Behavioural science in general practice

Dr Peter Sowerby has written an important criticism of Michael Balint's work based on his understanding of Karl Popper's writings. I dispute Sowerby's interpretation of Popper and disagree with his conclusions, which I suggest would lead general practice into a retreat. I believe Balint made a major contribution to general practice and has helped us towards practising whole-person medicine.     

Short latency activation of pyramidal tract cells by Group I afferent volleys in the cat

1. The contralateral bulbar pyramids were explored with low impedance micro-electrodes in cats anaesthetized with chloralose to reveal the effect of Group I afferent volleys (deep radial nerve of the forelimb) on pyramidal tract (Pt) cells.

2. Low rate (0·5/sec) stimulation of Group I afferents produced small responses (5-30 μV) in the bulbar pyramid which could be detected only with response averaging methods. The responses appeared with an initial latency of 7·0-11·2 msec and reached peak amplitude in 15·7 msec (mean latency). The pyramidal tract origin of the potential was demonstrated by its depression at stimulus rates above 1-2 sec and its disappearance at rates above 4/sec.

3. Recordings of neurones in the Group I cortical projection zone of the posterior sigmoid gyrus revealed that several types of cells, including Pt cells, were activated by Group I afferent volleys.

4. Pt cells responding to Group I afferent volleys frequently received convergent actions from low threshold cutaneous nerve volleys.

5. Averaged response recordings from electrodes positioned in the medial portions of the lateral funiculus of the spinal cord at the level of C₂, revealed a response to Group I afferent volleys as early as 7·4 msec which possessed the same characteristics as the relayed response to Group I in the bulbar pyramids. Some Pt cells, activated by Group I volleys orthodromically, could also be antidromically activated by stimulation of the recording site in C₂.

6. It was concluded that group I afferent volleys can influence, after short latencies, Pt and non-Pt cells and that some of these Pt cells gave rise to axons incorporated in the corticospinal tract.

     

Balint Groups for Foundation and GP Trainees

Balint groups are increasingly offered to doctors in training, both to give support to the doctors and to develop a deeper empathic understanding of their patients, the family and the clinical team. We describe Balint groups; the history of such groups and current applications. Using material from groups we ran over a three-year period, we consider practical and theoretical aspects of setting up short-term, contemporary Balint groups for doctors working in four-month psychiatric placements as part of their foundation or GP training in medicine. Current medical and psychiatric practice is gradually moving away from the dyadic doctor–patient relationship, with the use of wider team members and family as an integral part of patient care. In addition to the doctor–patient dyad traditionally explored in a Balint group we consider ways in which group analytic ideas have an important role to play. We consider that group analytic concepts enhance the Balint groups and add to the experience of those leading the groups. We describe how these can be used to illuminate unconscious factors within Balint and supervision groups. We use clinical vignettes to demonstrate some of our experiences, using both group analytic and Balint ideas.     

The coexistence of antibody with antigen during immunological paralysis to BSA

Nine adult rabbits averaging 2.55 kg were each given 1.275 g bovine serum albumin (BSA Fraction V) 6 days weekly for a period of 66 days and rechallenged with 50 mg BSA or human serum albumin (HSA) 139 days after the last injection of BSA. The sera from all rabbits were studied each week for concentrations of circulating BSA and for capacity to bind ¹³¹I-labelled BSA or HSA (I*BSA or I*HSA). Some sera were also studied after fractionation on Sephadex G-200 columns to remove the BSA which had been present in vivo. Serum levels of BSA were determined and the binding studies performed using variations of the ammonium sulphate method to detect I* antigen—antibody complexes. Some sera were also studied by radioimmunoelectrophoresis.

The observed steady-state serum levels of circulating BSA during the daily infusions were substantially less than the theoretical concentrations. In addition, the measured BSA levels were particularly low throughout two periods of the experiment. The first occurred between days 14 and 35 when the rabbits had significant proteinuria and the second between days 45 and 66 when maximum antibody activity was observed. Following cessation of infusions, BSA disappeared from the circulation with a 5.5 day half-life.

