Localization by autoradiography of tritiated isoproterenol in "infarct-like" lesions of rat myocardium. A number of physiopathogenic mechanisms have been outlined to explain the "infarct-like" lesions produced by isoproterenol (ISP) in the hearts of various animals: Excess of oxygen consumption and inotropic effect, coronary vasoconstriction, deleterious action on glucose and lipid metabolism, direct cardiotoxic effect, platelet aggregation in the small cardiac vessels and formation of microclots, excessive mobilization of fatty acids, fluid and electrolytic imbalances, loss of high-energy intracellular coupling, and inadequate activation of the "calcium pump." For this reason, localization of the tritiated ISP in the normal myocardial fibers and in the induced lesions was studied. The first control group (G-1), consisted of 40 Wistar rats, weighing from 180 to 200 grams; they were injected intraperitoneally with ISP sulfate (10 mg. per kilogram) and were killed under ether anesthesia after periods of 5, 30, and 120 minutes, and 12 and 24 hours. A similar group (G-2) was injected intraperitoneally with an equal dose of ISP plus 5 muCi of tritiated ISP sulfate (3H). In this group animals were killed at the same periods as above. In rats treated with ISP-3H an abundant amount of the labeled drug was observed on the sarcolemma surface and a smaller quantity was noted inside the myocardial fibers. This observation was noted in the autoradiographs obtained 5 minutes after the injection and persisted in all subsequent observation times. In those animals which were killed 5 and 30 minutes after injection, the deposit was noted in "grooves" along the edge of the sarcolemma, strongly suggesting a primary action on the cellular membrane. These findings and the peculiar topography suggest that (1) myocardial necrosis induced by ISP is probably due to an increased activation of the "calcium pump"; the early presence of contracture bands and the positivity of the ischemia test further emphasize this statement; (2) the ISP effect is rapid; (3) the morphologic alterations are similar to those recently described as "coagulation myocytolysis" and present in human infarctions or following sudden death.


Conduction disturbances of the bundle branches produced by lesions in the nonbranching portion of His bundle. The present experiments were conducted on isolated dog hearts to demonstrate that conduction disturbances can be induced in the bundle branches by transection of about 50 per cent of the cross-sectional area of the His bundle on the right or left side. The His bundle, the posterior and anterior divisions of left bundle, and the right bundle were exposed by careful dissection, and microelectrode techniques were used to record action potentials from the three bundle branches. Pacing stimuli were applied to the nonbranching portion of His bundle proximal and then distal to the site of transection to study the effect of such lesions on impulse conduction to the bundle branches. It was demonstrated that conduction to the bundle branches was not affected by such lesions in the His bundle at pacing rates slower than 100 per minute; however, conduction disturbances were rate-dependent and manifested at faster pacing rates. In nine out of all 16 experiments, partial or complete block occurred in all three bundle branches regardless of the side of the lesion. In the remaining seven experiments, they were observed in the bundle branch on the same side as the lesion. It was assumed that conduction disturbances of the bilateral bundle branches resulted from decremental conduction in the uncut portion of His at the level of lesion, and those of the ipsilateral branch from the functional failure of transverse crossover connections between the longitudinal His bundle fibers. The results indicate that localized lesions in the nonbranching portion of His bundle can indeed produce the pattern of bundle branch block under certain conditions.


Phentolamine.

Phentolamine. The clinical uses of phentolamine have widened since its introduction as an anti-hypertensive agent. The vasodilating action of the drug as well as its postive inotropic effects have led to its use in treating congestive heart failure. Recently, phentolamine has been use by several groups to improve left ventricular function in acute myocardial infarction. There appears to be great promise for the use of phentolamine in this clinical setting. The drug given intravenously or orally can suppress ventricular premature beats and supraventricular premature beats. However, the experience of phentolamine as an antiarrhythmic agent is still limited. Similarly, the relief of angina pectoris by phentolamine requires confirmation by additional clinical studies. Phentolamine can be used as a provocative test in idiopathic hypertrophic subaortic stenosis. Since it does not produce cardiac arrhythmias, it may be safer than isoproterenol. The comparative effectiveness of phentolamine and isoproterenol in diagnosing I.H.S.S. is unknown. Phentolamine has been advocated for several years as a beneficial agent for the treatment of shock. The experience is still limited to a few groups who have reported favorable results. Phentolamine has been used as a bronchodilator and a pulmonary artery dilator. The preliminary reports appear favorable. However, continused investigation is warranted. A sensitive measurement of the blood levels of phentolamine is not available. When this is accomplished, further insight into the metabolism of this drug will be forthcoming.


Adrenal medullary disease in multiple endocrine neoplasia, type 2: pheochromocytoma and its precursors. Multiple endocrine neoplasia, type 2 (MEN-type 2), designates the syndrome of medullary thyroid carcinoma, pheochromocytoma, and occasional parathyroid hyperplasia. The thyroid carcinoma, which is usually bilateral and multicentric, is preceded by multifocal C-cell hyperplasia. The adrenal gland manifests pheochromocytoma, which is frequently bilateral and multicentric, and may be malignant. To test the hypothesis that diffuse adrenal medullary hyperplasia is a precursor of pheochromocytoma in this syndrome, we studied the adrenal glands of 19 patients who had MEN-type 2. The findings in the adrenal medulla in these 19 patients were: synchronous bilateral pheochromocytoma in 9 (metastatic in 3); asynchronous bilateral pheochromocytoma in 1 (metastatic); unilateral pheochromocytoma with contralateral diffuse and nodular hyperplasia in 2; unilateral pheochromocytoma with contralateral diffuse hyperplasia in 2; unilateral pheochromocytoma in 1; bilateral nodular hyperplasia in 1; bilateral diffuse hyperplasia in 1; and no abnormality in 2. This spectrum of adrenal medullary pathology suggests that diffuse and nodular medullary hyperplasia are precursors of pheochromocytoma in MEN-type 2.


