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Biomedical subjects

S Lindgren

Publications and source records attributed to S Lindgren.

At least 127 records · Page 7Linked to original sources

Endoscopic dilatation and surgical myectomy of symptomatic cervical esophageal webs.

During a 10-year period a cervical esophageal web or stricture was diagnosed at rigid endoscopy in 57 patients. Of these patients 72% had restricted their dietary habits because of their symptoms of dysphagia. Cineradiography of the pharynx had revealed abnormalities in 90% of the patients. Dilatation of the webs was performed with semisolid bougies, the endoscope itself, or with balloon inflation. Twelve patients were treated by myectomy of the cricopharyngeal muscle because of unsatisfactory results from the dilatation treatment. Cineradiographic outcome and improvement in dietary habits as a result of the treatment are reported.

Adolescent↗

Comparison of the effects of milrinone and OPC 3911 with those of isoprenaline, forskolin and dibutyryl-cAMP in rat aorta.

1. OPC 3911 and milrinone, inhibitors of a cyclic nucleotide phosphodiesterase, and isoprenaline were more potent against contractions induced by phenylephrine (1 microM) than by K+ (60 mM). A similar tendency was found for dibutyryl-cAMP (db-cAMP) and forskolin, while the opposite was evident for nifedipine and diltiazem. 2. Contractions induced by Bay K 8644 (0.1 microM), in the presence of K+ (12 mM), were abolished by OPC 3911 (10 microM), milrinone (10 microM), db-cAMP (100 microM) and forskolin (1 microM). These agents had little effect on contractions induced by Bay K 8644 in the presence of K+ (20 mM), whereas diltiazem (10 microM) caused complete inhibition. 3. In nominally Ca(2+)-free medium, OPC 3911 (10 microM), milrinone (10 microM), db-cAMP (100 microM) and forskolin (1 microM) reduced phenylephrine-induced contractions. Db-cAMP and forskolin also attenuated contractions elicited by caffeine (20 mM). 4. Pretreatment by ryanodine (10 microM) reduced the effects of OPC 3911 (10 microM), milrinone (10 microM) and forskolin (1 microM) on phenylephrine-induced contractions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Pharmacokinetics and bioavailability of 2-mercaptopropionylglycine administered intravenously and orally in dogs.

The pharmacokinetic disposition of 2-mercaptopropionylglycine (2-MPG) given as a single intravenous injection and/or as a single oral dose was studied in 9 normal and 13 cystinuric dogs. After intravenous injection of approximately 10 or 20 mg/kg body weight the pharmacokinetics were best described by a three-exponential function. The first phase involved a distribution process apparently including establishment of drug-plasma protein and drug-tissue binding. The second phase involved rapid renal elimination and 60% of the drug was excreted within 3 h of administration. There was also a slow terminal third phase with a long half-life after both intravenous (t1/2 = 23 h) and oral (t1/2 = 22 h) administration. No dose dependency was observed. A deep pool of reversibly tissue-bound 2-MPG was indicated by a Vss of 3.3 +/- 0.9 l/kg body weight and the long terminal elimination phase. Total clearance was estimated as 4.1 +/- 0.9 ml/min/kg body weight. 2-MPG was eliminated mainly by renal excretion, but there was a difference in recovery of dose between normal and cystinuric dogs. During the first 24 h after intravenous and oral administration, 69% and 54%, respectively, of the drug was recovered in the urine of normal dogs. The corresponding figures in cystinuric dogs were 44% and 29%, respectively. The absolute bioavailability (FAUC) was 88 +/- 20% in normal dogs.

Administration, Oral↗

Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat.

1. Slices of rat cuneate nucleus were used to study whether or not gonadal steroids influence the gamma-aminobutyric acid (GABA) system in vivo. Females in different stages of the oestrous cycle as well as steroid-treated (oestrogen, progesterone or both) ovariectomized animals were used. 2. Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves. 3. The potentiating effect of the benzodiazepine, flurazepam was unchanged during the oestrous cycle, and the hormone treatments did not alter this effect. 4. During oestrus, an increase was seen in the potentiating effect of the barbiturate (pentobarbitone). This suggests a synergistic effect between barbiturates and gonadal steroids. Progesterone treatment also increased the effect of pentobarbitone. 5. The antagonistic action of picrotoxin was unaffected during the oestrous cycle. However, progesterone (or progesterone and oestrogen) treatment reduced the potency of picrotoxin. 6. This study supports the idea that endogenous steroids (presumably progesterone) affect the GABAA receptors during the oestrous cycle by a mechanism associated with the barbiturate site of the GABAA receptor complex.

