Supplementary orthopaedic screening for children and adolescents to prevent permanent skeletal deformities - protocol for the "OrthoKids" study.

BACKGROUND: Skeletal deformities (SD) in children and adolescents can lead to arthritic conditions, impairment of quality of life, and high treatment costs in the long term. However, comprehensive data on the prevalence of SDs in children and adolescents are limited and it remains therefore unclear whether there is a healthcare gap. "OrthoKids" is a project that addresses this evidence gap by implementing an orthopaedic screening for children and adolescents that supplements existing detection examinations within statutory standard care in Germany. OBJECTIVE: To detect SDs so that they can be treated as needed at an early stage. METHODS: The implementation of the supplementary orthopaedic screening will be evaluated through an exploratory cohort study that is set up in the German state Baden-Wuerttemberg. 20,000 children and adolescents aged 10 to 14 years will be recruited as a prospective cohort. A retrospective control cohort will be formed based on claims data provided by two cooperating statutory health insurances (SHIs). Participating children and adolescents receive a one-time orthopaedic screening. If at least one SD is diagnosed, treatment will be provided as part of the statutory standard care. Within the scope of the project, a follow-up examination will be performed after one year. An IT-platform will complement the study. The primary outcome measure is the point prevalence of scoliosis, genu varum/valgum, hip dysplasia, and flat feet. Secondary outcome measures are (i) the point prevalence of further less common SDs, (ii) health-related quality of life (HRQoL), (iii) sports ability based on activity (physical/athletic), physical constraints, and (sports) injuries, as well as (iv) monetary consequences of the orthopaedic screenings' implementation. Implementation determinants will be evaluated, too. DISCUSSION: If the supplementary orthopaedic screening proves to be viable, it could be considered as a supplementary examination for children and adolescents within the frame of SHI in Germany. This could relieve the burden of disease among children and adolescents with SDs. In addition, it could disburden SHIs in the medium to long term. TRIAL REGISTRATION: The OrthoKids study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 26th July 2022 under the number 00029057.

[Recommendations for the Stepwise Occupational Reintegration: Can the Characteristic of the Patients Explain the Differences Between the Rehabilitation Centers?]. / Nachsorgeempfehlungen zur stufenweisen Wiedereingliederung: Inwieweit erklären Rehabilitandenmerkmale die bestehenden Unterschiede zwischen den Einrichtungen?

BACKGROUND: The first step to initiate a stepwise occupational reintegration (SOR) is the recommendation of the rehabilitation centers. Therefore rehabilitation centers have a significant impact on the use of SOR. There is evidence that the recommendation rate between the rehabilitation centers differs clearly. The present survey therefore analyses in detail the differences of the recommendation rate and examines which patient-related factors could explain the differences. METHODS: This study is based on analysis of routine data provided by the German pension insurance in Baden-Württemberg (Rehabilitationsstatistikdatenbasis 2013; RSD). In the analyses rehabilitation measures were included if they were conducted by employed patients (18-64 years) with a muscular-skeletal system disease or a disorder of the connective tissue. Logistic regression models were performed to explain the differences in the recommendation rate of the rehabilitation centers. RESULTS: The data of 134 853 rehabilitation measures out of 32 rehabilitation centers were available. The recommendation rate differed between the rehabilitation centers from 1.36-18.53%. The logistic regression analysis showed that the period of working incapacity 12 month before the rehabilitation and the working capacity on the current job were the most important predictors for the recommendation of a SOR by the rehabilitation centers. Also the rehabilitation centers themselves have an important influence. DISCUSSION: The results of this survey indicate that the characteristic of the patients is an important factor for the recommendation of SOR. Additionally the rehabilitation centers themselves have an influence on the recommendation of SOR. The results point to the fact that the rehabilitation centers use different criteria by making a recommendation.

[The User Survey on the Revision of the Classification of Therapeutic Procedures]. / Die Anwenderbefragung zur Aktualisierung der Klassifikation therapeutischer Leistungen (KTL).

