No evidence for fixation of mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the differences in hernia recurrence and chronic postoperative inguinal pain (CPIP) in randomized, controlled trials comparing fixation and non-fixation of the mesh in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. METHODS: A multi-database systematic search was conducted for randomized, controlled trials comparing fixation versus non-fixation of the mesh in TAPP inguinal hernia repair. All eligible papers were assessed for risk of bias using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Quality of evidence was evaluated using the GRADE system. Meta-analyses were performed regarding recurrence and CPIP using RevMan. RESULTS: Seven prospective, randomized controlled trials were included. Laparoscopic TAPP inguinal hernia repair was performed in 1732 patients with 737 procedures performed without fixation and 995 procedures with fixation of the mesh. Despite all trials being RCTs, the trials were limited by substantial bias and the quality of evidence was low regarding hernia recurrence and very low regarding CPIP. Pooled estimates from meta-analyses were an OR of 2.80 (95% CI 0.61-12.77) for hernia recurrence and a mean difference in visual analogue scale (VAS) of 0.17 (95% CI 0.90-1.24) for CPIP, respectively. CONCLUSION: The current evidence is very uncertain and mesh fixation may have little to no effect regarding hernia recurrence and chronic postoperative inguinal pain in patients operated with TAPP inguinal hernia repair.

Initial Diagnosis of ALK-Positive Non-Small-Cell Lung Cancer Based on Analysis of ALK Status Utilizing Droplet Digital PCR.

We describe a novel droplet digital PCR (ddPCR) assay capable of detecting genomic alterations associated with inversion translocations. It is applied here to detection of rearrangements in the anaplastic lymphoma kinase (ALK) gene associated with ALK-positive non-small-cell lung cancer (NSCLC). NSCLC patients may carry a nonreciprocal translocation on human chromosome 2, in which synchronized double stranded breaks (DSB) within the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic material that forms the non-natural gene fusion EML4-ALK encoding a constitutively active tyrosine kinase that is associated with 3 to 7% of all NSCLCs. Detection of ALK rearrangements is currently achieved in clinics through direct visualization via a fluorescent in situ hybridization (FISH) assay, which can detect those rearrangements to a limit of detection (LOD) of ca. 15%. We show that the ddPCR assay presented here provides a LOD of 0.25% at lower cost and with faster turnaround times.

Characterizing the concept of activity pacing as a non-pharmacological intervention in rheumatology care: results of an international Delphi survey.

OBJECTIVE: To develop a consensual list of the most important aspects of activity pacing (AP) as an intervention within the context of non-pharmacological rheumatology care. METHOD: An international, multidisciplinary expert panel comprising 60 clinicians and/or healthcare providers experienced in AP across 12 different countries participated in a Delphi survey. Over four Delphi rounds, the panel identified and ranked the most important goals of AP, behaviours of AP (the actions people take to meet the goal of AP), strategies to change behaviour in AP, and contextual factors that should be acknowledged when instructing AP. Additionally, topics for future research on AP were formulated and prioritized. RESULTS: The Delphi panel prioritized 9 goals, 11 behaviours, 9 strategies to change behaviour, and 10 contextual factors of AP. These items were integrated into a consensual list containing the most important aspects of AP interventions in non-pharmacological rheumatology care. Nine topics for future research on AP with the highest ranking were included in a research agenda highlighting that future research should focus on the effectiveness of AP interventions and on appropriate outcome measures to assess its effectiveness, as selected by 64% and 82% of the panellists, respectively. CONCLUSIONS: The diversity and number of items included in the consensual list developed in the current study reflect the heterogeneity of the concept of AP. This study is an important first step in achieving more transparency and homogeneity in the concept of AP in both rheumatology daily clinical practice and research.

Metabolic syndrome in first-time hospitalized patients with depression: a 1-year follow-up study.