Binding of I*BSA was not detected in whole serum but was measurable between days 14 and 165 after fractionation by gel filtration with Sephadex G-200 to remove the unlabelled BSA. In contrast, Sephadex filtration was not required to demonstrate I*HSA binding in whole serum between days 14 and 198, even in the presence of excess unlabelled BSA.

The immunological specificities of the antibodies present during `immunological paralysis' to BSA were characterized by comparing the effectiveness of graded amounts of unlabelled BSA or HSA to inhibit the I*BSA and I*HSA binding. The binding specificities of sera during `immunological paralysis' were found to be similar in certain respects but distinctly different in others from either normally produced anti-BSA or anti-HSA.

Rechallenge with 50 mg HSA on day 139 produced significant I*HSA binding but only slight I*BSA binding. Specificity studies on these antibodies revealed characteristics more typical of the normally produced anti-HSA than were observed during `immunological paralysis'. However, some characteristics of normally produced anti-BSA remained.

Rechallenge with BSA produced significant binding of either I*BSA or I*HSA, and in some cases both. Specificity studies of these antibodies revealed more of the characteristics of normally produced anti-BSA than were observed prior to rechallenge but some of the characteristics of normally produced anti-HSA remained.

These results indicate that rabbits receiving large daily injections of BSA are `immunologically suppressed' rather than `immunologically paralysed' to BSA. A hypothesis is presented to explain the coexistence of BSA and antibodies having the I* antigen binding characteristics observed in the serum of these `immunologically suppressed' rabbits.

     

Operational, analogical and genuine definitions of psychophysiology

The reason for considering definitional issues is not that of arriving at a universally agreed-to definition, but rather that of illuminating scientific disagreements. From this viewpoint it will be argued that operational and analogical definitions which have been offered by psychophysiology are not useful, because they do not permit the settling of disputes on objective grounds. Those grounds are relevant only for genuine definitions, which can be tested in terms of the counter-example argument in general, and in particular in terms of whether they adequately differentiate psychophysiology from the closely related but diffent area of physiological psychology. One such genuine but inadequate definition is that offered by Stern (1964), which differentiates the two areas in terms of the dependent and independent variables being, respectively, manipulated and measured. The definition offered here is in terms of the interests of the investigator, and is that psychophysiology is the study of psychological processes in the intact organism as a whole by means of unobtrusively measured physiological processes. I shall argue that this definition more adequately differentiates psychophysiology from physiological psychology than does Stern's definition. In addition, I shall suggest that adopting this definition does not isolate the two areas from one another, but rather brings them into a more scientifically meaningful relationship. Finally, I shall illustrate, with some examples, how (implicity adopted) definitions that are different from the proposed one here lead to substantive differences in both the conduct and evaluation of research in psychophysiology. Definitional issues, in other words, are not only of relevance for ivory-tower, armchair philosophers. They affect not only the practice of empirical basic research, but also applied practice.     

Behavioral Medicine in Hungary: Past,Present, and Future

Abstract

During the socialist period before 1989, training in behavioral medicine and behavioral science was not a priority in Hungary's medical schools despite the nation's long tradition of psychosomatic and behavioral medicine. In this article, the authors review the development of behavioral medicine and behavioral science in Hungarian medical schools and outline some of the problems and future challenges these departments face. The resistance of faculty members has influenced the acceptance of behavioral medicine and behavioral science courses, attitudes toward the acceptance of departments of behavioral science, and evaluations of the staff's scientific research. Although research is emphasized in these departments of behavioral medicine, closer integration of teaching, research, and health policy is necessary. The primary message of this approach is that modern physicians should see beyond molecular substances and perceive humans from a total biopsychosocial perspective.     

