HYPOTHALAMIC DYSFUNCTION—A Review of Experimental and Clinical Observations of Cardiac and Renal Aspects

The nuclear cell masses of the hypothalamus act as autonomic regulators for visceromotor function. Through the correlation of impulses arising in or about the hypothalamus with the changes in cellular chemistry, there is provided, by mediation of the endocrines, a balanced control of water metabolism, renal function and cardiac action.Derangement of hypothalamic regulation causes specific clinical syndromes described by the general term “diencephalohypophyseal dystrophy.” Cardiac abnormalities attributable to hypothalamic dysfunction include alterations in rate and various arrhythmias. Alteration in renal function includes hematuria, polyuria or relative anuria, and specific effects on electrolyte and nitrogen output.     

WHO ARE PROSPECTIVE NEUROTICS?

Emotions of any kind and experienced at any age are etiologic factors of neuroses only in predisposed persons.Predisposed persons are those of neuropathic and psychoneuropathic constitution. This is characterized by excessive excitability and abnormal reactivity of the nervous system. This involves, in various degree and proportion, the autonomic nervous system as well as the higher cerebral functions including associative and emotional mental reactions.Objective signs of autonomic nervous imbalance can be detected by physical examination. In the mental sphere, psychoneurotic constitution can be recognized by emotional imbalance, excessive, inadequate, untimely reactions (“psychic dysmetry”).Neuropathic and psychoneuropathic constitution per se is compatible with perfect health. It deserves attention, however, in that its carriers may play an important role in cultural and social life and so exert a great suggestive influence on the mass of people.The type of neurosis or psychoneurosis and the symptoms of it depend chiefly on the constitutional morbid predisposition (constitutional biologic inferiority) of certain organs or organ systems and on the kind of emotional situations which the patient is unable to cope with.The great number of neuroses, psychoneuroses and psychosomatic diseases among patients consulting them makes it imperative that internists and general practitioners be capable of making the correct diagnosis and of carrying out the indicated treatments by “minor psychotherapy.”     

Lymphocyte Response Depressive Factor in Multiple Sclerosis

Normal serum contains a lymphocyte response depressive factor and this is more active against the lymphocytes of the blood from which the serum was obtained than against lymphocytes from a different normal blood. The suppressive factor is thus “tailor-made” to its own lymphocytes though cross-reactivity with other lymphocytes does occur. The significance of this is discussed. The suppressive factor has a higher titre in serum from patients with multiple sclerosis or other destructive neurological disease than in normal serum. This may be an instance of a general phenomenon in which lymphocyte sensitization is ordinarily accompanied by production of a suppressor factor able to damp down response so that this is controlled by an “acceleratorbrake” mechanism. The possibilities of imbalance in the pathogenesis of disease and therapeutic manipulation of the level of suppressor substance are briefly discussed.     

Relative Humidity and the Killing of Bacteria: The Survival of Damp Serratia marcescens in Air

The viability of washed moist cells of Serratia marcescens after storage has been measured in relation to variations in the prior treatment of the cells and in conditions of storage. The factors considered were: (i) water content during storage; (ii) method of arriving at water content (partial drying in vacuum or freeze-drying and addition of water); (iii) presence or absence of air during storage.

Increasingly rapid decay occurs as the water content at which the cells are stored is diminished from above 90% to 20 or 30% (“critical” water content). It occurs in presence or absence of air and it occurs whether the final water content is approached by removal of water from wet cells or by addition of water to freeze-dried cells.

The rate of decay during storage at 20 to 30% water is somewhat diminished by the presence of air (“protective” effect of air).

As the water content is further reduced to less than 10%, the stability of cells stored in a vacuum approaches that of wet cells. In presence of air the reverse is true: the stability decreases until at less than 1% water, the decay rate is about as great as at the “critical” water content (“toxic” effect of air).

