Alterations in lipid incorporation in Duchenne muscular dystrophy: Studies of fresh and cultured muscle

The incorporation of [³H]glycerol into lipids of fresh and cultured skeletal muscle obtained from patients with Duchenne muscular dystrophy (DMD), patients with myotonic dystrophy (My Dyst), controls, and aborted fetuses (10–12 weeks old) was studied. A significant increase of specific incorporation of [³H]glycerol into phosphatidylcholine (PCh), phosphatidylserine (PS), phosphatidylinositol (PI), and triglycerides (TRI) was found in DMD and fetal muscle in both fresh and cultured muscle. No significant differences, however, were noted between the values of glycerol incorporation in DMD and fetal muscle. The ratio between phospholipids and TRI changed significantly for fresh muscle in DMD (3.5) and fetal muscle (4.9) versus controls (24). The incorporation of glycerol into these lipids in My Dyst fresh and cultured muscle showed the same values as controls when expressed both as incorporation/mg protein and ratio between phospholipids and TRI.     

Distal slowing of motor nerve conduction velocity in diabetic polyneuropathy.

Using the latencies of M response and F wave, motor nerve conduction was assessed along the entire course of the nerve from the spinal cord to the muscle in 102 diabetics and 74 control patients. In diabetics, latencies were increased and conduction velocity decreased over both proximal and distal segments. However, the latency ratio of the proximal to distal segment (F ratio) was slightly but significantly smaller in diabetics (mean +/- SD:0.93 +/- 0.14, 1.35 +/- 0.20, 1.09 +/- 0.19 and 1.02 +/- 0.19 for median, ulnar, tibial and peroneal nerves, respectively) than in control patients (1.05 +/- 0.09, 1.41 +/- 0.12, 1.17 +/- 0.13 and 1.08 +/- 0.12). These findings suggest that motor conduction abnormalities in diabetic polyneuropathy are diffuse over the total length of the nerve, but more intense in the distal than proximal segment. An additional finding in diabetics was that both proximal and distal segments were more frequently affected in the lower than in the upper extremities.     

Biochemical abnormalities of muscle ribosomes during attacks of hyperkalemic periodic paralysis

Three familial cases (a mother and 2 sons) with hyperkalemic periodic paralysis are presented. Myotonia (orbicularis oculi and hands) was noted all 3 cases. Exposure to cold produced weakness in the 2 older patients. An oral KCl loading test induced paroxysmal weakness in all 3 cases. Ribosomes isolated in 2 cases from biopsied muscle during the induced attacks showed definite increases of protein synthesis in a group of rather heavy muscle polyribosomes. Electron microscopy revealed in both cases scattered small membrane-bound vacuoles, subsarcolemmal aggregates of myotubules, glycogen particles and occasional filamentous bodies.     

Dichotic listening pattern in relation to interhemispheric disconnexion

A distinctive pattern of dichotic listening abnormality has been described in a small number of callosotomised patients and it has been suggested that the abnormality relates to the severing of pathways connecting both auditory cortices. The present paper supports those findings by presenting two cases of non-surgical disconnexion of inter-auditory pathways in which the pattern of disability conforms to the expectation raised by the previous reports.     

Secondary depression in alcoholism: Implications for future research

While an association between excessive consumption of alcohol and depression has long been suspected it has only recently been demonstrated. This is probably due to the fact that only during the last 15 years have research diagnostic criteria for both alcoholism and depression been developed. The relationship between alcoholism and depression appears to be unidirectional in that the presence of an affective disorder does not seem to predispose to alcoholism (except perhaps in women), whereas the presence of alcoholism does appear to lead to subsequent development of depressive symptomatology. Unfortunately, there is a very wide range in the reported frequency of depression among alcoholics. We will examine the literature on secondary depression in alcoholism in an attempt to clarify the parameters which may account for this.     

Genetic investigations of atypical psychoses. I. Morbidity in parents and siblings.

In the literature a number of terms have been applied to psychoses that seem to be neither manic-depressive nor schizophrenic. In this report we have chosen the term atypical psychoses as being the most neutral. Whether these psychoses represent a separate psychosis or simply present atypical features of manic-depressive psychosis or schizophrenia is an unresolved issue. Family studies are one way of resolving such questions. Seven family studies of atypical psychoses were found that report age-corrected risks for psychoses in family members. Data from the studies were combined. The results do not support claims that atypical psychoses may be categorized as strictly manic-depressive or schizophrenic. There is some evidence that investigator bias may have skewed results away from finding an increased morbidity risk for atypical psychosis. The most striking finding is that the modal illness in parents and siblings is remitting. The genetic evidence would suggest that the relationship of atypical psychoses to schizophrenia is minor. The question now centers on the relationship between atypical psychoses and the affective disorders.     