INTRODUCTION: An extensive user survey was conducted in the context of updating the Classification of Therapeutic Procedures (KTL 2015). This paper reflects the results of the user survey and raises critical discussion points. METHODS: The user survey was sent to all rehabilitation centers contracted by the German pension insurance as well as professional associations. The user survey was available both as a paper questionnaire and as an online version. The feedback of the user survey provided an important basis for the revision of the KTL. RESULT: The survey yielded 1,868 suggestions from 360 users. Most of them related to chapters E ("occupational therapy, work therapy, other functional therapy") and C ("information, motivation, training"). The change from German diplomas to the international Bachelor's and Master's degrees, and the inclusion of diagnostic and work-related procedures were the main focus of the user feedback. CONCLUSION: For the revision of the KTL, the user survey provided valuable information. Only by the inclusion of practitioners can the KTL meet the requirements of realistic and comprehensive acquisition of data on therapeutic procedures also in future.

[Quality assurance in outpatient neurological rehabilitation: measuring the effects of rehabilitation with the competency rating scale]. / Qualitätssicherung in der ambulanten neurologischen Rehabilitation: Messung der Rehabilitationseffekte mit der Marburger Kompetenz Skala.

BACKGROUND: So far, there are only few studies concerning the outcome of outpatient neurological rehabilitation in Germany. Considering the statutory obligations of quality assurance there is an urgent need of appropriate instruments to assess the rehabilitation outcome. The aim of this study was to assess the appropriateness of the Competency Rating Scale (CRS), which was used to measure rehabilitation outcome, and to collect data of the effects of outpatient neurological rehabilitation as a measure of rehabilitation outcome. METHODS: The basis of this study was data collected between 2008 and 2011. During that period the data of all patients of an outpatient neurological rehabilitation center were consecutively collected. There were no exclusion criteria. To measure rehabilitation outcome patients' self ratings with the CRS were used. To check the appropriateness of the CRS the dropout rate and the missing values were analysed. In addition, the patients' self ratings were compared with the data of a near relative rating with the CRS. RESULTS: On examining the entire group of patients, statistically significant improvements over time were found in the motor as well as in the cognitive-psychosocial areas. The analysis of the data with regard to the appropriateness of the CRS showed considerable ceiling effects and a high dropout rate. Differences between the self and the near relative ratings could be detected. CONCLUSION: For the overall group of patients positive effects of outpatient neurological rehabilitation can be proven. The assessment instrument used in this study is only partially suitable for assessing the outcome of outpatient neurological rehabilitation. The comparison of self and near relative ratings can systematically be used in the therapy process.

[Degenerative rupture of the hip abductors. Missed diagnosis with therapy-resistant trochanteric pain of the hips and positive Trendelenburg sign in elderly patients]. / Degenerative Ruptur der Hüftabduktoren. Verpasste Diagnose bei therapieresistenter Periarthropathie der Hüfte und positivem Trendelenburg-Zeichen des älteren Patienten.

The cases of four elderly patients with persistent trochanteric pain and tears of the gluteus medius and/or gluteus minimus tendons detected in magnetic resonance imaging (MRI) are presented. There was no history of local trauma in any patient but three patients had a positive Trendelenburg sign. Magnetic resonance imaging showed either an obvious discontinuity of the affected tendon or an increased T2 signal above, or less specifically lateral to the greater trochanter. The presence of an elongated tendon on MRI is most likely indicative of a partial rupture of the tendon. Pain and local tenderness over the lateral aspect of the hip in clinical examination is commonly attributed to trochanteric bursitis or trochanteric pain syndrome. Partial or complete tears of the gluteus medius and/or gluteus minimus tendons are thought to represent an unusual finding. However, the true incidence and the clinical significance of hip abductor degeneration and rupture remain to be determined. More studies are needed to examine the prevalence of ruptures in asymptomatic patients, to evaluate the subsequent risk for developing osteoarthritis of the hip (caused by impaired protective reflexes originating from proprioceptive nerve endings in muscle spindles) and to determine the risk for falls related to weakness of hip abduction. Furthermore, no data exist regarding the success rate of conservative treatment. Tears of the gluteus medius and minimus tendons in the elderly population are likely to be a more common cause of pain in the greater trochanteric region than previously thought. In patients who do not respond to conservative treatment, weakness of hip abduction (positive Trendelenburg sign) and new limping should point to the possibility of hip abductor ruptures. The most useful examination technique for diagnosis is MRI.

[Symptoms and cognition in geriatric schizophrenia]. / Symptomatik und Kognition bei Schizophrenie im Alter.

