Non-cardiogenic pulmonary edema, rhabdomyolysis and myocardial injury following heroin inhalation: a case report.

BACKGROUND: Heroin use by non-injecting routes of administration (snorting, swallowing, "chasing the dragon") is considered to be safer but is not risk-free for fatal overdose or serious side effects. We report the case of an adolescent who was transferred unconscious to the emergency department after heroin inhalation. Description of the case: A 17-year-old male was transferred to the emergency department unconscious (Glasgow coma scale: 6/15) after heroin inhalation. He was treated with non-rebreather mask and intravenous infusion of naloxone with gradual improvement of consciousness and arterial blood gasses. The chest computed tomography showed signs of acute respiratory distress syndrome. Laboratory exams on the second day of hospitalization showed elevated creatine kinase (CK) and troponin-I levels while his electrocardiography (ECG) showed J-point elevation in V1, V2, and V3 precordial leads. On the second day of hospitalization the pulmonary infiltrates were not present in his chest X-ray while on the eighth day, troponin-I and CK levels were normalized without dynamic ECG changes and the patient was discharged uneventfully. CONCLUSION: Heroin inhalation may cause severe complications, such as non-cardiogenic pulmonary edema, rhabdomyolysis or myocardial injury. Hippokratia 2016, 20(1): 84-87.

Codon 12 ras mutations in patients with myelodysplastic syndrome: incidence and prognostic value.

To determine the prevalence of activated rasoncogenes (N-ras, Harvey-ras Kirsten-ras), DNA derived from peripheral blood of 51 patients with myelodysplastic syndrome (MDS) was investigated. The method was based on the polymerase chain reaction (PCR) technique to amplify DNA, followed by restriction fragment length polymorphism (RFLP) analysis. Among the French-American-British (FAB) subtypes, N-ras mutations were found in two patients with refractory anemia with excess of blasts (RAEB), in one patient with refractory anemia with excess of blasts in transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter survival duration than other MDS patients of the same FAB subtypes, although these findings proved to be not statistically significant (P > 0.1). Interestingly, all but one patient with N-ras mutation developed acute myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12 of the N-ras gene might serve as a negative prognostic factor at diagnosis of MDS.

Therapeutic effect of glibenclamide in a fixed combination with metformin or phenformin in NIDDM patients.

The combination of a sulfonylurea with a biguanide improves the pancreatic beta-cell insulin secretion and the insulin utilization in peripheral tissues in NIDDM. This open, crossover, randomised and prospective study was designed to compare the effects of the fixed combination glibenclamide-metformin (GL-METF)-2.5 and 400 mg respectively, with the fixed combination glibenclamide-phenformin (GL-PHEN)-2.5 and 25 mg respectively, on NIDDM diabetes control. Thirty NIDDM patients, in ideal metabolic control, who were being treated with GL-PHEN were divided in two groups. One group received GL-PHEN for 12 weeks followed by 12 weeks treatment with GL-METF and the reverse treatment was given to the second group. A statistically significant decrease of post-prandial blood glucose (p = 0.034) and glycosylated haemo-globin (p < 0.02) values was observed under GL-METF treatment compared to those with GL-PHEN. The values of lactic acid were within normal limits during both treatments. The insulin secretion after breakfast was similar with both drug compounds. The BMI of the patients remained the same during a follow-up study of 24 weeks. Lipid metabolism did not change significantly during the trial and the safety parameters (renal and liver function, full blood count) remained unchanged. In conclusion, the administration of GL-METF leads to better diabetes control in NIDDM patients compared to that of GL-PHEN.

delta-Aminolaevulinic acid dehydratase as an index of lead toxicity. Time for a reappraisal?

delta-Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured delta-aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [mean (SD)] did not differ between groups A and B [0.51 (0.21) and 0.43 (0.19) mumol L-1, respectively] while those of group C [2.28 (0.56) mumol L-1 were significantly higher (P < 0.001) as compared to the controls. delta-Aminolaevulinic acid dehydratase activity [mean (SD)] was significantly increased [3599 (1909) mumol L-1 h-1] in group B and decreased in group C [1052 (532) mumol L-1 h-1] as compared to the controls [2034 (446) mumol L-1 h-1] (P < 0.001). There was a significantly negative correlation of logarithm of delta-aminolaevulinic acid dehydratase with lead in both groups B (P < 0.05) and C (P < 0.001) but not in group A (P = 0.1). delta-Aminolaevulinic acid dehydratase activity had a high specificity (100%) but a low sensitivity (37%) as an index of toxic lead exposure. According to our data the value of delta-aminolaevulinic acid dehydratase measurement in the diagnosis of lead intoxication is doubtful in cases with low blood lead levels, while in the presence of iron deficiency its reliability is further reduced, since low blood lead levels may be falsely predicted. delta-Aminolaevulinic acid dehydratase activity should be restricted only to monitoring cases with moderate or severe lead poisoning.

