Cerebral blood flow and blood viscosity in patients with polycythaemia secondary to hypoxic lung disease.

Blood viscosity, cerebral blood flow (CBF) and cerebral oxygen carriage (CBF X arterial oxygen content) were measured in 12 patients with polycythaemia secondary to hypoxic lung disease. CBF and cerebral oxygen carriage were both significantly higher than in a comparative group of 20 patients with raised packed cell volumes and normal lung function. The patients with secondary polycythaemia then underwent venesection and their mean packed cell volume fell from 0.613 to 0.495. This led to a consistent reduction in blood viscosity, which fell by 44% at a low shear rate (0.67/s) and 33% at a high shear rate (0.91/s). CBF rose by 21% (p less than 0.01), but cerebral oxygen carriage did not significantly increase in the group as a whole. Four of the patients with secondary polycythaemia had complained of episodes of confusion before venesection, which improved considerably once the packed cell volume had been lowered. Headache was relieved in a further two patients and none of the subjects was adversely affected by venesection. It was not possible, however, to show a correlation between symptomatic improvement and an increase in cerebral oxygen carriage.     

Exchange Transfusion with Dextran 40 in Polycythaemia Secondary to Hypoxic Lung Disease

In eight patients with polycythaemia secondary to hypoxic lung disease 10 elective exchange transfusions were performed to reduce red cell mass, packed cell volume (P.C.V.), and whole blood viscosity. The rationale for reducing P.C.V. is discussed. It is concluded that patients with P.C.V. of 60% or over will benefit from exchange transfusion and that most patients with P.C.V. over 50% and true polycythaemia will also benefit. We also confirm that the technique of exchange transfusion is a rapid, safe, and effective method of achieving large venesections and reducing red cell mass.     

Intermittent hypoxia in patients with unexplained polycythaemia.

The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly.     

Plasma androstenedione in normotensive and hypertensive pregnancy

The average plasma concentration of androstenedione (A) in 67 hypertensive pregnant women (mean 25.7 nmol/L, SD 10.0) was significantly higher (p less than 0.001) than that in 71 normotensive pregnant women (mean 14.2 nmol/L, SD 5.6). Androstenedione concentration decreased significantly (p less than 0.01) from this higher level with increasing gestation in pregnancies complicated by hypertension. In the normotensive group there was no significant correlation between androstenedione concentration and gestation, but a sharp increase in androstenedione concentration occurred prior to delivery. The androstenedione concentration in 18 hypertensive patients with fulminating disease (mean 30.7 nmol/L, SD 11.9) was significantly higher (p less than 0.02) than that in 49 hypertensive patients (mean 23.9 nmol/L, SD 8.7). The correlation between androstenedione and 19-hydroxyandrostenedione (19-OH-A) concentrations in plasma was highly significant; for 98 pairs, r = 0.43, p less than 0.001.     

Hyaluronate in bronchoalveolar lavage fluid: a new marker in sarcoidosis reflecting pulmonary disease.

Hyaluronate (hyaluronic acid) was not detectable in bronchoalveolar lavage fluid from smoking or nonsmoking healthy volunteers but was present in fluid from 23 patients with sarcoidosis; the mean concentration was 16 micrograms/1 returned fluid (range less than or equal to 5-430) or, expressed in relation to the amount of albumin recovered, 0.22 micrograms/mg albumin (range less than or equal to 0.05-3.6). The serum hyaluronate concentrations in the patients with sarcoidosis were normal. There was a significant inverse correlation between vital lung capacity and hyaluronate concentrations in bronchoalveolar lavage fluid (p less than 0.001), and patients with abnormal lung volumes had hyaluronate concentrations that were on average six times higher than those in patients with normal vital capacity. Duration of disease, pulmonary radiological findings, and markers for macrophage activation (angiotensin converting enzyme) and lymphocyte activation (beta 2 microglobulin) were not correlated with bronchoalveolar lavage fluid hyaluronate. It was concluded that in sarcoidosis release of hyaluronate into the airways is related to lung volume and therefore to the course of the disease. Increased synthesis of hyaluronate in lung parenchyma may reflect activation of fibroblasts, and measurements of hyaluronate may have clinical value for prognosis and treatment.     

