Enteritis cystica profunda.

Enteritis cystica profunda. In addition to hamartomatous polyps of the small intestine, a patient with Peutz-Jeghers disease had gross and microscopic lesions of the ileum that were analogous to colitis cystica profunda in the large intestine and rectum. To the authors' knowledge, this is the first such case in an adult to be reported. They suggest the designation, "enteritis cystica profunda." The histology of the lesions and their association with a disease known to produce hamartomatous lesions lend support to the proposition that some cases of colitis cystica are also hamartamatous. It is also believed that some reported cases of small-intestinal adenocarcinoma in patients with Peutz-Jeghers syndrome are in reality examples of the benign process of enteritis cystica profunda.


Multicentric giant lymph node hyperplasia. A patient with retroperitoneal and axillary lymphadenopathy and splenomegaly was demonstrated histologically to have the hyaline vascular type of giant lymph node hyperplasia, with plasma cell infiltrates in each region. The abdominal lesions were not surgically resectable and did not respond to radiotherapy. The clinical findings included polyclonal gammopathy, high cold agglutinin titers, neuropathy, and bilateral papilledema. All of these abnormalities have persisted three years since the initial diagnosis.


Effects of magnesium deficiency on duodenal and ileal magnesium absorption and secretion. Intestinal adaptation by the growing rat to a low-magnesium diet was studied by in situ perfusion of duodenum and ileum in vivo. Rats were fed diets containing either 0.066 or 0.022% Mg for 3 weeks. Magnesium-restricted rats became hypomagnesemic and hypercalcemic. Net magnesium secretion was studied by perfusing an initially magnesium-free saline solution; secretion was higher in duodenum than in ileum, and decreased significantly in the duodenum in response to magnesium restriction. Net magnesium adsorption studied by intraluminal perfusion of 2.5 mM magnesium in saline was greater in duodenum than ileum in rats taking a low-magnesium diet, but duodenal and ileal absorption did not differ in animals taking the normal magnesium diet. Absorption did not adapt significantly to magnesium restriction in either segment. Adaptation of small-intestinal magnesium transport to a low magnesium diet is minimal, consisting mainly of reduced duodenal magnesium secretion.


Characterization and effect of phospholipid on bile acid absorption by villi isolated from hamster small intestine. The effects of phospholipid on absorption of bile acids by hamster small intestine were studied to determine if this compound inhibits absorption of bile acids. Absorption of taurocholic and cholic acids was studied using a new in vitro technique that relates uptake rates to the weight of the villi present on the intestinal sample rather than to the weight of the entire segment of intestine used for the study. This procedure removes from consideration various components of the intestinal wall that are not directly involved with the absorptive process. Using radioactive techniques absorption of each type of bile acid was determined over a broad range of concentrations both in the presence and absence of phospholipid in the incubation medium. Absorption of taurocholic acid by villi from jejunum was determined to be a passive process, as previously reported by others. Villi from ileum absorbed both bile acids by an apparent active process when initial concentrations of bile acids were below 2.0 mM. Above this concentration bile acid absorption by the ileum appeared to be mainly passive. Phospholipid was found to inhibit bile acid absorption by ileum when initial bile acid concentrations were moderately high. However, at low substrate concentration, phospholipid has no appreciable effect on bile acid transport.


Selectivity of small intestinal exudate in celiac disease and Crohn's disease. The small intestinal exudates of patients with protein-losing enteropathies produced by celiac disease or proximal jejunal Crohn's disease were compared with controls. The exudates in control subjects were highly selective, whereas those of the celiac and Crohn's disease subjects were relatively nonselective. It is believed that this loss of selectivity is secondary to basement membrane damage. An analogy is drawn with the renal lesion in nephrotic syndrome where basement membrane damage is associated with nonselective proteinuria.


Endoscopic retrograde cholangiography (ERC) in nonamebic liver abscesses. Two cases of liver abscess are reported in whom the diagnosis was suggested by a combination of liver scanning, ultrasonography, arteriography, and liver biopsy. The diagnosis was confirmed by ERC which showed intrahepatic extravasation of contrast from the biliary tree, a characteristic of liver abscess. The value of ERC in the search for an underlying cause as well as in delineating certain features of the absceses is shown.


Effect of various pyloroplasties on fecal fat excretion in dogs and humans. Fecal fat excretion has been measured both before and after truncal vagotomy and pyloroplasty in patients with chronic duodenal ulcer, and pyloroplasty alone, in dogs. In 13 patients the mean increase in fecal fat after truncal vagotomy and Heineke-Mikulicz pyloroplasty was 2.34 g/24 hr. After truncal vagotomy and Finney pyloroplasty in 12 patients the increase was similar and was 3.09 g/24 hr. Fecal fat was also measured before and after a 3-cm, a 6-cm Heineke-Mikulicz, and a Finney type of pyloroplasty in dogs. The area resulting from the pyloroplasties was measured. Pyloroplasty by itself resulted in a significant increase in fecal fat but no correlation could be found between the magnitude of the increase and the area that resulted from the pyloroplasties.


Effects of ethanol on sodium, 3-O-methyl glucose, and L-alanine transport in the jejunum. Effects of ethanol on Na+, Cl-, 3-O-methyl glucose (3-O-MG), and L-alanine fluxes were studied in the isolated rattit jejunal mucosa. Ethanol (3% v/v present on both sides of the mucosa) decreased electrical potential difference (PD), short-circuit current (Isc) and inhibited active transport of Na+, 3-O-MG, and L-alanine. This concentration also increased the permeability of the mucosa for Cl-, 3-O-MG, and L-alanine. Ethanol at 5.4% potentiated the effects on PD, Isc, and the permeability for electrolytes and organic substances. These effects of ethanol could not be fully explained by an osmotic action.


Quantitation and immunochemical characterization of carcinoembryonic antigen and glucose phosphate isomerase in blood and washings of patients with gastric and colonic diseases. Circulating levels of carcinoembryonic antigen (CEA) and glucose phosphate isomerase (GPI) have been measured and compared in 51 subjects with gastric and colonic diseases. Levels were higher in gastric and colonic cancer patients than in normals or patients with other diseases. Elevations of both these markers were most frequent in patients with metastases. Concentrations of CEA and GPI in gastrointestinal washings were also measured. No correlation was found between total protein content and concentrations of CEA or GPI in the washings. Further characterization of the perchloric acid-soluble material from colon washings by gel filtration indicated that the CEA-like substance from colon cancer patients was higher in molecular weight than standard radiolabeled CEA and CEA from normal colon washings. When tested against anti-CEA antiserum and pure CEA from a colonic cancer metastasis, all CEA preparations showed immunological identity in gel-diffusion plates; on immunoelectrophoresis similar mobility was indicative of a similar charge.


Time course of pancreatic protein synthesis following feeding. It is now well established that hormonal stimulation of the exocrine pancreas by pancreozymin and secretin results in enhanced enzyme secretion and a decrease in total protein synthesis in the early moments following application of the stimulus. The aim of the present study was to establish if the effects previously observed by these secretagogues were physiological. We thus verified the effects of feeding on pancreatic protein synthesis; data show that 45 min after a 15-min meal, protein synthesis is reduced by 18% while increases are observed at 90 and 105 min. These results indicate that the reduction in protein synthesis observed following feeding or hormonal stimulation is a physiological process.


Urinary excretion of dye in dogs infused with BSP or its glutathione conjugate. Renal clearance of BSP compounds was investigated in dogs during infusion of sulfobromophthalein (BSP) or its glutathione conjugate (BSP-GSH). Conjugated BSP compounds are more readily excreted into urine than unconjugated BSP. Dye clearance into urine was much less than simultaneously measured inulin clearance. This suggests that protein binding of BSP  compounds significantly retards the glomerular filtration of the dye. BSP was found to bind more avidly to albumin than BSP-GSH. The ratio of dye clearance to inulin clearance remained relatively constant over a broad range of plasma concentrations of dye. The data support but do not prove glomerular filtration of non-protein-bound dye as the major mechanism accounting of urinary elimination of BSP compounds in the dog.


Biliary lipid excretion in patients with pigment gallstones. A comparison with cholesterol gallstone patients. Pigment gallstone patients are believed to have normal biliary lipid excretion. In order to measure this and to better understand cholesterol gallstone formation, the kinetics of biliary lipid excretion were studied in three patients who had been cholecystectomized for pigment gallstones and the results compared to those previously obtained in patients cholecystectomized for cholesterol gallstone. Pigment-stone patients had hyperbolic relationships between cholesterol and phospholipid outputs and bile salt output which were similar to those seen in cholesterol-stone patients. However, pigment-stone patients excreted more cholesterol and phospholipid at high bile salt output but approached those levels more gradually than cholesterol-stone patients. As a result, pigment-stone patients produced bile undersaturated with cholesterol at a lower bile salt output than cholesterol-stone patients, and thus they would be less likely to produce supersaturated bile during low bile salt output such as that occurring during an overnight fast. The data suggest that cholesterol-stone patients, in addition to excreting more cholesterol and less bile salts than normals, have a defect in the rate of lipid output in response to decreasing bile salt output.


Pancreatic hypersecretion in liver disease. Abnormally large duodenal aspirates have been reported in a large percentage of patients with cirrhosis of the liver. The source of this fluid has been variously ascribed to the liver and/or pancreas. The present study was undertaken to clarify its source. Eleven patients with cirrhosis of the liver and one with cholestatic hepatitis underwent an intraductal secretin test during endoscopic cannulation of the pancreatic duct. Six patients with cirrhosis had pancreatic hypersecretion ranging from 7.8 to 26.0 ml/min, while three patients demonstrated low secretory flow rates. Bile flow was negligible or nonexistent in ten patients, while in two others, larger but unmeasurable amounts of bile secretion were present. This study conclusively demonstrates that pancreatic hypersecretion may occur in patients with cirrhosis during secretin stimulation. Impaired metabolism of secretin or the associated pancreatic hypersecretion of early pancreatitis may be responsible for this finding.


The effect of prostaglandins and other vasoactive substances on uterine blood flow and myometrial activity. The effects of prostaglandins (PG's), bradykinin, and adenosine on uterine blood flow (UBF) and intrauterine pressure (IUP) were investigated in conscious oophorectomized ewes. PGE1 and adenosine increased UBF to levels comparable to those induced by estradiol-17beta, whereas PGE2 and PGA1 achieved only 20 and 36 per cent of peak estradiol-induced levels, respectively. PGE1, PGE2, and adenosine all caused transient increases in IUP while PGA1 had no effect on myometrial activity. Bradykinin increased UBF to 60 per cent of peak estradiol-induced levels, with concomitant increases in IUP tonus. PGE2 and PGF2alpha decreased peak estrogen-induced UBF by 50 and 70 per cent, respectively, while inducing related increases in IUP. When compared with oxytocin, the effects of PGE2 at high flow appeared to be mediated only my myometrial activity, whereas PGF2alpha apparently caused vasoconstriction as well. These findings support the concept that PGE1 could play a role in mediating estrogen-induced uterine vasodilatation.


