IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life

We have tested the role of glial cell line-derived neurotrophic factor (GDNF) in regulating a group of putatively nociceptive dorsal root ganglion (DRG) neurons that do not express calcitonin gene-related peptide (CGRP) and that downregulate the nerve growth factor (NGF) receptor tyrosine kinase, TrkA, after birth. We show that mRNA and protein for the GDNF receptor tyrosine kinase, Ret, are expressed in the DRG in patterns that differ markedly from those of any of the neurotrophin receptors. Most strikingly, a population of small neurons initiates expression of Ret between embryonic day 15.5 and postnatal day 7.5 and maintains Ret expression into adulthood. These Ret-expressing small neurons are selectively labeled by the lectin IB4 and project to lamina IIi of the dorsal horn. Ret-expressing neurons also express the glycosyl-phosphatidyl inositol-linked (GPI-linked) GDNF binding component GDNFR-alpha and retrogradely transport 125I-GDNF, indicating the presence of a biologically active GDNF receptor complex. In vitro, GDNF supports the survival of small neurons that express Ret and bind IB4 while failing to support the survival of neurons expressing TrkA and CGRP. Together, our findings suggest that IB4-binding neurons switch from dependence on NGF in embryonic life to dependence on GDNF in postnatal life and are likely regulated by GDNF in maturity.     

Video game-related seizures: a report on 10 patients and a review of the literature

OBJECTIVE: To further describe the features, postulated pathophysiology, treatment, and outcome of seizures occurring while playing or watching video games (video game-related seizures (VGRS)). DESIGN: We evaluated retrospectively 10 patients with VGRS seen by us and reviewed 25 reported cases. RESULTS: The 35 patients ranged in age from 1 to 36 years (mean: 13.2); and 26 subjects (74%) were male. Eight individuals (29%) had prior infrequent nonfebrile seizures, 4 (11%) had febrile convulsions, and 2 (6%) had a family history of epilepsy. VGRS consisted of generalized tonic-clonic seizures in 22 of 35 individuals (63%); absences in 2 (6%); simple partial seizures in 6 (19%); complex partial seizures in 4 (11%); and other manifestations in 4. Neurologic examination and computed tomographic and magnetic resonance imaging scans were normal. Electroencephalograms demonstrated generalized or focal, interictal or ictal epileptic patterns in 11 of 21 patients (52%) and photoparoxysmal responses in 17 of 32 (53%). Eleven of 15 individuals (73%) treated with video game (VG) abstinence alone, 3 of 6 who received anticonvulsants but played VGs, and 7 of 12 treated with combined VG abstinence and anticonvulsants had no further seizures. CONCLUSIONS: We postulate that a special convulsive susceptibility of selected neurons in striate, peristriate, infratemporal, and posterior parietal cortices to particular visual stimuli plays a major role in VGRS. VG abstinence is the treatment of choice of VGRS. Anticonvulsant medication is suggested only for those individuals who continue to play VGs or suffer from seizures triggered by other, unavoidable visual stimuli, or from unprovoked attacks.     

The SPINRPHEX club

A 3-year-old Japanese domestic cat with a diagnosis of lymphocytic leukemia showed severe generalized seizures in the course of chemotherapy after leukemic condition was improved clinically. Computed tomography (CT) and magnetic resonance (MR) imaging of the brain were carried out. Both contrast procedures disclosed enhancements at the falx cerebri and the margin of cerebral cortex. Among these procedures contrast MR imaging demonstrated the lesion most clearly. Cytological examination of cerebrospinal fluid obtained by spinal puncture showed the infiltration of malignant cells and the diagnosis of meningeal syndrome associated with lymphocytic leukemia was defined. Intrathecal administration of cytosine arabinoside partially improved the neurologic dysfunction. Autopsy and histopathological examination confirmed the infiltration of leukemic cells in the areas of meningeal lesion demonstrated with contrast CT and MR imaging. Thus these imaging techniques, especially contrast MR imaging, are useful tools for rapid and precise diagnosis of meningeal syndrome.     

Leptospirosis in an urban setting: case report and review of an emerging infectious disease

Leptospiosis is a common zoonosis affecting most mammals. Leptospirosis has protean manifestations ranging from a flu-like illness to fulminant hepatic and renal failure culminating in death. Although the diagnosis is often not considered upon presentation, the literature suggests that leptospirosis is a reemerging infectious disease in urban centers throughout the industrialized world. It will be incumbent upon Emergency Physicians to include this spirochetal disease in the differential diagnosis of febrile patients with appropriate risk factors and symptomatology. We present the case of a 36 year-old woman who presented to the Emergency Department with fever and hypotension. We review the literature on leptospirosis with specific focus on risk factors and pathogenesis, clinical manifestations, diagnosis, treatment, and outcome.     

