Occurrence and determinants of parental psychosocial stress and mental health disorders in parents and their children in early childhood: rationale, objectives, and design of the population-based SKKIPPI cohort study.

PURPOSE: The postnatal period is a vulnerable time for parents and children but epidemiological and health care utilisation data for Germany on parental mental health during early childhood is scarce. This protocol describes the rationale, aim and study design of a population-based cohort study to assess the occurrence and determinants of psychosocial stress and mental health disorders, as well as the use and cost of health care and social services in early childhood. METHODS: As part of the collaborative SKKIPPI project, we will contact a random sample of 30,000 infants listed in the residents' registration offices of three German towns and we expect to include 6,000 mother-child pairs. Both parents are invited to fill out an online screening questionnaire. Mothers with indications of psychosocial stress will be interviewed to assess mental health disorders, regulatory problems of their children, as well as health care and social services utilisation, with a follow-up assessment after 6 months. RESULTS: After description of sociodemographic and health data, we will analyse occurrences, patterns, and potential determinants (maternal age, social status, household factors, migration status etc.) of psychosocial stress and mental health disorders in the mothers and their children in early childhood. CONCLUSIONS: Our study will identify potential risk and protective factors for postnatal mental health and health care utilization of psychosocially burdened families. This will help to improve prevention and treatment strategies to strengthen the parent-child relationship, to reduce persisting vulnerability of children, and to improve health care and social services. TRIAL REGISTRATION: The study has been registered in the German Clinical Trial Registry on February 8th 2019 (DRKS-ID: DRKS00016653).

Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease.

In cancer or hematologic disorders, chemokines act as growth- or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, -9, -10, CCL2, -5, and IL-12 in AML/MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blast-proportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, -9, -10 and lower release of CCL2 and -5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2-release at relapse were found compared to first diagnosis - pointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, -9, -10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and -5 but lower levels of CXCL8, -9, -10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, -9, -10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

[Abortive course of malignant hyperthermia following preclinical induction of general anesthesia using succinylcholine]. / Abortiver Verlauf einer malignen Hyperthermie nach präklinischer Narkoseinduktion mit Succinylcholin.

In a 59-year-old woman with a perforating eyeball injury to the right eye, the emergency physician induced a preclinical general anesthesia with propofol, fentanyl and the depolarizing muscle relaxant succinylcholine. Anesthesia was maintained using propofol and remifentanil infusion throughout the preoperative period and the subsequent surgical procedure. Postoperatively, isolated rhabdomyolysis with an increase in serum creatine kinase to >20,000 U/l was observed. The diagnosis of malignant hyperthermia (MH) susceptibility could be confirmed in the patient 4 months after the acute event by the in vitro contracture test and detection of the MH causative mutation p.Val4849Ile in exon 101 of the ryanodine receptor gene. Due to the variable expression, for a long time MH often remained unrecognized. Warning symptoms, such as unspecific tachycardia or masseter spasm following succinylcholine injection, should alert emergency physicians to include MH susceptibility in the differential diagnostics. With an estimated genetic MH prevalence of 1:2000-3000, individuals with known or so far unrecognized MH disposition are likely to be among patients treated in the preclinical setting. If a person develops MH symptoms after exposure to triggering agents, immediate hospital admission is essential in order to initiate guideline-conform treatment without further delay because preclinically the life-saving causal measures are not possible due to the lack of supply of dantrolene.

[Malignant hyperthermia]. / Maligne Hyperthermie.

Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage.

Sevoflurane is less sensitive than halothane for in vitro detection of malignant hyperthermia susceptibility.

BACKGROUND: Sevoflurane is a known triggering agent of malignant hyperthermia (MH). The present study analyzed different effects of sevoflurane on skeletal muscle of MH susceptible and nonsusceptible individuals in vitro and compared the results to the standardized test protocol with halothane and caffeine. A potential influence of a present ryanodine receptor type 1 (RyR1) mutation was investigated. METHODS: Muscle bundles of 24 MH-susceptible patients with or without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8 vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was performed. RESULTS: The in vitro parameters initial length, weight, predrug resting tension, and predrug twitch height did not differ between the groups. Sevoflurane caused significant contractures in MH-susceptible but not in MH-nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the susceptible patients developed contractures ≥ 2 mN after increasing concentrations while 83% did so after rapid bolus administration. Presence of an RyR1 mutation was detected in 36% of the examined MH-positive patients but had no influence on developing contractures. CONCLUSION: Sevoflurane-induced contractures do not reliably detect MH susceptibility on an individual level. Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation-specific effects regarding contracture sizes after incubation with sevoflurane, halothane, or caffeine were not found.