OBJECTIVE: Studies on metabolic syndrome (MetS) in younger patients with depression are few. We examined the prevalence and progression of MetS in first-time hospitalized patients with depression during 1 year of follow-up. Furthermore, we explored putative risk factors of MetS. METHOD: We evaluated MetS and its components in first-time hospitalized patients with depression (N = 52) and healthy controls (N = 50) (18-45 years). Physical activity, aerobic fitness, sleeping disturbances, smoking and dietary habits, and psychopharmacological treatment were recorded at baseline for all participants and after 1 year for the patients. RESULTS: Patients had significantly higher waist circumference (WC) and lower high-density lipoproteins compared with healthy controls (P < 0.05). Patients had higher prevalence of MetS, but this was not significant when adjusted for age. Patients had significant increase in WC and triglycerides and a non-significant increase in the prevalence of MetS. Antipsychotic medication (OR 10.5, 95% CI 1.18-94.14) and low aerobic fitness (OR 0.79, 95% CI 0.68-0.93) were significantly correlated with MetS (P < 0.05). CONCLUSION: Metabolic syndrome is highly prevalent in younger, severely depressed patients and the incidence increases during 1 year of follow-up. Low aerobic fitness and use of atypical antipsychotics are strongly correlated with MetS.

A new general model for predicting melting thermodynamics of complementary and mismatched B-form duplexes containing locked nucleic acids: application to probe design for digital PCR detection of somatic mutations.

Advances in real-time polymerase chain reaction (PCR), as well as the emergence of digital PCR (dPCR) and useful modified nucleotide chemistries, including locked nucleic acids (LNAs), have created the potential to improve and expand clinical applications of PCR through their ability to better quantify and differentiate amplification products, but fully realizing this potential will require robust methods for designing dual-labeled hydrolysis probes and predicting their hybridization thermodynamics as a function of their sequence, chemistry, and template complementarity. We present here a nearest-neighbor thermodynamic model that accurately predicts the melting thermodynamics of a short oligonucleotide duplexed either to its perfect complement or to a template containing mismatched base pairs. The model may be applied to pure-DNA duplexes or to duplexes for which one strand contains any number and pattern of LNA substitutions. Perturbations to duplex stability arising from mismatched DNA:DNA or LNA:DNA base pairs are treated at the Gibbs energy level to maintain statistical significance in the regressed model parameters. This approach, when combined with the model's accounting of the temperature dependencies of the melting enthalpy and entropy, permits accurate prediction of T(m) values for pure-DNA homoduplexes or LNA-substituted heteroduplexes containing one or two independent mismatched base pairs. Terms accounting for changes in solution conditions and terminal addition of fluorescent dyes and quenchers are then introduced so that the model may be used to accurately predict and thereby tailor the T(m) of a pure-DNA or LNA-substituted hydrolysis probe when duplexed either to its perfect-match template or to a template harboring a noncomplementary base. The model, which builds on classic nearest-neighbor thermodynamics, should therefore be of use to clinicians and biologists who require probes that distinguish and quantify two closely related alleles in either a quantitative PCR or dPCR assay. This potential is demonstrated by using the model to design allele-specific probes that completely discriminate and quantify clinically relevant mutant alleles (BRAF V600E and KIT D816V) in a dPCR assay.

The Effect of Performing Bi- and Unilateral Row Exercises on Core Muscle Activation.

The purpose of the study was to compare core muscle activation in 3 different row exercises (free-weight bent-over row, seated cable row and machine row) performed unilaterally and bilaterally, at matched effort levels. 15 resistance-trained men (26.0±4.4 years, 81.0±9.5 kg, 1.81±0.07 m) performed the exercises in randomized order. For erector spinae and multifidus, EMG activities in unilateral machine- and cable row were 60-63% and 74-78% of the bilateral performance (P≤0.036). For external oblique, the EMG activities recorded during bilateral exercises were 37-41% of the unilateral performance (P≤0.010). In unilateral cable- and machine rows, the EMG activities in external oblique and multifidus were 50-57% and 70-73% of the free-weight row (P≤0.002). In bilateral free-weight row, EMG activity in erector spinae was greater than bilateral machine- (+34%, P=0.004) and unilateral free-weight rows (+12%, P=0.016). For rectus abdominis there were no significant differences between conditions. In conclusion, 1) free-weight row provided greater EMG activity in erector spinae (bilaterally and unilaterally) and multifidus (unilaterally) than machine row; 2) unilateral performance of exercises activated the external oblique more than bilateral performance, regardless of exercise; and 3) generally bilateral performance of exercises provided higher erector spinae and multifidus EMG activity compared to unilateral performance.

The interactions between pain, pain-related fear of movement and productivity.