Missed abortion and uterine contractility. In missed abortion myometrial contractility is thought to be suppressed. However, such a simple procedure as sweeping of the fetal membranes by physiologic saline solution was found to provoke abortion within 24 hours in 10 of 12 cases of missed abortion, but not in any of 10 women admitted for therapeutic abortion. Myometrial contractility thus seems not to be diminished in missed abortion.


Quantitative indices of short- and long-term heart rate variability. Two quantitative indices of heart rate variability are proposed. Instantaneous variability is defined as the average of the absolute value of instantaneous rate differences over a 30 second interval. It is sensitive to short-term variability changes. Bandwidth variability is defined as twice the standard deviation of instantaneous heart rates over a 30 second interval, and it is a measure of long-term variability. The rationale for the choice of these indices is discussed, and they are compared with other published indices of variability. Samples of computer printout of instantaneous and bandwidth variability obtained from fetal heart rate records are given.


Lecithin/sphingomyelin ratio in amniotic fluid and its value for the prediction of neonatal respiratory distress syndrome in pregnant diabetic women. In 101 diabetic pregnant women (Classes A through D) 146 determinations of the lecithin/sphingomyelin (L/S) ratio were carried out. Gestational ages were verified by serial fetal cephalometry. No L/S ratios of more than 2.0 were found before 34-1/2 weeks' gestation; however, in 42 per cent of patients the L/S ratio was below 2.0 at 36 weeks' gestation or later. Respiratory distress syndrome (RDS) was found in 16 neonates of women with L/S ratios of 2.0 or higher; however, RDS incidence varied depending on the mode of delivery. Abdominal delivery was performed before 37 weeks' gestation in 19 patients with L/S ratios of 2.0 or higher and resulted in neonates with RDS in 41 per cent of cases. Vaginal delivery was accomplished below 37 weeks' gestation in 10 patients with L/S ratios of 2.0 or higher and no subsequent neonatal RDS was observed. After 37 weeks' gestation neonatal RDS is rare, irrespective of mode of delivery. The data presented suggest that similar numerical values of the L/S ratio at different gestational ages have a different predictive value for the occurrence of neonatal RDS.


Antigonadotropin (danazol) in the treatment of endometriosis. Evaluation of posttreatment fertility and three-year follow-up data. Ninety-nine women who completed danazol treatment for endometriosis proved by operation were re-evaluated clinically an average of 37 months later. The recurrence of symptoms was reported by 39 per cent and pelvic findings suggestive of endometriosis were noted in 33 per cent. An average time interval between the end of treatment and the recurrence was 15 months for the entire group. However, 31 women who conceived subsequent to treatment had a much lower recurrence rate of the disease (15 per cent) and a much longer average time until the recurrence (31 months). Of 84 infertile women who desired pregnancy after treatment, 39 conceived, for a pregnancy rate of 46.4 per cent. However, when patients with absolute sterility due to other causes were excluded, the corrected pregnancy rate was 72.2 per cent. The majority of conceptions (23) occurred within the first six months after discontinuation of danazol and a total of 30 occurred within the first year. Four second- and third-trimester intrauterine fetal deaths were observed among women who conceived within the first three cycles after discontinuation of the drug.


Influence of jejunoileal bypass on protein metabolism during pregnancy. Management of the pregnant patient who has undergone operation for jejunoileal bypass poses many problems for the attending obstetrician. Several recent studies have broadened our knowledge of this group of patients. Unfortunately, the significance of this form of weight loss upon the developing fetus is at best only poorly understood. In our study, amino acid chromatography was performed at 34 weeks' gestation and at delivery in order to assess the impact of this procedure upon maternal and fetal (cord blood) amino acid concentrations. Results suggest that protein metabolism in the patient who has had intestinal bypass without resulting complications and in her fetus is comparable to that in normal pregnancy. Altered amino acid profiles were observed in one twin gestation and in one patient who continued to lose weight throughout pregnancy. The significance of these observations is discussed with respect to the relationship of protein deprivation to neonatal development.


Surgical management of rectovaginal fistulas and complete perineal tears. Twenty-four patients with traumatic rectovaginal fistulas and 27 patients with complete perineal tears underwent secondary operative repair. Primary healing occurred in 50 cases and partial healing in the 51st case. Six patients had previously undergone one to three unsuccessful repairs. The advisability of early repair and the benefits of prophylactic antibiotics and of use of a Martius graft for operative failures are discussed.


The forensic laboratory evaluation of evidence in alleged rape. Serial vaginal fluid samples were obtained for laboratory analysis in 15 couples after voluntary intercourse. These samples were analyzed to determine the rate of decay of sperm and prostatic acid phosphatase as it pertains to alleged rape. An attempt was made to identify the male partner by laboratory examination of pubic hair combings and for foreign ABO antigens in vaginal fluid. If consideration is given to proper laboratory controls, examination for spermatozoa and prostatic acid phosphatase remains the primary test in alleged rape.


Plasma dopamine-beta-hydroxylase activity and norepinephrine levels during the human menstrual cycle. Plasma samples obtained throughout the normal menstrual cycles of six women were analyzed for dopamine-beta-hydroxylase activity (DBH), norepinephrine (NE), follicle-stimulating hormone, luteinizing hormone, and prolactin. Neither DBH activity nor NE concentrations paralleled changes in plasma gonadotropins and prolactin. No consistent pattern of either plasma DBH activity or NE concentrations during the normal menstrual cycle was noted. Thus, an association between peripheral sympathetic nervous system activity and the midcycle surge in plasma gonadotropins reported by others was not reproducible in our study of normally menstruating women.


A three-dimensional study of endometrial mitochondria during the menstrual cycle. Three-dimensional reconstruction of endometrial mitochondria during the menstrual cycle in the woman has produced three mitochondrial populations. These populations are seen to change in size, in number, and in complexity of structure as the menstrual cycle progresses. Through reconstruction and statistical analysis, morphologic data seem to support histochemical data relating to anaerobic and aerobic metabolism in endometrial gland cells.


Evaluation of a balloon dilator to augment midtrimester abortion. A new balloon-type cervical dilating device (CDD) was inserted just after intra-amniotic infusion of a combination of prostaglandin F2alpha and hypertonic saline in an effort to shorten the interval from infusion to abortion. The CDD has both dilator and anchor balloons which are inflated with normal saline after insertion into the cervical canal. The infusion-to-abortion interval was shorter in patients with the CDD dilator inflated (14.6 +/- 2.1 hours) than in those with both dilating and anchor balloons inflated or in those aborting without the device in place at all (23.0 +/- 1.7 and 18.8 +/- 1.0 hours, respectively).


Changes in fetal heart rate-uterine contraction patterns associated with eclampsia. Eclamptic seizures have been associated with fetal bradycardia and rapid onset or progression of labor. The fetal heart rate (FHR)-uterine contraction patterns during 14 seizures in 10 eclamptic patients were studied. Some seizures occurred in patients in whom magnesium sulfate levels were in the therapeutic range. The FHR response during an eclamptic episode was generally prolonged bradycardia. Uterine activity was noted to increase during seizure activity and preceded the fall in FHR. As seizure activity subsided, uterine hyperactivity diminished and the FHR rose, frequently demonstrating compensatory tachycardia. The clinical implications and possible pathophysiologic mechanisms of the FHR-uterine contraction observations are discussed.


Catecholamines during therapeutic abortion induced with intra-amniotic prostaglandin F2alpha. Serial plasma, amniotic fluid, and urine samples were analyzed for epinephrine (E) and norepinephrine (NE) in eight subjects during midtrimester abortion induced by intra-amniotic prostaglandin F2alpha (PGF2alpha). After PGF2alpha administration, plasma E increased and there was no change in plasma NE levels. Amniotic fluid levels of E and NE decreased initially. During the course of abortion the mean level of E in the amniotic fluid increased after fetal distress and decreased after fetal death, indicating that the midtrimester fetus of both E and NE increased following PGF2alpha. The observation that mean plasma levels and urinary excretion rate changes correlated better with the course of abortion and uterine contractility rather than with the time of PGF2alpha administration was consistent with the hypothesis that the catecholamine response may be due to the stress of labor rather than to the PGF2alpha per se.


Arachidonic acid and other free fatty acid changes during abortion induced by prostaglandin F2alpha. Serum free fatty acids (FFA's) were measured after intra-amniotic injection of prostaglandin F2alpha (PGF2alpha) for the induction of abortion in eight healthy women in the midtrimester of pregnancy. The total FFA levels increased in all cases during the period between PGF2alpha administration and abortion. This lipolysis most likely is secondary to the effect of the catecholamines as indicated by the temporal relationship between increased plasma and urine catecholamine and serum FFA levels. The percentage of arachidonic acid in the total amount of FFA's decreased after administration of PGF2alpha. This proportional decrease in arachidonic acid (p less than 0.05) may be due to selective utilization for the production of endogenous prostaglandins.


Inferior vena cava compression in the pregnant dog. Attempts were made to produce inferior vena cava (IVC) compression in 14 pregnant and 12 nonpregnant bitches. Ligation of the iliac veins, the IVC below the renal veins, or the left renal vein separately produced minimal hemodynamic disturbances. Only ligation of the two renal veins or of the IVC above the renal veins produced a moderate drop in blood pressure and blood flow. Shock and bradycardia, characteristic of the supine hypotension syndrome (SHS) as observed in human subjects, were never observed. Satisfactory collateral circulation was demonstrated radiologically. Since human SHS was not reproduced in the pregnant bitch by compression of the IVC alone, one may conclude that the SHS is not solely caused by the compression.


