PubMed Health⌕ Search

Biomedical subjects

T Curstedt

Publications and source records attributed to T Curstedt.

At least 91 records · Page 5Linked to original sources
PubMed1991

Lung lesions after combined inhalation of cobalt and nickel.

Rabbits inhaled 0.5 mg/m3 Co2+ as CoCl2, a combination of 0.5 mg/m3 Co2+ as CoCl2 and 0.5 mg/m3 of Ni2+ as NiCl2, or filtered air (controls) for 4 months, 5 days/week, 6 hr/day. The pattern of morphological effects on lung tissue and alveolar macrophages after the simultaneous exposure to Co2+ and Ni2+ was a combination of the patterns seen after exposure to Co2+ and Ni2+ alone. However, nickel seemed to potentiate the specific effect of cobalt, i.e., the formation of noduli of type II cells. Further, the increase in phospholipids, especially in 1,2-dipalmitoylphosphatidylcholine, appeared more pronounced after the combined exposure than after the additive combination.

Administration, Inhalation↗
PubMed1991

Extracellular matrix components in bronchoalveolar lavage fluid in quartz exposed rats.

To investigate the long term effects of quartz, bronchoalveolar lavage (BAL) and analysis of lung silica were performed in rats (n = 20) one, four, and 12 months after exposure to intratracheally instilled crystalline silica. Total and relative concentrations of silica in the lungs were highest one month after exposure. At this time BAL fluid concentrations of total cells, macrophages, and lymphocytes increased five to 10-fold compared with saline instilled controls (n = 19). The number of polymorphonuclear cells (PMNs) increased about 200-fold. The increased number of PMNs persisted during the year. Furthermore, albumin and fibronectin concentrations increased continually during the year, about two to fivefold the values of controls. Hyaluronan, by contrast, increased during the four month period (about eightfold) but decreased after one year to the one month concentration. Phospholipids in BAL fluid, raised already after one month, remained high at one year. The findings suggest progressive damage of the alveolar and interstitial tissues. Moreover, the increases in components of the extracellular matrix capable of building fibrotic networks are in agreement with the microscopical findings of fibrosis. Because only total cells, macrophages, and albumin concentrations correlated weakly with the silica contents of the lung, it is unlikely that the relation between quartz burden and the reaction in the lung is simple.

Animals↗
PubMed1991

Distribution of endotracheally instilled surfactant protein SP-C in lung-lavaged rabbits.

In lung-lavaged surfactant-deficient rabbits (n = 6) requiring artificial ventilation, porcine surfactant was instilled endotracheally. This resulted in improvement of lung function so that the animals could be weaned off artificial ventilation. The animals were killed 4 1/2 h after surfactant administration and the porcine surfactant protein was localized in the lung with a MAb. We found surfactant protein in all lobes of the lung but the distribution was not homogeneous. Surfactant protein C was found in less than 15% of the alveolar spaces and in less than 1% of the bronchi.

Animals↗
PubMed1991

Phagocytic functions and tumor necrosis factor secretion of human monocytes exposed to natural porcine surfactant (Curosurf).

In this study we have analyzed various phagocytic functions and tumor necrosis factor (TNF) secretion of human monocytes exposed to either a biochemically well-defined porcine surfactant or a purified phospholipid preparation. Adherence, random migration, and chemotactic response to zymosan activated serum and formyl-methionyl-leucyl-phenylalanine were normal in surfactant-treated monocytes; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of Staphylococcus aureus by monocytes exposed to surfactant (100 micrograms/mL) or phospholipids (100 micrograms/mL) was slightly impaired [surfactant: at 30 min (t30) 48.5 +/- 11%, t60 73.3 +/- 10.1%; phospholipids; t30 47.3 +/- 2.5%, t60 68.0 +/- 6.6%; controls: t30 66.6 +/- 9.9%, t60 81.0 +/- 6.6%, p less than 0.05 at t30 for both, p less than 0.05 at t60 for phospholipids]. Due to the smaller number of S. aureus ingested, bactericidal activity of surfactant- or phospholipid-treated monocytes was slightly reduced when compared with controls. Surfactant or phospholipids had no bactericidal activity. Uptake of Candida albicans was identical in surfactant- or phospholipid-treated monocytes and untreated controls; the same was true for the number of Candida organisms ingested per cell. Phagocytosis-associated chemiluminescence and production of superoxide anion by monocytes of either source in response to phorbol myristate acetate and opsonized zymosan were also unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Surfactant substitution in ventilated very low birth weight infants: factors related to response types.

