Non-specific effects of childhood vaccinations - A case control study nested into a Health and Demographic Surveillance System in rural Burkina Faso.

INTRODUCTION: Previous studies in African countries have been suggestive of non-specific effects (NSE) of vaccination on child survival. Live vaccines (e.g. measles, MV) have been found to reduce child mortality while inactivated vaccines (e.g. diphtheria-tetanus-pertussis, DTP) have been associated with increased mortality; NSE were often found to be sex-specific. METHODS: A case-control study nested into the Health and Demographic Surveillance System (HDSS) cohort of the Centre de Recherche en Santé de Nouna (CRSN) was conducted in northwestern Burkina Faso. A total of 3,010 children born in 2009-11, were included in the study, 375 cases and 2635 age and village matched controls. The main outcome measures were the mortality odds ratios for vaccinated versus unvaccinated children by antigen. The main outcome measures were the mortality odds ratios for vaccinated versus unvaccinated children by antigen. RESULTS: Most deaths occurred in late infancy, and there were significantly more deaths in males as compared to females (OR 1.29, CI 1.04-1.60). Overall, there was no statistically significant association between vaccine status and mortality. However, among children in the age group 2-8 months, there was a consistent sex-differential pattern for all doses of oral polio vaccine combined with pentavalent vaccine (OPV + Penta), with the vaccines being associated with lower mortality in boys, but not in girls. Routine MV + yellow fever vaccine was associated with reduced mortality, but only before mass vaccination campaigns with meningitis and measles vaccines took place. CONCLUSIONS: The findings of this study provide further support on the existence of NSE of childhood vaccinations in a large population of rural Burkina Faso. More randomized controlled trials are needed to confirm these observations.

[Patients at the end of life in the intensive care unit: cultural aspects of accompaniment]. / Patienten am Lebensende auf der Intensivstation: Kulturelle Aspekte der Begleitung.

The accompaniment of people in the face of death offers insights into dimensions which are mostly not seen in ordinary life. These insights also exist in intensive care in German hospitals and are highly relevant in medical decision making. End-of-life decisions in particular often determine medical, cultural and spiritual aspects concerning medical treatment and therapeutic targets and if necessary new therapy targets. The following article especially illuminates cultural aspects and their characteristics in patients at the end of life in the intensive care unit.

[Palliative care oriented therapy for all patients : recommendations of an expert circle]. / Palliativmedizinisch orientierte Therapieansätze für alle Patienten : Empfehlungen eines Expertenkreises.

BACKGROUND: Since 2011 palliative care has been a compulsory part of the German medical study course (so-called Q13 palliative and pain medicine). Palliative care content does not, however, as often taught, have to focus only on patients in the so-called palliative stages of disease. The aim of this investigation was to encourage a discussion concerning the integration of palliative care aspects into general medical treatment. METHODS: For data collection an open discussion of the main topics by experts in palliative medical care was used. The main outcome measures and recommendations included responses regarding current practices related to expert opinions, national and international literature and one case report. The literature search was performed using the databases "PubMed", "Medline" and "Google" (1990-2011). RESULTS: As an important consensus, the following recommendations for optimization of inpatient and outpatient care were: (1) integration of aspects of palliative care into medical curricula of all disciplines, (2) palliative care content should be extended to the general optimization of therapy for all patients, (3) palliative medicine should be part of the everyday medical practice in all disciplines and (4) palliative medicine should not be isolated as "death medicine" or medicine of the dying patient. CONCLUSIONS: Palliative care treatment is increasingly becoming integrated into medical education and into medical curricula of all disciplines. Palliative ideas and goals are focussed on patients in the so-called palliative stages of disease. Furthermore, palliative medicine is often described as the medicine of dying patients. As a result of this study it seems to make sense to extend palliative care aspects to all patients and to all patient care. The extent to which such opportunities exist and such health care is economically feasible remains to be the subject of further clinical studies.

