Heterogeneity of clonal development in chronic myeloproliferative disorders

A 4-kg male child, born at 34 weeks to a gestational diabetic mother, had a large ductus arteriosus aneurysm causing phrenic and recurrent laryngeal nerve palsies and large airway compression. The right and left atrial appendages and distal descending aorta were cannulated, allowing left heart partial or complete cardiopulmonary bypass as necessary. On bypass the ductus was ligated, decompressed, and oversewn but not excised. Examination 1 month later suggested resolution of the recurrent laryngeal palsy and echocardiography showed regression of the aneurysm. Ductus ligation and decompression was an effective surgical treatment, which is less likely to cause complications than resection.     

Relation of platelet abnormalities to thrombosis and hemorrhage in chronic myeloproliferative disorders

A single cohort of small individuals (31 mm mean shell length, 112 mg mean dry flesh weight) of the marine bivalve mollusc Mytilus galloprovincialis Lmk. was held sequentially for 2 wk at each of four food levels equivalent to ingested rations of less than 0.1%, 2.6%, 3.1%, and 7.4% of dry body weight per day. Growth rate reached a maximum at the highest ration level and was strongly correlated, amongst individuals, with mean heterozygosity measured across nine enzyme loci. Rates of energy expenditure were analysed separately as maintenance metabolic rate and the energy costs of growth (J mg-1 dry tissue). The maintenance metabolic rate correlated with traits of protein metabolism (protein synthesis, deposition, and breakdown), and the separate energy costs of both maintenance and growth correlated with the efficiency of protein deposition (protein growth as a proportion of synthesis). The energy costs of growth also varied in negative relation to mean individual heterozygosity. In a multiple regression analysis, the energy allocation to the costs of growth, body size, mean heterozygosity, and the efficiency of protein deposition together explained 90% of the variance amongst individuals in observed rates of growth. The results support the hypothesis that individual variability in the energy costs of protein turnover and in the efficiency of protein deposition during rapid growth are significant factors providing a link between individual genotype and its phenotypic expression as growth.     

The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview

The chronic myeloid disorders are collectively characterized by a stem cell origin of the clonal process and a variable tendency to undergo indigenous disease transformation and leukemic conversion. Classification of the chronic myeloid processes is based primarily on the presence or absence of the Philadelphia chromosome (bcr-abl translocation) and secondarily on the morphologic picture of the bone marrow in conjunction with the clinical manifestation. Essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid metaplasia (AMM) constitute the classical group of bcr-abl negative chronic myeloproliferative disorders. PV is characterized by a clonal increase in red blood cell mass, AMM by bone marrow fibrosis, and ET by thrombocytosis. Most of these features, however, are not diagnostically specific, and secondary causes of erythrocytosis, thrombocytosis, and bone marrow fibrosis must be excluded. Treatment may be deferred or limited to phlebotomy alone in some patients with ET or PV, respectively. In contrast, thrombosisprone patients with PV or ET require drug therapy, and new platelet-lowering agents are increasingly being used. In this article, current diagnostic and therapeutic issues of ET, PV, and AMM are discussed.     

Lymphoproliferative and myeloproliferative disorders

Nomenclature regarding neoplasia of the hematopoietic and lymphoid tissues in the horse is confusing. This article will clarify terminology, and discuss the individual lymphoproliferative and myeloproliferative disorders recognized in the horse. Diagnostic techniques that are useful in cases in which hematopoietic or lymphoid tissue neoplasia are suspected include histochemical staining profiles, bone marrow aspiration, and bone marrow biopsy.     

Megakaryoblastic termination of myeloproliferative disorders

Megakaryoblastic termination of myeloproliferative disorders is rare. The morphology of megakaryoblastic transformation can be subtle and is often mistaken for myeloid or lymphoid proliferations. Previously reported observations suggest a relatively poor prognosis for this category of patients, making precise diagnosis imperative. A multifaceted approach using morphology, ultrastructure, cytochemistry, and immunological membrane analysis may be helpful. We present two cases of myeloproliferative disorder with aggressive megakaryoblastic phases (myelofibrosis with agnogenic myeloid metaplasia and chronic myeloid leukemia with blast crisis). The clinical course is described and the results of the morphological, cytochemical, ultrastructural, and cytogenetic studies of both cases are presented. In addition, immunochemical studies (flow cytometry) and platelet function studies (aggregation, beta-thromboglobulin, and platelet factor IV release) were done for one of these patients.     

