Blinded clinical evaluation of positron emission tomography for diagnosis of probable Alzheimer's disease.

We evaluated the sensitivity and specificity of positron emission tomography for diagnosis of probable Alzheimer's disease under conditions similar to those encountered in the routine clinical practice of nuclear medicine. We obtained tomographic images of regional cerebral blood flow from three groups of subjects: (1) 13 subjects, ages 69 to 84, who had probable Alzheimer's disease diagnosed by validated clinical criteria; (2) 15 subjects, ages 57 to 77, who had Parkinson's disease without dementia; and (3) 11 subjects, ages 65 to 83, who were normal. Three blinded reviewers, who had not previously seen the images, categorized them as normal, bilateral temporoparietal flow defects typical of Alzheimer's disease, or other abnormality. Consensus interpretation demonstrated sensitivity of 0.38 (5/13) and specificity of 0.88 (23/26) for identifying patients with probable Alzheimer's disease. Thus, the criterion of bilateral temporoparietal reduction in cerebral blood flow used in this study did not have sufficient sensitivity to be of clinical value. While other criteria may be developed to improve diagnostic accuracy, clinical utility can be established only by testing for validity in patients with a full spectrum of complicating neurologic and psychiatric conditions for whom diagnosis is uncertain and who are then followed longitudinally to determine clinical outcome or pathologic findings.     

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.     

Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin's disease.

BACKGROUND: Positron emission tomographic (PET) scanning utilizing [18F]fluorodeoxyglucose (FDG) is a new method of tumor imaging based on the increased glucose metabolic activity of malignant tumors. In Hodgkin's disease (HD), PET has proven value for the evaluation of residual masses following treatment and for the early diagnosis of relapse. In the initial staging of HD, PET frequently shows a higher stage than conventional methods (upstaging by PET). In the present study, we evaluated the frequency of stage changes by PET in a multicenter setting and determined its prognostic relevance. PATIENTS AND METHODS: A total of 73 patients with newly diagnosed HD were staged with both conventional methods and whole-body PET scanning. All histological types and stages were represented. The median time of follow-up after the initial diagnosis was 25 months (range 1 month to 5 years). The response to treatment was determined by standard clinical and diagnostic criteria. For the purpose of this analysis, data from a PET center associated with a university medical center and a PET center associated with a group oncology practice were combined. RESULTS: A total of 21 patients (28.8%) were upstaged by PET compared with conventional methods. In two cases (2.7%), a lower stage was suggested by PET scanning. With one possible exception, the upstaging had no obvious clinical or biological correlate. Among 12 patients in stage I (A + B) by conventional methods, seven were upstaged by PET (58.3%), four to stage II, one to stage III and two to stage IV. Among 42 patients in stage II, eight were upstaged by PET (19.0%), six to stage III and two to stage IV. Among 12 patients in stage III, six (50%) were upstaged to stage IV by PET. If only early-stage patients and major changes are considered (stages IA-IIB to III or IV), among 49, 10 were upstaged to III or IV, whereas in 39 staging was unchanged following PET. In the former group, three relapsed or were refractory compared with none in the latter group (P<0.006). In advanced stage patients (IIIA or IIIB) a trend toward treatment failure was apparent in patients who were upstaged by PET. CONCLUSIONS: PET scanning is an interesting new modality for the accurate staging of patients with HD and frequently shows a higher stage than conventional methods. PET should be performed at initial diagnosis and should be included in prospective studies of patients with HD. Upstaging by PET may represent a risk factor for a more advanced stage or a biologically more aggressive tumor. Patients with early-stage disease as identified by conventional methods have a significant risk of treatment failure if a more advanced stage is indicated by PET. At present, major stage changes suggested by PET imaging should be confirmed by an independent diagnostic method.     

Fetal Electrocardiogram Extraction and Analysis Using Adaptive Noise Cancellation and Wavelet Transformation Techniques

Birth defect-related demise is mainly due to congenital heart defects. In the earlier stage of pregnancy, fetus problem can be identified by finding information about the fetus to avoid stillbirths. The gold standard used to monitor the health status of the fetus is by Cardiotachography(CTG), cannot be used for long durations and continuous monitoring. There is a need for continuous and long duration monitoring of fetal ECG signals to study the progressive health status of the fetus using portable devices. The non-invasive method of electrocardiogram recording is one of the best method used to diagnose fetal cardiac problem rather than the invasive methods.The monitoring of the fECG requires development of a miniaturized hardware and a efficient signal processing algorithms to extract the fECG embedded in the mother ECG. The paper discusses a prototype hardware developed to monitor and record the raw mother ECG signal containing the fECG and a signal processing algorithm to extract the fetal Electro Cardiogram signal. We have proposed two methods of signal processing, first is based on the Least Mean Square (LMS) Adaptive Noise Cancellation technique and the other method is based on the Wavelet Transformation technique. A prototype hardware was designed and developed to acquire the raw ECG signal containing the mother and fetal ECG and the signal processing techniques were used to eliminate the noises and extract the fetal ECG and the fetal Heart Rate Variability was studied. Both the methods were evaluated with the signal acquired from a fetal ECG simulator, from the Physionet database and that acquired from the subject. Both the methods are evaluated by finding heart rate and its variability, amplitude spectrum and mean value of extracted fetal ECG. Also the accuracy, sensitivity and positive predictive value are also determined for fetal QRS detection technique. In this paper adaptive filtering technique uses Sign-sign LMS algorithm and wavelet techniques with Daubechies wavelet, employed along with de noising techniques for the extraction of fetal Electrocardiogram.Both the methods are having good sensitivity and accuracy. In adaptive method the sensitivity is 96.83, accuracy 89.87, wavelet sensitivity is 95.97 and accuracy is 88.5. Additionally, time domain parameters from the plot of heart rate variability of mother and fetus are analyzed.     

