Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery

Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1-42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7-20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group. IMPLICATIONS: This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.     

Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma

To elucidate the relationship between genomewide DNA hypomethylation and chromosome instability, 55 prostate carcinoma specimens were analyzed for extent of hypomethylation by Southern blot analysis of LINE-1 sequence methylation and for loss or gain of chromosomal material by comparative genomic hybridization. Seventeen (31%) tumors showed strong hypomethylation of DNA, whereas four (7%) displayed slight hypomethylation and the rest of the tumors normal-level methylation. Chromosomal aberrations were observed in 34 carcinomas. The most frequent chromosomal alterations were loss of 13q in 18 cases and aberrations in 8p (loss) or 8q (gain) in 16 cases. The presence of chromosomal loss or gain was significantly associated with the presence of strong hypomethylation. A striking correlation (P = 0.00001) was observed between aberrations on chromosome 8 and hypomethylation, whereas no association was seen between DNA hypomethylation and loss of 13q. The association between DNA hypomethylation and the presence of metastases was statistically significant (P = 0.044), and both chromosomal alterations and DNA hypomethylation tended to be more frequent in higher-stage tumors. In conclusion, the data indicate that hypomethylation is associated with chromosomal instability in prostate cancer. Specifically, a surprisingly strong association between alterations on chromosome 8 and genomewide hypomethylation was found. This association suggests that DNA hypomethylation and alterations in chromosome 8 may be mechanistically linked to each other in prostate carcinoma.     

Cancer incidence among Finnish nuclear reactor workers

Because of their well-documented exposures to repeated low doses of ionizing radiation, nuclear reactor workers offer an opportunity to assess cancer risk from low-dose radiation. A cohort of all 15,619 Finnish nuclear reactor workers was established through dose-monitoring records. A questionnaire survey revealed no substantial differences in consumption of tobacco or alcohol between different exposure groups nor between nuclear power company employees and contract workers. In the follow-up for cancer incidence, no clear excess in cancer incidence was observed overall, nor was any observed in any of the specific cancer types studied. There was little evidence for an association between cancer incidence and cumulative radiation dose, but the statistical power was limited. More precise estimates will be available from an international collaborative study of nuclear industry workers, including our cohort.     

Maternal compared with infant vitamin D supplementation.

Vitamin D metabolites were studied in mother-infant pairs at delivery and eight and 15 weeks after that to evaluate the possibility of vitamin D supplementation of infant through the mother. Healthy mothers (n = 49) delivering in January received daily either 2000 IU (group 1), 1000 IU (group 2), or no (group 3) vitamin D. Their infants were exclusively breast fed, and those in group 3 received 400 IU of vitamin D a day. After eight weeks of lactation the infantile vitamin D concentrations were similar in groups 1 and 3 but significantly lower in group 2. The serum 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were also lower in group 2. The mean mineral, parathyroid hormone, and alkaline phosphatase values showed no intergroup differences at any point. No infants showed any clinical or biochemical signs of rickets, and their growth was equal. In conclusion, a daily postpartum maternal supplementation with 2000 IU of vitamin D, but not with 1000 IU, seems to normalise the vitamin D metabolites of breast fed infants in winter. Maternal safety with such supplementation over prolonged periods, however, should be examined.     

Double blind study on the need for vitamin D supplementation in prepubertal children

Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown.     

Lumbosacral fusion by standing H-graft technique

Summary Fusion of the lumbosacral spine was carried out on 44 patients. A modification of the standing H-graft technique was used in 41 of the patients. The operative diagnosis was degeneration of the lumbosacral spine in nearly two-thirds of the cases and spondylolisthesis in about one-third. Operations for low back or sciatic pain had previously been performed on 17 patients. The duration of postoperative bed rest ranged from one to six weeks; a lumbosacral corset was used at least for six weeks postoperatively. The average stay in hospital was 52 days. Complications occurred in five cases.The operative results of 40 patients were evaluated on the basis of a follow-up examination performed on average 3.6 years after operation. Nearly half the patients with radiologically successful fusions had a good subjective improvement and about one-fourth had returned to their previous or corresponding occupations. The operative result was at least fair in about half the patients, assessed by a measure of the patients' subjective improvement and working capacity. In the non-fusion group (six cases) the operative results were exclusively poor. Age over 40 years, long-standing preoperative disability and previous back operations proved prognostic factors for poor results.Assessed from functional radiographs, 63% of two-segment fusions and 95% of one-segment fusions were successful.The operative technique appeared simple and suitable for fusions of one spinal segment, but the value of the lumbosacral fusion in the treatment of low back pain seemed doubtful because of the great proportion of poor clinical results even following technically successful fusions.