Solo versus group practice in the medical profession: the influence of malpractice risk

While Partnerships are a significant form of business organization in many sectors of the economy, relatively little is known about the incentives which lead to their formation. This paper explores the formation of partnerships among office based physicians when facing some risk of malpractice litigation. Theoretical results indicate that malpractice exposure can increase the incentives to shirk within a partnership, and so exert a significant influence on the decision to form a partnership. Empirical results find that malpractice risk has the expected negative effect on some partnership formation.     

Echocardiographic and biochemical evaluation of the development and progression of carcinoid heart disease

OBJECTIVES: To study the applicability of a newly developed echocardiographic scoring system in the assessment of carcinoid valvular heart disease. BACKGROUND: We investigated prospectively the development, progression and regression of carcinoid valvular heart disease in patients with carcinoid syndrome by serial echocardiography, correlating these features with urinary 5-HIAA levels and clinical data collected during therapy with somatostatin analog. METHODS: Twenty-three patients with carcinoid syndrome underwent serial echocardiographic examinations. An echocardiographic carcinoid valvular heart disease (CVHD) % score was determined from points assigned for tricuspid and pulmonary valve structure and function. RESULTS: Fifteen patients had no CVHD at study entry (group 1), while 8 patients had findings of CVHD (group 2). Five patients in group q developed new CVHD (1B), while one demonstrated progression of CVHD (2B). The remaining patients did not develop (1A) or had no progression of CVHD (2B). Despite major declines in 5-HIAA levels during therapy in most patients, CVHD did not regress. There were significantly lower levels of median baseline 5-HIAA (98.8 vs. 256 mg/24 h), posttreatment 5-HIAA (50.3 vs. 324 mg/24 h) and posttreatment 5-HIAA time integral (37.3 vs. 192 g/24 h* days) in group A vs. B (p < 0.05). However, only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD by multiple step-wise regression analysis (p < 0.005), with a threshold observed in the 100 mg/24 h range. CONCLUSIONS: We designed a new echocardiographic scoring system to evaluate CVHD. Correlating echocardiographic scores with biochemical and clinical markers showed that only posttreatment 5-HIAA levels independently predicted the development or progression of CVHD. This study strengthens the association between serotonin secretion and CVHD, as well as introducing a new technique for serial follow-up of these patients.     

A survey of 251 patients with acute syphilis treated in the collaborative penicillin study of 1943-1950

The dramatic and apparently curative effect of penicillin for the treatment of acute syphilis led to follow-up studies for only comparatively brief periods, and the acceptance of the long-term benefit of penicillin has rested on uncontrolled clinical impressions. More certainty about the efficacy of penicillin was sought by a follow-up review of 251 patients treated between March 1944 and December 1950 under the Penicillin Study of the Office of Scientific Research and Development (OSRD) and continued under U. S. Public Health Service after World War II. Eighty-eight patients were interviewed and examined. Telephone conversation or correspondence was had with 43 subjects; an additional nine are known to be living but did not respond to letters. Thirty-two patients died greater than or equal to 20 years after treatment, and 21 patients died within less than 20 years of treatment. Fifty-eight patients could not be found. Treatment failures were documented. Syphilis was not shown to be the cause of disability or death, except for a patient with meningovascular syphilis who died soon after initial treatment. Disabilities recorded and deaths documented revealed only diseases common to any middle-aged population. The outcomes of 17 pregnancies of women treated for acute syphilis were documented. Blood samples obtained from the 88 subjects examined were tested at the Center for Disease Control (Atlanta, Ga.); the results are recorded and discussed. Methods for locating the patients are described, and the psychosocial findings for the 88 patients interviewed are presented. The study has confirmed the clinical impressions of the therapeutic effectiveness of penicillin, which have been accepted for greater than 30 years.     

Expression of the L8 lipopolysaccharide determinant increases the sensitivity of Neisseria meningitidis to serum bactericidal activity

The influence of lipopolysaccharide (LPS) expression on the sensitivity of Neisseria meningitidis to serum bactericidal activity was investigated by using a series of variants that expressed different LPS determinants. For each of two different strains, a series of three LPS variants that expressed L3,7, L8, or both were analyzed. LPS variants were identified and monitored by colony blotting with murine monoclonal antibodies specific for the L8 or the L3,7,9 immunotype determinants. Differences in LPS expression were verified by analysis of proteinase K lysates of whole cells by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then by silver staining or immunoblotting. The variants were used as test strains in bactericidal assays with human sera and with murine sera and monoclonal antibodies. Expression of the L8 LPS epitope was correlated with increased sensitivity to serum bactericidal activity. The geometric mean bactericidal titers of 12 to 16 sets of pre- and postvaccination sera were determined for each variant. Mean serum titers increased progressively with increased expression of L8 on the target strain. The bactericidal titers of anti-outer membrane protein monoclonal antibodies also increased with increased L8 expression.