Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing.     

Antithyreoglobulin und Antithyroxin

Zusammenfassung Der O₂-Verbrauch von mit parenteralem Thyreoglobulin längere Zeit hindurch behandelten weißen Ratten wird stark herabgesetzt. Die Reaktionsbereitschaft solcher Tiere ist auch subcutan eingespritztem Thyroxin gegenüber vermindert, so daß der O₂-Verbrauch der Tiere nur auf Thyroxingaben von über 15 mg eine deutliche Steigerung zeigt. Meerschweinchen verhielten sich ähnlich wie die Ratten. Bei Kaninchen zeigte sich dagegen im Verlaufe der Thyreoglobulinbehandlung eine deutliche Steigerung des Stoffwechsels, nach der Thyreoglobulinbehandlung wurde der O₂-Verbrauch dieser Tiere auf Thyroxineinspritzung entsprechend erhöht. Diese an Ratten und Meerschweinchen gemachte Beobachtung dürfte ihre Erklärung darin finden, daß in diesen Versuchen das Thyreoglobulin als Antigen in serologischem Sinne wirkte, so daß ihre parenterale Verabreichung die Entstehung von gegen Thyreoglobulin und Thyroxin gerichteten Antikörpern herbeigeführt hatte. — Es ist anzunehmen, daß in diesen Versuchen das Thyreoglobulin sich als ein chemospezifisches Antigen verhielt, in dem Sinne, daß das Thyroxin neben dem Eiweißschlepper die Rolle der spezifischen Gruppe spielte, wodurch sie die Spezifizität der entstandenen Antikörper beeinflußt bzw. bestimmt hatte. Diese Deutung wird nicht so sehr in den Ergebnissen der mitgeteilten serologischen Versuche ihre Bekräftigung finden, vielmehr aber in der Tatsache, daß der thyroxinhemmende Faktor bei Ratten durch Sera mit thyreoglobulinvorbehandelter Tiere auch auf Normaltiere übertragbar ist, d. h. bei Ratten durch eine mit Antithyreoglobulin-Immunserum durchgeführte passive Immunisierung die O₂-Verbrauch-steigernde Wirkung des eingespritzten Thyroxins aufgehoben wurde.Mit 7 Textabbildungen.     

A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R−) solid organ transplant recipients

Abstract:  Long-term prophylaxis against cytomegalovirus (CMV) started immediately after transplantation in (D+/R−) poses a higher risk of late-onset CMV disease. Delayed CMV prophylaxis could allow a transitory exposure of the immune system to CMV, which would let the immune system mount an adequate CMV-specific cytotoxic response in (D+/R−) patients and confer protection against CMV disease. We included all (D+/R−) solid organ transplant recipients (SOT) performed at our institution (January 3/October 6) who received CMV prophylaxis (mainly with oral valganciclovir) during 100 d. In the first period (until December 4), prophylaxis was initiated immediately after transplantation (conventional prophylaxis: CP). Since January 5, it was initiated after 14 d (delayed prophylaxis: DP). Incidence and severity of CMV disease was compared between both groups. A total of 44 SOT recipients were included (CP: 26 and DP: 18). CMV disease was diagnosed in eight patients (18%), seven of 26 (27%) in the CP group, and one of 18 (5.5%) in the DP group (p = 0.07). CMV colitis was reported in five of 26 patients in the CP group (19%), whereas there were no cases of visceral CMV disease in the DP group (p = 0.048). A 14-d delay in the beginning of long-term prophylaxis against CMV in (D+/R−) is safe and could prevent the onset of late-CMV disease.     

Complications of temporomandibular joint arthroscopy: a retrospective analytic study of 670 arthroscopic procedures.

