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The organization of spinal motor circuitry to the kidney is not well-characterized and changes in renal innervation have been associated with disease states such as hypertension found in the spontaneously hypertensive rat or renal hypertension. Here, we describe the segmental and intra-segmental organization of the spinal motor circuitry that was resolved after neurotropic viral injection into the kidney and retrograde transneuronal transport to the spinal cord. In the first experiment, the serial reconstruction of infected neurons in the thoracolumbar spinal cord from T8-L1 was performed following injection of pseudorabies virus (PRV, Bartha strain) into either the cranial pole, the caudal pole or both the cranial and caudal poles of the left kidney in male rats. In the second experiment, rats received injections of two different PRV strains that were genetically engineered to express unique reporter molecules; one of the engineered strains was injected into the cranial pole and the other was injected into the caudal pole. Either 3- or 4-day post-infection, the animals were anesthetized and sacrificed by transcardial perfusion. PRV-infected neurons were located by immunocytochemistry against either PRV itself (experiment 1) or the unique marker proteins (experiment 2). After injection of both poles of the kidney, the majority of the infected neurons were found in the ipsilateral intermediolateral cell column (IML) from T10 to T12 with the mode at T11. Infected neurons were found in discrete neuron clusters in the intermediolateral cell column along the longitudinal axis in a repeating pattern of high and low density that has been called "beading". Three observations indicated a topographic distribution of renal sympathetic preganglionic neurons (SPN). First, after injection into either the cranial or caudal poles of the kidney, the mode of infected cells was located in segments T11 and T12, respectively. The one spinal segment shift in the mode suggested a topographic distribution. Second, in spinal segments T8-L1, comparison of the distributions of the neurons innervating each pole of the left kidney revealed an overlap in the distribution, except in the T11 segment. In the T11 segment, the neurons projecting to each pole tended to segregate into separate populations. Third, in rats that received injections of two PRV strains that were genetically engineered to express unique markers into opposite poles of the kidney, a segregation of neurons projecting to the cranial and caudal poles of the kidney was noted again in the T11 spinal segment and the segregation at adjacent spinal levels was obvious. The analysis of the distribution of infected neurons within each spinal cord segment (intra-segmental distribution) revealed three different patterns along the cranial-caudal dimension. In segments T8-T10, >60% of the infected neurons were located in the caudal half of the spinal segment. In segments T12-L1, >60% of the infected neurons were located in the cranial half of the spinal segment. In segment T11, the neurons were more evenly distributed throughout the segment. These intra-segmental distribution patterns were found after both 3- or 4-day survival periods post-infection and were found in most animals. The distribution of clusters of neurons revealed a similar intra-segmental pattern. Thus, as was described previously for the sympathetic postganglionic neurons that innervate the kidney, the present work indicates a topographic organization in the second-order neurons in the renal sympathetic efferent pathway. The physiological significance of this anatomical organization remains to be determined.
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PMID:Distribution of sympathetic preganglionic neurons innervating the kidney in the rat: PRV transneuronal tracing and serial reconstruction. 1187 86

IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis (GN). However, its association with polycythemia vera (PV) has rarely been described. We report a case of IgAN combined with PV. The patient was a 46-year-old male with chronic renal failure, heavy proteinuria and erythrocytosis. He also presented hypertension and hematuria as well as splenomegaly, high arterial oxygen saturation and elevated leukocyte alkaline phosphatase activity. Possible causes of secondary erythrocytosis were ruled out. The renal biopsy revealed mesangial proliferative GN with predominant IgA deposition in mesangium. He was diagnosed as having IgAN and PV concomitantly. After administration of hydroxyurea, enalapril and felodipine, blood cell count and blood pressure normalized, while azotemia persisted. There was also a partial remission of the heavy proteinuria. We describe a case of IgAN associated with PV, and possible pathophysiologic relationships between two diseases are discussed with review of the literature.
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PMID:IgA nephropathy in a patient with polycythemia vera. Clinical manifestation of chronic renal failure and heavy proteinuria. 1216 77