BACKGROUND: Employees with physically heavy work have an increased risk of musculoskeletal disorders leading to reduced work ability. AIMS: To investigate if a high level of musculoskeletal pain or pain-related fear of movement was associated with low productivity among employees with physically heavy work and differing work ability levels. METHODS: The study was conducted at a Danish production site and employees with physically heavy work in the production line were included in the study. Work ability was assessed with the Work Ability Index (WAI), pain-related fear of movement with the Tampa Scale for Kinesiophobia and productivity and musculoskeletal pain by self-reported measures. Sickness absence records for construction of WAI were obtained from the workplace. RESULTS: There was a 77% response rate with 350 employees included in the final analysis. Among employees with only moderate work ability, there was neither an association between pain and productivity nor between pain-related fear of movement and productivity. For employees with good work ability, higher levels of pain and higher levels of pain-related fear of movement both raised the odds of low productivity significantly. CONCLUSIONS: Despite the fact that musculoskeletal pain increases the risk of reduced work ability significantly, musculoskeletal pain and pain-related fear of movement were associated with low productivity only among employees with good work ability.

Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis.

BACKGROUND: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. OBJECTIVE: To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. METHODS: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25(high) and CD26(high) cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses. RESULTS: The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05-1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk. CONCLUSIONS: MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.

Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis.

BACKGROUND: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent. OBJECTIVES: We studied the immunological response to GA and its relationship with disease activity. METHODS: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain reaction (PCR) analysis in 39 untreated and 29 GA-treated relapsing-remitting MS patients. Definition of breakthrough disease was based on the occurrence of relapses, disability progression, or gadolinium (Gd)-enhanced MRI. RESULTS: The expression of T helper type 1 (Th1) and Th17 cytokines and transcription factors was reduced during long-term treatment, but there was no relationship between the expression of cytokines and transcription factors and anti-GA antibodies. High expression of mRNA encoding GATA3 and lymphotoxin-ß (LT-ß) was associated with low disease activity in Gd-enhanced MRI studies. None of the variables studied were associated with clinical disease activity. GA treatment resulted in the development of IgG and IgG4 anti-GA antibodies during the first months of treatment, persisting during long-term treatment. CONCLUSIONS: The observed relationship between the expression of mRNA encoding GATA3 and LT-ß expression and MRI disease activity deserves further analysis in future studies. The development of anti-GA antibodies was observed in all patients treated with GA, but this was not related with measures of cellular immunity, clinical or MRI disease activity.

Differences between questionnaire- and interview-based measures of activities of daily living (ADL) ability and their association with observed ADL ability in women with rheumatoid arthritis, knee osteoarthritis, and fibromyalgia.

OBJECTIVES: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. METHOD: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. RESULTS: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. CONCLUSION: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.

Cognitive deficits in multiple sclerosis: correlations with T2 changes in normal appearing brain tissue.

OBJECTIVES: Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part of the cognitive impairment seen in MS and constitute a supplement to traditional measurement of T2 lesion volume. MATERIALS AND METHODS: Fifty patients with clinically definite MS were included (38 women, 12 men). Patients were MR scanned, neuropsychologically tested, and evaluated clinically with the Kurtzke Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. RESULTS: We found distinct clusters of voxels with T2 estimates correlating with CDF, mental processing speed, complex motor speed, verbal fluency, and MSIS. A significant negative correlation was found between total lesion volume and CDF (r = -0.34, P = 0.02), verbal intelligence (r = -0.40, P = 0.005), mental processing speed (r = -0.34, P = 0.03), visual problem solving (r = -0.40, P = 0.01), and complex motor speed (r = -0.39, P = 0.01). No significant correlation was detected between total lesion load and the clinical measures EDSS and MSIS. CONCLUSION: Our results suggest that even in the NABT MR detects changes likely to be associated with an underlying pathology and possibly contributes to the cognitive impairment in MS.

Disease protection and interleukin-10 induction by endogenous interferon-ß in multiple sclerosis?

OBJECTIVE: An immune activation response resembling virus or type I interferon responses has been observed in untreated multiple sclerosis (MS), but its pathogenic significance is uncertain. We studied the relationship between a type I interferon-like response in untreated patients with MS and disease activity. METHODS: Gene expression was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR) in whole blood samples and by microarray analysis of mononuclear cells from untreated patients with MS, patients with MS treated with IFN-ß, and patients with MS with anti-IFN-ß neutralizing antibodies (NAb). Disease activity was assessed by gadolinium-enhanced magnetic resonance imaging. RESULTS: Eight of 36 untreated patients with MS had spontaneously increased expression of the type I IFN-induced gene MX1. Microarray gene expression analysis demonstrated that patients with increased spontaneous MX1 expression also had increased expression of other genes induced by regular IFN-ß treatment of MS. MX1 expression correlated with FOXP3 and IL10 expression, and IL10 expression correlated negatively with disease activity on magnetic resonance imaging. Further, in vivo IL10 expression was lower in NAb-positive patients than in untreated patients with MS and healthy controls. Finally, ex vivo treatment of mononuclear blood cells with IFN-ß induced the expression of IL10, and this was blocked by the addition of serum from NAb-positive patients with MS. CONCLUSION: Our findings suggest that endogenous IFN-ß may induce the expression of immunoregulatory IL10 in MS and that this might be associated with dampening of inflammatory disease activity.