["Scores of Independence for Neurologic and Geriatric Rehabilitation (SINGER)" - development and validation of a new assessment instrument]. / "Selbständigkeits-Index für die Neurologische und Geriatrische Rehabilitation (SINGER)" - Entwicklung und Validierung eines neuen Assessment-Instruments.

In the context of developing and testing a procedure for "Outcome-oriented payment for rehabilitation after stroke", we found that the instruments commonly used to measure the outcomes of rehabilitation after stroke (e. g., Barthel-Index or FIM) were not meeting the special requirements of the new payment system. Therefore the "Scores of Independence for Neurologic and Geriatric Rehabilitation" (SINGER) was developed as a new assessment instrument. This instrument is based on the ICF and measures 20 aspects of "independence in activities of daily living". The characteristic feature of the SINGER is, above all, the way all items are graded in 6 steps: the gradation does not refer to the degree of disability but to the kind and amount of help required for the respective activity, i. e.: 0 = totally dependent on professional help; 1 = professional contact help needed; 2 = contact help by (instructed) lay persons sufficient; 3 = preparation or supervision by lay persons still needed; 4 = independent with assistive device or still slow; 5 = independent without assistive device. For experienced personnel in neurologic rehabilitation, these gradations are "intuitively plausible". A manual moreover describes each grade in detail for each item so that the instrument can be used in rehabilitation facilities without extensive training. The SINGER has been tested and validated in a pilot study (n = 100) and in 2 subsequent studies with large case numbers in neurologic rehabilitation (n = 1058 and n = 700 patients after stroke in all categories of severity). Factor analyses showed that the instrument contains 2 dimensions which can be interpreted as "physical activities" and "activities of communication and cognition". Each of these 2 dimensions can be split into 2 sub-dimensions that can be assigned to the tasks of therapeutical professions in care/Occupational Therapy, physiotherapy, logopedics, and neuro- psychology. The test criteria of reliability, sensitivity, convergent validity, floor and ceiling effects as well as sensitivity to change show good to very good results. Particular emphasis can be given to the high degree of interrater reliability and the wide range of possible applications in clinical practice as well as in research. A limitation of the instrument to be taken into account is the fact that the SINGER has not yet been tested and validated in geriatric rehabilitation facilities.

[Palliative care and end-of-life patients in emergency situations. Recommendations on optimization of out-patient care]. / Palliativpatienten und Patienten am Lebensende in Notfallsituationen. Empfehlungen zur ambulanten Versorgungsoptimierung.

BACKGROUND: At the end of life acute exacerbations of medical symptoms (e.g. dyspnea) in palliative care patients often result in emergency medical services being alerted. The goals of this study were to discuss cooperation between emergency medical and palliative care structures to optimize the quality of care in emergencies involving palliative care patients. METHODS: For data collection an open discussion of the main topics by experts in palliative and emergency medical care was employed. Main outcome measures and recommendations included responses regarding current practices related to expert opinions and international literature sources. RESULTS: As the essential points of consensus the following recommendations for optimization of care were named: (1) integration of palliative care in the emergency medicine curricula for pre-hospital emergency physicians and paramedics, (2) development of outpatient palliative care, (3) integration of palliative care teams into emergency medical structures, (4) cooperation between palliative and emergency medical care, (5) integration of crisis intervention into outpatient palliative emergency medical care, (6) provision of emergency plans and emergency medical boxes, (7) provision of palliative crisis cards and do not attempt resuscitation (DNAR) orders, (8) psychosocial aspects concerning palliative emergencies and (9) definition of palliative patients and their special situation by the physician responsible for prior treatment. CONCLUSIONS: Prehospital emergency physicians are confronted with emergencies in palliative care patients every day. In the treatment of these emergencies there are potentially serious conflicts due to the different therapeutic concepts of palliative medical care and emergency medical services. This study demonstrates that there is a need for regulated criteria for the therapy of palliative patients and patients at the end of life in emergency situations. Overall, more clinical investigations concerning end-of-life care and unresponsive palliative care patients in emergency medical situations are necessary.

