Noninvasive tissue oxygen saturation determined by near-infrared spectroscopy following peripheral nerve block.

BACKGROUND: Noninvasive physiologic measurement of cutaneous tissue oxygenation using near-infrared spectroscopy (NIRS) has become increasingly common in cardiovascular and plastic surgery. The aim of this study was to determine whether clinically available NIRS-based monitors could detect changes in tissue oxygen saturation (rSO(2)) following a variety of peripheral nerve blocks. We hypothesize that peripheral nerve blocks will produce detectable changes in cutaneous tissue oxygenation levels that can be measured by noninvasive NIRS-based oximetry. METHODS: Forty adult patients scheduled for pre-operative peripheral nerve block placement were enrolled. Prior to block placement, NIRS sensors were placed on the operative and nonoperative (control) limb. Baseline tissue oxygen saturation values were obtained prior to dosing of the nerve block, and measurements were recorded every 5 min thereafter. RESULTS: Initial rSO(2) values were higher in the operative vs. control limbs prior to nerve block placement. Tissue oxygen saturation increased in the blocked, but not control, limbs with time. Subgroup analysis suggested statistically significant differences in rSO(2) values in blocked vs. control limbs for cervical paravertebral, infraclavicular, and femoral nerve blocks. CONCLUSIONS: Our results demonstrated sustained increases in tissue rSO(2) values following peripheral nerve block placement, in addition to higher initial rSO(2) values in operative limbs prior to block placement. Further investigations are necessary to define the expected baseline rSO(2) values in operative and control limbs. Future efforts utilizing NIRS-based detection of tissue ischemia should consider the small but significant changes in rSO(2) resulting from a successful nerve block.

Fast-track management of malignant superior vena cava syndrome.

We report our experience with a combined approach of endovascular biopsy followed by immediate stenting in the management of superior vena cava (SVC) syndrome secondary to obstructing mediastinal masses. A diagnosis of malignancy was obtained in six of eight (75%) biopsies and symptomatic relief was accomplished in all patients. We have found this to be a rapid, safe and effective management strategy that we now consider for all patients presenting with de novo SVC syndrome.

Randomized trial of lidocaine vs lidocaine/bupivacaine periprostatic injection on longitudinal pain scores after prostate biopsy.

PURPOSE: Periprostatic lidocaine reduces immediate post-prostate biopsy pain but still many men will not consent to re-biopsy. We performed a randomized study to assess whether adding long acting local anesthesia to a short acting agent would further reduce pain. MATERIALS AND METHODS: A total of 300 men undergoing transrectal ultrasound guided prostate biopsy were sequentially randomized to receive either short acting local lidocaine (lid) or short and long acting lidocaine and bupivacaine (lid/bup). A 7-day questionnaire was used to study daily pain (10-point visual analog score), bleeding (hematuria, PR bleeding, hematospermia), visits to the family doctor and analgesic use, and whether they would agree to future re-biopsy. RESULTS: Of the 256 questionnaires returned 250 were suitable for analysis. Cross-sectional comparison showed no intergroup differences in mean pain scores immediately after biopsy (2.24, 95% CI 1.94-2.5 vs 2.61, 95% CI 2.3-2.9, p = 0.88 in lid and lid/bup groups, respectively). There was a significant rebound in visual analog scale at 1 hour in the lid group but not in the lid/bup group (+ 0.9 vs + 0.09, p = 0.0006). Longitudinal analysis showed the global pain experience after lid/bup was better compared to lidocaine alone, with significantly less pain every subsequent day (p = 0.0006 to 0.002). No difference was seen in morbidity, analgesia usage or number refusing future re-biopsy (9.6% vs 9.8%). CONCLUSIONS: Long and short acting local anesthetics together significantly attenuate the 1-hour rebound increase in pain scores seen after short acting anesthesia alone. Improved pain scores were sustained during the subsequent week and we advocate routine combination use for transrectal ultrasound guided prostate biopsy.

Resolving disparities in antidepressant treatment and quality-of-life outcomes between uninsured and insured primary care patients with depression.