---

Zusammenfassung Die dorsale Spondylodese der Lumbosakralregion wurde an 44 Patienten durchgeführt. Eine Modifizierung der stehenden H-Span-Technik wurde bei 41 Patienten angewendet. Lumbosakrale Degeneration war in fast zwei Drittel, Spondylolisthesis in etwa einem Drittel der Fälle die Operations-diagnose. Bei 17 Patienten waren bereits früher Operationen wegen Rückenschmerzen oder Ischiassyndrom durchgeführt worden. Die postoperative Bettruhe dauerte eine bis sechs Wochen. Nach der Operation wurde ein lumbosakrales Korsett mindestens sechs Wochen getragen. Der durchschnittliche Krankenhausaufenthalt betrug 52 Tage. In fünf Fällen kamen Komplikationen vor.Die Operationsergebnisse von 40 Patienten wurden auf Grund der Nachuntersuchung bewertet. Die Beobachtungszeit betrug im Durchschnitt 3,6 Jahre. Beinahe die Hälfte der Patienten mit röntgenologisch stabiler Fusion hatte ein gutes subjektives Endergebnis, und ein Viertel hatten ihre frühere oder eine entsprechende Arbeit wieder aufgenommen. Bei der Anwendung der subjektiven Symptome und der Arbeitsfähigkeit als Kriterien der Bewertung war das operative Resultat wenigstens mäßig bei etwa der Hälfte der Patienten. Bei den sechs Fällen, bei denen die stabile Fusion ausblieb, waren die Operationsresultate ausschließlich schlecht. Alter über 40 Jahre, langdauernde voroperative Arbeitsunfähigkeit und frühere Rücken-operationen becinträchtigten die Operationserfolge.Auf Grund der Bewertung funktioneller Röntgen-aufnahmen waren 63% der Versteifungen zweier Segmente und 95% der Versteifungen eines Segmentes erfolgreich.Die angewandte Operationstechnik erwies sich als einfach und angebracht für die Versteifung eines, aber nicht mehrerer Segmente. In der Behandlung von Kreuzschmerzen scheint aber der Wert der lumbosakralen Spondylodese fraglich zu sein, weil die klinischen Endergebnisse, selbst bei technisch erfolgreichen Fusionen, zum größten Teil schlecht waren.

     

Vaccination-induced HI antibody response to intraepidemic influenza A(H3N2) virus variants of the 1996-1997 epidemic season

Intraepidemic antigenic and genetic variation was indicated when H3N2-subtype influenza A virus strains isolated during the 1996-1997 epidemic season in Finland were studied for reactivity in the haemagglutination inhibition (HI) assay and for nucleotide sequences coding for the variable HA1 domain of viral haemagglutinin. Thirty prevaccination- and postvaccination-paired sera taken from subjects who had been vaccinated against influenza during the previous autumn were studied for the presence of HI antibody to the homologous vaccine virus A/Nanchang/933/95, and five field strains representing the genetic and antigenic variability of the 1996-1997 epidemic season. The lowest vaccination-induced HI titres in each of the three age groups were detected in the two field strains that had been isolated from vaccinated patients and belonged to two different genetic sublineages. The intraepidemic variability of the 1996-1997 field strains in HI reactivity may be indicative of circulation of virus strains that may be capable of breaking through vaccination-induced immunity better than the other strains.     

Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins

Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 ± 10% higher ( P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 ± 4.3 versus 9.0 ± 6.1 μmol (100 ml)⁻¹ min⁻¹, P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage ( P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake.     

Proliferative activity determined by DNA flow cytometry and proliferating cell nuclear antigen (PCNA) immunohistochemistry as a prognostic factor in prostatic carcinoma.

Proliferative activity was measured in 165 paraffin-embedded prostatic carcinomas using DNA flow cytometric analysis of the S-phase (SPF) and G2/M-phase fractions and CAS 200 image analysis of the proliferating cell nuclear antigen (PCNA) expression defined immunohistochemically by PC10 and 19A2 monoclonal antibodies. No significant associations were found between the flow cytometric and the two immunohistochemical measures of cell proliferation. Of the four indices, only SPF, S + G2/M, and immunostaining with 19A2 antibody were associated with the poor histological grade of the tumour. High SPF and S + G2/M were significantly associated with poor 10-year overall survival (P < 0.001) and prostatic carcinoma-specific survival (P < 0.01). Multivariate analyses of prostatic carcinoma-specific survival in patients with non-metastatic disease (M0-stage) indicated that only S + G2/M, T-stage, and histological grade (only if re-evaluated by a single pathologist) had independent prognostic significance. High-level PCNA staining (> 16 per cent of cells stained) with 19A2 antibody was associated with poor prognosis only in univariate analysis, and PC10 immunostaining had no prognostic value. In conclusion, a high proliferative activity as defined by flow cytometric S+G2/M is an independent predictor of poor survival in patients with non-metastatic prostatic carcinoma. PCNA immunostaining from formalin-fixed, paraffin-embedded prostatic carcinomas has little, if any, prognostic value.