Globin chain synthesis in myelodysplastic syndromes.

Globin chain synthesis was studied in the reticulocytes of 30 patients with various myelodysplastic syndromes (MDS) to determine the alpha:beta globin chain synthetic ratio and its probable prognostic value. The mean (SD) value of the total alpha:beta ratio was 0.82 (0.45) ranging from 0.05 to 1.73. The same ratio in 10 normal controls was 1.01 (0.04). This difference was significant. Furthermore, the alpha:beta ratios were lower than normal in 14 patients (alpha-thalassaemia-like) (group I), almost within normal limits in 11 (group II), and higher than normal in five (beta-thalassaemia-like) (group III). In each group almost all the FAB subtypes were represented. The addition of exogenous haem in several of the test samples resulted in a slight to pronounced increase in the alpha:beta ratios, particularly in group I. In 92% of the high risk cases (refractory anaemia with excess blasts (RAEB), chronic myelomonocytic leukaemia (CMML] or 87.5% of patients who finally developed acute non-lyphoid leukaemia (ANLL) low or normal alpha:beta ratios were found. No significant correlation was noticed between alpha:beta ratios and various haematological variables or survival. It is concluded that in MDS the alpha:beta ratio varied enormously across the entire population of patients, as well as within each FAB subtype, thereby restricting its prognostic value. Although haem deficiency may be implicated in some cases of MDS, why this should be remains unclear.

[Effect of starvation and phenobarbital on the activity of liver uroporphyrinogen synthetase]. / Effet du jeûne et du phénobarbital sur l'activité de l'uroporphyrinogène synthétase hépatique.

Liver uroporphyrinogen synthetase activity was measured in 45 mice, divided in three groups. The mice of the 1st group served as controls, those of the 2nd starved for 24 hours, while those of the 3rd were injected intraperitoneally with phenobarbital. The enzymic activity was found significantly (p less than 0.001) lower in the animals of the 2nd group (17.49 +/- 2.25 nmol/g/h) and higher in those of the 3rd (25.82 +/- 3.73 nmol/g/h) as compared to the controls (20.89 +/- 2.11 nmol/g/h). If these effects also exist in the human it could be suggested that starvation may be doubly harmful for the patients with acute intermittent porphyria by aggravating both their enzymic disorders. On the contrary, in the case of phenobarbital its undesired effect on porphyria may be moderated by a simultaneous induction of the uroporphyrinogen synthetase.

Duodenogastric reflux before and after surgical or medical therapy for duodenal ulcer.

Duodenogastric reflux was studied in 48 duodenal ulcer patients before and after medical (n = 8) or surgical therapy with either combined truncal vagotomy and gastrojejunostomy (n = 13) or pyloroplasty (n = 12), Polya partial gastrectomy (n = 8), or highly selective vagotomy (n = 7). Seven healthy subjects served as controls. The reflux was assessed both by using 99mTc diethyliminodiacetic acid (HIDA) scintigraphy and by measuring intragastric bile acid levels following endoscopic gastric juice aspiration. Before therapy, duodenal ulcer patients had significantly higher intragastric bile acid concentrations than did normal subjects (p less than 0.001). After truncal vagotomy and drainage, or partial gastrectomy, bile acid levels increased significantly, whereas they remained unchanged after medical therapy. Conversely, they were found to be significantly decreased after highly selective vagotomy. The results of HIDA scan measurements were compatible with those of gastric juice bile acids. We conclude that surgical treatment for duodenal ulcer by highly selective vagotomy is the only form of therapy, among the types considered, that leads to a reduction in duodenogastric reflux. It is of interest that medical therapy of the duodenal ulcer does not improve abnormal duodenogastric reflux, possibly contributing to both the failure of the medical treatment and recurrence of the ulcer.

Comparative study of the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide or chlorpropamide.

