Use of sophisticated intra-operative monitoring in resuscitation of unexpected cardiovascular collapse during general anaesthesia.

INTRODUCTION: The diagnosis of intraoperative anaphylaxis is important but can be difficult as the symptoms can be varying and dependent on patient factors. PRESENTATION OF CASE: We describe an acute, unexpected and life threatening cardiovascular (CV) collapse, presumed to be due to an acute anaphylactic reaction secondary to gelatin administration, following induction of general anaesthesia (GA), in an ASA 3 patient scheduled for axillo-bifemoral bypass. DISCUSSION: The management of the profound cardiovascular (CV) collapse was greatly assisted by sophisticated haemodynamic, depth of anaesthesia and cerebral oximetry monitoring.(1) As far as we are aware this is the first such case where the full haemodynamic, depth of anaesthesia and cerebral oxygenation changes during CV collapse, presumed due to an acute anaphylactic reaction under GA have been fully documented. CONCLUSION: The use of advanced monitoring intraoperatively proved extremely useful in guiding the resuscitation of a life threatening allergic reaction under general anaesthesia.

Advancing environmental toxicology through chemical dosimetry: external exposures versus tissue residues.

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions.

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial.

BACKGROUND: Relationships between plasma morphine concentrations and neonatal responses to endotracheal tube (ETT) suctioning are unknown in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned to placebo (n=449) or morphine (n=449). After an i.v. loading dose (100 microg kg(-1)), morphine infusions [23-26 weeks postmenstrual age (PMA) 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); and 30-32 weeks 30 microg kg(-1) h(-1)] were established for a maximum of 14 days. Open-label morphine (20-100 microg kg(-1)) was given for pain or agitation. Morphine assay and neonatal response to ETT suctioning was measured at 20-28 and 70-76 h after starting the drug infusion and at 10-14 h after discontinuation of the study drug. The concentration-effect response was investigated using non-linear mixed effects models. RESULTS: A total of 5119 data points (1598 measured morphine concentrations and 3521 effect measures) were available from 875 neonates for analysis. Clearance was 50% that of the mature value at 54.2 weeks PMA (CLmat(50)) and increased from 2.05 litre h(-1) 70 kg(-1) at 24 weeks PMA to 6.04 litre h(-1) 70 kg(-1) at 32 weeks PMA. The volume of distribution in preterm neonates was 190 litre 70 kg(-1) (CV 51%) and did not change with age. There was no relationship between morphine concentrations (range 0-440 microg litre(-1)) and heart rate changes associated with ETT suctioning or with the Premature Infant Pain Profile. CONCLUSIONS: A sigmoid curve describing maturation of morphine clearance is moved to the right in preterm neonates and volume of distribution is increased compared with term neonates. Morphine does not alter the neonatal response to ETT suctioning.

Is Parkinson's disease a primary olfactory disorder?

It has been known for over 30 years that olfactory function is disordered in idiopathic Parkinson's disease (IPD). The severity and partial specificity of anosmia was not realized until recently, with the advent of more detailed analysis and sophisticated measurement. The olfactory vector hypothesis suggests that the causative agent for IPD enters the brain via the nasal route, but the reason for olfactory dysfunction may be more subtle. Evidence for olfactory disturbance is reviewed from pathological, psychological, neurophysiological and genetic stand-points. It is proposed that the initial causative event in IPD may start in the rhinencephalon (olfactory brain) prior to damage in the basal ganglia.

Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization.

OBJECTIVE: The goals were to summarize the results of liver transplantation for chronic hepatitis B disease (HBV) at the University of Virginia, correlate pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBIg) requirements, and identify the relation between viral protein in the liver and clinical reinfection. SUMMARY BACKGROUND DATA: Liver transplantation is an accepted treatment for end-stage liver disease from chronic HBV infection, although lifelong antiviral treatment (with HBIg or antiviral agents) is still necessary. Patients with evidence of active viral replication (detectable serum HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft infection. Whether clinically stable patients receiving HBIg immunoprophylaxis have detectable viral products in their grafts remains unknown. METHODS: Forty-four transplants performed for HBV disease at the University of Virginia since March 1990 were reviewed. Most patients underwent aggressive passive immunoprophylaxis with HBIg to maintain serum HBV surface antibody (HBsAb) levels > or =500 IU/l for the first 6 months after the transplant, and > or =150 IU/l thereafter. Patients had viral markers quantified, underwent pharmacokinetic analysis of HBsAb levels to adjust dosing, and were biopsied routinely every 3 to 6 months and when indicated. RESULTS: Forty-four transplants were performed in 39 patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively, and 1-year and 3-year patient survival was 98% and 96%, respectively. After the adoption of indefinite HBIg prophylaxis, nine grafts became infected (all in recipients positive for HBV e antigen). Three occurred within 8 weeks of transplantation and were associated with a short HBsAb half-life and a wild-type virus. Six occurred >8 months after the transplant, and most of these were associated with viral mutation. Quantification of pretransplant markers was an overall poor predictor of HBIg requirements after the transplant. Immunohistochemistry demonstrated transient low-level expression of core protein in the liver in 23% of patients without serum or clinical evidence of recurrent hepatitis. CONCLUSIONS: An excellent outcome is possible after liver transplantation for chronic HBV disease using HBIg dosed by pharmacokinetic parameters. Currently, quantification of pretransplant serum markers of the HBV antigen load does not predict the intensity of posttransplant treatment required for good clinical outcomes. Because HBV is not eradicated from the patient, some form of indefinite antiviral therapy continues to be warranted.