Animals↗

Effects of selective phosphodiesterase inhibitors on isolated coronary, lung and renal arteries from man and rat.

The relaxant effects of some isozyme-selective phosphodiesterase inhibitors were evaluated in isolated human and rat coronary, lung and renal arteries. Milrinone and OPC 3911, inhibitors of a cGMP-inhibited cAMP phosphodiesterase (cGI-PDE), were shown to have distinct vasodilator actions. These agents were less potent as relaxants in rat lung and renal arteries than in the corresponding human tissues. OPC 3911, the more potent cGMP-inhibited cAMP phosphodiesterase inhibitor, was found to be the more potent vasorelaxant. Rolipram, a selective inhibitor of a cGMP-noninhibited cAMP phosphodiesterase, had small effects on coronary and lung arteries, but produced a slightly more pronounced relaxation of renal arteries from both man and rat. In human preparations contracted by 30 mM K+, milrinone and OPC 3911 had similar relaxant profiles, and were as potent in coronary as in renal arteries. These results do not support the notion that milrinone has reduced effects on renal vessels in man and show that there may be species differences in vascular responsiveness to cGMP-inhibited cAMP phosphodiesterase inhibitors.

Aged↗

Disturbed autonomic nerve function in patients with Crohn's disease.

Autonomic nerve function was evaluated in 33 patients with Crohn's disease (age range, 19-66 years; mean, 36 years) by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and to tilt (acceleration and brake indices). Peripheral nerve function was evaluated neurographically and by measuring thresholds to vibration and temperature changes. None of the patients were diabetic, and all had normal thyroid function. In spite of normal peripheral nerve function, almost half of the patients, 48% (16/33), showed signs of autonomic neuropathy (AN). The occurrence of AN was not related to duration or severity of Crohn's disease or to biochemical evidence of inflammation or malabsorption of vitamins and trace elements. We conclude that autonomic nerve dysfunction is a feature of Crohn's disease which may be relevant with regard to the frequent disturbance in bowel function in patients with this disorder.

Adolescent↗

High prevalence of autoimmune liver disease in patients with multiple nuclear dot, anti-centromere, and mitotic spindle antibodies.

We used HEp-2 cells to compare the occurrence of multiple nuclear dot (MND), anti-centromere (ACA), and mitotic spindle antibodies (MSA) in patients with primary biliary cirrhosis (PBC) (n = 32) and primary Sjögren's syndrome (n = 50). The predictive value of these antibodies for autoimmune liver disease was evaluated among patients with chronic liver or inflammatory connective tissue diseases. MND were found in 6%, ACA in 10%, and MSA in 6% of PBC sera. Among patients with primary Sjögren's syndrome, ACA were found in one, whereas another had both MND and MSA. MND were also detected in 1 of 25 sera from patients with other chronic inflammatory connective tissue diseases. Reexamination of these three patients showed evidence of PBC in two. In a blinded study of sera from 356 patients with chronic liver diseases, MND were detected in 10 (3%), ACA in 2 (0.9%), and MSA in 4 (1.2%). All patients with MND or ACA and two of four with MSA had PBC or autoimmune chronic active hepatitis, particularly of the cholestatic type. In four of these patients the liver disease had not previously been classified. We conclude that these antibodies have low sensitivity but high predictive value for autoimmune, cholestatic liver disease.

Aged↗

Outcome of habit cough in children treated with a brief session of suggestion therapy.

Nine patients with habit cough, initially misdiagnosed as asthma, were treated during a period of sustained repetitive symptoms with a brief session of suggestion therapy. Symptoms had previously been present for up to 2 years (median = 2 months). Five had been hospitalized for the cough. Evaluation revealed no physiologic or radiologic abnormality. All patients became symptom free during a 15-minute session of suggestion therapy. During the subsequent week, one remained completely asymptomatic and 8 had transient minor relapses that were readily self-controlled. Seven of the 9 could be contacted for determination of long-term outcome at periods up to 9 years (median 2.2 years) after the session. Six were totally asymptomatic; one had occasional minor self-controlled symptoms. A standardized questionnaire assessing psychologic symptoms at the time of follow-up revealed no somatization nor emotional distress. In contrast to this apparent cure, others have reported extended periods of continued symptoms in the absence of a uniform treatment plan for suggestion therapy even though the correct diagnosis was made. We conclude that the classical habit cough syndrome is amenable to immediate relief and long-term cure in most cases with a single session of appropriate suggestion therapy.

