Contact allergy and hand eczema in Swedish dentists

Hand eczema and contact allergy in Swedish dentists were studied in a multidisciplinary project. The aims of the study were to establish diagnoses, to investigate the occurrence of contact allergy, in particular to (meth)acrylates, and to evaluate certain consequences of hand eczema. A postal questionnaire on skin symptoms, atopy and occupational experience was mailed to 3,500 dentists aged <65 years, and licensed 1965-1995. The response rate was 88%. Among dentists living in 3 major cities, 14.9% (n= 191) reported hand eczema during the previous year. They were invited to a clinical examination, including patch testing with a standard and a dental series. 158/191 (83%) dentists attended, and hand eczema diagnosis was confirmed in 149/158 (94%). Irritant contact dermatitis was diagnosed in 67% and allergic contact dermatitis in 28%. On patch testing, 50% presented at least 1 positive reaction. The most frequent allergens were nickel sulfate, fragrance mix, gold sodium thiosulfate and thiuram mix. 7 (5%) had positive reactions to (meth)acrylates, all to 2-hydroxyethyl methacrylate and 6 also to ethyleneglycol dimethacrylate. 38% had consulted a physician, 4% had been on sick-leave and 1% had changed occupational tasks due to hand eczema. No dentist with allergy to acrylates had been on sick-leave or changed occupation. It is concluded that dentistry is a high-risk occupation for hand eczema, and that irritant contact dermatitis is most common. The prevalence of contact allergy to acrylates was below 1% in the population of responding dentists, and in most cases did not have serious medical, social or occupational consequences.     

Further characterization of an adenosine transport system in the mitochondrial fraction of rat testis

Previous work from our laboratory has demonstrated the presence of high-affinity binding sites for [3H]nitrobenzylthioinosine ([3H]NBTI), a marker of adenosine uptake systems, in the mitochondrial fraction of rat testis. Here, we characterize this system functionally through [3H]adenosine uptake assays. This system (K(m)=2+/-1.3 microM; V(max)=86.2+/-15.5 pmol/mg protein/min) was found to be saturable, non sodium-dependent and sensitive to temperature, pH and osmolarity. [3H]Adenosine incorporation was potently inhibited by hydroxynitrobenzylthioguanosine (HNBTG, IC(50)=3 nM) although NBTI inhibited this uptake weakly (IC(50)=72. 7+/-37.1 microM). Dilazep>dipyridamole>/=hexobendine inhibited [3H]adenosine incorporation at low micromolar concentrations. The nucleosides inosine and uridine were weak inhibitors of this system. The adenosine receptor ligands N(6)-phenylisopropyladenosine (PIA) and 2-chloroadenosine inhibited the uptake only at micromolar concentrations. Neither 5'-(N-ethylcarboxamido)-adenosine (NECA) nor theophylline inhibited adenosine uptake by more than 60% but the mitochodrial benzodiazepine receptor ligands 4'-chloro-diazepam (Ro 5-4864) and 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl) isoquinoline carboxamide (PK 11195) were able to inhibit it. The lack of inhibition by the blockers of the mitochondrial adenine-nucleotide carrier, atractyloside and alpha, beta-methylene-ATP, indicates that [3H]adenosine uptake occurs via a transporter other than this carrier. All these results support the existence of an equilibrative adenosine transport system, which might mediate the passage of adenosine formed in the mitochondria to the cytoplasm.     

Treatment of organophosphate poisoning in pigs: antidote administration by a new binary autoinjector

 The therapeutic effectiveness of a new binary autoinjector containing 500 mg HI-6 and 2 mg atropine sulphate was tested in anesthetized pigs poisoned by a lethal dose of soman i.v. (9 μg/kg per 20 min). Pharmacokinetics and pharmacodynamics of HI-6 were studied concomitantly on administration of HI-6 alone, together with atropine sulphate, or together with atropine sulphate during soman intoxication. Cardiopulmonary parameters were monitored and serum concentrations of oxime and acetylcholinesterase (AChE) were measured in blood samples taken at intervals over a 6-h period postinjection. Five minutes after the start of soman infusion, mean AChE activity was decreased to 27±4.3% of baseline and signs of poisoning appeared. The antidotes, HI-6 and atropine sulphate, were then administered i.m. One minute after this injection there was a transient significant increase in AChE activity of 76±8.2% of baseline (p<0.01). It then again decreased and remained suppressed throughout the experiment. Mean respiratory rate was significantly decreased (p<0.01) to 20±3.2% of baseline after 20 min of soman infusion and remained low during the rest of the experiment. The poisoning signs were counteracted 15–20 min after antidote therapy and all pigs survived soman intoxication without ventilatory assistance. Administration of either atropine or atropine and soman had no significant effect on the pharmacokinetics of HI-6 in anesthetized pigs. Received: 20 February 1995/Accepted: 3 May 1995     

