The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons.

Injury to the adult CNS often involves death of motoneurons, resulting in the paralysis and progressive atrophy of muscle. There is no effective therapy to replace motoneurons in the CNS. Our strategy to replace neurons and to rescue denervated muscles is to transplant dissociated embryonic day 14-15 (E14-15) ventral spinal cord cells into the distal stump of a peripheral nerve near the denervated muscles. Here, we test whether long-term delivery of two pharmacological inhibitors to denervated muscle, FK506 or SB203580, enhances reinnervation of muscle from embryonic cells transplanted in the tibial nerve of adult Fischer rats. FK506, SB203580 (2.5 mg/kg) or saline was delivered under the fascia of the medial gastrocnemius muscle for 4 weeks, beginning when muscles were denervated by section of the sciatic nerve. After 1 week of nerve degeneration, one million E14-15 ventral spinal cord cells were transplanted into the distal tibial nerve stump of each rat in the three treatment groups. Ten weeks later, all cell transplants had neuron-specific nuclear protein (NeuN) positive neurons. Neuron survival and axon regeneration were similar across treatments. An average (+/-S.E.) of 210+/-66, 100+/-36 and 176+/-58 myelinated axons grew distally from the cell transplants of rats with muscles treated with FK506, SB203580 or saline, respectively. Regenerating axons in muscles of all three treatments groups were detected with antibodies against phosphorylated neurofilaments and synaptophysin, and motor end plates were labeled with alpha-bungarotoxin. Muscles of rats that received transplants of media only had no axon growth, indicating that the muscles were denervated. The mean muscle fiber areas of rats that received cell transplants and had long-term delivery of FK506, SB203580 or saline to muscles were significantly larger than those of denervated muscle fibers. Thus, cell transplantation reduced muscle atrophy. Transplantation of embryonic cells also resulted in functional muscle reinnervation. Electromyographic activity and force were evoked from >90% of the muscles of rats with cell transplants, but not from denervated muscles. FK506-treated muscles were significantly more fatigue resistant than naive control muscles. FK506-treated muscles also had significantly stronger motor units than those in SB203580 or saline-treated muscles. These data suggest that a pathway regulated by FK506 improves the function of muscles reinnervated by embryonic neurons placed in peripheral nerve.

Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans.

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.

Primary amoebic meningoencephalitis with Naegleria fowleri: clinical review.

Two children with primary amoebic meningoencephalitis secondary to Naegleria fowleri are reported. Both children died, and the causative agent was identified at autopsy. Presentation and outcome conformed to the usual course of primary amoebic meningoencephalitis and reaffirm the gravity and rapid progression of this infection. The epidemiology, microbiology, diagnostic considerations, and treatment are discussed. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of children with meningitis or encephalitis.

Haemophilus influenzae meningitis with prolonged hospital course.

A retrospective evaluation of Haemophilus influenzae type b meningitis observed over a 2-year period documented 86 cases. Eight of these patients demonstrated an unusual clinical course characterized by persistent fever (duration: greater than 10 days), cerebrospinal fluid pleocytosis, profound meningeal enhancement on computed tomography, significant morbidity, and a prolonged hospital course. The mean age of these 8 patients was 6 months, in contrast to a mean age of 14 months for the entire group. Two patients had clinical evidence of relapse. Four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days. All patients received antimicrobial therapy until they were afebrile for a minimum of 5 days. Subsequent neurologic examination revealed a persistent seizure disorder in 5 patients (62.5%), moderate-to-profound hearing loss in 2 (25%), mild ataxia in 1 (12.5%), and developmental delay with hydrocephalus which required shunting in 1 (12.5%). One patient had no sequelae.

Gastrointestinal microecology in the critically ill neonate.

The fecal and gastric microflora of 178 critically ill neonates was compared with that of 30 normal full-term infants. Significant findings included increased frequency of single species retrieval and decreased frequency of mixed aerobic-anaerobic fecal cultures in the ill infants. Also noted were increased retrieval of pathogenic organisms, ie, staphylococcus aureus from gastric and fecal cultures of the ill infants, and decreased retrieval rates of Escherichia coli enterococcus, B fragilis, and other anaerobes in the feces of this group. Yeast retrieval was increased in the feces of the ill neonates. Statistical analysis showed that delivery route, birth weight, and antibiotic therapy were significantly related to the retrieval rates of certain organisms in the gastric and fecal flora of the ill neonate. Given the breast-fed and formula-fed infants have different normal floral patterns, this study suggests that the flora of the ill neonate conforms to a different pattern. Implications in the prevention and treatment of various neonatal septic processes may be drawn from this data.

Degree of pathology as related to readiness to accept labels in process and reactive schizophrenics.

Two experiments were performed in order to determine whether readiness to accept deviant labels, as measured by acquiescence set, interacts with type of schizophrenia (process vs. reactive) to influence level of pathology. It was found on both a behavioral measure and a psychometric measure of psychopathology that high acquiescent process schizophrenics manifested more pathology than did either low acquiescent process or reactive schizophrenics, both of whom showed more pathology than high acquiescent reactive schizophrenics. The results suggest that one's acceptance of deviant labels as well as one's past history of being assigned social and evaluative labels may influence the patient's level of pathology. Scheff (1966), in viewing the mental patient from a sociological perspective, suggests that an important determinant of mental disorder is the acceptance by the deviant individual of the various labels which stigmatize him as mentally ill. If this is the case, then individual differences in readiness to accept or agree with labels about oneself may be related to the degree of pathology manifested in a psychiatric population. The present authors sought to determine if acquiescence set, as measured by the Agreement Response Scale (Couch & Keniston, 1960), is related to degree of pathology in schizophrenic patients. The Agreement Response Scale was used as a measure of the general tendency to acquiesce to or agree with personality statements or labels. The investigators performed two experiments, in Experiment 1 a behavioral measure of pathology was used and in Experiment 2 a psychometric measure of pathology was used. In addition, the schizophrenic Ss were grouped according to the process-reactive distinction as the reactive schizophrenic may be expected to have a more favorable history of labeling than would the process schizophrenic.