We investigated factors than may influence the response to surfactant substitution. Thirty-five very low birth weight infants with respiratory distress syndrome were treated with Curosurf at 3-12 h of age. From the changes in oxygenation, the therapeutic response was categorized as rapid and sustained, rapid with relapse, or poor. Phospholipids and surfactant protein A were quantified in gastric aspirate samples obtained immediately after birth. They showed that 16 infants had accelerated lung maturity, despite clinical and radiologic signs of respiratory distress syndrome. Ten of them had suffered from birth asphyxia or connatal infection. Nevertheless, 12 of these 16 infants responded rapidly to surfactant substitution. Poor response was seen in four infants with connatal infection. Of 19 infants with immature lung profile, 18 showed a rapid initial response to surfactant substitution. Dynamic compliance of the respiratory system or arterial blood pressure before substitution, the ultrastructure of the surfactant preparation, or persistence of the ductus arteriosus did not influence the response type, but fraction of inspired oxygen was higher before surfactant substitution in infants with poor response. Prognosis was related to short-term response: Of 17 infants who showed a rapid and sustained response, none died, whereas eight of 18 infants with relapse after rapid initial response or poor response died (p less than 0.05). We conclude that surfactant substitution may be beneficial not only in babies with primary surfactant deficiency but also in other pulmonary disorders that are common in very low birth weight infants. The type of response may be of prognostic value.

Biological Products↗
PubMed1991

Steroid profile in serum: increased levels of sulphated pregnenolone and pregn-5-ene-3 beta,20 alpha-diol in patients with adrenocortical carcinoma.

A serum steroid profile was determined in 11 patients with adrenocortical carcinoma, 5 with adrenocortical adenoma and 10 healthy controls. Seven of the patients with carcinoma had different forms of endocrine symptoms, and of those with adenoma 3 had Cushing's syndrome and 2 primary hyperaldosteronism. Sulphated steroids dominated in serum from both patients and controls, whereas the levels of free and glucuronated steroids were low. All patients with adrenocortical carcinoma had increased levels of sulphated pregn-5-ene-3 beta-ol-20-one (pregnenolone) and pregn-5-ene-3 beta,20 alpha-diol compared with healthy controls and patients with adrenocortical adenoma. Serum levels of 11-deoxycortisol and/or its glucuronated metabolite tetrahydro-11-deoxycortisol were clearly elevated in 8 of the patients with carcinoma. The results are in agreement with those previously found for conjugated urinary steroids in patients with adrenocortical carcinoma. Thus, an impaired function or deficiency of 3 beta-hydroxysteroid dehydrogenase/delta isomerase and in some cases also of 11 beta-hydroxylase could explain the findings. The serum levels of sulphated pregnenolone and/or pregn-5-ene-3 beta,20 alpha-diol, possibly together with free 11-deoxycortisol seem to be useful for preoperative discrimination between malignant and benign adrenocortical tumours.

Adenoma↗
PubMed1990

Early versus late surfactant replacement therapy in severe respiratory distress syndrome.

26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III-IV), requirement of artificial ventilation and an FiO2 greater than or equal to 0.6. Nineteen neonates have been subjected to early treatment (2-15 h of age, mean birth weight SD: 1201 +/- 387 g) and 7 patients to late treatment (greater than 15 h to 48 h of age, birth weight SD 1624 +/- 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to greater than 21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD greater than 21% O2, greater than 90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.

Birth Weight↗
PubMed1990

[Surfactant substitution in severe respiratory distress syndrome in premature infants weighing less than 1,000 g].