From the first manifestation of schizophrenic psychosis onwards numerous psychopathological symptoms and cognitive impairments occur, which are affected by age and the aging process. Clinical trials report a pronounced incidence of positive symptoms in late-onset schizophrenia. Negative symptoms are often observed in chronic-course psychosis, but occur infrequently in late-onset-schizophrenia. With respect to cognitive performance neuropsychological studies have shown a decrease in the test performance of permanently hospitalised patients with chronic schizophrenia as age and illness duration increased. Comparative studies of early and late-onset patients in most cases have reported no differing profiles of cognitive performance. Some investigators propose that late-onset schizophrenia may be a prodromal symptom of dementia. However, current studies show that late-onset schizophrenia is basically comparable to its early-onset counterpart. The manifestation in youth and early adulthood may be prevented by specific protective factors until aging-related parameters lead to the onset of symptoms during late life.

Surface acoustic wave actuated cell sorting (SAWACS).

We describe a novel microfluidic cell sorter which operates in continuous flow at high sorting rates. The device is based on a surface acoustic wave cell-sorting scheme and combines many advantages of fluorescence activated cell sorting (FACS) and fluorescence activated droplet sorting (FADS) in microfluidic channels. It is fully integrated on a PDMS device, and allows fast electronic control of cell diversion. We direct cells by acoustic streaming excited by a surface acoustic wave which deflects the fluid independently of the contrast in material properties of deflected objects and the continuous phase; thus the device underlying principle works without additional enhancement of the sorting by prior labelling of the cells with responsive markers such as magnetic or polarizable beads. Single cells are sorted directly from bulk media at rates as fast as several kHz without prior encapsulation into liquid droplet compartments as in traditional FACS. We have successfully directed HaCaT cells (human keratinocytes), fibroblasts from mice and MV3 melanoma cells. The low shear forces of this sorting method ensure that cells survive after sorting.

Secondary prevention of minor trauma fractures: the effects of a tailored intervention-an observational study.

INTRODUCTION: Minor trauma fractures (MTF) in the elderly are associated with an increase in mortality, morbidity, and the risk of subsequent fractures. Often, these patients who sustain MTF have an underlying bone disease, such as osteopenia or osteoporosis. Osteoporosis is known to be underdiagnosed and undertreated, and adequate treatment is essential to reduce the occurrence of MTFs. At our hospital, this has led to the implementation of Osteofit, a patient-education-based intervention targeted at improving screening and prevention of osteoporosis, with the goal to reduce the rate of subsequent MTF. OBJECTIVE: The aim of this study was to assess the efficacy of Osteofit in improving osteoporosis screening and treatment in patients after an initial MTF episode. METHODS: The study is a prospective, single-center, cohort study of MTF patients aged 50 years or older. A standardized questionnaire and telephone interview were used to collect 1-year follow-up data. The primary outcome was the rate of patients undergoing Dual X-ray Absorptiometry (DXA) scanning. Secondary outcomes were the rate of patients with a diagnosis of osteoporosis or osteopenia, the rate of patients treated with anti-osteoporotic medication, and the rate of patients with a subsequent fracture. DXA scanning rate, the prevalence of a diagnosis (osteoporosis/osteopenia), and data on medical treatment for osteoporosis were compared to the results of a previous study in the same hospital, published in 2004. RESULTS: Between 2012 and 2015, 411 of 823 eligible patients consented to participate and were included in this study. The mean age was 72 ± 9.3 years. Sixty-three percent (63.3%, n = 252) of the patients received a DXA scan, compared to 12.6% reported in our previous study. Of all patients who received a DXA scan, 199 (82.9%) were diagnosed with osteoporosis or osteopenia. A total of 95 patients (23.1%) received specific medical treatment for osteoporosis and 59.8% reported the intake of any unspecific medication (vitamin D, calcium, or both). Fifteen patients (3.9%) had a subsequent fracture as a result of a minor trauma fall. CONCLUSION: The implementation of a MTF secondary prevention program with dedicated health professionals improved the rate of patients who underwent DXA screening by fivefold. Despite this improvement, DXA screening was missed in over a third of patients, with only 23% of eligible patients receiving specific medical treatment for osteoporosis at 1-year follow-up. Consequently, this tailored intervention is a promising first step in improving geriatric fracture care. However, further work to improve the rate of osteoporosis screening and medical treatment initiation for the long-term prevention of subsequent MTF is recommended. We believe osteoporosis screening and adequate osteoporosis medication should be integrated as standard procedure in the aftercare of MTF. LEVEL OF EVIDENCE: II.

