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Biomedical subjects

K R Larsen

Publications and source records attributed to K R Larsen.

At least 37 records · Page 2Linked to original sources

Three different mask physiotherapy regimens for prevention of post-operative pulmonary complications after heart and pulmonary surgery.

OBJECTIVE: An investigation into the incidence of post-operative complications after thoracic surgery with 3 different physiotherapy masks. DESIGN: A prospective, consecutive, randomized comparison. SETTING: Department of Thoracic and Heart Surgery at a University Hospital. The treatments were performed by experienced and specially trained physiotherapists. PATIENTS: 160 patients were evaluated. 60 patients undergoing heart surgery, 59 patients having pulmonary resection, and 41 patients with exploratory thoracotomy. INTERVENTIONS: In each operative category the patients were treated with one of three face mask systems used in addition to routine chest physiotherapy. These were either continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), or inspiratory resistance - positive expiratory pressure (IR-PEP). MEASUREMENTS AND RESULTS: Post-operative pulmonary complications were assessed by forced vital capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination, all measured pre-operatively and on the fourth and ninth post-operative day. The patients filled in a questionnaire expressing their opinion about their mask treatment. There was an equal decrease in FVC, FVC%, and PaO2, and equal frequency of atelectasis in the 3 mask treatments. More patients with the PEP mask favoured their system than did those with the other 2 systems. CONCLUSION: There was no statistically significant difference between the treatments: continuous positive airway pressure (CPAP), positive expiratory pressure (PEP), and inspiratory resistance - positive expiratory pressure (IR-PEP) on post-operative complications. Any of the three treatments may be used as supplement to standard chest physiotherapy.

Blood Gas Analysis↗

Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation.

Knowledge of the effect of differences in iodine intake levels on public health in areas with no endemic goiter is limited. Groups at risk when iodine intake is relatively low are pregnant and lactating women and their newborns. A prospective randomized study was performed to evaluate the effect of iodine supplementation in an area where the median daily iodine excretion in urine is around 50 micrograms. Fifty-four normal pregnant women were randomized to be controls or to receive 200 micrograms iodine/day from weeks 17-18 of pregnancy until 12 months after delivery. In the control group, serum TSH, serum thyroglobulin (Tg), and thyroid size showed significant increases during pregnancy. These variations were ameliorated by iodine supplementation. Iodine did not induce significant variations in serum T4, T3, or free T4. Cord blood Tg was much lower when the mother had received iodine, whereas TSH, T4, T3, and free T4 levels were unaltered. The results suggest that a relatively low iodine intake during pregnancy leads to thyroidal stress, with increases in Tg release and thyroid size. However, the thyroid gland is able to adapt and keep thyroid hormones in the mother and the child normal, at least under normal circumstances, as evaluated in the present study. It is not known whether this stress is sufficient to be of importance for late development of autonomous thyroid growth and function.

Adult↗

Circadian rhythm of pepsin efflux in the fasting rat stomach.

Gastric pepsin efflux, a putative aggressive factor because of its proteolytic activity, was examined to determine if it displays circadian rhythmicity as has been shown for other factors such as acid, bicarbonate, mucus, blood flow, potential difference, and tissue prostacyclin activity. Ninety-six fasted Sprague-Dawley male rats, 6-7 weeks of age were acclimated in sound-attenuating, light-proof chambers on a 12/12 light/dark schedule. They were studied in groups of 12 at 3-h intervals. After anesthesia and minor surgery, the stomach was cannulated and filled with 2 ml of saline for two sequential periods of 30 min. The samples were tested for pepsin according to the modified hemoglobin substrate colorimetric method. The data were analyzed with cosinor rhythmometric techniques. Pepsin efflux displayed significant (p < 0.05) circadian rhythmicity with an acrophase value or peak time at 06:49 h after lights on, during the lights-on resting phase. In contrast, the acrophase for acid secretion in the same model occurs during the dark period, when the rats are normally active. We postulate that differences in the circadian patterns of acid and pepsin may be protective.

Acclimatization↗

Gastric potential difference in fasted rats: circadian studies.