Particularly rapid decay of S. marcescens at the “critical” water content has escaped attention in aerosol studies because accurate control of relative humidity (RH) in this region, RH 94 to 99%, is virtually impossible in such studies. On the other hand, values of decay rates referred to measured water contents are quite unreliable in the 20 to 80% RH zone because the corresponding variation of water content is too small to measure reliably. Thus data of the kind reported in this paper cannot be directly compared to the published results of studies of air-borne bacteria, although they are relevant to the practical question of air-borne infection in humid atmospheres.

     

Acid Base Disorders—The Clinical Use of the Astrup Method of Determining pH. pCO2 and Base Excess

The Astrup method for determination of arterial pH, pCO₂, and “base excess” provides a simple and accurate means for quantitation of acid-base disorders. The “base excess” value, a measure of metabolic acidosis or alkalosis, gives the clinician a valuable tool with which to estimate electrolyte replacement. The pCO₂ is a measure of respiratory acidosis or alkalosis. The pH is used as a measure of the adequacy of compensation. Several representative cases illustrate the use and interpretation of the test.     

Drowning and the Influence of Hot Weather

Background

Drowning deaths are devastating and preventable. Public perception does not regard hot weather as a common scenario for drowning deaths. The objective of our study was to test the association between hot weather and drowning risk.

Materials and Methods

We conducted a retrospective case-crossover analysis of all unintentional drowning deaths in Ontario, Canada from 1999 to 2009. Demographic data were obtained from the Office of the Chief Coroner. Weather data were obtained from Environment Canada. We used the pair-matched analytic approach for the case-crossover design to contrast the weather on the date of the drowning with the weather at the same location one week prior (control period).

Results

We identified 1243 drowning deaths. The mean age was 40 years, 82% were male, and most events (71%) occurred in open water. The pair-matched analytic approach indicated that temperatures exceeding 30°C were associated with a 69% increase in the risk of outdoor drowning (OR = 1.69, 95% CI 1.23–2.25, p = 0.001). For indoor drowning, however, temperatures exceeding 30°C were not associated with a statistically significant increase in the risk of drowning (OR = 1.50, 95% CI 0.53–4.21, p = 0.442). Adult men were specifically prone to drown in hot weather (OR 1.67, 95% CI 1.19–2.34, p = 0.003) yet an apparent increase in risk extended to both genders and all age groups.

Conclusion

Contrary to popular belief, hot weather rather than cold stormy weather increases the risk of drowning. An awareness of this risk might encourage greater use of drowning prevention strategies known to save lives.     

Structural transition produced by electric fields in aqueous sodium deoxyribonucleate

It was found that the birefringence of aqueous solutions of sodium DNA is anomalous when electric fields of high intensity (≥10⁴ v/cm) are applied. The magnitude of the birefringence first rose upon application of the orienting pulse, then fell as the field was sustained above a critical value. The occurrence of the effect depended upon macromolecular and electrolyte concentrations. Upon removal of the field, the birefringence was rapidly restored and then it decayed with an increase of the reorientational relaxation times, relative to those observed below the critical field. It is proposed that the electric field may cause aggregation of the macromolecules and then produce a structural transition concomitant with the electric field orientation effect. This transition may correspond to the “B” “A” structures identified in x-ray studies, or to a “B” “V” structure change, where “V” is a postulated new helical form stabilized by cooperative interactions of base and dipoles in the electric field. Field induced transitions of this type would be of interest in connection with molecular mechanisms of transport through membranes, nerve impulse transmission, or information storage.     

CRANIOCEREBRAL INJURIES

The postconcussion syndrome is a definite entity, and the patient''s complaints are due to legitimate injury. The following three factors contribute to the symptomatology:1. Headaches, caused by the associated sprain of the cervical spine with resultant radiculitis—giving rise to muscle spasm and suboccipital headaches.2. Vertigo, due to trauma of the vestibular and labyrinthine apparatus.3. A vasomotor imbalance and instability resulting from the reaction to “stress.”In treatment of an unconscious patient great care must be taken to prevent anoxia and to balance the fluids and electrolytes.If coma develops following brain injury, hemorrhage into the cerebellar fossa as well as above the tentorium must be considered.     