[Bilateral Instability of the Interphalangeal Articulation of the Thumb in Hajdu-Cheney Syndrome]. / Instabilität der Daumenendgelenke beidseits bei Hajdu-Cheney-Syndrom.

We present the case of a 52-year-old lady suffering from Hajdu-Cheney syndrome, a rare hereditary disease, which was referred to our clinic on the basis of progressive instability of the interpalangeal articulations of both thumbs. Even if acroosteolysis of the distal phalangeal bones is typical for this disease, to the best of our knowledge the interphalangeal instability has not been described before.

Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

BACKGROUND: In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. METHODS: In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. RESULTS: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. CONCLUSIONS: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

Altered emotionality and neuronal excitability in mice lacking KCTD12, an auxiliary subunit of GABAB receptors associated with mood disorders.

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, is fundamental to brain function and implicated in the pathophysiology of several neuropsychiatric disorders. GABA activates G-protein-coupled GABAB receptors comprising principal GABAB1 and GABAB2 subunits as well as auxiliary KCTD8, 12, 12b and 16 subunits. The KCTD12 gene has been associated with bipolar disorder, major depressive disorder and schizophrenia. Here we compare Kctd12 null mutant (Kctd12(-/-)) and heterozygous (Kctd12(+/-)) with wild-type (WT) littermate mice to determine whether lack of or reduced KCTD12 expression leads to phenotypes that, extrapolating to human, could constitute endophenotypes for neuropsychiatric disorders with which KCTD12 is associated. Kctd12(-/-) mice exhibited increased fear learning but not increased memory of a discrete auditory-conditioned stimulus. Kctd12(+/-) mice showed increased activity during the inactive (light) phase of the circadian cycle relative to WT and Kctd12(-/-) mice. Electrophysiological recordings from hippocampal slices, a region of high Kctd12 expression, revealed an increased intrinsic excitability of pyramidal neurons in Kctd12(-/-) and Kctd12(+/-) mice. This is the first direct evidence for involvement of KCTD12 in determining phenotypes of emotionality, behavioral activity and neuronal excitability. This study provides empirical support for the polymorphism and expression evidence that KCTD12 confers risk for and is associated with neuropsychiatric disorders.

Visual areas in the dorsal and medial extrastriate cortices of the marmoset.

To define the number and limits of the visual areas in the primate extrastriate cortex, the visuotopy of the dorsal convexity and medial wall was studied by electrophysiological recordings in five marmosets anaesthetised with sufentanil and nitrous oxide and paralysed with pancuronium bromide. We identified five visuotopic representations in and around the densely myelinated zone between visual area 2 (V2) and the posterior parietal cortex. Most of the densely myelinated zone is formed by the homologue of the owl monkey's dorsomedial area (DM); thus, we also termed this area DM in the marmoset. Within DM, the lower quadrant representation is continuous, with central vision represented laterally, peripheral vision medially, the horizontal meridian caudally, and the vertical meridian rostrally. In contrast, the upper quadrant representation is split, with the central portion represented at the lateral edge of DM on the dorsal surface, and the periphery along the midline. Two other visual field representations, corresponding to the dorsointermediate area (DI) and to a new subdivision termed the dorsoanterior area (DA), are also densely myelinated but can be distinguished from DM based on the separation of the bands of Baillarger and visual topography. In addition, a homologue of the medial visual area (M) was identified. Our results reveal a highly complex visuotopy in primate cortex, with local discontinuities in representation and borders between areas that are often not coincident with either the horizontal or the vertical meridian. The topography of the dorsal extrastriate cortex in the marmoset strongly suggests that both visual area 3 (V3) and the parietooccipital area (PO) of other primates are portions of a single visuotopic representation, DM, and calls into question the existence of visual areas with partial or quadrantic representations of the visual field.

Connections of somatosensory cortex in megachiropteran bats: the evolution of cortical fields in mammals.