[Analgesia of the axilla using a paravertebral catheter in the lamina technique]. / Analgesie der Achselhöhle durch Paravertebralkatheter in Laminatechnik.

A 62-year-old female suffered from therapy-resistant pain in the axilla after lymphadenectomy. The pain ranged from 8-10 on the numeric rating scale (NRS) despite multimodal pain therapy (non-steroid anti-rheumatics, opioids, physiotherapy, acupuncture). A paravertebral trial injection was performed preoperatively on the laminae of the thoracic vertebrae Th 2-Th 4. As the patient responded well, a paravertebral catheter was inserted close to Th 4 directly before the revision operation took place the following day. The case study describes the possibilities of eliminating pain segmentally in the axilla and an alternative technique to a paravertebral block (lamina technique).

[Inadvertent intravenous infusion of 380 mg ropivacaine]. / Versehentliche intravenöse Infusion von 380 mg Naropin (Ropivacain).

This is a report about an inadvertent intravenous infusion of 380 mg ropivacaine in a 84-year-old patient over a period of 1.75 h. The level of serum ropivacaine measured immediately after the end of the infusion as well as 2 h and 7 h later, was initially in the lower toxic range (free concentration of 0.48 micro g/ml). The patient showed no symptoms of intoxication neither clinically nor during the technical examinations (EEG, ECG). This case confirms the wide therapeutic range of ropivacaine.

IGFs, basic FGF, and glucose modulate proliferation and apoptosis induced by IFNgamma but not by IL-1beta in rat INS-1E beta-cells.

We investigated the effects of glucose and beta-cell growth factors (IGF-I, IGF-II, bFGF) on growth and apoptosis in the presence and absence of apoptosis inducing cytokines (IFNgamma, Il-1beta, TNFalpha). Rat INS-1E beta-cell viability was measured by WST-1 viability assay and cell counting, apoptosis by FACS analysis of annexin-V-FITC and fluorescein-dUTP (TUNEL-staining)-positive cells. Glucose alone maintained INS-1E beta-cell viability at high physiological concentrations (6.2-12.5 mmol/l), addition of IGF-II alone or in combination with bFGF further increased these glucose effects. The cytokines IFNg and IL-1beta, but not TNFalpha strongly induced INS-1E beta-cell apoptosis. Interestingly, glucose alone induced apoptosis at extremely low or very high concentrations. In combination with IFNg, low glucose (1.6 mmol/l) increased apoptosis by 25.6% (1SD 5.0%) and high glucose (50 mmol/l) by 22.8% (1SD 2.8%) compared to 12.5 mmol/l glucose. In contrast, glucose failed to modulate IL-1beta-induced apoptosis. Most importantly, IGF-II and bFGF inhibited apoptosis induced by IFNg, but not by IL-1beta. Therefore, IGF signaling, supported by bFGF and optimal glucose levels, maintains beta-cell viability in vitro. Cytokines IFNg and IL-1beta differentially interfere with intracellular signaling cascades stimulated by IGFs and bFGF or glucose, respectively.

The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium-induced colitis.