The pathophysiology of gastroduodenal ulcer disease remains the subject of intense research and controversy. One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. Parallel circadian rhythms have been reported between acid secretion and gastric potential difference (PD) in in vitro models. The purpose of this study was to investigate the circadian measurements of PD, a parameter of intact gastric mucosal function and thus a putative parameter of gastric protection, in intact, fasted, anesthetized rats. Sixty-four male Sprague-Dawley rats were acclimatized in sound-attenuating, lightproof chambers for 3 weeks on a 12:12-h light-dark schedule. Eight rats were fasted 18 h before being sampled at each of eight times on the circadian clock (01:00, 04:00, 07:00, 10:00, 13:00, 16:00, 19:00, and 22:00 hours after lights on) (HALO). In each rat, after anesthesia (ketamine/acepromazine) and laparotomy, the tip of a catheter (pre-filled with KCl agar) was passed into the gastric corpus through the duodenum. The tip of a second KCl-agar catheter was placed within the peritoneal cavity. The position of the intragastric catheter was gently adjusted for obtaining the highest stable PD reading. The data showed significantly higher values at 07:00 and 10:00 HALO. The lowest value was at 13:00 HALO. The difference between high (10:00 HALO) and low (13:00 HALO) values was 4.5 mV or 13% of the mean. This difference was highly significant (p = 0.003) Analysis of variance showed that the values at 07:00 and 10:00 HALO were significantly higher than the values at 01:00, 13:00, and 16:00 HALO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antiulcer drugs and gastric mucosal integrity. Effects of misoprostol, 16,16-dimethyl PGE2, and cimetidine on hemodynamics and metabolic rate in canine gastric mucosa.

Although prostaglandins (PGs) of the E series have gastric antisecretory and cytoprotective properties, many have different effects on the barrier integrity of the gastric mucosa. The direct effect of antiulcer drugs on gastric mucosal blood flow, mucosal barrier permeability, and metabolic rate have not been adequately studied. These factors are important in the defense of the gastric mucosa. Part of the difficulty relates to the possible influence of gastric mucosal blood flow on gastric acid secretion. To rule out this confounding factor, omeprazole can be used to reveal the true pharmacologic effects of these antiulcer drugs independent of the effect of gastric secretion per se. The study examined the effects of 16,16-dimethyl PGE2 (dmPGE2), misoprostol, and cimetidine on gastric mucosal blood flow, oxygen consumption, potential difference (PD), electrolytes, and fluid flux using the ex vivo gastric chamber dog model. The PGs were administered intraluminally with an isotonic acid solution; cimetidine was administered by arterial infusion. None of the drug treatments had any significant effect on mean systemic arterial pressure, arterial blood gases, body temperature, or oxygen consumption. dmPGE2 significantly (P less than 0.001) decreased PD and enhanced the electrolytes (Na+, K+) and fluid flux across the mucosa (P less than 0.05). Misoprostol significantly increased gastric mucosal blood flow (P less than 0.02) and fluid efflux but decreased PD values. Cimetidine did not have any significant effects on barrier or metabolic functions of the stomach. These results suggest that a considerable difference exists in the pharmacology of gastric antisecretory drugs in relation to their effect on several factors affecting gastric mucosal integrity.

16,16-Dimethylprostaglandin E2↗

Circadian rhythm in prostacyclin activity in gastric tissue of the fasting rat.

Gastroduodenal ulcer disease may result from the desynchronization of the circadian rhythms of gastric protective and destructive factors. The purpose of this study was to evaluate whether gastric tissue 6-keto prostaglandin F1 alpha (PGF1 alpha), a catabolic derivative of the putative protective factor prostacyclin, is produced in a circadian fashion in the rat model. Forty-eight male Sprague-Dawley rats were acclimatized in sound-attenuated, lightproof chambers for 3 weeks on a 12:12 hour light/dark entrainment schedule. After an 18-hour fast, six rats were killed at each of eight sampling times. The stomachs were exposed, removed, and assayed for total 6-keto PGF1 alpha content by radioimmunoassay. Cosinor analysis of the data showed significant (p = 0.0262) circadian rhythmicity in 6-keto PGF1 alpha content with an acrophase (peak time) value of 0503 HALO (hours after lights on) or in the middle of the lights-on inactive period for the rats. Hypothetically, the circadian rhythm in some gastric protective factors may render the gastric mucosa vulnerable to injury in a circadian fashion.

6-Ketoprostaglandin F1 alpha↗

Circadian rhythms of gastric mucus efflux and residual mucus gel in the fasting rat stomach.