A regional quality control program in microbiology. I. Administrative aspects. Conventional proficiency testing programs in microbiology using recognizable materials yield limited information. To assess overall laboratory competence in the handling of routine clinical material, other methods are needed. This report describes the use of "blind," simulated clinical specimens in a regional quality control program. Details of the administration, including technics, costs, logistics, and limitations, are presented.


A column chromatographic method for the combined analysis of creatine kinase-MB (CPK-MB) and lactate dehydrogenase 1,2 (LDH 1,2) isoenzymes. A column chromatographic method for the simultaneous single-eluate isolation of CPK-MB and LDH 1,2 has been evaluated. The method is rapid in that the entire isolation is completed in less than an hour and subsequent analysis can be performed using presently available spectrophotometric methods and reagents without the need for electrophoresis equipment. In addition, since the isoenzymes are directly isolated, quantitation of enzymatic activity can be performed with precision. This technic permits detection of CPK-MB and LDH 1,2 in samples with normal values of total CPK and LDH utilizing a routine laboratory spectrophotometer. The sensitivities for diagnosis of acute myocardial infarction are 95% for LDH 1,2 and 100% for CPK-MB. The specificities for diagnosis of acute myocardial infarction are 86% for LDH 1,2 and 96% for CPK-MB.


A study of the nature of "hairy" cells, with emphasis on enzymatic markers. Studies of peripheral blood, bone marrow, and spleen cells from three patients with hairy-cell leukemia were performed. Two of the three patients had well-organized cytoplasmic, ribosome-lamellar inclusions in their leukemic cells. Blast transformation and 3H-thymidine incorporation of lymphocytes seemed to fall within normal ranges when the findings were related to the absolute numbers of lymphocytes. The enzymatic markers demonstrated in hairy cells-strong acid phosphatase activity in endoplasmic reticulum and lysosomes, marked alpha-naphthyl acetate esterase reaction, and weak beta-glucuronidase activity-as well as their phagocytosis of latex particles, indicate a common origin with monocytes or histiocytes. No decisive results were obtained by immunofluorescence. Evaluation of the significance of the formation by hairy cells of mouse erythrocyte rosettes, as well as the presence of the typical hair-like projections, may require additional knowledge concerning the membrane of these cells.


Normal hematocrits in preadolescent children. Hematocrits were studied in 471 children aged 11, 12, or 13 years who resided in an affluent suburb of Pittsburgh. It was found that different microhematocrit machines gave slightly different results, so all values were corrected to a reading that would have been obtained using a Wintrobe hematocrit tube. A true Gaussian curve was obtained, suggesting that these children are a valid source of "normal" values. Mean hematocrit was 43%, with 95% confidence limits of 39 to 47%, and was the same for boys and girls. These are slightly higher values than usually are accepted as normal for this age group, and for the girls, values are comparable to those of women. A group of 220 black children of the same age who participated in a sickle-cell screening program had comparable mean hematocrits, but the distribution curve was skewed, suggesting that a small but significant number were anemic.


Hemoglobin QIndia, alpha 64 (E13) Asp replaced by His, and beta-thalassemia in a Canadian family. Cellulose acetate electrophoresis at pH 8.4 showed a hemoglobin variant with the mobility of hemoglobin S in a Canadian family. Sequence analysis revealed that histidine was substituted for aspartic acid at position 64 in the alpha-chain. This variant was found in association with a beta-thalassemia trait condition.


Hemoglobin Bethesda, beta 145 (HC2) Tyr replaced by His, in a Canadian family. A hemoglobin mutant with the mobility of hemoglobin (Hb) A on alkaline cellulose acetate or starch gel electrophoresis and mobility between Hb A and Hb S on citrate agar electrophoresis was detected in a patient with erythrocytosis. Structural analysis shows a substitution of histidine by tyrosine at position 145 in the beta-chain.


Hemoglobin Jackson, alpha 127 (H10) Lys replaced by Asn. A new hemoglobin mutant was detected as a fast-moving variant on cellulose acetate electrophoresis at pH 8.4. The mutation is in the alpha-chain at position 127, where lysine is substituted by asparagine. This is an external residue, and mutation at this site does not lead to any altered physiologic function of the hemoglobin.


Pseudo-obstruction of the colon.

Pseudo-obstruction of the colon. "Pseudo-obstruction of the colon" refers to a condition in which physical and radiological findings identical to those associated with mechanical obstruction of the large bowel are found but in which no organic cause for the colonic distention is present. These cases may involve progressive proximal large bowel dilatation to the point of cecal perforation or necrosis. We have collected eight cases of our own which will be presented. The various etiologic factors reported in the literature will be discussed and analyzed and we will offer an anatomicophysiologic explanation of a possible mechanism, based on sympathetic-parasympathetic neurostimulatory imbalance.


