Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.

Indications and surgical outcome following pulmonary metastasectomy: a nationwide study.

AIM: The aim of this retrospective nationwide study was to investigate indications and surgical outcome after pulmonary metastasectomy (PM) in a well-defined cohort of patients and to calculate the proportion of cancer patients who were operated on. METHODS: Between 1984 and 2008, 81 patients (age 54.8 years, 50.6% men) underwent 100 PMs with curative intent in Iceland. For all patients, information on demographics, number of metastases, type of surgery, and complications were collected. Overall survival was estimated with median follow-up of 45 months. For the three most common malignancies, the proportion of patients who underwent PM was calculated using information from the Icelandic Cancer Registry on all cases diagnosed. RESULTS: Of 100 PMs, there were 62 wedge resections, 34 lobectomies, and 4 pneumonectomies. The most common complication was persistent air leakage (>96 hour; 11.1%), and operative mortality was 1.2%. Of the 12 kinds of primary malignancies operated, three were most common: colorectal carcinoma (CRC, n = 27), sarcoma (n = 21), and renal cell carcinoma (RCC, n = 14). The proportion of patients who underwent PM was 1.0% for CRC, 6.5% for sarcoma, and 1.4% for RCC, and their 5-year overall survival was 45.2, 18.6, and 38.5%, respectively (p = 0.11). Survival for all patients was 30.8%. CONCLUSION: The surgical outcome and survival of patients who underwent PM in Iceland are comparable to those in the other studies. Although there was no control group and selection bias cannot be eliminated, the survival of PM patients was better than for the nonoperated patients. However, a relatively small proportion of patients with CRC, RCC, and sarcoma underwent metastasectomy.

Duration of Parkinson disease is associated with an increased propensity for "reinvestment".

BACKGROUND: As a consequence of difficulties in movement initiation and execution, people with Parkinson's disease (PD) are typically encouraged to consciously monitor and control the mechanics of their actions. This is described as 'reinvestment' and has been shown to help mediate effective motor output. Paradoxically, in situations where people with PD are particularly motivated to move effectively, reinvestment may exacerbate existing movement deficits. OBJECTIVE: To examine the propensity for reinvestment in a sample of people with PD. METHODS: A volunteer sample of 55 people with PD was asked to complete a previously validated measure, the Reinvestment Scale. A sub-sample (and age matched controls) was asked to complete a recently developed, movement specific, version of the Scale. Data was collected on Mini Mental State Examination and the Hoehn & Yahr Scale. Participant demographics, including age of onset and duration of disease, were also collated. RESULTS: Multiple regression analyses showed that duration of disease was associated with reinvestment score on both the Reinvestment Scale and the Movement Specific Reinvestment Scale. CONCLUSIONS: Participants appeared to become more aware of the mechanics of their actions over time. Possible explanations for this finding are discussed with reference to rehabilitation.

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

Patients' experiences of deep brain stimulation for Parkinson's disease: a qualitative systematic review and synthesis.

OBJECTIVE: To review and synthesise qualitative research studies that have explored patients' experience of deep brain stimulation (DBS) in advanced Parkinson's disease (PD). DESIGN: Systematic review and meta-synthesis of 7 original papers, using metaethnography. SETTING: Studies conducted in Denmark, France and Sweden. PARTICIPANTS: 116 patients who had undergone DBS and 9 spouses of patients. RESULTS: Prior to surgery, the experience of advancing PD is one of considerable loss and a feeling of loss of control. There are significant hopes for what DBS can bring. Following surgery, a sense of euphoria is described by many, although this does not persist and there is a need for significant transitions following this. We suggest that normality as a concept is core to the experience of DBS and that a sense of control may be a key condition for normality. Experience of DBS for patients and spouses, and of the transitions that they must undertake, is influenced by their hopes of what surgery will enable them to achieve, or regain (ie, a new normality). CONCLUSIONS: There is a need for further qualitative research to understand the nature of these transitions to inform how best patients and their spouses can be supported by healthcare professionals before, during and after DBS. In assessing the outcomes of DBS and other treatments in advanced PD, we should consider how to capture holistic concepts such as normality and control. Studies that examine the outcomes of DBS require longer term follow-up.

Subacute polyradiculopathy with optic and auditory nerve involvement.

Two patients are described, who, after an otherwise trivial viral upset, presented with an acute syndrome consisting of polyradiculopathy affecting all four limbs, with additional severe optic and auditory nerve involvement and other central nervous system signs. A combination of some of the features of the Guillain-Barré syndrome and a simultaneous acute episode of demyelination in the central nervous system were seen in these patients.

An investigation into the role of reactive oxygen species in the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity using neuronal cell lines.