Efficient control of pandemic 2009 H1N1 virus infection with intravenous zanamivir despite the lack of immune function.

A teenager who acquired 2009 H1N1 influenza A lower respiratory tract infection during total bone marrow and lymphoid aplasia, in the setting of human leukocyte antigen-haploidentical hematopoietic stem cell transplantation, was successfully treated with intravenous zanamivir. This case demonstrates efficient control of pandemic influenza infection by intravenous zanamivir in the absence of any functional immune system, thus suggesting profound antiviral activity.

Epidemiology and clinical characteristics of pandemic (H1N1) 2009 influenza infection in pediatric hemato-oncology and hematopoietic stem cell transplantation patients.

BACKGROUND: For children with hemato-oncologic diseases, especially after hematopoietic stem cell transplantation (HSCT), the risk for developing complications related to pandemic influenza A (H1N1) 2009 (pH1N1) infection is largely unknown. METHODS: A retrospective chart study was performed of pH1N1 cases diagnosed between October 2009 to January 2010 in the hemato-oncologic unit of the University Children's Hospital of Düsseldorf, Germany. FINDINGS: In total, 21 children were diagnosed with laboratory-confirmed pH1N1; in 16 patients with malignancies (acute leukemia 7, lymphoma 4, solid tumors 2, others 3) and in 5 with benign hematologic disorders. Five patients had undergone prior HSCT, although 1 patient was diagnosed during conditioning therapy with high-dose chemotherapy in preparation for haploidentical HSCT. Most frequent symptoms were fever (>38.5°C) and cough (in 100%), and rhinorrhea (57%). The 2 patients acquiring pH1N1 infection under high-dose or intensive chemotherapy did not require intensive care or mechanical ventilation, and both recovered under antiviral therapy. Oseltamivir was administered to 11 patients; in 1 patient, therapy was switched, on a compassionate-use basis, to intravenous zanamivir because of lack of clinical improvement after oseltamivir therapy. Complications were hospitalization (19%), demand of oxygen supplementation, delay/interruption of antineoplastic therapy, and prolonged administration of antibiotics and antipyretics. CONCLUSION: In the investigated patient population, pH1N1 was mild in most cases, but was associated with substantial morbidity in a proportion of patients and led to interruption and delay in anticancer treatment.

An unusual manifestation of post-transplant lymphoproliferative disorder in the lip after pediatric heart transplantation.

PTLD is a serious and frequently observed complication after solid organ transplantation. We present a six-yr-old girl with a rapidly growing, solid tumor of the lip four yr after orthotopic heart transplantation, which was classified as monomorphic PTLD with the characteristics of a diffuse large B-cell lymphoma. Treatment with reduction in immunosuppression, ganciclovir, and anti B-cell monoclonal antibody (rituximab) resulted in full remission since 12 months. To the best of our knowledge, this report is the first description of PTLD in the lip in a pediatric patient after heart transplantation in the English literature.

Invasive aspergillosis in pediatric oncology patients: a rare event with poor prognosis--case analysis to plan better targeted prophylactic or therapeutic measurement.

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials. In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA. In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting.

Ultrasound guidance for neuraxial analgesia and anesthesia in obstetrics: a quantitative systematic review.

PURPOSE: The aim of this quantitative systematic review was to assess the efficacy and safety of ultrasound-guided neuraxial blocks in obstetric analgesia and anesthesia. MATERIALS AND METHODS: A systematic search for clinical trials investigating the efficacy and safety of ultrasound-assisted neuraxial blocks in comparison to any other technique was performed in MEDLINE, EMBASE, CINAHL and CENTRAL. Relative risks (RR) were calculated for dichotomous data (e. g. number of patients with vascular punctures), and mean differences (MD) were calculated for continuous outcomes (e. g. number puncture attempts), along with the respective 95 % confidence intervals (95 % CI). RESULTS: Six clinical trials (published between 2001 and 2009) including the data of 659 patients satisfied the inclusion criteria. Ultrasound-facilitated neuraxial blocks required a lower number of puncture attempts (MD: -0.92; 95 % CI: -1.11 to -0.74; p < 0.00001) and fewer puncture levels (MD: -0.2; 95 % CI: -0.31 to -0.1; p = 0.0002) in comparison with the more conventional loss of resistance. The success rate with the first attempt under ultrasound guidance in supposedly difficult patients was 71 % in comparison to 20 % using a conventional technique. Patients receiving ultrasound-assisted neuraxial blocks had a lower rate of procedure-related complications (post-dural puncture headache, spinal or vascular puncture). CONCLUSION: There is some evidence that ultrasound guidance may improve the efficacy and safety of neuraxial blocks in obstetrics. If technical difficulties are anticipated, ultrasound may lower the rate of procedure-related adverse events.

iNKT cell frequency in peripheral blood of Caucasian children and adolescent: the absolute iNKT cell count is stable from birth to adulthood.

