Haptoglobin is an independent marker for disease severity and risk for metabolic complications in hidradenitis suppurativa: A prospective study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is highly correlated with obesity. Haptoglobin serum levels have recently been recognized as an important biomarker linking obesity with chronic inflammation. OBJECTIVE: To compare haptoglobin with previously proposed serum biomarkers for the determination of disease severity in HS patients. For this purpose, disease severity of HS patients was determined by a panel of clinical scores as well as several risk factors, such as weight and smoking habits. METHODS: A prospective, diagnostic accuracy study was performed at the International Centre for Hidradenitis suppurativa/Acne inversa Bochum (ICH). The study included a total of 263 patients, including 131 who had a confirmed diagnosis of HS in Hurley I (n = 16), II (n = 56) and III (n = 59) HS, and 132 healthy controls. The main outcome was to identify serological inflammatory markers for HS disease severity [severe (III) vs. moderate/mild (II/I)] as assessed by Hurley classification. RESULTS: The serum levels of acute phase proteins haptoglobin and CRP, as well as the number of neutrophils in peripheral blood, number of monocytes, the systemic immune-inflammation index and the pan-immune-inflammatory value correlated with disease severity according to established clinical scores (mHSS, SAHS, Hurley, DLQI). HS patients had significantly higher haptologlobin levels compared to healthy controls. Logistic regression analysis revealed haptoglobin as the only independent marker predicting severe HS. CONCLUSION: In this prospective study, we discovered that the serum levels of the acute phase protein haptoglobin levels serve as an independent marker of disease severity in HS. While this presents the first study in the context of HS. Thus, the present data not only yield a highly promising serum marker to be further validated.

Comparing three machine learning approaches to design a risk assessment tool for future fractures: predicting a subsequent major osteoporotic fracture in fracture patients with osteopenia and osteoporosis.

Four machine learning models were developed and compared to predict the risk of a future major osteoporotic fracture (MOF), defined as hip, wrist, spine and humerus fractures, in patients with a prior fracture. We developed a user-friendly tool for risk calculation of subsequent MOF in osteopenia patients, using the best performing model. INTRODUCTION: Major osteoporotic fractures (MOFs), defined as hip, wrist, spine and humerus fractures, can have serious consequences regarding morbidity and mortality. Machine learning provides new opportunities for fracture prediction and may aid in targeting preventive interventions to patients at risk of MOF. The primary objective is to develop and compare several models, capable of predicting the risk of MOF as a function of time in patients seen at the fracture and osteoporosis outpatient clinic (FO-clinic) after sustaining a fracture. METHODS: Patients aged > 50 years visiting an FO-clinic were included in this retrospective study. We compared discriminative ability (concordance index) for predicting the risk on MOF with a Cox regression, random survival forests (RSF) and an artificial neural network (ANN)-DeepSurv model. Missing data was imputed using multiple imputations by chained equations (MICE) or RSF's imputation function. Analyses were performed for the total cohort and a subset of osteopenia patients without vertebral fracture. RESULTS: A total of 7578 patients were included, 805 (11%) patients sustained a subsequent MOF. The highest concordance-index in the total dataset was 0.697 (0.664-0.730) for Cox regression; no significant difference was determined between the models. In the osteopenia subset, Cox regression outperformed RSF (p = 0.043 and p = 0.023) and ANN-DeepSurv (p = 0.043) with a c-index of 0.625 (0.562-0.689). Cox regression was used to develop a MOF risk calculator on this subset. CONCLUSION: We show that predicting the risk of MOF in patients who already sustained a fracture can be done with adequate discriminative performance. We developed a user-friendly tool for risk calculation of subsequent MOF in patients with osteopenia.

Concurrent Vogt-Koyanagi-Harada disease and impressive response to immune checkpoint blockade in metastatic melanoma.

Background: Vogt-Koyanagi-Harada disease (VKHD)-like symptoms have previously been reported in 11 melanoma patients treated with immune checkpoint inhibitors. Materials & methods: We report a female patient with multilocular metastatic melanoma who was treated with nivolumab. Results: Following the first nivolumab dose, she experienced bilateral blurry vision, hearing loss, vertigo and ataxia. Ocular ultrasound was consistent with the diagnosis of uveitis. Audiography revealed severe bilateral sensorineural hearing loss. A high-dose corticosteroid regimen was initiated under which the patient developed generalized vitiligo. Abdominal and thoracic CT scans showed an almost complete response to nivolumab therapy. This patient fulfilled all criteria of VKHD which is characterized pathogenetically by an antimelanocytic autoimmune process. Conclusion: The present case showed an impressive response to antimelanoma immunotherapy. Based on these data, the occurrence of VKHD in melanoma patients appears to be a strong indicator for immune checkpoint inhibitor efficacy.