Why Has the Continuous Decline in German Suicide Rates Stopped in 2007?

Background

Whereas German suicide rates had a clear decreasing tendency between 1991 and 2006, they increased from 2007 to 2010. Deeper analyses of suicide data might help to understand better this change. The aim of this study was to analyze 1) whether recent trends can be related to changes in specific suicide methods and diverge by gender and age; 2) whether the decrease of suicide rates before 2007 as well as the increase from 2007 to 2010 are driven by the same suicide method.

Methods

Analyses were based on suicide data from the Federal Statistical Office of Germany. For 1998–2010, 136.583 suicide cases of men and women with known age and suicide method could be identified. These data were analyzed by joinpoint regression analysis, allowing identification of the best fitting point in time (“joinpoint”) at which the suicide rate significantly changes in magnitude or direction.

Results

The national downward trend between 1998 and 2007 was mainly due to corresponding changes in self-poisoning by other means than drugs (e.g., pesticides) (annual percentage change (APC) ≤ −4.33), drowning (APC ≤ −2.73), hanging (APC ≤ −2.69) and suicides by firearms (APC ≤ −1.46) in both genders. Regarding the overall increase of age-adjusted suicide rates in Germany 2007–2010, mainly the increase of self-poisoning (e.g., by drugs) and “being overrun” (APC ≥ 1.50) contributed to this trend.

Limitations

The true suicide rates might have been underestimated because of errors in the official death certificates.

Conclusions

Increase in suicide rates in Germany since 2007 went along with corresponding changes for “being overrun” and “self-poisoning”. Copycat suicides following the railway suicide of the goalkeeper Robert Enke partly contributed to the results. Thus, prevention of Werther effects and limitation of the availability of high pack sizes for drugs are of special relevance for the reversal of this trend.     

Neurological Factors in Reading Disability

An overview is presented of that portion of the literature on reading disability wherein neurological defect is seen as causal or correlative. From the publication of Hinshelwood''s “Congenital Word Blindness” (1917) to the present, investigators have considered the possible association of reading difficulty with genetically determined neurological defect, with cerebral damage, with biochemical imbalance inhibiting synaptic transmission, and with some form of maturational lag.     

Human Tau Isoforms Assemble into Ribbon-like Fibrils That Display Polymorphic Structure and Stability

Fibrous aggregates of Tau protein are characteristic features of Alzheimer disease. We applied high resolution atomic force and EM microscopy to study fibrils assembled from different human Tau isoforms and domains. All fibrils reveal structural polymorphism; the “thin twisted” and “thin smooth” fibrils resemble flat ribbons (cross-section ∼10 × 15 nm) with diverse twist periodicities. “Thick fibrils” show periodicities of ∼65–70 nm and thicknesses of ∼9–18 nm such as routinely reported for “paired helical filaments” but structurally resemble heavily twisted ribbons. Therefore, thin and thick fibrils assembled from different human Tau isoforms challenge current structural models of paired helical filaments. Furthermore, all Tau fibrils reveal axial subperiodicities of ∼17–19 nm and, upon exposure to mechanical stress or hydrophobic surfaces, disassemble into uniform fragments that remain connected by thin thread-like structures (∼2 nm). This hydrophobically induced disassembly is inhibited at enhanced electrolyte concentrations, indicating that the fragments resemble structural building blocks and the fibril integrity depends largely on hydrophobic and electrostatic interactions. Because full-length Tau and repeat domain constructs assemble into fibrils of similar thickness, the “fuzzy coat” of Tau protein termini surrounding the fibril axis is nearly invisible for atomic force microscopy and EM, presumably because of its high flexibility.     

