Four pedigrees of the cation-leaky hereditary stomatocytosis class presenting with pseudohyperkalaemia. Novel profile of temperature dependence of Na+-K+ leak in a xerocytic form.

We report four pedigrees of the group of Na(+)-K(+)-leaky red cell disorders of the 'hereditary stomatocytosis' class. Each showed pseudohyperkalaemia because of temperature-dependent loss of K(+) from red cells on storage of whole blood at room temperature. All pedigrees showed an abnormality in the temperature dependence of the 'passive leak' of the membrane to K(+). Two pedigrees, both of which showed a compensated haemolytic state with dehydrated red cells and target cells on the blood film, showed a novel pattern, in which the profile was flat between 37 degrees C and about 32 degrees C then dropped as the temperature was reduced to zero. The third showed the 'shallow slope' profile, with stomatocytes on the blood film and very markedly abnormal intracellular Na(+) and K(+) levels. Minimal haemolysis was present. The fourth pedigree, of Asian origin, showed the shoulder pattern (minimum at 32 degrees C, maximum at 12 degrees C) with essentially normal haematology. Both of these latter two forms have previously been seen in other pedigrees. The first variant represents a novel kind of temperature dependence of the passive leak found in these pedigrees presenting with pseudohyperkalaemia.

A family showing recessively inherited multisystem pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene.

The case of a French child, born of consanguineous parents of Tunisian origin, is described. He showed a severe multisystem disease with dyserythropoietic, sideroblastic anaemia, delayed neurological development with hypotonia and convulsions, salt-losing nephropathy, chronic watery diarrhoea, lactic acidosis with mitochondrial dysfunction, brittle hair, hypergammaglobulinaemia, fatty liver with intermittent transaminasaemia, and terminal pulmonary fibrosis. Two siblings, of both sexes, were stillborn; two more lived only a short time. One sister is alive and well. SDS gel analysis of the red cell membranes showed a deficiency within 'Band 7' at 32 kDa. Analysis of the gene encoding 'stomatin', or 'erythrocyte membrane protein 7.2b', the principal protein of 'Band 7', revealed a complex series of aberrant spliceforms centred around exon 3, for which no explanatory genomic lesion could be found. The true underlying molecular cause of this condition remains obscure, but it suggests that the stomatin gene should be studied in other cases.

Allogeneic bone marrow transplantation for severe post-splenectomy thrombophilic state in leaky red cell membrane haemolytic anaemia of the stomatocytosis class.

The tendency for thrombosis to occur if haemolysis persists after splenectomy is especially marked in "hereditary stomatocytosis", in which the red cell membrane "leaks" Na and K. A 21-year-old woman, who was splenectomized in childhood for a congenital haemolytic state, presented with major pulmonary embolism that recurred despite anticoagulation. Tests showed a significant cation leak with a "shallow-slope" abnormality in temperature dependence. Allogeneic bone marrow transplantation caused the thrombophilic state to cease and subsequently anticoagulation was stopped without recurrence of thromboembolism. However, she died 9 months after transplantation: iron overload, intensified by the transfusion demands of the transplant, was a major factor.

Two further British families with the 'cryohydrocytosis' form of hereditary stomatocytosis.

We describe two families with the 'cryohydrocytosis' form of stomatocytosis. Both show a mild stomatocytic anaemia with Hb levels of 12-16 g/dl and reticulocyte counts of 4.3-24%, with very marked autohaemolysis at refrigerator temperatures and pseudohyperkalaemia as a result of loss of K from red cells on storage at room temperature. The ouabain + bumetanide-insensitive 'passive leak' K influx showed a 'U'-shaped temperature dependence, with a minimum at 23 degrees C. In one family, there was consistent variation in haematological severity within the pedigree. In the other, the parents of the proposita were normal, but all three of her children were affected, consistent with a new mutation of a dominant condition. Cold storage of the red cells led to a very marked increase in osmotic fragility and macrospherocytosis, explaining why a diagnosis of 'hereditary spherocytosis' can easily be reached in these pedigrees.

Pseudohyperkalaemia and pseudomacrocytosis caused by inherited red-cell disorders of the 'hereditary stomatocytosis' group.

