18F-FDG PET and PET/CT in fever of unknown origin.

Fever of unknown origin (FUO) was originally defined as recurrent fever of 38.3 degrees C or higher, lasting 2-3 wk or longer, and undiagnosed after 1 wk of hospital evaluation. The last criterion has undergone modification and is now generally interpreted as no diagnosis after appropriate inpatient or outpatient evaluation. The 3 major categories that account for most FUOs are infections, malignancies, and noninfectious inflammatory diseases. The diagnostic approach in FUO includes repeated physical investigations and thorough history-taking combined with standardized laboratory tests and simple imaging procedures. Nevertheless, there is a need for more complex or invasive techniques if this strategy fails. This review describes the impact of (18)F-FDG PET in the diagnostic work-up of FUO. (18)F-FDG accumulates in malignant tissues but also at the sites of infection and inflammation and in autoimmune and granulomatous diseases by the overexpression of distinct facultative glucose transporter (GLUT) isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic enzymes in cancer cells and inflammatory cells. The limited data of prospective studies indicate that (18)F-FDG PET has the potential to play a central role as a second-line procedure in the management of patients with FUO. In these studies, the PET scan contributed to the final diagnosis in 25%-69% of the patients. In the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or soft-tissue infection, as well as chronic osteomyelitis, can be made with a high degree of certainty. Negative findings on (18)F-FDG PET essentially rule out orthopedic prosthetic infections. In patients with noninfectious inflammatory diseases, (18)F-FDG PET is of importance in the diagnosis of large-vessel vasculitis and seems to be useful in the visualization of other diseases, such as inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In patients with tumor fever, diseases commonly detected by (18)F-FDG PET include Hodgkin's disease and aggressive non-Hodgkin's lymphoma but also colorectal cancer and sarcoma. (18)F-FDG PET has the potential to replace other imaging techniques in the evaluation of patients with FUO. Compared with labeled white blood cells, (18)F-FDG PET allows diagnosis of a wider spectrum of diseases. Compared with (67)Ga-citrate scanning, (18)F-FDG PET seems to be more sensitive. It is expected that PET/CT technology will further improve the diagnostic impact of (18)F-FDG PET in the context of FUO, as already shown in the oncologic context, mainly by improving the specificity of the method.     

Utilization of preoperative cerebrospinal fluid drain in skull base surgery.

OBJECTIVE: Retrospectively assess the efficacy of lumbar cerebrospinal fluid (CSF) drainage placed preoperatively in skull base operations in decreasing the incidence of postoperative CSF fistula. METHODS: A retrospective review of 150 patients undergoing a posterior fossa craniotomy from 1989 to 2000 was conducted. Patients were divided into those receiving preoperative lumbar drains and those that did not. The rates of postoperative CSF leakage were compared between the two groups. Patient data were analyzed to determine if there were other comorbidities affecting the postoperative incidence of CSF leakage such as smoking, diabetes, or hypertension. RESULTS: Between 1989 and 1994, 25/72 (35%) patients with no preoperative lumbar drain had a postoperative CSF leak. From 1995 to 2000, 9/78 (12%) patients with a preoperative lumbar drain had a CSF leak. This was a 23% decreased incidence of postoperative CSF leakage and a significant decrease in the probability (p < 0.001) of CSF leakage in patients treated with a preoperative lumbar drain. The comorbidities of diabetes, smoking, or hypertension did not increase the probability of a CSF leak (p = 0.43). CONCLUSIONS: A preoperatively placed lumbar drain can significantly lower the rate of postoperative CSF leakage after skull base surgery. The drain is a well-tolerated adjunct to dural closure and helps increase surgical exposure of the posterior fossa. The comorbidities of diabetes, smoking, or hypertension do not contribute to an increased rate of CSF leakage.dagger Lyal Leibrock M.D., F.A.C.S. is Deceased.     

The impact of serum sodium concentration on mortality after liver transplantation: a cohort multicenter study.

