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Fifteen patients with potassium depletion were studied during the development and/or correction of their depletion. Alkalosis occurred in all these subjects. In every instance the alkalosis was associated with a positive cation excess: sodium was retained in excess of chloride in those patients depleted by sodium cycle exchange resins, and chloride was lost in excess of sodium in those patients depleted with diuretics. In every instance correction of the alkalosis was associated with a negative cation excess: chloride was retained in excess of sodium in those patients depleted with diuretics, and sodium was lost in excess of chloride in those patients depleted by sodium cycle exchange resins. Potassium depletion and particularly hypokalemia may be corrected independently of the alkalosis. Chloride is necessary for the correction of metabolic alkalosis only when there has been chloride loss during the development of alkalosis.

Summary Suppression of external pancreatic secretion in dogs was produced by exogenous serotonin (serotonin creatinine sulfate) despite constant secretin stimulation and despite vagotomy or atropine. Attempts to modify this response, and attempts to modify the similar response to intraduodenal hypertonic feedings, by pretreatment with a number of serotonin antagonists were unsuccessful. Possible mechanisms involved in these pancreatic responses are discussed.

The course of events in the solvation and reconstitution of collagen obtained from rat tail tendon is described as seen with the electron microscope. Under the influence of 0.01 per cent acetic acid the collagen fibers swell and dissociate into submicroscopic filaments, the smallest of which are probably beyond the resolution of the electron microscope. These filaments can be made to reconstitute into fibers either by the addition of neutral salts to the acid solution or by raising the pH. The structural form of the resulting fibers is influenced by the concentration of the salt and by the pH of the solution employed. Saline-concentrations around 1 per cent and pH's ranging from 4.8 to 6.8 lead to the formation of needle-shaped crystals, or tactoids, showing the striated structure characteristic of collagen. Saline concentrations outside of this range (0.5 per cent and 5.0 per cent) lead to the formation of long fibrils without evidence of striations. pH's on the alkaline side of 6.8 bring about the formation of long slender fibers. Some of the possible reasons for these different fiber forms are discussed. Apparently fibers are formed in vitro by the lateral and longitudinal association of the filaments seen in the original solutions. Some of the fibers thus formed may in turn associate laterally and longitudinally to form the larger fibers. The formation of the needle-shaped crystals appears to be an orderly process since it leads to the formation of a periodicity in the fibers. The striations in the smaller fibers are uniform and regularly spaced at around 210 A. With continued growth of these fibers there is a simultaneous development of a more obvious and precise banding. It is evident that two out of each group of three regularly spaced striae are more prominent. This produces the macroperiod of collagen measuring around 640 A in length.

Some information on the origin and development of collagenous fibers has been obtained from the study of cultured tissues1-4 and wound healing.5 In such material fine fibrils can be observed to develop between the cells. These subsequently increase in number and finally coalesce to form larger fibers. It is generally thought that the fibrils are organized from an intercellular protein that is produced by or at least influenced by the surrounding cells, but the precise mechanism is not understood.One approach to the examination of this problem is by way of direct observations on the early sub-microscopic sequences involved in fiber formation. To that end we have utilized the combined methods of electron microscopy and tissue culture.The material studied has included fibrous arrays formed in vitro in association with ex-plants of chick embryo skin and foregut, rabbit thymus and rat pericardium.† In preparation for microscopy the cultures containing these arrays were washed in a balanced salt solution, fixed...

A method is described for preparing purified collagen from the tail tendons of rats with minimal alteration from its native state. This purified collagen is soluble in dilute acetic acid and when injected intraperitoneally into rabbits induces complement-fixing antibodies in low titer. It has been demonstrated by the use of certain immunological tests, enzymatic analyses, and electron microscopy that these antibodies are probably directed specifically toward collagen rather than toward accompanying impurities such as tissue proteins or polysaccharides. Evidence is presented suggesting that collagen exhibits species specificity.

SODIUM retention and fluid accumulation manifested as edema are common in cancer patients. 1 This is usually secondary to pooling of fluids in a third space as occurs in ascites, pleural effusion, dependent edema secondary to obstruction of the inferior vena cava or lymphatics, peritonitis, or ileus. This abnormal accumulation of extracellular fluid is physiologically unavailable and results in a decreased effective circulating blood volume. Hyponatremia is common, but on a "dry weight" basis there is extra body sodium. A state of chronic protein depletion is common in cancer patients because of loss of protein into the malignant effusions and repeated drainage of these protein-rich fluids, loss of protein in diarrhea and external fistulae (especially pancreatic), decreased food intake and malnutrition, and hypercatabolism as a result of sepsis. Hypoalbuminemia with consequent decreased plasma oncotic pressure leads to a decreased plasma volume and facilitates the escape of fluid to these third

Renal biopsies performed in seven patients after methoxyflurane anesthesia followed by renal failure disclosed a striking degree of oxalate precipitation. The extent of the precipitation paralleled, but could not fully account for, the corresponding degree of azotemia. Urinary oxalate, determined in six patients, was elevated (96 to 480 mg per 24 hours). Methoxyflurane thus appears to cause secondary hyperoxaluria, and intrarenal oxalate precipitation may occur when renal function is compromised for any reason during or immediately after surgery. Oxalate deposition, when extensive, may contribute to the severity of the renal failure.