Changes in the relationships between dogs, owners and veterinarians in Norway and Iceland.

Norwegian and Icelandic dog owners were interviewed about aspects of their dog keeping and their attitudes to the veterinary profession. Dogs were found to play an important role in the lives of their owners, who had high expectations of their veterinarians, not only with respect to the treatment of their dogs but also with respect to themselves as clients. About one-third of owners reported problems related to a lack of trust and poor communications in encounters with their veterinarians.

Correlates of subjective and objective burden among caregivers of patients with bipolar disorder.

OBJECTIVE: We examined the relationship between mood symptoms and episodes in patients with bipolar disorder and burden reported by their primary caregivers. METHOD: Data on subjective and objective burden reported by 500 primary caregivers for 500 patients with bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were collected using semistructured interviews. Patient data were collected prospectively over 1 year. The relationship between patient course and subsequent caregiver burden was examined. RESULTS: Episodes of patient depression, but not mood elevation, were associated with greater objective and subjective caregiver burden. Burden was associated with fewer patient days well over the previous year. Patient depression was associated with caregiver burden even after controlling for days well. CONCLUSION: Patient depression, after accounting for chronicity of symptoms, independently predicts caregiver burden. This study underscores the important impact of bipolar depression on those most closely involved with those whom it affects.

Movement detection impaired in patients with knee osteoarthritis compared to healthy controls: a cross-sectional case-control study.

The purpose of this study was to clarify whether osteoarthritis (OA) patients have a localized or a generalized reduction in proprioception. Twenty one women with knee OA (mean age [SD]: 57.1 [12.0] years) and 29 healthy women (mean age [SD]: 55.3 [10.1] years) had their joint position sense (JPS) and threshold to detection of a passive movement (TDPM) measured in both knees and elbows. JPS was measured as the participant's ability to actively reproduce the position of the elbow and knee joints. TDPM was measured as the participant's ability to recognize a passive motion of the elbow and knee joints. The absolute error (AE) for JPS (i.e., absolute difference in degrees between target and estimated position) and for TDPM (i.e., the difference in degrees at movement start and response when recognizing the movement) was calculated. For TDPM a higher AE (mean [SE]) was found in the involved knees in patients than in the matched knees of healthy participants (AE: 2.41 degrees [0.20 degrees] versus 1.47 degrees [0.14], p=0.001). The same held true for the non-involved knees between OA and healthy subjects (AE: 2.20 degrees [0.20 degrees] versus 1.57 degrees [0.14 degrees], p=0.016). Furthermore TDPM was higher in OA patients' right elbows compared to healthy participants' right elbows (AE: 2.15 degrees [0.20 degrees] versus 1.45 degrees [0.15 degrees], p=0.011). No significant difference between healthy women and OA patients regarding the left elbow for TDPM, or JPS was observed. The present age-controlled, cross-sectional study suggests that there is an increase in threshold to detection of a passive motion in knees and elbows for patients with knee OA. This indicates that OA may be associated with a generalized defect in proprioception with possible implications for the pathogenesis of the joint degeneration.

Quantification of colour Doppler activity in the wrist in patients with rheumatoid arthritis--the reliability of different methods for image selection and evaluation.

