Extravascular lung water measurement in septic sheep

Sheep were prepared with a chronic lung lymph fistula and studied unanesthetized following septicemia by infusion of live Escherichia coli 10(9) ml/kg bw or injection of oleic acid 0.05 ml/kg bw. Extravascular lung water (EVTV) was measured with thermal-dye technique and compared to gravimetrically measured lung water (EVWV). Septic sheep had increased pulmonary artery pressure, reduced mean arterial blood pressure and reduced cardiac output. In control animals there was a correlation between EVTV-EVWV of r = 0.70. In animals given oleic acid lungs were macroscopically edematous and the correlation was r = 0.93. In septic sheep, however, no correlation could be found between EVTV and EVWV (r = -0.25). The thermal-dye technique was found to give erroneously high values. This finding could probably be due to erythrostasis and leukocyte plugging with uneven perfusion and prolonged transit times due to reduced cardiac output.     

Transvaginal ultrasonography and endometrial histology in peri- and postmenopausal women on hormone replacement therapy

Objective To determine the association between endometrial thickness and endometrial histology in a large sample of women using HRT.
Design Results from three multi-centre studies were combined.
Participants Five hundred and sixty-four climacteric women were treated with either sequential, continuous combined or long-cycle therapy.
Main outcome measures The women underwent 717 examinations with both transvaginal ultrasonography and histological examination of the endometrium. Endometrial thickness was measured and associated with the histological findings.
Results Eight cases of endometrial hyperplasia were diagnosed. All the hyperplasias were simple without atypia. Two cases had an endometrial thickness < 4 mm and two a thickness > 8 mm. The > 4 mm threshold for abnormal endometrium had a sensitivity of 75%, a specificity of 47%. a positive predictive value of 2% and a negative predictive value of 99%.
Conclusion No association could be found between the endometrial thickness measured by transvaginal ultrasonography and endometrial pathology. In six out of eight women with simple hyperplasia the endometrium measured > 4 mm.     

Validity evidence for a modified version of the Orthotics and Prosthetics Users' Survey

Purpose: To evaluate the validity of a modified version of the Orthotics and Prosthetics Users' Survey (OPUS) with persons using different prosthetic and orthotic (P&O) devices.Method: Two-hundred-and-eighty-two adults using prosthesis, orthosis, shoe insoles or orthopaedic shoes completed OPUS. OPUS comprises five modules - Lower and Upper Extremity Functional Status, respectively (LEFS and UEFS), Client Satisfaction with Device and Services, respectively (CSD and CSS), and, Health-Related Quality of Life (HRQoL). Eight new items were added to LEFS and six to UEFS. Rasch analysis was used for data analyses.Results: Rating scales functioned satisfactory after some modifications. All modules demonstrated a ceiling effect. Unidimensionality was satisfactory after deleting some items and dividing HRQoL into two subscales, although somewhat weak on CSD and CSS. Item reliability was excellent for all modules and person reliability good for all but CSD and CSS. Some items demonstrated differential item functioning related to sex and age, but the impact on person measures was small.Conclusions: This study supports the validity of a modified version of OPUS for persons using different P&O devices, but also reveals limitations to be addressed in future studies. OPUS could be useful in clinical rehabilitation and research to evaluate P&O outcomes. [Box: see text].     

Health-related quality of life after revascularization for peripheral arterial occlusive disease: long-term follow-up

AIM: This paper reports a study to measure quality of life, before and after revascularization, in patients with intermittent claudication and critical limb ischaemia from a long-term perspective. BACKGROUND: Patients with peripheral arterial occlusive disease have a number of problems which affect their quality of life and a successful revascularization results in immediate improvements in quality of life. However, knowledge of the durability of the improvements is sparse. Therefore, research on the outcomes of treatment and nursing care should investigate the long-term effects on quality of life and daily activities. METHODS: A quasi-experimental longitudinal follow-up study was conducted with 80 patients with intermittent claudication and 62 with critical ischaemia. Assessment with the Nottingham Health Profile was made before revascularization and 6 months, 12 months and up to 4 years afterwards. The data were collected between 1995 and 2000. RESULTS: Quality of life was improved 6 and 12 months after revascularization in patients with intermittent claudication in energy, pain, emotional reactions and physical mobility, while those with critical limb ischaemia also had improvements in pain and sleep. The improvement in pain was particularly evident for both groups and remained significantly improved up to 4 years after revascularization. Patients with critical limb ischaemia, however, deteriorated significantly with regard to physical mobility between 12 months and 4 years. Being a woman and belonging to the critical ischaemia group was significantly associated with high total Nottingham Health Profile score. Thus, patients with intermittent claudication had more durable benefits from revascularization than those with critical limb ischaemia. However, both groups had less pain than at baseline after 4 years. CONCLUSION: The degree to which quality of life was durable over time seems to depend on the severity of the disease and gender. Patients with critical limb ischaemia were older, had more other diseases and a lower quality of life than patients with intermittent claudication, which confirmed that patients with critical limb ischaemia need more ongoing nursing support to maintain independence in daily life a long time after revascularization.     