Etiology of recurrent large vessel occlusions treated with repeated thrombectomy.

BACKGROUND: Repeated mechanical thrombectomy for acute stroke treatment in individual patients has been proven feasible. However, less is known about the etiology of recurrent vessel occlusions after prior thrombectomy. We aimed to understand if the etiology of such recurrent events differs from the first stroke. METHODS: Retrospectively, we identified all patients at our center who received a repeated mechanical thrombectomy between 2007 and 2019. Clinical data were retrieved from medical records. Etiology of stroke was evaluated retrospectively, and angiographic studies were revisited. RESULTS: Twenty-three patients (1.5%) were identified. Median age was 68 years (IQR 56-77). Median NIHSS at first admission was 11 points (IQR 5-15). In nine cases (39.1%), the recurrent vessel occlusion was located exactly at the same position as the prior occlusion. Overall, five (21.7%) patients had a remarkable extracranial pathology as likely cause of stroke recurrence. In 16 patients (69.6%), the etiology of the first stroke and its recurrence was considered as likely being the same, mostly of cardioembolic or unknown origin. In the seven remaining patients (30.4%), the cause of stroke possibly differed from the first event, with five patients (21.7%) having a postinterventional intracranial intimal lesion as possible cause of stroke. CONCLUSION: Incidence of repeated thrombectomy was low. However, the high number of patients with known origin of stroke etiology raises the question how their monitoring may be optimized. The number of patients with remarkable extracranial pathologies or intracranial endothelial lesions supports current clinical practice to pay attention to final angiographic series.

[Interdisciplinary multimodal assessment and risk-tailored pathways for patients with back pain : Prospective evaluation of an integrated healthcare delivery project]. / Interdisziplinär-multimodales sektorenübergreifendes Assessment und bedarfsorientierte Steuerung für Patienten mit Rückenschmerzen : Prospektive Evaluation eines integrierten Versorgungsprojekts.

BACKGROUND: Back pain is prevalent in the population, sometimes recurrent and may result in everyday and work disabilities. It is often a reason for seeking healthcare support. Analyzing the need of treatment and chronification-risk tailored intervention is a particular demand in healthcare delivery. OBJECTIVES: Reducing downstream consequences of back pain (e. g. pain and disability) by using an interdisciplinary multimodal assessment followed by a risk-tailored intervention. METHODS: Patients with back pain (n = 1638) underwent assessments based on the German Pain Questionnaire (GPQ) and the diagnostic assessment each by a team comprising a physician, a psychologist and a physiotherapist. They were assessed answering a follow-up questionnaire after 6 and/or 12 months (n = 832) for success criteria sensitive to change as pain, everyday and work disability. RESULTS: Patients had on average 62.5 days of work disability and 53.3% had pain up to one year. After assessment, 1447 patients (88.3%) were assigned to receive an intensive interdisciplinary multimodal back pain intervention. Intervention groups were: 120 h of full-time treatment for 4 weeks (n = 1030) or 60 h (n = 224), 48 h part time treatment for 3 months (n = 87), and in-patient hospital treatment for about 17 days (n = 106). The effect sizes of success criteria were large to very large in all treatment groups. CONCLUSIONS: Tailored, interdisciplinary and intensive intervention is effective in reducing downstream consequences of back pain. The treatment assignment was based on patient reports (GPQ score) and multidisciplinary assessments (clinical evidence score). Tailored interventions should include sufficient intensity for highly disabled patients. Care integration such as timely communication between the health insurance system, back pain centers and usual healthcare services as well as patient- and process-related documentation are crucial for this intervention.

Zinc Deficiency-Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency.