BACKGROUND & AIMS: Differences in genetic background may play a role in the development of ulcerative colitis (UC)-related neoplasia. Loss of heterozygosity (LOH) of APC has been reported in human UC-associated neoplasia. To investigate the role of genetic differences in UC-associated neoplasia, we compared differences in dextran sodium sulfate (DSS) colitis-associated neoplasia between wild-type C57BL/6J mice (WT-DSS) and C57BL/6J mice with a germline mutation in Apc (Min-DSS). METHODS: DSS colitis was induced in female wild-type and Min mice. Age- and sex-matched non-DSS-treated Mins were also studied. Animals were sacrificed after 1 and 2 cycles of DSS. The cecums and large intestines were studied for numbers of dysplasias/cancers. Dysplasias were studied for LOH of Apc. RESULTS: No WT-DSS, 100% of Min-DSS, and 50% of non-DSS-treated Mins had dysplasia. The mean numbers of lesions per mouse were 0 (WT-DSS), 15.6 and 29.3 (1 and 2 cycles Min-DSS, respectively), 1.2 and 1.9 (age-matched control Min, 1 and 2 cycle equivalents, respectively; P < 0.0002, Min-DSS vs. WT-DSS and non-DSS-treated Min; P = 0.03, Min-DSS 2 cycle vs. Min-DSS 1 cycle). Cancers were seen in 0%, 22%, and 40% of non-DSS Min, Min-DSS-1 cycle, and Min-DSS-2 cycle animals, respectively. LOH of Apc was observed in 90.6% of dysplasias and 6% of nondysplastic mucosa. CONCLUSIONS: A germline mutation in Apc contributes significantly to the development of colitis-associated neoplasia. Colitis markedly accelerates the development of dysplasia and cancer in the Min mouse. Dysplasia in Min-DSS occurs through LOH of Apc.

Chronic dosing of oltipraz in people at increased risk for colorectal cancer.

The dithiolethione oltipraz is being developed as a chemopreventive agent for many malignancies, including colorectal cancer, on the basis of its in vivo protective activity against chemically induced tumors in a variety of animal models. This protection has been associated with an enhanced capacity to detoxify reactive carcinogens and, more recently, with increased DNA repair. In a previous single-dose study, elevated detoxification gene expression was observed in the days after oltipraz dosing. Now, in this clinical study, we evaluated the effects of oltipraz when given over a 3-month period. Fourteen individuals with increased risk for colorectal cancer were randomly assigned to one of two oral doses (125 or 250 mg/m2) of oltipraz twice weekly for 12 weeks. Two of seven subjects at the 250 mg/m2 dosage required dose reductions, owing to significant fatigue. The 125 mg/m2 dose level was well tolerated by all patients. Blood or colon tissue (or both) for evaluation of glutathione, glutathione S-transferase, DT-diaphorase activity, and DT-diaphorase mRNA expression were obtained prior to treatment and at weeks 6, 12, and 16. No significant modulation of phase II detoxification enzymes was seen at either dose studied during this period. Phase II trials evaluating a tolerable regimen of oltipraz (as demonstrated in this study) and other possible mechanisms that may be responsible for the protective activity of oltipraz should be pursued.

Disability and quality of life in Charcot-Marie-Tooth disease type 1.

OBJECTIVES: Charcot-Marie-Tooth disease type I (CMT1) is a hereditary sensorimotor neuropathy causing variable degrees of handicap. The risk for relevant disability in respect to genetic counselling is unknown. An attempt was made to define it. METHODS: Disability and ambulation of 50 patients with CMT1 were scored by the Hauser ambulation index score and the Rankin scale. Rankin score 2 was subdivided into 2a (independent without relevant slowness) and 2b (independent, though at the cost of excessive time consumption). The sickness impact profile was assessed and compared with patients 6 months after stroke who were without mental deficit. To define at which degree sickness and disability become relevant for genetic counselling, the patients were asked whether they would refrain from childbearing if the children were at risk of inheriting a disease that caused as much disability as they experienced themselves. RESULTS: Subdivision of Rankin score 2 was reliable and improved validity. High disability significantly predicted an attitude against childbearing (stepwise logistic regression) only with this subdivision. Thirty six per cent of the patients voted against childbearing. The cut off for relevant disability in respect to childbearing was a Rankin score higher than 2a, which was present in 44% of the patients. Psychosocial impact was comparable with patients with stroke and similar disability. Depression was present in 18% of the patients. CONCLUSION: Subdivision of Rankin score 2 is recommended for the assessment of longstanding disability in neuromuscular disorders. Disability becomes relevant for the attitude towards childbearing as soon as everyday activities become markedly slow (Rankin score 2b). Relevant disability occurred in 44% of the patients. Emotional stress in CMT is similar to that of patients with stroke and comparable disability.