Pathogenesis of marrow fibrosis in myeloproliferative disorders]

A postal questionnaire was sent on two occasions to specialist anaesthetists within New Zealand. Questions were related to fasting status, anti-aspiration prophylaxis, incidence of aspiration, definition of high risk groups for aspiration pneumonitis, and identification of departmental guidelines. Two-hundred-and-twenty-three replies were received (72% response rate). Most adults, children and infants were fasted for 6 hours for solids, whilst the majority fasted for 2 to 4 hours for liquids. Two-thirds indicated that they would delay emergency surgery (not life/limb threatening) to optimize gastric emptying. Histamine type 2 receptor antagonists, metoclopramide and cricoid pressure were used commonly, more so in the obstetric population compared to non-obstetric surgery. Preinduction nasogastric intubation and suction were used infrequently. Anti-aspiration prophylaxis was deemed important in morbidly obese patients, those in the third trimester of pregnancy and those with a hiatus hernia, whilst diabetes mellitus, sepsis and renal failure were not considered risk factors for aspiration pneumonitis. 71% of respondents had at least one episode of aspiration (range 0-10), with an overall mortality rate of 5%. Half of these cases of aspiration were deemed to be preventable by the respondent.     

Evidence from molecular genetic and cytogenetic analyses that bone marrow histopathology is reliable in the diagnosis of chronic myeloproliferative disorders

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.     

Splenic irradiation in the palliation of patients with lymphoproliferative and myeloproliferative disorders

INTRODUCTION: Splenic irradiation is an accepted mode of treatment for palliation of hypersplenism and splenic pain for patients with lymphoproliferative or myeloproliferative disorders. However, results are conflicting regarding the duration of palliation and the toxicity associated with this treatment. METHODS: Twenty-five patients with lymphoproliferative or myeloproliferative disorders were treated with splenic irradiation for palliation of splenomegaly and pain. The spleen was measured and pain and toxicity were assessed during radiation therapy. RESULTS: Splenomegaly and splenic pain decreased in 60 percent and 91 percent of patients, respectively. Radiation doses higher than 500 cGy appeared to be more effective than lower doses in reducing the spleen size in patients with chronic lymphocytic leukemia. Regression of splenomegaly and pain relief were maintained for less than one year and more than six months, respectively. Acute radiation toxicity resulted in the cessation of radiotherapy in two patients. CONCLUSION: Splenic irradiation is effective in the short-term palliation of splenomegaly and pain and may be most useful in the subset of patients with a life expectancy of less than one year. Terminally ill patients with splenomegaly secondary to lymphoproliferative or myeloproliferative disorders may benefit from splenic irradiation to minimize pain and pressure symptoms in addition to possible reduction of narcotic use.     

Occurrence of myelofibrosis in individual types of chronic myeloproliferative diseases

BACKGROUND: During the course of chronic myeloproliferative disorders (CMPD), myelofibrosis (MF) represents a negative prognostic factor. The data concerning the incidence and progression of MF are rather heterogenous. OBJECTIVES: The aim of the study was to evaluate the incidence and progression of MF in cases of CMPD registered in the Consultation Center for Haematopathology Biopsies in Martin Faculty Hospital. METHODS: Fibrotic changes involving bone marrow were evaluated histologically semiquantitatively using reticulin fiber impregnation (method of Gomori). The study included 77 cases of chronic myelocytic leukemia (CML), 99 cases of polycythaemia vera (PV), 38 cases of essential thrombocythaemia (ET), and 126 cases of the fourth type of CMPD, mostly known as myelofibrosis/osteomyelofibrosis type (MF/OMF). The occurrence and degree of MF were evaluated at the time of all primary biopsies; in 52 of cases also in rebiopsy material. RESULTS: At the time of primary diagnosis, MF occurred in 37/77 (48%) cases of CML, in 27/99 (27.3%) cases of PV, in 8/38 (21%) cases of ET, and in 119/126 (94.4%) cases of MF/OMF. In repeated (secondary) biopsies, the progression of MF or evolution to MF was most common in CML and MF/OMF types. CONCLUSIONS: At the time of the CMPD diagnosis, more than 50% of cases showed the presence of MF. During the course of CMPD, the MF seems to represent a dynamic process evolving the underlying disease. The early diagnosis of MF is important for the selection of the appropriate therapeutic regimen. (Tab. 3, Fig. 2, Ref. 23.)     

