Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy.

The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome.

OBJECTIVE: To identify brain regions generating tics in patients with Tourette syndrome using sleep as a baseline. METHODS: We used [15O]H2O PET to study nine patients with Tourette syndrome and nine matched control subjects. For patients, conditions included tic release states and sleep stage 2; and for control subjects, rest states and sleep stage 2. RESULTS: Our study showed robust activation of cerebellum, insula, thalamus, and putamen during tic release. CONCLUSION: The network of structures involved in tics includes the activated regions and motor cortex. The prominent involvement of cerebellum and insula suggest their involvement in tic initiation and execution.

Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease.

A 20-year-old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt-Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal-size TBP alleles with 37-38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)(15) sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegenerative disorders having phenotypic similarities with vCJD.

[How to quantify the severity of brain injury during intensive care after adult head trauma]. / Valutazione della gravità del danno cerebrale nel corso di terapia intensiva dopo trauma cranico nell'adulto.

Adequate early assessment of brain damage is essential. Location, extension and severity of structural damage affect brain function and ultimately determine the outcome. The extent of functional impairment, and the morphology of intracranial lesions, require specific treatment, often a combination of medical and surgical interventions. Brain damage usually evolves over time, and repeated assessments are necessary. Clinical evaluation is often biased by concomitant sedation and/or anesthesia, but remains necessary. A revision of the literature is presented. Brain damage is assessed combining clinical and instrumental data. Clinical examination is performed assessing the 3 components of the Glasgow Coma Scale. Spontaneous or stimulated (pain stimulus) eye opening, verbal and motor responses are observed after hemodynamic and respiratory stabilisation. Unfortunately a significant proportion of patients can not be properly examined for several reasons: eye opening can be altered by palpebral and facial injuries, verbal response can be impaired by maxillo-facial injuries or by endotracheal intubation, and motor response remains the most consistent parameter. Sedation, analgesia and myorelaxants, however, can profoundly diminish or abolish the motor response to maximal stimulation, so that examination should be performed after clearance of drugs. Often alcohol or other substances can further impair the neurological performances. Pupils diameter and reactivity to light should be observed, excluding pharmacologic effects (as dilation due to catecholamines) and direct ocular or orbital damage. The CT scan is necessary for disclosing surgical masses and for identifying the extent of diffuse damage and the location of focal lesions. These data should be combined with additional functional exploration, as provided by cerebral extraction of oxygen and electrophysiologic data. Early estimation of cerebral damage is complex and prone to mistakes. Accurate, repeated evaluations, based on the combination of clinical observation and imaging, are necessary.

Primary lateral sclerosis: A heterogeneous disorder composed of different subtypes?

OBJECTIVE: To determine identifiable subgroups of patients with primary lateral sclerosis (PLS) with distinct clinical features as a first step in identifying patients likely to have the same disorder. METHODS: Twenty-five patients meeting previously proposed diagnostic criteria for PLS were seen for examination, measurement of gait and finger tapping speed, and physiologic tests to assess motor pathways. Motor cortex excitability and central motor conduction time were assessed with transcranial magnetic stimulation. Brainstem motor pathways were assessed by the acoustic startle reflex. MRS was performed in a subgroup of patients to assess metabolites in the motor cortex. RESULTS: Fifty-six percent of the patients with PLS had a similar pattern of symptom progression, which the authors termed ascending. In these patients spasticity began in the legs and progressed slowly and steadily. Spasticity in the arms developed 3.6 years after the legs, on average, and speech impairment followed 1.5 years later. Motor evoked potentials were absent. MRS showed a mean reduction of N-acetylaspartate/creatinine in the motor cortex. The remaining patients with PLS had heterogeneous patterns of symptom progression and physiology. CONCLUSIONS: Patients with PLS with an ascending progression of symptoms form a distinct clinical subgroup that may be amenable to investigations of etiology and treatment.

Review of 17 cases of pneumonia caused by Streptococcus pyogenes.

Streptococcus pyogenes is an uncommon cause of community-acquired pneumonia and there have been few recent specific accounts of the condition. To describe the current nature of this disease in the UK, data was gathered on patients with clinical pneumonia from whom Streptococcus pyogenes was cultured principally from blood or other relevant normally sterile sites. In the Harrogate and Northallerton districts of North Yorkshire, pneumonia accounted for nine (20%) cases and a quarter of all deaths in a complete sequence of 45 patients with Streptococcus pyogenes bacteraemia detected during the 16-year-period 1981-1996. An analysis is presented of those cases together with eight recent cases from counties York, Durham and Isle of Wight during 1995-1997. Of the total 17 cases, nine occurred in women and eight in men; the age range was 30-92 years. The organism was isolated from blood culture in 15 (88%) patients. Eight (47%) patients died, five within 1 day of hospitalisation. Fourteen (82%) cases occurred in the winter months October to March, including all the fatal cases and all eight in which a clinical 'viral' prodrome was observed. Predisposing medical or surgical conditions were present in 65% of the patients. Major complications included septicaemia, pleural reaction, shock, pulmonary cavitation, osteomyelitis and metastatic abscesses. Seven serotypes of Streptococcus pyogenes were encountered, with M-type 1 predominating (the cause in 60% of cases). All infections were community acquired; two small clusters of fatal pneumonia were seen.

[The incidence, clinical characteristics and prognostic significance of a left bundle-branch block associated with an acute myocardial infarct]. / Incidencia, características clínicas y significación pronóstica del bloqueo de rama izquierda asociado a infarto agudo de miocardio.

