Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat

Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known. Using in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin-3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Quantitative analysis showed that the levels of mRNAs for NT3 and NGF increased in ipsilateral but not contralateral DRG after nerve injury. Noradrenergic sprouting around the axotomized neurons was associated with p75-immunoreactive satellite cells. Further, antibodies specific to NGF or NT3, delivered by an osmotic mini-pump to the DRG via the lesioned L5 spinal nerve, significantly reduced noradrenergic sprouting. These results implicate satellite cell-derived neurotrophins in the induction of sympathetic sprouting following peripheral nerve injury.     

Potential preventive strategies and therapies in urinary tract infection

There are perhaps five strategies either presently advocated or under investigation for prevention of recurrent urinary tract infection (UTI): antibiotics, including natural peptides; functional foods; vaccines; probiotics; and miscellaneous, including avoidance of spermicides and maintenance of good hygiene. It is not possible to state the proportion of patients using antibiotics versus foods such as cranberry or using alternative approaches such as avoidance of spermicides. The majority of women who are referred to specialists will be prescribed long-term, low-dose antibiotics. However, given the magnitude of the problem, it is safe to state that large numbers of women are at least experimenting with alternative remedies such as drinking of cranberry juice or ingestion of herbal remedies with a view to enhancing their immune response. Vaccine development remains a long way from human use and has yet to be developed for organisms other than Escherichia coli. The use of probiotics to restore the normal vaginal flora and provide a competitive bacterial barrier to pathogens is close to becoming available as an alternative preventive approach. The next decade should see the introduction of new methods for reduction of the high incidence of UTI and better management of recurring urogenital infections.     

Differential diagnosis of anterior segment cysts by ultrasound biomicroscopy

BACKGROUND: To describe the ultrasound biomicroscopic (UBM) features of anterior segment cysts. DESIGN: A retrospective case series. PARTICIPANTS: One hundred eighteen eyes with anterior segment cysts examined by UBM at The New York Eye and Ear Infirmary between August 1992 and November 1997 were included in this study. INTERVENTION: The authors reviewed demographic and diagnostic data from the medical record including ocular and medical history, age, race, gender, and intraocular pressure. Ultrasound data concerning the type, number, position, and acoustic characteristics of cysts were recorded. The authors then correlated the written, clinical, and UBM characteristics. RESULTS: One hundred eyes (92.6%) had neuroepithelial cysts. Ninety (83.3%) of these had primary neuroepithelial cysts, 10 (9.3%) had cysts associated with uveitis, 7 (6.5%) had implantation cysts, and 1 (0.9%) had a cavitated ciliary body tumor. Neuroepithelial cysts typically were round or ovoid, thin-walled, and echolucent. Of the 90 eyes with primary neuroepithelial cysts, 56 (62.2%) had 3 or fewer cysts; multiple cysts (>3 per eye) were found in 34 eyes (37.8%). The multiple cysts occupied more than 180 degrees in 12 patients (13.3%). Primary neuroepithelial cysts were located at the iridociliary junction (74.2%), pars plicata (14.0%), pars plana (6.8%), and iris (5.0%). Implantation cysts (seven eyes) tended to have thicker walls and two contained a copious, echogenic material. CONCLUSION: The UBM results provide important information regarding location and extent of anterior segment cystic lesions. Ultrasound characteristics may help differentiate between neuroepithelial, implantation, and neoplastic cysts.     

Pertussis toxin does not affect the adenosine-induced inhibition of the efferent function of cardiac capsaicin-sensitive nerves

Summary The negative inotropic effect of adenosine (1–100 M) was abolished in isolated guinea-pig atria obtained from pertussis toxin-pretreated guinea pigs electrically driven at 4 Hz. However, the inhibitory effect of the same concentrations of adenosine on the cardiac response to stimulation of non-adrenergic non-cholinergic (NANC), capsaicin-sensitive sensory nerves, was not modified by the toxin.These results suggest that, while pertussis toxin-sensitive G proteins are involved in the negative inotropic effect of adenosine, they do not mediate the inhibitory effect of adenosine on cardiac NANC neurotransmission.     