Human invariant natural killer T cells (iNKT cells) are a unique population of T cells that express a semi-invariantly rearranged T cell receptor (TCR) and are involved in a variety of immunoregulatory processes. We assessed the frequency of peripheral blood iNKT cells in 64 healthy Caucasian children from 7 months to 18 years of age and five cord blood samples by flow cytometry. iNKT cells were measured as CD3(+) cells co-expressing TCRVα24 and TCRVß11 and using the monoclonal antibody 6B11, which recognizes specifically their invariant TCR rearrangement. The absolute number of iNKT cells ranged from 86 to 10,499 (CD3(+) /TCRVα24(+) / TCRVß11(+)) and 233 to 11,167 (CD3(+) /6B11(+)) iNKT cells per millilitre of blood. This range is stable from birth to adulthood. The relative iNKT cell count was found to be 0.003-0.71% (CD3(+) /TCRVα24/TCRVß11) and 0.019-0.776% (CD3/6B11) of peripheral blood T cells and shows only a slight increase with age.

Growth of chromium carbide in a hot wall DLICVD reactor.

Chromium carbide coatings were grown at 748 K in a hot wall CVD reactor fed by sublimation of bis(benzene)chromium, BBC (MOCVD) and by direct liquid injection using a BBC/toluene solution (DLICVD). The two types of coatings exhibit an amorphous structure and the same C content (22 at.%). DLICVD permits delivering higher mass flow rate of precursors and consequently the growth rate is 3 times higher and the thickness uniformity is better than using MOCVD. Chromium metal deposition has also been investigated by DLICVD in this hot wall reactor using BBC/toluene/additive as precursor. The purpose of the additive is to block carbide formation. Two additives have been studied: (i) hexachlorobenzene (C6Cl6) and (ii) thiophenol (C6H5SH). The ratio additive/BBC required for Cr metal deposition is a few percent. In this process, C6Cl6 is not decomposed and only traces of Cl (0.4 at.%) are found in the coatings. For a ratio C6Cl6/BBC > 27% the growth of any coating is blocked. The gas phase containing C6H5SH is more reactive since the onset of deposition occurs approximately 50 K before the temperature of the chlorinated compound. Furthermore, a sulfur contamination of 3 at.% has been analyzed in the coatings revealing a partial decomposition of the additive. The results are detailed and discussed in relation with previous works.

Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in 'DC-culture-media' shifts correlations of released chemokines with antileukemic T-cell reactions.

Dendritic cells (DC) and T-cells are mediators of CTL-responses. Autologous (from patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS)) or allogeneic (donor)-T-cells stimulated by DCleu, gain an efficient lysis of naive blasts, although not in every case. CXCL8, -9, -10, CCL2, -5 and Interleukin (IL-12) were quantified by Cytometric Bead Array (CBA) in supernatants from 5 DC-generating methods and correlated with AML-/MDS-patients' serum-values, DC-/T-cell-interactions/antileukemic T-cell-reactions after mixed lymphocyte culture (MLC) and patients' clinical course. The blast-lytic activity of T-cells stimulated with DC or mononuclear cells (MNC) was quantified in a cytotoxicity assay. Despite great variations of chemokine-levels, correlations with post-stimulation (after stimulating T-cells with DC in MLC) improved antileukemic T-cell activity were seen: higher released chemokine-values correlated with improved T-cells' antileukemic activity (compared to stimulation with blast-containing MNC) - whereas with respect to the corresponding serum values higher CXCL8-, -9-, and -10- but lower CCL5- and -2-release correlated with improved antileukemic activity of DC-stimulated (vs. blast-stimulated) T-cells. In DC-culture supernatants higher chemokine-values correlated with post-stimulation improved antileukemic T-cell reactivity, whereas higher serum-values of CXCL8, -9, and -10 but lower serum-values of CCL5 and -2 correlated with post-stimulation improved antileukemic T-cell-reactivity. In a context of 'DC'-stimulation (vs serum) this might point to a change of (CCL5 and -2-associated) functionality from a more 'inflammatory' or 'tumor-promoting' to a more 'antitumor'-reactive functionality. This knowledge could contribute to develop immune-modifying strategies that promote antileukemic (adaptive) immune-responses.