A new endoscopic classification of Chronic Esophagitis. Based on our experience of 97 cases of chronic esophagitis diagnosed endoscopically and histologically by guided biopsies, a new macroscopial classification is suggested as follows: Type I: Erosive-ulcerative form; Type II: Granulative form;; Type III: Barrett-type ulcers; Type IV: Esophagogastric or marginal ulcerations; Type V: Stenosing form. Type I (44.2%) and Type IV (26.7%) are commonly seen. Type II (15.4%) and Type V (11.3%) are healing stages of peptic esophagitis. Type III (2.4%) is rare. The above described classification is clearly correlated with the clinical symptoms of the disease.


Endoscopic identification of esophageal involvement by carcinoma of the stomach. Correlation between esophagoscopic findings of the lower esophagus and cardia and the extent of esophageal involvement by carcinoma of the stomach was studied in 67 patients operated upon for adenocarcinoma involving the cardia. Of 44 patients with such endoscopic signs as a mass, with or without ulceration, mucosal elevation or thickened folds in the lower esophagus, 43 had carcinomatous invasion over 1 cm. from the esophagogastric mucosal junction. On the other hand, only two of 23 patients without those endoscopic signs had esophageal involvement more than 1 cm. above the junction line. When the cardial orifice was stenotic or asymmetrically open, minimal esophageal involvement was noted in 10 patients. No tumorous invasion to the esophagus was seen in 13 patients with symmetrically open cardia. It seems appropriate to state that when endoscopic examination reveals signs suggestive of esophageal involvement by carcinoma of the stomach, thoracotomy should be performed to attain radical operation. This is so except for those with minimal carcinomatous involvement of the lower esophagus.


Total gastrectomy: twenty years' experience. The management and treatment of patients with gastric cancer is all encompassing. It includes preoperative care, operative resection postoperative sympathetic encouragement with therapeutic and nutritional guidance. This has been the experience with 62 human beings afflicted with malignant disease of the stomach. The end result has been that approximately 50% of these patients survived five years or more. This is a comparative favorable percentage when considering cancer elsewhere in the gastrointestinal tract. What is more enlightening is that the patients were comfortable and able to enjoy a pleasant personal diet during the five or more years following surgery. This salubrious state is attributed to the preservation of a small segment of stomach which enabled the intrinsic factor in the gastric mucosa to participate in and contribute to the normal hemopoietic physiological process.


Reserpine-induced dissociation of canine pancreatic secretion. In five dogs, provided with chronic pancreatic and gastric fistulas (Thomas' cannula), the effects on exocrine pancreatic secretion of an intravenous continuous perfusion of gastrin (Eurorga, hog gastrin I-II, 6 mug./kg./hr.) and secretin (GIH, 0.5 C.U./kg.hr.) was studied before and after 48 hours of reserpine treatment (0.1 mg./kg./24 hr.). When compared with the pretreated plateau levels, reserpine induced a significant pancreatic secretion dissociation, a depressive of the alkaline and a rising of the protein component. The former phenomenon suggests a participation of a catecholamines in the secretin-elicited pancreatic electrolyte secretion. The latter, an enhanced sensitivity of intranpancreatic and/or acinar cells of the "pancreon" to gastrin stimulation.


Tuberculosis of the esophagus.

Tuberculosis of the esophagus. A case of tuberculosis of the esophagus is presented in a patient with pulmonary tuberculosis. The patient, complaining of dysphagia, had esophagoscopic examination which showed a submucosal tumor with central ulceration. Tissue biopsy, under direct vision from the tumor mass, confirmed the diagnosis of tuberculosis. The patient has been asymptomatic under treatment. Both esophageal and pulmonary lesions are largely improved.


Simultaneous perforation of a gastric and a duodenal ulcer. This is a case report of simultaneous perforation of a gastric and duodenal ulcer. Perusal of the literature shows the rarity of this occurrence. Consideration is given to the difficulty of handling such a case in the presence of severe generalized peritonitis and the precarious condition of the patient.


Endoscopic retrograde cholangiopancreatography in the infant. Endoscopic retrograde cholangiopancreatography can safely be performed in the infant, using the standard adult cannulating instrument. Children must be examined under general anesthesia and care must be taken to insure adequate pressure of injection to fill the proximal branches of the intrahepatic radicals.


Stability of injectable medications after reconstitution. The stability of injectable medications after reconstitution is presented. The following information about each drug is given in tabular format: drug to be reconstituted and size of package; recommended route(s) of administration; recommended diluent, quantity to be used and resultant concentration; stability after initial dilution; and stability after further dilution; and stability of frozen antibiotics.


Drug-related hospital admissions.

Drug-related hospital admissions. The association between hospital admissions and drug-related problems was studied in 216 patients. All patients admitted to a general 100-bed ward in a large teaching hospital over a two-month period were interviewed by the pharmacist to determine (1) prescription and nonprescription drugs regularly administered by the patient, (2) method of administration, (3) patients' compliance with prescribed therapy, and (4) signs and symptoms of adverse drug reactions. Fifty-nine (27.3%) patients were found to have a drug-related problem associated with their hospital admission. Twenty-four patients (11.1%) had an adverse drug reaction associated with their hospital admission; in only 17 (7.9%) of the patients did the adverse reaction cause the hospital admission. Adverse drug reactions and noncompliance (10.5%) appeared to be the principal factors in hospital admission. To a lesser extent, inadequate therapy, improper or erroneous drug use and drug overdose were found to be associated with hospital admissions. As to mechanism of drug reaction, a drug side effect was involved in most cases. While hospital pharmacists have traditionally concentrated on improving inpatient distribution services, this study indicates a need for the improvement of drug monitoring and education services available to patients in outpatient settings.