Attachment,culture, and gene-culture co-evolution: expanding the evolutionary toolbox of attachment theory

ABSTRACT

I argue that attachment relationships, and particularly secure ones, are important contexts for social learning and cultural transmission. Bowlby originally treated the attachment-behavioral system as serving only one evolutionary function: protection, via physical proximity. Yet the time is ripe to consider learning, especially social learning, as an additional functional consequence of attachment. Updated accordingly, attachment theory has the potential to serve as a much-needed developmental anchor for models of cultural evolution and gene-culture co-evolution. To support my arguments, I review progress in evolutionary science since Bowlby’s lifetime, highlighting the growing recognition of ecological flexibility and the cultural embeddedness of animal behavior. I also review research pointing to a facilitating role of secure attachment relationships for social learning from caregivers among humans. For illustrational purposes, I show how one important aspect of human culture – religion – is culturally transmitted within attachment relationships, and of how the generalization of attachment-related working models biases the cultural transmission of religion from parents to offspring. I end the paper with a call for empirical research to test the role of attachment in cultural transmission beyond religion.     

Immunological responsiveness following the continuous circulation of soluble antigen—antibody complexes

Following the continuous circulation of soluble bovine serum albumin—anti-bovine serum albumin complexes, adult rabbits rapidly lose the ability to synthesize specific antibodies to bovine serum albumin (BSA). This tolerant state appears to be similar to that produced in adult rabbits by large doses of antigen.

(1) The animals showed delayed elimination of injected [¹²⁵I]BSA.

(2) Immunization with human serum albumin (HSA) enhanced the elimination of intravenously injected [¹²⁵I]BSA.

(3) BSA failed to stimulate the in vitro incorporation of [¹⁴C]thymidine by spleen cell suspensions from these tolerant animals.

(4) Although some animals made a small amount of anti-BSA antibodies in vivo there was no response in vitro to the same antigen.

     

Music,movement, and emotions: an inquiry with suggestions for the practice of dance/movement therapy

ABSTRACT

Emotions play a significant role in our lives. While the literature has shed some light on how emotions are evoked, not all aspects are well understood. Music and dance or movement have been shown to stimulate an aesthetic or emotional response and seem to affect each other. However, these cross-modal influences have only been studied in individuals who are passively engaged . Missing are accounts of how music affects dancers and moving affects making music, a gap which is especially salient considering the frequent application of music during dance/movement therapy sessions. In this paper, I present a vignette from a creative arts studio class and subsequently describe the use of a heuristic arts-informed methodology as a means of gaining greater understanding about the connection between music and movement and their influences on emotions. I connect extant literature to my own findings and derive suggestions for the field of dance/movement therapy.     

Localization of 125I-labelled antigen in germinal centres of mouse spleen: effects of competitive injection of specific or non-cross-reacting antigen

Studies were performed on localization of ¹²⁵I-human γ-globulin in spleen lymphatic tissue germinal centres during the primary and secondary immune response as influenced by competitive injections of specific or non-cross-reacting antigens. Isologous mouse 7S serum protein labelled with ¹²⁵I was used as the control. The results of these studies support the following conclusions:

(1) Antigen retention in germinal centres during the primary immune reaction is a dynamic process. For some antigens there may be opsonins available at the the time of injection which promote initial localization in germinal centres. However, the continued localization of antigen over weeks and months is a function of specific antibody production.

(2) For some period of time, germinal centres are specific to the antigen that stimulated their development, and eventually these centres will respond to a different antigen.

(3) Antigen persisting in germinal centres is functional in the development of the secondary immune potential.

     

Metabolizing Difficult Doctor–Patient Relationships: Reflections on A Balint Group for Higher Trainees

This paper describes a Balint group in Leeds which, so far as we are aware, is unique in the UK for being aimed at higher level trainees. The paper is written from the trainee's perspective. The experience has been so useful that the group has concluded that this should be an integral part of all higher training schemes. The paper discusses two cases we brought to the group which illustrate some of the challenges faced by trainees at this level of their training. It also aims to inform the reader of the need for such an experience for higher level trainees. The cases presented were experienced by the doctors involved as troubling and disturbing to their sense of self. The Balint group provides a safe environment for discussion of the most disturbing cases, especially those which involve a hard‐to‐bear countertransference, and as such, fosters ongoing personal development. Standard supervisory models are considered unable to provide such a space. The Leeds group, which is made up of trainees from all specialties, have rated the Balint experience as one of the most important in their professional lives.     