19 preterm infants with severe respiratory distress syndrome (RDS) were treated with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). 9 patients had a birth weight of less than 1000 g (845 +/- 112 g, mean +/- SD and the mean gestational age was 27.2 +/- 2.1 weeks). The other 10 had a birth weight of greater than 1000 g (1521 +/- 218 g and a mean gestational age 31 +/- 2.8 weeks). Age at treatment was 3 h in infants less than 1000 g and 4 h in patients greater than 1000 g. Both groups of infants showed a rapid improvement in oxygenation and gas exchange within minutes after surfactant replacement. Exposition to greater than 60% and greater than 40% oxygen was identical in both groups. However, time in greater than 21% oxygen was significantly longer in infants less than 1000 g (median 30 days, 8.5 days in patients greater than 1000 g, p less than 0.01). The duration of mechanical ventilation was 33 days, in patients greater than 1000 g and 5 days; p less than 0.01. None of the infants developed a pneumothorax, but 6 out of 9 patients less than 1000 g developed mild bronchopulmonary dysplasia. 2 infants less than 1000 g died at day 5 and day 11 from cardio-circulatory arrest following ligation of a patent ductus arteriosus, and nosocomial septicaemia, respectively. Prolonged mechanical ventilation and exposure to oxygen in patients less than 1000 g cannot be attributed to surfactant deficiency alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1990

Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups.

Pulmonary surfactant contains two hydrophobic polypeptides, SP-B and SP-C, with known amino acid sequences and with truncated subforms lacking the N-terminal residues. Treatment of SP-C with KOH releases fatty acids (palmitic acid to more than 85%) in molar ratios of 1.8-2.0 relative to the polypeptide. Furthermore, plasma-desorption mass spectrometry shows native SP-C of both the intact and truncated types to be monomers with masses about 500 units higher than those expected for the polypeptide chains. After treatment with KOH, trimethylamine, or dithioerythritol, the polypeptide masses are obtained. These results prove that native SP-C is a lipopeptide with two palmitoyl groups covalently linked to the polypeptide chain. The deacylation conditions, the presence of two cysteine residues in the polypeptide, and the absence of other possible attachment sites establish that the palmitoyl groups are thioester-linked to the two adjacent cysteine residues. In contrast, the major form of porcine SP-B is a dimer without fatty acid components. That SP-C is a true lipopeptide with covalently bound palmitoyl groups suggests possibilities for functional interactions. It gives a direct physical link between SP-C and surfactant phospholipid components. Long-chain acylation may constitute a means for association of proteins with membranes and could conceivably modulate the stability and biological activity of surfactant films.

Amino Acid Sequence↗
PubMed1990

Passive expiratory flow-volume recordings in immature newborn rabbits. Effect of surfactant replacement on the time constant of the respiratory system.

Immature newborn rabbits with a gestational age of 27 days were paralyzed and kept in body plethysmographs. They were ventilated for 10 min with a tidal volume of approximately 10 ml/kg, with or without previous surfactant treatment via the airways. Tidal volumes and flow were recorded with a pneumotachograph connected to the body plethysmograph, and the expiratory time constant of the respiratory system (trs) was determined from flow-volume diagrams. The values of trs after 10 min were significantly higher in surfactant-treated animals than in controls (50 +/- 7 vs. 23 +/- 4 ms; p less than 0.002), indicating stabilization of the alveoli. There was also a close correlation between trs and the compliance values calculated from tidal volumes and ventilator pressure (r = 0.80; p less than 0.001), as well as between trs and the alveolar volume density in histological lung sections, determined by automated image analysis (r = 0.71; p less than 0.001).

Animals↗
PubMed1990

Surfactant replacement in spontaneously breathing babies with hyaline membrane disease--a pilot study.

In a neonatal unit which, at that time, had no facilities for artificial ventilation, 14 newborn infants with birth weight greater than or equal to 1,500 g fulfilling the diagnostic criteria for severe hyaline membrane disease (HMD) were treated by tracheal instillation of bovine surfactant (200 mg/kg). Twelve of these babies showed increased transcutaneous PO2/FiO2 ratio within 2 min, the average therapeutic response being sustained for at least 72 h. One of the two babies who did not respond to treatment was later diagnosed as a case of group B streptococcal pneumonia. One baby with favorable initial response died from sepsis at the age of 7 days; the other patients survived without sequelae. We conclude that treatment with exogenous surfactant might be considered as an alternative to ventilator treatment in babies with severe HMD.