Sensitivity and specificity of different conduction block criteria.

OBJECTIVES: To resolve the discrepancy between conduction block criteria derived from healthy controls and stricter criteria suggested by computer simulation of interphase cancellation through altered motor units. METHODS: An EMG database provided control nerves from patients with amyotrophic lateral sclerosis (ALS) or neural muscular atrophy (CMT1) (disease controls) and from subjects without neuromuscular diseases (healthy controls). We estimated normal limits from the healthy controls (criterion A) and from the pooled sample of healthy and disease controls (criterion B). We compared their sensitivity with that of an arbitrary limit of 0.5 (criterion C) in acute (AIDP) and chronic inflammatory demyelinating neuropathy (CIDP) and in multifocal motor neuropathy (MMNP). Specificity was assessed in ALS and CMT1. RESULTS: Limits estimated from healthy controls (criterion A: amplitude ratio of <0.7 in median and peroneal nerves and <0.8 in the ulnar nerve) gave false positive results in 17.3% of the ALS nerves. High scatter of the amplitude ratio of the nerves with distal response amplitudes below 1 mV required amplitude-dependent limits (0.36 for distal responses below 1 mV, 0.56 between 1 and 2 mV, and between 0.67 and 0.73 for higher response amplitudes) for criterion B. It was false positive in 4.3% of the ALS nerves and in 28.3% of the CMT1 nerves. A limit of 0.5 for nerves with distal responses above 1 mV and a limit of 0.36 for smaller responses (criterion D) avoided false positive results in ALS without further impairing sensitivity per patient in MMNP. Sensitivity in AIDP was 34.9% for criterion A, 19.5% for criterion B, and 10.2% for criterion D. Amplitude ratios were more sensitive than area ratios in CIDP and MMNP, but less specific in CMT1. CONCLUSIONS: Limits derived from healthy controls are unspecific in chronic neuromuscular diseases and in nerves with low response amplitudes. Criterion D should be used if motor unit restructuring or conduction delays have to be taken into account. Criterion A may be applicable in early AIDP if the distal response amplitude is above 1 mV.

Benign prostatic hyperplasia. A review of diagnostic and treatment options.

Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland caused by histologic hyperplasia that produces an inward transmission of pressure on the urethra and an increased resistance to urine flow. The dominant risk factors for the disease are age and male gender. Weak urine stream and hesitancy are the cardinal obstructive features in BPH. Other signs and symptoms include inability to terminate micturition abruptly, sensation of incomplete emptying and occasionally, urinary retention. Many men with prostate enlargement can be successfully treated with lifestyle modification and medication. But if symptoms persist, with no significant improvement after 6 months of finasteride or 2 to 3 months of an alpha-1 blocker, consider a urology consultation. Several surgical options are available.

The diagnostic power of motor unit potential analysis: an objective bayesian approach.

The notion of a "myopathic" or "neuropathic" electromyogram (EMG) is usually based on qualitative visual and acoustical impressions. Conventional quantification defines abnormality but not diagnosis, which requires interpretation of patterns of change. Discriminant analysis is a model for this multivariate decision. It tells how probable it is that a motor unit potential (MUP) comes from a normal, myopathic, or neuropathic muscle. Accumulation of single MUP information by a sequential Bayesian algorithm produced diagnostic probabilities above 0.95 in 91% of all muscles (223 biceps brachii muscles from 80 patients with motoneuron disorders, 56 patients with neuropathies, 71 patients with myopathies, and 34 controls). Two muscles from patients with neurogenic disorders were misclassified as "myopathic." Misclassification was more frequent only in myositis (4 of 28 muscles) and in oculopharyngeal muscular dystrophy (2 of 4 muscles). MUP discriminant classification was as sensitive as, and more specific than, conventional quantitative EMG, which discriminated between myopathic and neuropathic in only 22% of the muscles. This rate was 59% for discriminant analysis. As a knowledge-based expert system, MUP discriminant analysis successfully distinguishes between myopathic, neuropathic, and unclassifiable MUP samples. It discloses more information than conventional quantitative MUP analysis.