We hypothesized that two putative gastric protective factors, mucus efflux and residual mucus gel content, would manifest circadian rhythms, as reported in several other gastric functions. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18-hr and studied at 3-hr intervals. Under anesthesia, the stomachs were cannulated and filled with test solution. Thirty minutes later, they were drained and the luminal fluid was analyzed for mucus content by Alcian blue binding. Residual mucus gel was determined by direct injection of dye into the lumen. Alcian blue binding of rat mucus was expressed as equivalent milligrams of porcine mucin. Both parameters showed a significant (P less than 0.001) circadian rhythm. Mucus efflux peaked at 5:03 +/- 0:52 HALO (hours after lights on), and residual mucus at 6:00 +/- 0.46 HALO. Thus, the interplay of circadian rhythms in aggressive and defensive gastric mucosal functions is supported.

Animals↗

Circadian rhythm in gastric mucosal blood flow in fasting rat stomach.

Circadian rhythms are present in several gastric functions including acid secretion and emptying rates. We hypothesize that aggressive and defensive factors in the gastric mucosa follow similar circadian rhythms. The purpose of this study was to determine if gastric mucosal blood flow, a known defensive factor, manifests a circadian rhythm in fasting rats. Ninety-six male Sprague-Dawley rats were light-adapted in isolation chambers for 3 weeks prior to the study. Half the rats experienced light from 6:00 AM to 6:00 PM, the other half from 6:00 PM to 6:00 AM. After an 18-hr fast, 12 rats were studied at each of eight sampling times: 0100, 0400, 0700, 1000, 1300, 1600, 1900, and 2200 hr after lights on (HALO). After anesthesia and laparotomy, the stomachs were opened along the anterior surface, gently stretched with mucosal surface upmost, and trapped between two lucite rings, with blood supply intact. Mucosal blood flow (ml/min/100 g) was measured in the forestomach, corpus, and antrum with a laser Doppler flowmeter (TSI Laserflo BPM 403). Cosinor analysis showed a significant (P less than 0.01) circadian rhythm in gastric mucosal blood flow within the corpus and antrum, but not in the forestomach. Peak time for corpus blood flow was 21:45 +/- 0:56 HALO (3:45 AM). In the antrum it was 0:51 +/- 1:08 HALO (6:51 AM). These results support the hypothesis that circadian rhythms in mucosal defensive functions are an integral part of normal gastric physiology.

Animals↗

Circadian rhythms of acid and bicarbonate efflux in fasting rat stomach.

One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. The purpose of this study was to compare circadian rhythms in gastric production of H+ and HCO3- in fasted rats. Sprague-Dawley rats were acclimatized in sound-attenuating, light-proof chambers for 3 wk on a 12:12-h light-dark schedule. Eighteen-hour fasted rats were studied at each of eight sampling times. After anesthesia, the stomachs were cannulated and filled with test solution. Thirty-minute gastric samples were titrated for H+ or assayed for HCO3-. Cosinor analysis of the data showed significant (P less than 0.05) circadian rhythms for both H+ and HCO3-. Peak times were 22:45 HALO (hours after lights on) (4:45 A.M.) for H+ and 05:41 HALO (11:41 A.M.) for HCO3-. These data demonstrate that H+ and HCO3- secretion in the fasting rat gastric lumen follow circadian rhythms with different peak times. Theoretically, this may result in circadian rhythmicity of relative mucosal vulnerability to injury.

Animals↗

[Fertility after extrauterine pregnancy. A 16-year retrospective study].

A retrospective investigation of fertility following extrauterine pregnancy during a period of 16 years in a central hospital was carried out. Out of 283 women with extrauterine pregnancy, if proved possible to investigate the postoperative fertility in 181 women. It was found that 71.8% of the patients conceived and 49.2% were delivered of living infants while 16% developed renewed extrauterine pregnancies. No significant differences were found in the frequencies of renewed extrauterine pregnancy and the number of liveborn infants between women who had been submitted to radical operation and women in whom conservative operative methods were employed. On the basis of this investigation and review of the literature, the present authors consider, that conservative operation should be employed where this is technically possible.

Female↗

Omeprazole and cimetidine versus pentagastrin in canine ex vivo gastric chamber.