Acute severe asthma

Acute exacerbations of asthma are very common reasons for a presentation to emergency departments. This paper focuses on defining the high‐risk group, consideration of the concept of phenotypes of acute asthma, the assessment of severe and life‐threatening exacerbations and an emphasis on the management of the more severe end of the exacerbation severity. A number of evidence‐based guidelines exist throughout the world and are all slightly different. This reflects the poor evidence base for some of those recommendations. Thus, a large variation of treatment drugs, doses and regimen are used and clearly not standardised. This paper aims to present a summary of the best evidence and discuss some of these controversies. The most important aspect of treating an exacerbation of acute asthma is to review regularly and assess response to treatment. Severe and life‐threatening episodes should be treated with early use of intravenous treatment in a stepwise manner following the local guidelines. Non‐invasive ventilation and high flow nasal cannulae delivery of oxygen in the emergency department are evolving modalities, but evidence for their use is currently limited.     

Alloimmunization Against Well Defined Polymorphic Major Histocompatibility or Class I MHC Transfected L Cells Antigens Can Prevent Poly IC Induced Fetal Death in Mice

METHOD : It is possible to induce increased fetal resorption in a number of inbred murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a maneuver associated with natural killer-mediated damage to the feto placental unit such as occurs in spontaneous fetal resorptions. RESULTS : We show here that alloimmunization can block this effect. In addition, maternal immune responses induced by alloimmunization against isolated mutant class I or class II, as well as by immunization with class I MHC alloantigens (K^d) transfected L cells are sufficient to restore normal fetal viability. It is not necessary that the maternal immune response be specifically directed against paternal alloantigens fr the fetal protecton to ensue, since the effect occurs in inbred matings when the mother is immunized against unrelated class I or class II alloantigens. As in previous studies conducted in the murine species, not all MHC alloimmunizations are protective. In addition, as control, immunization with a monomorphic class I MHC molecular (37), transfected L cells, sheep red blood cells or hen egg lysozyme is without effect. CONCLUSION : These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.     

Primary Ewing sarcoma of the orbit

PURPOSE: To report the clinicopathologic features of a 17-year-old patient with primary Ewing sarcoma of the orbit. METHODS: The patient was evaluated clinically before surgery with computed tomography scans of the orbit. After surgery, the patient was staged with computed tomography scans and bone scan and was treated with systemic chemotherapy and radiation therapy to the orbit. The orbital biopsy was evaluated with conventional light microscopy and immunohistochemistry. RESULTS: Clinical evaluation revealed proptosis and limited upgaze. Computed tomography scans disclosed a mass involving the superior orbit, anterior cranial fossa, and temporal fossa. Microscopic examination revealed small, poorly differentiated cells with medium-sized nuclei containing finely granular chromatin and small nucleoli. The cytoplasmic borders of the cells were indistinct. A PAS stain revealed modest glycogen in many of the tumor cells. The tumor stained positive for O-13 and vimentin and was negative for neural, skeletal, and lymphoid cell markers. Computed tomography scan, bone scan, and blood chemistries revealed no other site of involvement. After treatment, the clinical symptoms and signs resolved, and there has been no evidence of residual orbital tumor or metastasis. CONCLUSIONS: Primary Ewing sarcoma of the orbit should be considered in the differential diagnosis of children or young adults with proptosis, diplopia, or periorbital swelling. Immunohistochemistry is essential to distinguish Ewing sarcoma from other small round cell tumors.     

The Role of Catheter Ablation Techniques in the Treatment of Classic (Type 1) Atrial Flutter

Several attempts at circuit interruption of type 1 atrial flutter by means of surgical or catheter techniques have been published. We recently reported the results of a series of patients who underwent catheter fulguration of the low septal right atrium, with a mean follow-up of almost 3 years. True electrophysiological success was observed in 7/14 patients (50%). Clinical success, defined as absence of symptoms, was observed in 8/14 (57%) in this patient population. No serious complications were encountered, but the potential risks of DC shock, and the experience that we gained in right atrial mapping using this approach, led us to reconsider the role of atrial DC ablation in these patients. Additional studies assessing the meaning of fragmented electrograms, and identification of one for of severall slow conduction areas of the reentrant circuit are ongoing.