Caregiver involvement in psychiatric inpatient treatment - a representative survey among triads of patients, caregivers and hospital psychiatrists.

AIMS: Studies on the frequency of caregiver involvement in representative inpatient samples are scarce. The aim of our study was to conduct a representative survey on caregiver involvement in routine inpatient care involving all three parties (patients, caregivers, psychiatrists). Therefore, we performed face-to-face interviews consisting of open-ended questions to gain a deeper understanding of when and how caregivers are involved in care treatment and to identify which topics are mainly discussed. METHODS: This cross-sectional survey included inpatients from 55 acute psychiatric wards across ten psychiatric hospitals, their treating psychiatrists and, when possible, their caregivers. In total, we performed semi-structured face-to-face interviews with 247 patients, their treating psychiatrists and 94 informal caregivers. Each psychiatrist named the next two to three patients to be discharged. After a patient had given informed consent, the interview was performed by a researcher. In addition, the psychiatrist and, when possible, the primary caregiver identified by the patient, were also interviewed. RESULTS: It was perceived by both patients and psychiatrists that contact between caregiver and psychiatrist had taken place in one-third of the patient cases. Predictors for psychiatrist-caregiver-contact were revealed in the patient's diagnosis (schizophrenia), a lower history of inpatient stays, and the respective hospital. According to psychiatrists the most frequent subjects of discussion with caregivers involved therapeutic issues and organisational and social-psychiatric topics (e.g. work, living and social support). Patients and caregivers stated that psychiatric treatment and the diagnostic classification of the mental illness were the most frequent topics of conversation. For all three groups, the most often cited reason for missed caregiver involvement was the subjective perception that a caregiver was not in fact needed. CONCLUSIONS: Whether or not caregivers were contacted and involved during an inpatient stay strongly depended on the individual hospital. The frequency of involvement of caregivers can certainly be increased by changing processes and structures in hospitals. All three parties (patients, caregivers and psychiatrists) most often stated that the caregiver was not involved in the treatment because they thought it was unnecessary. Evidence demonstrates the positive effect of caregivers' involvement on the therapeutic process but also on the well-being of the caregiver, therefore it is necessary to increase awareness of this evidence among all three interest groups.

Efficacy of Parent-Infant-Psychotherapy with mothers with postpartum mental disorder: study protocol of the randomized controlled trial as part of the SKKIPPI project.

BACKGROUND: After the birth of a child, many mothers and fathers experience postpartum mental disorders like depression, anxiety, obsessive-compulsive disorder, stress or other illnesses. This endangers the establishment of a secure attachment between the children and their primary caregivers. Early problems in parent-child interaction can have adverse long-term effects on the family and the child's well-being. In order to prevent a transgenerational transmission of mental disorders, it is necessary to evaluate psychotherapeutic interventions that target psychologically burdened parents of infants or toddlers. The aim of this trial is to investigate the efficacy of Parent-Infant-Psychotherapy (PIP) for mothers with postpartum mental disorder and their infants (0-12 months). METHODS/DESIGN: In this open, randomized controlled intervention trial 180 mother-infant-dyads will be included and randomly allocated to 12 sessions of PIP or care as usual. The interventions take place either in inpatient adult psychiatric departments or in outpatient settings with home visits. The primary outcome is the change in maternal sensitivity assessed by the Sensitivity subscale of the Emotional Availability Scale (EAS) through videotaped dyadic play-interactions after 6 weeks. Secondary outcomes are maternal psychopathology, stress, parental reflective functioning, infant development and attachment after 6 weeks and 12 months. In addition, maternal attachment (AAI) and reflective functioning (AAI) will be analyzed as potential moderators, and resource usage in the German health system as well as associated costs will be evaluated. DISCUSSION: There is increasing demand for well-controlled studies on psychotherapeutic interventions in the postpartum period that do not only focus on particular risk groups. This randomized controlled trial (RCT) represents one of the first studies to investigate the efficacy of PIP in inpatient psychiatric departments and outpatient care centers in Germany. The results will fill knowledge gaps on the factors contributing to symptom reduction in postpartum mental disorders and improvements in mother-child relationships and help in developing preventive and therapeutic strategies for the fragmented German health care system. TRIAL REGISTRATION: German Register for Clinical Trials, ID: DRKS00016353.

Infectious agent from a free-living soil amoeba, Naegleria gruberi.

