Experience and philosophy with regard to case registers in health and welfare

A well designed and executed case register for mental illness or other conditions can provide information not readily obtainable by any other method. This includes unduplicated counts of diagnosed cases of the disease and longitudinal information such as changes in diagnosis, outcome, and survival information. Registers often are the only way in which new cases can be identified with any certainty. Also, the register can serve as a sampling frame for more intensive studies of services and of prevalence of the disease in the community, genetic studies, studies of the cost of treating various types of patients, before and after comparisons, and many other sociological and epidemiologic investigations. At the same time, there are many problems and pitfalls to case registers. This paper outlines some of these difficulties and suggests that registers be established only after careful planning and preparation.This paper is based on a presentation for a Workshop on Case Registers, American Orthopsychiatric Association Meeting, Chicago, Illinois, March 20, 1964. An extended bibliography on case registers is available from the author.     

Quantitative analysis of “synaptic” ribbon profiles in the pineal complex of male and female Pirbright-White guinea pigs

Summary Previous studies have pointed in the direction of sex differences as well as regional differences in the pineal gland of guinea pigs. In the present investigation these aspects were studied at the electron-microscopic level by quantitating different types of synaptic bodies, intrinsic to pinealocytes. The two major types of synaptic organelles, ribbons and spherules, did not exhibit regional or sex differences. Synaptic structures intermediate in appearance to ribbons and spherules were significantly larger in number in males in the distal region of the pineal gland, compared to females. As previous studies have shown that ribbon and spherule numbers undergo characteristic changes depending on the functional state of the pineal gland, it is concluded that, as far as the synaptic organelles are concerned, no clear-cut sex or regional differences appear to exist in the guinea pig pineal gland.     

Potential role of transforming growth factor-β1 in terminating the immune response in patients with Guillain-Barré syndrome

T-cell activation and proinflammatory cytokines seem to be important in promoting the disease activity in Guillain-Barré syndrome (GBS). Transforming growth factor-1 (TGF-1) is a multifunctional peptide with potent immunosuppressive activity, and can therefore be considered a putative disease-limiting cytokine. We determined levels of soluble TGF-1 in the serum of 12 patients with GBS in serial investigations during the course of the disease, in 12 patients with other non-inflammatory neurological diseases (OND), and in 12 healthy control subjects. Levels of biologically active and total TGF-1 were significantly increased in patients with GBS compared with patients with OND and healthy controls. During the course of GBS, levels of TGF-1 peaked in the plateau phase before onset of recovery. During the recovery phase levels of TGF-1 decreased but still exceeded significantly the levels in patients with OND and healthy controls. The differences were more marked with biologically active than with total TGF-1. The temporal relationship between increased serum levels of TGF-1 and the end of the progressive phase indicates that TGF-1 has a role in terminating the pathological immune response in GBS. These findings suggest that TGF-1 may be important in recovery from GBS.     

Immunohistochemical study on the distribution of α and β subunits of S-100 protein in brain tumors

Summary The immunohistochemical distribution of and subunits of S-100 protein (S-100, S-100, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 (+) and/or S-100 (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 (+) and S-100 (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 (-) and S-100 (+)]; acoustic Schwannoma. Group 4 [S-100 (-) and S-100 (-)]; medulloblastoma, malignant lymphoma, germinoma. The S-100 immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 than for S-100 with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 immunoreactivity decreased according to degree of malignancy, while that of S-100 varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 and S-100 might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation     

Somatosensory evoked potentials in patients with thalamic lesions

Summary Somatosensory evoked potentials (SEPs) were recorded in 20 patients with thalamic lesions confirmed by CT (10 with infarction, 10 with haemorrhage). The changes in SEP configuration are discussed in their relationship to clinical symptoms. Four types of SEP abnormality produced by thalamic lesion are distinguished: (1) FF type, (2) N20/P23 dissociation type, (3) N18/N20 false shift type, and (4) reduced early component type. It was shown that clinically similar lesions might produce different SEP patterns.     

