Screening for psychiatric illness in general practice: the general practitioner versus the screening questionnaire

This study compares the characteristics of general practitioners and a pen and paper test in the detection of psychiatric disorder in primary care settings. A psychiatrist interviewed a stratified sample of 283 patients drawn from 590 consecutive new illnesses seen in 15 general practices. Research diagnoses could be made in between one-quarter and one-third of the consecutive new illnesses. Two different research diagnostic systems agreed quite well with one another about who should be regarded as a psychiatric 'case' - although agreement between them for individual diagnoses was less impressive. Research diagnoses of psychiatric illnesses could be made in approximately 30% of new episodes of illnesses seen. If the DSM-3 system was used as a criterion of 'caseness', the specificity of the general health questionnaire was 75.4%, and the sensitivity was 87.1%. The general practitioners had fewer false positives than the questionnaire, but they were much more likely to miss psychiatric cases. Use of the general health questionnaire could increase their sensitivity from about 50% to 95%.     

Preoperative staging with computerized axial tomography and biochemical laboratory tests in patients with hepatic metastases.

Preoperative biochemical liver function tests and computerized axial tomographic (CAT) scans were performed on 100 patients as part of a prospective randomized study of treatments for liver metastases from colorectal cancer. The CAT scans reliably reflected the presence of disease in most patients but only accurately demonstrated the number and location of metastases in 43% of the patients. Extrahepatic metastases were present in 35 patients but were only seen on the CAT scans in three of these patients. The biochemical tests, which were useful for detecting hepatic metastases, were alkaline phosphatase (AP), lactic dehydrogenase (LDH), and carcinoembryonic antigen (CEA). When hepatic disease was minimal, these tests were less likely to be elevated than when there was extensive disease. Even with the combination of late generation CAT scans and biochemical tests, the accurate quantification and location of hepatic metastases and extrahepatic disease require a surgical assessment.     

Torsional loads in the early postoperative period following total hip replacement

Torques generated in one subject during the early postoperative period were measured with a telemeterized total hip component. The patient was examined during gait, stair ascent, rising from a chair, and single-limb stance. The torques were plotted against both the resultant joint contact force and the force component directed along the stem axis. During gait, the maximum torque was 35 Nm, recorded at a walking velocity of 1.7 m/sec. The peak torques during stair ascent and during rising from a seated position were found to be 23 and 15 Nm, respectively. The maximum value for torque measured in this study was 37 Nm during one attempt at single-limb stance. Comparison of plots for torque versus stem-axis component for the four activities shows that the torque increased more rapidly for chair exits than for gait up to resultant contact force values of as much as 1,000 N. For stair ascent, the same was true to values of 1,400 N. Within any given activity, the relationship between stem torque and resultant or stem-axis force showed considerable variability. These results indicate that experiments evaluating the stability of femoral components in total hip arthroplasty should incorporate a component directed along the stem axis, as well as a component normal to the plane of the prosthesis. The results also suggest that theoretical stress analysis models should consider the broad variability in the orientation of the joint force at the hip.     

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley-Liss, Inc.     

Performance of schizophrenic patients on putative neuropsychological tests of frontal lobe function

Though individual tests thought to assess frontal lobe function have been administered to patients with schizophrenia for many years, approaches in which a number of tests thought to tap a single function or brain region have rarely been used. Such an approach might define a critical test or a common dysfunctional cognitive process. In the present study four putative neuropsychological tests of frontal lobe integrity, namely, the Wisconsin Card Sorting Test, the Category Test, Trail Making B, and verbal fluency, were administered to 28 patients with schizophrenia. Seventy-five percent performed abnormally on at least one test. However, relationships among the test results were difficult to characterize, either by correlation or factor analysis. A hierarchical arrangement in which "higher order" tests proscribe performance on "lower order" tests did not appear to be present. Regarding sensitivity, Trails B, the only timed test, was most frequently impaired and verbal fluency was least frequently impaired. The results suggest that the tests assess somewhat different aspects of frontal lobe function, and that no single frontal lobe test is uniquely sensitive to cognitive impairment in schizophrenia.     

