (CBC) with differential count(DC) and C-reactive protein(CRP) tests, and in children below 14 years anti-Streptolysin O(ASO) tests ( 75) were prescribed. Patients treated with antibiotics previously two weeks before the study period were not included. Qualitative and quantitative tests were performed on all patients’ samples included in the study depending on the need/prescription by the physician or paediatrician. CBC, neutrophil count and CRP have been very useful indicators and significant in the diagnosis and treatment as well as follow-up of the febrile condition of the patients specially in patients suffering with bacterial infections. Even in patients with Dengue and malaria it gives a fair idea if there were leucocytosis or leukopenia, neutrophilia or neutropenia, thrombocytosis or thrombocytopenia. CBC: Complete blood count, DC: Differential count; MP: malarial parasite, CRP: C-reactive protein, ASO: Anti-Streptolysin O.

Tumor Necrosis Factor-Alpha as Differential Diagnostic Marker for Patients with Fever of Unknown Origin

Febrile conditions of unidentified origin are still unknown in modern medicine despite the development of diagnostic procedures. There are various agents of long-term temperature encompassing numerous infectious or non-infectious diseases. The aim of this study was to determine if there was a statistically significant difference in the values of proinflammatory cytokines (IL-1, TNFα, IL-6) in patients who meet the criteria for febrile conditions of unidentified origin, between the group of infectious, malignant, rheumatic, “other” diseases and undiagnosed patients. The study was conducted in the Immunology laboratory of the Center for Molecular Medicine and Stem Cells Research of the Faculty of Medical Sciences in Kragujevac. Blood samples were taken from patients tested at the Clinic for Infectious Diseases, of the Clinical Center of Kragujevac, in the period from 2014 to 2016. The study included 70 patients. The measured values of the level of TNFα showed significantly higher values in a group of malignant diseases than in the group of infectious diseases, while the values of IL-1 and IL-6 did not show statistical significance. TNFα can improve diagnosing in case of patients with an unknown febrile condition, which can shorten the length of the hospital stay and reduce the volume of performance of diagnostic procedures.

The Value Assessment of Clinical Trials Based on Electrophysiologically Verified Lumboischialgia

Introduction: Lumboischialgia is defined as pain in the distribution of ischemic nerve caused by a pathological change in the nerve itself, whereas lumbago is a localized spondylogenic pain that is not followed by a neurological deficit, and is a consequence of muscular bone dysfunction of the lumbosacral region. Previous studies which investigated the value of clinical trials in the diagnosis of lumboischialgia did not find a high sensitivity and specificity in those tests.Objective: Our objective was to define clinical tests that indicate the existence of radiculopathy and to determine the value of the overall diagnostic finding in relation to the findings of the EMNG examination.Methods: The sample consisted of 100 patients of both genders, aged 18-65. The inclusive criteria were: strong lower back pain propagating in one of both legs and lasting for 1-3 months and the medical history suggesting a radicula lesion. Non-inclusion criteria were the following: symptoms of cauda equine, acute febrile condition, existence of tumors, vertebral fractures, lesions of central motoneuron, inability to perform the EMNG examination, acute psychotic conditions, operations of the spine and pregnancy. Immediately before each EMNG examination, medical history was taken with defined questions on the existence of pain stronger in the leg than in the spine, dermatome deficit, pain during labor and weakness in the leg.Results: Patients usually have a total of two (31%) and three (26%) positive clinical signs of lumboischialgia. By statistical analysis, three clinical trials proved to be discriminatory in terms of verification of radiculopathy: positive Lazarevic test, paresis of a particular muscle group, and absence or reduction of the patellar or Achilles reflex. After processing with logistic regression, the statistically predictive value is retained by a positive Lazarevic test. The analysis of the surface under ROC curve shows that the positivity of four or more clinical tests is statistically the best limit value, with a specificity of 67% and a sensitivity of 56%.Conclusion: The conducted study indicates the statistical significance of the frequency of positive clinical trials: Lazarevic test, objective muscular weakness and absent reflex, in persons with electrophysiologically verified lumboischialgia.