An examination of certain factors which might, or do, affect the vascular response to oxytocin

1. A number of different observations were made on anaesthetized rats and some dogs to try to discover why it is that oxytocin is a vasodilator in dioestrus and anoestrus, and develops constrictor properties in oestrus and following sympathectomy.

2. In those circumstances in which oxytocin in small or moderate doses raises blood pressure in the rat, the pressor effect is eliminated if the hormone is given during an infusion of adrenaline. In this respect the rat is closely similar to the dog.

3. It was confirmed in anaesthetized oestrous rats that intravenous eserine eliminated the pressor response to oxytocin, and it was found that prostigmine did not reduce or change it. Thus, it may be concluded that the effect of eserine depends on its central sympathetic stimulant action and not on a peripheral effect.

4. Rats which had been acutely or chronically adrenalectomized responded normally to oxytocin and both eserine and adrenaline were able to reduce, though not wholly eliminate, the pressor type of response. These results indicate that neither the adrenal medulla nor the cortex is essential for the action of oxytocin, nor for a large part of the action of eserine and adrenaline.

5. The plasma concentrations of sodium, potassium and calcium were studied in a number of conditions affecting the response to oxytocin, namely, dioestrus, oestrus, and after administration of oestrogens, progesterone, adrenaline, eserine, hexamethonium, and dihydroergotamine. The cation changes observed could not be correlated with the type of response to oxytocin. The only measure found to affect the response was raising the plasma Na concentration by the infusion of disodium hydrogen phosphate. This reduced the pressor effect of oxytocin seen in oestrous female rats and in oestrogen treated males. The pressor response returned before the plasma sodium had fallen to normal levels.

6. The administration of the oxytocin analogue, tyrosine-methyl² oxytocin which has a high receptor affinity and a low intrinsic activity, prevented the pressor response to oxytocin of oestrous rats, and the vasodilator response in the hind limb vessels of normal dogs. It is concluded that there is probably a single receptor for oxytocin from which both the constrictor and dilator effects are initiated.

7. Oxytocin exerted apparently normal effects on the systemic blood pressure of oestrous or dioestrous rats given the β-blocking agents pronethalol or propranolol.

8. The present results, like previous ones, indicate that adrenaline is the factor linking both the gonadal state and the peripheral sympathetic nervous system with the type of response to oxytocin.

9. An incidental observation was that male and female rats show differences in their response to sympathetic blocking agents and to a raised plasma sodium concentration.

     

‘Humans and Other Animals’—On the Scope of Brain Science

Abstract: This essay is dedicated to Obaid on the occasion of his 80th birthday. We both worked on the behavior of Drosophila and on what underlies behavior in the fly brain. Is that the fly's mind? The essay is about some limitations of brain science. It is just a little piece of writing. It is meant to honor Obaid for his contributions to Drosophila neurogenetics in 40 years and to science in India. I hope he takes it instead of a bowl of flowers—adding to the praise.     

Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases

Background

This study investigated variation in NR1I2 and NR1I3 and its effect on plasma efavirenz levels in HIV/AIDS patients. Variability in plasma drug levels has largely led research on identifying causative variants in drug metabolising enzyme (DME) genes, with little focus on the nuclear receptor genes NR1I2 and NR1I3, coding for PXR and CAR, respectively, that are involved in regulating DMEs.

Methods

464 Bantu-speaking South Africans comprising of HIV/AIDS patients on efavirenz-based treatment (n=301) and 163 healthy subjects were genotyped for 6 SNPs in NR1I2 and NR1I3. 32 of the 301 patients had their DNA binding domains (DBDs) in NR1I2 and NR1I3 sequenced.