Pharmacy-coordinated process for evaluating physician drug prescribing

A pharmacy-coordinated process is described in which the frequency and types of inappropriate drug prescribing are evaluated as part of the medical staff quality assurance and physician credentialing program. A pharmacist intervention program was implemented at an 838-bed private hospital to review all medication orders for appropriateness and to intervene with physicians and nurses when problems in drug prescribing or administration were identified. During a five-year period there were more than 6500 drug therapy interventions. Because of the recurrent problems identified, the medical staff asked the pharmacy department to develop a process for objectively evaluating the quality of prescribing practices that could be used in the medical staff quality assurance program and in physician credentialing. The drug-prescribing activities of physicians applying for clinical privileges are subjected to a "macro" review by using a computerized clinical financial information system to extract drug-use information from patients' bills. In a "micro" review, patient records are retrospectively analyzed by Pharm.D. clinical specialists; all medications prescribed by the physician for those patients being evaluated are scrutinized. Appropriate response scores are calculated by dividing the number of appropriate responses by the total responses. The pharmacy department in this hospital has assumed a more active role in patient care through its participation in a process for objectively evaluating the quality of prescribing practices.     

Global dendritic calcium spikes in mouse layer 5 low threshold spiking interneurones: implications for control of pyramidal cell bursting

Interneuronal networks in neocortex underlie feedforward and feedback inhibition and control the temporal organization of pyramidal cell activity. We previously found that lower layer neocortical interneurones can reach action potential threshold in response to the stimulation of a single presynaptic cell. To better understand this phenomenon and the circuit roles of lower layer neocortical interneurones, we combined two-photon calcium imaging with whole cell recordings and anatomical reconstructions of low threshold spiking (LTS) interneurones from mouse neocortex. In both visual and somatosensory cortex, LTS interneurones are somatostatin-positive, concentrated in layer 5 and possess dense axonal innervation to layer 1. Due to the LTS properties, these neurones operate in burst and tonic modes. In burst mode, dendritic T-type calcium channels boosted small synaptic inputs and triggered low threshold calcium spikes, while in tonic mode, sodium-based APs evoked smaller calcium influxes. In both modes, the entire dendritic tree of LTS interneurones behaved as a 'global' single spiking unit. This, together with the fact that synaptic inputs to layer 5 LTS cells are facilitating, and that their axons target the dendritic region of the pyramidal neurones where bursts are generated, make these neurones ideally suited to detect and control burst generation of individual lower layer pyramidal neurones.     

Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions.     

Significance of PBMC response of rheumatic fever patients and control individuals to immunodominant streptococcal M5 protein epitopes

β-hemolytic streptococcal infection in developing countries still causes thousands of cases of Rheumatic Fever (RF). Molecular mimicry between streptococcal M protein (strep M) and heart components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility, which is linked to different HLA-DR alleles in different populations. In our hands, RF was significantly associated to HLA-DR7/53. Previous work in our lab has shown that heart-infiltrating T cells that simultaneously recognize strep M and heart proteins. Further, such T cells predominantly recognized the 81-103 strep M5 epitope. In this work, we analysed the proliferative response of peripheral blood mononuclear cells of 99 RF patients and 40 normal controls. Eighty-nine of the RF patients were HLA-typed. As among heart-infiltrating T cells, the 81-103 strep M5 protein epitope is the most frequently recognized epitope among RF PBMC (35.4%), against a 7.5% frequency of proliferation among normal controls (p=0.0018, chi square). However, the 81-103 epitope was as frequently recognized by HLA-DR7,53 positive as by negative individuals (45.2% vs 54.8%, respectively). Taken together, the results suggest that the 81-103 strep M5 epitope may be the immunodominant epitope, “promiscuously” recognized by T cells in a genetically diverse population. The demonstration that molecular mimicry is targeted to a discrete immunodominant “promiscuous” epitope in strep M5 may allow the development of a safe anti-streptococcal synthetic vaccine devoid of such epitopes.     

Postnatal development of hypoglossal motoneurons that innervate the hyoglossus and styloglossus muscles in rat

Postnatal development of hyoglossus and styloglossus motoneurons was studied in this investigation of the hypoglossal nucleus. Our findings show separate and distinct locations for hyoglossus and styloglossus motoneurons within the retrusor (dorsal) subdivision of the hypoglossal nucleus for all age groups. Hyoglossus and styloglossus motoneuron cross-sectional area reached their adult size at different times (by weeks 2 and 3, respectively). Cell roundness, as measured by form factor (measure of cell perimeter relative to its area), decreased with advancing postnatal age for both populations of motoneurons. Differences in the direction of the dendritic projection between hyoglossus and styloglossus motoneurons were found. Hyoglossus and styloglossus motoneuron development was compared to genioglossus motoneuron postnatal development.