The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (IMF), have overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Phenotypic mimicry amongst these disorders and between them and nonclonal hematopoietic disorders, lack of clonal diagnostic markers, lack of understanding of their molecular basis and paucity of controlled, prospective therapeutic trials have made the diagnosis and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak introduces current clinical controversies involving the CMPD, in particular the diagnostic challenges. Two new molecular assays may prove useful in the diagnosis and classification of CMPD. In 2000, the overexpression in PV granulocytes of the mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA appeared to be specific for PV since it was not observed in secondary erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1 in the presence of an elevated red cell mass supports a diagnosis of PV; absence of PRV-1 expression, however, should not be grounds for excluding PV as a diagnostic possibility. Impaired expression of Mpl, the receptor for thrombopoietin, in platelets and megakaryocytes has been first described in PV, but it has also been observed in some patients with ET and IMF. The biologic basis appears to be either alternative splicing of Mpl mRNA or a single nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead to impaired posttranslational glycosylation and a dominant negative effect on normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the best clinical evidence for treatment strategy design in PV and ET. Current recommendations for cytoreductive therapy in PV are still largely similar to those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep it at a safe level (hematocrit < 45%) remains the cornerstone of treatment. Venesection is an effective and safe therapy and previous concerns about potential side effects, including severe iron deficiency and an increased tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no other therapy for many years. For others, however, poor compliance to phlebotomy or progressive myeloproliferation, as indicated by increasing splenomegaly or very high leukocyte or platelet counts, may call for the introduction of cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic events and increasing the risk of leukemia with the use of cytoreductive drugs should be approached by patient risk stratification. Thrombotic deaths seem very rare in low-risk ET subjects and there are no data indicating that fatalities can be prevented by starting cytoreductive drugs early. Therefore, withholding chemotherapy might be justifiable in young, asymptomatic ET patients with a platelet count below 1500000/mm(3) and with no additional risk factors for thrombosis. If cardiovascular risk factors together with ET are identified (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet-lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni discusses the role of aspirin therapy in PV based on the recently completed European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a multi-country, multicenter project aimed at describing the natural history of PV as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular mortality were also reduced by 46% and 59%, respectively. Major bleedings were slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95% CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current understanding of the pathophysiology of IMF and, in particular, the contributions of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+) stem cell trafficking to disease pathogenesis. The role of newer therapies, such as low-conditioning stem cell transplantation and thalidomide, is discussed in the context of a general treatment strategy for IMF. The results of a Phase II trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis with meloid metaplasia (MMM) using a dose-escalation design and an overall low dose of the drug (The European Collaboration on MMM) will be presented. Considering only patients who completed 4 weeks of treatment, 31% had a response: this was mostly due to a beneficial effect of thalidomide on patients with transfusion dependent anemia, 39% of whom abolished transfusions, patients with moderate to severe thrombocytopenia, 28% of whom increased their platelet count by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of whom reduced spleen size of more than 2 cm.
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PMID:Chronic myeloproliferative disorders. 1463 83

Decreased visual acuity and loss of visual ability are devastating anesthetic and surgical complications. The incidence is greater in patients with preexisting hypertension, diabetes, sickle cell anemia, renal failure, gastrointestinal ulcer, narrow-angle glaucoma, vascular occlusive disease, cardiac disease, arteriosclerosis, polycythemia vera, and collagen vascular disorders. Precipitating factors for ischemic optic neuropathy include prolonged hypotension, anemia, surgery, trauma, gastrointestinal bleeding, hemorrhage, shock, prone position, direct pressure on the globe, and long operative times. Prone and Trendelenburg positions can lead to visual loss related to decreased venous return from the head. Visual impairment may result from increased intracranial pressure, which contributes to undue pressure on the optic nerve. The prone position increases the risk of direct compression injury to the orbit and corneal abrasion. Astute attention to positioning is imperative, especially with the prone position. At-risk patients should receive transfusion once the calculated allowable blood loss has been surpassed. Unacceptable hemoglobin and hematocrit values should be corrected preoperatively and levels monitored during the case to avoid intraoperative anemia in at-risk patients. The blood pressure of patients with predisposing diseases should be kept within normal limits. To avoid this devastating complication, it is imperative that anesthesia providers understand contributing factors and prevention strategies.
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PMID:Visual loss as a complication of nonophthalmologic surgery: a review of the literature. 1563 61

