Filaggrin gene mutations and the distribution of filaggrin in oral mucosa of patients with oral lichen planus and healthy controls.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disease of unknown aetiology affecting the skin and oral mucosa. Oral lichenoid lesions (OLLs), like oral contact reactions, may resemble oral lichen planus (OLP) both clinically and histopathologically. As OLP and OLL are hyperkeratotic diseases and filaggrin is essential to keratinization, the distribution of filaggrin may be altered in these lesions. OBJECTIVES: To investigate whether patients with OLP/OLL have (i) altered distribution of filaggrin in the oral mucosa; (ii) a higher incidence of mutations in the filaggrin gene (FLG); (iii) active dermatoses, apart from cutaneous LP, than healthy controls; and (iv) patients with OLP/OLL and a defect in the FLG have more widespread oral lesions and report more symptoms than OLP/OLL patients without a concomitant defect in the FLG. METHODS: Forty-nine Caucasian patients (42 women and 7 men, mean age 61.0 ± 10.3 years), with symptomatic OLP, OLL or stomatitis, and 29 matched healthy controls underwent a clinical oral and dermatological examination, oral mucosal biopsy and filaggrin genotyping (testing for R2447X, R501X, 2282del4). Smear tests for Candida spp. were performed in all patients to exclude oral candidiasis. Immunohistochemistry were performed using poly- and monoclonal filaggrin antibodies. RESULTS: The immunoreactivity for filaggrin was significantly more intense in the oral mucosa in the patients with OLP/OLL compared with healthy controls (P = 0.000025). No difference was noted in the incidence of defects in the FLG and active dermatoses between patients and healthy controls. No difference was noted in extension and number of symptoms reported by patients with OLP/OLL with or without a concomitant defect in the FLG. CONCLUSION: OLP/OLL is associated with an altered distribution of filaggrin in the oral mucosa independently of defects in the FLG. Patients with OLP/OLL did not display more active dermatoses other than cutaneous LP when compared to healthy controls.

Symptomatic oral lesions may be associated with contact allergy to substances in oral hygiene products.

OBJECTIVE: Dental materials and oral hygiene products may be responsible for oral contact allergic reactions. We aimed to determine the occurrence of allergies in patients with symptomatic oral lichen planus (OLP), oral lichenoid lesions (OLLs) and stomatitis and investigate if patch testing could identify contact allergies to dental materials and oral hygiene products in these patients. METHODS: Forty-nine patients (7 men, 42 women) aged 31 to 77 years (61 ± 10.3 years) with symptomatic OLP, OLL or stomatitis and 29 healthy age- and gender-matched control subjects were included. They underwent an interview, clinical examination, oral mucosal biopsy and epicutan testing to the European baseline series, a toothpaste and dental material series. RESULTS: Nineteen patients had OLP, 19 OLL and 11stomatitis. Oral burning/itching was the most common symptom (83.7%), and 65.3% patients had more than one symptom. Patients visited their dentist more often than the healthy subjects and had statistically higher DMF-T and DMF-S scores. Nineteen patients (38.8%) and 10 healthy control subjects (34.5%) had allergic contact reactions primarily to fragrance ingredients. No differences could be found between OLP, OLL, stomatitis and healthy controls with regard to allergic contact reactions. However, contact allergy to aroma substances differed significantly between the patients and the healthy control subjects (p = 0.02). This type of contact allergy was most common in patients with OLP and OLL (p = 0.01). Avoidance cleared symptoms in all cases. CONCLUSION/CLINICAL RELEVANCE: Allergic reactions to aroma substances in oral hygiene products are common in patients with symptomatic OLP, OLL and stomatitis.

Effect of high-volume systematic local infiltration analgesia in Caesarean section: a randomised, placebo-controlled trial.

BACKGROUND: Pain after Caesarean section is often treated with opioids with a risk of side effects. Wound infiltration with local anaesthetics is effective and has few side effects, but volume vs. dose concentration has not been examined. METHODS: Ninety patients scheduled for elective Caesarean section included in a randomised, double-blinded, placebo-controlled trial receiving infiltration with 50 ml ropivacaine 0.5% or 125 ml ropivacaine 0.2% or 50 ml 0.9% saline (placebo) during surgery. Surgery was performed under lumbar spinal anaesthesia. Primary endpoint was post-operative pain. Secondary endpoints were rescue analgesic, post-operative nausea and vomiting, time spent in the postanesthesia care unit (PACU) and time to first mobilisation. RESULTS: No difference in pain response between groups, but time until maximum pain score was prolonged in the ropivacaine 0.5% group compared with the placebo group (P = 0.0493). The administration of ketobemidone at 24 h post-operatively in the ropivacaine 0.5% group was reduced compared with the placebo group (P = 0.020), and between the ropivacaine 0.2% group and the ropivacaine 0.5% group (P = 0.044). No significant differences between groups were found concerning time spent in the PACU, to first mobilisation or in number of women with nausea/vomiting (P ≥ 0.05). No complications related to ropivacaine were observed. CONCLUSIONS: Systematic infiltration with a high concentration, low volume compared with low concentration, high volume showed no significant effect on post-operative pain intensity. However, a statistically significant, but clinically limited opioid sparing effect was demonstrated compared with placebo in the high concentration, low volume group.