The cortical connections of the primary somatosensory area (SI or 3b), a caudal somatosensory field (area 1/2), the second somatosensory area (SII), the parietal ventral area (PV), the ventral somatosensory area (VS), and the lateral parietal area (LP) were investigated in grey headed flying foxes by injecting anatomical tracers into electrophysiologically identified locations in these fields. The receptive fields for clusters of neurons were mapped with sufficient density for injection sites to be related to the boundaries of fields, and to representations of specific body parts within the fields. In all cases, cortex was flattened and sectioned parallel to the cortical surface. Sections were stained for myelin and architectonic features of cortex were related to physiological mapping and connection patterns. We found patterns of topographic and nontopographic connections between 3b and adjacent anterior parietal fields 3a and 1/2, and fields caudolateral to 3b (SII and PV). Area 1/2 had both topographic and nontopographic connections with 3b, PP, and SII. Connections of SII and PV with areas 3b, 3a, and 1/2 were roughly topographic, although there was clear evidence for nontopographic connections between these fields. SII was most densely connected with area 1/2, while PV was most densely connected with 3b. SII had additional connections with fields in lateral parietal cortex and with subdivisions of motor cortex. Other connections of PV were with subdivisions of motor cortex and pyriform cortex. Laminar differences in connection patterns of SII and PV with surrounding cortex were also observed. Injections in the ventral somatosensory area revealed connections with SII, PV, area 1/2, auditory cortex, entorhinal cortex, and pyriform cortex. Finally, the lateral parietal field had very dense connections with posterior parietal cortex, caudal temporal cortex, and with subdivisions of motor cortex. Our results indicate that the 3b region is not homogeneous, but is composed of myelin dense and light regions, associated with 3b proper and invaginations of area 1/2, respectively. Connections of myelin dense 3b were different from invaginating portions of myelin light area 1/2. Our findings that 3b is densely interconnected with PV and moderately to lightly interconnected with SII supports the notion that SII and PV have been confused across mammals and across studies. Our connectional evidence provides further support for our hypothesis that area 1/2 is partially incorporated in 3b and has led to theories of the evolution of cortical fields in mammals.

Retinotopic organization of the primary visual cortex of flying foxes (Pteropus poliocephalus and Pteropus scapulatus).

The representation of the visual field in the occipital cortex was studied by multiunit recordings in seven flying foxes (Pteropus spp.), anesthetized with thiopentone/N2O and immobilized with pancuronium bromide. On the basis of its visuotopic organization and architecture, the primary visual area (V1) was distinguished from neighboring areas. Area V1 occupies the dorsal surface of the occipital pole, as well as most of the tentorial surface of the cortex, the posterior third of the mesial surface of the brain, and the upper bank of the posterior portion of the splenial sulcus. In each hemisphere, it contains a precise, visuotopically organized representation of the entire extent of the contralateral visual hemifield. The representation of the vertical meridian, together with 8-15 degrees of ipsilateral hemifield, forms the anterior border of V1 with other visually responsive areas. The representation of the horizontal meridian runs anterolateral to posteromedial, dividing V1 so that the lower visual quadrant is represented medially, and the upper quadrant laterally. The total surface area of V1 is about 140 mm2 for P. poliocephalus, and 110 mm2 for P. scapulatus. The representation of the central visual field is greatly magnified relative to that of the periphery. The cortical magnification factor decreases with increasing eccentricity, following a negative power function. Conversely, receptive field sizes increase markedly with increasing eccentricity, and therefore the point-image size is approximately constant throughout V1. The emphasis in the representation of the area centralis in V1 is much larger than that expected on the basis of ganglion cell counts in flat-mounted retinas. Thus, a larger degree of convergence occurs at the peripheral representations in the retino-geniculo-cortical pathway, in comparison with the central representations. The marked emphasis in the representation of central vision, the wide extent of the binocular field of vision, and the relatively large surface area of V1 reflect the importance of vision in megachiropterans.

Monocular focal retinal lesions induce short-term topographic plasticity in adult cat visual cortex.

Electrophysiological recording in primary visual cortex (VI) was performed both prior to and in the hours immediately following the creation of a discrete retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21-64 mm2) were defined in the visual cortex by mapping the extent of the lesion onto the topographic representation in cortex. There was no effect on neuronal responses to the unlesioned eye or on its topographic representation. However, within hours of producing the retinal lesion, receptive fields obtained from stimulation of the lesioned eye were displaced onto areas surrounding the scotoma and were enlarged compared with the corresponding field obtained through the normal eye. The proportion of such responsive recording sites increased during the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed neurons responsive to the lesioned eye. This is an equivalent proportion to that previously reported with long-term recovery (three weeks to three months). Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ. The reorganization of the lesioned eye representation produced binocular disparities as great as 15 degrees, suggesting interactions between sites in VI up to 5.5 mm apart.

