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Biomedical subjects

A Josephson

Publications and source records attributed to A Josephson.

At least 19 recordsLinked to original sources
PubMed2001

NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury.

Nogo is a myelin-associated protein known to inhibit growth of neurites. In order to understand possible physiological roles of Nogo, we performed in situ hybridization using rat and human probes complementary to a Nogo-A-specific sequence and a sequence shared by all known Nogo transcripts recognizing nogo-A, -B, and -C. We studied the cellular distribution of nogo-mRNA in fetal and adult human and rat tissues, with a focus on the spinal cord and ganglia. Rat mRNA expression was also studied in a spinal cord weight-drop model and in animals exposed to kainic acid. In human fetal tissue, nogo-A was strongly expressed in the ventral two-thirds of the spinal cord, the dorsal root ganglia, and autonomic ganglia. Similarly, nogo-A mRNA expression was observed in the adult human spinal cord and ganglia. High levels of nogo-A message were observed in neurons, such as motor neurons and sensory ganglia neurons. The distribution of nogo message in rats resembled that seen in human tissues. Thus, nogo mRNA was expressed in neurons and oligodendrocytes, but not astrocytes or Schwann cells. In addition, expression of nogo-A mRNA was observed in human and rat developing muscle tissue. High level of nogo-mRNA were also expressed in the rat trigeminal ganglion and trigeminal pontine nucleus. In fetal rats the adrenal gland and cell clusters in the liver were positive for the nogo-ABC pan-probe, but negative for the nogo-A probe. While neurons in the adult rat brain were generally positive, very prominent nogo-A mRNA and nogo-ABC mRNA signals were obtained from neurons of the hippocampus, piriform cortex, the red nucleus, and the oculomotor nucleus. Nogo-A mRNA expression was markedly reduced in the epicenter of a lesion in the spinal cord of adult rats 6 and 24 h after a weight-drop injury, while no perifocal upregulation of nogo mRNA was seen. No obvious change of nogo expression was detected in kainic acid exposed animals. In conclusion our in situ hybridization study has demonstrated widespread expression of nogo mRNA in the fetal, developing and adult nervous system of rat and man. In addition to oligodendroglial cells, high levels of nogo-A mRNA expression were found in neurons, raising important questions about the function of neuronal nogo mRNA. No obvious regulation of nogo was detected following injury.

Adult↗
PubMed2001

A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

OBJECTIVE: Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. METHODS: Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. RESULTS: Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. CONCLUSION: Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Animals↗
PubMed2000

Functional MRI at 4.7 tesla of the rat brain during electric stimulation of forepaw, hindpaw, or tail in single- and multislice experiments.

Stimulation of peripheral nerves activates corresponding regions in sensorimotor cortex. We have applied functional magnetic resonance imaging (fMRI) techniques to monitor activated brain regions by means of measuring changes of blood oxygenation level-dependent contrast during electric stimulation of the forepaw, hindpaw, or tail in rats. During alpha-chloralose anesthesia, artificial respiration, and complete muscle relaxation, stimulations were delivered at 3 Hz via subcutaneous bipolar electrodes with 500-microseconds-current pulses of 0.2-2.0 mA. Single- or multislice gradient echo images were collected during recording sessions consisting of five alternating rest and stimulation periods. Stimulation of the right and left forepaws and hindpaws repeatedly led to robust activation of the contralateral sensorimotor cortex. There was a significant correlation (P < 0.05) between current pulse strength and amount of activation of the sensory cortex during forepaw stimulation. The center of the main cortical representation of the forepaw was situated 3.4 mm lateral to the midline and 5 mm posterior to the rhinal fissure. The main representation of the hindpaw was 2.0 mm lateral to the midline and 6 mm posterior to the rhinal fissure. Tail stimulation gave rise to a strikingly extended bilateral cortical activation, localized along the midline in medial parietal and frontal cortex 4 and 5 mm posterior to the rhinal fissure. In conclusion, the experiments provide evidence that peripheral nerve stimulation induces a fMRI signal in the respective division of the somatosensory cortex in a stimulus-related manner. The marked cortical activation elicited by tail stimulation underlines the key importance of the tail.

Afferent Pathways↗
PubMed2000

A characteristic serpin cleavage product of thyroxine-binding globulin appears in sepsis sera.

T4-binding globulin (TBG), the principal thyroid hormone-binding protein of serum, is a member of the serine protease inhibitor (serpin) superfamily. We report a characteristic serpin cleavage product of TBG in sepsis sera. At 49-50 kDa, the TBG remnant is 4-5 kDa smaller than the intact protein and is the same molecular mass as a TBG cleavage product produced by incubation with polymorphonuclear elastase. Incubation with polymorphonuclear leukocytes also produces the 49- to 50-kDa remnant, and this proteolysis is stimulated by zymosan activation. Polymorphonuclear cell cleavage of TBG increases the ratio of free/bound T4. As previously described, in vitro cleavage of TBG by elastase also increases free/bound T4. These findings are consistent with the hypothesis that serine proteases present at inflammatory sites cleave TBG, releasing its hormonal ligands.

Adult↗
PubMed1995

Meeting infection control standards in the OR.

Quality health care is associated with the absence of negative outcomes in patients. Institutions realize that quality cannot be assured but it can be assessed and methods can be developed to improve patient care. Many heath care institutions, therefore, have begun the conceptual transition from quality assurance model to principles of continuous quality improvement (CQI). This article describes a CQI project that was developed to enhance infection control standards in OR settings. The project involved three phases: development of a survey tool, implementation of an environmental assessment and monitoring model, and transfer of the model to OR staff members. Five months after implementation of the model, the chi-square test revealed there was a significant improvement in compliance (chi 2 = 5.0, P < .03). After 22 months of using the model, compliance to infection control standards remains high and OR staff members have taken ownership of the model by incorporating it into their departmental CQI process.