The effects of dopamine of blood pressure and heart rate of the unanesthetized fetal lamb. The effects of dopamine on blood pressure and heart rate have been studied in continuously cannulated fetal lambs and adult sheep. Drugs were administered by direct intravenous injection into either the fetus or the adult sheep, and blood pressure was measured from an arterial cannula and heart rate was computed from the electrocardiogram (ECG). The magnitude of the fetal pressor response to dopamine increased slightly as the dose of dopamine (1, 10, 50, 100, and 200 mcg. per kilogram was increased, but the magnitude of the response did not increase with advancing gestation (112 to 145 days). However, in the adult sheep, the dose-response relationship was much steeper. In both cases the pressor response was accompanied by a reflex bradycardia that was blocked by atropine (1 mg. per kilogram). In the atropinized fetus, doses of 50 to 200 mcg. per kilogram of dopamine produced tachycardia (30 to 120 b.p.m) and a greater pressor response than that in the unatropinized fetus. Thus, the fetal cardiovascular system is capable of responding to relatively large amounts of dopamine injected as a bolus, suggesting that relatively large amounts of endogenous dopamine would have to be secreted by the mast cells to significantly alter fetal cardiovascular function.


Detectability and pattern of immunoglobulins in normal amniotic fluid throughout gestation. Immunoglobulin (Ig) M, IgA, and IgD class and IgA, and IgA2 subclass levels were detected in normal amniotic fluid throughout gestation with a hemagglutination-inhibition assay: IgG was measured by single radial immunodiffusion. In 161 tested samples, IgA, IgA, IgA2, and IgG were measurable in all cases; IgM was measurable in 99.4 per cent and IgD, in 90.6 per cent of the fluids. IgA, IgG, and IgD concentrations increased toward midpregnancy and thereafter decreased to term in a pattern similar to that for amniotic fluid total protein. IgM, on the other hand, remained relatively constant through week 35 of gestation; thereafter, it increased to term. There was no correlation in this normal group between amniotic fluid and cord blood levels of Ig class or subclass at term. Mean IgA values were 2.2 times higher in amniotic fluid than in cord serum. This was in sharp contrast to IgM, which was 16 times higher, IgG, which was 66 times higher, and IgD, which was 2.4 times higher in cord serum than in amniotic fluid. The inverse data for IgA as compared to other Ig classes suggest that amniotic fluid IgA may be partially derived from IgA in fetal gastrointestinal and pulmonary secretions. Determination of the concentration of the different Ig classes (and eventually subclasses) in amniotic fluid may be useful in diagnosis of intrauterine infections, malformations, and immunodeficiencies.


Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Four patients with symptomatic superior limbic keratoconjunctivitis underwent resection of the superior bulbar conjunctiva. One of these patients also underwent a tarsal conjunctival resection in the other eye. Three of the patients had previously been treated by various regimens without resolution; the fourth had had no prior treatment. All four patients had immediate and continued relief of the ocular symptoms after the superior bulbar conjunctiva was excised. The patient who underwent tarsal conjunctival resection experienced only short-term relief. We studied the conjunctival tissue by light and transmission electron microscopy. Both techniques revealed abnormalities related to the bulbar conjunctival surface with keratinization of the epithelium, acanthosis, degeneration of the nuclei, and intracellular accumulation of glycogen. Inflammatory cells were minimally present. The tarsal conjunctiva appeared essentially normal.


Neuroparalytic keratitis in Goldenhar-Gorlin syndrome. A 2-year-old boy had bilateral corneal ulceration with the Goldenhar-Gorlin syndrome. Initially, the patient received subconjunctival and topical antibiotics with minimal effect. With subsequent treatment of atropine, sterile ophthalmic petrolatum ointment, and humidification of the patient's crib, ulcers in both eyes healed in two weeks without further problems. He had a neuroparalytic keratitis with corneal anesthesia and decreased tear production bilaterally. Our evidence suggested that aplasia or hypoplasia of the trigeminal nuclei was the probable cause.


Aeromonas hydrophila corneal ulcer.

Aeromonas hydrophila corneal ulcer. Two healthy men developed acute corneal ulcers caused by Aeromonas hydrophila after receiving traumatic foreign body injuries to the cornea. The ulcers resolved after treatment for gram-negative bacterial corneal ulceration. A history of contamination by water, soil, or material from an aquatic source was a significant factor in each case.


Tobramycin levels in human eyes.

Tobramycin levels in human eyes. Tobramycin, a new aminoglycoside antibiotic, penetrated the aqueous humor of human eyes after parenteral administration, either intramuscularly or intravenously, in 36 cataract patients with a presumably normal blood aqueous barrier. Tobramycin administered subconjunctivally to eyes with a normal blood aqueous barrier is capable of achieving therapeutic aqueous humor levels that exceed the minimal inhibitory concentration of most isolates of Pseudomonas and Staphylococcus. No adverse effects were noted in the subjects studied. This drug may be used in the treatment of acute ocular infections.


A new iris retractor.

A new iris retractor. I successfully used the iris-lasso, a new iris retractor in the form of a stainlless steel wire. The iris-lasso is simple to maneuver, suitable for microsurgery, and particularly useful in patients with small pupils.


A comparison of 500 Binkhorst implants with 500 routine intracapsular cataract extractions. We compared 500 Binkhorst lens implants with 500 routine intracapsular cataract extractions. The two groups consisted of consecutive cases matched according to surgeons, surgical technique, time interval of the study, and ocular status. The results of visual acuity were comparable in the two groups; 89.0% of the implant group and 85.4% of the routine intracapsular group achieved 6/12 (20/40) or better visual acuity. The rate of complications in each group was comparable except in the case of corneal edema, which was higher in the implant group (1.2%) than in the routine intracapsular group (0.4%). The rate of clinically significant cystoid macular edema was higher in the routine intracapsular group (2.2%) than in the implant group (1.4%).


Prevalence of senile cataract, diabetic retinopathy, senile macular degeneration, and open-angle glaucoma in the Framingham eye study. Of the Framingham, Massachusetts Heart Study population, 2,675 individuals underwent an ophthalmologic evaluation that stressed detection of senile cataract, diabetic retinopathy, open-angle glaucoma, and senile macular degeneration. Those examined were 52 to 85 years old at the time this study was initiated. The prevalence rate of each of these ocular conditions increased with age. Prevalence of senile cataracts ranged from 4.6% for those between the ages of 52 to 64 years to 46% for those 75 to 85 years of age. Diabetic retinopathy was present in 2% of those between 52 and 64 years of age or older. Overall prevalence of senile macular degeneration was 9%, with a prevalence rate of 2% in our youngest age group and 28% in the oldest age group. Open-angle glaucoma had an overall prevalence of approximately 3%. This disease also showed a statistically significant (P less than .01) increase with age from 1.4% (52 to 64 years old) to 7.2% (75 to 85 years old).


Measurement of episcleral venous pressure. Using materials available in any ophthalmology clinic, we constructed a useful and reliable instrument for measuring episcleral venous pressure. The instrument, a modification of the pressure chamber method of Seidel, utilizes a latex membrane and an air-filled chamber. These modifications facilitated ease of preparation for the measurement. Episcleral venous pressure in normal subjects was 9.0  +/- 1.6 mm Hg (mean +/- S.D.). Measurement of episcleral venous pressure facilitated diagnosis of diseases such as arteriovenous fistula and superior vena caval obstruction, which block drainage of venous blood from the orbit.


Phenylephrine provocative testing in the pigmentary dispersion syndrome. Forty-nine patients with bilateral pigmentary dispersion syndrome (abnormal accumulation of pigment in the anterior chamber, principally from the posterior layers of the iris), including 31 patients with pigmentary glaucoma, underwent 10% phenylephrine testing in one eye for evaluation of liberation of pigment floaters into the anterior chamber and the influence of phenylephrine on the intraocular pressure. Ten patients with pigmentary glaucoma developed a 3+ to 4+ pigment response, but only two demonstrated a pressure rise greater than 2 mm Hg. The highest pressure rise observed was 7 mm Hg. Nine patients with pigmentary dispersion syndrome but without glaucoma also developed a 3+ to 4+ pigment response, but none of these had a pressure rise. The incidence of pigment liberation was higher in older patients and in pigmentary glaucoma patients receiving topical antiglaucoma therapy at the time of testing. The extent of iris transillumination did not correlate with the grade of phenylephrine-induced pigment liberation. Two pigmentary glaucoma patients, who did not liberate pigment or have a pressure rise when tested with phenylephrine, did exhibit spontaneous or exercise-induced liberations of pigment into the anterior chamber, with marked rises of intraocular pressure and obstruction of aqueous outflow.


Orbital dermoid diagnosed by computed tomographic scanning. In a 20-year-old man, computed tomography revealed that an orbital mass in the region of the lacrimal gland fossa had low density attenuation values (below water), indicating a fat-containing tumor. At surgery, we found a dermoid cyst of the oil cyst type.


Choroidal melanoma clinically simulating a retinal angioma. An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.


The incidence of macular pucker after retinal detachment surgery. In a study of 63 cases of macular pucker among 857 patients who underwent retinal detachment repair, we isolated several statistically significant risk factors: preoperative vision of less than 6/15 (20/50); preoperative presence of rolled edges, starfolds, or equatorial ridges; re-operations; choroidal hemorrhage; and age past 30 years. We were unable to confirm the risk associated with vitreous loss, vitreous hemorrhage, and degeneration. Results suggested that macular pucker after detachment surgery is produced by a membrane similar in origin to those causing other forms of periretinal proliferation.


Rubella retinopathy and subretinal neovascularization. Diseases that primarily affect the pigment epithelium, Bruch's membrane, or the choroid may lead to secondary subretinal neovascularization and its sequelae of hemorrhage and scarring. We studied three cases of presumed congenital rubella retinopathy with congenital deafness, which developed unilateral subretinal neovascularization, hemorrhage, and scarring.


Inferior oblique muscle recession.

Inferior oblique muscle recession. Surgical recession of the inferior oblique muscle is simpler to perform if the inferior rectus muscle, rather than either the lateral rectus muscle or the inferior oblique muscle insertion, is used as a landmark. We measured 200 consecutive autopsy eyes to determine the distance from the commonly used 8-mm recession site determined by the Fink technique to the lateral border of the inferior rectus muscle insertion. It was easier to reach this point by measuring 4.0 mm posterior and 4.4 mm superior to the lateral insertion of the inferior rectus muscle, or 2.9 mm superior (on a line parallel to the corneoscleral limbus) and 5.1 mm posterior (on the line perpendicular to the corneoscleral limbus) to the lateral insertion of the inferior rectus muscle. We made anatomical studies to grade the amount of inferior oblique muscle recession and to evaluate the proper placement of the posterior border of the recessed inferior oblique muscle.