BACKGROUND: Zinc deficiency-like (ZDL) syndrome is an inherited defect of Fleckvieh calves, with striking similarity to bovine hereditary zinc deficiency (BHZD). However, the causative mutation in a phospholipase D4 encoding gene (PLD4) shows no connection to zinc metabolism. OBJECTIVES: To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype. ANIMALS: Nine hospitalized calves with crusting dermatitis and confirmed mutation in PLD4 and medical records from 25 calves with crusting dermatitis or suspected zinc deficiency. METHODS: Prospective and retrospective case series. RESULTS: The 9 calves (age: 5-53 weeks) displayed a moderate to severe crusting dermatitis mainly on the head, ventrum, and joints. Respiratory and digestive tract inflammations were frequently observed. Zinc supplementation did not lead to remission of clinical signs in 4 calves. Laboratory variables revealed slight anemia in 8 calves, hypoalbuminemia in 6 calves, but reduced serum zinc concentrations in only 3 calves. Mucosal erosions/ulcerations were present in 7 calves and thymus atrophy or reduced thymic weights in 8 calves. Histologically, skin lesions were indistinguishable from BHZD. Retrospective analysis of medical records revealed the presence of this phenotype since 1988 and pedigree analysis revealed a common ancestor of several affected calves. CONCLUSIONS AND CLINICAL IMPORTANCE: ZDL syndrome should be suspected in Fleckvieh calves with crusting dermatitis together with diarrhea or respiratory tract inflammations without response to oral zinc supplementation. Definite diagnosis requires molecular genetic confirmation of the PLD4 mutation.

The complexities of pain after stroke--a review with a focus on central post-stroke pain.

Pain is frequently reported following stroke, but seems to be an underemphasized phenomenon since it can importantly impact rehabilitation and long-term outcomes. Two major forms of pain have to be distinguished in patients with post-stroke pain: central, neuropathic pain, arising from the vascular lesion defined as central post-stroke pain (CPSP) and pain primarily triggered by peripheral mechanisms such as hemiplegic shoulder pain and spasticity-related pain. Headache after stroke is difficult to classify since the pathophysiology is unclear. The suggested underlying mechanisms as well as treatment strategies of post-stroke pain differ according to the origin (peripheral versus central). This article aims at reviewing the pertinent evidence regarding clinical characteristics and mechanisms of post-stroke pain generation with a focus on CPSP. We discuss possible treatment options and highlight current pathophysiological concepts.

[Efficacy and patient benefit of treatment of irritated skin with ointments containing dexpanthenol: health services research (observational study) on self-medication in a pharmaceutical network]. / Patientennutzen und Anwendungsmerkmale der Behandlung irritierter Haut mit dexpanthenolhaltiger Salbe: Versorgungsstudie (Anwendungsbeobachtung) zur Selbstmedikation in einem Apothekennetzwerk.

BACKGROUND: Products containing dexpanthenol are used to treat irritated and inflamed skin. So far there is a lack of data for the evidence of patient-relevant benefits. OBJECTIVE: Assessment of the patient-relevant benefit of ointments containing dexpanthenol in the self-medicated therapy of irritated skin. METHODS: Prospective, observational study in a network of 392 pharmacies. Consecutive recruitment of n=1,886 patients with symptoms of irritated skin, including non-inflammatory intervals of atopic eczema, other xerotic skin conditions and impairment of skin barrier. The patient-relevant benefit was ascertained prior to and 7-10 days after treatment through the patient-benefit index (PBI). RESULTS: The PBI showed that 91.5% of the patients experienced a relevant benefit from treatment. 94.7% directly indicated to have had achieved successful therapeutic results. All symptoms of irritated skin (e.g. xerosis, erythema, desquamation) significantly improved (p

Assessing the value of supportive skin care: development and validation of an instrument for evaluating patient-relevant benefit.

BACKGROUND: Supportive skin care for irritated and inflamed skin is one of the most important measures in the prevention and treatment of eczema and sensitive skin. OBJECTIVES: To develop and validate an instrument for the evaluation of patient-relevant benefit in the supportive care of irritated skin with nonpharmacological topical agents. METHODS: Patient-defined treatment objectives and benefits of supportive skin care were determined in an open survey of patients with irritated skin. A pilot questionnaire was constructed according to the Patient Benefit Index (PBI). The questionnaire was tested for feasibility and validity in 1,886 patients with various irritated skin conditions. RESULTS: From a total of 90 characteristics of basic therapy benefit, a 23-item questionnaire was constructed. This questionnaire ('PBI-k') proved to be feasible, reliable and was associated with a high level of patient acceptance in the surveillance field. The questionnaire showed good internal consistency, distribution characteristics and convergent validity with patient satisfaction. CONCLUSION: The PBI-k is the first specific instrument developed for the evaluation of patient-defined benefit in supportive skin care with nonpharmacological topical agents. Feasibility and psychometric properties make this questionnaire suitable for application in studies involving patients with irritated, sensitive skin.