Results

Significantly decreased efavirenz plasma concentrations were observed in patients carrying the NR1I3 rs3003596C/C and T/C genotypes (P=0.015 and P=0.010, respectively). Sequencing resulted in the discovery of a further 13 SNPs, 3 of which are novel variants in the DBD of NR1I2. There were significant differences in the distribution of NR1I2 and NR1I3 SNPs between South Africans when compared to Caucasian, Asian and Yoruba population groups.

Conclusion

For the realisation of personalised medicine, PXR and CAR genetic variation should be taken into consideration because of their involvement in the regulation of DMEs.

     

The effects of a single injection of progesterone on the oestrous cycle, thyroid gland activity and uterus-plasma concentration ratio for radio-iodide in the rat

1. A single subcutaneous injection of 5 mg, 1·25 mg or 625 μg, but not 312 μg, of progesterone in oil delayed ovulation in the rat by 1 or more days, when injected at the dioestrous stage of a 4-day oestrous cycle.

2. When ovulation was delayed in this way the expected increase in the thyroid-serum concentration ratio for ¹³¹I was also delayed but the ratio did increase when delayed ovulation occurred.

3. A single injection of progesterone resulted in an increase in the uterus-plasma and oviduct-plasma concentration ratios for ¹³¹I; the increase was greatest when steroid was injected at the dioestrous stage of the cycle and was delayed and least when the steroid was given at the pro-oestrous stage.

4. Ovulation was advanced by 1 day when progesterone was injected on the second day of dioestrus in rats showing regular 5-day cycles; this ovulation was not accompanied by an increase in the thyroid-serum concentration ratio. In these experiments a dose of progesterone that failed to advance ovulation produced a rise in uterus-plasma and oviduct-plasma ratio for ¹³¹I but no rise was seen when ovulation was induced, suggesting that oestrogen secretion had been stimulated.

5. 20α-Dihydroprogesterone (pregn-4-en-20α-o1-3-one) was not effective in delaying or advancing ovulation at a dose level of 2·5 mg per rat and had no effect on the uterus-plasma concentration ratio for radio-iodide.

6. These results are discussed in relation to the hypothesis that the increase in thyroid gland activity at the oestrous stage of the cycle is related to the neuro-endocrine changes that lead to ovulation.

     

Projection to cerebral cortex of Group I muscle afferents from the cat's hind limb

1. Muscle afferent projections from the contralateral hind limb to the postsigmoid gyrus of the cerebral cortex were investigated in cats anaesthetized with chloralose. The evoked potentials were recorded from the cortical surface or from deeper layers by penetrating micro-electrodes. Graded electrical stimulation of the nerves was used.

2. Group Ia as well as Ib muscle afferents from the contralateral quadriceps, posterior biceps-semitendinosus, gastrocnemius-soleus and deep peroneal muscles projected to two different loci in the postsigmoid gyrus. One of these was located on the dorsal surface of the hemisphere 4-5 mm lateral to the mid line and 1-3 mm posterior to the cruciate sulcus, thus rostro-medial to the postcruciate dimple. The other was located on the medial surface of the hemisphere adjacent to the cruciate sulcus. There was no overlap between the two loci.

3. There was no significant difference in thresholds or latencies of the Group I responses in the two loci. The latency was short and similar to that of the potential evoked by the cutaneous afferents in the somatosensory primary projection areas.

4. The Group Ib path was largely independent of the Ia path, because a maximal Group I volley evoked a response, when the Ia path was made refractory by simultaneous stimulation with a maximal Ia volley at 20 per second.

5. The cortical potentials evoked by the Group I muscle afferents from the contralateral hind limb did not change after transection of the dorsal columns at C1-C3 levels but disappeared after a superficial section in the dorsolateral fascicle at C1 level. The responses were not affected by cerebellectomy. It was concluded that the path travelled with the dorsal spinocerebellar tract or utilized brain stem collaterals of this tract.