This study was designed to compare the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide, chlorpropamide or biguanides in non-insulin-dependent diabetes. It is divided into two parts: a) in the retrospective study (473 subjects), glucose control of patients who were transferred from chlorpropamide, gliclazide, glibenclamide, glibenclamide + biguanide or metformin to the fixed combination glibenclamide-phenformin in the same tablet (2.5 mg and 25 mg, respectively) was monitored. A statistically significant decrease of blood glucose and glycosylated hemoglobin values was found under the combination of glibenclamide-phenformin contained in the same tablet in contrast to the values obtained with the treatment with glibenclamide, gliclazide, chlorpropamide, combination of glibenclamide and biguanides, metformin, and insulin. b) In the prospective study (57 subjects), the patients were transferred from chlorpropamide or gliclazide to glibenclamide for 3 months and then reallocated to the previous treatment for 3 additional months. It was found that under glibenclamide, glucose control was significantly better than under chlorpropamide or gliclazide. In conclusion, glibenclamide, a second generation sulfonylurea, and the fixed combination glibenclamide-phenformin in the same tablet are more effective compared to the other antidiabetic agents here studied and lead to a better control of type II diabetic patients. There was no increase in plasma lactic acid concentration in all patients studied before and after having received the fixed combination of glibenclamide-phenformin in the single tablet form.

Effect of isoniazid, a haem inhibitor, on globin chain synthesis in reticulocytes from non-thalassaemic and beta thalassaemic subjects.

The effect of isonicotinic acid hydrazide (INH), a potent haem inhibitor, on globin chain synthesis was studied in reticulocytes from the following groups of patients: four non-thalassaemic patients (group i); five beta thalassaemia heterozygotes (group ii); three Hb S/beta thalassaemia heterozygotes (group iii); and two additional patients--one with homozygous beta thalassaemia and the other with thalassaemia intermedia (group iv). This was done to determine whether haem inhibitors depress alpha globin chain synthesis. The progressive increase of INH concentration (10-40 mmol l-1) in reticulocytes from a beta thalassaemia heterozygote resulted in a remarkable decrease of the alpha and beta chain synthesis, ranging from 80% to 97% and from 74% to 96% of control values, respectively, and in a gradual drop of alpha:beta ratio from 1.87 to 1.38. Furthermore, in the samples incubated with 40 mmol l-1 INH, a pronounced inhibition of globin chain synthesis 77 (19%) for alpha chain and 67 (27%) for beta or beta S chain) and a substantial drop of the alpha:beta or beta S ratio in samples with INH (median 1.16) compared with that in samples without INH (median 1.70) were observed. The inhibitory effect of INH was significantly or completely corrected by adding exogenous haem. It is suggested that haem inhibition and the resulting preferential diminution of alpha chain synthesis could provide a new approach to the treatment of homozygous beta thalassaemia with an excess of detrimental free alpha chain in erythroid cells.

Estimation of glycated fetal hemoglobin in normal cord blood by isoelectric focusing. Correlation with maternal glycated hemoglobin and birth weight.

Glycated fractions of hemoglobin F and A (F1, A1c) were measured simultaneously in cord and maternal blood, respectively, in 109 normal women at delivery using an isoelectric focusing, method in polyacrylamide gel plates. Cord blood hemoglobin F1 values (mean +/- SD) were 5.92 +/- 1.09% and maternal blood hemoglobin A1c values were 6.51 +/- 0.92%. The difference was statistically highly significant (p less than 0.001) and their values were also significantly correlated (p less than 0.001). Moreover, both values were also well correlated with those of maternal blood glucose (p less than 0.01), actual birth weight (p less than 0.01) and birth weight ratio (p less than 0.01). It is concluded that hemoglobin F1 can be successfully separated and measured by isoelectric focusing. However HbF1 estimation seems to have no obvious advantages against the maternal HbA1c measurement as an index of fetal exposure to glucose during the last weeks of pregnancy.

Some parameters of haem synthesis in dialysed and non-dialysed uraemic patients.