Single drug therapy for intractable epilepsy

Summary Single drug therapy with either phenytoin or primidone resulted in complete seizure control in 11 of 35 patients (31%) referred to an epilepsy clinic for treatment of uncontrolled chronic epilepsy with complex-partial seizures. Complete seizure control was associated with an increase in the mean plasma concentrations from 14 g/ml to 23 g/ml phenytoin and from 34 g/ml to 40 g/ml phenobarbitone with no change in the antiepileptic drug. Insufficiently low plasma concentrations of less than 11 g/ml phenytoin or phenobarbitone were measured at the first visit in 14 patients (40%). Non-compliance was admitted by eight patients (23%). Optimum single drug therapy is of considerable clinical value in intractable epilepsy with complex-partial seizures.

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Zusammenfassung Eine Monotherapie mit Phenytoin oder Primidon führte zur Anfallsfreiheit bei 11 von 35 Patienten (31%), die wegen schwerbehandelbarer psychomotorischer Anfälle eine Epilepsieambulanz aufsuchten. Anfallsfreiheit trat auf bei einem Anstieg der mittleren Plasmakonzentration von 14 g/ml auf 23 g/ml Phenytoin und von 34 g/ml auf 40 g/ml Phenobarbital. Ein Wechsel der Medikamente war nicht notwendig. Während der ersten Untersuchung wurden bei 14 Patienten (40%) zu niedrige Plasmakonzentrationen von weniger als 11 g/ml Phenytoin oder Phenobarbital gefunden. 8 Patienten (23%) gaben eine unregelmäßige Einnahme der Medikamente (non-compliance) zu. Eine konsequente Monotherapie ist von klinischem Wert für die Behandlung von schwerbehandelbaren Epilepsien mit psychomotorischen Anfällen.

     

Neuroectodermal tumors of the peripheral and the central nervous system share neuroendocrine N-CAM-related antigens with small cell lung carcinomas

Summary The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize neural/neuroendocrine or neural antigens, as defined by their reaction pattern in normal tissues and tumors. At least five of them recognize different epitopes of the neural cell adhesion molecule (N-CAM). It was found that all of 12 neuroblastomas, 2 ganglioneuroblastomas and 4 ganglioneuromas as well as 23 central primitive neuroectodermal tumors, 13 astrocytomas and 4 ependymomas share neural/neuroendocrine antigens (as defined by the anti-N-CAM antibodies Moc-1,-21,-32,-52 and-191) with SCLC. The neural/neuroendocrine antigen defined by Moc-171 was also found in all peripheral tumors, but only in further differentiated central tumors. Non-N-CAM related neural antigens (as defined by Moc-51 and-172) were found only in better-differentiated peripheral and central tumors, but they could be demonstrated in all three medulloblastoma cell lines studied. In addition, the antigen defined by Moc-51 was demonstrated in an immunoblot of a neuroblastoma cell line. Antibodies recognizing epithelia antigens of SCLC and other epithelia and their tumors (Moc-31 and-181) were non-reactive. It was concluded that these findings give further support for a relation between neural and neuroendocrine tumors and that some of the antibodies may be useful for the detection of differentiation in neural tumors. Antibodies with an epithelia recognition pattern may serve to distinguish neural from neuroendocrine tumors.Supported by NIH grant CA 36245 W.M.M. was a Fullbright scholar     

Visual pattern evoked responses and blink reflexes in assessment of MS diagnosis

Summary VEPs were measured after pattern reversal in 135 MS patients and 30 control subjects. Neurological findings were documented in a standard manner. An extensive ophthalmological examination of all subjects was part of the study. The latency of P₂ was abnormally delayed in 82% of the definite, in 60% of the probable and in 65% of the possible MS groups respectively. The VEP was more often delayed in relation to ophthalmological disturbances. Changes in the MS classification had to be made in more than 10% of the patients, due to delay of VEP latency. These were patients with a spinal form of MS, which is known to create diagnostic problems.Optically and electrically evoked blink reflexes were recorded in 107 MS patients. All patients with mesencephalic lesions had delayed responses of the optically evoked reflex. 74% of the patients with caudal brainstem lesions had delayed latencies of the components of the electrically evoked blink reflex. The blink reflex was delayed in 18 additional patients without brainstem signs. The possibility of delineating clinically silent brainstem lesions by investigating blink reflexes is discussed.Supported by the Deutsche Forschungsgemeinschaft (Dr. Fischer Bosch-Stiftung).     

Does social deprivation during gestation and early life predispose to later schizophrenia?