“Organic” and “psychotic” symptoms in unipolar (UP) vs bipolar (BP) depressions

Delusions and hallucinations are often part of the symptomatology in patients with affective disorders. The frequency of these symptoms in an outpatient population has been documented in a recent article by Guze et al.¹ They found that primary bipolar (BP) patients reported delusions and hallucinations in 53% of cases and primary unipolar (UP) patients in only 17% of the cases. These data suggest that there might be differentiating clinical symptoms that could distinguish BP depressed from UP patients.An earlier attempt was made to separate UP from BP depressed patients by Beigel and Murphy² on the basis of symptom complex. They found in this inpatient group matched for age, sex, and level of depression that there was no statistical difference (p > .05) in the psychotic symptoms between UP ($\text{9}\text{25}\text{–36\%}$) and BP ($\text{3}\text{25}\text{–12\%}$) depressed patients. Though these did not reach statistical significance, the trend was the opposite of that reported by Guze.This contradiction could be explained by the rather apparent differences between these studies. Guze did not distinguish in his paper whether he was working with BP manic phase, BP depressed phase, or both. One would assume both. Beigel rated his BP patients specifically during the depressed phase of illness for at least two weeks.It has been noted that bipolar illness is characterized by a greater family history of affective disorder than unipolar illness; therefore, it may be considered more “genetic” or biological.³ This finding makes it worthwhile to compare bipolar and unipolar depressions on the variable of organic (sensorium) symptoms as well as on psychotic symptoms.     

Parental psychiatric illness associated with schizophrenia in the siblings of schizophrenics

The diagnostic boundaries of schizophrenia remain controversial. Although there may be little disagreement about classifying process schizophrenia as schizophrenia, the inclusion of good-prognosis schizophrenia,¹ borderline syndromes, or nonpsychotic conditions has engendered more debate. The issue regarding good-prognosis schizophrenia has been clarified by a number of studies^2–6 indicating that this group has clinical and family differences from process schizophrenia. Progress in classifying borderline syndromes and nonpsychotic conditions has not been as great. As we have previously stated,⁷ the reasons seem to be difficulty in defining these disorders as well as a lack of data regarding their occurrence in the general population.Because of this impasse, we have looked for indirect ways of defining the boundaries of schizophrenia. One approach has been to compare positive family history schizophrenics with negative family history schizophrenics on the assumption that schizophrenics with a loaded family history for process schizophrenia should also have a loaded family history for other disorders that are related to schizophrenia. The frequency of other psychiatric disorders in these two groups were not significantly different;⁸ thus failing to support the extension of the concept of schizophrenia to include such nonpsychotic conditions as neuroses or personality disorder.Because there is a positive association between schizophrenia in the siblings of schizophrenics and parental schizophrenia,⁹ the present report makes the following assumption: If there are borderline or nonpsychotic psychiatric illnesses that are genetically related to schizophrenia, their occurrence in parents should be associated with schizophrenia in the siblings of schizophrenics. Conversely, if there are parental illnesses that are distinct from schizophrenia, they should be associated with other illnesses in the siblings because most mental disorders, regardless of their etiology, have been shown to run in families.¹     

Permeability of the blood-brain barrier to neuropeptides: The case for penetration

Evidence that peptides can cross the blood-brain barrier (BBB) is reviewed. Penetration is suggested by the observations that blood levels correlate with cerebrospinal fluid levels for many peptides and that peripheral administration of peptides results in effects on the CNS. Passage is confirmed by experiments involving administration of a peptide (immunoactive or radioactive) in one compartment and identification of its appearance in the other, supported by such methods as selective labeling, cross-reactivity with highly specific antibodies, and chromatography. The degree of passage varies among peptides and their analogs. The major route of passage is probably by a non-competitive, non-saturable mechanism, with the physicochemical characteristics of the peptide (e.g. lipophilicity, charge, molecular weight, and protein binding) determining the degree of passage. A competitive transport mechanism also exists for some peptides. Penetration of the BBB via large pores or by pinocytosis does not appear to be of major importance for peptides. Permeability of the BBB to peptides, but not to the larger iodinated albumin, is affected by intraperitoneal administration of aluminum, apparently by an increase in the permeability of the membrane to lipophilic materials.     

The role of relaxation in systematic desensitization: Revisiting an unresolved issue

Forty-three socially anxious females received systematic desensitization, noncontiguous relaxation, hierarchy exposure only, or no treatment. Analysis of pre-posttest fear in a laboratory social interaction task revealed virtually no treatment effects on self-report or behavioral measures. Analysis of continuously monitored heart rate, however, indicated reduced anticipatory activity among subjects receiving relaxation training and reduced reactive activity for desensitization subjects.     