Pharmacy, pharmaceutics and modern drug delivery. Recent developments in the area of drug delivery are reviewed. Controlled delivery of drug substances (including controlled-release oral products, the Folkman-Long silastic device and membrane-medicated delivery systems) are discussed. The prodrug approach is illustrated by discussion of the esterification of epinephrine and the production of the dihydro form of 2-PAM (pro-2-PAM). It is suggested that the pharmacist study the release pattern of drug devices and the pharmaceutics of prodrugs in order to maintain his responsibility as the expert on drugs.


Comparison of commercial pyrogen testing laboratories. The pyrogen test results of four laboratories were compared to determine if any inconsistencies existed. Samples submitted for pyrogen testing were of two types: (1) radiopharmaceuticals which had been allowed to decay to negligible activity or mock radiopharmaceuticals prepared with saline instead of pertechnetate, and (2) positive controls of bacterial endotoxin. The drugs used in the eight-rabbit tests included 99mTc-macroaggregated albumin, 99mTc-human serum albumin, 99mTc-sulfur colloid, saline and iodinated fibrinogen. Laboratory A showed a 52% failure rate for the testing of 36 preparations. Samples identical to those not passed by laboratory A were passed by laboratories B, C and D. It is recommended that all users of pyrogen testing laboratories periodically submit samples of known apyrogenicity for testing.


Legal implications of preparing and dispensing drugs under conditions not in a product's official labeling. The legal issues surrounding the potential liability of a pharmacist for dispensing or preparing drugs under conditions not contained in the official labeling of a product are examined. Although the specific issue of liability of a pharmacist for preparing a drug in a nonapproved manner or dispensing a drug for a nonapproved use has not been adjudicated, based on evolving legal principles it appears that the pharmacist will be held responsible for the drugs so prepared or dispensed. Preparation of a drug which is adulterated under the federal Food, Drug and Cosmetic Act appears to be negligent, although its precise effect will be dependent upon state law. Liability for dispensing for nonapproved uses may be minimized if the pharmacist, in the exercise of sound professional judgment, concludes that the use is rational, safe and reasonable.


Drug information services on a subscription basis. A hospital-based drug information service (DIS) which provides services to five hospitals and a local pharmaceutical association on a subscription basis is described. The two methods of subscription are (1) a monthly fee based on hospital bed size, and (2) a fee per question. The fee based on hospital bed size allows unlimited DIS use and provides a guaranteed income. The fee per question is suitable for private practitioners and those hospitals requiring less frequent DIS use. The pharmaceutical association is billed a flat monthly rate which is paid out of membership dues. The DIS staffing, work load, reference sources, budget and mode of operation are discussed.


Lithium-induced nephrogenic diabetes insipidus. The etiology, diagnosis and management of lithium-induced diabetes insipidus (LIDI) is discussed, including the presentation of a case report. It is suggested that lithium provokes LIDI by decreasing the responsive ness of the kidney to the antidiuretic hormone. Lithium-induced polyuria may be managed by concomitant treatment with a thiazide diuretic or discontinuation of the lithium. Caution must be employed, however, when using thiazides with lithium as these diuretics decrease renal clearance of lithium.


Optic disk neovascularization associated with chronic uveitis. Disk neovascularization associated with chronic uvetitis occurred in five patients. The uveitis was most frequently diagnosed as chronic cyclitis, with a marked inflammatory cell response in the vitreous body. Using direct and indirect ophthalmoscopy, slit-lamp biomicroscopy with the Goldmann contact lens, perimetry, and fluorescein angiography and angioscopy, we found no areas of vascular occlusion or nonperfusion. Inflammation probably produced chemical mediators capable of traveling to the optic disk and inducing neovascular proliferation, in the absence of retinal vascular occlusion.


Optic neuropathy due to brain abscess.

Optic neuropathy due to brain abscess. A 26-year-old man went blind as part of a multifocal central nervous system disease. Bilateral optic nerve head pallor developed four weeks later. There had been no papilledema. In this setting, the appearance of optic atrophy without preceding papilledema in part led to the clinical diagnosis of severe disseminated encephalomyelitis. At autopsy multiple brain abscesses were found, including an area of inflammation within the chiasm.


Choroidal leiomyoma of vascular origin.

Choroidal leiomyoma of vascular origin. A 57-year-old man had a clinically suspected malignant melanoma in his left eye. On microscopic study, the enucleated eye harbored an unusual choroidal tumor that had extended extraocularly. This tumor had been variously interpreted microscopically as an angiosarcoma, an atpical angioma, a glioma, or a neurilemoma. Electron microscopic examination of deparaffinized tissue established the smooth muscle nature of the tumor cells as well as the presence of numerous pericytes associated with conspicuous vascular channels. This unique myogenous tumor of the choroid probably had a vascular origin.


Time and dose for optimum radioactive phosphorus uptake measurement in rabbit uveal melanoma. Radioactive phosphorus uptake (32P) testing was performed on implanted uveal melanomas in the rabbit to determine how the percentage uptake value was affected by the dose of 32P and by the interval of time between 32P administration and 32P counting. There was no difference in percentage uptake comparing doses of 50, 100, and 200 muCi/kg, but these were relatively high doses. There was no difference in the mean percentage uptake value at two, five, or nine days after 32P administration. The range of percentage uptake values widened with successive days.