A comparison of the migration patterns of normal and malignant cells in two assay systems. The migration patterns of normal mouse embryo fibroblast (MEF) cells and mouse fibrosarcoma (FS) cells were compared in two assay systems. The two assay systems used were themodified Boyden chamber (micropore membrane) assay and the agarose drop explant assay. In both assays the major population of MEF cells exhibited a greater rate of migration than the major population of FS cells. However, a small subpopulation of FS cells which had a much greater rate of migration than the major population of either MEF or FS cells was detected in the agarose drop assay. A number of drugs which are known to inhibit the migration of leukocytes were tested against the MEF and FS cells. Concentrations were found that inhibited the major population of both groups by greater than 90%. However, at concentrations which inhibited the migration of the major population of FS cells by greater than 90%, a small group of fast-moving cells was still detected. Although the fast-moving cells were relatively resistant to treatment with the various drugs, this group was sensitive to a factor in serum. When normal human serum was used in place of fetal calf serum, the migration of the major population of FS cells was inhibited very little but movement of the fast-moving population was completely eliminated. We speculate that the small subgroup of fast-moving cells may be responsible for the invasive nature of the FS cells.


A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat. Subtotal nephrectomy in the rat is followed by glomerular hypertrophy, glomerulosclerosis, and, ultimately, renal failure. To gain more insight into this sequence, we have made a morphometric study of the glomerular changes following subtotal nephrectomy in the rat during the period of functional compensation before glomerulosclerosis appears. We found a twofold increase in glomerular volume as compared with controls 2 weeks after operation (to approximately 2 X 10(6) cu mu) followed by a linear increase to approximately 5 X 10(6) cu mu at 21 weeks. The rate of increase in glomerular volume in controls did not significantly exceed that of body weight. The volume increase after subtotal nephrectomy is a true hypertrophy, since other morphometric parameters expressed per unit glomerular volume (surface and length densities) were approximately 80% of control values at 2 weeks and constant thereafter. Glomerular hypertrophy up to 21 weeks is accompanied by a stable BUN and a gradually increasing proteinuria. We conclude that glomerular hypertrophy in this system is a pathologic rather than a compensatory process and suggest that it may represent a counter-productive response to hemodynamic changes serving to increase the glomerular filtration rate.


A microanalysis approach to investigate problems encountered in mycology. X-ray microanalysis has been applied to the study of pathogenic fungi for the acquisition of chemical information. The technique of combined scanning electron microscopy and wavelength dispersive spectrometry is described. The chemical analysis depends on the characteristic x-ray spectrum excited by the electrons passing through the sample. This spectrum is analyzed by x-ray wavelength dispersion using crystal spectrometers. All the elements of the periodic system above beryllium can be detected with good sensitivity.


Neuroendocrine cells in dysplastic bronchi: ultrastructural observations and quantitative analysis of secretory granules and the golgi complex. Ultrastructural and biochemical studies have suggested that bronchopulmonary carcinoids and oat cell carcinomas may be derivatives of neuroendocrine cells; their amine and/or peptide secretory capabilities may at times be reflected in clinical hormonal syndromes. This investigation was prompted by the hypothesis that dysplastic neuroendocrine bronchial cells may also exhibit structural and functional aberrations of their secretory apparatus. Surgical specimen samples from 5 human dysplastic bronchi were studied ultrastructurally; 7 normal bronchi served as controls. Golgi complexes of dysplastic cells were distinctly less prominent than those of the controls. Moreover, the Golgi vesicles of dysplastic cells appeared significantly smaller than their counterparts in normal cells (P less than 0.01). Also, dysplastic neuroendocrine cells displayed significantly fewer secretory granules per cell than the controls (P less than 0.05). These findings indicate structural abnormalities in the secretory apparatus of neuroendocrine cells in dysplastic bronchi and correlate with experimental observations of aberrant hormonal production associated with bronchial dysplasia. Thus, the possibility arises that bronchial epithelial dysplasias may be detected and monitored through laboratory determinations of their secretory products.


Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Surgical occlusion of the left coronary artery of the rat is a relatively simple, economical technique for producing experimental myocardial infarction (MI). Histologic study of 1- to 21-day-old MI in rats showed that following a mild and brief acute inflammatory response at the margins of the necrotic myocardium, there is chronic inflammation, vascular and collagenous proliferation, and resorption of necrostic tissue which progresses until scar formation is complete, usually by 21 days. From Day 1 to Day 21 the volume of infarcted myocardium decreases from 45.9 +/- 5.9% (mean +/- SEM) to 26.1 +/- 3.2% of the left ventricle and infarct thickness decreases from 1.30 +/- 0.06 mm to 0.47 +/- 0.02 mm. Concomitantly, the percent of the surface area of the left ventricle which is infarcted decreases insignificantly from 55.7 +/- 7.2% to 48.3 +/- 4.2%, indicating that the decrease in volume of the infarcted tissue occurs primarily as a result of thinning of the MI. This study provides qualitative and quantitative information on the natural history of MI in rats, which should be useful as a baseline for future studies.


Acute lung injury induced by cadmium aerosol. II. Free airway cell response during injury and repair. This paper presents a study of the effects of cadmium chloride aerosol on free airway cell populations. Rats were given a single exposure to aerosolized 0.005 M CdCl2 dissolved in physiologic saline. CdCl2 exposure induced a fivefold increase to 43.2 X 10(6) total cells at 4 days as compared with 11.1 X 10(6) in saline-exposed controls and 8.4 X 10(6) in unexposed rats (P less than 0.001). Differential counts showed a peak of polymorphonuclear leukocytes (PMN) at 3 days after CdCl2 exposure, whereas values for saline-exposed animals showed no change from values for unexposed animals (P less than 0.001). Four days after CdCl2 exposure thepredominant cell was the alveolar macrophage (AM), which showed a highly significant increase in number and size over saline-exposed and unexposed animals. A significant increase in lymphocytes also occurred, with a peak at 4 days. At 10 days after exposure, AM were still more numerous after CdCl2 exposure (P less than 0.001), but all other cell types had returned to control levels. Correlation with previous ultrastructural studies on CdCl2 exposure suggested the peak of PMN coincided with Type I cell necrosis. In contrast, AM predominated durion and phagocytosis occur.


The type 1 alveolar lining cells of the mammalian lung. I. Isolation and enrichment from dissociated adult rabbit lung. With removal of large numbers of macrophages by airway lavage, Type 1 cells were isolated in heterogeneous cell populations following the stepwise dissociation of lung tissue. Using a carefully timed collagenase-trypsin digestive sequence at 37 C, unwanted cellular and noncellular lung components were minimized prior to selective release of Type 1 cells. Resulting heterogeneous cell suspensions containing well-preserved Type 1 cells, as determined by electron microscopy, were layered onto a shallow gradient (3 to 6% Ficoll in minimal essential medium [MEM]) and separated at unit gravity into enriched subpopulations of various cell types. These included various fractions enriched with respect to Type 1 cells (70%), Type 2 cells (82%), and macrophages (81%). Identification of Type 1 cells following their isolation and gradient enrichment was established by light microscopic staining techniques and by specific cell surface characteristics in vitro as visualized by electron microscopy.


Fetotoxicity in rats following chronic exposure to halothane, nitrous oxide, or methoxyflurane. An animal model was used to investigate the comparative fetal toxicities of three inhalational anesthetics. Pregnant Sprague-Dawley rats were exposed for eight hours a day throughout the 21 days of gestation to graded concentrations of halothane (0.16-0.32 per cent), or nitrous oxide (1-50 per cent), or a nitrous oxide (10 per cent) and halothane (0.16 per cent) mixture, or methoxyflurane (0.01-0.08 per cent). High subanesthetic concentrations of all the inhalational anesthetics could cause fetal growth retardation (e.g., 3-21 per cent decreases in normal fetal weights), but this was unaccompanied by significant fetal loss (overall rate: 4.8 +/- 1.2 per cent, mean +/- SE, in anesthetic groups) or any evidence of skeletal or gross abnormalities related to treatment. It is concluded that these rodent studies do not implicate any specific inhalational anesthetic agent in fetal toxicity, and that the effects of additional factors, such as stress, must be considered.


Hemodynamics of increased intra-abdominal pressure: Interaction with hypovolemia and halothane anesthesia. The hemodynamic interaction of acute hypovolemia and halothane anesthesia in dogs with increased intra-abdominal pressure caused by intraperitoneal instillation of N2, N2O and CO2 was studied. During normovolemia and just basal pentobarbital anesthesia, the response to increase of intra-abdominal pressure to 40 torr consisted of a 35 per cent decrease in cardiac output, which was equal to the decrease in magnitude of inferior vena caval blood flow. During basal pentobarbital anesthesia, the addition of halothane anesthesia (1 MAC) in combination with hypovolemia (15 per cent blood volume loss) depressed the pre-inflation cardiac output more than addition of halothane anesthesia alone or induction of hypovolemia alone. During each of these conditions, superimposition of increased intra-abdominal pressure to 40 torr caused a further 26-43 per cent decrease in cardiac output compared with the pre-inflation value. Therefore, the greatest cardiovascular depression occurred when the animals were both hypovolemic and anesthetized with halothane. There was no difference in the responses to increased intra-abdominal pressure with the different inflating gases at any time. These findings indicate that in the presence of halothane anesthesia or hypovolemia, induction of pneumoperitoneum may cause severe cardiovascular depression.


Acetylcholine concentrations and turnover in rat brain structures during anesthesia with halothane, enflurane, and ketamine. Acetylcholine and choline concentrations in brain structures of rats during anesthesia with halothane (0.7-1.0 per cent inspired), enflurane (2.7-3.0 per cent, inspired) and ketamine (40 mg/kg, iv) were measured by gas chromatography. The turnover rate (biosynthesis) of acetylcholine in vivo was estimated by infusing phosphoryl(Me-14C)choline intravenously, determining specific activities of choline and acetylcholine, and applying principles of steady-state kinetics to compute the fractional rate constant of acetylcholine. Acetylcholine concentrations in brain structures did not change during anesthesia. Halothane decreased the acetylcholine turnover rates in all parts of the brain. Enflurane decreased the acetylcholine turnover rate in the cerebral cortex only, but not in the caudate nucleus, the hippocampus, and the hypothalamic and thalamic regions. During anesthesia with ketamine, acetylcholine turnover rates were reduced in the caudate nucleus and the hippocampus, but not in the cerebral cortex and the hypothalamic and thalamic regions. The results suggest that acetylcholine turnover rate and utilization are related to anesthetic induced electrophysiologic changes in cortical and subcortical structures.