Renal nerve and blood pressure responses to stimulation of cardiac receptors in dogs and cats by bradykinin

Summary It has been recently demonstrated in anesthetized, sinoaortic denervated-vagotomized (SAD+V_x) cats that epicardial or intracoronary (IC) bradykinin (BK) evokes an increase in efferent renal nerve activity (RNA) and a pressor response which is mediated by the cardiac sympathetic afferent nerves. The purpose of this study was to compare the effect of epicardial, IC, and left atrial (LA) administration of BK on arterial blood pressure (ABP) and RNA in intact and SAD+V_x cats and dogs. A total of seven cats and eight dogs anesthetized with chloralose were prepared with a left circumflex coronary arterial catheter (dogs) or a LA catheter (cats). Changes in ABP and RNA were determined in both dogs and cats when 1 to 100 g/ml of BK was applied to the anterior surface of the left ventricle or injected IC or LA (0.3 and 3.0 g/kg BK) in the intact and SAD+V_x state. In both the intact and SAD +V_x cat, a pressor response was consistently elicited with epicardial BK. In the SAD+V_x state, epicardial BK increased ABP by 33.4±4.7 mm Hg (p<.001). RNA followed this same trend showing a consistent and significant increase with both LA and epicardial BK (+24.8±8.4% in the SAD+V_x state; P<.05). Changes in RNA in dogs were highly variable with epicardial and IC BK in intact and in SAD V_x dogs, resulting in insignificant changes in this parameter. The results of this study demonstrate that the reflex effects of stimulation of cardiac sympathetic afferents by BK are species specific and need not evoke an increase in peripheral sympathetic outflow.Supported by National Institutes of Health Gran #HL-22594 and American Heart Association Grant # 81672.     

Neutropenia, fever, and infection

With the advances in the management of various neoplastic diseases and subsequent improvement in "disease-free" states, complications of therapy--particularly, infectious complications--have evolved as stumbling blocks to survival. Among neutropenic (absolute neutrophil count below 1,000/mm3) patients with cancer, infection is the major autopsy-determined cause of death. With expected "cure rates" of childhood leukemia approaching 60 to 70 percent, it seems unreasonable to lose such patients to an infectious cause of death, yet this, indeed, happens. The purpose of this review is to (1) define the magnitude of the problem; (2) describe the various agents responsible for infections in neutropenic patients; (3) attempt to more sharply define degrees of neutropenia and mechanical defenses; and (4) consider various approaches to studying and treating these infections.     

Hemispherectomy — 25 years later — findings and concepts

Summary In the first part the case of a then 27 year old female patient with right-sided infantile spastic hemiplegia after left-sided porencephaly is described, in whom hemispherectomy was performed 25 years ago. The postoperative state and the development are described as well as the social outcome and the present neurological status. A computer-tomogram shows the actual state of the brain.The second part is devoted to a scientific discussion of the supplementary motility after pyramidal lesions which is defined as the action of descending subcortico-spinal pathways starting probably in the mesencephalon, whereas an ipsilateral pathway is unlikely. Comparative neurological experiments serve to support such a concept as well as similar observations in traumatic cerebral lesions in man. In the light of the far more skilled motility in cerebral lesions of the young as well as the possibility of a shift of neuropsychological functions of the dominant to the contralateral hemisphere in children up to the age of 8–10 the possibility is discussed that plasticity — the concept of Albert Bethe — could form the mechanism of auxiliary function.Furthermore the surprising sensory performances in some of the patients with hemispherectomy are emphasized and the possibilities of anipsilateral substratum are discussed; however, this contrasts with the concepts formulated for the auxiliary motility after pyramidal lesions. Clarification of these problems will probably follow only after further experimental work.

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Zusammenfassung Im ersten Teil der Arbeit wird der Fall einer damals 27-jährigen Patientin beschrieben, die eine rechtsseitige infantile spastische Hemiplegie nach linksseitiger Porencephalie hatte. Bei ihr war 25 Jahre zuvor eine Hemisphärektomie durchgeführt worden. Der postoperative klinische Status und die Entwicklung der Syndrome wird beschrieben und über die soziale Situation berichtet. Schließlich wird der derzeitige neurologische Status genau wiedergegeben. Erstmalig zeigt ein Computer-Tomogramm den Zustand des Hirns nach diesem Zeitraum.Im zweiten Teil der Arbeit wird die Entstehung der Ersatz-Motilität diskutiert, die als eine Aktion deszendierender subkortiko-spinaler Bahnen definiert wird, die wahrscheinlich vom Mittelhirn ihren Ausgang nehmen, während die Tätigkeit ipsilateraler Systeme für unwahrscheinlich gehalten wird. Vergleichende Tierexperimente am Hirn unterstützen eine solche Auffassung, ebenso wie auch die Beobachtung bei umschriebenen Hirnverletzungen des Menschen.Dann wird die Möglichkeit von Ersatzfunktionen durch Plastizität diskutiert — ein Begriff von Albert Bethe. Dies erscheint im Lichte vieler Beobachtungen wichtig, da die Ersatz-Motilität bei Hirnläsionen junger Menschen sehr viel höhere Geschicklichkeit ermöglicht als bei Läsionen von Älteren; weiter ist zu beachten, daß neuropsychologische Funktionen bei einer Hirnläsion vor dem 8. bis 10. Lebensjahr von einer dominanten Hemisphäre noch auf die andere Seite verlegt und dort lokalisiert werden können. Schließlich wird bei diesen Patienten auf die erstaunlichen Fähigkeiten der sensiblen Systeme nach Hemisphärektomie hingewiesen und hier die Möglichkeit eines ipsilateralen anatomischen Apparates diskutiert. Jedoch können bei der Sensibilität so genaue funktionell-morphologische Vorstellungen noch nicht formuliert werden, wie sie sich z. Zt. schon für die Ersatz-Motilität nach Pyramidenbahnläsion ergeben. Erst genauere Experimente im Tierversuch können weitere Aufklärung bringen.

