The varicocele: diagnostic dilemmas,therapeutic challenges and future perspectives

A varicocele is defined as the abnormal dilation of the internal testicular vein and pampiniform venus plexus within the spermatic cord. If a semen analysis is not obtained from the adolescent male, in the absence of other symptoms, the main clinical indication used by many urologists to recommend repair is testicular atrophy. The varicocele may result in testicular damage in some males causing testicular atrophy with impaired sperm production and decreased Leydig cell function, while in other males the varicocele may seemingly cause no ill effects. In adult men, varicoceles are frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight according to a Cochrane review. While occurring more commonly in infertile men than fertile men, only 20% of men with a documented varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during a routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. However, unlike an adult varicocelectomy (the microsurgical approach is the most common), treatment for an adolescent varicocele is more often laparoscopic. Nevertheless, the goals of treatment are the same in the adolescent and adult patients. Controversy remains as to which patients to treat, when to initiate the treatment, and what type of treatment is the best. This review will present the current understanding of the etiology, diagnosis and treatment of the adolescent varicocele.     

Emphysema and dust exposure in a group of coal workers

The lungs of 450 coal miners who had been studied previously in a long-term epidemiologic project at 24 British mines have been examined post-mortem for signs of dust-related fibrosis and emphysema. Reliable estimates of cumulative (working-life) exposures to respirable mine dust were available for 342 of the men. The relative frequency of emphysema increased with age at death, and both panacinar and centriacinar emphysema occurred more frequently in smokers than in nonsmokers. The proportion of subjects with any emphysema was 47% in 92 men with no palpable dust lesions, 65% in 183 with small, simple pneumoconiotic lesions, and 83% in 175 miners with massive fibrosis (PMF). The chance of finding centriacinar emphysema in those with PMF increased significantly with increasing exposure to coal dust in life (p less than 0.025). A similar but less convincing relationship was found in those with simple pneumoconiosis (p less than 0.11), but in both groups, increasing amounts of ash with a given exposure to coal reduced the probability of finding centriacinar emphysema. The occurrence of centriacinar emphysema was associated also with increasing amounts of dust retained in the lungs. A preliminary exploration of this association did not support the hypothesis that emphysematous lungs clear dust less efficiently. We conclude that the association observed between exposure to respirable coal dust and emphysema in coal miners indicates a causal relationship. However, because it can be demonstrated only for men whose lungs show some dust-related fibrosis, it is suggested that the extent and nature of such fibrosis may be a crucial factor in determining the presence of centriacinar emphysema.     

Effects of age and smoking on intima of muscular pulmonary arteries.

The lungs of twenty three subjects, 12 non-smokers and 11 smokers, age range 19-81 years, were studied. All were free from cardiopulmonary disease. The cross sectionally cut muscular pulmonary arteries of each subject were measured in sections obtained from 12 representative tissue blocks using a digitiser. Intimal area was measured and artery size defined as total length of internal elastic lamina (IEL). Intimal abnormality was expressed in the form of an intima index calculated by dividing intimal area by the area enclosed by the IEL in its theoretically unwrinkled state. Mean intima indices were calculated for arteries in four size groups: less than or equal to 600 micron, 601-1200 micron, 1201-1800 micron and greater than 1800 micron length of IEL. For all subjects intimal abnormality was most severe in the smallest muscular pulmonary arteries; values for mean intima indices decreased with increasing size of artery. There were no lobar differences. The amount of intimal abnormality increases with age in all sizes of artery: in the 600 micron size group this could average a 32% reduction in lumen calibre in those aged 60 or more. We were unable to detect any correlation between intimal abnormality and the subject's smoking history.     

Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.

The exotoxins produced by certain strains of Staphylococcus aureus are able to stimulate powerful polyclonal proliferative responses and to induce nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. This paper examines the ability of S. aureus enterotoxins to modulate the responsiveness of human CD4+ T lymphocytes with defined antigen specificity. It was observed that certain S. aureus toxins were able to activate and induce anergy in hemagglutinin-reactive T cells expressing V beta 3+ elements. After exposure to S. aureus enterotoxins A, B, and D in the absence of antigen-presenting cells, the T cells failed to respond to their natural ligand presented in an immunogenic form, despite enhanced proliferation to exogenous interleukin 2. The S. aureus toxin-induced anergy was associated with modulation of T-cell membrane receptors; down-regulation of the T-cell antigen receptor was concomitant with enhanced expression of CD2 and CD25. Interestingly, CD28 was increased only on stimulation, suggesting this protein may be differentially expressed by activated and anergic T cells. These results indicate that bacterial toxins are able to induce antigen-specific nonresponsiveness in human T cells, the application of which may be relevant in the regulation of T cells expressing a particular family of V beta gene products.     