Goiter in Tibetan Medicine

The visit of two Tibetan physicians provided a unique opportunity to gain insight into a practice of medicine very different from that of Western civilization. Initial discussions indicated that the practice of medicine and mysticism were inextricably interwoven in the Tibetan culture. Accordingly, the focus of the study was directed to goiter, which is both common in the Himalayas and easy to define.In Tibetan medical practice, illness is considered to be derived from both proximate and distant causes. Three humors, “wind,” “bile,” and “phlegm” are thought to be responsible for normal mental and physical functions when in balance, but disease when out of balance. Goiter was thought to be due to an imbalance of these humors. The Western discovery that endemic goiter in the Himalayas was due to iodine deficiency explained the proximate cause but did not explain why some individuals have goiter and others do not in the same iodine deficient village.     

Phenotypic stability in scalar calcium of freshwater fish across a wide range of aqueous calcium availability in nature

Spatial environmental gradients can promote adaptive differences among conspecific populations as a result of local adaptation or phenotypic plasticity. Such divergence can be opposed by various constraints, including gene flow, limited genetic variation, temporal fluctuations, or developmental constraints. We focus on the constraint that can be imposed when some populations are found in locations characterized by low levels of an essential nutrient. We use scales of wild fish to investigate phenotypic effects of spatial variation in a potentially limiting nutrient—calcium. If scale calcium (we use “scalar” calcium for consistency with the physiology literature) simply reflects environmental calcium availability, we expect higher levels of scalar calcium in fish from calcium‐rich water, compared to fish from calcium‐poor water. To consider this “passive response” scenario, we analyzed scalar calcium concentrations from three native fish species (Lepomis gibbosus, Percina caprodes, and Perca flavescens) collected at multiple sites across a dissolved calcium gradient in the Upper St. Lawrence River. Contradicting the “passive response" scenario, we did not detect strong or consistent relationships between scalar calcium and water calcium. Instead, for a given proportional increase in water calcium across the wide environmental gradient, the corresponding proportional change in scalar calcium was much smaller. We thus favor the alternative “active homeostasis” scenario, wherein fish from calcium‐poor water are better able to uptake, mobilize, and deposit calcium than are fish from calcium‐rich water. We further highlight the importance of studying functional traits, such as scales, in their natural setting as opposed to only laboratory studies.     

Fragilities Caused by Dosage Imbalance in Regulation of the Budding Yeast Cell Cycle

Cells can maintain their functions despite fluctuations in intracellular parameters, such as protein activities and gene expression levels. This commonly observed biological property of cells is called robustness. On the other hand, these parameters have different limitations, each reflecting the property of the subsystem containing the parameter. The budding yeast cell cycle is quite fragile upon overexpression of CDC14, but is robust upon overexpression of ESP1. The gene products of both CDC14 and ESP1 are regulated by 1∶1 binding with their inhibitors (Net1 and Pds1), and a mathematical model predicts the extreme fragility of the cell cycle upon overexpression of CDC14 and ESP1 caused by dosage imbalance between these genes. However, it has not been experimentally shown that dosage imbalance causes fragility of the cell cycle. In this study, we measured the quantitative genetic interactions of these genes by performing combinatorial “genetic tug-of-war” experiments. We first showed experimental evidence that dosage imbalance between CDC14 and NET1 causes fragility. We also showed that fragility arising from dosage imbalance between ESP1 and PDS1 is masked by CDH1 and CLB2. The masking function of CLB2 was stabilization of Pds1 by its phosphorylation. We finally modified Chen''s model according to our findings. We thus propose that dosage imbalance causes fragility in biological systems.     