Changes in electrolyte metabolism in patients with neoplastic disease can be divided into three categories: 1. 1. Alterations resulting from mechanical interference by the tumor with the function of an organ. 2. 2. Abnormalities in electrolyte metabolism observed in patients with chronic disease, inanition and wasting. 3. 3. Alterations in electrolyte metabolism resulting from humoral or hormonal action of the tumor itself. Secretion of ACTH by tumors of various organs has been established and is responsible for the development of hypokalemic alkalosis. Secretion of ADH induced by tumors of the bronchus and the brain has been described in patients with hyponatremia and urinary sodium loss.

FLUID retention presents a problem in the management of many diverse clinical conditions. It is most commonly associated with congestive heart failure and Laennec's cirrhosis, but may also be present in patients with diffuse or localized carcinomatosis that manifests as pleural effusion, ascites, lymphedema of extremities or generalized edema, and may be very difficult to mobilize. In many cases the fluid retention can be adequately controlled by the administration of mercurial diuretics,1 chlorothiazide and related compounds2 or carbonic anhydrase inhibitors.3 However, not uncommonly patients with fluid retention may not respond to these agents from the beginning or may become refractory . . .

REPORTS in the literature have indicated that the infusion of tris (hydroxy-methyl) amino methane (tris) results in increased blood pH and carbon dioxide content, with no change or a lowering of Pco2 (ref. 1). Pulmonary ventilation has been reported to decrease, while large amounts of ‘bicarbonate’ are excreted through the kidneys2. These results have been interpreted in part as showing a respiratory centre responsiveness to pH in the absence of a change in Pco2 (ref. 2).

The renal transport of urate, phosphate and glucose was studied under conditions of glucose and phosphate loading in 2 patients with Fanconi syndrome and in a control subject. A definite relationship between the reabsorption of these 3 substances was established in the patients with Fanconi syndrome. Phosphate abolished the normally found uricosuric effect of glucose in the patients with Fanconi syndrome, but not in the control subject. In the absence of a glucose load, phosphate infusion had no effect on urate transport in either the patients with Fanconi syndrome or the control subject. Phosphate depressed the reabsorption of glucose during glucose loading in the patients with Fanconi syndrome, whereas little or no effect was observed in the normal subject. The administration of a phosphate load, with or without an additional glucose load, caused the complete inhibition of phosphate reabsorption in the patients with Fanconi syndrome. At similar phosphate load, phosphate reabsorption in the cont...

Sodium lactate was infused and urate clearance was measured under conditions of osmotic diuresis alone, as well as during simultaneous urate infusion. Urate clearance in the Dalmatian was not depressed by the administration of sodium lactate of 1.2–9.3 mEq/kg dl-sodium lactate, indicating that sodium lactate has no inhibitory effect on tubular secretion of urate. dl-Sodium lactate, 0.54–11.8 mEq/kg, was administered to four mongrel dogs in five experiments. In three experiments a significant drop of urate clearance in relation to filtration rate was observed. In two experiments in which urine flows exceeded 10 ml/min no significant decrease in urate clearance was recorded following dl-sodium lactate administration. The depression of urate clearance in the mongrel under conditions of moderate urine flow where reabsorption of solutes is more easily accomplished, and the absence of this effect in the Dalmatian as well as in the mongrel under conditions of vigorous diuresis where reabsorption of solutes is greatly diminished, lends support to the belief that sodium lactate depresses urate clearance by facilitating urate reabsorption in the mongrel.

SummaryRestraint-stress was induced in female CFE rats weighing between 150 and 200 g by stapling them in envelopes made of aluminum wire screening. Five mg of bovine growth hormone dissolved in 1 ml of buffer was administered subcutaneously immediately after stapling and again 10 hr later. Controls received injections of buffer or bovine serum albumin. The animals were sacrificed at 24 hr and the number of animals developing gastric erosions, the number per animal and the severity of erosions were determined with a dissecting microscope. Growth hormone provides partial but significant protection against the production of restraint-stress produced erosions, both in terms of incidence of erosions and their severity.

Summary Secretin was treated with acetic anhydride and the resulting preparation (Sa) was tested in dogs with Thomas duodenal cannulas for its effect on pancreatic flow. Sa caused pancreatic secretion when given as a constant infusion or as a single intravenous injection. A single injection of a large dose of Sa was apparently less stimulatory than a comparable amount of secretin. When a large dose of Sa in the form of a single injection was superimposed on a constant infusion of either secretin or Sa, there was a significant suppression of pancreatic flow. It is postulated that acetylated secretin competes with secretin for receptor sites in the pancreas. The failure to suppress pancreatic flow completely may be related to deacetylation or to residual secretory activity of the acetylated material.