The study of oxygen radical generation and effects during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) metabolism was undertaken in an in vitro test system. Three neurochemically discrete neuronal cell lines, B50 (cholinergic) and B65 rat cell lines and SKNSH human neuroblastoma (both catecholaminergic), were exposed to MPTP (0-200 microM). Parallel experiments were performed using reagent H2O2, an intermediate which may be generated during MPTP metabolism, to determine whether MPTP and H2O2 had any selectivity of toxicity and whether the mechanisms of cell death were similar. MPTP toxicity was shown to be reduced by monoamine oxidase B inhibitors, pargyline (P < 0.01) and selegiline (P < 0.05), indicating that toxicity was due to metabolism of MPTP rather than the parent compound. Cytotoxicity was also decreased in the presence of antioxidants, most notably in the presence of superoxide dismutase and catalase together (P < 0.01), suggesting that reactive oxygen species (ROS) play a role in MPTP-induced cell death. Attempts to determine the intracellular target for oxidative attack did not identify significant levels of lipid peroxidation products, but did demonstrate nucleoid expansion, possibly the result of double stranded DNA breaks induced by ROS.

Urinary levels of neopterin and biopterin in autism.

The pterins, neopterin and biopterin, occur naturally in body fluids including urine. It is well established that increased neopterin levels are associated with activation of the cellular immune system and that reduced biopterins are essential for neurotransmitter synthesis. It has been suggested that some autistic children may be suffering from an autoimmune disorder. To investigate this further we performed high performance liquid chromatography analyses of urinary pterins in a group of pre-school autistic children, their siblings and age-matched control children. Both urinary neopterin and biopterin were raised in the autistic children compared to controls and the siblings showed intermediate values. This supports the possible involvement of cell-mediated immunity in the aetiology of autism.

Ocular toxicity of desferrioxamine--an example of copper promoted auto-oxidative damage?

Three patients with rheumatoid disease were given the 'iron chelating' drug desferrioxamine (DFX), which also has an appreciable affinity for copper. The drug was injected cautiously, in lower doses than in patients with thalassaemia, and intramuscularly to evaluate its anti-inflammatory effects. Two of the three patients developed ocular abnormalities. One patient, who also received methyldopa, developed severe but reversible visual failure associated with an abnormal electro-oculogram (EOG); another showed reversible depression of the EOG. Analysis of the cerebrospinal fluid (CSF) of this patient showed an increase in phenanthroline detectable (non-caeruloplasmin-bound) copper. Analysis of the CSF of the third patient, who did not develop any clinical or electrophysiological ocular abnormalities, was normal. Haematological assessments indicated that all three patients probably had reduced iron stores. With in-vitro systems DFX was shown to mobilise copper from albumin and to facilitate copper movement across a cell membrane model, a property that was enhanced by methyldopa. Our observations are consistent with the concept that in rheumatoid patients low iron stores may result in binding of copper by DFX and that this may be of central importance in causing the ocular toxicity of DFX.

Abnormalities in urinary pterin levels in Rett syndrome.

The pterins, neopterin and biopterin, occur naturally in body fluids including urine. Increased neopterin levels are associated with activation of the cellular immune system and reduced biopterins are essential for biosynthesis of the monoamine neurotransmitters. The present study measured urinary neopterin and biopterin by high-performance liquid chromatography in 40 subjects with Rett syndrome, eight of their healthy sisters and 29 female control volunteers (age range 2-54 years). The results confirm earlier preliminary findings that urinary neopterin levels are raised in a proportion of young girls with Rett syndrome but not in the older women. In contrast urinary biopterin levels are not different from controls in the youngest children but remain low while control values increase with age. These findings may indicate immune activation during the regression phase of Rett syndrome but also raise the possibility that an inherited fault in tetrahydrobiopterin metabolism increases the risk of developing the disorder.

Loss of heterozygosity at the FHIT gene in different solid human tumours and its association with survival in colorectal cancer patients.

BACKGROUND: Genomic alterations and abnormal expression of the FHIT gene have been reported for a number of cancers. FHIT encompasses FRA3B, the most common fragile site in the human genome, and is suggested to be a candidate tumour suppressor gene. MATERIALS AND METHODS: We analysed and compared the loss of heterozygosity (LOH) pattern in 397 solid human tumours from 9 different locations, using four polymorphic microsatellite markers within the gene (D3S1234, D3S1300, D3S2757 and D3S4260), and two markers (D3S1313 and D3S1600) flanking the gene. In addition, we tested whether there was an association between FHIT LOH and overall patient survival in colorectal cancer. RESULTS: LOH at the FHIT gene affecting at least one of the investigated markers was detected in 166 out of 332 informative tumours, or 50%. The highest detected LOH was in lung tumours (66%) while the lowest was in thyroid and endometrium tumours, (30% and 31%, respectively). Breakpoints were found inside the gene in all tumour types in 12-80% of the tumours with FHIT LOH depending on tumour type, and up to 41% could additionally be located adjacent to the 3' or 5' end of the FHIT gene. Thus we were able to locate breakpoints within or in the vicinity of the FHIT gene in 25-100% of different tumours with LOH. Although not statistically significant, we observed a trend towards a poorer survival of patients with FHIT LOH versus those with retention of heterozygosity. CONCLUSION: Based on our results, LOH of the FHIT gene is a common event in all tumour types analysed with a possible association with poorer survival in colorectal cancer patients. LOH at all markers analysed was, in most of the tumour types, a more common pattern of alterations than breakpoints.

