The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences.

OBJECTIVES: To project the likely worldwide increase in the prevalence of erectile dysfunction (ED) over the next 25 years, and to identify and discuss some possible health-policy consequences using the recent developments in the UK as a case study. METHODS: Using the United Nations projected male population distributions by quinquennial age groups for 2025, the prevalence rates for ED were applied from the Massachusetts Male Aging Study (MMAS) to calculate the likely incidence of ED. The MMAS has the advantage of being the first study to provide population-based rates rather than rates based on clinical samples. All the projections were age-adjusted. RESULTS: It is estimated that in 1995 there were over 152 million men worldwide who experienced ED; the projections for 2025 show a prevalence of approximately 322 million with ED, an increase of nearly 170 million men. The largest projected increases were in the developing world, i.e. Africa, Asia and South America. DISCUSSION: The likely worldwide increase in the prevalence of ED (associated with rapidly ageing populations) combined with newly available and highly publicized medical treatments, will raise challenging policy issues in nearly all countries. Already under-funded national health systems will be confronted with unanticipated resource requests and challenges to existing government funding priorities. The projected trends represent a serious challenge for healthcare policy makers to develop and implement policies to prevent or alleviate ED.     

Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths in plasma: significant variations with extent of breast cancer, duration of pregnancy and aging

The composite methylene (chemical shift range 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) resonances of the 1H NMR spectrum were analyzed in plasma samples from breast tumor patients, pregnant women, and healthy subjects. Using a 500 MHz NMR instrument operating at 25 degrees C, the peaks were analyzed for line width at half height and then averaged. A statistically significant difference (p less than 0.001) was found between the average (mean +/- SD) line width in the plasma samples from the 30 patients with metastatic breast cancer (34.1 +/- 5.0 Hz) and the controls matched for age and sex (38.7 +/- 4.4 Hz). In the 16 patients with localized breast cancer and the 16 with regional spread, the average line width was not different from that of matched controls. In 21 patients with benign tumor in the breast, the average line width was not different from that of matched controls. A difference in the average line width was found between 31 pregnant women in the third trimester (32.5 +/- 3.4 Hz) and their controls matched for age and sex (42.7 +/- 4.6 Hz) (p less than 0.001). The average line width was lower in the late (31.5 +/- 3.3) than in the early (34.5 +/- 2.5 Hz) part of the third trimester (p = 0.022). In 54 healthy male and 130 healthy female controls, line widths declined gradually with increasing age by decades, except in the fifth decade for the men and the sixth decade for the women.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effective Hemostasis in Severe Mesenteric Vein Laceration with Tachosil<Superscript>®</Superscript>, using a Low- or Non-thrombogenic Patch to Prevent Tachosil<Superscript>®</Superscript>-induced Thrombosis

Fibrinogen- and thrombin-coated collagen fleece (FTCC) facilitates surgical hemostasis, and is of particular value during resection of parenchymatous organs. Since thrombosis may ensue if the preparation is unintentionally applied intravascularly, it has not been recommended for treating lacerations of large veins, and no previous reports describe its use in vein repair. Our observations in two patients suggest, however, that FTCC might be indicated for hemostasis in vein injury where vascular suture is difficult or not possible, provided a low- or non-thrombogenic patch is interposed to prevent FTCC-induced vein thrombosis. Our two patients had severe lacerations of the proximal superior mesenteric vein (SMV) not amenable to conventional vein repair. Rapid hemostasis was obtained without suturing using Tachosil^?, an FTCC preparation, covered with omentum. In the first patient hemostasis was obtained at the expense of vein thrombosis, apparently due to contact between the coagulant-containing side of Tachosil^? and the inside of the vein wall. In our second patient we therefore put a small patch of parietal peritoneum on the section of the Tachosil^? targeted to cover the vein tear to avoid direct contact between Tachosil^? and the vein lumen. Ultrasound examination 3 days postoperatively, and autopsy 11.5 months later showed that the vein was widely patent with no stenosis or thrombus. Our observations in these two patients were that an FTCC-omentum pack alone secured rapid hemostasis in severe SMV laceration, and when a peritoneal patch was interposed between FTCC and a lacerated SMV, FTCC-induced vein thrombosis did not occur.     