Adolescent↗

HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission.

Forty-four HIV-1-seropositive women and their children were followed-up and examined in connection with the course of pregnancy, mother-to-infant transmission of HIV and clinical outcome. Twelve out of 48 children were known to be infected and two children were lost to follow-up. Of the remaining 34 children, 22 are not infected, and 12 are clinically and immunologically normal at less than 18 months. There was no difference in intrauterine growth between infected and uninfected children. Forty-six per cent of the 39 mothers seen after delivery progressed to a more advanced stage of HIV infection during a mean follow-up time of 33 months after delivery. Although comparable in age, clinical and immunological status at delivery, and follow-up time, mothers of infected children had longer durations of HIV infection and were symptomatic and/or had low CD4 cell counts to a significantly greater extent at follow-up than mothers of uninfected children.

Child, Preschool↗

Pharmacokinetics of intravenous 2-mercaptopropionylglycine in man.

The pharmacokinetics of 2-mercaptopropionylglycine (2-MPG) was studied in ten healthy volunteers after a single i.v. injection of 250 mg (1532 mumol). The total and non-protein-bound concentrations versus time curves were best described by a three-exponential function with terminal half-lives of 55 and 59 h respectively. Body clearance based upon the total concentration was estimated to be 105 and 231 ml/min based on the non-protein-bound 2-MPG. The corresponding values for Vss were 99 l and Vss,n 173 l, and for V gamma 485 l and V gamma,n 1121 l respectively. 75% of the dose was excreted in the urine, mainly during the first 6 h after injection. The proportion of non-protein-bound 2-MPG diminished exponentially during the first 15 h and then levelled off at about 30%. There was a nonlinear increase in the non-protein-bound fraction of 2-MPG as the total plasma concentration of the drug increased.

Adult↗

Screening for HIV in pregnant women: a study of maternal opinion.

Pregnant women residing in the metropolitan area of Stockholm were screened for HIV in a 12-month pilot programme. The acceptance rate was 99.3%. Three HIV-antibody-positive women (0.04%) were identified. The screening was followed up by a study designed to ascertain the attitudes of the women towards the test. The vast majority had a positive attitude to HIV screening out of consideration for the health of the expected child. One out of seven felt uneasy while awaiting the test result. Significantly more women among those who thought repeatedly about the test had already considered having an HIV test before pregnancy. Once the women found out that their HIV test was negative it did not affect their subsequent experience of pregnancy.

AIDS Serodiagnosis↗

Cricopharyngeal myotomy in the treatment of dysphagia.

Cricopharyngeal myotomy was performed on 60 patients suffering from cervical oesophageal dysphagia. Of 37 that had a Zenker diverticulum the diverticulum was excised in 24. All patients were free of symptoms on post-operative follow-up at 2-10 years. In 10 patients with a cervical oesophageal web or postcricoid stenosis, the ability to eat normal food was restored. In 7 of 9 patients with neuromuscular diseases affecting swallowing and 2 of 4 patients with cricopharyngeal achalasia, food intake improved after myotomy. Apart from 4 transient palsies of the left recurrent nerve and 2 patients with aspiration pneumonia, no serious complications occurred. Cricopharyngeal myotomy can be a safe and effective method to improve the swallowing and quality of life of patients suffering from cervical oesophageal dysphagia of varied aetiology.

Adult↗

A double-blind comparative multicentre study of remoxipride and haloperidol in schizophrenia.