Defective platelet lipid peroxidation in myeloproliferative disorders: a possible defect of prostaglandin synthesis

The author discusses a number of genetically determined diseases, such as hemoglobinopathies, acute intermittent porphyria, familial Mediterranean fever and so-called acquired hypogammaglobulinemia from the geographical point of view. Possible factors explaining localized increases in incidence are discussed. The importance of isolates for the development of such foci is stressed.     

Leukocyte mobilization by epinephrine and hydrocortisone in patients with chronic renal failure

The mobilization of WBC from the bone marrow, as judged from hydrocortisone-induced leucocytosis, is markedly impaired in dialyzed and nondialyzed uremic patients. The release of WBC from the marginal pool by epinephrine was found to be normal.     

Histopathological findings in chronic tendon disorders

Tendon injuries and other tendon disorders represent a common diagnostic and therapeutic challenge in sports medicine, resulting in chronic and long-lasting problems. Tissue degeneration is a common finding in many sports-related tendon complaints. In the great majority of spontaneous tendon ruptures, chronic degenerative changes are seen at the rupture site of the tendon (1). Systemic diseases and diseases specifically deteriorating the normal structure of the tendon (i.e. foreign bodies, and metabolic, inherited and infectious tendon diseases) are only rarely the cause of tendon pathology. Inherited diseases, such as various hereditary diseases with disturbed collagen metabolism and characteristic pathological structural alterations (Ehlers-Danlos syndrome, Marfani syndrome, homocystinuria (ochronosis)), represent approximately 1% of the causes of chronic tendon complaints (2), whereas foreign bodies are somewhat more common and are found in less than 10% of all chronic tendon problems (1). Rheumatoid arthritis and sarcoidosis are typical systemic diseases that cause chronic inflammation in tendon and peritendinous tissues. Altogether, these 'specific' disorders represented less than 2% of the pathological alterations found in the histological analysis of more than 1000 spontaneously ruptured tendons (1, 3, 4). In this material, degenerative changes were seen in a great majority of the tendons, indicating that a spontaneous tendon rupture is a typical clinical end-state manifestation of a degenerative process in the tendon tissue. The role of overuse in the pathogenesis of chronic tendon injuries and disorders is not completely understood. It has been speculated that when tendon is overused it becomes fatigued and loses its basal reparative ability, the repetitive microtraumatic processes thus overwhelming the ability of the tendon cells to repair the fiber damage. The intensive repetitive activity, which often is eccentric by nature, may lead to cumulative microtrauma which further weakens the collagen cross-linking, non-collagenous matrix, and vascular elements of the tendon. Overuse has also been speculated to cause chronic tendon problems, by disturbing the micro- and macrovasculature of the tendon and resulting in insufficiency in the local blood circulation. Decreased blood flow simultaneous with an increased activity may result in local tissue hypoxia, impaired nutrition and energy metabolism, and together these factors are likely to play an important role in the sequence of events leading to tendon degeneration (4). A sedentary lifestyle has been proposed as a main reason for poor basal circulation of the tendon, and presumably is at least partly responsible for the high number of tendon problems in people with a sedentary lifestyle who occasionally take part in high physical activity sports events.     

Electroencephalographic findings in liver function disorders

Abnormal rhythmisations in the EEG are described in hepatoportal encephalopathy as an expression of a disturbance of more profound cerebral structures. The EEG gives an actual information about the state of the cerebral functions of all stages of a hepato-cerebral decompensation and allows a reliable prognostic estimation during the observation of the course. Practically significant are also bioelectric findings of a disturbance of the cerebral function with clinically symptom-poor course in compensated liver cirrhosis or obstructive icterus.     

Menstrual disorders in patients undergoing chronic hemodialysis

OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.     

Cognitive disorders in patients with chronic renal insufficiency

Papillomaviruses are pathogens which induce cutaneous and mucosal lesions in man and in many animal species. The characterization of these viruses was rather low, because viral infection cannot be fully reproduced in cell culture. The development of molecular biology techniques in the 1970s permitted to establish the remarkable plurality of the viruses, the tissue specificity and pecular pathogenicity linked to the type. Studies of the genome organization, the gene expression regulation and the protein characterization gave many informations leading to understand the mechanisms of viral-related carcinogenesis, especially the role of HPV16, the major risk factor for the development of squamous cervical carcinoma.