Platelet aggregation following heparin and protamine administration. The effects of heparin, protamine, and the heparin-protamine complex on the abilities of platelets to aggregate in vitro in response to adenosine diphosphate (ADP) and epinephrine were determined. Citrated blood was obtained from normal volunteers and portions were treated with heparin, protamine, and three different ratios of heparin and protamine. The threshold concentrations of ADP and epinephrine required to produce complete platelet aggregation were then determined. Compared with control citrated plasma, the geometric mean of the threshold concentration for ADP in the heparinized sample was decreased twofold, from 1.88 to 0.94 micrometer; and that for epinephrine more than threefold, from 0.5 to 0.14 micrometer. In contrast, the threshold concentration for ADP was increased to 3.68 micrometer in the neutralized and to 2.78 micrometer in the overneutralized samples and that for epinephrine to 1.62 micrometer in the neutralized and 1.82 micrometer in the overneutralized samples. These data indicate that heparin increases the sensitivity of platelets to ADP and epinephrine as determined by platelet aggregation, and protamine added to heparinized blood not only reverses this effect, but decreases platelet sensitivity when it is added in concentration that neutralize heparin. Additional protamine has no further effect, and protamine alone has no effect on platelet aggregation.


Unilateral hyperlucent lung (Swyer-James syndrome) after severe Mycoplasma pneumoniae infection. An 11-year-old girl contracted pneumonia with consolidation of the left lower lobe, infiltrates in the lingula and left upper lobe, and a large left pleural effusion, accompanied by a Mycoplasma complement-fixation titer increasing to 1:16,384. Serial chest radiographs demonstrated resolution of the pneumonia and effusion, followed by development of a hyperlucent left lower lobe. This diagnosis was supported by abnormalities discovered by chest cinefluoroscopic examination and lung scans of ventilation and perfusion. Unilateral hyperlucent lung should be considered as a possible sequel to severe Mycoplasma pulmonary infection.


Immunologic reactivity of the lung: the in vivo and in vitro generation of a neutrophil chemotactic factor by alveolar macrophages. The generation of a chemotactic factor by guinea pig alveolar macrophages after phagocytosis of heat-killed Staphylococcus aureus was studied. These studies demonstrated that after phagocytosis, alveolar macrophages secrete a small molecular weight (less than 5,000 daltons) chemotactic factor that preferentially attracts neutrophils. The chemotactic factor can be generated in vivo and in vitro, and its chemotactic activity can be detected both in vitro by a chemotactic assay and in vivo by an increase in the absolute number of neutrophils in bronchoalveolar lavage fluid and in lung tissue histologic specimens. Generation of the chemotactic factor was inhibited by 20 microgram of actinomycin D per ml and by 10 microgram of cycloheximide per ml. The factors were stable after incubation at 56 degrees C for 45 min, but not after incubation at 100 degreeg C for 10 min. These studies show that alveolar macrophages can serve as an initiator of pulmonary inflammatory responses by secreting a potent mediator of neutrophil locomotion.


Mycobacterium terrae synovitis and osteomyelitis. An immunocompromised patient with Mycobacterium terrae synovitis and osteomyelitis is presented. Therapeutic recommendations are made based upon existing knowledge of the pathogenesis, course, and outcome of similar infections with nontuberculous mycobacteria.


Ear oximetry in clinical practice.

Ear oximetry in clinical practice. The arterial blood O2 saturation measurement obtained by the Hewlett-Packard ear oximeter was compared to that derived from the arterial PO2 in 41 patients with various pulmonary diseases and in 11 jaundiced patients with serum bilirubin concentrations between 2.7 and 35 mg per 100 ml. There was a good correlation between results obtained with the 2 methods in the jaundiced group (r = + 0.85, n = 19) and in the patients with pulmonary disease (r = + 0.90, n = 57); however, in the jaundiced patients, the ear oximeter arterial O2 saturation was significantly lower (-6.06 per cent, n = 19, P less than 0.01) than the arterial O2 saturation derived from the arterial PO2. There was a significant correlation between the serum bilirubin concentration and the magnitude of difference between the oximeter arterial O2 saturation and the arterial PO2-derived arterial O2 saturation (r = + 0.848, n = 16, P less than 0.001). In the nonjaundiced patients, the difference between the 2 measurements was small when the arterial P(02) was greater than 61 mm Hg; the variation increased with lower arterial PO2 concentrations, but the difference was not significant.


A graphic approach to assessing interrelationships among minute ventilation, arterial carbon dioxide tension, and ratio of physiologic dead space to tidal volume in patients on respirators. A graphic analysis of the relationships among minute ventilation, arterial PCO2, and the ratio of physiologic dead space to tidal volume is presented for the bedside clinical evaluation of patients receiving continuous respiratory support. With simultaneous measurement of minute ventilation and arterial PCO2, the graph can be used to determine the patient's ratio of dead space to tidal volume. This information can subsequently be used (1) for respirator adjustments to obtain the desired arterial PCO2; (2) to assess the severity of ventilation/perfusion unevenness; and (3) to follow the patient's response to respiratory therapy. It provides the clinician with a conceptual tool with which he can assess the status of a patient's gas exchange and more accurately evaluate and plan his course of treatment.


Pulmonary and systemic hemodynamic evolution in chronic bronchitis. Hemodynamic values obtained during right heart catheterization in about 35 patients with chronic bronchitis were compared with the same variables 3.3 years later (range, 2 to 5 years). In the group of 13 patients with mean pulmonary arterial pressure less than 20 mm Hg at the first catheterization, the average value was 15.8 mm Hg at rest and 25.2 mm Hg during moderate exercise at the first investigation, and 16.9 and 26.3 mm Hg, respectively at the second catherization; the changes were not significant. In the group of pulmonary hypertensive patients, the mean pulmonary arterial pressure was 27.0 mm Hg at rest and 44.1 mm Hg during moderate exercise at the first catheterization, and 26.8 and 38.9 mm Hg, respectively, at the second catheterization. Thus, even in this group, there was no deterioration in pulmonary hemodynamics, because there was no significant change in right or left filling pressure, or in cardiac output. There was, however, a marked decrease in systemic arterial pressure, which was significant in the group with pulmonary hypertension. This decrease in left ventricular afterload could be partly responsible for the stabilization of pulmonary hemodynamics, and it could be due to the peripheral vasodilating effect of hypoxia and hypercapnia.


Effect of aminophylline on ventilatory responses in normal man. The bronchodilator effects of aminophylline have been well documented but its effect on ventilatory drives has not been systematically evaluated. Accordingly, the ventilatory responses to hypoxia and to hypercapnia were measured before and after the intravenous administration of 5 mg of aminophylline per kg of body weight to 6 normal subjects. Hypoxic ventilatory response, as measured by an index of the relation between ventilation and hypoxia (parameter A) increased from a mean +/- SE control value of 146 +/- 25 to 254 +/- 35 75 min after the infusion (P less than 0.05). Significant increases in A were also noticed immediately after and 35 and 50 min after the aminophylline infusion. Oxygen consumption increased from a control value of 235 +/- 21 to 263 +/- 21 ml per min STPD (P less than 0.03), and CO2 production increased from 184 +/- 12 to 202 +/- 13 ml per min STPD (P less than 0.01) after aminophylline. Hypercapnic ventilatory response, measured as the slope of the ventilatory response to hypercapnia, was not altered after the aminophylline. Thus, in addition to bronchodilation, the augmentation of the ventilatory response to hypoxia may be a useful factor when this drug is used in acute respiratory failure secondary to airway obstruction.


A comparative study of tuberculous and other mycobacterial infections and their associations with malignancy. We reviewed 162 cases of bacteriologically proved mycobacterial disease. Nontuberculous acid-fast bacilli were responsible for 27 per cent of the infections, a higher frequency than has previously been reported, and Mycobacterium kansasii and Mycobacterium avium-intracellulare were isolated with equal frequency. This indicates that Mycobacterium avium-intracellulare may be a significant agent of disease in the Midwest as well as the Southeast. There are no useful clinical, radiographic, or laboratory features to distinguish between tuberculous and other mycobacterial infections. Mycobacteria act as opportunistic pathogens in persons with malignant diseases. The attack rate was 607 of 100,000 persons verus 95 of 100,000 persons in our general hospital population. Mycobacterium tuberculosis and the nontuberculous mycobacteria were of equal virulence in this regard.


Spirometric changes in normal children with upper respiratory infections. Recent evidence that certain uncomplicated upper respiratory infections induce pulmonary function abnormalities in adults prompted a prospective study in children, in whom such infections occur more frequently. In a longitudinal study, 55 children 2.5 to 11 years of age were observed for a mean duration of 2 years. Spirometry and lung volume studies were obtained routinely every 3 months, during each upper respiratory infection, and 4 weeks after illnes, providing data for 617 "well" and 237 "illness" observations. After grouping of data by sex and age (less than 84 of greater than 84 months), each spirometric parameter was analyzed using linear regression with individual identification, height, and clinical status (normal versus upper respiratory illness) as independent variables. Adjusted mean values of forced vital capacity, 1-sec forced expiratory volume, peak expiratory flow, maximal mid-expiratory flow, and expiratory flow at 50 per cent of the forced vital capacity all decreased during upper respiratory illness. The data suggest that lower respiratory tract involvement without signs or symptoms of lower airway or alveolar disease occurs with upper respiratory illnesses of varied etiologic origin in childhood.


Cell-mediated immune responses in sarcoidosis. In an attempt to understand divergent observations regarding the in vitro lymphocyte responsiveness to antigens and mitogens, the frequency of cutaneous reactivity, and the relationship of these variables to clinical features of sarcoidosis, we examined cell-mediated immune responses in 75 untreated patients. In vitro lymphocyte responses to phytohemagglutinin and concanavalin A were significantly decreased among the group of patients with chronic active disease. In vitro lymphocyte responses to streptococcal antigen paralleled the patient's cutaneous reactivity; however, when compared to healthy persons, patients with sarcoidosis responded significantly less often to streptococcal skin tests. Twelve of 13 persons expected to be tuberculin positive by clinical history were found to be dermally reactive, and 11 these 12 exhibited positive in vitro lymphocyte responses to purified protein derivative. Among the remaining 62 patients, failure to respond to all stimuli in vivo and in vitro occurred in only 10. No evidence was found to support the general view that sarcoidosis is characterized by anergy to specific antigens. The patterns of responses to mitogens were neither characteristic nor unique for sarcoidosis. In patients in whom diminished specific cellular immune reactivity was observed, no correlation was evident with specific clinical features of the disease.