Unusual dominantly inherited conditions of the red cell, collected under the generic title 'hereditary stomatocytosis and allied disorders', exist, in which the red cell 'leaks' the univalent cations sodium (Na+) and potassium (K+). In some kindreds with these disorders, bizarre temperature effects can occur that have profound effects on the way in which the cells behave when removed from the body and cooled to either room or refrigerator temperatures. In some types, the cells lose K+ at room temperature, giving rise to pseudohyperkalaemia; in others, this occurs in concert with swelling of the red cell and pseudomacrocytosis. In some of these conditions, a red-cell abnormality is clearly demonstrated by the presence of haemolytic anaemia; however, routine haematology can be virtually normal in the milder versions. All are inherited as dominants, although new mutations can be seen.

Familial pseudohyperkalaemia Chiswick: a novel congenital thermotropic variant of K and Na transport across the human red cell membrane.

Two families with inherited abnormalities in Na and K transport across the red cell membrane are described. Both presented with 'pseudohyperkalaemia' as a result of loss of K from the red cells on storage at room temperature. Routine haematology was essentially normal, except for macrocytosis in one family. Studies of the temperature dependence of the passive leak to K showed a novel shoulder pattern with a minimum at 25 degrees C, a maximum at 10 degrees C, followed by a further fall. As in other cases of red cell-based pseudohyperkalaemia, the abnormal temperature dependence of this 'leak' flux could be held to account for the loss of K from the cells at room temperature. These cases represent a novel variant of the temperature dependence of the passive leak of K and Na across the red cell membrane, and can be classified as a mild, non-haemolytic form of the group known as the hereditary stomatocytosis and allied disorders'.

Two British families with variants of the 'cryohydrocytosis' form of hereditary stomatocytosis.

We describe two British families with similar, dominantly-inherited, temperature-related variants of hereditary stomatocytosis, consistent with the original description of 'cryohydrocytosis'. The cells show a 5-6-fold increase in passive permeability at 37 degrees C with abnormal intracellular Na and K levels at 15-20 and 60-65 mmol/(l cells) respectively. Marked temperature effects were evident: lysis of red cells on storage in the cold was blatant and when whole heparinized blood was stored at room temperature, K accumulated in the plasma, producing 'pseudohyperkalaemia'. Studies of the temperature dependence of passive permeability showed that the minimum in the passive permeability, which is seen in normal cells at 8-10 degrees C, was shifted up to 23 degrees C in these abnormal cells, such that the permeability at 0 degrees C exceeded that at 37 degrees C. The abnormal temperature dependence in these genetically abnormal red cells strongly resembles that seen in normal cells when suspended in media in which either Na or Cl has been replaced by an organic cation or anion: it could be said these cells had a genetic mutation that somehow rendered the cell resistant to the stabilizing action of NaCl at low temperatures.

A variant of hereditary stomatocytosis with marked pseudohyperkalaemia.

A family with an unusual form of hereditary stomatocytosis is described. The affected members showed a mild, dominantly-inherited, haemolytic anaemia with intracellular Na and K levels of 41-48 and 44-53 mmol/(l cells) respectively. This anaemia was associated with marked 'pseudohyperkalaemia': that is, loss of K from red cells on storage at room temperature. At 37 degrees C, 'leak' tracer flux rates (assessed as the ouabain + bumetanide-resistant K fluxes) showed a roughly 5-fold acceleration compared to normal, and an abnormal temperature dependence with a shallow slope between 37 and 20 degrees C (mean Q10 (ratio of reaction rates at temperature T and T - 10) over this interval, 1.6; normal 2.2). The pseudohyperkalaemia could be attributed to the disparity between pump and leak at 20 degrees C. This is an identical mechanism to that previously shown for the haemato logically trivial condition, 'familial pseudohyperkalaemia. No protein or lipid abnormality was found in the membrane of these cells.

A long-term prospective assessment of home nebulizer treatment.