To assess the current incidence and meaning of left bundle-branch block associated with acute myocardial infarction we studied 1,239 patients consecutively admitted in three hospitals. Left bundle branch block was present in 42 cases (3.3%). Compared to the patients without left bundle-branch block, those with left bundle-branch block were older (70 +/- 8.8 versus 63.9 +/- 11.4 years; p < 0.001), and had a more prevalent history of diabetes, angina, myocardial infarction and heart failure. Left bundle-branch block was associated more frequently with female gender and poor left ventricular ejection fraction. Patients with left bundle branch block were admitted with a longer interval from the onset of the symptoms (7.8 +/- 6.3 versus 5.4 +/- 6.7 hours; p < 0.01) and received in a lesser rate thrombolytics agents (21% versus 56%; p < 0.001), than those without left bundle-branch block. Complications significatively associated with left bundle-branch block were: complete AV block; heart failure and one-year mortality (40.4% versus 19.5%, p < 0.01). Female gender, age and heart failure were independent predictors of mortality whereas left bundle-branch block was not. In conclusion, current incidence of left bundle-branch block in acute myocardial infarction is lower than that referred in the pre-thrombolytic era. Left bundle-branch block is accompanied by a low rate of thrombolysis, whereas a higher mortality rate of these patients seems to depend on their clinical characteristics.

[Effect of the location of myocardial infarction on the variability of heart rate: a study during the acute phase]. / Efecto de la localización del infarto de miocardio sobre la variabilidad de la frecuencia cardíaca: estudio en la fase aguda.

OBJECTIVES: The influence of the location of acute myocardial infarction on the autonomic tone and its evolution during the first hours post-infarct has not been fully evaluated. The aim of this study was to analyze this effect using a spectral analysis of the heart rate variability. PATIENTS AND METHODS: Forty-nine consecutive patients with acute myocardial infarction (22 anterior and 27 inferior) in sinus rhythm and free of diseases and drugs which could affect heart rate variability were studied. Five-minute Holter recordings within each hour between 10 and 33 hours after the onset of symptoms were analyzed, calculating the standard deviation of NN intervals and the spectral power of the high and low frequency bands using normalized units. RESULTS: The standard deviation was higher in inferior infarcts (51.4 +/- 23.4 ms vs. 38.6 +/- 14.8 ms in anterior location; p < 0.05) and gradually decreased over time in both locations. The relative distribution of high- and low-frequency bands did not show significant differences related to the infarct location. An inverse significant correlation between the high-frequency component and time was observed for anterior infarcts (r = -0.98; p < 0.001) as well as in the inferior group (r = -0.75; p = 0.04). Conversely, the low-frequency power gradually increased in anterior infarcts (r = 0.98, p < 0.001) while remaining stable in inferior locations (r = -0.08; NS). CONCLUSIONS: A gradual reduction of heart rate variability was observed in patients with acute myocardial infarction during the time of monitorization. The spectral analysis suggests that anterior infarcts present a progressive increase of sympathetic activity and a reduction of vagal tone, whereas inferior infarcts show a parallel reduction in both components of the autonomous nervous system.

Protection from oxidation enhances the survival of cultured mesencephalic neurons.

Oxidative stress has been linked to the destruction of dopaminergic neurons in the substantia nigra and may be a significant factor in both Parkinson's disease and MPTP toxicity. Using primary cultures of embryonic rat mesencephalon and standard immunocytochemical techniques, we have examined the survival of tyrosine hydroxylase-containing (TH+) neurons cultured in the presence of antioxidants and/or in an environment of low oxygen partial pressure. The number of TH+ neurons increased approximately twofold if superoxide dismutase, glutathione peroxidase (GP), or N-acetyl cysteine (NAC) were added to the culture media. Exposure of the neurons to a 5% oxygen environment (38 torr, i.e., 38 mm Hg) also increased the survival of TH+ neurons by about twofold. A dramatic enhancement of survival, however, was seen when NAC was used in combination with the 5% oxygen environment. In this case, the number of TH+ neurons increased fourfold from nontreated controls. Morphological changes were also noted. GP increased the average neurite length while NAC increased the average area of the cell body in the TH+ neuron. These results suggest that manipulation of oxidative conditions by changing the ambient O2 tension or the level of antioxidants promotes survival of TH+ neurons in culture and may have implications for transplantation therapies in Parkinson's disease.

What cord care--if any?

The use of antiseptic treatment during cord care varies from unit to unit. Although it may reduce bacterial colonisation it may also delay cord separation. Where antiseptic treatment is used there is uncertainty as to the best agent. Hexachlorophane powder (0.3%) and 4% chlorhexidene detergent were each compared with dry cord care as a control on a two ward maternity unit in a six month open study. Of 133 infants treated with hexachlorophane 44 (33%) became heavily colonised with Staphylococcus aureus compared with 80 (47%) of 171 controls; a reduction of one third. Chlorhexidene reduced colonisation by more than half; 17 (16%) of 104 compared with 41 (42%) of 98 controls. Chlorhexidene was associated with cord attachment at 10 days in 29 (28%) infants compared with 31 of 515 (6%) infants when it was not used. Hexachlorophane was more acceptable to the nursing staff. The reduction in colonisation with the two compounds was largely due to the suppression of cross infection.

Antibiotics for gram-positive organisms.

Most infections due to Gram-positive organisms can be treated with quite a small number of antibiotics. Penicillin, cloxacillin, and erythromycin should be enough to cover 90 per cent of Gram-positive infections. The relatively narrow spectrum of these drugs should be the incentive to prescribers to use them selectively, together with adequate bacteriological investigation, in order to achieve effective treatment with a minimum of disturbance to the patient's normal bacterial flora and without any other harmful side effects.