Modification of the current allocation system for donor livers in the United States to incorporate recipient serum sodium concentration ([Na]) has recently been proposed. However, the impact of this parameter on posttransplantation mortality has not been previously examined in a large risk-adjusted analysis. We assessed the effect of recipient [Na] on the survival of all adults with chronic liver disease who received a first single organ liver transplant in the UK and Ireland during the period March 1, 1994 to March 31, 2005 (n=5,152) at 3 years, during the first 90 days, and beyond the first 90 days, adjusting for a wide range of recipient, donor, and graft characteristics. Compared to those with normal [Na] (135-145 meq/L; n=3,066), severely hyponatremic recipients ([Na]<130 meq/L, n=541), had a higher risk-adjusted mortality at 3 years (hazard ratio [HR] 1.28; 95% confidence interval [CI], 1.04-1.59; P<0.02). The excess mortality was, however, confined to the first 90 days (HR 1.55; 95% CI, 1.18-2.04; P<0.002) with no significant difference thereafter. This was also true for hypernatremic recipients ([Na]>45 meq/L, n=81), who had an even greater risk-adjusted mortality compared to normonatremic recipients (overall: HR 1.85; 95% CI, 1.25-2.73; P<0.002; 90 days: HR 1.12; 95% CI, 0.55-2.29; P=0.8), whereas mildly hyponatremic recipients ([Na] 130-134 meq/L, n=1,127) had similar risk-adjusted mortality to those with normal [Na] at the same time points. In conclusion, recipient [Na] is an independent predictor of death following liver transplantation. Attempts to correct the [Na] toward the normal reference range are an important aspect of pretransplantation management.     

Cerebral Cortical Aquaporin-4 Expression in Brain Edema following Cardiac Arrest in Rats

OBJECTIVES: Brain edema occurs following clinical as well as experimental cardiac arrest (CA) and predicts a poor neurologic outcome. The objective of this study was to determine the expression of cerebral cortex aquaporin (AQP)-4, a member of a family of membrane water-channel proteins, in brain edema formation following normothermic or hypothermic CA. METHODS: Twenty-four rats were subjected to time-matched normothermic (N-Sham, 37.5 degrees C +/- 0.5 degrees C, n = 6) or hypothermic (H-Sham, 34 degrees C +/- 0.5 degrees C, n = 6) sham experiments and normothermic (N-CA, n = 6) or hypothermic (H-CA, n = 6) CA induced by asphyxiation for 8 minutes. Hypothermia was induced before CA. The animals were resuscitated with cardiopulmonary resuscitation, ventilation, and epinephrine administration. Brain edema was determined by brain wet-to-dry weight ratio at one hour of resuscitation. AQP4 immunoactivity in the cerebral cortex was determined using immunohistochemical staining and was semiquantified as an intensity of staining with an automated cell imaging system. RESULTS: Mild hypothermia in the sham experiments did not alter cerebral cortex AQP4 immunoactivity (mean +/- SD) (55.0 +/- 3.7 in H-Sham vs. 53.3 +/- 1.7 in N-Sham, p > 0.05). N-CA resulted in a significant increase in AQP4 immunoactivity (61.8 +/- 4.5) compared with N-Sham (p = 0.01) and H-Sham (p = 0.03). H-CA attenuated AQP4 compared with N-CA (53.4 +/- 1.3, p = 0.01). Brain wet-to-dry weight ratios were 4.41 +/- 0.07 in N-Sham, 4.40 +/- 0.08 in H-Sham (p > 0.05 vs. N-Sham), 4.55 +/- 0.04 in N-CA (p = 0.004 vs. N-Sham; p = 0.005 vs. H-Sham), and 4.43 +/- 0.09 in H-CA (p = 0.02 vs. N-CA; p > 0.05 vs. N-Sham and H-Sham). CONCLUSIONS: Cerebral cortical AQP4 expression is up-regulated after normothermic CA, which is attenuated by hypothermia induced before CA.     

Mammalian nuclear transfer.

During development, the genetic content of each cell remains, with a few exceptions, identical to that of the zygote. Differentiated cells, therefore, retain all the genetic information necessary to generate an entire organism (nuclear totipotency). Nuclear transfer (NT) was initially developed to test experimentally this concept by cloning animals from differentiated cells. It has, since then, been used to study the role of genetic and epigenetic alterations during development and disease. In this review, we highlight some of the milestones in mammalian NT reached in the 50 years after the first nuclear transplantations in frogs. We also address problems associated with mammalian nuclear transfer and provide a survey on current NT and stem cell technology. In the long term, nuclear transfer or alternative strategies aim to generate customized pluripotent cells, which would be invaluable to medical research and therapy.     

