Siegfried Meryn

Wilson's disease in patients presenting with liver disease: A diagnostic challenge

BACKGROUND & AIMS In patients with Wilsons disease presenting with liver involvement, the correct diagnosis is often missed or delayed. The aim of this study was to find an algorithm for diagnosis of this difficult patient group. METHODS Clinical and laboratory findings of 55 patients with Wilsons disease were evaluated at diagnosis before treatment. Presenting symptom was chronic liver disease in 17 patients, fulminant hepatic failure in 5 patients, hemolysis in 3 patients, and neurological disease in 20 patients, and 10 patients were detected by family screening (siblings). Evaluation included neurological and ophthalmologic examination, routine laboratory tests, and parameters of copper metabolism including liver copper content in 43 liver biopsy specimens. RESULTS In the whole group, serum ceruloplasmin level was <20 mg/dL in 73%, urinary copper excretion was increased in 88%, and liver copper content was elevated in 91% at diagnosis. Kayser-Fleischer rings were detected in 55%. In contrast to patients with neurological disease (90% Kayser-Fleischer rings, 85% low ceruloplasmin), only 65% of patients presenting with liver disease were diagnosed by these typical findings. Ceruloplasmin levels were lower in patients with Kayser-Fleischer rings or with neurological disturbances than in patients without these symptoms. CONCLUSIONS The commonly used clinical and laboratory parameters are not sufficient to exclude the diagnosis of Wilsons disease in patients with liver disease of unknown origin.

The effect of age and gender on bladder cancer: a critical review of the literature

While patient age and gender are important factors in the clinical decision‐making for treating urothelial carcinoma of the bladder (UCB), there are no evidence‐based recommendations to guide healthcare professionals. We review previous reports on the influence of age and gender on the incidence, biology, mortality and treatment of UCB. Using MEDLINE, we searched for previous reports published between January 1966 and July 2009. While men are three to four times more likely to develop UCB than women, women present with more advanced disease and have worse survival rates. The disparity among genders is proposed to be the result of a differential exposure to carcinogens (i.e. tobacco and chemicals) as well as reflecting genetic, anatomical, hormonal, societal and environmental factors. Inpatient length of stay, referral patterns for haematuria and surgical outcomes suggest that inferior quality of care for women might be an additional cause of gender inequalities. Age is the greatest single risk factor for developing UCB and dying from it once diagnosed. Elderly patients face both clinical and institutional barriers to appropriate treatment; they receive less aggressive treatment and sub‐therapeutic dosing. Much evidence suggests that chronological age alone is an inadequate indicator in determining the clinical and behavioural response of older patients to UCB and its treatment. Epidemiological and mechanistic molecular studies should be encouraged to design, analyse and report gender‐ and age‐specific associations. Improved bladder cancer awareness in the lay and medical communities, careful patient selection, treatment tailored to the needs and the physiological and physical reserve of the individual patient, and proactive postoperative care are particularly important. We must strive to develop transdisciplinary collaborative efforts to provide tailored gender‐ and age‐specific care for patients with UCB.

Improving doctor-patient communication. Not an option, but a necessity.

In most Western countries healthcare systems are changing; political and economic forces are behind the growth of profit driven medicine, managed care, and an increasingly technological focus. Paradoxically, at a time of global communication and the “Net generation,” we are faced with a breakdown in communication between patients and doctors, increasing patient dissatisfaction, rising numbers of complaints and claims for malpractice, and abandonment of conventional medicine for alternatives that are often unproved.1 What do patients want? Most complaints by patients and the public about doctors deal with problems of communication not with clinical competency.2 The commonest complaint is that doctors do not listen to them. Patients want more and better information about their problem and the outcome, more openness about the side effects of treatment, relief of pain and emotional distress, and advice on what they can …

Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil

A patient with portal-systemic encephalopathy refractory to standard therapy (40-g protein diet, oral neomycin and lactulose, supplementation of diet with branched chain amino acids) following extensive liver resection and construction of a portacaval shunt was treated with 25 mg of flumazenil twice daily by mouth. Before treatment with flumazenil she was encephalopathic and experienced 12 attacks of coma within 2 yr. When treated with flumazenil all signs of encephalopathy abated in spite of an unrestricted dietary intake of protein. Two days after discontinuation of flumazenil treatment she became comatose again. She remained chronically encephalopathic and had four further episodes of coma during the subsequent 3 mo. Since reinstitution of flumazenil treatment she has been well for 14 mo during follow-up without any signs of encephalopathy while on an unrestricted protein diet. Furthermore, flumazenil therapy reversed abnormalities of recordings of multimodality evoked potentials that were associated with hepatic encephalopathy. The striking remission of encephalopathy by treatment with flumazenil suggests that this benzodiazepine antagonist may be valuable in the long-term management of portal-systemic encephalopathy.

