Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Progression and regression of cervical lesions: Review of smears from women followed without initial biopsy or treatment

Cervical smears were reviewed from patients in whom a cytological abnormality was followed, after an interval without interference, either by regression to `negative' or else by progression to invasive carcinoma. Twenty-eight cases were from a previously analysed series with positive smears and an interval of at least two years before investigation, resulting from refusal or failure to trace. Slides were also reviewed from 25 cases in which `positive' smears had regressed to negative without escaping from surveillance, and from 10 patients subsequently developing invasive carcinoma whose previous slides, taken several years earlier, showed abnormalities on review. None of these 63 patients had any biopsy or other surgical procedure to the cervix between the initial smear and the outcome.

Slides showing `superficial cell dyskaryosis' and/or well-differentiated `parabasal cell dyskaryosis' were found only among the groups with subsequent regression. Those showing dissociated poorly differentiated dyskaryotic parabasal cells regressed to negative in two cases and progressed to invasion in nine. This suggests that many examples of spontaneous regression correspond to mild dysplasias which are not precancerous, and overdiagnosis must often have resulted in unnecessary surgical procedures in the past.

`Regressing' and `progressing' groups both included cases in which the spatula had removed coherent pieces of undifferentiated epithelium. These are difficult to interpret cytologically. In nine of them (including four which regressed) the cytological picture was that of carcinoma in situ. The remainder (14 cases) were probably examples of reserve cell hyperplasia, and it is noteworthy that, of the 21 cases subsequently progressing to invasive carcinoma, five were preceded by appearances of this type. It is concluded that cell aggregates suggesting an unusual degree of reserve cell hyperplasia are a danger signal and require careful surveillance.

     

Adoptive transfer of protection against Trypanosoma cruzi with lymphocytes and macrophages.

Female C57BL/6J mice were infected with Trypanosoma cruzi and subsequently given macrophages or lymphocytes from syngeneic donors which had recovered from the acute infection. Mice which received immune peritoneal macrophages, splenic lymphocytes, or lymph node lymphocytes developed lower mean parasitemias and cumulative mortalities than did recipients of nonimmune cells. Neither peritoneal lymphocytes nor splenic macrophages were protective, however. These studies indicate that splenic and lymph node lymphocytes are effective in transferring protection against T. cruzi, whereas the macrophage is somewhat less effective.     

Irreversible neutrophil aggregation. A mechanism of decreased newborn neutrophil chemotactic response.

To investigate the neutrophil-neutrophil interactions of the newborn for possible clues to the etiology of decreased newborn neutrophil (PMN) chemotaxis, the authors compared adult and newborn C5a-induced PMN aggregation and chemotaxis at various PMN concentrations. Using Craddock's technique of C5a-induced aggregation, the authors found that the newborn lacks the normal biphasic aggregation-deaggregation seen in the adult, suggesting irreversible aggregation similar to that seen when adult PMNs are pretreated with cytochalasin-B. Chemotaxis of adult and newborn PMNs was studied with a modified Gallin radiolabel technique. A linear correlation between PMN concentration and corrected chemotactic response was found with both adult (r2 = 0.93) and newborn (r2 = 0.90) PMNs in the range 0.1 X 10(6) to 20 X 10(6) PMNs/ml. Random migration was not augmented by increased PMN concentration. The augmentation of newborn PMN chemotaxis was less than that of the adult (adult slope = 2426; newborn slope = 983). Irreversible newborn PMN aggregation may be the underlying event producing decreased PMN chemotaxis and interfering with the normal chemotactic augmentation caused by increased PMN concentration.     

Human observer detection experiments with mammograms and power-law noise

We determined contrast thresholds for lesion detection as a function of lesion size in both mammograms and filtered noise backgrounds with the same average power spectrum, P(f)=B/f3. Experiments were done using hybrid images with digital images of tumors added to digitized normal backgrounds, displayed on a monochrome monitor. Four tumors were extracted from digitized specimen radiographs. The lesion sizes were varied by digital rescaling to cover the range from 0.5 to 16 mm. Amplitudes were varied to determine the value required for 92% correct detection in two-alternative forced-choice (2AFC) and 90% for search experiments. Three observers participated, two physicists and a radiologist. The 2AFC mammographic results demonstrated a novel contrast-detail (CD) diagram with threshold amplitudes that increased steadily (with slope of 0.3) with increasing size for lesions larger than 1 mm. The slopes for prewhitening model observers were about 0.4. Human efficiency relative to these models was as high as 90%. The CD diagram slopes for the 2AFC experiments with filtered noise were 0.44 for humans and 0.5 for models. Human efficiency relative to the ideal observer was about 40%. The difference in efficiencies for the two types of backgrounds indicates that breast structure cannot be considered to be pure random noise for 2AFC experiments. Instead, 2AFC human detection with mammographic backgrounds is limited by a combination of noise and deterministic masking effects. The search experiments also gave thresholds that increased with lesion size. However, there was no difference in human results for mammographic and filtered noise backgrounds, suggesting that breast structure can be considered to be pure random noise for this task. Our conclusion is that, in spite of the fact that mammographic backgrounds have nonstationary statistics, models based on statistical decision theory can still be applied successfully to estimate human performance.     

Immunoblot analysis of immunoglobulin G response to the Lyme disease agent (Borrelia burgdorferi) in experimentally and naturally exposed dogs.

Immunoblots were used to study the immunoglobulin G response to Borrelia burgdorferi in experimentally and naturally exposed dogs. Adsorption studies confirmed that the antibodies were specific for B. burgdorferi. Experimentally exposed dogs were asymptomatic. Naturally exposed dogs included both asymptomatic animals and animals showing signs compatible with Lyme disease. Naturally exposed dogs were from four geographic regions of the country. No differences were detected between immunoblot patterns of naturally exposed symptomatic or asymptomatic dogs from different areas of the country. The immunoblot patterns obtained with sera from experimentally exposed dogs were different from those obtained with sera from naturally exposed dogs and were characterized by reactivity to fewer and different protein bands. Immunoblot analysis using an OspA-protein-producing Escherichia coli recombinant showed that experimentally exposed dogs produced antibodies to OspA, whereas naturally exposed dogs did not. Modifications of the immune response over time, different routes of antigen presentation, and strain variation are factors postulated to account for the observed differences.     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

Do adults in contact with Australia's public sector mental health services get better?

This paper describes the outcomes of episodes of care for adults in public sector mental health services across Australia, with a view to informing the debate on service quality. Health of the Nation Outcome Scales (HoNOS) change scores and effect sizes were calculated for 14,659 acute inpatient episodes and 23,692 community episodes. The results showed that people in contact with public sector mental health services generally do get better, although the magnitude of improvement depends on the setting and episode type. This confirmatory finding is particularly positive, given current community concerns about the quality and effectiveness of mental health services.