The outcome of nonoperatively treated complete tears of the anterior cruciate ligament in active young adults

The results of nonoperative treatment of 72 patients with complete anterior cruciate ligament (ACL) tears, documented by examination under anesthesia and arthroscopy, were evaluated. All patients had an acute injury with hemarthrosis in a previously normal knee. Patients having meniscal repair were excluded as were those with collateral or posterior cruciate ligament tears or associated fractures. Treatment in all cases consisted of a standard protocol of early rehabilitation and bracing. A detailed rating of symptoms and function was performed at an average of 38 months postinjury (range, eight to 84 months). Overall results were 11% excellent, 20% good, 15% fair, and 54% poor. Thirty-five percent had ACL reconstruction during the follow-up period. Results indicate that young adults who return to a vocation requiring strenuous physical activity frequently can expect unsatisfactory results after nonoperative treatment of an acute complete tear of the ACL.     

Clinical and legal issues in the management of patients with diabetes

Retinopathy is a likely complication of diabetes mellitus, and optometrists who manage patients with diabetes must be prepared to recognize the disease, educate the patient, communicate with the physician treating the disease, and follow up as appropriate to minimize the opportunity for undiagnosed complications. Liability most often results from failure to diagnose diabetic retinopathy, failure to monitor retinopathy adequately, and failure to refer or obtain consultation in a timely manner. Care for patients with diabetes should include appropriate record-keeping and documentation.     

Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

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Zusammenfassung Beim Morbus Wilson handelt es sich um eine autosomal rezessiv vererbte Störung des Kupferstoffwechsels. Der Genort konnte auf dem langen Arm des Chromosoms 13 lokalisiert werden. Klinisch können aufgrund ihrer Symptomatik drei Verlaufsformen (hepato-zerebraler, abdominalhepatischer und zerebraler Typ) unterschieden werden. Die Vielfalt der Symptome kann differentialdiagnostische Schwierigkeiten bereiten. Das Beispiel eines jungen Mannes mit einer traumatischen Hirnstammkontusion zeigt, wie die Diagnose der hepato-lentikulären Erkrankung dadurch erschwert wurde, daß die Pathogenese der Symptome durch die Hirnstammkontusion und darauf folgende Anpassungsstörungen erklärt worden war. Die Symptomatik bestand aus linksseitiger Hemiparese, lateralem Blickrichtungsnystagmus, Dysarthrie mit nachfolgendem universalem Mutismus, choreo-athetodischen Bewegungsstörungen, Torticollis spasmoidicus und blickrichtungsabhängigem Auftreten von Doppelbildern. Bei der Spaltlampenuntersuchung stellte sich der Kayser-Fleischer Ring dar. EEG- und computertomographische Untersuchungen erbrachten nur unspezifische Befunde. Die Behandlung erfolgte mit D-Penicillamin. Die alternative Behandlung mit oraler Gabe von Zinksalzen wird diskutiert.

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Résumé La maladie de Wilson est une affection héréditaire autosomale recessive concernant le métabolisme cuivré. Le locus du gène a été situé sur le bras long du chromosome 13. Du point de vue clinique on distingue trois formes symptomatologiques: le type hepato-cérébral, hepato-abdominal et cérébral. La diversité des signes cliniques peut poser des problèmes de diagnostic différentiel, car d'autres affections peuvent se présenter avec cette même Symptomatologie. Nous rapportons ici l'exemple d'un homme jeune, porteur d'une maladie de Wilson et victime d'une contusion traumatique du tronc cérébral, dont les signes cliniques ainsi que les troubles du comportement pouvaient été autant rapportés à la contusion du tronc cérébral qu'à l'affection métabolique.La Symptomatologie comprenait une hemiparesie gauche, un nystagmus lateralisé, une dysarthrie avec mutisme secondaire universel, des mouvements choréo-athétosiques, un torticolis spasmodique et une diplopie dépendante de la direction du regard. L'examen à la lampe à fente permettait à mettre en evidence un anneau de Kayser Fleischer. L'EEG et le scanner cérébral ne montraient pas d'anomalies specifique.Le traitement a consisté en l'administration de D-Penicillamine. Traitment alternative avec les sels de zinc est discuté.