Frequent loss of the 11q14-24 region in chronic lymphocytic leukemia: A study by comparative genomic hybridization

The genetic basis and molecular pathogenesis of chronic lymphocytic leukemia (CLL) and the molecular mechanisms responsible for its progression remain poorly understood. Here, karyotyping techniques specifically optimized for CLL, comparative genomic hybridization (CGH), and fluorescence in situ hybridization were used to search for CLL-specific genetic aberrations. CGH and karyotyping both revealed copy number changes in 12 of the 25 CLL cases (48%) analyzed. Loss at 11q emerged as the most common aberration (6 cases), followed by a gain of chromosome 12 (4) and loss at 13q (3). Concordance between CGH and G-banding was found in 23 of the 25 cases (92%), which is more than reported in a recent similar CGH study of CLL. Owing to the basic differences in G-banding and CGH, however, their simultaneous clinical application is recommended. The frequent loss of 11q14-24 suggests that this chromosomal region deserves further attention as a candidate locus involved in the pathogenesis of CLL. Genes Chromosom. Cancer 19:286–290, 1997. © 1997 Wiley-Liss, Inc.     

A novel human leucocyte antigen-DRB1 genotyping method based on multiplex primer extension reactions

We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.     

Physical work capacity in dynamic exercise with differing muscle masses in healthy young and older men

Ten young (aged 23–30 years) and nine older (aged 54–59 years) healthy men with similar estimated limb muscle volumes performed, in random order, three different types of ergometer exercise tests (one-arm cranking, two-arm cranking, and two-leg cycling) up to the maximal level. Values for work load (WL), peak oxygen consumption , peak heart rate (HR), peak ventilation , respiratory gas exchange ratio (R), recovery blood lactate concentration [La^–], and rating of perceived exertion (RPE) were compared between the age-groups in the given exercise modes. No significant age-related differences in WL, peak , peak HR, R, [La^–], or RPE were found in one-arm or two-arm cranking. During one-arm cranking the mean peak was 1.65 (SD 0.26)1 · min^–1 among the young men and 1.63 (SD 0.10)1 · min^–1 among the older men. Corresponding mean peak during two-arm cranking was 2.19 (SD 0.32)1 · min-1 and 2.09 (SD 0.18)1 · min^–1, respectively. During one-arm cranking peak was higher (P < 0.05) among the older men compared to the young men. During two-leg cycling the young men showed higher values in WL (P < 0.001), peak (P < 0.001), and peak HR (P < 0.001). The mean peak was 3.54 (SD 0.24)1 · min^–1 among the young men and 3.02 (SD 0.20)1 · min^–1 among the older men. Corresponding mean peak HR was 182 (SD 5) beats · min^–1 and 170 (SD 8) beats · min^–1, respectively. During two-leg cycling, peak , R, [La^–], and RPE did not differ between the two age-groups. In summary, the older men with similar sizes of estimated arm and leg muscle volumes as the young men had a reduced physical work capacity in two-leg cycling. In one-arm or two-arm cranking, no significant difference in work capacity was found between the age-groups. These results indicate, that in healthy men, age, at least up to the 6th decade of life, is not necessarily associated with a decline in physical work capacity in exercises using relatively small muscle groups, in which the limiting factors are more peripheral than central.     

Medical and psychology students' self-assessed communication skills: A pilot study

Objective

The purpose of this study was to describe how psychology and medical students assess their own competency and skills before and after training, in which role-play was used to teach interpersonal and communication skills.

Method

Interpersonal and communication skills were assessed with a semi-structured questionnaire before and after the training.

Results

The students of both medicine and psychology estimated their skill levels to be higher after the course. The psychology students estimated their skills for communication, motivating interviewing, empathy and reflection, and change orientation to be better at the end of the course. Medical students estimated their communication skills, motivating interviewing skills, and change orientation skills to be better at the end of the course.

Conclusion

Even a short period of training in interpersonal and communication skills can positively affect the self-assessed skills of the medical students.

Practice implications

In the future, it would be worthwhile to pay attention to reflective teaching practices in the training of both medical and psychology students. The cognitive and emotional components of these practices help students to develop their own communication skills.     