Vitreous hemorrhages and disseminated intravascular coagulation in the newborn. Of 164 consecutive newborns seen in consultations, three babies had either a preretinal or a vitreous hemorrhage,  a rare occurrence. Two of these babies had a mild form of disseminated intravascular coagulation. The hemorrhages cleared within a few months after birth. Each of the three babies was premature, had a respiratory distress syndrome, and was born to a primiparous mother. The possibility of a coagulation defect causing intraocular hemorrhage in newborns should be considered along with the tranditional mechanical theories.


Hamartoma of the retinal pigment epithelium. A 9-year-old boy had a unilateral ocular lesion characterized by a broadly elevated mass at the level of the retinal pigment epithelium. The mass showed hyperpigmented borders, overlying retinal constracture, retinal vessel tortuosity, and vitreous condensations. Electrophysiologic testing revealed an abnormal electrooculogram.


Occlusive retinal vascular disease and deafness. An 8-year-old white girl with a history of vertigo, nausea, and vomiting developed a progressive hearing loss, bilateral retinal arteriolar narrowing in each eye, vasoproliferation, and subsequent intravitreal hemorrhage. An attempt at peripheral retinal ablation with cryotherapy in the left eye resulted in retinal detachment. Spontaneous retinal detachment occurred in the right eye and was successfully repaired. Repeated intermittent hemorrhages occurred despite intraocular diathermy. Three years after onset, visual acuity was R.E.: 6/21 (20/66) and L.E.: light perception. She remains totally deaf. A 20-year-old white woman developed severe bilateral sensorineural hearing loss with poorly functioning labyrinths, followed by midperipheral retinal arteriolar occlusions and vasoproliferation on the optic nerve head. Progressive retinal neovascularization was followed by rubeosis iridis and repeated episodes of intravitreal bleeding. Six years after onset, visula acuity was R.E.: hand motions, and L.E.: 6/3 (20/100). She remains totally deaf. Both patients were of normal gestation, development, and mentality, without evidence of other systemic disease. The cause of this disease was not found.


Visual loss and perioptic vascular malformations in the eye and orbit. Three patients with monocular visual symptoms had intraocular vascular malformations, presumably congenital, in the affected eye. Special radiographic techniques (magnification of the orbit with subtraction of overlying bone during carotid arteriography) were necessary to demonstrate the orbital perioptic vascular malformations that were responsible for the visual symptoms.


Detachments of the retinal pigment epithelium at the posterior pole. Multiple vitelliform cysts of the retina, a disorder of unknown cause in which there are multiple detachments of the retinal pigment epithelium at the posterior pole, occurred in five patients. In four patients all lesions were located outside the parafoveal area while one patient showed bilateral foveal elevations associated with more eccentric detachments. Several patients showed slow resolution of some of the detachments with mild disturbances of the pigment epithelium.


Choroidal neovascular membrane in Best's vitelliform macular dystrophy. The right eye of a 9-year-old white boy with Best's vitelliform macular dystrophy had an intact egg-yolk lesion and a retinal pigment epithelial defect superiorly, suggesting an early pseudohypopyon stage. The disruptive phase of the left eye showed subretinal hemorrhages, a "signet ring," and a subretinal neovascular membrane.


Vitelliform dystrophy in a 64-year-old man. A 64-year-old white man had many large bilateral vitelliform-like lesions. A normal electroretinogram, abnormal elector-oculogram, and a pattern of blocked choroidal fluorescence were obtained. The yellowish appearance of the lesions progressed to absorption of yellow material and mottling with maintenance of relatively good visual acuity.


Primary familial amyloidosis of the cornea. A case of primary familial amyloidosis of the cornea in a 13-year-old boy was confirmed by histopathologic examination of material obtained by penetrating keratoplasty. Elevated subepithelial nodules of amyloid were present centrally. Extensive nonelevated subepithelial amyloid deposition was present in areas where either clinically gray, nonelevated subepithelial opacities or apparently normal cornea was present. Nonelevated subepithelial corneal deposits clinically similar to amyloid deposits in the proband were present in two siblings. The genetic pattern of the corneal amyloid deposits in this family appears to be autosomal recessive. Cataracts were present in two of the three affected members. Aspirated lens material from two of the affected members did not contain amyloid.


Complications of chronic cyclitis.

Complications of chronic cyclitis. Follow-up examinations, ranging from four to more than 20 years, were performed on 100 patients with chronic cyclitis whose ages at onset were from 4 to 58 years. Cataracts were found in 42% of eyes and macular disease secondary to macular edema in 28% of eyes. Band keratopathy, glaucoma, retinal detachment, retinoschisis, vitreous hemorrhage, retinal hemorrhage, and vessels leaving the disk margin were also noted. The complications resulting in decreased vision in chronic cyclitis were macular edema in active cases and macular degenerative changes in the late inactive stages. Of all eyes with final visual acuity of 6/12 (20/40) or less, 74% had permanent, late macular changes secondary to earlier cystoid macular edema. Vitreous opacities or cells, or both, caused decreased visual acuity in the early active stages of chronic cyclitis but were not major factors in the ultimate visual prognosis in the late inactive stages. At the final examination, vitreous opacities caused a visual loss in only 9% of the eyes that had visual acuity of 6/12 (20/40) or less. It was difficult to determine whether corticosteroids caused cataract formation and glaucoma.