BACKGROUND: Efforts to improve primary care depression treatment should penetrate to vulnerable uninsured populations. OBJECTIVE: To assess a primary care intervention's impact on treatment and quality-of-life outcomes in uninsured and insured depressed patients during the acute treatment phase. RESEARCH DESIGN: Twelve community primary care practices were randomized to 'enhanced' (intervention) and usual care conditions. Physicians, nurses and administrative staff in enhanced care practices received training to improve detection and management of depression. SUBJECTS: In 1996 to 1997, 383 nonelderly depressed patients who were either uninsured or covered by private insurance/Medicaid were enrolled; 343 (89.6%) completed six-month follow-up. MEASURES: Adequate pharmacotherapy (>or=3 months of antidepressants at therapeutic doses); adequate psychotherapy (>or=8 counseling visits); improvement in mental-health-related-quality-of-life (MHQOL), assessed by Mental Component Summary scale for SF-36. RESULTS: Multivariate results showed that 54.6% of uninsured enhanced care (UEC) patients received adequate pharmacotherapy, compared with 14.3% of uninsured usual care (UUC) patients (P = 0.0005); however, receipt of adequate psychotherapy was comparable between these two groups (18.2% UEC, 11.9% UUC; P = 0.42). Intervention effects on insured patients' treatment were modest to minimal. Among usual care patients, the insured had 5.4 points greater improvement in MHQOL at 6 months than the uninsured (12.4 points insured, 7.0 points uninsured; P = 0.02); however, among patients receiving the intervention, the insured and uninsured had comparable MHQOL improvement (12.3 points insured, 11.6 points uninsured; P = 0.76). CONCLUSIONS: The intervention improved antidepressant treatment rates in uninsured patients and helped resolve quality-of-life outcome disparities observed between insured and uninsured patients receiving usual care.

A primary care intervention for depression.

To assess a guideline-based intervention's impact on depression care provided in rural vs. urban primary care settings, 12 community primary care practices (four rural, eight urban) were randomized to enhanced (i.e., intervention) and usual care study conditions. The study enrolled 479 depressed patients, with 432 (90.2 percent) completing telephone follow-up at six months. Multilevel analytic models revealed that rural enhanced care patients had 2.70 times the odds (P = 0.02) of rural usual care patients of taking a three-month course of antidepressant medication at recommended dosages in the six months following baseline; urban enhanced care patients had 2.43 times the odds compared with their urban usual care counterparts (P = 0.007). Rural enhanced care patients had 3.00 times the odds of rural usual care patients of making eight or more visits to a mental health specialist for counseling in the six months following baseline (P = 0.03). Comparisons of patients in enhanced care practices showed that rural enhanced care patients had 2.00 times the odds (P = 0.12) of urban enhanced care patients of making at least one visit to a mental health specialist for counseling in the six months following baseline and had comparable odds to urban enhanced care patients (odds ratio [OR] = 1.06, P = 0.77) of making eight or more visits to such specialists during that interval. The study's intervention improved the care received by both rural and urban depressed primary care patients. Moreover, the intervention's effect appears to have been greater in rural settings, particularly in terms of increasing depressed rural patients' use of mental health specialists for counseling.

Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms.

Plectin is a widely expressed protein that is very large in size and that has all the attributes of a multifunctional crosslinking and organizing element of the cytoskeleton. It displays a multidomain structure, versatile binding activities, and subcellular localizations that enable it to strengthen cells against mechanical stress forces. Moreover, hereditary gene defects in plectin cause epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with muscular dystrophy. Here we report the analysis of the exonintron organization of the rat plectin gene and the identification of several different isoforms on the transcriptional level. We show that of 35 coding exons identified, 4 serve as alternative first exons splicing into the same successive exon 2, which is the first of 7 exons encoding a highly conserved actin-binding domain. RNase protection mapping of transcripts containing 3 of the identified 4 alternate first exons revealed their coexpression in rat glioma C6 cells and in a series of different rat tissues that we examined. Significant variations in expression levels of first exons indicated the possibility of tissue-specific promoter usage. In addition, plectin splice variants lacking exon 31 (> 3 kb), which encodes the entire rod domain of the molecule, were identified in a variety of rat tissues. This study provides first insights into a complex plectin gene regulatory machinery with similarities to that of dystrophin.

Maternal attachment status, psychosocial stressors and problem behaviour: follow-up after parent training courses for conduct disorder.