Olfactory disorder in motor neuron disease.

In Parkinson's disease and Alzheimer's disease there is profound disorder of olfaction. The extent to which this modality is involved in motor neuron disease (MND) has been studied little. To address this further we assessed olfaction by three methods-a smell identification test ("UPSIT") in 58 patients and 135 controls; olfactory-evoked response (OEP) to H2S in 15 patients, and pathological examination of olfactory bulbs obtained from 8 cadavers. It was found that smell identification compared with the controls was slightly worse overall in the MND group as a whole, but only the bulbar patients scored significantly less on the UPSIT. Patients displayed a subtle defect in cheese odor recognition. OEPs were normal in 9 subjects and delayed in 1 subject. The remaining 5 OEPs were unsuccessful. Histopathological studies of olfactory bulbs showed excess lipofuscin deposition in all 8 cases examined, indicating subclinical neuronal damage. Olfactory neurons with a degree of antioxidant defect may be more susceptible to cellular damage than other neuronal groups because of their direct relationship to environmental agents. Overall we found the degree of olfactory dysfunction in MND to be mild and in contrast with the marked changes described by others.

Olfactory evoked responses and identification tests in neurological disease.

UNLABELLED: To assess the value of smell testing we used olfactory evoked potentials (OEP) and an identification test in multiple sclerosis, Parkinson's disease, motor neuron disease and Alzheimer's disease. METHODS: The OEP to H2S (20 ppm) was obtained using an olfactometer designed to stimulate olfactory nerve endings only. Odor recognition was assessed by the University of Pennsylvania Smell Identification Test (UPSIT). In all instances the disease was 'definite' based on standard diagnostic criteria. Controls were derived from 156 healthy people. RESULTS: 1) Multiple Sclerosis: 11/72 patients (15%) were abnormal on UPSIT. For OEP there was significant increase of latency and decrease in amplitude in 6/26 patients (23%). 2) Parkinson's Disease: 126/155 (81%) patients had an abnormal UPSIT score. 12/37 (32%) had prolonged latency with normal amplitude measurement on OEP, but 27 had absent or unclear readings. 4/10 with normal UPSIT displayed abnormality on OEP. 3) Motor Neuron Disease: 9/58 (16%) were abnormal on UPSIT. There was significant delay in 1/10 (10%) patients on OEP. 4) Alzheimer's Disease: UPSIT scores were abnormal in all 8 patients examined. OEP was normal in 4 of these who could be tested. CONCLUSION: Smell dysfunction was found in all 4 conditions but most severely in Parkinson's Disease (over 80%). The UPSIT in general showed abnormality more frequently than OEP. The olfactory defect probably involves peripheral structures in all diseases tested except Alzheimer's. A patient with normal olfaction is unlikely to have idiopathic Parkinson's disease.

Assessment of olfaction in multiple sclerosis: evidence of dysfunction by olfactory evoked response and identification tests.

OBJECTIVE: To resolve whether the olfactory pathways are affected in multiple sclerosis. METHODS: Olfaction was assessed by: (1) The University of Pennsylvania smell identification test (UPSIT, which uses microencapsulated odours that are released when scratched with a pencil) in 72 patients with multiple sclerosis and 96 controls, (2) olfactory evoked potentials (OEP) to 20 ppm H2S by volume, and 50% CO2 in air for 45 patients with multiple sclerosis and 47 controls. The abnormality rate in patients with multiple sclerosis for both tests (1) and (2) was compared with that for visual evoked potentials measured using a standard checquerboard technique. RESULTS: By comparison with controls, patients exhibited significantly low scores on the smell identification test with 15% of patients scoring outside the 95% confidence intervals for controls. The UPSIT was occasionally abnormal when the visual evoked potential (VEP) was normal. In general UPSIT scores correlated well with the H2S-evoked response in controls and patients. For H2S, there was a statistically significant increase of latency and decrease of amplitude for patients compared with controls. Increased H2S latency and reduced UPSIT score correlated with greater disability on conventional rating scales. Overall, H2S responses were abnormal in about one quarter of patients with multiple sclerosis. The sensitivity of UPSIT and OEP was similar although disorder on one test did not necessarily indicate abnormality in the other. The visual evoked potential was found to be a more sensitive indicator of disease than OEP or UPSIT. CONCLUSION: These findings confirm the existence of olfactory dysfunction in multiple sclerosis and validate a new evoked potential technique.

Olfactory dysfunction in Parkinson's disease.