A noninvasive method for measuring the PCO2 of mixed venous blood. A breath-holding method for measuring the PCO2 of mixed venous blood has been developed. Two gas mixtures, 100 per cent O2 and 12 per cent CO2 in O2, were inspired, and the expired gas was analyzed after 5 and 15 sec of breathholding. The oxygenated mixed venous PCO2 was calculated using an exponential equation. The method was applied in healthy subjects, patients with lung disease, and unconscious mechanically ventilated patients. The mixed venous PCO2 correlated well with arterial PCO2 (r = 0.96), the PCO2 obtained by rebreathing (r = 0.97), and the PCO2 in blood drawn from the pulmonary artery (r = 0.97). The method is noninvasive, has a low coefficient of variance, and allows arterial PCO2 to be estimated by multiplying the breath-holding mixed venous PCO2 by 0.8.


Physiologic and morphologic observations of the effects of intravenous elastase on the lung. Intravenous administration of porcine pancreatic elastase to hamsters produced significant loss of elastic recoil at low volumes. Histology and mean linear intercept of the lungs fixed at a pressure of 20 cm H2O and studied for 3 weeks after administration of elastase were normal. Larger doses of elastase caused immediate fatal, hemorrhagic pulmonary edema. These results confirmed previous morphologic observations of the effects of intravenously administered elastase, but demonstrated that the loss of elastic recoil at low lung volumes is not invariably associated with histologic changes or morphologically with loss of elastin fibers. These observations suggest that submicroscopic lesions may be present and may antedate the earliest morphologic evidence of emphysema and aging in the lung.


Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects. We studied 270 Saudi Arabs with homozygous sickle cell anemia, using chart review, a register (since 1969), and home visiting in 42 cases. Average follow-up for the total group was 10 years. Seventy-four percent of those diagnosed by age 3 years presented on screening or with merely anemia; 26% presented with illness, abnormal physical findings, or pain. Compared with American or Jamaican blacks, serious complications occurred only 6% to 25% as frequently; leg ulcers did not occur at all; the mortality under age 15 years was 10% as great; mean levels of blood hemoglobin were higher (10 g/dl), reticulocyte count was lower (5% to 6%), and mean fetal hemoglobin (HbF), which was inversely correlated with reticulocytes, was higher (22% to 26.8%). The high HbF is believed to account for the very mild clinical manifestations.


Renal vasculature in essential hypertension: racial differences. In an attempt to explain the greater morbidity from essential hypertension in the black as compared with the white race, we evaluated the intrarenal vasculature of 27 patients with hypertension (19 white and 8 black). All patients had mild-to-moderate hypertension (mean arterial pressure, 110 to 125 mm Hg), normal renal function, and minimal target-organ damage. All patients had selective renal angiograms, which were evaluated for arterial nephrosclerosis. Additionally, renal blood flow was estimated by the clearance of para-aminohippurate. Patient age, blood pressure, and plasma renin activity did not differ between the two races. Black hypertensives had significantly (P less 0.01) more severe nephrosclerosis than the white patients. Renal blood flow was lower (P less than 0.05) in black patients (390 +/- 35 ml/min - m2 body surface area) than white patients (473 +/- 19 ml/min - m2 body surface area). These findings may help to explain racial differences in morbidity and mortality from essential hypertension.


Radiofrequency-triggered pacemakers: uses and limitations. A long-term study. Seven patients with either recurrent paroxysmal supraventricular tachycardia (five), alternatinng bradycardiatachycardia (one), or ventricular tachycardia (one) underwent insertion of permanent radiofrequency-triggered pacemakers. Follow-up evaluation (36 +/- 24 months, mean +/- SD) revealed that arrhythmias were well controlled in five of seven patients, although three of the five required medication to decrease frequency of arrhythmias. Overdrive pacing was ineffective in one patient with Wolff-Parkinson-White syndrome who had recurrent bouts of atrial fibrillation or atrial flutter. One additional patient with ventricular tachycardia became refractory to overdrive atrial pacing. These studies document the long-term effectiveness of radiofrequency pacemakers in some patients with recurrent refractory arrhythmias. Careful patient selection and electrophysiologic studies are mandatory before implantation of a permanent radiofrequency pacemaker. Physicians must be aware of both the benefits and possible limitations of radiofrequency pacemakers in order to choose between pacemaker versus surgical intervention in patients with cardiac arrhythmias refractory to standard drug therapy.


Effect of saralasin in hypertensive patients on chronic hemodialysis. Hypertension in patients on chronic hemodialysis is thought to be largely of two types--volume dependent or renin dependent. If renin-dependent hypertension is mediated by angiotensin II, then angiotensin II antagonism should lower blood pressure. To test this hypothesis, the angiotensin II antagonist saralasin was given to 15 hypertensive patients on chronic hemodialysis. Patients were separated into two groups by their blood pressure response. In responders blood pressure was 191/112 mm Hg and fell to 147/85 during saralasin administration (P less than 0.01). In contrast, nonresponders had blood pressures of 190/111 mm Hg before and 188/110 during saralasin administration. Five responders subsequently ahd nephrectomies with normalization of their blood pressures. Plasma renin activity averaged 70 ng/ml . 3 h of angiotensin I in responders and increased to 110 after saralasin (P less than 0.05), while nonresponders had values of 21 before and after saralasin. These results offer strong support for the hypothesis that renin-dependent hypertension is an important mechanism in certain patients on chronic hemodialysis and that such patients will respond to angiotensin II antagonism.


Septicemia in patients on chronic hemodialysis. Bacterial sepsis, a major complication of chronic hemodialysis, is due mainly to infections of the vascular access site despite increasing use of internal fistulas. Sixty episodes of septicemia occurred in two chronic dialysis centers, with an incidence of 0.15 episodes of significant bacteremia per patient-dialysis-year in each. Forty-four of the 60 episodes were judged to be due to vascular access site infection by clinical, bacteriologic, and histologic criteria. Seventy percent (31 of 44) of the vascular access site-related episodes were due to staphylococci and 25% (11 of 44) to Gram-negative bacilli; nonvascular access site-related episodes were often due to transplant site infections caused by Gram-negative bacilli or streptococci. Mortality was about 18% in both vascular access site-related and nonrelated septic episodes. Bovine heterograft arteriovenous fistulas more often led to sepsis than did Brescia arteriovenous fistulas. Treatment with appropriate antibiotics was successful in most cases. Routine removal or ligation of the vascular access site was not necessary.


Rectilinear thyroid scanning as a predictor of malignancy. Rectilinear scan findings were correlated with the surgically documented size, location, and histology of thyroid carcinoma in 67 patients. At the site of the carcinoma, 36 (54%) had hypofunction, associated with a palpable abnormality in all but one patient; 16 (24%) had an abnormality on palpation but not on scanning; 11 (16%) had both a normal clinical examination and a normal scan, associated with a benign abnormality in another part of the thyroid; and four (6%) had a patchy uptake. A literature review established that use of the gamma camera with pinhole collimator does not increase the specificity of carcinoma predictability, despite the enhanced sensitivity. The scan may still be used in evaluating the clinically solitary nodule that is not obviously malignant. However, unless that module is hyperfunctioning, clinical criteria rather than appearance of the scan should contribute most to the decision of whether to treat surgically.


Endogenous activation in blastomycosis.

Endogenous activation in blastomycosis. Recent work established the fact that the portal of entry in blastomycosis is the lung. After the initial exposure to the fungus, a pneumonic process develops that may heal spontaneously or progress locally or at distant sites, or both. Frequently, however, patients present with disseminated disease, whose chest roentgenograms do not show any lesions. We have recently seen three patients with disseminated blastomycosis with negative chest roentgenograms at the time of diagnosis. Past history showed a pneumonic illness 33, 32, and 4 months before diagnosis. Chest roentgenograms from the time of the original illness showed a pneumonic process compatible with blastomycosis in all three. Examination of postbronchoscopy sputa showed the characteristic yeasts of Blastomyces dermatitidis. These three patients document for the first time apparent endogenous activation in blastomycosis. A possible explanation for this apparent endogenous activation may reside in the histopathologic similarity between blastomycosis and other chronic granulomatous diseases, especially tuberculosis.


Effects of disulfiram and pyridoxine on serum cholesterol. Disulfiram, 500 mg/day, raised serum cholesterol levels in alcoholic persons from a mean of 193 +/- 16.4 mg/dl to 227.2 +/- 17.2 mg/dl after 3 weeks and 264 +/- 40 mg/dl after 6 weeks. This increase was not seen in a group taking pyridoxine 50 mg/day in addition to disulfiram 500 mg/day. In contrast to the disulfiram and disulfiram-pyridoxine treatment groups, control groups receiving pyridoxine alone, or no drug, had a 33 mg/dl reduction in serum cholesterol during the first 3 weeks of abstinence, a finding consistent with other evidence showing a rapid decrease in serum lipids on abstinence from alcohol. Patients taking disulfiram 250 mg/day, with or without pyridoxine, did not have this expected decrease in serum cholesterol. Since increased serum cholesterol is one of the risk factors in a coronary heart disease, chronic disulfirm therapy may increase the incidence of arteriosclerotic cardiovascular disease, as has been the case with chronic exposure to carbon disulfide, a principal metabolite of disulfiram.


Platelet hyperaggregability and thrombosis in patients with thrombocythemia. The relation between platelet hyperaggregability and thrombosis was assessed in 28 patients with thrombocythemia due to myeloproliferative diseases and 11 with reactive thrombocytosis. None of the patients with reactive thrombocytosis had thrombotic or hemorrhagic complications, but thrombosis was noted in seven patients and bleeding in two patients with thrombocythemia. Nineteen were asymptomatic. In patients with thrombosis, bleeding time, platelet glass retention, and clot retraction were normal, but evidence of platelet hyperaggregability was present in all but one. Serial studies on six patients revealed a close association between platelet hyperaggregability and ischemic attacks. Neither patient with bleeding complications had evidence of platelet hyperaggregability, although poor platelet function was found in one. Platelet function in asymptomatic patients can be classified as hyperactive, hypoactive, or normal.


Amebiasis: epidemiologic studies in the United States, 1971-1974. Seven investigations of suspected foci of amebiasis between October 1971 and June 1974 lead to three conclusions. (1) A number of laboratories have vastly overdiagnosed amebiasis and have reported leukocytes in stools as Entamoeba histolytica. Two laboratories found to be in error were in community hospitals, and one was at a teaching hospital associated with a medical school and a school of public health. These three laboratories had been diagnosing more than 1200 cases of amebiasis a year for 20 years. (2) When amebiasis does occur, it is likely to be misdiagnosed. In one outbreak with four cases and three deaths, amebiasis was not diagnosed until two patients had died and another was critically ill. Sporadic cases may be mistakenly diagnosed as ulcerative colitis and inappropriately treated with steroids. (3) Foci of endemic amebiasis continue to exist in the United States, both in institutions and in noninstitutional settings.