Some Peculiarities of Water Transport through Plasticized Nonporous Membranes

“Liquid” and “plasticized” solvent membranes are of interest as possible analogues of biological systems. Semipermeable homogeneous films are prepared by plasticizing polyvinylchloride with organic phosphates. Water permeability of such films is relatively high. For a material containing 70% of 1.4-dihydroxyphenyl-bis(dibutylphosphate), the diffusion coefficient of water at room temperature was estimated to be about 1 × 10^-6 cm²/sec. Conditioning of a plasticized membrane, under the osmotic gradient of solution of sodium nitrate, leads to profound changes in its morphology and to a drastic increase of its water permeability. The induced changes are reversible to a large extent. Their reversibility in various solutions may be correlated with the respective differences in permselectivity. The structure of expanded membranes and the mechanism of changes taking place under the osmotic gradients are discussed.     

USE OF THE ARTIFICIAL KIDNEY—Its Place in the Treatment of Acute Renal Failure

Of 57 patients with severe, but potentially reversible, acute renal failure who were observed during a recent four-year period, some had dialysis with an artificial kidney and some did not.Twenty survived with the standard “conservative” management alone; 19 survived with a combination of “conservative” and “intensive” (that is, artificial kidney) treatment; 18 patients died.One error that was made in the management of all 18 patients who died, was excessive delay in the use of the artificial kidney.Hemodialysis should be used whenever serious electrolyte abnormality exists, whenever the blood urea nitrogen exceeds 150 mg. per 100 cc. or whenever clinical signs of uremia first appear. One or more of these indications will usually, but not always, become evident between the fifth and the eighth day of virtual anuria.     

CALIFORNIA MEDICAL ASSOCIATION

Any patient with so-called “refractory” heart failure should be looked upon as suboptimally handled. The patient should be studied for possible development of new disturbances, either inside or outside the vascular system, which, at the same time, have a bearing upon the heart failure.The entire therapeutic program should be reviewed to be sure that all aspects of therapy have been evaluated satisfactorily and established optimally. If diuretics, especially mercurial diuretics, have been given, the possible complications of such therapy, particularly in terms of electrolyte imbalance, should be considered. It is only through a general survey of the patient for an evaluation of these factors that they may be found and therapy instituted to minimize or eliminate them.     

LEG CRAMPS

Foot and leg cramps are among the most frequent complaints presented by patients of both sexes, especially older persons. Similar cramping may occur in the thighs or in other skeletal muscles of the extremities and trunk. Foot and leg cramps usually occur after unusual exertion or during sleep. “Nocturnal leg cramps” may be of sufficient intensity to prevent sleep. “Pregnancy cramps” are particularly distressing.Effective treatment of foot and leg cramps requires an understanding of the etiology, pathophysiology and diagnostic techniques. Weight reduction and improved diet are essential. Among the useful supplementary medications are calcium lactate or gluconate, vitamin-mineral supplements, sympathetic blocking agents, vasodilators, ataraxics, muscle relaxants, quinine, hydrochloride, antihistamines, and nonmercurial diuretics.Improved foot care and correction of foot imbalance is usually required. Edema and venous insufficiency are improved by elastic support, by repeated foot elevation for massages, by manipulations and exercises and by the use of diuretics. There may be need for operations on the veins and for sclerotherapy. Patients with arterial insufficiency are often benefited by lumbar sympathetic blocks with long-acting anesthetics and intra-arterial injections with relaxants, vasodilators, thrombolytic enzymes and anticoagulants. Sympathectomy, angiography and reconstructive arterial operations are indicated in only a small proportion of patients with foot and leg cramps.     

Blood Pressure: A Consideration of Terminology

Concepts of hypertension have changed and changes in terminology to reflect this state of affairs are suggested. Statistically, the best mortality experience is associated with blood pressure commonly regarded as subnormal, and increments of blood pressure above this level are associated with progressive increases in mortality. The terms “normal”, “benign” and “essential” in relation to blood pressure should be abandoned. “Optimal”, “acceptable” and “hypertensive” ranges of blood pressure are suggested. Hypertension is regarded as a symptom of disease, rather than as a disease in itself, and “hypertension”, when used as a diagnostic label, should be qualified always by the primary disease, if known, or by the modifying phrase, “of unknown cause”, if not known.