[Contact heat evoked potentials for the evaluation of pain pathways]. / Kontakthitzeevozierte Potenziale. Diagnostische Option für die Evaluation des Schmerzsystems.

Pain evoked potentials offer a possibility for the evaluation of nociceptive pathways. Contact heat evoked potentials (CHEPS) represent a novel technique allowing to investigate peripheral pain pathways represented by small-diameter nerve fibers (A-delta and C fibers) and to study the spinothalamic tract. In contrast to more time-consuming methods such as quantitative sensory testing, CHEPS enables an objective investigation of pain pathways. This article reviews and discusses the technique, possible indications, and pitfalls in the context of clinical cases.

Is HSV serology useful for the management of first episode genital herpes?

BACKGROUND: First episode genital herpes simplex virus (HSV) infections can be classified into three groups, primary genital herpes (no previous exposure to HSV), non-primary first episode (IgG antibody to HSV of the non-presenting type), and first episode with pre-existing IgG HSV antibodies. The use of IgM to classify first episode genital herpes has not been evaluated. OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HSV-1 and HSV-2 IgM antibodies for the diagnosis of first episode genital herpes, when compared with clinical diagnosis. METHODS: Patients with a first clinical episode of genital herpes were recruited. Sera were tested for IgG antibodies to HSV-2 using an indirect enzyme linked immunosorbent assay (ELISA). Equivocal results were resolved by western blot. HSV-1 IgG and IgM and HSV-2 IgM antibodies were detected using western blot. RESULTS: 157 patients were recruited. 31 were excluded (missing data or no detectable antibodies and negative viral isolation). Therefore, 126 patients were included in the analysis. 23 (18.3%) had primary genital herpes, 34 (27.0%) non-primary first episode, and 69 (54.8%) had pre-existing genital herpes. The specificity and PPV of HSV IgM was 100%; the sensitivity was 79% and the NPV 85%. CONCLUSION: IgM HSV serology may be useful in the management of some patients with first episode genital herpes and provide an indication of the source of infection. Drawbacks include the low sensitivity and NPV, lack of availability, IgM antibodies may occasionally be produced in response to recurrent infection and, finally, IgM antibodies may take up to 10 days to develop and last 7-10 days.

Sexual behaviour and social class in Australian women.

Sexual behaviour is determined by social, cultural and personal factors. Sexual behaviour studies have been conducted in many countries. However, information from Australia is limited. This study was conducted in Obstetrics Department, Westmead Hospital, Sydney. Questionnaire-derived demographic and behavioural characteristics for public and private patients were compared using bivariate and logistic regression analyses. Of the patients, 3036 were public, and 595 private. On bivariate analysis some significant differences were private patients more likely to be born in Australia and have a higher education level whereas public patients were more likely to have had a greater number of lifetime sexual partners and younger age at first sex. Public patients were more likely to be herpes simplex virus type 2 (HSV-2) antibody positive (12%) than private patients (6%). On logistic regression significant variables included country of birth, being HSV-2 antibody positive, and age at first sex. A number of sexual and social variables were significantly different, comparing patients in the public and private sectors. Evaluation of interventions to reduce the sexual risk to women in the public sector should be considered, including encouraging young women to delay their sexual debut, and reducing the number of sexual partners.

Thrombolytic fibrin specificity influences activated partial thromboplastin time prolongation in vitro.

Despite limited comparative data, guidelines suggest the same concomitant unfractionated heparin (UFH) dose for all fibrin-specific thrombolytic agents in acute myocardial infarction. Since a supratherapeutic activated partial thromboplastin time (aPTT) correlates with adverse outcomes, clarifying effects of various agents on aPTT are needed. The present in vitro study evaluated the influence of alteplase (rt-PA), reteplase (r-PA), and tenecteplase (TNK) on aPTT prolongation. Blood samples from healthy volunteers (n = 12) were treated with equipotent concentrations of rt-PA, r-PA, and TNK, with and without UFH. Samples of each treatment group were incubated at 37 degrees C; aPTT and fibrinogen activity were measured after 4 h. Mean aPTT values for rt-PA alone and r-PA alone were prolonged versus those of TNK alone (P = 0.001 for both). Combined with UFH, rt-PA and r-PA increased the aPTT versus UFH alone (P < 0.05 for both). Interestingly, TNK + UFH reduced the aPTT versus UFH alone (P < 0.001). A negative correlation existed between fibrinogen activity and aPTT for all treatments, except TNK alone. The present investigation illustrates that an agent with maximal fibrin specificity (TNK) has minimal effect on the aPTT, while agents with less fibrin specificity are more likely to prolong the aPTT, with and without UFH present.