Ichthyosiform sarcoidosis.

Ichthyosiform sarcoidosis. A 31-year-old black woman had acquired ichthyosis. Histologic examination of her skin revealed a sarcoidal reaction in the dermis. The diagnosis of sarcoidosis was supported by negative tuberculin (intermediate strength purified protein derivative) and Candida albicans extract intradermal skin tests; by a positive Kveim test; and by roentgenographic evidence of bilateral hilar adenopathy, paratracheal node enlargement, and diffuse pulmonary parenchymal changes. Sarcoidosis must be considered when acquired ichthyosis develops in a patient.


Dystrophic xanthomatosis in mycosis fungoides. The condition of a patient with advanced mycosis fungoides was treated with cyclic combination chemotherapy. At the sites of regressing tumors, yellow nodules appeared that were clinically and histologically benign xanthomata. The probable multifactorial pathogenesis of dystrophic xanthomata is discussed and previous case reports are reviewed.


Smooth muscle hamartoma associated with Becker's nevus. Two cases of smooth muscle hamartoma with Becker's nevus are reported. Clinically and histologically the lesions resemble Becker's nevi with the exception that on histologic examination a hamartomatous proliferation of smooth muscle is prominent.


Subcutaneous cysticercosis.

Subcutaneous cysticercosis. Subcutaneous cysticercosis occurred in a 34-year-old man who had multiple asymptomatic subcutaneous nodules. Surgical excision of one lesion revealed a cystic structure with a fibrous capsule that embraced a pork tapeworm larva (Cysticercus cellulosae). Such esoteric afflictions as cysticercosis may be seen with increasing frequency in an age of accelerated international travel.


Balloon cell nevus. Summary of the clinical and histologic characteristics. A 45-year-old man requested excision of an ordinary intradermal nevus. Histologic examination showed that it was composed entirely of balloon cells; to our knowledge, this is only the fifth such case reported.


Pathogenesis of erythromelalgia.

Pathogenesis of erythromelalgia. A defective prostaglandin metabolism in patients with erythromelalgia may explain several of the clinical features of this condition, such as the red discoloration and burning sensations of the skin. In two patients with erythromelalgia a grossly abnormal bullous reaction to intradermally injected PGE1, PGE2, and PGF1alpha occurred, whereas a normal reaction appeared after injection of histamine, serotonin, and  bradykinin. Furthermore, prostaglandin-like material was detected in increased concentration in skin perfusates from these patient. In PGE1-equivalents the concentration amounted to 2.0 and 3.2 ng/ml of the original perfusate, as compared to 0.1 ng/ml in normal skin. The capacity of synthesizing prostaglandins was increased in skin biopsy material from both patients. At least part of the therapeutic effect of aspirin in these patients may be due to the influence of this drug on prostaglandin metabolism.


Trichophyton simii infection in the United States not traceable to India. To our knowledge, this communication reports the first case of Trichophyton simii infection in the United States not traceable to India, The patient was a 40-year-old Nigerian male student who had not been out of the United States for more than three years. He had never been in India or had contact with animals or poultry. A brief review of the literature is included.


Crude coal tar plus near ultraviolet light suppresses DNA synthesis in epidermis. Crude coal tar and a refined product, when they are combined with near ultraviolet (UV) light (UVA, 320-400 nm), depress DNA synthesis in vivo in normal and proliferating skin of the hairless mouse. Near ultraviolet light alone does not interfere with DNA synthesis, but coal tar without UVA does have an inhibitory effect on DNA synthesis of normal skin. This effect of coal tar without UVA is not as great as the effect of the combination of UVA and coal tar. Between 0.9 and 1.6 joules/sq cm of UVA are required for its biologic effect on DNA synthesis in coal-tar-treated skin.


Sunburn protection by longwave ultraviolet radiation-induced pigmentation. The role of melanin pigment in sunburn protection was investigated. Deep tans were induced over the backs of volunteers with repeated exposure to longwave ultraviolet radiation (UV-A). Melanogenesis was stimulated without an appreciable thickening of the stratum corneum. Two to three times the minimal erythema dose was required to produce redness in UV-A-tanned skin. Transmission studies through isolated corneum sheets revealed that specimens from tanned skin were about twice as efficient in filtering sunburn rays as stratum corneum from untanned skin. Tanning with UV-A does not provide a substantial resistance against sunburn.


Large cell acanthoma. One of the actinic keratoses. Large cell acanthoma (LCA), which was first introduced to the dermatologic literature in 1970 and has had no major presentation since then, is not an uncommon lesion. The lesion is a circumscribed hyperkeratotic epidermal growth with the outstanding pathologic feature being large cells. Clinical diagnoses have included several benign and malignant skin conditions. Large cell acanthoma may be related to lichen planus-like keratosis and lentigo senilis. We diagnosed 38 instances of LCA among 34,000 specimens received in our dermatopathology laboratory.


Radiation dermatitis following electron beam therapy. An evaluation of patients ten years after total skin irradiation for mycosis fungoides. Ten patients, who had been treated for mycosis fungoides with electron beam radiation ten or more years previously, were examined for signs of radiation dermatitis. Although most patients had had acute radiation dermatitis, only a few manifested signs of mild chronic changes after having received between 1,000 and 2,800 rads.


Epidermotropically metastatic malignant melanoma. Differentiating malignant melanoma metastatic to the epidermis from malignant melanoma primary in the epidermis. In four instances, metastases to epidermis from primary cutaneous malignant melanomas at different sites showed histological features similar to those of cutaneous malignant melanoma primary in the epidermis. In these metastases, atypical melanocytes were present within the epidermis and in the upper part of the dermis much as in primary cutaneous malignant melanoma. Therefore, the presence of atypical melanocytes within the epidermis is not in itself an absolute criterion of malignant melanoma primary in skin. Nor does that finding absolutely deny malignant melanoma metastastic to the skin. Features that may enable histologic differentiation of epidermotropically metastatic malignant melanoma from primary cutaneous malignant melanoma are emphasized.


Cutaneous ciliated cysts.

Cutaneous ciliated cysts. We studied 11 patients with a cutaneous cyst lined by a simple columnar ciliated epithelium. All of the patients were women in the second or third decade of life. Each had only a single lesion, located on the lower extremity. Clinical examination showed a cyst without specific identifying characteristics. The cyst is considered benign, because of the high degree of differentiation and lack of cellular atypia. The origin of the cyst is unknown. We favor the theory of sequestration and migration over that of transplantation or metaplasia.


Clinical syndrome of chemotaxis defect, infections, and hyperimmunoglobulinemia E. A case report. A 17-year-old girl had a clinical syndrome that consisted of neutrophil chemotaxis defect, recurrent bacterial infections, and hyperimmunoglobulinemia E. Neutrophil chemotaxis was quantitated by a radioassay technique that used 51Cr-labeled neutrophils and a double micropore filter chemotaxis chamber. A table of the features of other cases of this syndrome is presented. Since ten of the 13 patients who are described had a chronic eczematoid dermatitis, we suggest that this may be a fourth feature of this syndrome. Red hair and fair skin were not consistent findings in these patients. In the evaluation of patients with chronic, recurrent bacterial infections of the skin of undetermined origin, we recommend determination of serum IgE levels. If IgE is found to be elevated, one should consider the presence of this syndrome, and neutrophil chemotaxis should then be examined.


Primary cutaneous aspergillosis in a leukemic child. Primary cutaneous aspergillosis is rare. In this report we describe a primary skin infection by Aspergillus flavus in a child with leukemia. The lesions were characterized by erythematous macules and papules associated with pain and itching, followed by a rapid progression to ulcers and central black eschars with a raised erythematous border. A favorable response to topical nystatin therapy was observed. The multiple cutaneous lesions seen in our patient were most likely due to primary inoculation near the site of intravenous infusion with subsequent local lymphatic spread.


Hand-Schüller-Christian disease in a septuagenarian. Hand-Schüller-Christian disease is a disease primarily affecting children, occasionally young adults, and rarely older adults. Very few cases have been reported in individuals past their fifth decade. A review of the English language literature indicates that the onset of Hand-Schüller-Christian disease occurs after the fifth decade in less than 4% of reported cases. A 75-year-old woman's symptoms of Hand-Schüller-Christian disease began in her 76th year, and her cutaneous symptoms were controlled with a topically applied nitrogen mustard.


Dermatofibrosarcoma protuberans with lymph node involvement. A case report of simultaneous occurrence with an atypical fibroxanthoma of the skin. A 40-year-old man had dermatofibrosarcoma protuberans of the neck with rapid local recurrence, satellite nodules, and a cervical lymph node metastasis, occurring simultaneously with an atypical fibroxanthoma of the scrotum. These two tumors, with distinct clinical and pathologic features, are classified as histogenetically related lesions within the spectrum of the fibrous histiocytomas. The place for the dermatofibrosarcoma protuberans at the malignant end of this spectrum is clinically and ultrastructurally documented further in our patient.


Angioimmunoblastic lymphadenopathy. A generalized lymphoproliferative disorder with cutaneous manifestations. Angioimmunoblastic lymphadenopathy (AIBL) is a recently described, systemic disorder characterized by an excessive proliferation of transformed lymphocytes, possibly the result of chronic antigenic stimulation, frequently by drugs. Cutaneous involvement, usually in the form of a pruritic, generalized, maculopapular rash, occurs in about 40% of cases. We saw a patient with AIBL who had an unusual, primarily plaque- and nodular-type of skin involvement and who had been receiving drugs not previously reported as being associated with this disorder. Because cutaneous involvement is a frequent, presenting complaint, dermatologists should be able to recognize this unusual, clinicopathologic entity.


Linear unilateral basal cell nevus with comedo-like lesions. A 20-year-old woman had linear unilateral basal cell nevus with comedo-like lesions. Numerous papules were distributed on the left side of the upper aspect of the trunk in a zosteriform fashion. The indivisual lesions were hemispherical, pearly, and waxy tumors, some of which had central plugs. Histologic examination revealed polymorphous patterns that suggested that the tumor cells differentiated toward the apocrine glands, hair structures, and sebaceous glands. Ultrastructurally, the tumor strands were composed of fairly mature basal cells with well-developed tonofilaments and desmosomes.