Summary We employed a case-control study design to investigate whether schizophrenic patients differed from non-psychotic psychiatric patients in terms of place of birth and paternal occupation. Cases were first-contact schizophrenic patients ascertained from the Camberwell Cumulative Psychiatric Case Register. Controls were the next (non-psychotic) patient on the Register matched for age and sex. In comparison with controls, cases were more likely to have: (1) been born in the deprived innercity Camberwell catchment area (odds ratio 2.3), and (2) had fathers who had manual as opposed to non-manual occupations (odds ratio 2.1). The results were compatible with the notion that socio-economic deprivation during gestation and early life predisposes to later schizophrenia.     

Hyperkinetic children: Early indicators of potential school failure

Hyperkinetic children are identified as a population-at risk upon admission to kindergarten. The etiology of hyperkinetic behavior is controversial. Organic driveness, hyperkinetic behavior disorder, postencephalitic behavior, brain damage with behavioral and conceptual deficit, Strauss syndrome, have all been used to label essentially similar symptom constellations. Bypassing the area of controversy, a study is reported that demonstrates that children who were identified as hyperkinetic (using behavioral criteria developed in an earlier study) were (1) absent from school more frequently, and (2) did remarkably less well on standardized tests of school readiness than their peers rated nonhyperkinetic. The implications are discussed and suggestions made for the development of intervention programs.An earlier version of this paper was presented at the Annual Meeting of the American Orthopsychiatric Association, March, 1967.     

Lack of correlation between DST results and urinary MHPG in depressed inpatients

Summary Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in supressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG (high MHPG and low MHPG), the high MHPG group included significantly more non suppressors then the low MHPG one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.     

Diagnosing Depression in African Americans

Since the 1970s, articles have noted the increased presence of psychotic symptoms among depressed African Americans, the presence of diagnostic bias identified when structured clinical interviews are used, and the identification of misdiagnosis of affective illness among chronically, mentally ill, African Americans. This paper reviews this literature and describes three alternative presentations of depressive illness among African Americans that differ from the DSM IV criteria for Major Depressive Disorder: the stoic believer, the angry, evil one with a personality change, and the John Henry doer. Clinicians are encouraged to recall these presentations of depression when evaluating African American patients.     

The effect of a 5-HT3 receptor antagonist,ondansetron, on brain stimulation reward,and its interaction with direct and indirect stimulants of central dopaminergic transmission

Summary 5-HT₃ receptors are abundant in central dopamine (DA) terminal areas. They do not affect basal DA turnover but appear to modulate DA release by e.g. morphine and nicotine. The interpretation of these findings is uncertain, and it is unclear whether 5-HT₃ receptors also influence the activity of compounds such as amphetamine and cocaine, which act more directly on the DA synapse. Variable-interval (VI), threshold-current hypothalamic self-stimulation can provide a continuous index of central dopaminergic activity, but is relatively insensitive to changes in 5-HT and thus offers a means of investigating this question. In the present study, a selective 5-HT₃ receptor antagonist, ondansetron (GR 38032F) (1.0 to 1000 g/kg sc), had no effect on VI self-stimulation, nor did a 100 g/kg dose affect facilitation of responding byd-amphetamine (500 jig/kg ip). Ondansetron (100 g/kg) reduced the initial depression of self-stimulation by high-dose nicotine (400 g/kg), but not the ensuing facilitation. Similar results were obtained in rats sensitized to nicotine by prior chronic exposure. These results support the proposal that 5-HT₃ receptors, normally quiescent under basal conditions, mediate the excitatory effect of compounds acting upstream from the DA neuron, such as nicotine, but do not affect the dopaminergic synapse directly.     

DL-lysine-H3 uptake in “light” and “dark” neurons of the inferior olivary nucleus of euthyroid and dysthyroidal rats

Summary Uptake of DL-Lysine-H³ into light and dark cells of the rat inferior olivary nucleus was studied by radioautographiy. Uptake in light cells was higher than in dark cells and appears to be possibly related to the greater frequency of relationship with glial satellites. Dysthyroidal states were also observed to increase uptake of radioactivity which was prominently observed in hypothyroid rats. Since dark cells appear to take up less lysine than normal cells and are less frequently closely associated with glial satellites it is suggested these cells may represent a less physiologically active unit than the light cells rather than being simply artifactually produced by the procedures employed.