In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans

Magnetic resonance spectroscopy of fluorine (19F) has been used to noninvasively study the in vivo pharmacokinetics of a model drug, fleroxacin (a fluoroquinolone antibiotic agent), in healthy human subjects. After oral administration, fleroxacin was detected in 19F magnetic resonance spectra from both liver and calf muscle and four magnetic resonance examinations were undertaken during a 24-hour period. By combining plasma analysis by high performance liquid chromatography with the magnetic resonance data, the following pharmacokinetic parameters (mean values) were obtained: tmax, 1.4, 4.6, and 5.6 hours in liver, plasma, and muscle, respectively; Cmax, 53, about 250, and about 60 mumol/L in plasma, liver, and muscle, respectively; t1/2, 4.4 hours (fast phase) and 10.8 hours (slow phase) in liver and 14.2 hours in plasma. The study documents for the first time the potential use of 19F magnetic resonance spectroscopy to noninvasively observe the time-related changes of a fluorine-containing drug in human tissues after oral administration.     

Influences of gamma interferon on synovial fibroblast-like cells. Ia induction and inhibition of collagen synthesis

The shape and function of adherent cells cultured from rheumatoid synovial membranes are influenced by immune cells, and their products. The synovial cells produce collagenase and prostaglandin E2 (PGE2), the levels of which are increased when the cells are incubated with the monokine, mononuclear cell factor/interleukin 1. The majority of adherent synovial cells are fibroblastlike in appearance and synthesize collagens and fibronectin; the synthesis of collagens and fibronectins are also increased by a monocyte factor. In the present study we found that the fibroblastlike cells expressed major histocompatibility complex class II (Ia-like) antigens after initial dispersion from the synovial membrane. Monocyte lineage antigens were detected on some round cells in early passage, but no T lymphocytes were identified in established cultures. There was loss of Ia expression on the fibroblastlike cells with age and passage in culture. The addition of the lymphokine, gamma interferon (recombinant), induced class II antigen (DR and DS/DQ) expression in early or late passage cells in a time- and dose-dependent manner and required protein synthesis. Furthermore, the adherent synovial fibroblastlike cells continued to be Ia-positive when examined as long as 10 d after the removal of gamma interferon. Ia expression was also induced by gamma interferon in normal skin fibroblasts. Synovial cells that could be induced to express Ia also bound a monoclonal antibody to type III collagen (a fibroblast marker). Gamma interferon, while inducing Ia expression, decreased the binding of type III collagen antibody on unstimulated as well as monokine-stimulated cells. Analysis of [3H]proline-labeled medium by SDS polyacrylamide gel electrophoresis showed that gamma interferon decreased the synthesis of type I and III collagens and fibronectin by adherent synovial cells in a dose-dependent manner. These findings suggest that Ia expression by synovial tissue cells is not cell-specific, but reflects one or several related events, such as the degree of T lymphocyte infiltration, the presence of factors that stimulate gamma interferon release, or an increased sensitivity of the cells to gamma interferon. Whereas the synthesis of class II antigens is enhanced by the lymphokine gamma interferon, and a monocyte factor(s) stimulates collagen, collagenase and PGE2 synthesis by the same cells, gamma interferon inhibits basal and monokine-induced collagen synthesis. Thus, lymphokines and monokines may influence the extent of fibrosis as contrasted to matrix destruction at various stages of the rheumatoid lesion by affecting the function of fibroblastlike synovial cells.     

Sample sizes for clinical trials with time-to-event endpoints and competing risks

We consider clinical trials where the time to occurrence of events in the presence of competing risks is the primary endpoint for treatment evaluation. The number of events with regard to the defined primary endpoint required to ensure the specified power can be calculated according to Schoenfeld's formula like in classical survival studies. However, determination of the number of patients that have to be recruited to observe the calculated number of events requires specification of the length of the accrual period, the trial duration and assumptions about the event-specific hazard functions. Information from previous studies about expected failure rates for the reference treatment is useful and can be translated into assumptions about the appropriate model parameters. A formula for sample size computation is presented for two competing outcome states. Nomograms help to communicate different alternatives of duration and size of the trial to interdisciplinary committees whose members plan and monitor the clinical trial. The 4D trial (Die Deutsche Diabetes Dialyse Studie) designed to compare lipid lowering treatment with HMG-CoA reductase inhibitor atorvastatin with placebo in type 2 diabetic patients on hemodialysis with respect to time to the composite event "cardiovascular death or non-fatal myocardial infarction" is used as an example to outline the statistical methods.