Effect of the amplitude and frequency of sinusoidal stimulation on the harmonic distortion of the response of sensory terminations of muscle spindles

Harmonic distortion (HD) from 1,055 responses of muscle spindles sensory endings to sinusoidal stretches (frequency range 0.0008 to 0.8333 Hz, amplitude range 0.019 to 3.09 mm) has been studied in the cat soleus muscle. Sixty-six per cent were primary afferents (Ia) and 34% secondary (II). HD mean value (0.28) did not show any significant differences between both types of endings. Analysis of variance for HD versus stimulation amplitude showed a greater HD when stretch amplitudes were beyond 1.599 mm or less than 0.031 mm on primary afferents (p less than 0.001) and less than 0.070 mm on secondary (p less than 0.001). The effect of stimulus frequency was also significant (p less than 0.01 Ia and p less than 0.001 II), however only at 0.8333 Hz and in secondary endings HD was significantly higher. The silent period in the response, at release of stretch, caused by half wave rectification could explain about 50% of measured HD.     

Haptoglobin patterns in essential hypertension and associated conditions--increased risk for Hp 2-2

Blood samples from 257 hypertensive patients and 180 normotensive controls were analysed for their association with haptoglobin levels and phenotypes. Compared to controls, patients with Hp 2-2 phenotype showed a significantly increased risk for essential hypertension (p less than 0.001) and hypertension associated with ischaemic heart disease (p less than 0.05). There was a significant decrease in the mean levels of serum haptoglobins in hypertension as compared to controls, suggesting the possibility for intravascular haemolysis due to vascular damage leading to further complications.     

Control of ventilation in elite synchronized swimmers

Synchronized swimmers perform strenuous underwater exercise during prolonged breath holds. To investigate the role of the control of ventilation and lung volumes in these athletes, we studied the 10 members of the National Synchronized Swim Team including an olympic gold medalist and 10 age-matched controls. We evaluated static pulmonary function, hypoxic and hypercapnic ventilatory drives, and normoxic and hyperoxic breath holding. Synchronized swimmers had an increased total lung capacity and vital capacity compared with controls (P less than 0.005). The hypoxic ventilatory response (expressed as the hyperbolic shape parameter A) was lower in the synchronized swimmers than controls with a mean value of 29.2 +/- 2.6 (SE) and 65.6 +/- 7.1, respectively (P less than 0.001). The hypercapnic ventilatory response [expressed as S, minute ventilation (1/min)/alveolar CO2 partial pressure (Torr)] was no different between synchronized swimmers and controls. Breath-hold duration during normoxia was greater in the synchronized swimmers, with a mean value of 108.6 +/- 4.8 (SE) vs. 68.03 +/- 8.1 s in the controls (P less than 0.001). No difference was seen in hyperoxic breath-hold times between groups. During breath holding synchronized swimmers demonstrated marked apneic bradycardia expressed as either absolute or heart rate change from basal heart rate as opposed to the controls, in whom heart rate increased during breath holds. Therefore the results show that elite synchronized swimmers have increased lung volumes, blunted hypoxic ventilatory responses, and a marked apneic bradycardia that may provide physiological characteristics that offer a competitive advantage for championship performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum free thyroxine and thyroxine-binding globulin concentrations in early phase of subacute thyroiditis