Resident interpretation of emergency CT scans in the evaluation of acute appendicitis.

PURPOSE: Radiology resident interpretation of computed tomographic (CT) scans at academic institutions often guides management of cases of suspected acute appendicitis in the emergency department. The purpose of this study was to compare resident and faculty interpretation of CT scans obtained for acute appendicitis. MATERIALS AND METHODS: From December 16, 1999, to July 13, 2000, CT was performed in 103 consecutive patients between the hours of 9:00 PM and 8:00 AM who were suspected of having acute appendicitis. The authors compared the residents' preliminary written interpretations with both the final reports written by the faculty and the surgical findings. The faculty interpreting the CT scans were aware of resident interpretations but were not aware that a study was being conducted. RESULTS: The final faculty interpretation and the preliminary resident interpretation were identical in 96 of the 103 patients (93%; 95% confidence interval: 87.8%, 97.2%). In only one patient was a scan originally interpreted as negative interpreted as positive by the faculty member. Clinically, the patient did not have acute appendicitis, and surgery was not perforrmed. CONCLUSION: In the diagnosis of acute appendicitis, image interpretations made by adequately trained radiology residents can be expected to closely match those of the radiology faculty, and the practice of after-hours interpretation of such studies by radiology residents is safe.

Sexual and demographic risk factors for herpes simplex type 1 and 2 in women attending an antenatal clinic.

OBJECTIVE: To establish risk factors for the presence of HSV-2 and HSV-1 infections in pregnant women. DESIGN, POPULATION, AND SETTING: A prospective study of 3306 women attending the antenatal department Westmead Hospital, Sydney, between June 1995 and April 1998. METHODS: Women completed a self administered questionnaire to establish risk factors for the presence of HSV-2 and HSV-1. Sera were tested for antibodies to HSV-2 and HSV-1. Data were analysed using SPSS and SAS. MAIN OUTCOME MEASURES: Seroprevalence of and risk factors for HSV-2 and HSV-1. RESULTS: 375 (11.3% (95% CI 10.3-12.5)) women were HSV-2 antibody positive. Increasing age, Asian country of birth, lower education level, public hospital status, confirmed genital herpes, a partner with genital herpes, early age of first sex, more than one lifetime sexual partner, and previous chlamydia infection were independently associated with HSV-2 seropositivity. Of 408 women tested for HSV-1 antibodies, 323 (79.2% (95% CI 74.9-83.0)) were positive. Oral herpes, oral blisters or sores, and being HSV-2 seropositive were independently associated with HSV-1 seropositive status. When the logistic regression model was rerun without HSV-2 status, parity of two or more and one or more sexual partners in the past 3 months were significant predictors of HSV-1 seropositivity. CONCLUSIONS: The presence of antibodies to HSV-2 and HSV-1 is related to a number of sexual and demographic risk factors. Public health campaigns directed at encouraging young people to delay the onset of sexual activity and reduce the number of sexual partners need to be evaluated. However, the possible availability of an HSV-2 vaccine that is able to protect over 70% of women offers the best hope for control of genital herpes.

Identification and expression of the genes and purification and characterization of the gene products involved in reactivation of coenzyme B12-dependent glycerol dehydratase of Citrobacter freundii.

The coenzyme B12-dependent glycerol dehydratase of Citrobacter freundii is subject to suicide inactivation by the natural substrate glycerol during catalysis. We identified dhaF and dhaG as the genes responsible for reactivation of inactivated dehydratase. Northern blot analyses revealed that both genes were expressed during glycerol fermentation. The dhaF gene is transcribed together with the three structural genes coding for glycerol dehydratase (dhaBCE), whereas dhaG is coexpressed with the dhaT gene encoding 1,3-propanediol dehydrogenase. The dhaF and dhaG gene products were copurified to homogeneity from cell-free extracts of a recombinant E. coli strain producing both His6-tagged proteins. Both proteins formed a tight complex with an apparent molecular mass of 150 000 Da. The subunit structure of the native complex is probably alpha2beta2. The factor rapidly reactivated glycerol- or O2-inactivated hologlycerol dehydratase and activated the enzyme-cyanocobalamin complex in the presence of coenzyme B12, ATP, and Mg2+. The DhaF-DhaG complex and DhaF exhibited ATP-hydrolyzing activity, which was not directly linked to the reactivation of dehydratase. The purified DhaF-DhaG complex of C. freundii efficiently cross-activated the enzyme-cyanocobalamin complex and the glycerol-inactivated glycerol dehydratase of Klebsiella pneumoniae. It was not effective with respect to the glycerol dehydratase of Clostridium pasteurianum and to diol dehydratases of enteric bacteria.