Connective Tissue Growth Factor and Its Correlation to Other Growth Factors in Experimental Granulation Tissue

Connective tissue growth factor (CTGF) is upregulated in a variety of fibrotic disorders, probably secondary to the activation and production of transforming growth factor-beta (TGF- &#103 ). We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry. The expression of CTGF mRNA in Northern blot and immunohistochemistry were correlated to the expression of TGF- &#103 1 and platelet-derived growth factor (PDGF). Northern hybridization showed the maximum expression of CTGF mRNA on day 14, whereas TGF- &#103 1 expression was maximal on days 7 and 14 and the time-related changes were smaller than for CTGF. PDGF A and PDGF B mRNA expressions were at maximum on day 14 and on day 21, respectively. In situ hybridization showed that fibroblast-like cells expressed CTGF most intensively, expression declining rapidly after day 14. CTGF mRNA and protein were found in blood vessel cells during the first week. In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7. These results demonstrate that CTGF expression together with TGF- &#103 and PDGF are upregulated in wound healing, and CTGF expression in blood vessels suggests that CTGF is involved in angiogenesis.     

Evaluation of the thermal insulation of clothing of infants sleeping outdoors in Northern winter

It is a common practice in Northern countries that children aged about 2 weeks to 2 years take their daytime sleep outdoors in prams in winter. The aim was to evaluate the thermal insulation of clothing of infants sleeping outdoors in winter. Clothing data of infants aged 3.5 months was collected, and sleep duration, skin and microclimate temperatures, humidity inside middle wear, air temperature and velocity of the outdoor environment were recorded during sleep taken outdoors (n = 34) and indoors (n = 33) in families’ homes. The insulation of clothing ensembles was measured by using a baby-size thermal manikin, and the values were used for defining clothing insulation of the observed infants. Required clothing insulation for each condition was estimated according to ISO 11079. Clothing insulation did not correlate with ambient air temperature. The observed and required insulation of the study group was equal at about −5°C, but overdressing existed in warmer and deficiency in thermal insulation in colder temperatures (r _s 0.739, p < 0.001). However, even at −5°C a slow cooling (ca. 0.012°C/min) of mean skin temperature (T _sk) was observed. When the difference between observed and required insulation increased, the cooling rate of T _sk increased linearly (r _s 0.605, p < 0.001) and the infants slept for a shorter period (r _s 0.524, p = 0.001). The results of this study show the difficulty of adjusting systematically the optimal thermal insulation for outdoor sleeping infants during northern winter. Therefore, the necessity for guidelines is obvious. The study provides information for adequate cold protection of infants sleeping in cold conditions.     

Alcohol consumption and the risk of stroke among hypertensive and overweight men

High blood pressure and overweight are risk factors for stroke. The aim of the present study was to examine the association between alcohol consumption and the risk of stroke according to the level of blood pressure and body weight. This study is a population-based sample of men with an average follow-up of 14.9 years from eastern Finland. A total of 2,599 men with no history of stroke at baseline participated. During the follow-up period, 224 strokes occurred, of which 181 were ischemic strokes. After adjustment for age, year of examination, socioeconomic status, serum LDL cholesterol, body mass index, smoking and energy expenditure of physical activity (kcal/day), there was a significant trend of an increased risk for any and ischemic stroke among hypertensive men. Hypertensive (blood pressure of over 140/90 mm Hg) men, who did not consume alcohol had a 1.72-fold (95 % CI 1.12–2.66; p = 0.014) relative risk (RR) for any stroke and a 1.90-fold (95 % CI 1.15–3.13; p = 0.012) RR for ischemic stroke. Among hypertensive men who consumed alcohol RR was 1.86-fold (95 % CI 1.20–2.89; p = 0.005) for any stroke and 2.02-fold (95 % CI 1.21–3.35; p = 0.007) for ischemic stroke. Men who did not consume alcohol with elevated BMI (≥26.4 kg/m²) had a 1.63-fold RR (95 % CI 1.11–2.40; p = 0.013) for any stroke and a 1.33-fold RR (95 % CI 0.87–2.04; p = 0.199) for ischemic stroke after adjusting for risk factors. Overweight men (≥26.4 kg/m²) who consumed alcohol had a 1.73-fold RR (95 % CI 1.18–2.54; p = 0.005) for any stroke and a 1.71-fold RR (95 % CI 1.14–2.57; p = 0.010) for ischemic stroke after being adjusted for risk factors. In conclusion, this population-based prospective study shows that hypertensive and overweight men who consumed alcohol had an increased risk for stroke.     

