Fungal arthritis. II. Coccidioidal synovitis: clinical, diagnostic, therapeutic, and prognostic considerations.

This is the second phase of a review of fungal arthritis that will be presented in three parts. Coccidioidal synovitis will be discussed in this issue. Part I was a review of Candida arthritis; part III will be a review of cryptococcal, sporotrichal, histoplasmal, and blastomycotic arthritis.     

Mechanism of escape, extrasystolic, and parasystolic arrhythmias. Study on an electrical analogue.

A simple analogue of the heart consisting of a system of neon relaxation oscillators is presented. The analogue may display rhythm patterns similar to sinus rhythm, escape rhythm, isorrhythmic dissociation with synchronization, atrial extrasystoles, ventricular extrasystoles, and parasystole. The strict rules followed by these arrhythmias, as well as the deviations from the rules commonly followed by the equivalent heart arrhythmias, may be easily reproduced on the analogue. Such features are the Treppe phenomenon and captured beats in escape rhythm, fixed coupling intervals in extrasystoles, partial or complete atrioventricular block in very premature atrial extrasystoles, prolongation of the period following an atrial extrasystole, interpolated premature beats, complete compensatory pause and the rule of bigeminy in ventricular extrasystoles, slight instability of the parasystolic period, multiple length parasystolic periods slightly different from the exact multiples of the parasystolic idioperiod, preference of the parasystoles for certain phase in the sinus cycle, synchronization at a phase difference and fluctuation repeatedly and without interruption from a parasystolic to an extrasystolic rhythm and synchronization in escape rhythm with isorrhythmic dissociation. The mechanisms involved in these phenomena are discussed in detail. The striking similarity between the properties of the cardiac pacemakers and those of the relaxation oscillators on the one hand and betwen the rhythm patterns of the heart and those of the analogue on the other may permit the hypothesis that the mechanisms operating in the analogue may be used in analyzing and understanding heart arrhythmias.     

Immunodeficiency, malabsorption and secretory diarrhea. A new syndrome.

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.     

Third F. Raymond Keating, Jr., Memorial Symposium--parathyroid hormone, calcitonin and vitamin D: clinical considerations. II. Vitamin D--1973

The recent advances in our understanding of the functional metabolism of vitamin D to 25-hydroxyvitamin D (25-(OH)D) and subsequently to 1,25-dihydroxyvitamin D (1,25-(OH)₂D) are presented with a review of current views on the regulation of vitamin D metabolism at the 25-hydroxylation and 1-hydroxylation stages. It seems clear that, physiologically, the latter regulation is governed by parathyroid hormone (PTH) under conditions of hypocalcemia and by serum inorganic phosphorus levels under conditions from normal to hypercalcemia. The molecular mechanism of the regulation of the renal hydroxylations remains unknown.The metabolism of 25-(OH)D₃ to 24,25-(OH)₂D₃ and further to 1,24,25-(OH)₃D₃ has been established. The significance of these reactions is unknown, but 1,24,25-(OH)₃D₃ preferentially stimulates intestinal calcium transport.The mechanism whereby 1,25-(OH)₂D₃ stimulates intestinal calcium transport and the receptors of this metabolite in intestine are discussed. In addition, the application of the metabolites of vitamin D to clinical problems has been considered and 1α-(OH)D₃, an important analog of 1,25-(OH)₂D₃, has been introduced as a potentially important therapeutic compound.     

Myocardial infarct size. Part 2. Comparison of anti-infarct effects of beta-blockade, glucose-insulin-potassium, nitrates, and hyaluronidase

Based on the principles discussed in the first part of this review, the following interventions (Table I) could be expected to limit infarct size: (1) relief of vascular obstruction, (2) increased collateral flow or diffusion to the ischemic zone, (3) relief of the load on the heart, thereby promoting a more favorable balance between the oxygen supply and demand, (4) catecholamine antagonism, and (5) specific metabolic measures. Table I lists those agents tested in patients for therapeutic effects on indices of infarct size. Because the role and exact nature of the vascular obstruction is so controversial, agents acting at that level have been omitted from further consideration, and one agent has been selected from each of the remaining categories (2 to 5) of Table I.Thus the four anti-infarct agents selected for consideration in further detail are: β-blockade, glucose-insulin-potassium, nitrates, and hyaluronidase. β-blockade is selected because of the exceptionally full experimental and clinical studies now available and because of a combined hemodynamic and metabolic action. Glucoseinsulin-potassium is selected as one of the first interventions introduced, and now well studied over many years; it is an agent likely to counteract undesirable metabolic changes in acute infarction. Glucose-insulin-potassium is compared with the use of a nicotinic acid analog which also has an antilipolytic action. Nitrates are selected because of their dual mechanism of action, both by causing coronary vasodilation and by reducing the pre- and afterload on the heart. In addition, nitrates, as therapeutic agents, are well known to all practicing cardiologists. Nitroprusside is considered together with the nitrates, although nitroprusside has a more definitive effect on the afterload than do nitrates. Finally, hyaluronidase is chosen as a well-investigated agent with minimal side effects and no known hemodynamic mode of action.Other promising agents have been omitted, although of great potential interest, because of the limited number of patient studies available. For example, the effects of steroids are well documented in experimental preparations. Although they diminish the features of acute ischemic injury, probably acting by means of “membrane stabilization,” they also inhibit wound healing¹³⁰ and hence increase the risk of ventricular rupture or aneurysm² (See also Table I, references 250, 251, 256, and 257). Another interesting category of agents, the calcium antagonists, are only now being studied in patients.     