Depletion of colonic detoxication enzyme activity in mice with dextran sulphate sodium-induced colitis.

BACKGROUND: The increased risk of colonic malignancies in individuals with ulcerative colitis has prompted a search for early biomarkers of disease progression. AIM: To characterize Phase II detoxication enzyme expression during acute and chronic colitis. The mouse model of dextran sulphate sodium (DSS)-induced colitis represents a relevant system with which to sequentially evaluate the spectrum of biochemical changes associated with colorectal cancer risk. METHODS: Acute and chronic colitis were induced in Swiss Webster mice by administering DSS in the drinking water (5%) for 1-4 cycles. Each cycle consisted of 7 days DSS and 14 days of water. The glutathione S-transferase (GST) activity, gamma-glutamylcysteine synthetase (gamma-GCS) activity and glutathione content of the colonic tissues were determined at various time points throughout the experiment. Alterations in GST isozyme expression were confirmed by Western and Northern blot. RESULTS: GST activity was reduced significantly in the colon by the end of Cycle 1 (84% of control values). Specific activities continued to decrease with subsequent cycles of DSS exposure. By the end of Cycle 4, glutathione levels and gamma-GCS activity had reached 29% and 56% of control, respectively. CONCLUSIONS: These data suggest that detoxication enzyme depletion is associated with both acute and chronic colitis and may be an important event in the progression of ulcerative colitis to colon cancer.

Neurophysiology of orthostatic tremor. Influence of transcranial magnetic stimulation.

A 74-year-old patient suffers from painful muscle cramps when he stands since 30 years. He has no visible tremor but 16 Hz burst activity on EMG, indicating orthostatic tremor. Previous diagnosis was hysteria, stiff person syndrome or dystonia. This shows that EMG during standing should be part of the examination of patients with stiff muscles or muscle cramps. Tremor was not strictly orthostatic. It appeared in back muscles while sitting, when the patient supported a weight with outstretched arms. Phase between muscles differed between normal standing and standing on heels. Subthreshold transcranial magnetic stimulation modulated timing of the tremor bursts and inhibited them at higher intensity stimulation.

[Dysautonomia in Guillain-Barré syndrome]. / Dysautonomie bei Guillain-Barré-Syndrom.

About 20% of all GBS patients have symptoms of dysautonomia: labile hypertension, orthostatic hypotension, sinustachycardia or sinus arrest. This rate rises to 75% in patients with tetraplegia. Proprioceptive loss predicts dysautonomia independently from the severity of weakness. It is frequently responsible for dysautonomia. The afferent limb of cardiovascular regulation contains more myelinated fibers than the sympathetic and parasympathetic efferences, which determine the common classification of dysautonomia. The frequence of mixed sympathetic and parasympathetic hyperactivity is hard to explain by efferent lesions. Afferent conduction block releases the sympathetic efference of the baroreceptor reflex. The resulting catecholamine excess explains hypertension, tachycardia, ECG-changes and hyperglycemia. Norepinephrine sensitizes left ventricular stretch receptors. They induce cardiovascular depression and neurocardiogenic syncope which has a temporal behaviour similar to the blood pressure variations of GBS. Conduction block of sinoatrial stretch receptors causes inappropriate secretion of ADH and renin. Dysbalance between myelinated and unmyelinated afferents which decrease and increase heart rate may cause parasympathetic hyperactivity, as exemplified by pulmonary stretch receptors that are stimulated by artificial ventilation. Wrong afferent feedback is responsible for many cardiovascular instabilities in GBS. Blockade of misguided efferent reactions is an attractive therapeutical approach.