Forty-nine patients (15 asthma, mean FEV1/FVC 1.3/2.1; 34 COPD, mean FEV1/FVC 0.7/1.8) were referred for consideration of home nebulizer treatment. All were monitored for 2 weeks while using their usual inhaled treatment followed by 2 weeks using a 'Nebuhaler' spacer to deliver 1 mg of terbutaline and 80 micrograms of ipratoropium bromide (IB) four times daily. They then borrowed a System 22 nebulizer to self-administer salbutamol nebulizer solution (5 mg), IB unit dose vials (0.5 mg) or a mixture of these drugs four times daily for 1 month each. Both asthmatic and bronchitic patients had a significant rise in their mean daily peak flow rate (PFR) during home nebulizer treatment (P < 0.03) and the COPD patients also had a significant PFR rise during Nebuhaler treatment (P = 0.0004). The mean daily peak flow rates (PFR 1 min-1 were: baseline 179, Nebuhaler 195, salbutamol nebulizer 200, IB nebulizer 198, mixed nebulizer 216). Four patients failed to respond subjectively or objectively to either Nebuhaler or nebulizer treatment. Five patients responded well to Nebuhaler treatment and did not proceed to a home nebulizer trial. Eight further patients preferred Nebuhaler to nebulizer treatment or could not tolerate nebulizer treatment (two cases). Thirty-two patients requested home nebulizer treatment for long-term use (nine salbutamol, five IB, 18 mixture). Twenty-seven of these patients had an increased mean daily PFR (compared to their usual therapy) while using their chosen nebulized treatment. The mean increase in PFR for all 32 patients was 191 min-1 (11%).(ABSTRACT TRUNCATED AT 250 WORDS)

Nelson's syndrome and behavioural changes reversed by selective adenomectomy.

A man with Nelson's syndrome developed severe associated behavioural and psychiatric problems, which completely resolved following selective resection of his pituitary tumour. It is postulated that ACTH, beta-endorphin, or related peptides may have caused these problems.

An assessment of the Coulter Counter Models S Plus II and III.

The Coulter Counter Models S Plus II and III have been evaluated. No serious safety hazards were identified. Scientific assessment showed some non-linearity in the Hb which caused the MCH and MCHC to vary as samples were diluted. Precision and carry-over were satisfactory. The results obtained compared well with those of the Coulter Counter Model S, except for WBC; reference methods showed better accuracy on the Models S Plus II and III. Platelet counts agreed with those by phase-contrast microscopy and the lymphocyte percentage was similar to that from the blood film except in the lymphoproliferative disorders. The whole blood and pre-dilute modes gave similar results though the platelet count was slightly higher in the whole blood mode. In the National External Quality Assessment Scheme results were in accordance with those from other Model S Plus Users. Time did not allow a detailed evaluation of the cell volume distribution curves but it was noted that the white cell profile was useful for detecting platelet aggregation. Efficiency assessment showed throughputs of 66 and 93 samples per hour on the Models S Plus II and III respectively. The platelet count was clinically useful as was the lymphocyte percentage measurement which rendered some differentials unnecessary. Rejection of the white cell profile was a helpful index of abnormality on the Model S Plus II but occurred non-specifically on the Model III tested.

Estimation of lymphocyte percentage and number on the Coulter Counter, Model S Plus Phase II.

The Coulter Counter Model S Plus Phase II provided precise measurements of lymphocyte percentage and count and carry-over was negligible. Lymphocyte percentage values agreed well with those from the stained blood film except when the percentage was high and in these circumstances the instrument gave underestimates. When making artificial mixtures with increasing lymphocyte count a progressive underestimation of the lymphocyte percentage was also noted. The display of leucocyte volume distribution was found to be a useful attribute particularly when the instrument alerted the operator to "rejected" profiles. Rejection by the instrument proved to be a helpful function occurring in the myeloid leukaemias, erythroblastosis, and in some cases when the lymphocytes differed from normal--for example, glandular fever and chronic lymphocytic leukaemia.

An assessment of the Ortho ELT-8.

The Ortho ELT-8 is an automated blood counter which appears to be safe, precise and free from carry-over. Red and white cell results generally agree with those on the Coulter Counter, Model S, though discrepancies were noted with the WBC and PCV. Reference methods showed the Model S WBC results tended to be inaccurate on the discrepant samples though neither instrument was predominantly responsible for the PCV discrepancies. The ELT-8 platelet count tended to be higher than with the Thrombocounter/Thrombofuge system. When packed cells were diluted in autologous plasma serious variations in the red cell indices (MCV, MCH & MCHC) were first found due to incorrect voltage-frequency converter setting. Even after this setting had been corrected some variations in the MCH and MCHC were still apparent. In the UK National External Quality Assessment Scheme the ELT-8 results on animal bloods did not agree with those produced by Model S users; this discrepancy probably being due to differences between the light-scattering and aperture-impedance technology.