Changing role of non-invasive investigation in the preoperative assessment of congenital heart disease: a nine year experience

The total surgical experience of a supraregional paediatric cardiology unit over a nine year period (January 1980 to December 1988) was reviewed to assess the effect of the introduction of the full range of ultrasound techniques. A total of 1517 patients underwent cardiac surgery (955 cardiopulmonary bypass, 562 closed procedures). Of these, 485 patients (32%) did not undergo cardiac catheterisation before operation: 217 bypass (23% of all procedures under cardiopulmonary bypass) and 268 closed procedures (48%). The overall ratio of catheterisations to operations for patients undergoing palliative or corrective surgery fell from 0.97 (1980) to 0.38 (1988). The patients were classified as (a) neonates (0-28 days), (b) infants (one to 12 months), and (c) children (one to 14 years). The main impact of non-invasive surgical referral was in neonates (total catheter:operation ratio 0.38; neonates 0.2 for 1988). The surgical population was further divided according to the principal echocardiographic technique available: (a) 1980-4 cross sectional imaging; (b) 1985-6; imaging plus spectral Doppler ultrasound; (c) 1987-8; imaging plus spectral Doppler ultrasound and colour flow mapping. A fall in the catheter:operation ratio for all age groups was most pronounced in the last four years. This reflects increased familiarity and surgical confidence with non-invasive diagnostic assessment. The introduction of each new echocardiographic technique was associated with a significant fall in the total catheter:operation ratio compared with the preceding period. Six incorrect ultrasound diagnoses were made during the entire period; one of these patients died in the early postoperative period. The integration of Doppler ultrasound with cross sectional imaging has made non-invasive assessment an increasingly practical alternative to preoperative cardiac catheterization.     

A placebo‐controlled exploratory study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK‐369,003 for the treatment of men with storage lower urinary tract symptoms associated with a clinical diagnosis of overactive bladder

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVES

To evaluate the efficacy and safety of the phosphodiesterase type 5 inhibitor, UK‐369,003 modified release (MR), for the treatment of storage lower urinary tract symptoms (LUTS) in men with and without erectile dysfunction (ED).

PATIENTS AND METHODS

This was a multicentre, double‐blind, placebo‐controlled, parallel‐group study conducted across 50 centres in North and South America, Europe and Australia. In all, 310 men aged ≥18 years with a clinical diagnosis of overactive bladder (OAB; voiding frequency ≥8 times/24 h, urgency episode frequency once or more per 24 h and a mean voided volume of <300 mL) and maximum urinary flow rate of >5 mL/s in a voided volume of >150 mL were stratified into two groups (with or without ED) and randomized to one of five treatment groups (10, 25, 50 or 100 mg UK‐369,003; or placebo once a day) for 12 weeks. The primary study endpoints were those derived from the bladder diary that recorded the number of voluntary urinary voids, volume of urine per void, leaks and urgency episodes over a 72‐h period, before baseline and again at 2, 4 and 12 weeks. Secondary efficacy measures included the International Prostate Symptom Score (total and storage and voiding subscores), International Index of Erectile Function–Erectile Function domain (IIEF‐EF), questions 5 and 6 of the Quality of Erection Questionnaire (QEQ), the Overactive Bladder Questionnaire Short Form, the Patient Perception of Bladder Condition, the International Consultation on Incontinence Questionnaire–Male LUTS, and the patient‐reported treatment impact questionnaire.

RESULTS

Overall, there were no clinically relevant treatment differences in voiding frequency, mean voided volume, urgency episode frequency, or nocturia frequency for any dose of UK‐369,003 MR compared with placebo. In the subset of patients with ED there were improvements in the IIEF‐EF and QEQ scores in all UK‐369,003 treatment groups compared with placebo.

CONCLUSIONS

These data provide no evidence of efficacy for UK‐369,003 in the treatment of storage LUTS in men (based on classic OAB eligibility criteria). However, although the endpoints on these classic OAB efficacy variables were negative, there is evidence to suggest a greater preference, satisfaction and willingness to use UK‐369,003 again for all treatment groups compared with placebo.     

Correlation between ultrasound characteristics, mammographic findings and histological grade in patients with invasive ductal carcinoma of the breast

AIM: To investigate the relationship between ultrasound characteristics, mammographic findings and histological grade in cases of invasive ductal carcinoma which produce a mass on ultrasound. MATERIAL AND METHODS: A retrospective review was performed of the imaging findings in 120 patients diagnosed with invasive ductal carcinoma of the breast between January 1996 and December 1997. Imaging findings were correlated with the histological grade of tumour. RESULTS: High-grade tumours were significantly larger both on ultrasound and mammography (P < 0.016). A spiculated margin on mammogram was documented in 72% of low-grade tumours compared with only 24% of high-grade tumours (P = 0.001). Twenty-two per cent of low-grade tumours had a poorly defined margin on mammography compared with 66% of high-grade tumours (P = 0.001). At ultrasound, 16% of high-grade tumours (95% confidence limits 7-29%) had a well-defined margin. Acoustic enhancement was seen in 36% of high-grade tumours compared with only 9% of low and intermediate-grade tumours (P = 0.003): 22% of all tumours showed acoustic enhancement. Acoustic shadowing was seen in 71% of low-grade tumours compared with only 28% of high-grade tumours (P = 0.003). Malignant-type microcalcification was seen on mammogram in 6% of low-grade tumours compared with 31% of high-grade tumours (P = 0.045). CONCLUSION: The classical appearance of a malignant breast mass as a spiculated mass on mammogram associated with acoustic shadowing on ultrasound is more typical of a low-grade tumour. In comparison, high-grade tumours are more likely to demonstrate posterior acoustic enhancement, and a proportion has a well-defined margin on ultrasound. Therefore, high-grade invasive ductal carcinoma may paradoxically display similar imaging features to a benign breast mass.     

Height growth velocity, islet autoimmunity and type 1 diabetes development: the Diabetes Autoimmunity Study in the Young

Aims/hypothesis  

Larger childhood body size and rapid growth have been associated with increased type 1 diabetes risk. We analysed height, weight, BMI and velocities of growth in height, weight and BMI, for association with development of islet autoimmunity (IA) and type 1 diabetes.