The nystagmus compensation (blockage) syndrome. The nystagmus compensation syndrome identified in 12 to 247 consecutive patients with congenital esotropia had these characteristic features: onset of esotropia in early infancy, pseudoparalysis of both abducens nerves, head turn toward the side of the fixating eye, absence fo nystagmus with the fixating eye in adduction, and appearance of a manifest jerky nystagmus as the fixating eye moved into primary position and abduction. The nystagmus may be actively neutralized by convergence innervation, the esotropia being caused by sustained convergence and secondary changes in the medial rectus muscles. The differential diagnosis includes crossed fixation and bilateral sixth nerve paralysis.


Mangement of infantile esotropia.

Mangement of infantile esotropia. We evaluated the management of infantile esotropia-constant, alternating esotropia before 6 months of age-in 34 children. Planned one-state surgery for satisfactory mechanical alignment was highly predicatable (79 to 84%), and was obtained at any age. Stable bifoveal motor fusion was also obtained but was more frequent with alignment before 2 years of age. The use of postsurgical spectacle orthoptics (minus lenses or prisms, or both) increased the incidence of bifoveal fusion. Surgery alone resulted in bifoveal fusion in 6% of the cases, whereas an overall incidence of 33% bifoveal fusion resulted after the use of postsurgical spectacle orthoptics by some patients. Of those receiving postsurgical spectacle orthoptics, 53% obtained bifoveal fusion. This study demonstrated a correlation between the incidence of secondary A patterns (after surgery for V esotropia) and the amount of horizontal muscle surgery done in combination with bilateral inferior oblique muscle myectomies.


Synthetic absorbable suture for strabismus surgery. Polyglactin 910 (Vicryl), a synthetic absorbable braided suture in 5-0 or 6-0 size, was satisfactory for recession and resection of extraocular muscles. It produced an acute allergic reaction in only one of 89 cases (1.5%) as compared to a 19% reaction when collagen suture of like size was used. Polyglactin 910 suture, when left partially exposed, may be irritating and can cause excessive reaction when used at the conjunctival limbus.


Electron microscopic study of extraocular muscles in myotonic dystrophy. The extraocular muscles of two middle-aged men with ophthalmoplegia secondary to myotonic dystrophy were studied by electron microscopy. The main change was disorganization in the arrangement of myofibrils rather than degeneration of the cells. Diseased muscle cells contained randomly distributed, short and irregular myofibrils and individual myofilaments. The cytologic appearance of these muscle cells was similar to that of developing muscle cells. The pathogenesis of the myopathy in myotonic dystrophy may be related to myofibrillogenesis and its maintenance.


Experimental inhibition of prostaglandin-like inflammatory response after cryotherapy. To determine the effect of aspirin as an inhibitor of the prostaglandin-induced inflammatory reaction that follows cryotherapy, 12 rabbits were pretreated with aspirin and 12 were controls. The aspirin-pretreated animals showed less inflammatory reaction after cryotherapy and significantly less protein in the aqueous humor than did the control animals (P less than .01). We believe that the conjunctival hyperemia and chemosis, and the increase in protein concentrations in the aqueous humor that follow cryotherapy, are prostaglandin-related, because pretreatment with aspirin inhibited these phenomena.


Miniature dark adaptometer using tritium as a light source. A miniature dark adaptometer to measure monophasic rod function, used with disposable masks, permitted 11 measurements to be taken in 1 1/2 hours. The light source, tritium-phosphoric sulfide gas, had a known brightness decay rate incorporated in the calibration table which is provided with the instrument.


Incidence of photophobia in peripheral and sector iridectomy. Fifth patients had bilateral intracapsular cataract extractions with a peripheral iridectomy in one eye and a sector iridectomy in the opposite eye. There was no difference in photophobia between the two eyes in 78% of patients. Twelve percent of the patients had greater photophobia in the eye with the peripheral iridectomy, and 10% had greater photophobia in the eye with the sector iridectomy.


Contact lens remover adherent to cornea. A patient inadvertently applied a contact lens remover to her cornea and the remover adhered, causing pain but no serious sequelae. The device was slid from the cornea to the conjunctiva before successful removal.


[Effect of high dosages of fentanyl and piritramide upon haemodynamics, coronary blood flow and myocardial oxygen consumption (author's transl)]. High dosages of narcotic analgesics are frequently utilized as the sole anaesthetic agents for patients requiring open-heart surgery. The purpose of this study was to investigate the effect of high dosages of fentanyl and piritramide upon the cardiovascular system. In anaesthetized dogs (N2O:O2=2:1; 0.5 vol% halothane) 0.03 mg/kg fentanyl (=8) and 1.5 mg/kg piritramide (n=8) respectively were given intravenously as a bolus. After the administration of fentanyl there was a slight decrease in blood pressure (10%). The hypotension was the result of a decrease in cardiac output (thermodilution technique) by 13% due to bradycardia. Total peripheral resistance and myocardial contractility remained unaffected. Similar effects were only found late after injection of piritramide, since there was an initial cardiovascular response to piritramide characterized by a marked fall in blood pressure (29%). The major cause of arterial hypotension was peripheral vasodilatation. Load data and the decrease in max dp/dt however indicated also a slight myocardial depression. The altered haemodynamics led to a decrease in myocardial oxygen consumption with both narcotics, which was nearly paralleled by a reduction in coronary blood flow. The narrowing of arteriovenous oxygen difference of the heart proved coronary dilatatory properties of fentanyl and especially of piritramide. This study indicated that high dosages of fentanyl have advantages in comparison to high dosages of piritramide. The clinical implications of the results are discussed.