The infusion of ammonium acetate has been shown to cause an increased respiratory rate and results in respiratory alkalosis in unanesthetized dogs. Convulsions and electrocardiographic changes also...

Nutritional impairment often occurs after gastrectomy. In a recent review article, Randall1estimated that about one-half of all patients subjected to subtotal gastrectomy have sufficient nutritional problems to prevent their regaining normal preoperative weight, and from 2 to 10% are severely disabled as a result of their operation. With total gastrectomy, at least two-thirds of the patients have nutritional problems, one-third of which are severe. Few such patients regain their preoperative weight. Nutritional impairment after gastrectomy implies either inadequate intake of food, malabsorption of ingested food, increased metabolic requirements, or a combination of all of these factors. The object of this discussion is to evaluate each of these factors in order to present a more comprehensive program for care of the nutritionally disabled patient after gastrectomy. Inadequate Intake of Food There is evidence that gastrectomized patients eat far less than they did prior to surgery. In a study of

The electrolyte abnormalities which have been described in hepatic failure include a decrease in plasma sodium, chloride, and carbon dioxide content and an elevation of lactic and pyruvic acid.* Elevation of the blood ammonia has also been reported, and, while there seems to be poor correlation between actual blood levels and symptoms of hepatic coma, there is increasing evidence that ammonia plays at least an indirect role in the production of coma.† The studies reported here were carried out in patients with liver coma in an attempt to evaluate these electrolyte alterations and to correlate the clinical symptomatology with alterations in blood ammonia levels. The results of these studies indicate that hepatic coma may in some cases be associated with a respiratory alkalosis, as evidenced by a high blood pH and a low pCO 2 level. Although there was poor correlation between blood ammonia levels per se and symptomatology, it

• High-dose methylprednisolone sodium succinate (Solu-Medrol) therapy was administered to two patients with acute renal failure and anuria secondary to cancer-related urinary tract obstruction. Following the administration of intravenous methylprednisolone, obstruction was relieved, as evidenced by increased urinary flow and improvement of renal function. The salutary effect of methylprednisolone is probably related to the relief of obstruction secondary to a decrease in tumorassociated edema similar to the effect obtained in patients with brain tumors and spinal cord compression by epidural metastases. The temporary improvement in renal function allowed time for more definitive therapy to be instituted under more favorable clinical conditions. ( Arch Intern Med 1986;146:58-61)

Human growth hormone was effective in healing erosions and controlling hemorrhage in six of eight patients with stress ulcers. This approach was based on known beneficial effects of growth hormone on nucleic acid and protein synthesis, demonstration of deleterious effects of stress on nucleic acid and protein synthesis, and demonstrated protective effects of growth hormone on animals subjected to stress. Bleeding cessation within 24 hours of its administration in two patients suggests the possible role of additional mechanisms involved in hemostasis. In a comparable group of eight patients with stress ulcer hemorrhage not treated with this agent, six died with continued bleeding. This high mortality represented the usual outcome in our patients with stress ulcer hemorrhage. These observations need to be extended to additional patients with stress ulcers in a larger randomized study.

To the Editor:— The common blackfly (biting gnat; order Diptera; family Simuliidae) has long been a plague to explorers, hunters, fishermen, etc, in the spring and summer in northern climates. Not only do these flies attack in droves and bite voraciously, but the bite may lead to large weals and inflammatory lesions with severe pruritus which may last for days. Some 20 years ago I learned that the inflammatory reaction and pruritus could be regularly controlled by the topical application of an antihistamine paste made by grinding a 50-mg tablet of tripelennamine, (Pyribenzamine) hydrochloride in cold cream. A 2% topical ointment or cream is now available which serves the same purpose. Recently a neighbor of mine was so impressed with the efficacy of this remedy for blackfly bites that she applied it to an emerging cold sore (presumably herpes simplex) and duly reported equally good results: lessening of pain within

A CONTINUING problem in vascular surgery is the prevention and control of infection in the presence of artificial grafts. The infection rate associated with artificial grafts has ranged from 1.3%1 to 6%2 with the final outcome from this complication frequently being either death or a major amputation. The purpose of this paper is to describe an experimental study devised to prevent infection from occurring with vascular prostheses and for controlling infections, even if only temporarily, when it occurs. Material and Methods Thirty-eight dogs of both sexes, weighing between 9.5 and 22.7 kg (21 and 50 lb), were divided into two series: A and B. Series A—Potential Vascular Infection. —Twenty dogs were divided into two groups of ten each and were alternately operated upon. One group of dogs underwent laparotomy, at which time a section of their abdominal aorta between the renal arteries and the aortic bifurcation, approximately 4 cm