The effects of acid inhibitory doses of omeprazole were compared with equieffective doses of cimetidine in the canine ex vivo stomach model (n = 30). Systemic blood pressure, temperature, stomach fluid and ion fluxes, potential difference, blood flow rates, and arterial and venous blood gases were monitored during each of nine 30-min periods. Two resting periods preceded seven periods of pentagastrin stimulation. During the last four of these, the drug effect was recorded (cimetidine 1.2 or 4.8 mumol.kg-1.h-1; omeprazole 0.3, 0.6, or 1.2 mumol/kg). Omeprazole (1.2 mumol/kg) produced 100% inhibition of stimulated acid efflux, no significant decrease in total gastric blood flow (venous outflow), 90% return of potential difference (PD) toward resting values, and a 55% reduction in stimulated oxygen consumption. Omeprazole also showed a dose-dependent K+ efflux at the two lower doses. Cimetidine (4.8 mumol.kg-1.h-1) given during pentagastrin stimulation showed a 70% decrease in total gastric blood flow, a 40% return of PD toward resting, and a 77% reduction in stimulated oxygen consumption. Neither drug showed significant changes in mucosal blood flow from resting values, thus supporting the principle that changes in gastric acid secretion and changes in blood flow are not necessarily correlated.

Animals↗

AM and PM measurement of gastric potential difference and prostacyclin production in humans: effects of ranitidine.

It has been previously documented that aspirin induced gastric injury of healthy male volunteers was greater in the morning than in the evening. We have also reported that fasting gastric acid secretion rates and gastric retention times for solids were lower in the morning hours of the circadian cycle. We hypothesized, therefore, that defensive factors in the human stomach may exhibit circadian rhythmicity with greater vulnerability to noxious agents during the morning hours. It has also been hypothesized that an antisecretory agent, with reported protective effects, such as Ranitidine, would affect gastric defense mechanisms differently at different times in the circadian cycle. Transmural electrical potential difference (PD) and prostacyclin (PGI2) production by mucosal biopsy specimens were chosen as putative indicators of gastric defensive status. Accordingly, morning (1000) and evening (2200) studies were performed on 10 fasting healthy male subjects with and without oral Ranitidine (150 mg) given 3 hr before oro-gastric intubation for the measurement of PD and the removal of mucosal biopsy samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An evaluation of naloxone as a gastric cytoprotective agent during hemorrhagic shock.

Administration of naloxone, an opiate antagonist, is known to improve survival from hemorrhagic shock and to reverse the effects of septicemia on gastric mucosal O2 tension and potential difference (PD). We tested these potentially cytoprotective actions in the ex-vivo canine gastric chamber model with acid, bile, and hemorrhagic hypotension. Naloxone (2 mg/kg IV bolus, then 2 mg/kg/hr IV) was given before or during shock. Naloxone did not affect oxygen consumption, the bile-induced drop in PD, or the transmucosal oxygen consumption, the bile-induced drop in PD, or the transmucosal movements of H+, Na+, K+, and fluid. The reduction in average mucosal lesion formation with naloxone pretreatment (5.4 +/- 1.2 vs. 2.8 +/- 0.5%) was not statistically significant (p = 0.07). Similarly, administration of naloxone after the onset of shock also failed to protect the mucosa from stress ulceration. We conclude: 1) naloxone does not inhibit the effects of topical bile on the gastric mucosal barrier; 2) naloxone has no apparent effect on local gastric vascular resistance during hemorrhagic shock; and 3) the therapeutic potential of naloxone as an anti-ulcer drug is questionable. 24GM 23095

Acute Disease↗

The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model.

A number of vasoactive substances, including serotonin, have been implicated in the pathophysiology of burn shock. Ketanserin, a specific serotonin antagonist, was investigated in a porcine burn shock model. Fifteen swine were given a mean 44% total body surface area full-thickness scald burn and received fluid resuscitation with Ringer's lactate for 24 hours postburn. The swine were divided into three groups: Group I (control group) received no ketanserin; Group II received ketanserin as a single intramuscular dose preburn and continuously via intravenous drip postburn; and Group III received ketanserin continuously via intravenous drip postburn only. The ketanserin-treated groups demonstrated improved cardiac index, decreased pulmonary artery pressures, and smaller arteriovenous oxygen content differences compared to the control group in the early postburn period. Ketanserin should be investigated further as a possible adjunctive therapeutic agent during burn shock resuscitation.

Animals↗