Animals↗
PubMed1990

Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma.

The urinary steroid profile was determined in 24 patients with adrenocortical carcinoma. Seventeen of the patients had Cushing's syndrome, virilization or feminization, and 7 had no signs of endocrine disease. Seven of the 11 patients still alive are free of disease, after a follow-up period of 5-75 months. The steroid profile varied widely between the patients with adrenocortical carcinoma. Patients with Cushing's syndrome had increased levels of cortisol metabolites and those with virilism had raised excretion of androgen metabolites. Six of the patients with adrenocortical carcinoma showed normal values of these metabolites. In 23 of the 24 patients the excretion of 3 beta-hydroxy-5-ene steroids and/or metabolites of cortisol precursors, such as tetrahydro-11-deoxycortisol, were significantly increased, compared with healthy controls or patients with adrenal adenomas. These findings suggest a relative deficit or low activity of 3 beta-hydroxysteroid dehydrogenase/delta isomerase and/or 11 beta-hydroxylase in tumour tissue. In the single patient where the steroid profile failed to indicate malignancy, hypercortisolism was seen and the tumour mass was small. The steroid excretion normalized after radical surgery and decreased in patients responding to chemotherapy. During recurred disease the metabolites of 3 beta-hydroxy-5-ene steroids and/or cortisol precursors increased, but in some patients the excretory pattern then was different from that seen before treatment.

Adrenal Cortex Neoplasms↗
PubMed1990

[Effect of natural porcine surfactant (Curosurf) on the function of neutrophilic granulocytes].

In this study we have analyzed various phagocytic functions of human neutrophils exposed to either biochemically well defined porcine surfactant (Curosurf) or a phospholipid preparation. Adherence, random migration and chemotactic response to zymosan activated serum and formyl-methionyl-leucyl-phenylalanine were normal in surfactant treated neutrophils; surfactant was not a chemotactic stimulus. In contrast, phagocytosis of S. aureus by neutrophils exposed to surfactant (100 micrograms/ml) or phospholipids (100 micrograms/ml) was impaired (surfactant: t30 49.5 +/- 9.0%, t60 65.0 +/- 8.0%; phospholipids: t30 66.3 +/- 12.6%, t60 78.0 +/- 7.8%; controls: t30 78.1 +/- 8.9%, t60 90.1 +/- 6.2%; p less than 0.001 at t30, t60 for surfactant, p less than 0.05 at t60 for phospholipids). Due to the smaller number of S. aureus ingested, bactericidal activity of surfactant or phospholipid treated neutrophils was slightly reduced when compared to controls (surfactant t30 p less than 0.05, surfactant t60 p less than 0.001, phospholipids t60 p less than 0.05). Surfactant or phospholipids had no bactericidal activity. Uptake of candida was identical in surfactant or phospholipid treated neutrophils with untreated controls; the same was true with the number of candida per cell ingested. Phagocytosis-associated chemiluminescence and production of superoxide anion by neutrophils of either source in response to phorbol myristate acetate and opsonized zymosan was also identical.

Adult↗
PubMed1990

[Treatment of severe hyaline membrane disease with a single-dose of natural exogenous surfactant of porcine origin. A randomized trial: immediate effects and outcome at 28 days of life].

The results obtained with porcine surfactant (Curosurf) administration for the treatment of hyaline membrane disease (HMD) are reported. Thirty premature infants weighing 700 to 2,000 g with severe HMD (mechanical ventilation and oxygen requirement (FiO2) greater than 60% were randomly allocated at 2 to 15 hours postnatal age. Eight of the 30 patients included in this group participated in a multicenter european trial. The fifteen infants with mean gestational age (GA) of 29.5 weeks included in the treatment group (T), were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group (C). Infants in the T group showed an immediate, dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour. This significant improvement in favor of T group (p less than 0.005) persisted for 2 days when control infants began to recover. This improvement in oxygenation allowed a significant decrease of FiO2 (p less than 0.005) and mean airway pressure (p less than 0.01) in the T group within 1 hour and up till the second day. Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified. However the tendency was towards decreased respiratory morbidity. The discussion will consider the value of multiple doses.