OBJECTIVE: To evaluate olfactory function in Parkinson's disease. METHODS: A standardised odour identification test was used, together with an evoked potential assessment with hydrogen sulphide. In addition, histological analysis was performed on the olfactory bulbs of cadavers who died from Parkinson's disease. RESULTS: Over 70% of patients studied (71 of 96) were outside the 95% limit of normal on the identification test in an age matched sample and there was an unusual pattern of selective loss to certain odours, not hitherto described. The evoked potentials were significantly delayed but of comparable amplitude to a control matched population. Of the 73 patients studied only 37 had a technically satisfactory record containing a clear response to both gases and of these, 12 were delayed. For H2S there was more delay on stimulating the right nostril than the left. Some patients with normal smell identification test scores had delayed evoked potentials. In the pathological examination of olfactory bulbs from eight brains, changes characteristic of Parkinson's disease (Lewy bodies) were seen in every olfactory bulb, particularly in the anterior olfactory nucleus, and were sufficiently distinct to allow a presumptive diagnosis of Parkinson's disease. CONCLUSIONS: Olfactory damage in Parkinson's disease is consistent and severe and may provide an important clue to the aetiology of the disease.

Masculinity and the male role in sexual health.

PIP: The program of action of the 1994 International Conference on Population and Development defines reproductive and sexual health as a state of complete physical, mental, and social well-being. Sexual health therefore involves enhancing the quality of life and personal relations. Programs to promote sexual health must address a broad range of social and personal problems. Reproductive health programs need to abandon their exclusive focus upon women to give attention and services to men, women, and couples. Male rights and duties, targeting men who act responsibly as heads of households, cultural models of masculinity, men's contempt of femininity, and recognition of homophobia and misogyny as the most powerful mechanisms of social repression are discussed. Sexual education programs, violence prevention programs, and education from the gender perspective all need to focus directly upon the themes of gender equality and sexual diversity.^ieng

Olfactory function in atypical parkinsonian syndromes.

INTRODUCTION: Olfaction is markedly impaired in patients with idiopathic Parkinson's disease (IPD). This deficit contrasts with reports of preserved or only mildly reduced olfaction in patients with atypical parkinsonism. However, the sensitivity and specificity of olfactory function testing in the differential diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory function in patients with corticobasal degeneration (CBD) is unknown. MATERIAL AND METHODS: Using the University of Pennsylvania Smell Identification Test (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in patients with IPD as well as other parkinsonian syndromes including CBD and progressive supranuclear palsy (PSP). RESULTS: UPSIT scores in 118 patients with IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well as in 123 healthy control subjects revealed a marked impairment in the IPD group in contrast to mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity of 85% in differentiating IPD from atypical parkinsonism. CONCLUSIONS: These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Devascularization and staged resection of giant sacrococcygeal teratoma in the premature infant.

Sacrococcygeal teratoma identified in utero is associated with 50% fetal demise, which is caused by hyperdynamic cardiac failure, hemorrhage, and polyhydramnios-induced preterm labor. A premature infant (26 weeks' gestation) with prenatally diagnosed sacrococcygeal teratoma was managed successfully with initial devascularization to control the hyperdynamic state, followed by staged resection.

The effects of epinephrine and nicotine on gingival blood flow in the rabbit.

Using the thermal diffusion principle, the reduced marginal gingival blood flow measured indicated that epinephrine and nicotine were both able markedly to reduce the marginal gingival circulation.

The oral effects of prolonged intermaxillary fixation by interdental eyelet wiring.

The oral effects of prolonged intermaxillary fixation were investigated in 106 severely obese patients who had been jaw wired as an aid to weight loss. The principal complications during fixation were episodes of periodontal pain and tooth mobility (40%). After removal of fixation, the principal sequelae were residual periodontal problems (9%) and mandibular limitation (9%). These findings were confirmed in a subgroup of 11 patients who had detailed measurements made of their periodontal index, oral hygiene index and range of jaw movements. These findings were discussed in relation to other methods of management of obesity.

The effects of intra-arterial epinephrine and nicotine on gingival circulation.

The purpose of this study was to test the hypothesis that acute necrotizing ulcerative gingivitis (ANUG) was the result of ischemia resulting from three predisposing factors. Vascular stasis, stress, and smoking were said to combine and induce severe vascular constriction at the end arterial locations of the gingivae, resulting in necrosis of the part. The experimental animal used was the rabbit; clinical doses of epinephrine and nicotine were infused intraarterially and the gingival circulation was monitored by the heat-diffusion principle. It was found that the chemicals caused a severe reduction in flow rates in spite of greatly increased pressure within the system. The finding supports the hypothesis that ischemia could play an important role in the initiation of ANUG.

The acute effects of Dramamine on uterine contractability during labor.

The acute effects of intravenously administered Dramamine or placebo on uterine activity were studied in 32 primigravida patients during the active phase of spontaneous labor. Uterine activity was monitored by invasive quantitative techniques. The results showed no change in uterine activity in the placebo group, but there was a significant increase in activity in the Dramamaine-treated women. The increased activity was primarily the result of an increase in the frequency of contractions.