Recurrent respiratory papillomatosis in northern Sweden: Clinical characteristics and practical guidance

Conclusion: Recurrent respiratory papillomatosis (RRP) patients with high surgical treatment frequency (≥ 1/year, HF) were significantly younger and had a more widespread laryngeal disease compared to a low frequency treated group (< 1 treatment/year, LF). This study confirms the existence of a clinical RRP group, not primarily related to HPV sub-type, but more care-intensive and in need of more vigilant follow-up. Objectives: RRP is associated with high morbidity due to its influence on breathing and voice. The purpose of this study was to characterize RRP patients in northern Sweden and investigate possible predictor factors affecting therapeutic needs. Method: Patients from the regional referral area (northern Sweden) were categorized for age, disease duration, juvenile or adult onset, profile of disease development, number of surgical sessions in relation to disease duration, laryngeal deposition of papilloma, gender, and HPV sub-types, in order to identify patients with increased need for frequent surgical treatment. Results: The median age of the RRP patients (n = 48) was 44.5 years; 34 (71%) were males and 14 (29%) females, most were infected with HPV 6. Patients with high surgical treatment frequency/year were significantly younger and showed more widespread papillomatous vegetation in the larynx, compared to the low frequency treated group.     

Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers

Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release (ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine and metoprolol when administered as ER formulation. Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis in six subjects. Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding C_max of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding pharmacodynamics was detected between the fixed combination and the corresponding free combination. Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination. Received: 29 October 1996 / Accepted in revised form: 21 March 1997     

Relation between mood, social support and the quality of life in patients with laryngectomies

Two hundred laryngectomized members of the Norwegian Society of Laryngectomies (NSL), a subsidiary of the Norwegian Cancer Society, were invited to answer the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 QOL questionnaires to assess their quality of life (QOL). The Beck Depression Inventory (BDI) scores, their levels of social support and their marital and educational statuses were also determined. In addition, the activity levels of each patient within the NSL were assessed. The questionnaires were returned anonymously by 104 patients. The results of this sample were compared with the responses to the EORTC QLQ C30/H&N35 by all of the survivors of treatment for head and neck squamous cell carcinoma (HNSCC) in western Norway between 1992 and 1997. This sample included 96 of 106 eligible patients. The QLQ-C30 symptom scores include, e.g., dyspnea, smell and taste. However, neither the QLQ-C30 functional scores nor the disease-specific scores of the people with laryngectomies differed from the general HNSCC-treated population. The level of social support by family, friends and neighbors was not associated with the QOL, whereas high BDI scores were associated with reduced QOL by most measured indexes. Furthermore, a positive association was determined between the level of activity within the NSL and QOL. This relation was to some extent secondary to differential BDI scores. In conclusion, the QOL of people with laryngectomies is relatively similar to a general population of patients treated because of HNSCC, is related to the activity level within a patient interest organization and is associated with a lower mood level.     

Heterogeneity of squamous cell carcinomas of the oral cavity studied by flow cytometry

The DNA pattern was determined by flow cytometry in 76 samples from 16 squamous cell carcinomas of the oral cavity to assess intratumour DNA heterogeneity. Heterogeneous DNA content was found in 2 tumours (12%); both containing DNA diploid and DNA aneuploid cell clones. The remaining 14 tumours showed a homogeneous DNA distribution in the different specimens; 9 (56%) were diploid, 3 (19%) aneuploid and 2 (12%) were polyploid. The DNA non-diploid tumours were clinically more advanced than the DNA diploid ones (p less than 0.05). The tumour proliferation rate (fraction of cells in S-phase) was higher in aneuploid tumours than in diploid ones (p less than 0.01).     

Altered Homeostasis of Extracellular Matrix Proteins in Joints of Standardbred Trotters During a Long‐term Training Programme

This study evaluates how strenuous training, age and lameness influence the release of cartilage oligomeric matrix protein (sf‐COMP), aggrecan and collagen type II into synovial fluid in 28 (19.5–40 months) Standardbred trotters (STB), during a long‐term training programme (24 months). All the horses were trained by the same trainer and were healthy on entering the training programme. Synovial fluid (sf) from the left middle carpal joint in each subject was sampled every third month. Enzyme‐linked immunosorbent assay was used to determine the concentrations of sf‐COMP, sf‐aggrecan and sf‐collagen type II. Concentration of sf‐COMP decreased with increasing age and total days of training. The concentration of sf‐COMP was found similarly related to both age and total days of training, so they could not be differentiated. It was also shown that the concentration of collagen type II degradation products increased with total days of training. The study shows that extensive and long‐term training programme induces metabolic changes in articular cartilage exemplified by reduced release and synthesis of COMP. This is most likely due to strenuous training leading to inappropriate load on the articular cartilage.     