Hospitals, University↗
PubMed1993

The numbers game: sample-size determination.

Sample-size determination is a crucial component of study design. Estimates of sample size are influenced by the amount of change that must occur between study groups and the degree of risk that the investigator is willing to accept in evaluating the null hypothesis. A complete understanding of the impact of sample size on the interpretation of study data is therefore a prerequisite for quality, innovative, valid research.

Epidemiologic Factors↗
PubMed1993

Difficult parents. From adversaries to partners.

The pediatrician's job becomes frustrating when it is necessary to deal with difficult parents. Some physicians may not have the training or inclination to engage such parents in a therapeutic partnership. This paper discusses tools available to physicians which will help them develop an effective partnership that includes uncovering the hidden meaning behind a child's illness; understanding the reciprocal nature of partnerships; and the importance of determining each party's goals, roles, and expectations. Negotiating these steps enables physicians to develop a productive relationship with difficult parents of sick children. This strategy can facilitate the child's medical care and improve the parents' and physician's satisfaction with the services rendered. This paper also discusses steps to take when these attempts are not sufficient to handle the situation.

Adolescent↗
PubMed1992

A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit.

OBJECTIVE: To describe the epidemiology of a cluster of vancomycin-resistant Enterococcus faecium (VAREC) in a cardiothoracic surgery intensive care unit. DESIGN: A case series of patients identified through review of surveillance data on nosocomial infections, review of microbiologic records, and culture survey of patients in the unit. RESULTS: Six patients in the cardiothoracic surgery intensive care unit had VAREC with identical antimicrobic susceptibility patterns over a 6-month period. Four patients were identified with VAREC through prospective surveillance and 2 through retrospective review. Prior vancomycin use was seen more commonly in patients with VAREC (6/6, 100%) than in those without VAREC (3/12, 25%) (Fisher's exact test, p = .01). Six of the 7 patients with prior infection developed VAREC (85.7%). A prior nosocomial infection and prior exposure to vancomycin were found to be important variables in a logistic regression analysis. VAREC also was isolated from the environment. A combination of cohorting of patients and staff, and modifications of standard contact isolation practices eliminated the presence of VAREC from the cardiothoracic surgery intensive care unit. CONCLUSIONS: The results suggest that prior administration of vancomycin, especially in the patient who develops nosocomial infection, can influence the acquisition of vancomycin-resistant enterococci and that VAREC may be transmitted from patient to patient. Using a modification of the standard infection control practice of isolation, we were able to control the spread of this resistant strain of E faecium.

Cross Infection↗
PubMed1991

Risk-specific nosocomial infection rates.

Because nosocomial infection rates vary by hospital area and service, most infection control programs calculate area-specific rates to augment the reporting of their hospital-wide data. Rate development is often limited by the availability of appropriate specific denominator data to support important comparisons. Our university hospital reports a 20 month experience in which numerator data was collected as per the National Nosocomial Infections Surveillance System criteria for hospital-wide, high-risk nursery and ICU surveillance. These data were then combined with data in our hospital's patient-specific denominator file. This has enabled the development of risk-specific infection rates based on the analytic control of important variables available in both the numerator and denominator files. We found rate differences that were length of stay cohort specific, hospital day specific, age specific, birthweight specific, and survival cohort specific when examining our data by both the cumulative incidence and incidence density methods.

Adolescent↗
PubMed1990

Strategies for the management of varicella-susceptible healthcare workers after a known exposure.

Three different sequentially applied post-varicella zoster virus (VZV) exposure management strategies were employed over a 43-month period. We began by using a standard post-exposure protocol in which 50 susceptible healthcare workers (HCW) involved in hospital exposures were furloughed from work at a loss to the hospital of 424 workdays and $46,000. Of the eight nosocomial cases of VZV infection in HCWs, four (50%) caused future HCW and patient exposure. In trial I, we substituted a post-exposure screening procedure for the standard work furlough procedure. We screened 77 exposed staff resulting in one nosocomial VZV infection that was the source of another exposure incident. No secondary cases of varicella resulted from this exposure and only 20 days of furlough time were used during trial I. As VZV resulting from a home exposure source was responsible for most hospital exposures in which HCWs were the source, our trial II protocol added the Centers for Disease Control's (CDC) off-duty procedure, but limited its use to susceptibles exposed at home. The 43-month overall attack rate of nosocomial varicella was 4.7%, while the true home exposure attack rate was 79% (p less than .00001). There was an average of 42.4 lost workdays charged to the hospital per incident under the standard protocol and three days per incident in the combined experience of trials I and II (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chickenpox↗
PubMed1985

The relationship between intravenous fluid contamination and the frequency of tubing replacement.

Medical patients receiving IV therapy were randomly assigned to one of two IV tubing change groups. One group had a 48-hour tubing change and the other had no tubing change for the remainder of the cannula placement. A daily IV fluid specimen was processed microbiologically. To complete the study, a minimum of 3 continuous days of therapy and three fluid specimens was required. There were two contaminated specimens, one in each tubing change group. The contamination rate in the 48-hour change group was 0.87% and 0.96% in the no change group. The rate difference of 0.09% has a 95% confidence interval (-0.035 to +0.036) which includes zero. Survival analysis also revealed no significant difference in the cumulative probability of survival, however the mean duration of continuous tubing use of 4.3 days in the no change group and 1.8 days in the 48 hour change group were significantly different (p less than 0.05). The cumulative probability of surviving contamination free was 0.988 in the 48-hour group and 0.987 in the no-change group. We conclude that it is safe to change IV tubing at intervals up to but not exceeding 4 days.

Catheterization↗