Serum total thyroxine (T4), total triiodothyronine (T3), T4-binding globulin (TBG), free T4(FT4) and free T3(FT3) concentrations and the T3-uptake(T3-U) value were estimated in 11 patients with subacute thyroiditis, and compared with the same parameters in 11 patients with Graves' disease, whose serum T4 concentrations were similar to the former group. Seven patients with subacute thyroiditis, who were treated with dicrofenac sodium alone, were investigated as to the sequential changes in serum parameters during their clinical courses. The mean serum T3-U value and FT4, T3 and FT3 concentrations in patients with subacute thyroiditis were increased, but all were significantly lower than those in patients with Graves' disease (p less than 0.01, p less than 0.001, p less than 0.001 and p less than 0.001, respectively). Three patients with subacute thyroiditis, who showed shorter duration of symptoms than 10 days, had serum TBG excess. Thus the mean (+/- SD) serum TBG concentration (26.5 +/- 8.4 micrograms/ml) was significantly higher than that (18.3 +/- 2.9 micrograms/ml) in patients with Graves' disease (p less than 0.02). The ratios of serum T3 to T4 and FT3 to FT4 in patients with subacute thyroiditis were also significantly lower than those in patients with Graves' disease (p less than 0.001 and p less than 0.001, respectively). The serum FT4 in 7 patients treated with dicrofenac sodium alone decreased to the normal range after 3 to 8 weeks from the onset of the illness. In 3 patients with TBG excess and one patient (TBG; 29.0 micrograms/ml), serum TBG declined in consequence of the serum FT4 normalization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium derived relaxing factor

Inhibition of the synthesis of endothelium derived relaxing factor by NG-monomethyl-L-arginine, a competitive inhibitor of the synthesis of nitric oxide from L-arginine, enhances hypoxic pulmonary vasoconstriction in pulmonary artery rings and isolated, Krebs albumin perfused rat lungs. L-arginine rapidly reduces hypoxic vasoconstriction, particularly in lungs treated with NG-monomethyl-L-arginine. Following administration of NG-monomethyl-L-arginine, bradykinin-induced vasodilatation is inhibited (p less than 0.01) and a bradykinin-induced vasoconstriction develops (p less than 0.001). NG-monomethyl-L-arginine does not significantly diminish acetylcholine-induced vasodilatation in the isolated lung. NG-monomethyl-L-arginine causes an endothelium-dependent vasoconstriction in pulmonary artery rings.     

Morbidity and survival in neonates ventilated for the respiratory distress syndrome.

In a retrospective analysis the records of all (210) infants ventilated to treat the respiratory distress syndrome over three years were reviewed. A mortality of 19% was found. Intraventricular haemorrhage was associated than a significant increase in mortality in infants of less with 30 weeks'' gestation (p less than 0.001) and was the commonest cause of death. Pneumothoraces developed in one third of babies regardless of gestational age but were significantly associated with an increase in mortality only in infants of 27-29 weeks'' gestation. Patent ductus arteriosus was present in 31 infants and was commoner in babies of very low birth weight. The presence of a patent ductus arteriosus was not associated with decreased survival but was significantly related to an increased need for prolonged respiratory support (p less than 0.001). Thirty six infants developed chronic lung disease, three of whom died. Comparison with data from earlier studies indicated a steady improvement over the past decade in outcome for infants ventilated for the respiratory distress syndrome.     

Reduced plasma lipoprotein lipase activity in patients with malignancy-associated weight loss

Post-heparin plasma lipoprotein lipase activity was measured in 28 cancer patients with varying degrees of weight loss, and in 16 normal volunteers. Total lipoprotein lipase activity was decreased by 35.4% (P less than 0.001) in the cancer group. The component lipase activities, hepatic (HLPL), and peripheral (PLPL), were decreased by 40% (P less than 0.001) and 38% (P less than 0.005) respectively. In addition, the level of total peripheral lipoprotein lipase correlated well with the percent body weight lost by these patients (r = 0.6, P less than 0.01). Regardless of extent of disease, patients with lung cancer showed the lowest enzyme activity (mean 191 mU/ml +/- 30 SEM, P less than 0.001) and the greatest percent of weight loss (mean 16%), while patients with breast cancer had nearly normal lipase activity (mean 315 mU/ml +/- 50 SEM, normal 340 mU/ml +/- 22 SEM, P less than 0.10) and minimal weight loss (mean 8.4%). Fasting serum triglycerides were significantly elevated in the patient group (mean 120 mg/dl +/- 9.7 SEM) as compared to normal (mean 71 mg/dl +/- 7 SEM, P less than 0.001). The mean fasting insulin level was elevated in the patient group (13 mU/ml +/- 3.0 SEM), although in the majority of the patients it was found within the normal range (4-24 mU/ml). We conclude that the significant decrease in the total LPL activity may be responsible in part for the characteristic hypertriglyceridemia present in cancer patients.     

