Special Clinical Settings Research Articles

Biologic and structural differences of thrombopoietic growth factors

The search for a thrombopoietic agent has resulted in the identification of numerous cytokines and growth factors with thrombopoietic activity. However, with the exception of interleukin (IL)-11 and thrombopoietin (TPO), the megakaryopoietic activity of most of these molecules has not produced clearly identifiable clinical benefits. Despite the relatively modest effect of IL-11 on megakaryocyte and platelet production in vitro and in vivo, it does reduce the need for platelet transfusions in specialized clinical settings. In contrast, the c-Mpl ligand TPO has been shown to be a potent stimulator of megakaryocyte and platelet production both in vitro and in vivo. Clinical studies are being conducted with two different preparations of the c-Mpl ligand: recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). A recombinant form of the complete human molecule, rhTPO is glycosylated and produced in mammalian cells. PEG-rHuMGDF consists of only the receptor-binding domain linked to a polyethylene glycol (PEG) moiety and is generated in Escherichia coli. Although c-Mpl ligands are still being evaluated, preliminary evidence indicates that these molecules can elevate platelet counts and may be useful in a range of clinical contexts. This report discusses aspects of the biology behind the clinical actions of IL-11 and the c-Mpl ligands.

Transvenous liver biopsy

In patients with an indication for histological evaluation of diffuse liver disease a transvenous approach may be advisable if a percutaneous technique is contraindicated by severe coagulopathy or ascites. In general, the procedure may be performed as an aspiration core, or forceps biopsy technique using a transjugular approach. Alternatively, the forceps biopsy technique may be performed via a transfemoral access. Adequate specimens for histologic diagnosis may be obtained in 77-100% with either biopsy technique. Complications after transvenous liver biopsies occur in 0-20% with an overall mortality rate below 0.5%. Although the transvenous liver biopsy techniques take more time and are more expensive than percutaneous biopsy techniques, they represent a safe and effective alternative for obtaining adequate liver samples for histological diagnosis in special clinical settings.

Lessons from the Human Brain: Neuronal Activity Related to Cognition

Several special clinical settings provide opportunities for extracellular recording of neuronal activity in the human brain during measures of cognition. The limited experience with recordings obtained from human temporal and frontal cortex, medial temporal lobe, and subcortical structures in association with language, visuospatial processes, memory, learning, and music is reviewed here. The frequency of activity in a high proportion of neurons changes with a specific behavior. These neurons are widely distributed in both hemispheres. Relative inhibition of activity is prominent in cortical recordings made during language measures, particularly in the dominant hemisphere. Widespread excitation is prominent in recordings made during measures of recent explicit memory and learning. However, any individual neuron often has a narrow behavioral repertory, with activation to only one specific behavior in a range of behaviors. Some of the behaviors associated with consistent changes are not intuitively obvious. Nearby neurons often have different behavioral repertories. A few patterns of activity that may represent specific coding for a behavior, in some cases even sparse coding, have been identified. Neuronal recording in humans during cognitive measures provides an additional perspective on the neurobiological substrate of cognition that complements findings from other techniques.

Frequency of platelet-specific alloantigens in a Danish population.

This study reports the first data on gene frequencies of platelet alloantigens HPA-1, HPA-2, HPA-3, HPA-4 and HPA-5 in a population of unrelated Danish blood donors using PCR-techniques. The observed gene frequencies fit the Hardy-Weinberg equilibrium, and the calculated phenotype frequencies are similar to those obtained in other Caucasian populations: HPA-1a and -1b occur in 96.6% and 30.3% of 557 unrelated respectively. HPA-2a and -2b in 99.4% and 15.9% of 163 tested, HPA-3a and -3b in 88.3% and 63.2% of 163 tested, HPA-4a and -4b in 100% and 0% of 131 tested, and finally HPA-5a and -5b in 100% and 15.7% of 427 tested. It is a major technical improvement to use PCR techniques for genomic typing of HPA. Not only is it possible to perform HPA typings in severely thrombocytopenic patient and on amniotic fluid cells of the fetus of alloimmunized mothers, but it must be expected that accuracy of the HPA typing will increase considerably, as has been the case with genomic HLA class II typing. Finally, use of PCR technique combined with allele-specific primers is suitable for accurate large scale typing of platelet donors, which may be useful in special clinical settings.

Arterially misplaced Swan-Ganz catheter in a hypotensive and hypoxic COPD patient

Arterial misplacement of the Swan-Ganz catheter occurs occasionally and usually can be easily detected. However, in some special clinical settings, the problem may become more complicated. We report a case of chronic obstructive pulmonary disease in which, because of severe hypoxemia, systemic hypotension, and pulmonary hypertension, conventional methods failed to recognize the misplacement, until confirmed with blood gas analysis.