Atypical Kawasaki Disease in a 4 Years Old Child with Mumps

Kawasaki disease is an acute febrile condition seen in children. However, it is also well recognized that some patients do not fulfill the classic diagnostic criteria for the diagnosis of Kawasaki disease. The incomplete form of Kawasaki disease is termed as ‘Incomplete KD’ or ‘Atypical KD’. This is a case of 4 years old child with fever and mumps. He had bilateral cervical adenitis. Patient failed to respond to IV antibiotics fulfilled the criteria of incomplete Kawasaki disease. The child was managed with high dose aspirin until the child was afebrile for 48 hours. Kawasaki disease is a common vasculitis in children. Atypical cases might be missed if there is concomitant viral illness. Hence the identification and management of Kawasaki disease is paramount to decrease the mortality related to the cardiac disease.

A Case Report on Fever of Unknown Origin in a School Going Child– An Uncommon Answer in a Common Question

Fever is one of the commonest complaints in paediatrics outpatient as well as inpatient department. Fever of unknown origin (FUO) is a diagnosis of exclusion given to the febrile condition lasting more than three weeks with temperature 38.30C or more with unknown cause despite of one week in patient care. Here we present a case of FUO in a child which was investigated thoroughly and managed on the line of enteric fever. However, the patient remained febrile. Hence, further investigations were undertaken and finally, bone marrow culture grew a very uncommon organism- Escherichia coli. The child was treated as per the sensitivity and responded well to treatment and was discharged after improvement. Here, we would like to present this case of FUO to highlight the possibility of bone marrow invasion by an uncommon organism as a source of fever in children.

TNFRSF1A gene variant identified in a boy with recurrent episodes of fever

Introduction. Fever of unknown origin is an important diagnostic challenge. Although rare, periodic fever syndromes may often present with a chronic or recurrent febrile condition with a variable temporal pattern of occurrence. Although clinical characteristics often indicate the syndrome in question, there are many atypical forms, and the genotype?phenotype relationship is highly complex, warranting in many cases the designation of a ?syndrome spectrum? rather than a syndrome per se. The aim of this paper was to present a boy with recurrent fever of unknown origin. Case outline. We hereby present a boy with recurrent fever of unknown origin who was by clinically guided partial exome sequencing found to have a heterozygous variant 434A>G in the TNFRSF1A gene, otherwise connected with tumor necrosis factor receptor-associated periodic fever syndrome. The patient responded well to short courses of glucocorticoids and is no longer subjected to unnecessary antibiotic treatment he had frequently received in the past. Conclusion. Periodic fever syndromes should be kept in mind as a differential diagnostic possibility in children with fever of unknown origin.

Low current Cd4+T cell count: prediction, for persistent herpetic gingivostomatitis in HIV-positive patients under antiretroviral therapy

Background: Oral viral lesions associated with HIV infection are important since they affect the quality of life of the patient and are useful markers of disease progression and immunosuppression. The purpose of this study was to correlate the persistence of herpetic gingivostomatitis lesions with the current CD4+ T cell count for adherence of HIV-infected individuals to anti retroviral therapy (ART) and antiviral therapy.Methods: 302 HIV +ve patients developing oral ulcers were included in this study. The herpes simplex viral infections associated with the oral manifestations were detected through Immuno histochemical staining. The quantitative analysis of oral ulceration was done by using mucositis index.CD4T cell count was correlated with clinical manifestations of extensiveness of oral ulcers, acute febrile condition and other constitutional symptoms during follow up of cases for the treatment with anti viral therapies.Results: Association of herpes simplex viral infections was found in 72 out of 302 HIV+ ve cases. All the HSV +ve patients developed extensive oral mucsal lesions during the 1st week. Extensive lesions developed within 7 days in patients with CD4 count <200 due to HSV infection, remained more or less unchanged in the oral cavity up to 90 days although they were receiving antiretroviral and antiviral therapies. In HIV + patients with CD4 count >500, manifestation of mucosal ulcers due to acute herpetic gingivostomatitis was limited to a period of 1 to 2 weeks. Patients with CD4 count >200 <500 did not follow a definite pattern.Conclusions: Persistent oropharyngeal mucosal ulcers along with acute febrile condition due to herpes simplex virus infection are associated with low CD4 T cell count in HIV + patients under antiretroviral therapy.