Effect of hypoxia on the synthesis of glycosaminoglycans and collagen by rabbit aortic smooth muscle cells in culture

This study evaluated the effect of hypoxia on the connective tissue metabolism of rabbit aortic smooth muscle cells (SMCs) in culture. When the oxygen saturation of the incubation medium was lowered from 20% to 2-3%, synthesis of sulphated glycosaminoglycans (GAGs) and hyaluronic acid, as determined from the incorporation of [3H]glucosamine, was stimulated. However, this occurred only after 24 h preincubation of the SMCs in hypoxia. The collagen synthesis of the cells was determined from the incorporation of [3H]proline into protein hydroxyproline and calculated in mass units from the specific intracellular precursor radioactivity. The total protein synthesis was similarly determined from the incorporation of [3H]proline into protein-bound proline. Hypoxia decreased the collagen synthesis, but did not affect the total protein synthesis of the cells. When compared with the control cultures the cell protein of the SMC cultures kept in hypoxia, decreased on the first day in hypoxia whereafter it increased. These results may explain the mechanisms by which hypoxia affects the connective tissue metabolism of the arterial wall in vivo.     

Effects of verapamil in patients with acute myocardial infarction: Hemodynamics and function of normal and ischemic left ventricular myocardium

We evaluated the effects of intravenous verapamil, a calcium antagonist, on hemodynamics and regional left ventricular (LV) performance in patients with acute myocardial infarction (AMI). Twenty patients having uncomplicated infarction or moderate heart failure were randomized to receive either verapamil or placebo and were studied a mean of 12 hours after onset of symptoms. Verapamil, 7.5 mg intravenously, acutely reduced systolic arterial pressure (p < 0.0005), systemic vascular resistance, and LV stroke work (p < 0.005) and rate-pressure product (p < 0.05); the heart rate did not alter. The Frank-Starling relationship by Swan-Ganz catheter did not change for 1 hour. Segmental wall motion amplitudes were recorded from eight standardized segments around the left ventricle by a multidirectional M-mode echocardiographic technique. The systolic wall motion of the uninvolved LV segments and LV cavity size did not change after verapamil. Verapamil improved mechanical performance in the ischemic segments (p < 0.005). Therefore, the overall regional contractile function of the left ventricle improved as well (by 11% to 13%, p < 0.05). This echocardiographic improvement continued after the acute vasodilatory response of intravenous verapamil subsided and was preserved for 1 week, the patients having had oral verapamil, 240 mg daily. Chest pain was relieved in five of the six patients having ongoing slight pain before verapamil injection. No sequential hemodynamic or echocardiographic changes occurred in the placebo-treated patients. Thus, in patients with uncomplicated AMI, verapamil improve contractile function of the acutely ischemic LV segments by hemodynamic unloading and/or by direct myocardial effect, without manifest depression of the uninvolved myocardium.     

Accuracy and reproducibility of a retrospective outcome assessment for lumbar spinal stenosis surgery

Background

Rheumatoid arthritis is a chronic inflammatory condition that affects the joints causing unpredictable episodes of pain, stiffness and disability. People with rheumatoid arthritis usually require lifelong specialist follow-up but frequently have periods when their disease can be managed through self-care or that provided by their general practitioner. Compared to the traditional clinician-driven care in rheumatoid arthritis, patient-initiated care has proven to be more beneficial in terms of reducing unnecessary medical reviews, providing greater satisfaction to patients and staffs and maintaining the patient??s physical and psychological status. We aim to evaluate the implementation of a patient-initiated review system in a routine secondary care rheumatology service in a public hospital in England, where patients get the opportunity to self-manage their disease by requesting specialist reviews at times of need instead of clinician-scheduled appointments.

Methods/design

Three hundred and eighty patients attending routine review at Plymouth Hospitals NHS Trust will be randomised to either enrol immediately into a patient-initiated review system (direct access group), or to be seen regularly by a clinician at the hospital (regular clinician-initiated group). Patients (or their general practitioner) in the direct access group can arrange a review by calling a rheumatology nurse-led advice line that enables telephone delivered clinical advice, or where appropriate, an appointment with a rheumatologist within 10 working days. Patients in the regular clinician-initiated group will attend their planned appointments at regular intervals during the intervening period of 12 months. The primary outcome of interest is patient satisfaction; secondary outcomes include service use, waiting times and clinical measures. Semi-structured, in-depth interviews will be conducted with a subset of patients and staff with the aim of identifying facilitators/barriers in implementing patient-initiated clinics.

Discussion

The implementation of a patient-initiated review system in routine care rheumatology will replace the fixed clinician-driven review system with a more flexible patient-driven system where patients usually self-manage their disease, but can request prompt help when required. We believe that this study will enable a comparison of the changes in local services and will be helpful in exploring the benefits/drawbacks of such implementation, thus providing lessons for implementation in other hospitals and for other chronic diseases.