Emotion work and job stressors and their effects on burnout.

Abstract This article reports research on emotion work, organizational as well as social variables as predictors of job burnout. In burnout research, high emotional demands resulting from interactions with clients are seen as a core characteristic of service jobs. However, these emotional demands were seldom measured in a direct manner. It was only recently that emotional demands were included in studies on burnout referring to the concept of emotion work (emotional labor). Emotion work is defined as the requirement to display organizationally desired emotions. A multi-dimensional concept of emotion work was used to analyze the relations of emotion work variables with organizational and social variables and their joint effect on burnout in five samples including employees working in children's homes, kindergartens, hotels, banks and call centers. Emotion work variables correlated with organizational stressors and resources. However, hierarchical multiple regression showed a unique contribution of emotion work variables in the prediction of burnout. Moreover, the analysis of interaction effects of emotional dissonance and organizational and social stressors showed that for service professionals, the coincidence of these stressors led to exaggerated levels of emotional exhaustion and depersonalization.

Toxic metronidazole-induced MRI changes.

OBJECTIVE: To report a case of changes documented by magnetic resonance imaging (MRI) of the head probably due to accumulation of metronidazole in a patient with liver dysfunction. CASE SUMMARY: A 34-year-old Hispanic man with cirrhosis and hepatitis C being treated with metronidazole for Bacteroides fragilis meningitis and bacteremia developed ataxia, disorientation, and peripheral neuropathy. An MRI at the time meningitis was diagnosed was negative. After the patient received > 60 g of metronidazole, an MRI revealed increased signal intensity below, behind, and lateral to the fourth ventricle. Concomitant metronidazole serum concentration was toxic at 35.1 micrograms/mL. DISCUSSION: This is the second reported case of metronidazole-induced MRI changes. Metronidazole is known to accumulate in patients with liver dysfunction and can cause peripheral neuropathy and central nervous system (CNS) dysfunction; these effects may take up to two years to completely resolve. CONCLUSIONS: Metronidazole dosages should be reduced in patients with liver dysfunction to prevent the accumulation of metronidazole, which can lead to CNS dysfunction and peripheral neuropathy.

Nociceptive fingertip stimulation inhibits synergistic motoneuron pools in the human upper limb.

BACKGROUND: Activation of distinct muscle groups organized in a stereotyped manner ("muscle synergies") is thought to underlie the production of movement by the vertebrate spinal cord. This results in movement with minimum effort and maximum efficiency. The question of how the vertebrate nervous system inhibits ongoing muscle activity is central to the study of the neural control of movement. OBJECTIVE: To investigate the strategy used by the human spinal cord to rapidly inhibit muscle activation in the upper limb. METHODS: The authors performed a series of experiments in 10 healthy subjects to assess the effect of nociceptive cutaneous stimulation on voluntarily contracting upper limb muscles. They recorded the electromyogram (EMG) with surface electrodes placed over various upper limb muscles. RESULTS: The authors found evidence of a simple inhibitory strategy that 1) was dependent on the intensity of the stimulus, 2) was maximally evoked when stimulation was applied to the fingertips, 3) preceded the earliest onset of voluntary muscle relaxation, and 4) produced inhibition of EMG activity in specific upper limb muscle groups. Nociceptive fingertip stimulation preferentially inhibited contraction of synergistic muscles involved in reaching and grasping (intrinsic hand muscles, forearm flexors, triceps) while having little effect on biceps or deltoid. CONCLUSIONS: Neural circuitry within the human spinal cord is organized to inhibit movement by rapidly deactivating muscles that constitute distinct muscle synergies. This strategy of selective and concurrent deactivation of the same basic elements that produce synergistic movement greatly simplifies motor control.