The triad of erectile dysfunction, hypogonadism and the metabolic syndrome

Aim:  To identify the relationship of erectile dysfunction, hypogonadism and the metabolic syndrome in the context of men’s health.

Has total bowel rest a beneficial effect in the treatment of Crohn's disease?

Twenty patients with Crohns disease were treated with parenteral nutrition (PN). The indication for PN was a bodyweight of less than 80% ideal bodyweight and/or a Crohns disease activity index (CDAI) above 150 despite conventional therapy. A complete nutrition solution containing per litre 150 g glucose, 50 g sorbitol, 50 g amino acids, 50 g fat, electrolytes, trace elements and vitamins was infused via a central venous catheter to provide 72 kcal per kg bodyweight and day. No other medications were given during the study. The patients were randomized into two groups: both groups received PN in identical fashion. Group 1 was not allowed to eat or drink to reach total bowel rest; Group 2 ate formula diets and low residue diet ad libidum in addition to PN. Criteria for the nutritional status were bodyweight, serum albumin, prealbumin and hemoglobin and for disease activity the CDAI. Mean duration of treatment was 28 days in group 1 and 33.5 days in group 2. At the beginning both groups were comparable with respect to disease activity, nutritional status and extent of Crohns disease. At the end of the study nutritional status was improved (increase of bodyweight and prealbumin) and disease activity was decreased by therapy in both groups with no significant difference between the two regimens. We conclude that PN improves the nutritional status and reduces the activity of Crohns disease. The combination of PN and total bowel rest resulted in the same improvement as with PN alone. Total bowel rest is therefore unnecessary, when PN is given in patients with Crohns disease.

Upper gastrointestinal endoscopy findings in patients with long-standing bulimia nervosa

Bulimia nervosa, an eating disorder now recognized with increasing frequency, is receiving growing attention because of purported complications. Recent claims of a high frequency of erosions, ulceration, and bleeding in the esophagus, ascribed to repeated, self-induced vomiting, prompted us to investigate by endoscopy the upper gastrointestinal mucosa in 37 consecutive patients with long-standing bulimia nervosa. The endoscopic appearance of esophageal and gastric mucosa was normal in 23 patients. Signs of mild esophagitis observed in eight patients were not related to the duration or severity of bulimic behavior or to symptoms of gastroesophageal reflux; two of these eight patients had sliding hiatal hernias. The remaining six patients were found to have superficial mucosal erythema in the stomach or duodenum, but none showed actual erosions, ulcers, or bleeding. Our observations suggest that, in contrast to reports by others, mucosal injury consequent to chronic, self-induced vomiting in patients with bulimia nervosa is relatively infrequent and limited.

Sex Disparities in Cancer Mortality: The Risks of Being a Man in the United States

PURPOSE In the United States more men are diagnosed with cancer than women. We quantified the differential mortality rates of nonsex specific cancers between the sexes and compared cancer stage distributions. MATERIALS AND METHODS In this descriptive epidemiological study we obtained the incidence of new cancer cases, cancer deaths and stage distributions for the last 10 years in the United States from SEER (Surveillance, Epidemiology and End Results) program results. Sex specific cancers were excluded from study. We compared male-to-female relative mortality rate for all cancers as well as the average male-to-female relative mortality rate weighted by cancer incidence in the last 10 years. Sex specific stage distributions were also compared with the Kendall τ-c test. RESULTS The male-to-female relative mortality rate for any cancer was 1.060 (95% CI 1.055-1.065). The average male-to-female relative mortality rate for the same cancer was 1.126 (95% CI 1.086-1.168). The discrepancy in incidence and mortality rates was stable for the last 10 years. Of the top 10 most common cancers men had an unfavorable stage distribution in all except colorectal, bladder and brain cancers. CONCLUSIONS Men are more likely to have nonsex specific cancer than women and more likely to die of the cancer even after controlling for the incidence. This discrepancy has been stable for the last decade. For 7 of the 10 most commonly occurring nonsex specific cancers, representing 78% of all incident cancers, men are more likely to be diagnosed with advanced stage.

