Clinical aspects of pelvic inflammatory disease

Pelvic inflammatory disease (PID) is a common and poorly managed condition. Untreated or inadequately treated, it leads to tubal infertility, ectopic pregnancy and chronic pelvic pain. Diagnostic difficulties are compounded by the wide variety of clinical presentations and the insensitivity and poor specificity of laboratory tests. Better recognition of mild and atypical disease needs a high index of suspicion whenever young, sexually active women present with gynaecological symptoms. Laparoscopy supplemented by microbiological tests and fimbrial minibiopsy should be regarded as the diagnostic 'gold standard' for research studies; new studies are required to identify techniques which might reduce under- and over-diagnosis. Early treatment reduces the risk of an adverse effect on fertility. Any therapeutic regimen selected should be effective against the common aetiological agents Chlamydia trachomatis, Neisseria gonorrhoeae, genital mycoplasmas and aerobic and anaerobic bacteria. Since at least 60% of cases of PID can be attributed to infection with a sexually transmitted organism, partner notification forms an essential part of management.      

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Sociomedical aspects of malaria control in Colombia.

A household interview survey combined with a serological survey on the incidence of malaria attacks and prevalence of antibodies has been carried out in rural and urban areas of the pacific coast of Colombia. Additional information on people's knowledge, attitudes and behaviour towards malaria was collected by means of participant observation and informal interviews. The results show that people incorporate modern and traditional elements into their concepts of the disease and treatment strategies. The deficiencies of the official control programmes are shown from the people's point of view. Some human factors which influence malaria transmission are discussed and an estimate of the accuracy of self-diagnosis presented.     

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.     

Chest radiography in general practice: indications, diagnostic yield and consequences for patient management

BACKGROUND: Chest radiography (CXR) is frequently performed in Western societies. There is insufficient knowledge of its diagnostic value in terms of changes in patient management decisions in primary care. AIM: To assess the influence of CXR on patient management in general practice. DESIGN OF STUDY: Prospective cohort study. SETTING: Seventy-eight GPs and three general hospitals in the Netherlands. METHOD: Patients (n = 792) aged > or =18 years referred by their GPs for CXR were included. The main outcome was change in patient management assessed by means of questionnaires filled in by GPs before and after CXR. RESULTS: Mean age of the patients was 57.3+/-16.2 years and 53% were male. Clinically relevant abnormalities were found in 24% of the CXRs. Patient management changed in 60% of the patients following CXR. Main changes included: fewer referrals to a medical specialist (from 26 to 12%); reduction in initiation or change in therapy (from 24 to 15%); and more frequent reassurance (from 25 to 46%). However, this reassurance was not perceived as such in a quarter of these patients. A change in patient management occurred significantly more frequently in patients with complaints of cough (67%), those who exhibited abnormalities during physical examination (69%), or those with a suspected diagnosis of pneumonia (68%). CONCLUSION: Patient management by the GP changed in 60% of patients following CXR. CXR substantially reduced the number of referrals and initiation or change in therapy, and more patients were reassured by their GP. Thus, CXR is an important diagnostic tool for GPs and seems a cost-effective diagnostic test.     

Smad4 overexpression causes germ cell ablation and leydig cell hyperplasia in transgenic mice

Members of the transforming growth factor-beta (TGF-beta) superfamily play a variety of important roles in testicular development and function. The tumor suppressor gene, Smad4, is a common mediator of TGF-beta, activin, and bone morphogenetic protein-mediated signaling pathways. To investigate the role of the Smad4 gene during testicular development and function, transgenic mice were generated using a Flag-tagged Smad4 gene driven by 180-bp fragment of the Mullerian inhibiting substance upstream promoter sequence. Three Smad4 transgenic founders (A, B, and G) were detected by Southern blot analysis; line B showed the highest expression of the Smad4 transgene and was further studied. The fertility in F1 generation (B) and F2 generation (BB) of the Smad4 transgenic mice was not impaired. However, in the F3 generation (B2x) all animals were impacted by the overexpression of the Smad4 transgene and two kinds of phenotypes were observed. In one group animals were completely infertile, while in the other group animals were fertile and sired the normal number of pups/litter. These groups are designated as infertile and fertile in the text. Histological evaluation of the testes from the infertile group showed variable degrees of Leydig cell hyperplasia, apoptosis of germ cells, spermatogenic arrest, seminiferous tubule degeneration, and infertility. In the fertile group, there was no apparent change in the histology of the testis except for a slight increase in the number of Leydig cells. Serum follicle-stimulating hormone levels in the adult animals of both groups of Smad4 transgenic male mice were not significantly different from normal littermates; however, testosterone levels in both groups were significantly (P < 0.05) increased. These results suggest that overexpression of Smad4 leads to testicular abnormalities and infertility supporting the hypothesis that the TGF-beta signaling pathways are carefully orchestrated during testicular development. In the absence of normal levels of Smad4 testicular function is compromised.     

The natural history of the double pylorus

A study of 11 patients with "double pylorus" revealed that a second channel between the gastric antrum and the duodenal bulb is the result of ulcer penetration. The fistula can be a sign of spontaneous recovery from ulcerative disease; the fistula occurred in conjunction with clinical improvement in the majority of the patients. The advantages of radiological vs. endoscopic diagnostic procedures are discussed.