PURPOSE: The amount of colour Doppler activity in the inflamed synovium is used to quantify inflammatory activity. The measurements may vary due to image selection, quantification method, and point in cardiac cycle. This study investigated the test-retest reliability of ultrasound colour Doppler measurements in the wrist of patients with rheumatoid arthritis (RA) using different selection and quantification methods. MATERIALS AND METHODS: 14 patients with RA had their wrist scanned twice by the same investigator with an interval of 30 minutes. The images for analysis were selected either by the anatomical position only or by the anatomical position with maximum colour Doppler activity. Subsequently, the amount of colour Doppler was measured in an area defined by either the synovial tissue or by specific anatomical structures surrounding the synovial tissue. RESULTS: The best test-retest reliability was obtained when the images were selected guided by colour Doppler and the subsequent quantification was done in an area defined by anatomical structures. With this method, the intra-class coefficient ICC (2.1) was 0.95 and the within-subject SD (SW) was 0.017, indicating good reliability. In contrast, poor test-retest reliability was found if the images were selected by anatomical position only and the quantification was done in an area defined by the synovial tissue (ICC [2.1] = 0.48 and SW = 0.049). CONCLUSION: The study showed that colour Doppler measurements are reliable if the images for analysis are selected by anatomical position in combination with colour Doppler activity and the subsequent analysis is performed in an area defined by anatomical structures.

Aquatic exercise for the treatment of knee and hip osteoarthritis.

BACKGROUND: Clinical experience indicates that aquatic exercise may have advantages for osteoarthritis patients. OBJECTIVES: To compare the effectiveness and safety of aquatic-exercise interventions in the treatment of knee and hip osteoarthritis. SEARCH STRATEGY: We searched MEDLINE from 1949, EMBASE from 1980, CENTRAL (Issue 2, 2006), CINAHL from 1982, Web of Science from 1945, all up to May 2006. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised clinical trials. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed the internal validity of included trials and extracted data. Pooled results were analyzed using standardized mean differences (SMD). MAIN RESULTS: There is a lack of high-quality studies in this area. In total, six trials (800 participants) were included. At the end of treatment for combined knee and hip osteoarthritis, there was a small-to-moderate effect on function (SMD 0.26, 95% confidence interval (CI) 0.11 to 0.42) and a small-to-moderate effect on quality of life (SMD 0.32, 95% CI 0.03 to 0.61). A minor effect of a 3% absolute reduction (0.6 fewer points on a 0 to 20 scale) and 6.6% relative reduction from baseline was found for pain. There was no evidence of effect on walking ability or stiffness immediately after end of treatment. No evidence of effect on pain, function or quality of life were observed on the one trial including participants with hip osteoarthritis alone. Only one trial was identified including knee osteoarthritis alone, comparing aquatic exercise with land-based exercise. Immediately after treatment, there was a large effect on pain (SMD 0.86, 95%CI 0.25 to 1.47; 22% relative percent improvement), but no evidence of effect on stiffness or walking ability. Only two studies reported adverse effects, that is, the interventions did not increase self-reported pain or symptom scores. No radiographic evaluation was performed in any of the included studies. AUTHORS' CONCLUSIONS: Aquatic exercise appears to have some beneficial short-term effects for patients with hip and/or knee OA while no long-term effects have been documented. Based on this, one may consider using aquatic exercise as the first part of a longer exercise programme for osteoarthritis patients. The controlled and randomised studies in this area are still too few to give further recommendations on how to apply the therapy, and studies of clearly defined patient groups with long-term outcomes are needed to decide on the further use of this therapy in the treatment of osteoarthritis.

Carnitine palmitoyltransferase: characterization of a labile detergent-extracted malonyl-CoA-sensitive enzyme from rat liver mitochondria.

Rat liver mitochondria were preextracted with Triton X-100 in the absence of salts to remove malonyl-CoA-insensitive carnitine palmitoyltransferase. From the remaining membrane residues a malonyl-CoA-sensitive enzyme was solubilized with octyl glucopyranoside in the presence of KCl. Significant enzyme activity, [2-14C]malonyl-CoA binding and malonyl-CoA inhibition of this enzyme was present only after removal of detergent by precipitation with poly(ethylene glycol). The enzyme activity was rapidly lost in the solubilized form. High concentrations of glycerol protected the enzyme. The alkylating irreversible inhibitor, S-(4-bromo-2,3-dioxobutyl)-CoA, strongly inhibited the malonyl-CoA-sensitive enzyme in the membrane residues. The enzyme was protected against this inhibitor by malonyl-CoA and palmitoyl-CoA. The more loosely membrane-bound malonyl-CoA-insensitive enzyme failed to bind malonyl-CoA, was stable in the presence of detergents and was not inhibited by S-(4-bromo-2,3-dioxobutyl)-CoA. It is suggested that two different carnitine palmitoyltransferase proteins exist in the inner mitochondrial membrane and that the detergent-labile malonyl-CoA-sensitive enzyme is the less easily extracted of the two.