Long-term results after surgical management of partial Achilles tendon ruptures

Although Achilles tendon injuries are common overuse injuries in sports, the exact incidence is unknown, primarily as a result of varying definitions and diagnoses of the underlying pathological changes. Despite numerous studies of treatment of the Achilles tendon injuries, the longterm results are not well known. The results after surgical treatment of chronic partial Achilles tendon ruptures in 64 patients with a follow-up of 6 (1.5–11) years were evaluated in a retrospective study. The ruptures were divided into three groups: (I) proximal (more than 3 cm above the calcaneus), (II) distal and (III) combined (proximal and distal). All patients underwent an operation involving the excision of the devitalized tendon tissue and, in groups (II) and (III), also the excision of the deep Achilles bursa and removal of the dorsal corner of the calcaneus. The functional results were satisfactory in 43 (67%) patients and unsatisfactory in 21 (33%). The results were better in patients with proximal ruptures than in patients with either distal or combined ruptures. Males experienced better results than females. Post-operative immobilization in a plaster cast had no significant influence on the final result. Nine (14%) patients with either a distal or a combined rupture were re-operated on and in seven of them the final result was satisfactory. The conclusion of this study is that partial Achilles tendon ruptures are often difficult to treat and only two out of three patients can be expected to obtain satisfactory results after surgical treatment.     

Model-Based Adaptive Optimal Design (MBAOD) Improves Combination Dose Finding Designs: an Example in Oncology

Design of phase 1 combination therapy trials is complex compared to single therapy trials. In this work, model-based adaptive optimal design (MBAOD) was exemplified and evaluated for a combination of paclitaxel and a hypothetical new compound in a phase 1 study to determine the best dosing regimen for a phase 2 trial. Neutropenia was assumed as the main toxicity and the dose optimization process targeted a 33% probability of grade 4 neutropenia and maximal efficacy (based on preclinical studies) by changing the dose amount of both drugs and the dosing schedule for the new drug. Different starting conditions (e.g., initial dose), search paths (e.g., maximal change in dose intensity per step), and stopping criteria (e.g., “3?+?3 rule”) were explored. The MBAOD approach was successfully implemented allowing the possibility of flexible designs with the modification of doses and dosing schedule throughout the trial. The 3?+?3 rule was shown to be highly conservative (selection of a dosing regimen with at least 90% of the possible maximal efficacy in less than 21% of the cases) but also safer (selection of a toxic design in less than 2% of the cases). Without the 3?+?3 rule, better performance was observed (>67% of selected designs were associated with at least 90% of possible maximal efficacy) while the proportion of DLTs per trial was similar. Overall, MBAOD is a promising tool in the context of dose finding studies of combination treatments and was showed to be flexible enough to be associated with requirements imposed by clinical protocols.     

Immediately loaded implants supporting fixed prostheses in the edentulous maxilla: a preliminary clinical and radiologic report

PURPOSE: To evaluate the survival rate of immediately loaded ITI sand-blasted, large-grit, acid-etched (SLA) solid-screw dental implants in the edentulous maxilla after 8 months of loading. MATERIALS AND METHODS: Twenty-eight patients (mean age 63 years) with edentulous maxillae each received 6 implants and 1 implant-supported fixed provisional prosthesis within 24 hours after surgery. After a mean healing time of 15 weeks, the patient received a definitive, screw-retained, implant-supported fixed prosthesis. A total of 168 implants were placed. Clinical parameters were registered after 1 month of loading with the implant-supported fixed prostheses as well as 8 months after implant placement. Radiologic examinations and assessments were made at implant placement and after 8 months. RESULTS: The mean marginal bone level at implant placement was 1.6 mm (range 0 to 5.1; SD 1.1) apical of the reference point (the implant shoulder). The mean marginal bone level at the 8-month follow-up was 3.2 mm (range 0.4 to 5.9; SD 1.1) apical of the reference point. Three implants failed during the healing period. DISCUSSION: The improved results in the present study might be a result of the positive effect of splinting the implants immediately after placement. CONCLUSION: ITI SLA solid-screw implants immediately loaded (ie, loaded within 24 hours of placement) and supporting fixed prostheses had successful survival rates after 8 months. The present results constitute a solid baseline for future follow-up studies.     

A multifactorial intervention program reduces the duration of delirium, length of hospitalization, and mortality in delirious patients

OBJECTIVES: To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients. DESIGN: Prospective intervention study. SETTING: Department of General Internal Medicine, Sundsvall Hospital, Sweden. PARTICIPANTS: Four hundred patients, aged 70 and older, consecutively admitted to an intervention or a control ward. INTERVENTION: The intervention consisted of staff education focusing on the assessment, prevention, and treatment of delirium and on caregiver-patient interaction. Reorganization from a task-allocation care system to a patient-allocation system with individualized care. MEASUREMENTS: The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1, 3, and 7 after admission. Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Delirium was equally common on the day of admission at the two wards, but fewer patients remained delirious on Day 7 on the intervention ward (n=19/63, 30.2% vs 37/62, 59.7%, P=.001). The mean length of hospital stay+/-standard deviation was significantly lower on the intervention ward then on the control ward (9.4+/-8.2 vs 13.4+/-12.3 days, P<.001) especially for the delirious patients (10.8+/-8.3 vs 20.5+/-17.2 days, P<.001). Two delirious patients in the intervention ward and nine in the control ward died during hospitalization (P=.03). CONCLUSION: This study shows that a multifactorial intervention program reduces the duration of delirium, length of hospital stay, and mortality in delirious patients.     