37 Mothers of children with conduct disorder who had received Parent Management Training (PMT) were interviewed using the Adult Attachment Interview, 13-43 months after treatment. Child behaviour levels at follow-up were strongly associated with the scores at referral in the unresolved attachment group, but not in the resolved group. This was reflected in a statistical interaction between referral behaviour score and resolved/unresolved attachment status in a regression model. This model, which also included a strong independent contribution from a composite psychological stress index, explained 66% of the variance in follow-up behaviour scores. The implications of these results for predicting the outcome of PMT are discussed.

Impact of functional severity on self concept in young people with spina bifida.

This study examines the relationship between medical and functional severity of disability and levels of self esteem and self concept in 79 young people with spina bifida. Greater feelings of global self worth and of self esteem in physical appearance were associated with greater severity of disability. This was only in part an effect of lower IQ among the most disabled young people. Many of the least disabled had marked impairment of self esteem. Analysis of the impact of individual aspects of disability confirmed the association between increased self esteem in physical appearance and global self worth, and diminished functional ability. Academic self ratings, however, were higher in the less disabled. Hydrocephalus and continence appeared to have minimal effect on self esteem. The relationship between severity of disability in spina bifida and self concept is complex and mediated by a range of factors. It is incorrect to assume that the psychological impact is less in the mildly disabled young person.

Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4.

A member of the ionotropic family of glutamate receptors, hGluR4, was isolated from a human cDNA library and characterized following expression in mammalian cell lines. Human GluR4 possessed a 99% amino acid and 92% nucleotide homology to that of its rat counterpart with sequence differences restricted to the carboxy and amino terminal regions of the molecule. Transfection of simian kidney cells (COS-1) with an hGluR4 expression plasmid resulted in the transient formation of a membrane protein that possessed high specific binding for [3H](RS)-alpha-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) but not [3H]kainate. Competition studies yielded a displacement profile of AMPA = quisqualate > glutamate > domoate > kainate >> N-methyl-D-aspartate (NMDA) or dihydrokainate. Whole-cell, voltage-clamp recordings from a human embryonic kidney cell line (HEK 293) stably expressing hGluR4 confirmed the presence of constitutively active, ligand-gated ion channels activated by AMPA, glutamate and kainate but not N-methyl-D-aspartate. Kainate-evoked currents were reversibly attenuated by 6-cyano-7-nitro- quinoxaline-2,3-dione (CNQX) but not DL-2-amino-5- phosphonovalerate (DL-AP5). Agonist-evoked currents exhibited inward rectification and ion substitution experiments indicated that hGluR4 receptor-linked ion channels in their homomeric state are permeable to both CA2+ and Na+ ions. In the same cell line antibody to rat GluR4 immunoprecipitated a major protein band at approximately 108 kDa and a minor one at approximately 340 kDa. The immunoblot analysis of membranes chemically crosslinked with dithiobis(succinimidylpropionate) showed a broad band at 550-600 kDa suggesting that the GluR4 receptor forms a pentamer in situ. This is the first report of the cloning of hGluR4 receptor and its stable expression in a human cell line.

cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration.

We have isolated a new member of the human glutamate receptor family from a fetal brain cDNA library. This cDNA clone, designated EAA3a, shares a 90% nucleotide identity with the previously reported rat GluR5-2b cDNA splice variant and differed from human GluR5-1d in the amino and carboxy terminal regions. Cell lines stably expressing EAA3a protein formed homomeric ligand-gated ion channels responsive, in order of decreasing affinity to domoate, kainate, L-glutamate and (RS)-alpha-amino-3-hydroxy-5- methylisoxazole-propionate (AMPA). Kainate-evoked currents showed partial desensitization that was reduced on incubation with concanavalin A (conA) but not cyclothiazide and were attenuated by the non-N-methyl-D-aspartate (NMDA) receptor antagonist CNQX (6-cyano-7-nitro-quinoxalinedione). Coexpression of EAA3a and human EAA1 cDNAs in HEK 293 cells formed a heteromeric channel with unique properties. Kainate and AMPA activated the heteromeric channel with significantly higher affinities than observed for EAA3a alone. Ligand binding studies with the recombinant EAA3a receptor expressed in mammalian cells indicated a high affinity kainate binding site (Kd = 120 +/- 15.0 nM). The relative potency of compounds in displacing [3H]-kainate binding to EAA3a receptor was: domoate > kainate > L-glutamate = quisqualate > 6,7-dinitroquinoxaline-2,3-dione (DNQX) = CNQX > AMPA > dihydrokainate > NMDA.