PURPOSE: Temporomandibular joint (TMJ) arthroscopy has been considered a safe surgical procedure in the treatment of TMJ derangement. However, it is not exempt from complications. This study evaluates the complications of arthroscopy in patients with internal derangement of TMJ. PATIENTS AND METHODS: Five hundred consecutive patients (670 joints) with TMJ derangement who underwent arthroscopy between 1995 and 2004 were retrospectively analyzed. All the patients were classified as II to V in the Wilkes classification. Lysis and lavage, electrocautery of the posterior ligament, injection of corticoids, injection of ethanolamine, myotomy of lateral pterygoid muscle attachments, myotomy and electrocautery, motor debridement, injection of sodium hyaluronate, and meniscal suture were performed in different patients. RESULTS: Complications were recognized during or immediately after the surgery. They were observed in 5 of 341 (1.26%) arthroscopies of the right TMJ and 4 of 329 (1.21%) arthroscopies of the left TMJ. A 1.34% complication rate was found in the whole series. No blood clots within the external auditory canal were observed. Bleeding within the superior TMJ space was observed in 57 cases (8.5%), 36 of them in the right TMJ and 21 in the left TMJ, but they were not considered as true complications. Lacerations of the external auditory canal were found in 2 cases (0.3%), with no cases of perforation of the tympanic membrane. Lesion of the auriculotemporal nerve was observed in a case. Paresia of the facial nerve was found in 4 cases (0.6%). Alteration of visual accuracy of the ipsilateral eye was also observed in a patient immediately after the surgery. CONCLUSION: Special care must be taken to reduce complications within the upper joint space by means of an adequate instrumentation and by paying attention to essential points of the arthroscopic technique.     

Overexposure of radiation therapy patients in Panama: problem recognition and follow-up measures.

This report summarizes and analyzes the responses of various organizations that provided assistance to the National Oncology Institute (Instituto Oncológico Nacional, ION) of Panama following the overexposure of 28 radiation therapy patients at the ION in late 2000 and early 2001. The report also looks at the long-term measures that were adopted at the ION in response to the overexposure incident, as well as implications that the incident has for other cancer treatment centers worldwide. In March 2001, the director of the ION was notified of serious overreactions in patients undergoing radiation therapy for cancer treatment. Of the 478 patients treated for pelvic cancers between August 2000 and March 2001, 3 of them had died, possibly from an overdose of radiation. In response, the Government of Panama invited international experts to carry out a full investigation of the situation. Medical physicists from the Pan American Health Organization (PAHO) were among those invited. They ascertained that 56 patients treated with partially blocked teletherapy fields for cancers of the uterine cervix, endometrium, prostate, or rectum, had had their treatment times calculated using a computerized treatment planning system. PAHO's medical physicists calculated the absorbed doses received by the patients and found that, of these 56 patients, only 11 had been treated with acceptable errors of +/-5%. The doses received by 28 of the 56 patients had errors ranging from +10 to +105%. These are the patients identified by ION physicists as overexposed. Twenty-three of the 28 overexposed patients had died by September 2005, with at least 18 of the deaths being from radiation effects, mostly rectal complications. The clinical, psychological, and legal consequences of the overexposures crippled cancer treatments in Panama and prompted PAHO to assess radiation oncology practices in the countries of Latin American and the Caribbean. ION clinicians evaluated the outcome of 125 non-overexposed patients who had been treated in the same time period and for the same cancer sites as the overexposed patients. The clinicians uncovered a larger recurrence of cervical cancers than expected. The finding prompted PAHO to launch an initiative for the accreditation of radiation oncology centers in Latin America and the Caribbean, working in collaboration with professional societies for radiation oncologists, medical physicists, and radiotherapy technologists. The Latin American Association for Radiation Oncology (Asociación Latinoamericana de Terapia Radiante Oncológica) has established an accreditation commission. Accreditation will require that centers implement a comprehensive radiation oncology quality assurance program that follows international guidelines. Statistical data on patient outcomes will be collected in order to document needs in radiotherapy centers in Latin America and the Caribbean and to define future strategies for cancer treatment.     

Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon.

1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model.

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hepatobiliary sampling method showed that verapamil did not affect the transport of fexofenadine in the intestine or liver. In this model the E(H) values for both verapamil and antipyrine were similar to the corresponding values in vivo in humans.