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.

Controlled intragastric pH and cimetidine inhibition of histamine-stimulated gastric acid secretion in the dog.

This study tested a circulating intragastric titration system with an examination of the kinetics of cimetidine inhibition of histamine-stimulated gastric acid secretion of pH 7.0. Dogs were anesthetized, intubated with a biluminal nasogastric device, and connected to the titrating system. The dogs were stimulated with histamine at 0.0, 0.25, 0.50, 1.0, 2.0, and 4.0 microgram/kg/min IV. The dose variations were repeated on separate days with cimetidine infusion at 0.0, 20, and 40 microgram/kg/min IV. Calculated maximal response was 4.52 mEq/kg/hr. Histamine D50 was 0.60 microgram/kg/min. Cimetidine ID50 was 22.6 microgram/kg/min when histamine was given at 1.0 microgram/kg/min. Although acid secretion was higher than other published values, cimetidine inhibition kinetics were not significantly different from published values. A positive correlation was found between cimetidine ID50 and the logarithm of the histamine infusion rate. Our data suggest that (1) a simple circulating intragastric titration system can give accurate results in acid secretion studies, (2) increased gastric pH may enhance histamine-stimulated acid secretion, (3) neutralization of gastric contents does not interfere with cimetidine inhibition kinetics which is competitive, and (4) at artifically high rates of histamine infusion, cimetidine can actually increase acid secretion. We suggest that a circulating intragastric system may be tested in a surgical intensive care unit to evaluate potential clinical value in antiulcer therapy.

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.

Cardiopulmonary function at rest and during exercise after resection for bronchial carcinoma.

BACKGROUND: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function. METHODS: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively. RESULTS: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection. CONCLUSIONS: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.

A comparison of two different dosages of pivampicillin and doxycycline in patients with gynaecological infections.

The efficacy of 500 mg pivampicillin twice daily, 350 mg pivampicillin 3-times daily and 100 mg doxycycline daily was compared in 106 patients with salpingitis, parametritis or endometritis. Both the pivampicillin regimens were equally effective. The average duration of therapy needed to produce a satisfactory clinical response was shorter with pivampicillin (14 days) than with doxycycline (21 days). Pivampicillin improved the patients' gynaecological status in 90% of the subjects treated compared to only 70% of patients given doxycycline. Fewer relapses were recorded in women given pivampicillin (4%) than in subjects treated with doxycycline (15%). Gonococci were isolated from 10% of vaginal swabs. The involvement of Chlamydia and Mycoplasma was not studied. However, the high cure rate indicated that, if present, they did not pose a therapeutic problem. Side-effects, mainly dyspepsia, were observed in 2 patients in each group. The twice-daily administration of pivampicillin is recommended, since it is more practical and increases patient compliance.

Should older patients undergo ileal pouch-anal anastomosis?

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is a technically demanding, lengthy procedure with substantial associated morbidity. Some have suggested that this procedure should not be performed in older patients. This study was conducted to evaluate whether older patients have a poorer functional outcome and higher complication rate than younger patients who undergo IPAA. METHODS: The 455 patients who have undergone IPAA at this institution were stratified according to age (< 55 versus > 55) to compare functional outcome and complication rates. The data were prospectively collected. The groups included 32 patients > 55 (7%) and 423 patients < 55. Comparisons were made with regard to stool frequency, incontinence rates, post-IPAA complications, postileostomy closure complications, and results 12 months postileostomy closure. RESULTS: Preoperative anal sphincter resting and squeeze pressures were significantly lower in the > 55 group. Most complication rates were similar after IPAA except dehydration rates, which were higher in the older patients than the younger ones (27% versus 11%, respectively). Pre-ileostomy closure anal sphincter resting and squeeze pressures were not significantly lower in patients older than 55. Twenty-four hour daytime and nighttime stool frequencies were significantly higher in the > 55 group, as were daytime and nighttime stool incontinence. CONCLUSION: Although functional outcome is poorer and some complications are higher in the > 55 group, the procedure can be safely performed with acceptable results and is greatly preferred by this population over permanent ileostomy.

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.

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)

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.

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)

Comparability of albuterol delivered by a piezoelectric device versus metered dose inhaler in patients with chronic obstructive airways disease.

