Inherited mutations in the erythropoietin receptor (EPOR) causing premature termination of the receptor cytoplasmic region are associated with dominant familial erythrocytosis (FE), a benign clinical condition characterized by hypersensitivity of erythroid progenitor cells to EPO and low serum EPO (S-EPO) levels. We describe a Swedish family with dominant FE in which erythrocytosis segregates with a new truncation in the negative control domain of the EPOR. We show that cells engineered to concomitantly express the wild-type (WT) EPOR and mutant EPORs associated with FE (FE EPORs) are hypersensitive to EPO-stimulated proliferation and activation of Jak2 and Stat5. These results demonstrate that FE is caused by hyperresponsiveness of receptor-mediated signaling pathways and that this is dominant with respect to WT EPOR signaling.

In this retrospective investigation from Malmö, a city well‐suited for epidemiologic studies, 177 patients (88 males and 89 females) with polycythemia vera (PV) were identified between 1950 and 1984. The incidence rate (number of cases/100 000/yr) in both sexes increased significantly, being 1.0 in 1950–1959 and 2.6 in 1980–1984 (adjusted to the European age‐standardized population). This is the highest rate reported to date. In 1970–1984 the highest age‐specific incidence rates (number of cases/100 000/yr) were found in males ≥ 80 yr and females 70–79 yr of age, being 18.3 and 14.6, respectively. A subgroup of 12 (7%) was identified where the PV diagnosis was not obvious on entry into the study but where it became clear during follow‐up. 16 PV patients (9%) had verified or suspected arterial hypoxemia caused by a concomitant condition. We conclude that the increasing PV incidence rates, mainly confined to older age groups, are probably due to better case ascertainment.

To assess the importance of occult atrial disorder with possible embolization as a cause of non-hemorrhagic stroke, 68 patients with neurologic symptoms lasting 24 hours or more and 18 patients with transient ischemic attacks were examined by long-term electrocardiographic recording (LTER). Lacking matched controls we used a reference population of 103 elderly subjects selected at random from the general population for a previous LTER study. Permanent or episodic atrial arrhythmias of types known to cause cerebral embolization were detected by LTER in 32 (47%) of the 68 patients with a clinical diagnosis of cerebral embolization or thrombosis and in 6 (33%) of the 18 patients with transient ischemic attacks. Of the 38 patients with atrial arrhythmia during LTER 17 had such arrhythmias in their standard ECGs. This frequency of atrial arrhythmias during LTER differs from that of the reference population (p less than 0.025). Thirteen of 16 patients with multiple cerebral lesions had signs of atrial arrhythmia during LTER. Patients having occult atrial disorder with episodic atrial arrhythmia may be an important and common risk group for non-hemorrhagic stroke in addition to the previously recognized group of patients with atrial arrhythmia detectable in the standard ECG. LTER may be important in the evaluation of patients with unexplained stroke.

Erythrocytosis was found in 6 members of one family and was associated with the presence of a new abnormal haemoglobin, Hb Malmö β 97 (FG 4) His → Gln showing increased affinity for oxygen. Radiological pulmonary changes, possibly precancerous, also occurred in several members of the family. The pulmonary changes and Hb Malmö are thought to be caused by separate genes, and the mode of inheritance of both is considered autosomal dominant.

ABSTRACT.Purpose: To determine if dark adaptation is reduced in individuals with polycythemia and if so whether there is any improvement in dark adaptation after treatment. Methods: Dark adaptation was recorded monocularly by automatic dark adaptometry in ten consecutive patients with polycythemia before and after treatment. Analogue investigations were performed in 31 healthy control subjects. Results: Dark adaptation was markedly impaired in the patients as compared with the control subjects. After reduction of the red cell count and normalization of the hematocrit and hemoglobin the dark adaptation was markedly improved. There was no significant change in dark vision in the control subjects negating a confounding learning effect. Conclusion:The findings indicate a sustained but reversible neuronal hypofunction secondary to polycythemia. As the rheological abnormality was normalized, dark adaptation was improved, probably secondary to normalized microcirculation within the retina or the brain, or both, possibly with reactivation of formerly inactive neuronal cells.Key words: dark adaptation -polycythemia -phlebotomy -chronic penumbra Acta Ophthalmol. Scand. 1999: 77: 00-00 Copyright c Acta Ophthalmol Scand 1999. ISSN 1395-3907 I t has recently been shown that dark adaptation is highly reduced in patients with symptomatic carotid artery stenosis (Havelius et al. 1997a) and that this reduction is bilaterally reversible after endarterectomy (Havelius et al. 1997b). Although the improvement in dark adaptation is secondary to the removal of high degree carotid artery stenoses at the carotid artery bifurcations, it could not easily be explained by gross hemodynamic changes (Havelius et al. 1997b). Consequently, we became interested in how rheological abnormalities may affect dark adaptation by means of a perturbed microcirculation within the retina and brain. This was the impetus for this study of dark adaptation in patients with polycythemia studied pre-and posttreatment. Subjects and MethodsTen consecutive patients (six men and four women; age 44-75, mean 64.2 years) with polycythemia were examined by dark adaptometry. Eight patients had polycythemia vera and two patients suffered from polycythemia secundaria. One of the latter had an erythropoietin producing renal adenocarcinoma and the other respiratory insufficiency. Only anamnestically ophthalmologically healthy patients were included. Visual acuity was 1.0 in 18 eyes, 0.9 in one eye and 0.5 in one eye (due to a moderate cataract). The refractions were between ª1.25 and π5.0. The degree of astigmatism was between 0 and ª1.25.Clinical details about the patients are presented in Table 1. 31 control subjects (18 men and 13 women; age 47-79, mean 64.4 years) were examined by dark adaptometry. These individuals have been described in detail in earlier publications (Havelius et al. 1997a(Havelius et al. , 1997b. The control subjects were ophthalmologically healthy with a visual acuity of 1.0 (62 eyes), refractions betweeen ª1.75 and π4.0 and astigmatism ranging b...