Using data preprocessing and single layer perceptron to analyze laboratory data.

During daily work in hospitals a large amount of clinical data is produced each day. Totally computerized patient records are not yet widely used but a large part of essential information is already stored on computer files. These include laboratory test results, diagnoses, codes for operations, codes of histopathological diagnoses and maybe even the patient's medication. Accordingly, these databases include much clinical knowledge that would be useful for clinicians. Laboratories try to support clinicians by producing reference values for laboratory tests. It is, of course, necessary information but, however, it does not give very much information about the weight of evidence that an abnormal laboratory test will give in special clinical settings. We have developed a software package - DiagaiD - in order to build a smart link between patient databases and clinicians. It utilizes neural network-based machine learning techniques and can produce decision support which meets the special needs of clinicians. From example cases it can learn clinically relevant transformations from original numeric values to logical values. By using data transformation together with a single layer perceptron it is possible to build nonlinear models from a set of preclassified example cases. In this paper, we use two small datasets to show how this scheme works in the diagnosis of acute appendicitis and in the diagnosis of myocardial infarction. Results are compared with those obtained using logistic regression or backpropagation neural networks. The performance of our neuro-fuzzy tool seemed to be slightly better in these two materials but the differences did not reach statistical significance.

Should an axis for defense mechanisms be included in DSM-IV?

The purpose of this review is to address empirical evidence bearing on the desirability of including a Defense Mechanisms Axis in DSM-IV. The authors reviewed studies based on standardized clinical or self-report methods for assessing defense mechanisms. Information was sought pertinent to methods for assessment, relevance to clinicians with diverse theoretical perspectives, definitions, suitability for an axial format, complexity, reliability, clinical utility, and relationship to existing axes. Methods for reliably rating defense mechanisms have been developed, and data on the clinical utility of ratings have begun to accumulate. A consensus on definitions is emerging, and evidence supports a hierarchy of defenses based on their adaptiveness. Since training in psychodynamic theory and treatment approaches is required of residencies performed in the United States, all psychiatrists should be able to evaluate patient defenses. However, new methodologies have not been tested under usual clinical conditions with limited, “live” clinical data. A viable option for DSM-IV is the inclusion of a defense mechanisms axis in an appendix of optional axes for use in special clinical and research settings. In addition to providing dynamically meaningful diagnostic data, this axis would facilitate expansion of the empirical data base on a standardized measure of defenses under conditions of routine clinical practice.

Abnormalities of hemostasis in ischemic stroke

Despite important new diagnostic laboratory and imaging technologies, the cause of brain infarction remains unexplained in 20% to 40% of subjects. Most stroke patients do not require extensive evaluations of coagulation, but hypercoagulability may account for a significant proportion of unexplained strokes. Hemostatic abnormalities associated with stroke may be broadly classified as familial or acquired. Principal among the familial thrombotic coagulopathies are deficiencies in concentration or function in protein-C, protein-S, and antithrombin III, but other hereditary abnormalities include sickle cell disease, homocystinuria, and dysfibrinogenemia. The acquired disorders of hemostasis associated with stroke probably constitute a larger proportion of the important stroke-related coagulopathies. In particular, the aPL antibody syndrome is now strongly associated with thrombotic events including stroke, although neither the mechanism of thrombosis nor effective therapies for this syndrome have been clearly elucidated. Many of the acquired hemostatic abnormalities exist within a special clinical setting such as with malignancy or with myeloproliferative diseases, nephrotic syndrome, and liver disease. Presumably many of these share common pathways of coagulation activation or dysfunction with the inherited disorders. Most of the hemostatic disorders in stroke are associated with dysfunction of vascular endothelium and abnormalities of or interference with the natural anticoagulant proteins: protein-C, protein-S, and antithrombin III. Improved understanding of these relationships should lead to better diagnosis and treatment for people at risk of stroke.

PROSTHETIC MANAGEMENT OF CHILDREN WITH LIMB DEFICIENCIES

Children with amputations present challenging management problems. Surgical management, prosthetic fitting options, and training regimens have progressed substantially over the past several decades. Clinicians should be familiar with the available technological options to provide children with amputations the best possible care. The plethora of small components available for lower- and upper-limb prostheses indicates the desirability of managing juvenile patients in an interdisciplinary, specialized clinical setting where the advantages and disadvantages of prosthetic options can be related to the particular needs and wishes of each young client and the client's family. Although prostheses are not anatomical avatars, careful appliance prescription and training, coordinated with the child's growth and developmental changes, can optimize the benefits the child derives from the prosthesis.