In recent years, there has been increased interest in developing propellant-free inhalers for the treatment of patients with chronic obstructive airways disease. Various powder inhalators have been developed. A recent alternative to the dose-metered aerosols has been produced using the piezoelectric effect. This double-blind, double-dummy, randomized, dual-dose, four-period crossover study was designed to compare the effect of albuterol inhaled from the piezoelectric device (PED) and albuterol inhaled from the metered dose inhaler (MDI). The primary efficacy variables were forced expiratory volume in one second (FEV1) and area under the curve (AUC). Although we found a statistically significant device effect for the primary efficacy variables, the two treatments (PED [test] and MDI [reference]) are comparable. The only variable for which comparability was not found was time of onset. We found no dose differences. In conclusion, we found a similar effect of albuterol inhaled by a PED versus an MDI in patients with chronic obstructive airways disease.

[Broncholithiasis and lithoptysis]. / Broncholithiasis og lithoptysis.

Broncholithiasis and lithoptysis are rare phenomenons. A case of broncholithiasis in a woman, 58 years of age, with previous tuberculosis is presented, and the literature on broncholithiasis and lithoptysis is reviewed.

[Fertility after extrauterine pregnancy. A 16-year retrospective study]. / Fertilitet efter ekstrauterin graviditet. En 16 års retrospektiv opgørelse.

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.

[Methotrexate treatment of patients with prednisolone dependent bronchial asthma]. / Methotrexatbehandling af patienter med prednisolonafhaengig asthma bronchiale.

In this review we went through eight placebo-controlled clinical trials of the folic acid antagonist methotrexate in the treatment of bronchial asthma. The studies, which differ in their methods and findings, are reviewed critically. Some studies seem to give documentation of methotrexate as an effective drug in reducing the corticosteroid requirements in patients with chronic corticosteroid-dependent asthma. Adverse effects are wellknown from the use of methotrexate in patients with rheumatoid arthritis and include nausea, diarrhoea, vomiting, transient increases in liver enzymes, alopecia and stomatitis. Rare but potentially life-threatening adverse effects are interstitial pneumonitis, opportunistic infections, bone marrow- and renal insufficiency. The role of methotrexate in patients with chronic corticosteroid-dependent asthma still needs to be clarified. Practical guide-lines in treating asthma patients with methotrexate are suggested.

[Mask physiotherapy for prevention of pulmonary complications after heart surgery. A controlled study]. / Fysioterapi med maskebehandling til forebyggelse af pulmonale komplikationer efter hjertekirurgi. Et kontrolleret studie.

The objective of this prospective, consecutive, randomized, controlled study was to investigate the effects of mask physiotherapy on postoperative complications after heart surgery. Sixty-six low-risk male patients undergoing coronary artery by-pass graft surgery were evaluated. The patients were treated with routine chest physiotherapy alone or supplied with either positive expiratory pressure (PEP), or inspiratory resistance-positive expiratory pressure (IR-PEP). Postoperative pulmonary complications were assessed by forced vital capacity (FVC), arterial oxygen tension (PaO2), and chest X-ray examination. There was an almost equal decrease and subsequent rise in spirometric and blood gas values in all three groups, but patients treated with the PEP mask had a borderline significantly higher increase in PaO2 from day three to day six compared with patients treated with no mask. There was an almost equal frequency of atelectasis in the three treatment groups. It is concluded that no significant differences in outcome were found between the three groups.

[Primary lung cancer in patients under 40 years of age]. / Primaer lungekraeft hos patienter under 40 år.

There seems to be a resistance of patients and physicians towards aggressive diagnostic evaluation of the symptoms of lung cancer in young people. We here review nine series of young patients with primary lung cancer. Patients below 40 years of age represent between 1.2 and 5% of the total lung cancer population. The distribution of sex and histopathologic findings is different, there being more women, fewer cases of squamous cell and more cases of small anaplastic and adenocarcinoma in the young group. Between 87 and 96% are smokers. There is a delay from the debut of symptoms to the first contact with a general physician of 2.4 to 10.8 months. There is a wide variation concerning tendency to operate with a frequency of curative resection of between 15 and 57%. Based on the survival of young patients who are treated by curative surgical resection, the outcome of surgical treatment for young patients does not differ from the general experience concerning resection in patients of all ages. Young patients who are found inoperable have worse survival than the older patients. Seventy to 90%, more than in the group of patients of all ages, have stadium II or III at the time of diagnosis. In conclusion, physicians should be aggressive with respect to the diagnostic evaluation even of young patients with symptoms suggestive of lung cancer.

[Disseminated primary bronchogenic carcinoma in 3 young patients]. / Dissemineret primaert bronkogent karcinom hos tre unge patienter.

Primary lung cancer in young patients is rare, patients under 40 years of age constituting between 1.2 and five percent of all cases. Three cases of primary lung cancer in young patients are presented, and the typical manifestations of primary lung cancer in young patients are discussed.