Acute renal failure in IgA nephropathy.

Twenty-five (3%) of 865 patients with IgA nephropathy presented with acute renal failure (ARF). These patients were matched with 25 patients in the same series who presented with irreversible renal impairment. Patients with acute renal failure had a significantly higher incidence of macroscopic hematuria and red blood cells in tubules. Conversely, a greater percentage of patients with irreversible renal failure had > or = 40% sclerosed glomeruli. The long-term prognosis for patients presenting with ARF appears excellent with only 1 (4%) patient developing chronic renal failure after a mean follow-up of 65 months. Mechanisms of acute renal failure in IgA nephropathy are discussed.

Human glutamate receptor hGluR3 flip and flop isoforms: cloning and sequencing of the cDNAs and primary structure of the proteins.

Several cDNA clones encoding the human glutamate receptor subunit GluR3 flip and flop isoforms, were isolated from human hippocampus and fetal brain libraries. DNA sequence analysis revealed overlapping clones permitting the reconstruction of full-length GluR3-flip and GluR3-flop cDNAs. The GluR3 cDNAs demonstrated an 94.1-94.7% nucleotide (nt) identity with the corresponding rat cDNAs. The nt sequence of the GluR3 cDNAs would encode 894 amino acid proteins that have a 99.4% identity with the rat GluR3 isoforms. The human GluR3 cDNAs predict an additional 6 amino acid in the N-terminal signal peptide as compared to the rat GluR3.

The self-concept of young people with spina bifida: a population-based study.

Seventy-nine young people with spina bifida were given a psychological, medical, carer and occupational therapy assessment. 79 matched able-bodied young people received the psychosocial interview. The disabled group felt themselves to be less competent in academic, athletic and social aspects of self-concept, less supported by classmates, equally supported by parents and friends and more supported by teachers than the able-bodied group. Disabled subjects did not discount the importance of any area of personal-social functioning, and experienced greater discrepancies between competence and importance in most academic, athletic, social and physical appearance aspects of self-concept. Disabled girls assigned very high importance to physical appearance. Physical appearance was more strongly associated with general self-esteem than any other area of self-concept.

Functional expression and pharmacological characterization of the human EAA4 (GluR6) glutamate receptor: a kainate selective channel subunit.

A cDNA encoding an ionotropic glutamate receptor subunit protein humEAA4 (GluR6), has been cloned from a human fetal brain library. This cDNA when expressed in COS or HEK-293 cells is associated with high-affinity kainate receptor binding and ion channel formation. We have successfully established cell lines stably expressing humEAA4 in HEK-293 cells This is the first report of the establishment of stable cell lines expressing a glutamate receptor channel. The relative potency of compounds for displacing [3H]-kainate binding to humEAA4 receptors expressed in COS or HEK-293 cells is domoate > kainate > quisqualate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate = 6,7- dinitroquinoxaline-2,3-dione > dihydrokainate. Applications of kainate, glutamate, and domoate but not AMPA evoked rapidly desensitizing currents in cells expressing homo-oligomeric humEAA4 in a concentration dependent manner. The order of potency was: domoate > kainate > L-glutamate. Although AMPA did not itself activate humEAA4 receptors it did reduce, to a limited extent, kainate-evoked responses. AMPA may therefore be a weak partial agonist for this receptor. To date this effect has not been demonstrated with rat GluR6. It is possible that subtle species differences may exist in the nature of agonist receptor interaction. Kainate evoked currents were attenuated by the quinoxalinediones CNQX and DNQX but not by DAP5. The receptor desensitization was attenuated on application of concanavalin A. Ion-permeability studies indicated that the receptor-linked ion channel is permeable to both Na+ and Ca2+ ions.

Molecular characterization of the human EAA5 (GluR7) receptor: a high-affinity kainate receptor with novel potential RNA editing sites.