Relationship between presence of coronary heart disease (CHD), coronary risk factors (parameters of lipid transport system and hypertension) and disturbances of microcirculation was studied in patients with myeloproliferative blood disease Polycythemia Vera (PV). Probability of tissue (including blood vessel wall) cholesterol accumulation was estimated by measurement of its content in skin surface layers. PV patients (n=55, including 27 patients with CHD) had predominant hypolipoproteinemia with normal proportion of various lipoprotein classes. Absence of substantial increase of skin surface cholesterol content both in patients with and without CHD was considered to be a sign of low probability of the presence of severe atherosclerotic processes. However patients with CHD had substantially more pronounced disturbances of microcirculation. Basing on these data the authors suggest that CHD in PV patients had non-lipoprotein genesis and present discussion of alternative mechanisms of vascular changes.
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PMID:[Hypolipoproteinemia and secondary role of atherosclerosis in the development of ischemic heart disease in patients with polycythemia vera]. 1569 34

Erythromelalgia is a kind of cutaneous manifestation, which appears as a thrombotic complication in patients with myeloproliferative disorders such as essential thrombocythemia and polycythemia vera. It is characterized by red, congested distal extremities and a painful burning sensation, and is usually confined to the feet and one or more toes or fingers. A 28-year-old woman visited our hospital due to severe pain in the left thumb, index fingers and right toes. Her right toes and left thumb were erythematous, congested, and warm. She had a high blood pressure level of 190/100 mmHg, and laboratory evaluation revealed marked thrombocytosis. Bone-marrow findings were compatible with essential thrombocythemia. Renal angiography showed obvious stenosis in unilateral right renal artery. Her erythromelalgia immediately disappeared following interventional therapy along with aspirin. A careful history and appropriate evaluation of underlying diseases are important, because erythromelalgia as a microscopic thrombotic complication may be accompanied by vascular stenosis and all the resulting manifestations.
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PMID:Erythromelalgia as a presenting manifestation in a patient with essential thrombocythemia complicating renovascular hypertension due to unilateral renal artery stenosis. 1575 Aug 23

Polycythemia vera is a myeloproliferative syndrome. This clonal disorder involves a pluripotent stem cell capable of differentiating into red blood cells, granulocytes, and platelets. Polycythemia vera is characterized by the overproduction of mature red blood cells in the bone marrow. Myeloid and megakaryocytic elements are also often increased. Polycythemia vera (PV) is rarely associated with pregnancy. About 20 cases have been reported. Prognosis of PV is not influenced by pregnancy. Conversely, pregnancy outcome is poor, due to the occurrence of gestational hypertension, stillbirth and induced prematurity. During pregnancy, clinical management needs to be close including a collaborative approach between obstetricians, hematologists and anesthesists. The risk of poor outcome may be reduced by the association of antiaggregant and anticoagulant therapy. Phlebotomy can be provided in order to maintain hemoglobin level under 42%.
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PMID:[Polycythemia vera and pregnancy: difficulties for diagnosis and treatment]. 1587 88