Controlled trial of azathioprine in chronic ulcerative colitis.

A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction was greater among those who took azathioprine (p less than 0.001). Activity of the disease apparently improved in both treatment groups but a significant (p less than 0.001) trend was observed only in those patients treated with azathioprine. No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea. Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual, or for whom continuous systemic corticosteroid treatment is needed to control symptoms, and for whom surgical treatment is inappropriate.     

Correlation of persistently high serum amyloid A protein and C-reactive protein concentrations with rapid progression of secondary amyloidosis.

The importance of serum amyloid A protein in the progression of renal failure was studied over three years in 28 patients with secondary (amyloid A type) amyloidosis predominantly due to rheumatoid arthritis. Creatinine clearance, the amount of protein in the urine, and serum amyloid A and C-reactive protein concentrations were determined regularly. Linear regression analysis showed a close correlation between the change in creatinine clearance each year and both serum amyloid A concentrations (20 patients: r= -0.83, p less than 0.001) and C-reactive protein concentrations (28 patients: r= -0.80, p less than 0.001). The correlation between serum amyloid A and C-reactive protein concentrations was also significant (317 parallel measurements: r=0.81, p less than 0.001). These findings suggest that monitoring serum amyloid A or C-reactive protein concentrations is valuable in assessing the prognosis in secondary amyloidosis and that therapeutic measures that lower serum amyloid A concentrations may reduce the formation of amyloid.     

Empirical risk of oligophrenia in siblings of proband-oligophrenics in populations with high levels of inbreeding]

An investigation is carried out on 214 patients with oligophreny with regard to the secondary risk of the same disease for their four sibs. All patients were divided into 4 groups according to etiological symptoms, and it was found that maximal risk of the secondary disease with oligophreny was for the sibs of probably genetic group, and minimal one--for the sibs of the exogenic group. Maximal resemblance in the degree of the defect in the pair of proband-sibs was found both in probably-genetic and presumably-genetic groups. The risk of secondary oligophreny was significantly higher in sibs-probands with relatively lower degree of weak-mindedness than in those with severe mental defects. The frequency of the secondary oligophreny amond sibs of the inbred origin (18.9%) was more than twice as high (P less than 0.001) as in those of outbred origin (8.3%).     

Effect of venesection on calf blood flow in polycythaemia.

Calf blood flow at rest and during postocclusive reactive hyperaemia was measured using an electrocardiogram-triggered plethysmograph in 14 patients with polycythaemia (nine with primary disease and five with polycythaemia secondary to cyanotic heart disease) before and after a course of venesection. The mean packed cell volume was reduced from 0.57 to 0.47, and whole-blood viscosity fell by 50% at low shear rates. Venesection did not affect rest flow, but peak flow was increased by 18%. The increase in peak flow failed to compensate for the reduced haemoglobin content of the blood, calculated haemoglobin delivery being reduced by 23% at rest and 10% during reactive hyperaemia. These results indicate that while venesection improves blood viscosity, this does not necessarily lead to improved delivery of oxygen to the tissues.     