Sexual health as a portal to men's health: a problem turned around into an opportunity

The prevalence of genitourinary problems and associated health concerns is high in middle-aged and older men. A representative survey among men in Australia over the age of 40 years indicated that 34% reported one or more reproductive health disorder (1). There is a belief that men, compared with women, make less use of health services. This was not confirmed in the above study. About 88% of men in this study had consulted a health professional in the past 12 months, and health service utilisation increased with age. However, the research showed also that sexual and reproductive health problems are often not explicitly discussed with a health professional. Clinicians, while often seen as the primary source of contact for reproductive health problems, are often reluctant to initiate discussions with older patients about sexual health (2). In our view many opportunities to improve ageing mens health are thus not utilised. We propose a view here that genitourinary (including sexual) health is a ‘portal’ to mens health. Symptoms of genitourinary problems, such as erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) (3) are significantly associated with the metabolic syndrome and type 2 diabetes mellitus. The main components of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and hyperlipidaemia, all of which are etiological factors of ED. The metabolic syndrome and one of its consequences, type 2 diabetes mellitus, are, in turn, associated with lower-than-normal serum testosterone (T) levels (late onset hypogonadism). It is noteworthy that late onset hypogonadism is frequently symptomatic. In men 45 years or older surveyed in 130 primary care practices in the USA, the presence of one or more symptoms occurred in 66% of men deemed hypogonadal based on their T levels(4). The relationship between the metabolic syndrome and type 2 diabetes mellitus and hypogonadism is probably bidirectional. A large degree of obesity and hyperinsulinism suppresses production of T, but low T levels predict the metabolic syndrome and type 2 diabetes mellitus. So, there is a close relationship between ailments frequently occurring in the ageing male (ED, LUTS, visceral obesity, cardiovascular disease and diabetes mellitus) on the one hand and hypogonadism on the other. This close relationship probably indicates that late onset hypogonadism is an expression of poor health, as may be concluded from a recent study. Low testosterone levels were associated with increased mortality in male veterans (5), but this association was not confirmed in another study (6). This is as yet not sufficient evidence to treat all ageing men with hypogonadism with T. Lifestyle changes are associated with improvement in sexual function in about one-third of obese men with ED at baseline. Weight loss and increased physical activity appeared to have a favourable effect on erectile and endothelial functions in obese men (7,8). The Massachusetts Male Aging Study has estimated the frequency of ED progression and remission among ageing men, and assessed the relation of progression/remission to demographics, socioeconomic factors, comorbidities and modifiable lifestyle characteristics. Natural remission and progression occur in a substantial number of men with ED. Age and body mass index were associated with progression and remission of ED. The association of body mass index with remission and progression, and the association of smoking and health status with progression, offer potential avenues for facilitating remission and delaying progression. The benefits of such interventions for overall mens health may be far reaching and confirm the position that ED is a portal to mens health (9). Treatment of ED when associated with hypogonadism may entail T administration (10) and these interventional studies may provide an opportunity to assess benefits, yield, and justification of T administration on the closely interrelated ailments of ED and the metabolic syndrome of which epidemiologically hypogonadism is a correlate. The first results of T administration to elderly men show that this may lead to improvement of both ED and elements of metabolic syndrome (11) but the administration of T to men with diabetes mellitus is disappointing (12). Shabsigh (13) have argued that ED can calculate mens health risks. Elements in the calculation of health risks (hypertension, diabetes, angina or hyperlipidaemia) in men presenting with ED are: health status on a scale of 1–7 (1 = excellent, 7 = poor), waist size, severity of ED, presence/absence of a sexual partner. The calculation produces scores of ranges of 1–7. If the score is 1.5–2.5 = medium risk (30–59% probability); ≥ 2.5 = high risk (≥ 60% probability of having the condition) and < 1.5 = low risk (< 30% probability). In conclusion, physicians confronted with elderly men with genitourinary problems are in a unique position to address general health questions of the patient. A holistic approach will not only benefit the presenting complaint but improve the general health and well-being of the patient.

Multimedia Communication: Quo Vadis?

SUMMARY New interactive multimedia products including CD-ROM, video, online service and Web-TV have grown rapidly over the past several years. Since the acceptance of the World Wide Web (WWW) as a global standard for information, a medical online environment has evolved creating new forms of communications in medicine including desktop videoconferencing, multimedia interactive educational tools, online representation of literature, bibliographic databases and tools for authoring new-generation scientific publications. But the general and health over-information and the use of computer technology in medicine have already changed our communication behaviour, introducing fractal communication and the use of infoids. Concerns have been raised that these developments may on one hand lead to disinformation and on the other may have a significant impact on communication between patient and doctor. The new interactive electronic media and the entirely new forms of communication are discussed.