Progressive cribriform and zosteriform hyperpigmentation. Five cases of progressive cribriform and zosteriform hyperpigmentation are described. The following criteria were fulfilled: (1) uniformly tan cribriform macular pigmentation in a zosteriform distribution; (2) a histologic pattern that consisted of a mild increase in melanin pigment in the basal cell layer and complete absence of nevus cells; (3) no history of rash, injury, or inflammation to suggest postinflammatory hyperpigmentation; (4) onset well after birth with gradual extension; and (5) lack of other associated cutaneous or internal abnormalities. This appears to be a newly described entity, although it resembles a Becker's nevus without hypertrichosis or an typical café au lait spot. We believe that such progressive cribriform and zosteriform pigmentation is not uncommon.


The clinical use of the naso-gastric duodenal mercury tip sump tube in abdominal surgery and in the management of intestinal obstruction. A naso-gastric duodenal mercury tip weighted sump tube has been developed that will efficaciously decompress small bowel in cases of paralytic ileus, partial or complete mechanical obstruction, and can easily be introduced into the duodenum by a nurse, house staff or attending physician. The tube also may be used for diagnostic purposes to obtain gastrointestinal, pancreatic or biliary secretions.


Reserpine treatment of Raynaud's disease. Six patients with primary Raynaud's disease were investigated with magnification hand arteriography, measurement of finger systolic pressure and response to a newly devised local cooling test. They were treated with reserpine 0.5 mg injected into the brachial artery, and the clinical effects were followed by a scoring system and by the change in digital arterial tone during local cooling. The latter was registered as the change in systolic finger blood pressure measured indirectly by a finger-plethysmograph during stepwise decrease in finger temperature, until at a critical temperature complete closure of the digital arteries occurred. Shortly after injection the clinical condition improved, and closure of the digital arteries during local cooling was impeded. But within a week the cooling test showed a transient deterioration with closure of the digital arteries at the same or a somewhat higher temperature than before the reserpine injection. The clinical score followed this trend. According to animal experiments the shortlasting vascular effect of reserpine on primary Raynaud's disease might be due to depletion of the sympathetic nerve terminals for norepinephrine.


Frozen section diagnosis of breast lesions. Recent experience with 556 consecutive biopsies. Experiences with frozen sections performed on 556 consecutive breast biopsies were reviewed. There were no false positive reports among the 145 (26%) lesions interpreted as carcinoma. Among 381 (68.6%) biopsies in which no carcinoma was found on frozen section, eight proved to contain carcinoma in other areas. Seven of the false negatives contained noninvasive carcinoma (six--in situ lobular; 1--intraductal). A small infiltrating lesion was found in the eighth case. The diagnosis was deferred to paraffin section in 30 (5.4%) of biopsies. Ten lesions proved to be noninvasive carcinoma and one was an infiltrating lobular carcinoma. Frozen section diagnosis is a highly reliable procedure for the diagnosis of infiltrating breast carcinoma. Noninvasive carcinoma may be overlooked at frozen section because of the limitations of sampling. Consequently, patients should be cautioned to await the paraffin section report if the frozen section does not reveal carcinoma. A frozen section diagnosis of carcinoma does not necessarily commit the surgeon to further surgery at that time and the information obtained from the frozen section may be helpful in beginning to plan further treatment with the patient.


Albumin uptake by skin, skeletal muscle and lung in living and dying patients. Quantitative changes in albumin and water content which occur in skin and muscle tissue obtained by biopsy from clean surgical incisions at the time of skin incision and at the time of wound closure were assessed in seven patients who had major abdominal and vascular operations. Biopsies from skin, muscle and pulmonary tissue were obtained in a second group of nine patients who had thoracotomy for suspected bronchogenic carcinoma. The intravascular albumin mass decreased linearly with the duration of the operation (r = 0.69, p <0.01) and was correlated significantly with a linear increase of extravascular albumin content in muscle (r = 0.63, p < 0.01). A significant increase of extravascular albumin occurred from the time of incision to the time of wound closure in the skin and muscle samples from both groups (p < 0.05-p < 0.001). Extravascular albumin and water content were assessed in a third group of three postoperative patients who died with acute respiratory failure. Although the concentration of extravascular albumin in pulmonary tissue taken from this group was not different from the thoracotomy group, calculations based on the mean combined post mortem lung weights showed two to three times more extravascular albumin content. The histopathological findings are consistent with these changes. Thoracotomy was not associated with an abnormal increase in pulmonary extravascular albumin and water content, possibly because albumin does not gain access to the pulmonary extravascular space in increased amounts during operation in this clinical setting.


Dearterialization of the liver for metastatic cancer. Clinical, angiographic and pathologic observations. Five cases of dearterialization of the liver for metastatic cancer are presented. Subjective and objective improvement was accomplished in three patients. Pre- and postoperative arteriography demonstrates the extent of devascularization and the routes of reestablished collateral. Microscopic studies demonstrated effects on tumor and on hepatic parenchyma and biochemical data indicate the extent and duration of hepatic dysfunction.


A "new" diaphragm following prosthetic repair of experimental hemidiaphragmatic defects in the pup. Hemidiaphragmatic defects were created in ten pups and repaired with Silastic Sheeting (Dow-Corning .007 u) to determine the long-term results of prosthetic replacement of the diaphragm in growing subjects. All animals survived the operation without complication and grew and developed normally, weighing between 35 and 40 pounds at one year of age. The prosthesis gradually became located in the extreme left anterolateral costophrenic sulcus in nine of the ten dogs studied by sequential chest x-rays. Slight paradoxical movement was visible to fluoroscopy without eventration of the diaphragm. One animal developed an asymptomatic posterolateral diaphragmatic hernia nine months following operation. The other animals were sacrificed at one year of age. The liver, spleen and stomach were partially covered by a "new" muscle containing diaphragm having a mean area of 176 +/- 8.3 cm, compared to the original defect which measured 15.89 +/- 1.2 cm. Skeletal muscle cells extended into the margins of the prosthesis. The dorsolateral location of the "new" diaphragm is evidence that postnatal skeletal muscle growth may be derived from persisting precursor tissues.


The effect of jejunoileal bypass on bile composition and the formation of billiary calculi. In our series of 101 patients with small bowel bypass for morbid obesity, nine developed biliary calculi postoperatively during a mean follow-up of 29.6 months. The development of gallstones depends in part on biliary cholesterol saturation and on the zeta potential of bile. In eight consecutive patients, the lithogenicity of bile was assessed by the methods of Small, Swell and Isaksson, which are dependent on cholesterol saturation. Postoperatively, the lithogenic score decreased in six and increased in two patients, one of which developed gallstones. Taurine bile salt conjugation tends to prevent aggregation of micelles by increasing the zeta potential. The biliary glycine/taurine ratio increased (p less than 0.05) from 4.6 to 5.9 postoperatively. These results suggest that the increased incidence of cholelithiasis following small bowel bypass is not only due to a relative change in bile composition but is probably more significantly due to an increase in the biliary glycine/taurine ratio and a consequent decrease in the biliary zeta potential.


A density test for the intraoperative differentiation of parathyroid hyperplasia from neoplasia. A simple, instant, and reliable test called the Density Test, based on the difference in density between the normal and the diseased parathyroid tissue, was performed intraoperatively in 73 patients with primary hyperparathyroidism. Whereas the normal parathyroid tissue floated, the diseased tissue invariably sank in a mannitol solution with a density range between 1.049 and 1.069. With the aid of this test, a diagnosis of adenoma was made in 66 patients and of primary hyperplasia in the remaining seven. In every case the diagnosis was subsequently confirmed. Forty-two of the 66 patients with an adenoma (64%) had a unilateral exploration of the neck. The Density Test saved these patients from an unnecessary contralateral exploration by the finding of an adenoma and a normal second gland in the same side of the neck. These data show that the Density Test is useful in the intraoperative diagnosis of a diseased from a normal parathyroid tissue. Tissue that sinks within the density range of 1.049 and 1.069 is without exception diseased and should therefore be either partially or completely excised even if the gland is of average size or only of slight enlargement. If it does not sink, it is virtually certain to be normal and should be spared. The Density Test provides a valuable clue in the differentiation of primary parathyroid hyperplasia from neoplasia.


Multiple carcinomas of the large bowel: a natural experiment in etiology and pathogenesis. One hundred twenty-one patients with two or more large bowel cancers have been studied. An evaluation of the site of incidence of second cancers in patients presenting with metachronous disease supports the concept that increased delivery of bile acids to the colon may play a role in tumor pathogenesis. Because of the extremely high incidence of advanced tumors in patients with metachronous disease, every effort should be made to identify those patients who should undergo a preventive total abdominal colectomy. Newer methods with increased sensitivity are required to improve the follow-up of patients who are prone to develop second neoplasms of the large bowel.


Human parathyroid cryopreservation: in vitro testing of function by parathyroid hormone release. The functional viability of cryopreserved human parathyroid tissue was assessed by determining suppressibility of parathyroid hormone release by evaluation of ambient calcium concentration. Parathyroid hormone release from dispersed human parathyroid cells prepared from both fresh tissue and tissue cryopreserved for up to 200 days was suppressed 0-90% in response to four-fold increases in calcium concentration. In the tissue that demonstrated suppression precryopreservation, the suppression curve was similar in form postcryopreservation. The ability to retain functional integrity within human parathyroid cells by cryopreservation, allows preservation for periods of time probably sufficient to determine the presence of the aparathyroid state, and allows for subsequent successful parathyroid autotransplantation. This technique has particular applicability to patients reoperated upon for persistent hyperparathyroidism where the remaining amount of normal parathyroid tissue is obscure or unknown.


Control of gastric emptying: interaction of the vagus and pyloric antrum. Gastric emptying of liquids and solids was evaluated in ten dogs with gastric fistula before and after either truncal vagotomy, antrectomy, or pyloroplasty. In subsequent operations, the vagotomy group underwent either antrectomy or pyloroplasty, and the antrectomy and pyloroplasty groups were vagotomized. Vagotomy significantly inhibited the emptying of both liquids and solids (p less than 0.001) when the pyloric antrum was intact. When the antropyloric mechanism was removed by antrectomy, the effect of vagotomy was to accelerate the emptying of liquids (p less than 0.05) but to impair the emptying of solids (p less than 0.001). When the pylorus was destroyed by pyloroplasty, vagotomy markedly accelerated the emptying of liquids but had little effect on the emptying of solids. Neither antrectomy nor pyloroplasty had any significant effect on the emptying of solids. Pyloroplasty caused minor acceleration of emptying of liquids while antrectomy had no effect.