Aggregative behavior and calcium content of platelets in thrombocythemia and thrombocytosis]

Patients with thrombocythaemia due to myeloproliferative disorders (n = 21), with secondary thrombocytosis of various origin (n = 16), and a control group of healthy donors (n = 20) were investigated with respect to the aggregation behaviour and the total calcium content of blood platelets. The calcium content was significantly lower in both groups of patients as compared to controls (2 p less than 0.001). In 16 of 21 patients with myeloproliferative disorders platelet rich plasma did not respond to epinephrine (15 mumol/l), a concentration which induced at least weak aggregation in 14 of 16 patients with secondary thrombocytosis and also in healthy subjects. In patients with thrombocythaemia the mean extent of aggregation induced by epinephrine, collagen or adenosin diphosphate was significantly lower as compared to controls (2 p less than 0.001).     

Haemocompatibility of extracorporeal circulation technique with autooxygenation: influence on platelet function and homologous blood requirement.

Forty male patients: group A-autooxygenation and group B-bubble oxygenator used in extracorporeal circulation (ECC) were studied to evaluate the haemocompatibility of 2 types of ECC. The Plt count dropped significantly in group B patients: -73% of initial value vs only -27% in group A, (p less than 0.001). In both groups a rise in BTG was shown, but higher in group B, p less than 0.001. At the end of CPB aggregation decreased only slightly in group A after epinephrine and 4-ADP, and decreased hardly in group B with the significant difference between two groups (p less than 0.02 and p less than 0.001, respectively). In group A the mean blood loss was 278 +/- 49 ml/m2 and 483 +/- 67 ml/m2 in group B, p less than 0.001. The mean blood transfusion in group A and B was 198 +/- 82 ml/m2 and 427 +/- 85 ml/m2, respectively (p less than 0.001). We are positive that the elimination of artificial oxygenator from the ECC diminished markedly the decline in Plt count and Plt activation during CPB.     

Intravitreal bevacizumab (Avastin) in treatment of neovascular age-related macular degeneration

To evaluate the efficacy and safety of intravitreal bevacizumab in treatment of minimally classic and occult choroidal neovascularization secondary to age-related macular disease 48 eyes of 48 patients (mean age of 74.8) included in this prospective, noncomparative, interventional case series. Median follow-up was 18 weeks (6-24). Intravitreal bevacizumab injection of 0.05 mL (1.25 mg) was administered at baseline and in 6 week intervals until leakage resolved, and repeated in case of leakage recurrence. Visual acuity (VA) improved in the majority of patients (mean baseline VA = 1.078 log MAR) by mean increase of 1.32 lines (last follow-up) (p = 0.001). Central foveal thickness and total macular volume decreased by 51 microm (p = 0.01) and 0.84 mm3 (p < 0.0001) respectively. No serious complications were observed. As initial therapy, intravitreal bevacizumab appears to be safe and effective. A significant functional and anatomical improvement was noted in majority of patients and maintained during follow-up.     

Serum beta-glycosidases in diabetes mellitus

Levels of fasting blood glucose, serum beta-glucuronidase and beta-N-acetylglucosaminidase in 47 Libyan diabetic patients were determined. The respective mean values were 254.5 +/- 11 mg/dl, 74 +/- 5.7 Sigma units/ml and 171.8 +/- 25.5 microM PNP/dl. The mean body mass index and duration of diabetes of the patients were 30.5 +/- 0.91 kg/m2 and 7.5 +/- 1.16 years, respectively. Statistically significant correlations were found between fasting blood glucose and serum beta-glucuronidase levels (r = 0.65; p less than 0.001) and also between fasting blood glucose and beta-N-acetylglucosaminidase levels (r = 0.58; p less than 0.001). The activities of these two enzymes increase in serum with increasing fasting blood glucose levels. Patients with positive family history of diabetes have higher activities of these two enzymes than those without positive history of diabetes in the family. Patients with secondary complications have both enzymes elevated as compared with patients without secondary complications. Female patients have higher beta-N-acetylglucosaminidase activity and lower beta-glucuronidase activity than males. Age and duration of diabetes do not appear to have any effect on the activities of these enzymes.