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Zusammenfassung Die Aufnahme von DL-Lysin-H³ in hellen und dunklen Zellen im unteren Olivenkern der Ratte wurde mit Autoradiographie beobachtet. Die Aufnahme war höher in den hellen Zellen als in den dunklen, was möglicherweise mit einer größeren Häufigkeit von Glia-Satellit-Verbindungen in Zusammenhang gebracht werden könnte. Veränderungen im hormonalen Zustand der Schilddrüse konnten auch dazu beitragen, die Aufnahme von Radioaktivität zu erhöhen, was besonders bei Ratten mit niedriger Schilddrüsenaktivität hervortrat. Da dunkle Zellen offenbar weniger Lysin aufnehmen als normale Zellen, und sie seltener mit Glia-Satelliten verbunden sind, wird angenommen, daß diese Zellen möglicherweise eine weniger aktive physiologische Einheit darstellen als die hellen Zellen und daß es sich nicht einfach um ein Kunstprodukt handelt.

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This investigation was supported in part by a PHS research grant (NB-456802) from the division of Neurological Disease and Blindness and in part by Contract NONR 4018(01), (NR 101-592), between the Office of Naval Research, Department of the Navy, and the Research Foundation of the State University of New York.     

Predictors of poor outcome after selective dorsal rhizotomy in treatment of spastic cerebral palsy

Objectives The purpose of the study was to determine if there are preoperative clinical characteristics that might be predictive of a poor outcome after selective dorsal rhizotomy (SDR) surgery in children with spastic cerebral palsy (CP).Methods A retrospective analysis was performed on 174 children who had undergone SDR from 1983 to 2001. Patients were divided into two groups according to their outcome at approximately 1 year after surgery: acceptable or poor outcome. As predictors of outcome, the factors compared were age at operation, types of CP (diplegia, quadriplegia), history of prematurity, prior lower limb orthopedic surgeries, history of seizures, dystonic limbs, opisthotonic posturing, lumbar hyperlordosis, truncal hypotonia, preoperative ambulatory function, preoperative Gross Motor Function Classification System (GMFCS) scores, and presence of intellectual delay and speech delay.Results Eleven children (6.3%) had a poor outcome. The type of CP (P<0.001) and intellectual delay (P=0.015) were significant predictors of outcome in the univariate regression analysis, but only the type of CP retained significant predictive power in the multivariate analysis.Conclusion These data suggest that preoperative diagnosis is the strongest predictor of outcome after SDR. Intellectual delay demonstrated predictive power only in the univariate model, suggesting that it might have some prognostic value but less than the diagnosis.     

Analytic work with LSD 25

Summary In this paper, work with LSD 25 as an aid to analysis has been described. Of particular interest, has been theseeming unpredict-ability and arbitrariness of experiences elicited by the drug, and an attempt has been made at finding the determining factor in emerging material. This appears to be the selection of complementary and compensatory unconscious contents; selected in accordance with Jung's idea of the psyche as a self-regulating system, striving toward wholeness.Clinical material has been grouped in five categories, in which different aspects of complementation are illustrated. Some questions of transference and resistance in connection with LSD treatment have been discussed; and ideas about typical mechanisms in certain categories of neuroses, as suggested by the patient's response to the drug, have been put forward.This report is based on a paper read at a meeting of the (British) Society of Analytical Psychology in 1957.     

AMP-rated psychopathology in chronic alcoholics

Summary In a group of 39 alcoholics within a withdrawal process, the psychical situation was rated using AMP scales (Angst et al. 1969). Cluster analysis of the items rendered the following five-cluster solution: (1) aggressive-depressive patients, (2) less impaired persons, (3) slowed persons with diminished contact, (4) emotionally inadequate persons, (5) appealing depressive persons. These results are discussed with respect to other data from clinical history and diagnostic findings.Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 115, Teilprojekt C21     