Mitigating acute skin rashes and nausea from lithium

Effective in treating and preventing particular types of mental illness, lithium has recently been reported to cut the costs of medical care and improve the quality of life of many appropriately selected patients.¹ Unfortunately, some patients who are selected as appropriate for starting lithium are greatly discomforted by some of its side effects.Prominent among the discomforting effects are resting tremors, nausea and vomiting, and excessive thirst and urination; these are rarely severe enough for the physician to recommend lithium discontinuance. On the other hand, it is common to see patients who have quit their lithium on their own complaining of annoying side effects. Among the few circumstances in which physicians recommend lithium discontinuance is when an intense skin rash appears within a few hours of administration.The life prospects for many patients who cannot or will not take lithium are gloomy: they will likely experience repeated episodes and exacerbations of their psychiatric illness and their careers and personal lives will suffer the discouragements of interruptions. Those who take neuroleptics in place of lithium experience a more subtle handicap, that of mental inertia and emotional blunting from tranquilization.As good medical practice it seems prudent to try to help patients accommodate to lithium with various pharmacological maneuvers when these side effects interfere with reliable lithium administration.In this report some cases will be reviewed in which side effects of an acute skin reaction or nausea threatened to take precedence over lithium's therapeutic effects.     

Immunocytochemical localization of thymosin-α1 in thymic epithelial cells of normal and myasthenia gravis patients and in thymic cultures

Thymosin α₁ (α₁) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin α₁, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or “involuted” thymus of myasthenia gravis (MG) patients. α₁ was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells; this was markedly evident in thymomas. “Involuted” MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-α₁ stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone α₁ to be thymic epithelial cell; (b) raise the possibility that excess α₁ may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) suggest that epithelial cells may be autonomous for the production of α₁ as evidenced by their positivity in tissue culture.     

The effects of orienting task on differential hemispheric EEG activation

Sixteen right-handed men heard 12 brief cue questions pertaining to each of four tasks. Each cue question was followed by the announcement of a single trait adjective, which was either positive, neutral or negative. Judgements of self reference and volume discrimination evoked greater relative left hemispheric EEG activation than judgements of evaluation and rhyme. Differential hemispheric EEG activation was not affected, however, by the depth-of-processing. Once the assigned task was completed, affect-laden (positive or negative) adjectives elicited less relative left hemispheric EEG activity than neutral words.     

Delusional disorder (paranoia)

A definition of delusional disorder is given. This definition comes from clinical practice and is quite rigorous. Delusional disorder exists but is uncommon. It is likely to be called schizophrenia (paranoid schizophrenia) because it fills published criteria for such a diagnosis. It is more likely seen in men than women. It bears no relation to I.Q. It does not destroy the ability to function socially but does create problems in living because of interpersonal conflicts. Familially it bears no relation to affective disorder. It seems to breed true within families but this is not proven. What is necessary to settle major issues is a multicentered systematic blind family study and follow-up with a group of nonparanoid schizophrenics as controls.     

Plasma cyclic nucleotide responses to methacholine in patients with Adie's syndrome

The purpose of the present study was to show anomalies of the plasma cyclic nucleotide responses of patients with Adie's syndrome to an intramuscular injection of methacholine (80 μg/kg body wt). The methacholine-induced increase in plasma cGMP was much larger in patients with Adie's syndrome than in controls. There was also a small but significant rise of plasma cAMP in patients with Adie's syndrome, while no change was observed in controls, following the methacholine challenge. It is likely that cholinergic receptor responses are enhanced in patients with Adie's syndrome, in good agreement with the postulated pupillary postganglionic denervation in affected pupils.     

Modulation of spinal synaptic transmission by beta-melanocyte stimulating hormone (beta-MSH)

Synaptic modulation refers to altered excitability of a synapse by a substance that does not produce a spike potential at the synapse. Available evidence points to the conclusion that beta-melanocyte stimulating hormone (beta-MSH) modulates synaptic transmission through monosynaptic pathways in the cat spinal cord. Earlier evidence is reviewed, and new data are presented. In the first experiments populations of cells contributing to a knee jerk were studied using the Lloyd preparation, and MSH was found to increase the monosynaptic reflex. With intracellular single unit recording techniques, beta-MSH was found to facilitate recovery from synaptic transmission. With extracellular single unit recording techniques and iontophoretic methods for drug application, beta-MSH has been found to increase the probability of generation of single spike potentials by alpha-motoneurons in response to orthodromic stimulation. Administration of beta-MSH did not cause spontaneous discharge of alpha-motoneurons. The physiological and pharmacological importance of synaptic modulation is discussed.