The predictive value of cranial ultrasound and of somatosensory evoked potentials after nerve stimulation for adverse neurological outcome in preterm infants

Thirty-nine preterm infants were studied to compare the predictive value of somatosensory evoked responses (SEPs) following median-nerve and posterior tibial-nerve stimulation with the predictive value of cranial ultrasound. With regard to the SEP, a normal median-nerve response was by no means a guarantee of a normal outcome. A normal posterior tibial-nerve response, however, almost guaranteed a normal outcome, but the test was very time consuming and the number of false positive responses was high (sensitivity. 95.6%, specificity 50%). The presence of parenchymal involvement, either due to a haemorrhage or cystic leukomalacia predicted cerebral palsy with a sensitivity of 95.6% and a specificity of 68.5%. The combination of an abnormal posterior tibial response and the presence of parenchymal brain lesions had the best predictive value with a sensitivity of 91.3% and a specificity of 81.2%. These results show that, although posterior tibial-rferve responses have a better predictive value than median-nerve responses, these values were lower than that of cranial ultrasound. The best prediction was obtained when a combination of posterior-tibial responses and cranial ultrasound was used.     

Epidemiologic studies of low-back pain

The records of 3920 patients (2068 females, 1852 males) entering a model family practice unit between 1975 and 1978 have been analyzed. Eleven percent of males and 9.5% of females reported an episode of low-back pain during that 3-year interval. The complaint of medically reported low-back pain was significantly related to occupational factors such as truck driving (p < 0.001), lifting, carrying, pulling, pushing, and twisting (P < 0.001 for all variables) as well as nondriving vibrational exposure (P < 0.001). Patients reporting low-back pain also reported more episodes of anxiety (P < 0.001) and depression (P < 0.001) and had more emotionally stressful occupations (P < 0.001). The mean number of pregnancies was greater in women with low-back pain (2.6) than in those without (1.6) (P < 0.001). The low-back pain sufferers were more likely to be cigarette smokers (P < 0.001), particularly when smoking was accompanied by a chronic cough (P < 0.001). This population is currently under prospective study to define the relevance of each of these risk factors to the complaint of low-back pain.     

Use of real-time telemedicine in the detection of diabetic macular oedema: a pilot study

PURPOSE: The high prevalence of diabetic retinopathy (21-36%) and 2 yearly reviews recommended by the National Health and Medical Research Council for diabetics with no retinopathy creates a considerable burden for review in rural and regional Australia. Screening for diabetic retinopathy using telemedicine has significant implications. If effective, such a tool would have an impact on finance and resource allocation. The purpose of the study was to establish if telemedicine could distinguish clinically significant macular oedema (CSME) from eyes free of this form of disease. METHODS: A study population with representative examples of normal fundi and the different grades of retinopathy was chosen from existing records. The specificity and sensitivity of telemedicine diagnosis was compared with fundus photography and examination by an experienced ophthalmologist as a 'gold standard', in a blinded manner. Real-time telemedicine assessment was performed with live video and audio connections with the transmitting and receiving units set in different areas of the ophthalmology department. The transmission end consisted of a video camera mounted on a slit lamp and the receiving unit consisted of a 21' LCD monitor. A video conference link was established using three ISDN lines capable of 128 kb per second transfer per line allowing for a total of 348 kb per second when utilizing all three lines for high resolution images. Fundus photographs were taken with a Zeiss FF 450 Plus Digital imaging system. RESULTS: For telemedicine, sensitivity was 38% (95% CI, 35-40%) and specificity was 95% (95% CI, 91-99%). For photography, sensitivity was 75% (95% CI, 71-79%) and specificity was 95% (95% CI, 91-99%). CONCLUSIONS: In this pilot study, sensitivity of detection of CSME by photography was considerably better than for live-link telemedicine. This study tends to confirm the continued superiority of examination of the patient by an experienced ophthalmologist as the best method of screening for CSME, a sight threatening form of diabetic retinopathy.     

Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages

Background and purpose:

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo.

Experimental approach:

Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation.

Key results:

Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-κB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor PP2.

Conclusions and implications:

Our findings suggest a selective role for NOD1 in VSM cells, and highlight NOD1 as a potential novel therapeutic target for the treatment of vascular inflammation.     

Activation of submucosal 5-HT3 receptors elicits a somatostatin-dependent inhibition of ion secretion in rat colon

Background and purpose:

5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT₃ receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect.

Experimental approach:

Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current (I_sc) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay (elisa). Immunohistochemical techniques were used to study the expression of 5-HT₃ receptors, somatostatin and somatostatin receptors in colonic tissue.

Key results:

In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT₃ receptor antagonists enhanced 5-HT-induced increases in I_sc. However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT₃ receptor antagonists inhibited 5-HT-induced ΔI_sc. Pretreatment with a somatostatin-2 (sst₂) receptor antagonist in mucosa/submucosa preparations augmented 5-HT-induced ΔI_sc. Combination of sst₂ and 5-HT₃ receptor antagonists did not cause further enhancement of 5-HT-induced ΔI_sc. Moreover, both sst₂ and 5-HT₃ receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/submucosa preparations, an effect prevented by pretreatment with 5-HT₃ receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT₃ receptors on submucosal somatostatin neurons and of sst₂ receptors on colonic mucosa.

Conclusion and implications:

Activation of neuronal 5-HT₃ receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons.     

The extent of undiagnosed HIV infection among emergency department patients: results of a blinded seroprevalence survey and a pilot HIV testing program

This study was performed to determine the rate of previously undiagnosed HIV infection among patients presenting to an urban emergency department (ED) and to assess the feasibility of routinely offering voluntary HIV testing in this setting. HIV serostatus was determined anonymously among consecutive acute medicine and trauma ED patients (aged 18-55) who had blood drawn as part of their medical care. Excess serum was aliquoted and coded with an anonymous study code. Before performing HIV testing, the number of persons with previously reported HIV infection was determined by linkage with the state HIV/AIDS reporting registry. Concurrent with the blinded HIV serosurvey, ED patients were offered voluntary HIV testing in a pilot program. Overall, 76 of 2,155 (3.5%) adult ED patients in the blinded survey were HIV-seropositive, 15 of whom (0. 7% of those tested, 20% of those HIV-seropositive) had no infection previously reported to the state HIV/AIDS registry. In the pilot program, six of the 156 (3.8%) individuals who underwent voluntary HIV testing were HIV-seropositive, including three of 53 (5.6%) individuals without prior HIV testing. Of the six HIV-seropositive subjects, one was previously diagnosed, while five of the remaining 155 (3.2%) represented previously undiagnosed infections. Overall, 3. 5% of ED patients from whom blood was obtained for other reasons tested positive for HIV antibody, 20% of whom were previously undiagnosed. Implementation of the voluntary testing program uncovered newly diagnosed infection among 3.2% of those tested. An ED may be an important setting for routinely offering HIV testing, especially for patients who have not been previously tested for HIV.