Prosthetic Management of Children with Limb Deficiencies

Children with amputations present challenging management problems. Surgical management, prosthetic fitting options, and training regimens have progressed substantially over the past several decades. Clinicians should be familiar with the available technological options to provide children with amputations the best possible care. The plethora of small components available for lower- and upper-limb prostheses indicates the desirability of managing juvenile patients in an interdisciplinary, specialized clinical setting where the advantages and disadvantages of prosthetic options can be related to the particular needs and wishes of each young client and the client's family. Although prostheses are not anatomical avatars, careful appliance prescription and training, coordinated with the child's growth and developmental changes, can optimize the benefits the child derives from the prosthesis.

Special aspects of human alcohol withdrawal.

There are still surprising gaps in our knowledge of alcohol withdrawal. While quantitative alcohol consumption accounts for about one third of the variability in severity of acute withdrawal, there is little systematic knowledge about the other factors involved. Thus, we cannot precisely predict the severity of withdrawal in individual patients. Controversy exists as to the role of medical vs. social detoxification approaches to acute withdrawal, the influence of acute withdrawal and its treatment on the long-term outcome of alcoholism, and the importance (or even existence) of chronic withdrawal. There is little systematic data to guide withdrawal treatment in special clinical settings, e.g., with concurrent medical or psychiatric illness or with mixed substance dependence. This chapter reviews the published literature, tries to point out methodological and conceptual problems, and suggests areas for future research.

Viability and Function of Stored Sickle Erythrocytes

Functional and metabolic characteristics of fresh and three-week stored erythrocytes from patients with sickle cell anemia were compared. The storage-related changes in ATP, 2,3-DPG, and P50 in sickle erythrocytes were similar to those in control (HbA) red blood cells. After storage in CPD, sickle erythrocytes maintained significantly higher levels of 2,3-DPG (mean 2.20 +/- 0.73 mM/ml RBC) than did control cells (mean 0.36 +/- 0.13 mM/ml RBC). The posttransfusion recovery and survival of stored SS erythrocytes in autologous recipients and in an animal test system were at least as good as those before storage. Tolerance of the storage lesion by sickle erythrocytes is probably related to their young mean cell age. These results also suggest that the option of autotransfusion should be explored for selected patients with sickle cell disease in special clinical settings.

Comment on Tart's “Approaches to the Study of Hypnotic Dreams”

It appears, on the basis of Tart's note (1969), that our views on hypnotic dreams may not be remarkably different. I agree that There is no doubt that hypnotic dreams read like nocturnal dreams . and I have always favored the qualifying some regarding patients and experimental subjects and their hypnotic behavior. Sweeping generalizations are usually naive. Certainly nocturnal dreams as well as hypnotic dreams of any one person, no less of many, may vary considerably. Tart and I are aware of this. I must reiterate that I see the essential structural similarity in many hypnotic and nocturnal dreams. The functional or psychodynamic implications differ with the nuances of the special experimental or clinical settings. While pointing out the structural similarities of hypnotic and nocturnal dreams, I have always stressed the importance of transference elements in relation to their function. I have also discussed in articles and books ( 1954, 1963, 1965 ) the dynamic implications of responses to hypnotic suggestions when these responses are not consistent with implied expectations. A non-dream response to a suggestion to dream is only one example. An hypnotic dream can be evaluated as a dream only when it is in fact so constituted structurally. If not, it is to be evaluated as a response, but not a dream response. Many fleeting nocturnal images, often referred to as dreams, do not approximate the aura and complexity of certain hypnotic dreams. The structural similarity of hypnotic and nocturnal dreams is most noticeable in clinical settings when they are furnished by the same patient. Yet one often encounters considerable variability in the structure of nocturnal dreams of any one patient. It is not surprising that variability also exists in hypnotic dreams. I believe Tart recognizes my awareness of the interest inherent in broad scale investigations of nocturnal and hypnotic dreams.

PSYCHOSIS OF INFANCY AND EARLY CHILDHOOD, AS MANIFESTED BY CHILDREN WITH ATYPICAL DEVELOPMENT.

PSYCHOSIS of infancy and early childhood has been studied for the past twenty years by a few investigators in highly specialized clinical settings. The fact that this severe disorder of human development is not more widely known and understood throughout the general medical realm, especially among physicians who deal with children, represents an unfortunate failure in intramural medical communication. Scientific papers dealing with infantile psychosis have appeared usually in journals limited to distribution within a particular specialty. Problems of terminology have further compounded the difficulties of dissemination, with various individual investigators coining diagnostic labels other than infantile psychosis that nevertheless . . .