A subcellular infectious material has been found in a strain of the amoeba Naegleria gruberi, strain EG, which is capable of infecting chick embryo cells and causing them to undergo cytopathic changes with the release of more infectious material. The material is present in two lines of the amoeba which were separated shortly after the isolation of the strain and subsequently maintained in separate laboratories.

Arteriovenous extracorporeal lung assist as integral part of a multimodal treatment concept: a retrospective analysis of 22 patients with ARDS refractory to standard care.

BACKGROUND AND OBJECTIVES: Pumpless arteriovenous extracorporeal lung assist is increasingly used as a rescue therapy in acute respiratory distress syndrome. Arteriovenous extracorporeal lung assist is highly efficient in eliminating carbon dioxide and allows the application of ventilator techniques that prioritize lung protection and aim to reduce ventilator-induced lung injury and remote organ dysfunction. METHODS: Retrospective data analysis performed in a 12-bed university hospital ICU. In all, 22 patients with acute respiratory distress syndrome refractory to standard care were included. Arteriovenous extracorporeal lung assist as central part of a multimodal treatment concept was combined with tidal volume (VT) reduction below 4 mL kg-1 predicted body weight, a positive end-expiratory pressure titrated to optimize oxygenation and continuous axial rotation. RESULTS: Hypercapnia was reversed within 24 h in survivors (39 mmHg (35-42) (median and interquartile range) vs. 65 mmHg (54-72), P < 0.05) and non-survivors (5.2 kPa (5.5-6.0) vs. 10 kPa (6.9-13.9), P < 0.05). Oxygenation was significantly improved in survivors after 24 h (PaO2/FiO2 ratio 20.7 kPa (17.4-22.7) vs. 11.7 kPa (7.3-20.8), P < 0.05). All patients required norepinephrine infusion and volume resuscitation. The overall complication rate was 23%, predominantly due to reversible lower limb ischaemia. One patient (5%) was permanently disabled due to amputation of a seriously injured lower leg 9 days after initiation of arteriovenous extracorporeal lung assist therapy; however, the patient survived without neurological deficits despite an initial oxygenation index of 4.4 kPa. The overall mortality rate was 27%. CONCLUSIONS: A multimodal treatment concept with arteriovenous extracorporeal lung assist as its central part provides reversal of hypercapnia and stabilization of oxygenation. In an attempt to maximize lung protection and potentially reduce ventilator-induced lung injury, a further VT reduction below 4 mL kg(-1) predicted body weight combined with a high mean airway pressure and continuous axial rotation is safely possible.

[In-vivo diagnosis of malignant hyperthermia susceptibility: a microdialysis study]. / In-vivo-Diagnostik einer malignen-Hyperthermie-Disposition: Eine Mikrodialysestudie.

BACKGROUND: In malignant hyperthermia (MH), volatile anesthetics induce hypermetabolism, lactic acidosis and rhabdomyolysis in predisposed patients. The authors hypothesized that intramuscular caffeine and halothane application would increase local lactate concentration in MH susceptible (MHS) individuals more than in non-susceptible (MHN) subjects without initiating the full MH syndrome. METHODS: In 14 MHS, 12 MHN and 7 control individuals, microdialysis probes were placed in the rectus femoris muscle and perfused with Ringer's solution at 1 microl/min. After equilibration, 250 microl caffeine (80 mM) was injected through the first microdialysis probe, halothane 10 vol% dissolved in soybean oil was perfused through a second microdialysis probe and a third probe was used for control measurements. Dialysate samples were analyzed for lactate spectrophotometrically. Systemic hemodynamic and metabolic parameters were measured. Data are presented as median and quartiles. RESULTS: Intramuscular caffeine and halothane significantly increased local peak concentrations of lactate in MHS probands [5.0 mM (3.4-8.1 mM) and 3.7 mM (2.6-5.0 mM), respectively] compared to MHN [1.6 mM (1.3-2.0 mM) and 1.9 mM (1.6-2.0 mM)] or control individuals [2.1 mM (1.9-2.3 mM) and 2.0 mM (1.6-2.1 mM)]. This was accompanied by a higher serum creatine kinase level in the MHS group. Hemodynamic and metabolic parameters were normal in the investigated groups. CONCLUSION: Intramuscular caffeine and halothane application induces a temporary and abnormal increase of local lactate in MHS individuals. No serious systemic side effects occurred. This study presents evidence that metabolic monitoring with local stimulation by caffeine and halothane may allow a minimally invasive diagnosis of MH susceptibility.