Postpartum depression and mother–offspring conflict over maternal investment

Background and objectivesAs the mother–offspring relationship is central to human reproduction, postpartum depression symptoms are difficult to explain in evolutionary terms. We proposed that postpartum depression might arise as a result of evolutionary mother–offspring conflict over maternal investment, and investigated the association between postpartum depression symptoms, infant night waking, maternal sleep disturbance and breastfeeding frequency.MethodologyWe conducted a cross-sectional analysis using survey responses at 6 months postpartum from 1598 Finnish mothers. We hypothesized that infant night waking at 6 months postpartum would be associated with postpartum depression symptoms, and that this association would be mediated by maternal sleep disturbance and a higher breastfeeding frequency.ResultsInfant night waking was moderately associated with postpartum depression symptoms, and this association was mediated by maternal sleep disturbance (R²=0.09). Contrary to our prediction, we found that increased breastfeeding was associated with less postpartum depression symptoms.Conclusions and implicationsWe conclude that postpartum depression symptoms might partly be the result of increased maternal fatigue stemming from high offspring demands on maternal investment, but that this is not due to the metabolic strain from increased breastfeeding. Studying postpartum depression from the mother–offspring conflict perspective can potentially improve our understanding of the involved behavioral processes of both mother and offspring, and allow interventions designed to benefit the well-being of both parties. Lay Summary: We proposed that postpartum depression is due to an evolutionary conflict between mother and infant, where the infant tires the mother to delay the arrival of a sibling. We found a link between infant night waking and postpartum depression, mediated by the mother’s sleep, but not by breastfeeding frequency.     

A Pediatric Bone Mass Scan Has Poor Ability to Predict Adult Bone Mass: A 28-Year Prospective Study in 214 Children

As the correlation of bone mass from childhood to adulthood is unclear, we conducted a long-term prospective observational study to determine if a pediatric bone mass scan could predict adult bone mass. We measured cortical bone mineral content (BMC [g]), bone mineral density (BMD [g/cm²]), and bone width (cm) in the distal forearm by single photon absorptiometry in 120 boys and 94 girls with a mean age of 10 years (range 3–17) and mean 28 years (range 25–29) later. We calculated individual and age-specific bone mass Z scores, using the control cohort included at baseline as reference, and evaluated correlations between the two measurements with Pearson’s correlation coefficient. Individual Z scores were also stratified in quartiles to register movements between quartiles from growth to adulthood. BMD Z scores in childhood and adulthood correlated in both boys (r = 0.35, p < 0.0001) and girls (r = 0.50, p < 0.0001) and in both children ≥10 years at baseline (boys r = 0.43 and girls r = 0.58, both p < 0.0001) and children <10 years at baseline (boys r = 0.26 and girls r = 0.40, both p < 0.05). Of the children in the lowest quartile of BMD, 58 % had left the lowest quartile in adulthood. A pediatric bone scan with a value in the lowest quartile had a sensitivity of 48 % (95 % confidence interval [CI] 27–69 %) and a specificity of 76 % (95 % CI 66–84 %) to identify individuals who would remain in the lowest quartile also in adulthood. Childhood forearm BMD explained 12 % of the variance in adult BMD in men and 25 % in women. A pediatric distal forearm BMD scan has poor ability to predict adult bone mass.     

Effect of external dead space removal on CO2 homeostasis in mechanically ventilated adult Covid-19 patients

Background

Patients with Covid-19 respiratory failure present with hypoxemia, often in combination with hypercapnia. In this prospective, observational study we examined the effect of removing external dead space (DS) on CO₂-homeostasis in mechanically ventilated Covid-19 patients. In addition, volumetric capnography was validated for its ability to estimate external DS volume using in vitro measured DS volumes as reference.

Methods

In total, 10 patients with acute respiratory distress syndrome from Covid-19 were included. Volumetric capnography, mechanical ventilation, and arterial blood gas data were analyzed before and after removal of external DS and analyzed for potentially significant changes in response to DS removal. Measurements of external DS were obtained in circuit using volumetric capnography and compared to actual measured DS volumes off the circuit.

Results

After the removal of external DS, the alveolar minute ventilation and CO₂ elimination improved, notwithstanding unchanged respiratory rate and tidal volumes. The increase in CO₂ elimination was associated with a decrease in arterial CO₂ partial pressure (PaCO₂)_. The volumetric capnography method for assessment of external DS showed a low bias of −9 mL (lower limit of agreement −40, 95% CI −60 to −20 mL, upper limit of agreement 21 mL, 95% CI: 1–40 mL) and a percentage error of 48% compared to absolute values measured in vitro.

Conclusion

Removal of external DS increased alveolar minute ventilation and CO₂ elimination in Covid-19 patients with respiratory failure in the current study. This was associated with a decrease in PaCO₂. This may indicate a decreased CO₂ production due to decreased work of breathing and more effective gas-exchange in response to DS removal. In addition, volumetric capnography appears to be a clinically feasible method for continuous measurement of external DS in the current study and may be of value in optimizing ventilator treatment.