     

Effect of low-dose phenobarbital on hepatic microsomal UDP-glucuronyl transferase activity

To determine whether hepatic microsomal enzyme induction occurs in rats following administration of phenobarbital at doses similar to those used in humans (0.5 to 7.5 mg/kg), UDP-glucuronyl transferase (UDPGT) and cytochrome P-450 activities were measured in liver homogenate and microsomal preparations from control rats and rats treated for 6 days with phenobarbital at 1 and 3 mg per kg per day. While no significant increases in liver weight and protein content of homogenate and microsomal preparations were observed with either dose of the drug, both UDPGT and P-450 activities were enhanced significantly following administration of phenobarbital at 3 mg per kg per day. The activity of P-450 was increased by approximately 30% and that of UDPGT by 15-24 and 45-66%, respectively, employing bilirubin and p-nitrophenol as the acceptor substrate. The extent of induction of bilirubin or p-nitrophenol UDPGT was similar when measured with "native" enzyme or with enzyme activated by UDP-N-acetyl glucosamine, digitonin or deoxycholate. These data suggest that the discordant effects of phenobarbital on UDPGT and cytochrome P-450 previously reported in humans and rats may not be attributable solely to differences in the drug doses employed.     

A reevaluation of the functional organization and cytoarchitecture of the feline lateral posterior complex, with observations on adjoining cell groups

The organization of the cat's lateral posterior complex was reevaluated and its cytoarchitecture described. Analysis of visual representations within the complex confirmed that the pulvinar, lateral zone (LPL), and interjacent zone (LPi) correspond to separate representations of the visual field and established that the zones exhibit heterogeneous connections as a result of retinotopic interconnections with extrastriate areas which represent varying amounts of the visual field. A common system of visual representation extending through layers with differing anatomical connections was identified within zone LPL. The concept of an "isorepresentation cord" was introduced to describe these variable correspondences between sensory representations and connectional relationships. Isorepresentation cords are conceived as holding in common representation of a common locus on a sensory surface without functioning as a unit with respect to connections. Visual representations within the lateral posterior complex consist of many such cords arranged in orderly array. Zone LPm (medial) was also delineated more accurately on the basis of its connections with the ectosylvian visual area. Analysis of termination patterns which occupy boundary regions adjacent to and between the principal zones further established the existence of a collection of cell groups which form a thin, irregular shell investing the principal zones. The identification of these additional cell groups and the recognition of connectional heterogeneity within the principal zones of the complex made it possible to identify and describe the subtle cytoarchitectural differences which characterize the subdivisions of the lateral posterior complex and their boundaries with adjoining nuclear groups. The present findings are discussed with respect to the functions of the lateral posterior complex in interconnecting cortical visual and visuomotor areas, and with respect to the conceptual issues raised by variable correspondences between sensory representations and connectional relationships within thalamus.     

Focal segmental membranous glomerulonephropathy associated with other glomerular diseases

In four patients with the nephrotic syndrome, renal biopsy revealed focal segmental membranous glomerulonephropathy (FSMGN) associated with the histologic patterns of "nil" disease (two cases), hereditary nephritis and diffuse diabetic glomerulosclerosis. The occurrence of FSMGN in association with other glomerular diseases, presumably unrelated to immune complex deposition, is infrequent in our experience. Rather than necessarily representing an early stage or milder form of membranous glomerulonephropathy, it may be an epiphenomenon. This interpretation has prognostic and therapeutic implications and raises important pathogenetic questions. In particular, this study suggests that in some instances, preexisting functional and structural abnormalities may play a role either in the deposition of preformed circulating immune complexes or in the local formation of immune complexes.