Periosteal transplantation to the rabbit patella

Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.     

Gender differences in patients treated for critical limb ischemia.

OBJECTIVE: To investigate, in patients treated for critical limb ischemia, how pre-operative conditions, localisation of lesions and outcome varied according to gender. DESIGN: Retrospective cohort study. METHODS: Medical records were analysed for all patients treated with vascular reconstruction or PTA for critical limb ischemia 1993-1994 (119 women, 115 men) at the Karolinska Hospital. All events such as secondary intervention, amputation and death occurring until 2003 were included in the analysis. RESULTS: The preoperative conditions were similar between women and men apart from higher mean age (74 years in women vs 69 in men, p=0.0002), fewer subjects with a smoking history (63 vs 82%, p=0-005) and diabetic disease (22 vs 43%, p=0.0004) among females. More interventions were performed suprainguinally in women (44% in women vs 19% in men). Amputation and survival rates were similar in women and men, even after matching for age and diabetes. CONCLUSION: Women were older, had a lower frequency of diabetes, smoked less and had more proximal lesions than treated men. Outcome was identical for both genders. Biological and anatomical differences could possibly explain several of the found gender differences. Gender differences in risk factors and possibly in the selection process also may have contributed to our findings.     

Survival in patients with abdominal aortic aneurysms. Comparison between operative and nonoperative management

This study evaluates the risk benefit relationship in the surgical treatment of abdominal aortic aneurysm (AAA). Two hundred and thirteen patients with AAA diagnosed by CT were selectively managed depending upon the size of the aneurysm, and were followed with a mean follow-up time of 5 years and 4 months. Aneurysms greater than 5 cm were generally operated on if no serious contraindication existed. Aneurysms less than 5 cm were followed by repeated examinations and operated on if an increase in size occurred. Some small aneurysms were operated on for other reasons. Elective surgical management of 134 patients resulted in a thirty day mortality of 7.5%. Later, seven additional patients died from causes related to the surgery. Survival of electively operated patients by life table analysis was 68% at 5 years. A significantly higher mortality was noted among those who had evidence of coronary heart disease at the time of operation. Forty-two patients with AAA less than 5 cm at the initial examination were not operated on and three ruptured, but all had grown to a size greater than 5 cm at the time of rupture. Patients with AAA less than 5 cm that were not operated on had a slightly but not significantly higher mortality than those who were operated on electively. This difference was mainly attributable to deaths from cardiac causes and not to ruptures. Patients with aneurysms greater than 5 cm who were not operated on had a significantly higher mortality than those that were, only 14% in the former group survived.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver.

Apolipoprotein-B 48 (apoB 48) and apoB 100 expression and the editing of apoB mRNA have previously been shown to be hormonally regulated in rat liver. We have investigated the effects of hypophysectomy and replacement therapy with T4, cortisol (C), and GH in vivo on the proportion of edited apoB mRNA in rat liver and cultured rat hepatocytes as well as the synthesis and secretion of apoB 48 and apoB 100 in cultured rat hepatocytes. Hypophysectomy decreased the proportion of edited apoB mRNA in intact liver from 62% in normal rats to 29% in hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C did not influence the proportion of edited apoB mRNA, whereas treatment with GH, either alone or together with T4 and C, increased the proportion of edited apoB mRNA to the levels observed in normal rats. In cultured hepatocytes isolated from normal rats, the proportion of apoB 48 (percentage of total labeled apoB) was 78% and decreased to 40% in cells isolated from hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C had no effect on the proportion of apoB 48 present in isolated cells, whereas it increased to 60% after treatment with GH together with T4 and C. The proportion of apoB 48 in the medium was affected by hypophysectomy and the various hormonal treatments in a similar way to that observed in the cells. Results from in vivo labeling experiments suggested that GH alone had the capacity to increase the percentage of apoB 48 in hypophysectomized rats. On the contrary, T4 and C was needed, in addition to GH, to increase the proportion of apoB 48 in isolated hepatocytes from hypophysectomized rats. Our results suggest that this discrepancy is due to a difference between the effect of GH alone on apoB mRNA editing in the intact liver and that in isolated hepatocytes. The total secretion of apoB into the cell culture medium was not affected by hypophysectomy and hormonal treatments of the rats. In conclusion, these results indicate that GH is involved in the regulation of editing of apoB mRNA and the proportion of apoB 48 synthesized and secreted in rat liver. Thus, our observations emphasize the importance of GH as a regulator of lipoprotein metabolism.