Animals↗
PubMed1989

Inhibition of exogenous surfactant in ventilated immature newborn rabbits.

Immature newborn rabbits were treated at birth by tracheal instillation of porcine surfactant (100 microliters, phospholipid concentration 80 mg.ml-1), to which [14C]dipalmitoylphosphatidylcholine had been added as a marker. They were kept in a body plethysmograph/pneumotachygraph system at 37 degrees C. During a 120 min period of artificial ventilation with a peak insufflation pressure of 20 cm H2O, there was a gradual decrease in tidal volumes (36%.h-1). This decrease was correlated to an elevation of minimum surface tension (r = 0.81; P less than 0.01) and to a prolongation of the adsorption rate (r = 0.80; P less than 0.01) of surfactant recovered by lung lavage from the same animals. There was also correlations between duration of ventilation and minimum surface tension (r = 0.56; P less than 0.01), and between duration of ventilation and adsorption rate (r = 0.73; P less than 0.01). The surface properties of phospholipids extracted from the lavage fluid were similar to those of the original surfactant preparation. Our data suggest that, in immature newborn rabbits subjected to artificial ventilation, exogenous surfactant may become inactivated, probably due to protein leakage into the airspaces.

Animals↗
PubMed1989

Lung lesions after experimental combined exposure to nickel and trivalent chromium.

Rabbits were exposed to a combination of 0.7 mg/m3 of Ni2+ as NiCl2 and 1.2 mg/m3 of Cr3+ as Cr(NO3)3, to 0.6 mg/m3 of Ni2+ as NiCl2, or to filtered air for 4 months (5 days/week, 6 hr/day). Light microscopy of the lung tissue showed widespread areas with nodular accumulation of macrophages in all rabbits exposed to both metals, in two rabbits exposed to nickel alone, and in none of the controls. Electron microscopy of the lung showed attenuated septa and alveoli stuffed with surfactant-like material in the group exposed to both metals. In two of these rabbits, groups of alveoli were filled with densely packed debris and type I cell borders were obscure. The reaction in the group exposed to nickel alone was less prominent. The volume density of alveolar type II cells showed a fourfold increase after exposure to both metals and a twofold increase following exposure to nickel alone compared to controls. The lung tissue content of total phospholipids and especially phosphatidylcholines and phosphatidylinositols was significantly higher in the groups exposed to both metals than in controls or in animals exposed to nickel only. In lung tissue the molar percentage of 1,2-dipalmitoylphosphatidylcholine was significantly higher in the group exposed to both metals than in the other groups. The results indicate that trivalent chromium potentiates the effect of nickel on the type II cells resulting in an increased surfactant production; in addition, trivalent chromium probably reduces the catabolism of surfactant in alveolar macrophages. Our observations raise the concern that noxious effects might occur also in humans exposed to a combination of nickel and trivalent chromium.

Animals↗
PubMed1989

The adult respiratory distress syndrome: first trials with surfactant replacement.

Following diverse insults, patients may develop a high permeability lung oedema which results in tachypnoea, cyanosis, hypoxaemia, and pan-lobar infiltrates on the chest radiograph. Although a variety of interventional therapies have been evaluated, none has been found effective, and current treatments are entirely supportive. Recently, cellular and biochemical analyses of bronchoalveolar lavage fluid have disclosed abnormalities which suggest that acute inflammatory events and surfactant abnormalities are present in the lungs of patients with adult respiratory distress syndrome (ARDS). The similarities to abnormalities seen in neonates with respiratory distress syndrome are striking. Treatment of those infants with surfactant replacement has been of both short-term and long-term benefit. Therefore, it is rational to investigate the benefits which surfactant administration may have for patients with ARDS. We present an overview of ARDS, and our initial experience with surfactant replacement in three patients.

Adult↗