Neuroleptanalgesia in acute myocardial infarction: effects of hemodynamic parameters and plasma catecholamines.

The use of neuroleptanalgesia in acute myocardial infarction offers the possibility of reducing pain and emotional stress. The influence of such treatment on hemodynamic parameters (heart rate, cardiac output, stroke volume, peripheral resistance, systemic blood pressure, and pulmonary pressure) and on the plasma level of adrenaline and noradrenaline has been studied in 6 patients with acute myocardial infarction. This results demonstrate that during neuroleptanalgesia the already elevated levels of noradrenaline and adrenaline further increase. This increase was most pronounced in the patients with the highest initial levels of catecholamines. Since the peripheral resistance and systolic and diastolic blood pressures decrease concomitantly, it is concluded that the increase in levels of noradrenaline and adrenaline further increase. This increase was most pronounced in the plasma catecholamines is due to a reaction of the sympathetic nervous system to the alpha-adrenergic receptor blocking activity of droperidol causing vasodilation. The data indicate that pain, emotional stress, and anxiety in the acute phase of myocardial infarction do not play the expected essential role for the activation of the sympathetic nervous system generally observed in acute myocardial infarction. Additionally, the data demonstrate that drugs producing a vasodilation can have a deteriorating effect on the hemodynamic situation and that a reduction of the afterload by vasodilating drugs can result in a further increase in the release of catecholamines.

[Haemodynamic effects of depot zinc protamine glucagon in heart failure (author's transl)]. / Hämodynamische Wirkungen von Depot-Zink-Protamin-Glukagon bei kardialer Dekompensation.

In contrast to intravenously-administered crystallene glucagon, which acts for 20 minutes only, the depot form, zinc protamine glucagon, shows a prolonged haemodynamic action. Fourteen patients with pre-existing heart failure received a single dose of 20 mg Zn protamine glucagon intramuscularly. The stroke volume and cardiac output were increased, whereas the mean and end-diastolic pulmonary pressure were decreased, indicating a positive inotropic action of the administered drug. Heart rate and mean arterial pressure remained almost unchanged. The haemodynamic changes started 60 minutes after intramuscular administration of the drug, reached a maximum effect at 3 hours and started to decrease after the fourth hour. Zn protamine glucagon can, therefore, be considered a beneficial drug in the treatment of digitalis-resistant heart failure on the basis of its long duration of action and easy route of administration.

[Emergency treatment with a temporary balloon-floated pacemaker electrode (author's transl)]. / Notfalltherapie mit der temporären Schrittmacher-Ballonelektrode.

The "blind" insertion of a balloon-tipped pacemaker electrode is a suitable method when emergency pacing at the bedside is needed. The disadvantage of placement of the electrode without fluoroscopic control is counter-balanced by the saving of time and the lesser stress and risk involved for the patient, who is not required to be moved to a fluoroscopic room.

[Severe intoxication with leponex (author's transl)]. / Schwere Leponex-Vergftung und ihre Intensivbehandlung

The clinical picture and the therapeutic management of a severe case of self-poisoning with Leponex (clozapin) are presented. In particular, the grave complications, their possible aetiology and the value of the administration of cortisone are discussed. Forced diuresis or haemodialysis are ineffective measures on account of the low serum concentrations of Leponex.

[Angiotensin - a possible cause of acute renal failure (author's transl)]. / Angiotensin - mögliche Ursache eines akuten Niervenversagens

The hypertensive action of angiotensin is purely brought about by peripheral vasoconstriction and may, thus, lead to reduced perfusion of vital organs, especially the kidneys. The dangers of angiotensin in triggering off acute renal failure are illustrated by a case report in which this drug was administered to a comatose patient with hypovolaemic hypotension following barbiturate self-poisoning.

[Clinical results with dopamine in acute renal failure (author's transl)]. / Erfahrungen mit Dopamin beim akuten Nierenversagen

Dopamine possesses specific pharmacological actions which distinguish it from the other catecholamines. Apart from its positive inotropic effect, dopamine exerts a favourable influence on renal function with an increase in renal blood flow and alterations in intrarenal haemodynamics. The use of dopamine in the early stages of acute oliguric failure is recommended on the basis of the good therapeutic response achieved in a series of cases.

[Haemodynamic changes in acute myocardial infarction following high doses of furosemide (author's transl)]. / Anderungen der Hämodynamik beim akuten infarkt nach hohen Dosen Furosemid

Haemodynamic measurements were carried out after administration of furosemide to 10 patients suffering from acute myocardial infarction and congestive heart failure. It was observed that a transient deterioration in cardiac function (decreased cardiac output, increased enddiastolic pulmonary arterial pressure and increased pulmonary and systemic resistance) occured in the pre-diuretic stage in these failing hearts. After the onset of diuresis the haemodynamic parameters showed a reversal of the previous trends (increased cardiac output, decreased enddiastolic pulmonary arterial pressure and pulmonary resistance). The consistently lower enddiastolic pulmonary arterial pressure in the diuretic phase as compared with the pre-diuretic value ensured an improvement in cardiac haemodynamics. An attempt was made to interpret the haemodynamic results in the light of the Frank-Starling's curve.