Serum thyroxine, free T4, triiodothyronine, and reverse-T3 in diphenylhydantoin-treated patients.

In order to determine the effects of the administration of diphenylhydantoin (DPH) on various parameters of thyroid function, serum samples from 47 male adults receiving therapeutic doses of DPH and 45 euthyroid control subjects were analyzed for total thyroxine (T₄) and an index of free T₄ concentration, using both a competitive protein-binding assay (CPBA) and a solid-phase radioimmunoassay (RIA), total 3,5,3′-triiodothyronine (T₃), 3,3′,5′-triiodothyronine (reverse-T₃, rT₃), and TSH, each measured by specific RIA. Mean total T₄ by both methods was depressed in the DPH group to 0.78 of the control level. Free T₄ Index by RIA was decreased on the average in DPH-patients exactly in proportion to the depression in total T₄. By the CPBA, the difference between two groups in Free T₄ Index was less marked but still significant (DPH/controls = 0.86, p < 0.01). The concentrations of total T₃ were virtually identical in the DPH and the control groups. The average $\text{T}{}_3\text{T}{}_4$ ratio was significantly higher in the DPH patients than in the controls (0.0178 versus 0.0132, p < 0.001). Serum rT₃ was depressed by DPH-treatment in approximately the same proportion to the decrease in total T₄. None of the DPH-patients had an elevated serum TSH. The above findings are interpreted as indirect evidence in support of the view that DPH stimulates T₄ metabolism, particularly the conversion of T₄ to T₃. The normal level of free T₃ may help to maintain a euthyroid state in spite of the decrease in free T₄. The data also define the “euthyroid” ranges for total and free T₄ levels by these methods in patients receiving DPH.     

Rales, peripheral edema, retinal hemorrhage and acute mountain sickness.

Rales, peripheral edema and retinal hemorrhage have been reported in sojourners at high altitudes. The purpose of this study was to determine their incidences and their associations with acute mountain sickness.Two hundred trekkers were studied at an altitude of 4,243 m in the Himalayas on the trail to Mount Everest. The subjects either flew to an altitude of 2,800 m and then proceeded on foot (four to six days) or walked in from Kathmandu at 1,300 m (14 to 18 days), all arriving at 4,243 m on foot. They were examined during ascent to an altitude of 5,545 m and again during descent.The age of the population (mean ± 1 standard deviation (SD)) was 33 ± 12 years, and 70 per cent were male. The incidence of acute mountain sickness was 49 per cent in those flying to an altitude of 2,800 m and 31 per cent in those walking to the same altitude (P < 0.001).Rales were found in 23 per cent and were associated (P < 0.05) with acute mountain sickness, peripheral edema and retinal hemorrhage. Peripheral edema occurred in 18 per cent of the subjects and retinal hemorrhages in 4 per cent. Both conditions were associated with acute mountain sickness (P < 0.05) and were more common in women (P < 0.01). We conclude that rales and peripheral edema are common in high-altitude visitors at 4,243 m and that, together with retinal hemorrhage, they are associated with acute mountain sickness.     

Remission and recovery from chronic, established, complete heart block.

The return of A-V conduction is described in a patient after two decades of high-grade or complete congenital heart block. Similar cases have been reported by others, with remission or even recovery commencing up to the fourth decade or later. A similar phenomenon is also described in four patients with acquired heart block of four to ten years' duration; in them, remission was usuallly brief but persisted for seven years in one patient. No full report of this seems to have been published previously. Possible explanations are discussed, but no conclusion is reached. Apart from its interest, the phenomenon is of importance with respect to the selection of demand-type electronic pacemakers in the management of patients with heart block.     