Some parameters of haem synthesis were estimated in 60 uraemic patients (30 non-dialysed, 30 dialysed) and in 30 matched controls. Serum delta-aminolaevulinic acid and erythrocyte coproporphyrin and protoprophyrin were found significantly higher in the non-dialysed uraemics than in the controls. Erythrocyte delta-aminolaevulinic acid dehydrase (ALA-D) activity was 498 +/- 174 mumol/h.l in the non-dialysed patients, 321 +/- 146 in the dialysed (just before haemodialysis) and 833 +/- 281 in the healthy controls, the differences between these groups all being statistically significant (p less than 0.001). After haemodialysis the enzymic activity in the dialysed group increased significantly (380 +/- 167, p less than 0.001), but remained lower than normal (p less than 0.001). A similar pattern - although with less statistical significance of the differences between groups - was observed concerning erythrocyte uroporphyrinogen I synthase activity. Incubation of normal erythrocytes with uraemic plasma resulted in a considerable decrease of their ALA-D activity (from 830 +/- 263 to 616 +/- 126) while incubation of uraemic erythrocytes with normal plasma increased their ALA-D (from 384 +/- 139 to 494 +/- 77). Addition of zinc in the haemolysate caused a similar induction of ALA-D in both controls and uraemics. The zinc-induced uraemic ALA-D practically reached normal levels. The mechanism of enzymic depression and the possible role of elevated delta-aminolaevulinic acid concentrations (to which depressed ALA-D activity considerably contributes) in the pathogenesis of the neurologic manifestations of uraemia, are discussed.

Effect of uremic plasma on mouse liver delta-aminolevulinic acid synthetase activity.

delta-Aminolevulinic acid (delta-ALA) synthetase in mouse liver homogenate was significantly (p less than 0.001) higher in the presence of uremic compared with normal plasma, the ratio of the two values being 1.36 +/- 0.24 in 30 paired experiments. This effect does not seem to be due to increased concentrations of urea or creatinine nor to any possible dialyzable substances. Its relationship to the retention of an inducing factor or decreased production of erythropoietin in uremic patients is discussed. A possible inhibitory effect of erythropoietin on liver delta-ALA synthetase is suggested.

Effect of abnormal atmospheric pressure conditions upon mouse liver delta-aminolevulinic acid synthetase activity.

Liver delta-aminolevulinic acid synthetase activity was measured in mice living under abnormal atmospheric pressure conditions for 15 h. In the group living under low atmospheric pressure (51 kPa) the enzymic activity, either basal or induced by starvation and/or allylisopropylacetamide, was significantly (p less than 0.001) lower than that of the control group. In the group living under high atmospheric pressure (153 kPa) the enzymic activity was significantly (p less than 0.001) higher than the one of the controls. Our results might possibly be explained by changes in the cellular redox state, the heme oxygenase activity or the serum erythropoietin levels.

Rapid proteolysis of puromycyl peptides in non-thalassaemic and thalassaemic erythroid cells.

The proteolytic degradation of labelled pyromycyl polypeptides was investigated in human intact erythroid cells derived from the bone marrow of eight non-thalassaemic patients and the peripheral blood of eleven thalassaemics (eight splenectomized beta thalassaemia heterozygotes and three sickle-cell beta thalassaemics). These abnormal polypeptides are rapidly degraded to soluble trichloroacetic-acid (TCA) fragments with a half-life of 12 min both in bone marrow and peripheral blood. This comes very close to the half-life reported for the puromycyl peptide degradative system in rabbit reticulocytes (15 min). The relationship of the present proteolytic system to the ATP-dependent one, described in rabbit reticulocytes, and to that responsible for the free alpha-chain degradation in beta thalassaemia is discussed.

Plasma alpha-lipoprotein pattern and LCAT activity in acute viral hepatitis in children.

The alpha-lipoprotein (a-Lp) electrophoretic pattern on agarose gel was studied serially in 65 children with acute viral hepatitis. In seven cases the high-density lipoprotein fractions (HDL) were also separated by ultracentrifugation and studied in relation to lecithin: cholesterol acyltransferase activity (LCAT) during the acute phase and recovery. The a-Lp band was initially absent on electrophoresis in 36 cases and never appeared in 3 of the children who died. In those who survived a-Lp reappeared with clinical improvement even before a definite increase in S-ASAT and bilirubin was evident. In the seven children in whom it was measured LCAT activity ranged during the acute phase from 17.4 to 57 nmol h-1 ml-1. In patients with initially 'normal' LCAT activity (group I, no. = 3) HDL was normal both in amount and composition. In patients with 'low' LCAT (group II, no. = 4) HDL was reduced and of abnormal composition. In both groups the a-Lp band was absent or considerably reduced on electrophoresis. In the latter group LCAT activity increased significantly on recovery, as did the amount of HDL which became normal in composition. These results suggest that in acute viral hepatitis in children changes in composition and concentration of HDL depend on the degree of hepatic functional disturbance, as judged by plasma LCAT activity. Nevertheless, it appears that HDL electrophoretic behaviour may be abnormal during the early stage of the disease while plasma LCAT activity is not significantly affected.