6. Group II muscle afferents evoked a response near the border of the Group I loci, but not in the positions where the Group I responses were maximal in amplitude.

7. The receptor origin of the stimulated Group I afferents, the location of the medullary relay in the Group I path and the destination of the efferent outflow from the Group I loci were discussed.

     

Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve

1. The innervation of carotid body Type I cells has been investigated in seventeen cats. At a sterile operation the glossopharyngeal and vagus nerve roots were cut intracranially on one side.

2. From 1½ to 378 days after the operation the carotid bodies were fixed in situ and prepared for electron microscopy. Nerve endings on Type I cells were found to degenerate with a prolonged time course. In each cat there was a decrease in the number of nerve endings on the operated side as compared with the non-operated side.

3. Before the carotid bodies were fixed, recordings were made from chemoreceptor, and baroreceptor, afferent fibres in the sinus nerve on the operated side. The chemoreceptors responded in the usual way to changes in arterial O₂, CO₂ and pH; the injection of cyanide evoked a brisk response.

4. It is concluded that the nerve endings on Type I cells are efferent rather than afferent and the cell bodies of their axons are probably in the brain stem.

     

Location of U.V.-absorbing substance in isolated skeletal muscle fibres: the effect of stimulation (frog, snake)

1. In an attempt to study the intracellular location of ATP in skeletal muscle the distribution of substances which absorb light at 260 nm wave-length has been studied in isolated muscle fibres with the aid of a modified U.V.-microscope.

2. U.V.-absorption in resting frog fibres was found to be higher in the I band than in the A band which confirms earlier findings. In stretched fibres (sarcomere length 2·9-3·6 μm) an absorbing substance could be seen to be concentrated in a pair of narrow lines, centred at the Z-line. The separation of the lines increased with increasing sarcomere length.

3. Snake fibres, with sparse triads located at the A-I junction, displayed an absorption pattern very similar to that of frog fibres. It is concluded that it is unlikely that the absorbing substance is associated with the sarcotubular system.

4. The absorption pattern of frog fibres remained unchanged during a tetanus. No clear changes could be detected after a period of stimulation, neither after single twitches nor after repeated tetani.

5. In further attempts to cause exhaustion, metabolically poisoned fibres were stimulated repetitively until they went into rigor. The absorption pattern was essentially unchanged also when rigor tension started to develop.

6. The characteristic absorption pattern was observed also in glycerol-extracted fibres. It was confirmed by spectrophotometry that glycerol-extraction led to the disappearance of a large amount of a substance with the spectral characteristics of ATP.

7. The higher U.V.-absorption in the I band does not prove that the major part of the ATP in the fibre is concentrated here; the absorption could either be due to a minor fraction of the ATP or to RNA.

     

Über ein an den Toxoplasma-Stamm BK (Winsser,van Thiel, 1948) gekoppeltes infektiöses Agens

Zusammenfassung Mit dem Toxoplasma-Stamm BK wird ein für verschiedene Säugetiere pathogenes Agens mindestens schon seit 1955 mitgeführt. Das Agens läßt sich von den Toxoplasmen trennen und weist Charakteristica eines Virus auf.

---

Summary The aim of this paper is to point out that the BK-strain of Toxoplasma gondii is associated with an agent pathogen to some mamals. The parenteral application of this agent leads to death of mice and guinea pigs within 6 to 10 days. The agent possesses the character of a virus, but we can't find any identity with the known pathogen virusses of the laboratory animals. It is possible to separate the Toxoplasma from this virus by passages on chorio-allantois membran. The pathological lesions of experimental infection by this strain are changed by this virus.

---

---

Die Untersuchungen wurden mit finanzieller Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.

---

Für die technische Hilfe bei der Ausführung der Arbeit danken wir Frau H.Dignath und Frau I.Lippel.