A developmental study of progesterone, corticosterone, cortisol, and cortisone in the adrenal glands of the embryonic chick.

Pairs of adrenal glands were removed from embryonic chicks at 2-day intervals between 9 and 21 days of incubation. Four corticosteroids (progesterone, corticosterone, cortisol, and cortisone) were separated by column chromatography and their concentrations were determined using the competitive protein-binding assay of Murphy [(1967) J. Clin. Endocrinol. Metab.27, 973–990]. Further identification of cortisol in embryonic chicks was carried out using thin layer and paper chromatography followed by the double isotope assay. Total corticosteroid/pair adrenal glands rose from 9 ng at 9 days to a peak of 38 ng at 15 days. The concentration declined to 21 ng at 19 days and then rose again at hatching.Over the 12-day period studied corticosterone accounted for one third of the total adrenal corticosteroids measured. At hatching corticosterone and its precursor, progesterone accounted for 71% of the total, indicating establishment of the adult pattern of predominance of corticosterone.This report, along with our previous paper [(1974) Gen. Comp. Endocrinol.24, 364–372], provides base line normal gland and circulating steroid levels. It emphasizes that several corticosteroids are being synthesized and secreted during embryonic development.     

External validation and comparison of the scoring systems (S.T.O.N.E,GUY, CROES,S-ReSC) for predicting percutaneous nephrolithotomy outcomes for staghorn stones: A single center experience with 160 cases

The aim of this study was validation and comparison of stone scoring systems (S.T.O.N.E, GUY, CROES, S-ReSC) used to predict postoperative stone-free status and complications after percutaneous nephrolithotomy (PCNL) for staghorn stones. A total of 160 patients who had staghorn renal stones and underwent PCNL between January 2012 and August 2015 were included in the current retrospective study. Guy, S.T.O.N.E., S-ReSC (Seoul National University Renal Stone Complexity) and CROES (Clinical Research Office of the Endourological Society) nephrolithometry scores were calculated for each patient, and their potential association with stone-free status, operative and fluoroscopy time, and length of hospital stay (LOS) were evaluated. Postoperative complications were graded according to the modified Clavien classification, and the correlation of scoring systems with postoperative complications was also investigated. The mean CROES, S.T.O.N.E, Guy and S-ReSC scores were 143.5 ± 33.6, 9.7 ± 1.6, 3.5 ± 0.5 and 6.2 ± 2.0 respectively. The overall stone-free rate was 59%. All scoring systems were significantly correlated with stone-free status in univariate analysis. However, Guy and S-ReSC scores were the only significant independent predictor in multivariate analysis. And all four nomograms failed to predict complication rates. Current study demonstrated that Guy and S-ReSC scoring systems could effectively predict postoperative stone-free status for staghorn stones. However all four scoring systems failed to predict complication rates.     

Aortic stenosis, angina pectoris, and coronary artery disease.

The relationships between aortic stenosis, coronary artery disease, angina pectoris, and myocardial infarction were examined in 173 patients with isolated calcific aortic stenosis who had coronary arteriography as well as cardiac catheterization. All were over age 40 and had definite cardiac symptoms; 156 later had aortic valve replacement. Coronary lesions narrowing the lumen by 50% or more were present in 37% of patients aged 40 to 59 and 68% of those aged 60 to 82. Coronary disease was present in 64% of patients with angina pectoris and 33% of those without angina. Angina which occurred only in association with dyspnea on exertion was associated with coronary disease in 45% of instances, whereas angina which also occurred on exertion without any dyspnea or which occurred with emotional stress, after meals, during sleep, or at rest unprovoked was associated with coronary disease in 80% of instances. Patients with coronary disease without any chest pain or with atypical pain considered nonanginal were men, usually over age 60, with congestive heart failure as the predominant symptom. Electrocardiograms showing transmural inferior or anterolateral infarction nearly always indicated coronary disease, while QS patterns in Leads V1-2 occurred frequently with normal coronary arteries. Serum cholesterol was elevated in 23% of those with coronary disease and 8% of those without. A group of patients with moderate aortic stenosis could be identified, with aortic valve areas of 0.55 to 0.80 cm. per square meter, in whom coronary disease was the sole or chief cause of symptoms. The operative mortality rate with aortic valve replacement was 9.6% in those with coronary disease and 1.4% in those without significant coronary disease. Coronary disease is frequently present in patients with calcific aortic stenosis, particularly in those over 60, those with angina, and those with symptoms despite only moderate aortic stenosis. The type of anginal syndrome, the ECG evidence of transmural infarction, and the coronary risk factors provide additional clues for clinical diagnosis.