Fibrinogen St. Gallen I (gamma 292 Gly--> Val): evidence for structural alterations causing defective polymerization and fibrinogenolysis.

Fibrinogen St. Gallen I was detected in an asymptomatic Swiss woman. Routine coagulation tests revealed a prolonged thrombin and reptilase time. Functionally measured fibrinogen levels were considerably lower than those determined immunologically. Polymerization of fibrin monomers derived from purified fibrinogen was delayed in the presence of either calcium or EDTA. Normal fibrinopeptide A and B release by thrombin was established. An abnormal degradation of fibrinogen St. Gallen I by plasmin was observed. Fragment D1 of normal fibrinogen was fully protected against further proteolysis in the presence of 10 mM calcium, whereas fibrinogen St. Gallen I was partially further degraded to fragments D2 and D3. In the presence of 10 mM EDTA, the conversion of variant fragment D1 to D2 was accelerated whereas the degradation of fragment D2 to D3 was delayed in comparison to degradation of fragments D1 and D2 of normal fibrinogen. Three high-affinity calcium binding sites were found in both normal and variant fibrinogen. Mutation screening with SSCP analysis suggested a mutation in exon VIII of the gamma-chain gene. Cycle sequencing of this gene portion revealed a single base substitution from G to T of the base 7527, leading to replacement of gamma 292 glycine by valine. The same mutation has already been described for the fibrinogen variant Baltimore I. Molecular modeling was performed of a part of the gamma-chain containing the mutation site, based on recently published X-ray crystal structures of human fibrinogen fragment D and of a 30 kD C-terminal part of the gamma-chain. Significant structural alterations due to the substitution of glycine by valine at gamma 292 were observed, e.g. spreading of the protein backbone, probably leading to a modified accessibility of the plasmic cleavage sites in the gamma-chain at 356 Lys and 302 Lys. A shift of gamma 297 Asp that is involved in interactions of fragment D with the Gly-Pro-Arg-Pro-peptide was noted by molecular modeling. The latter observation is compatible with delayed polymerization of fibrin monomers.

Panic disorder in patients with chest pain and angiographically normal coronary arteries.

Although patients with angiographically normal or near normal coronary arteries are at low risk for cardiac disease, several follow-up studies have shown that many continue to report recurrent chest pain associated with social and work dysfunction. Three diagnostic entities have been proposed to explain the morbidity of this group: microvascular angina, esophageal motility disorders and panic disorder. The purpose of this study was to test the hypothesis that panic disorder is found frequently in patients with chest pain who have normal epicardial vessels. Ninety-four subjects with angiographically normal coronary arteries were interviewed according to a structured psychiatric protocol within 24 hours of their catheterizations. Thirty-two (34%) fit Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria for current panic disorder. Because panic disorder can be effectively treated, physicians should consider this diagnosis in this group of patients. Current research findings suggest that panic disorder, microvascular angina and esophageal disorders may each form the basis for chest pain in approximately 25% of these patients. Miscellaneous problems account for the other 25%.

Cellular and serum immune response to dinitrophenol in adult Rana pipiens.

A rabbit anti-Rana anti-DNP antiserum was used in order to estimate changes in frequency of bone marrow (BM) cells containing cytoplasmic anti-DNP antibodies (cId+) for eight weeks following a single injection. We found that (i) cId+ cells increased from 0.2 to 4.3 percent of total mononuclear cells (MNC's) during the first 8 weeks, (ii) BM granulocytes increased in frequency up to week 2, then gradually decreased to week 8, and (iii) serum anti-DNP antibody levels, evaluated by ELISA, increased to week 8. Our observations (i) support those which suggest that Rana BM resembles mammaliam BM as a source of antibody-producing cells, (ii) indicate that specific immune responses in BM may result in a 20-fold increase in the frequency of antigen-related plasma cells among total MNC's, and (iii) suggest that BM B cell clonal expansion, maturation and secretion may result in an increase in specific antibody levels in serum.