The occupational therapist on a geriatric rehabilitation team. This article describes a rehabilitation services team at a skilled nursing facility. The objectives were to explore what occupational therapy can offer nursing home residents and to provide a model in the delivery of rehabilitation services to the institutionalized elderly. Emphasis is placed upon program structure and rationale, staff interrelationships, and the role of the occupational therapist on the team.


Neonatal blood pressures.

Neonatal blood pressures. Arterial blood pressures were taken by the Doppler ultrasound method in 134 unselected mature neonates (birthweights 2,600-3,900 grams) who were managed in the same manner after birth. Blood pressures were measured at 3-5, 10 and 30 minutes of life and, if indicated, intermittently during the next 24-48 h. Left and right arm pressures were identical or differed by only 1-2 mm Hg. Lower than normal blood pressures were found in 4 groups of infants: those born by cesarean section, those recovering from intrauterine asphyxia, those exposed to maternal anti-hypertensive therapy, and those whose mothers received thiopental within four minutes of delivery. Return of the low pressures to within the normal range was fastest following thiopental induction in the absence of fetal asphyxia and slowest after antihypertensive therapy.


Teaching stroke patients to dial the telephone. Two purposes of this study were to determine what percentage of adults who had had cerebrovascular accidents were able to dial and recall telephone numbers, and whether or not the device, the Dial-a-Phone, was an effective instrument to use to teach these patients to dial the telephone. Results indicated that of 73 patients tested, 42 were unable to dial on the pretest. The Dial-a-Phone was effective in teaching 36 of the 42 patients in the mean time of 4.8 minutes of instruction. Right hemiplegics experienced no more difficulties than left hemiplegics. Those who learn to dial the telephone could use this ability as a life-saving skill, as motivation to improve development of communication skills, and as encouragement for functional independence.


[Effect of enflurane (ethrane) on intracranial pressure in comparison with halothane (author's transl)]. Enflurane (Ethrane) was given before operation to 13 neurosurgical patients. 11 of them received halothane for comparison of effects on intracranial pressure (ventricular catheter), blood pressure and central venous pressure during controlled ventilation. Neuroleptanalgesia was used as basic anaesthesia. The results showed that enflurane, when initial pressure levels were between 0-20 mm Hg, had better properties with regard to intracranial pressure than halothane. The intracranial pressure of 6 patients under enflurane rose. Of the remaining patients pressure did not change or even fell. Under halothane, given in a comparable doses, there was always a marked increase of intracranial pressure. If intracranial pressure of one patient under enflurane rose, then the increase by halothane always was more pronounced. The results from 1 patient had to be excluded because of spontaneously occurring plateau waves. Blood pressure was lowered by both agents while central venous pressure remained unchanged.


[The effect of halothane and enflurane as well as of propanidid and ketamin on the aortic baroreceptor discharge of decerebrated cats (author's transl)]. The effect of halothane, enflurane, propanidid and ketamine on the sensitivity of the aortic baroreceptors and its quantitative relationship with arterial pressure were studied in decerebrated cats. Receptor response curves (single baroreceptor fibres of the depressor nerve) were constructed by plotting the average discharge rate (spikes/sec) against the aortic mean pressure and the effect of the anaesthetics on them was analysed. The blood pressure was changed over wide ranges by inflating a balloon placed in the thoracic part of the descending aorta through a femoral artery. Receptor sensitivity increased with halothane and enflurane, yet it decreased with propanidid. It remained uneffected duringanesthesia with ketamine. Thus, different anesthetics act differently on the afferent impulse traffic of baroreceptors. The possible role of these effects on blood pressure control during anaesthesia is discussed.


Mediastinal displacement to the sound side following pneumonectomy. A case report. Following pneumonectomy, it is usual to see a degree of mediastinal displacement in the direction of the empty cavity. In the present case however, the displacement was towards the sound side. Description and management of this situation is presented.


The occupational therapist and terminal illness: Learning to cope with death. Working with terminally ill clients is legtimately within the scope of occupational therapy. Yet two students attempting to define and learn a role in this area discovered that few therapists reported they were treating dying people. Findings from a review of the literature and in talking with therapists and dying people suggested that an occupational therapy role in this area was not clearly nor attractively defined. In addition, no suggestions were found to show how one learns such a role. This paper reports the conclusions arrived at by these students and their instructor. Using the occupational performance frame of reference, they propose a unique occupational therapy role for assisting a dying client to relinquish his occupational roles. In addition, functions of listening to, accepting, and understanding the feelings of the dying person, his family, and the staff caring for him are described. The paper concludes with examples of specific experiences for learning this role and functions based upon the premise that people must come to terms with their own feelings about death and dying before they can work effectively with a terminally ill client.


Voice terminal may offer opportunities for employment to the disabled. A rapidly growing information industry based on the combined technologies of the digital computer and telecommunications offers unique opportunities for employment of the physically handicapped. In the studies reported here, the use of voice control was investigated as an alternative to mechanical control for two quadriplegic clients too severely disabled to successfully operate a typewriter keyboard. Using a recently developed voice terminal, the clients were able to type finished copy and program a remotely located computer entirely by voice control. The voice terminal is presently in production. An evaluation of the vocational potential of the voice terminal is currently being conducted by the Rehabilitation Services Administration, DHEW.