Zur Frage des Off-On-Effektes bei Levodopa-Behandlung des Parkinsonismus

Zusammenfassung Tagesschwankungen der Leistungsfähigkeit bei Parkinsonkranken unter langdauernder Levodopabehandlung sind als sogenanntes Off-On-Phänomen bekannt. Reduzierter Proteingehalt in der Nahrung soll diesen Effekt bei Kranken, die nur mit L-Dopa allein behandelt werden, beheben können, nicht aber bei denjenigen, die eine Behandlung mit L-Dopa Dekarboxylasehemmer erhalten (Cotzias et al.). Die Hypothese von Cotzias beruht auf der Annahme, daß eine Transportkonkurrenz zwischen L-Dopa und Aminosäuren zu den Hirnganglien besteht.Um diese Ergebnisse zu prüfen, wurde bei 23 Parkinsonkranken mit Off-On-Phänomen der Einfluß einer proteinarmen Nahrung untersucht.Alle Patienten waren 5–8 Jahre mit L-Dopa vorbehandelt und erhielten zumindest in den letzten 3 Jahren eine Kombinationsbehandlung mit Dopa/Dekarboxylasehemmer. Der Eiweißgehalt der Nahrung wurde auf 25 g pro Tag beschränkt (weniger als 0,5 g pro kg Gewicht) und dies für eine Zeit von 1–4 Monaten.In 6 Fällen konnte eine deutliche Besserung mit Verminderung des Off-On festgestellt werden, in 1 Fall kam es zum völligen Verschwinden des Phänomens. Eine auffallende Besserung der allgemeinen Leistungsfähigkeit konnte in weiteren 5 Fällen beobachtet werden und eine objektive Besserung der Symptome, aber nur während der Off-Periode, festgestellt werden. Die restlichen 12 Fälle haben nicht angesprochen. Bei allen Patienten mit Hyperkinesie wurde eine Steigerung des Symptoms während der Diätperiode beobachtet. Eine Abhängigkeit von Diät zum Alter, Schwere, Dauer der Krankheit und der Dopabehandlung konnte nicht festgestellt werden. Der mögliche Mechanismus des Off-On-Phänomens sowie einige Vorschläge es zu beeinflussen werden dargestellt.

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The off-on phenomenon during treatment of Parkinson's disease with Levodopa

Summary The fluctuation in daily performance of Parkinson patients on long-term L-dopa therapy is known as the so called off-on phenomenon. Cotzias et al. found that a low protein diet is able to control this phenomenon in patients taking L-dopa alone but not in those receiving a combination of L-dopa and decarboxylase inhibitor. The author's hypothesis was based on the competition between the alimentary aminoacids and L-dopa for transport to the brain ganglia.In our attempt to prove the findings of Cotzias group we tested the influence of a low protein diet on 23 Parkinson patients manifesting the off-on phenomenon. All had been pretreated with L-dopa for 5–8 years and taking dopa DI for a minimum of 3 years. The protein intake was limited to 25 g/day (which is less than 0.5 g/kg body weight) for 1–4 months.In 6 cases there was a marked improvment with reduction of the off-on effect, and in one it disappeared completely.A distinct improvement of general capability was seen in the other 5 cases, and an objective improvement of the symptoms was noted, exept during the off period. No response could be observed in the remaining 12 cases. All cases with hyperkinesia showed an augmentation of this symptom during the use of the diet. The diet restriction was not found to be correlated with age, stage, duration of illness or duration of dopa treatment. The possible mechanism of the off-on phenomenon and some suggestions to influence it, are presented.

     

Über Xanthurensäure-Bestimmung bei Ertrankungen des Nervensystems

Zusammenfassung Bei 91 Patienten und zehn Normalpersonen wurde die Xanthurensäure-Ausscheidung kontrolliert. Der Begriff Normalperson wird diskutiert. Für die Vergleichsgruppen werden Extrem- und Durchschnittswerte der Urin- und Xanthurensäure-Ausscheidung in 12- und 24 Std-Portionen vor und nach Belastung angegeben. Unter 39 sicher pathologischen Reaktionen fallen als relativ geschlossene Gruppen die Schizophrenien, Depressionen, Manien und die Fälle mit Chorea Huntington und chronischem Alkoholismus auf. In einigen Fällen, besonders solchen mit symptomatischem Parkinson-Syndrom ist eine negative Belastungsreaktion zu beobachten. Differenzen zwischen diagnostischen Gruppen und verschiedenen Altersklassen werden ebenso wie die Deutung der Befunde an Hand der einschlägigen Literatur besprochen.