In a double-blind multicentre study of parallel group design the efficacy and safety of remoxipride and haloperidol were compared in a total of 96 patients with acute episodes of schizophrenic or schizophreniform disorder according to DSM-III. There were 48 patients in each treatment group; 27 men and 21 women in the remoxipride group, 33 men and 15 women in the haloperidol group. The median duration of illness was 7 years in both groups. The mean daily dose was 437 mg for remoxipride and 10.6 mg for haloperidol during the last week of treatment. No statistically significant differences in total BPRS scores were found between remoxipride and haloperidol. The median total BPRS scores at the start of active treatment were 26 in the remoxipride and 27 in the haloperidol group; these were reduced to 16 and 12.5, respectively, at the last rating. According to Clinical Global Impression (CGI), 43% of patients in the remoxipride group and 68% of those in the haloperidol group improved much or very much during treatment. This difference was not statistically significant. Treatment-emergent extrapyramidal side effects such as akathisia, tremor, and rigidity occurred significantly more frequently in the haloperidol group; this group also made more frequent use of anticholinergic drugs. Neither of the trial drugs seriously affected laboratory or cardiovascular variables. It is concluded that remoxipride has an antipsychotic effect in a dose range of 150-600 mg per day comparable to that of haloperidol in doses up to 20 mg per day but with fewer extrapyramidal side effects.

Acute Disease↗

Role of the renin-angiotensin system in liver blood flow reduction produced by positive end-expiratory pressure ventilation.

Positive end-expiratory pressure (PEEP), often used in critically ill patients, reduces cardiac output, and its adverse effects on splanchnic circulation imply a risk of regional secondary organ failure. To investigate if the renin-angiotensin system (RAS) mediates PEEP-induced circulatory changes, hemodynamic effects of PEEP were measured in four groups of pigs: controls (C), nephrectomized (N), or given enalaprilate, an angiotensin-converting enzyme inhibitor (E), or saralasin, a competitive inhibitor of angiotensin II (S). Groups N, E and S represented interference with RAS effects at different sites. With PEEP at 10 cmH2O, mean arterial pressure, cardiac index, portal venous and hepatic arterial blood flow decreased in all groups, while portal and central venous pressures rose, without significant intergroup difference. Systemic and preportal bloodflow resistance increased in groups S and N, and hepatic arterial resistance in group C. Accentuation of the flow and pressure changes occurred with 20 cm PEEP in all groups, with increase of systemic and hepatic resistance in S and N, or preportal resistance in group N and protal resistance in group C. The study suggested that RAS is not a major mediator of PEEP-induced circulatory changes. Differing responses within groups N, S and E may have been due to interference with the action of RAS and of other vasoactive substances.

Animals↗

Lack of beneficial effects of milrinone in severe septic shock.

The effects of milrinone were investigated in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli. Anesthetized pigs were treated with milrinone before the E. coli infusion or were left untreated as septic controls. E. coli caused a significant reduction of cardiac index, renal blood flow, and portal blood flow. Pulmonary vascular resistance was significantly increased, as were the systemic and preportal vascular resistances. One of the seven septic control pigs died. In milrinone-treated septic animals cardiac index was maintained for a longer period of time but blood pressure was significantly reduced compared with the control pigs. Pulmonary vasoconstriction was little affected by pre-treatment with milrinone. Four out of seven milrinone-treated pigs died during the observation period. It is concluded that in the settings of the used porcine septic shock model milrinone treatment has no beneficial effect.

Animals↗

Early detection of gastrointestinal mucosal ischemia in porcine E. coli sepsis.

The aim of this study was to investigate the oxygenation of the gastrointestinal tract mucosa using indirect pH measurements in a porcine septic model (intravenous infusion of live E. coli). By means of intraluminally placed balloon catheters (Tonomitior) permeable to CO2, intramucosal pH (pHi) was calculated using the Henderson-Hasselbalch equation. Cardiopulmonary hemodynamics and portal blood flow were measured using Swan-Ganz catheters. Samples were taken from the gastrointestinal tract for histological examination. Nine pigs were given i.v. E. coli infusion while six pigs served as sham controls and were given an equivalent amount of Ringer's solution only. All septic animals developed hemodynamic signs of septic shock. Gastric, small intestinal and sigmoid colonic pHi decreased gradually during the four hour observation period. In the small intestine and the sigmoid colon the decrease was significant already after one hour (p less than 0.01 and p less than 0.02, respectively). Microscopic examination of tissue specimens obtained 4 hours following induction of sepsis revealed normal or close to normal findings in all the sham and in more than half of the septic animals. These findings indicate that abnormally low gastrointestinal intramucosal pH may be found early in septicemia, preceding microscopically detectable damage by several hours. It is concluded that the tonometer technique does provide early detection of gastrointestinal ischemia in septic shock.

Animals↗