Several cDNA clones encoding EAA5 receptor polypeptides were isolated from a human fetal brain library. The EAA5 cDNAs demonstrated an 88.7-90.1% nucleotide identity with rat GluR7 cDNAs. The nucleotide sequence of EAA5 would encode a 919-amino acid protein, that has a 97.7-98.9% identity with the rat GluR7 receptor. Two variation of the EAA5 cDNA were identified which result in amino acid substitutions in the predicted extracellular amino-terminal region; Ser310-->Ala and Arg352-->Gln. These variations can be attributed to RNA editing involving T-->G and G-->A substitutions. Both the location (with respect to glutamate receptors), and the nucleotides involved, in this putative RNA editing are novel and may therefore involve novel mechanisms. Ligand binding studies with membranes of transfected COS-1 cells expressing EAA5 polypeptides demonstrate a rank order of ligand affinity similar to that observed with the rat GluR7 receptor, and a dissociation constant for kainate (2.72 +/- 0.12 nM (n = 3)) that is approximately 20- to 30-fold higher than that observed for the rat GluR7 receptor. All of the ligands tested had a higher affinity for the human EAA5 receptor as compared to the rat GluR7 receptor. This report provides another example of pharmacological differences for similar receptors across species.

Obstetrics in a small maternity hospital.

This paper presents the case for continuing to practise safe obstetrics in a small suburban hospital. Boothville Maternity Hospital, Brisbane, is a Salvation Army hospital of 20 beds. Seven thousand births during the years 1975 to 1989 are reported. Perinatal mortality rate was 4.9/1000 total births, forceps rate 7.1%, caesarean rate 9.3% and transfer rate to larger centres 1.6% for babies and 1.2% for mothers. Personalised family-centred care in congenial surroundings serves to maximise the factors that favour uncomplicated delivery. Large centralised and small peripheral hospitals should be seen not as competitive but as complementary. Boothville provides mutually satisfying co-operation for care-givers and care-receivers.

Ten cases of acute lead intoxication among bridge workers in Louisiana.

We report the cases of ten construction workers who developed acute lead intoxication while repairing a bridge in Louisiana. All but one patient received a five-day course of edetate calcium disodium (calcium EDTA) chelation therapy; one patient received five doses instead of five days of treatment. Calcium EDTA 25 mg/kg q12h was administered for ten consecutive doses by intravenous infusion over two hours. Each dose was diluted in NaCl 0.9% 500 mL. No adverse drug effects were observed during treatment. The posttreatment mean whole blood lead (PbB) concentration was significantly reduced compared with the pretreatment mean PbB (1.48 +/- 0.70 vs. 3.8 +/- 1.68 mumol/L; p = 0.0012, Student's paired t-test). This indicates that the body lead burden of these patients was effectively reduced with calcium EDTA. Eight patients had complaints on admission that were suggestive of lead intoxication. These included malaise, numbness of the extremities, arthralgia, myalgia, abdominal discomfort, sleep disturbance, and lower back pain. Patients had no complaints on discharge. Eight patients had mild anemia that was consistent with acute lead intoxication (mean pretreatment hemoglobin (+/- SD), 128.6(+/- 17.2 g/L), but calcium EDTA therapy did not appear to effect any change in the pretreatment hemoglobin values. The Occupational Safety and Health Administration (OSHA) lead standard requires that manufacturers provide employees at risk for occupational lead exposures with proper respirators and medical surveillance to prevent lead intoxication. The construction industry is exempted from these standards except in Maryland. We believe that amendment of the OSHA lead standards, to provide specific lead regulation of the construction industry, would be helpful in preventing similar cases of occupational lead intoxication.

Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE.

We investigated the effects of the amino acid and vitamin mixture SAAVE in inpatient, chemically-dependent subjects to evaluate the role of neurotransmitters in facilitating recovery and adjustment to a detoxified, sober state. SAAVE is formulated from amino acids that are precursors for neurotransmitters and neuromodulators thought to be involved in alcohol and drug seeking behavior. In a double-blind, placebo-controlled, randomized study of 62 alcoholics and polydrug abusers, SAAVE patients had a significantly reduced stress response as measured by the skin conductance level (SCL), and significantly improved Physical Scores and BESS Scores (behavioral, emotional, social and spiritual). After detoxification there was a six-fold decrease in AMA rates when comparing SAAVE vs. placebo groups. In this inpatient treatment experience SAAVE facilitated the rate of recovery and allowed patients to respond more fully and more quickly to the behavioral goals of the program, for example as measured by the BESS Score. The use of SAAVE to achieve enkephalinase inhibition and precursor amino acid loading in the acute inpatient treatment environment provides the practitioner with the potential ability to restore the neurochemical changes inherent to alcoholism and drug abuse. These findings increase our understanding of the clinically relevant neurobiological mechanisms which underlie compulsive disease.