Decreased visual acuity and loss of visual ability are devastating anesthetic and surgical complications. The incidence is greater in patients with preexisting hypertension, diabetes, sickle cell anemia, renal failure, gastrointestinal ulcer, narrow-angle glaucoma, vascular occlusive disease, cardiac disease, arteriosclerosis, polycythemia vera, and collagen vascular disorders. Precipitating factors for ischemic optic neuropathy include prolonged hypotension, anemia, surgery trauma, gastrointestinal bleeding, hemorrhage, shock, prone position, direct pressure on the globe, and long operative times. Prone and Trendelenburg positions can lead to visual loss related to decreased venous return from the head. Visual impairment may result from increased intracranial pressure, which contributes to undue pressure on the optic nerve. The prone position increases the risk of direct compression injury to the orbit and corneal abrasion. Astute attention to positioning is imperative, especially with the prone position. At-risk patients should receive transfusion once the calculated allowable blood loss has been surpassed Unacceptable hemoglobin and hematocrit values should be corrected preoperatively and levels monitored during the case to avoid intraoperative anemia in at-risk patients. The blood pressure of patients with predisposing diseases should be kept within normal limits. To avoid this devastating complication, it is imperative that anesthesia providers understand contributing factors and prevention strategies.
 ...
PMID:Visual loss as a complication of non-ophthalmic surgery: a review of the literature. 1594 13

Thrombosis is a frequent complication of polycythemia vera and essential thrombocythemia, but its incidence and predisposing factors in idiopathic myelofibrosis (IM) are unknown. In 18 (11.6%) of 155 patients diagnosed with IM in a single institution, 31 thrombotic events (19 arterial, 12 venous) were registered after a mean follow-up of 4.2 (s.d.: 4.5) years. In six patients, the thrombosis was simultaneous to or appeared a few months before IM diagnosis and 14 had one or more thrombotic episodes. When compared with the general population, a significant increase was observed in the incidence of venous thrombosis (odds ratio 17.5, 95% confidence interval: 10.3-31.4). At multivariate analysis, the initial variables associated with an increased risk of thrombosis were thrombocytosis (platelets >450 x 10(9)/l, P=0.001), presence of one cardiovascular risk factor (arterial hypertension, smoking, hypercholesterolemia, or diabetes, P=0.003), cellular phase of myelofibrosis (P=0.005), and Hb >11 g/dl (P=0.02). Considering post-diagnosis events, the 5-year thrombosis-free survival probability was 90.4% in the series, 80.6% for patients with platelets >450 x 10(9)/l, 82.6% for patients with one cardiovascular risk factor, and 85.1% for those in cellular phase. These results indicate an increased thrombotic risk for IM patients with hyperproliferative features and/or coexistent cardiovascular risk factors.
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PMID:Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution. 1630 11

A 39-yr-old man presented to our hospital with unexplained erythrocytosis and hypertension. His follow-up for erythrocytosis had begun 2 yr earlier in another hospital and he had been diagnosed with polycythemia rubra vera. On admission to our hospital he was hypertensive (165/95 mmHg) and, except for the presence of moon-like face and facial plethora, his physical examination was normal. His hemoglobin concentration was 19.2 g/dl, and hematocrit was 58.9% with an increased red blood cell mass of 58 ml/kg as measured by radioisotope (Cr51). Blood film, other hematological indices except for elevated leukocyte alkaline phosphatase score, arterial gas analysis, and examination of aspirated bone marrow were all normal. An abdominal ultrasonography showed no evidence of splenomegaly. A diagnosis of probable secondary erythrocytosis was made. Early-morning serum cortisol and 24-h urinary free cortisol concentration as well as serum ACTH were high. Serum cortisol was not suppressed by low-dose dexamethasone, but suppressed by high-dose dexamethasone. Pituitary magnetic resonance imaging showed no lesion. After inferior petrosal sinus sampling suggesting right-central ACTH secretion, the patient underwent transnasal-transsphenoidal pituitary adenomectomy. Both hypercortisolemia and erythrocytosis regressed completely after the adenomectomy. After the operation, the patient's hemoglobin concentration and hematocrit decreased steadily, and 1 month post-adenomectomy his hemoglobin is 14.9 g/dl and hematocrit 44.8%. Thus, Cushing's syndrome should be a routine part of evaluation of unexplained polycythemia.
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PMID:Polycythemia as the first manifestation of Cushing's disease. 1909 3


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