The disappearance of multiresistant Staphylococcus aureus in Denmark: changes in strains of the 83A complex between 1969 and 1989.

During the 1960s multiresistant strains of Staphylococcus aureus were problematic in Denmark and other countries. An analysis of the phage types and antibiotic resistance patterns of S. aureus strains collected from approximately 20,000 Danish patients per year has given us a general picture of the evolution of S. aureus in Denmark during the last 30 years. Multiresistant S. aureus (i.e., strains resistant to penicillin, streptomycin, and tetracycline and often to methicillin and erythromycin as well) belonged mostly to the 83A complex, a relatively homogeneous subset of group III strains that can be further divided into six subtypes. The disappearance of multiresistant strains in Denmark began with a decline in the frequency of isolation of the most resistant subtypes, which was followed by a gradual decrease in the resistance of all 83A subtypes; thus strains of the 83A complex ultimately became no more resistant than other strains. As the proportion of strains of S. aureus accounted for by the 83A complex declined from 24% in 1969 to 6% by the late 1980s, this complex was replaced by strains of type 95, the 94,96 complex, and group II, all of which only rarely show resistance to multiple agents.     

A dietary and behavioural programme for the treatment of obesity. A 4-year clinical trial and a long-term posttreatment follow-up

OBJECTIVES: To evaluate weight loss maintenance after 4 years of nonpharmacological, nonsurgical obesity treatment, including a very low calorie diet (VLCD), diet and behavioural support. Furthermore, to assess weight development amongst completers and noncompleters beyond the active 4-year treatment period. DESIGN: Clinical trial. SETTING: Two Swedish county hospitals. SUBJECTS: A total of 113 patients were randomized to a 2-year treatment programme with or without an initial VLCD period. The 87 patients who completed the 2-year programme were offered the chance to continue a support programme for another 2 years. A total of 55 patients completed the entire 4-year programme. INTERVENTIONS: All the patients took part in a comprehensive support programme, including a hypocaloric diet and behavioural support, either as single treatment (non-VLCD group) or following the VLCD period (VLCD group). RESULTS: Significant 4-year weight losses were found in both groups, 7.6 +/- 12.2 kg (VLCD group) and 6.3 +/- 8.5 kg (non-VLCD group), (P < 0.01, n.s. between groups). The completers (n = 55) had maintained a weight loss of 3.3 +/- 10.7 kg (P < 0.05) 8 years after randomization. After 6 years, the noncompleters (n = 58) had gained 3.2 +/- 9.7 kg compared with baseline (P < 0.05). The difference in weight change between completers and non-completers was highly significant (P < 0.01). CONCLUSIONS: Highly significant weight losses can be maintained after a 4-year comprehensive treatment programme, including a hypocaloric diet and behavioural support. An initial VLCD period did not significantly affect the long-term weight loss. The posttreatment long-term weight loss was larger amongst completers than amongst patients who did not complete the treatment.     

Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m² was administered in a 1-h infusion on a weekly basis to 35 patients who may previously have received adjuvant chemotherapy (but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m² per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR+PR+SD_{≥24 weeks}) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 neurotoxicity. Thus, this study has shown that weekly paclitaxel as first-line therapy for metastatic or advanced breast cancer produces comparable response rates and less toxicity than when the drug is given every three weeks.     

Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer

Kallikreins (KLKs) are highly conserved serine proteases that play key roles in a variety of physiological and pathological processes. KLKs are secreted proteins that have extracellular substrates and function. For example, prostate-specific antigen (or KLK3) is a secreted protein that is widely used as a diagnostic marker for prostate cancer. KLK4 is a recently identified member of the kallikrein family that is regulated by androgens and is highly specific to prostate for expression. Here, we show that the gene product of KLK4, hK4, is the first member of the KLK family that is intracellularly localized. We provide strong evidence that the previously assigned first exon that was predicted to code for a signal peptide that would target hK4 for secretion is not part of the physiologically relevant form of KLK4 mRNA. In addition to detailed mapping of the KLK4 mRNA 5' end by RT-PCR, this conclusion is supported by predominantly nuclear localization of the hK4 protein in the cell, documented by both immunofluorescence and cell fractionation experiments. Furthermore, in addition to androgens, hK4 expression is regulated by estrogen and progesterone in prostate cancer cells. Finally, in situ hybridization on normal and hyperplastic prostate samples in tissue microarrays indicate that KLK4 is predominantly expressed in the basal cells of the normal prostate gland and overexpressed in prostate cancer. These data suggest that KLK4 has a unique structure and function compared with other members of the KLK family and may have a role in the biology and characterization of prostate cancer.