[Intraoperative autotransfusion in gynecology and surgery (author's transl)]. The technique of intraoperative autotransfusion (AT) is being used to date only in a few individual clinics. Since there is a clinically safe and economical AT-apparatus available the routine application of this rational blood replacement method is easy to perform. The authors have used this technique altogether in 111 patients, applying the Bentley-ATS-machine in the last 69 cases. In a previous series of 42 cases AT was used for ruptured ectopic pregnancy, in the series of 69 surgical cases for hemothorax or intraabdominal hemorrhages of mainly traumatic origin. The most frequent indications for AT in emergency surgical operations were ruptures of spleen and liver, and in elective surgery for portocaval shunt. Altogether 247 litres of blood have been retransfused with an AT-volume per patient ranging from 0,5 to 15 litres. For anticoagulation generally ACD was used, only in vascular surgery was heparin preferred. Methodical complications have not been seen. Technique, indications, consequences and possible complications of AT are described. The main advantages of autologous intraoperative transfusion are the immediate availability of blood, the absence of the risk of hepatitis and of incompatibility reactions, reduction of pressure on the blood banks and lower transfusion costs. The authors therefore believe that the possibility of intraoperative AT should exist at every surgical and gynecological clinic.


[Regional block for reduction of a dislocated shoulder (author's transl)]. The authors describe a simple method for blockade of the nerve supply to all the shoulder muscles using a single injection. The advantages and possible complications are discussed.


[Morphokinetic reactions in the adrenal gland of the albino rat after anaesthesia with inactin (author's transl)]. A marked decrease in the nuclear size in the adrenal medulla and a slight increase in the nuclear volume of the zona glomerulosa was found in the Inactin anaesthetized Wistar rat. The nuclear volumes in the zona fasciculata did not show any alteration. The influence on the activity of the cells in the adrenal medulla is supposed to be due to a depression in the central nervous system by Inactin. The slight activation of the zona glomerulosa is attributed to stimulation of the renin-angiotensine-system by an Inactin induced change in renal function. A failing dose dependent effect is taken as a sign of compatibility of the administered drug.


[Experiences with continuous infusions of etomidate in cardiac surgery (author's transl)]. The hypnotic agent etomidate was added by infusion to a fentanyl-N2O-O2-anaesthesia for patients (n=15) requiring open heart surgery. The purpose of this procedure was to avoid awareness during operation (mean duration 187 min). The average amount of etomidate infused was 2.55 mg/kg, which seemed to be an overdose. The fentanyl consumption was slightly reduced as compared with a control group. No patients complained of awareness. The anaesthetic method studied is not thought to be superior to a high-dose fentanyl anaesthesia.


[Measurement of bronchopulmonary elastance and airway resistance: comparison between common methods and automatic continuous measurement by the system AUPREM (author's transl)]. The system AUPREM is a new measurement device, which allows continuous measurement of the mechanical properties of the lung and bronchial system. Pulmonary elastance and airway resistance can be measured continuously even in extremly debilitated or unconscious patients. Transpulmonary pressure change, airflow and tidal volume are used as input. From these values airway resistance and pulmonary elastance are calculated. Comparative measurements in a group of healthy subjects and in a group of patients with pathological resistance and elastance values revealed that there was no significant correlation between the system AUPREM and the commonly used methods bodyplethysmography and elastance measurement by oesophageal balloon. However, the differences are in a low order of magnitude.


[Rapid intravenous injection of streptokinase in a high initial dose for therapy of a fulminant pulmonary embolism (author's transl)]. As a result of the case described the administration of streptokinase in a high initial dosage of about 750,000-1,000,000 U within a few minutes appears to be effective in serious lethal pulmonary embolism. In spite of hypoxic cardiac arrest a 35-year-old female patient was reanimated successfully 20 minutes after the occurrence of pulmonary embolism on the 10th day after caesarian section. The development indicated that the high dosage of streptokinase led to lysis of the embolus and thus to perfusion of the lungs. In spite of complications haemothorax 4,000 ml, uterine haemorrhage the fibrinolytic and later the anticoagulante therapy was continued until lysis of the embolus was assumed as judged by the condition of the patient. To prevent a renewed cardiac arrest a temporary pacemaker was applied. The patient survived without evidence of a cerebral lesion. This paper wants to advocate the administration of streptokinase in "exorbitant" dosage in hopeless cases of serious pulmonary embolism of which a high percentage die. It is essential that the injection be made within a few minutes and must not be extended over the normally recommended period of time.


[Blood-oxygen analyzer boa 802 (author's transl)]. Experiences with a new blood oxygen analyzer (BOA 802, Dräger-Bio Marine) are reported. In the range up to 100 mm Hg data about 6 mm Hg to high were found compared with the AVL Gas Check. In the range between 100-300 mm Hg there was an increasing difference between values measured with the BOA 802 and a conventional oxygen electrode, however this does not seem to be of clinical relevance.


Angiography of equine metacarpus and phalanges: alterations with medial palmar artery and medial palmar digital artery ligation. Vascular supply of the equine forelimb was partially disrupted by ligation of the medial palmar and medial palmar digital arteries. Vascular architecture was evaluated before and after ligation by angiography. It was apparent from the present study that existing collaterals or newly formed collaterals, or both, were sufficient to maintain limb viability.


Virologic studies on cattle with naturally occurring and experimentally induced malignant catarrhal fever. Malignant catarrhal fever is an important disease of cattle and certain wild ruminants. It occurs in sporadic and epizootic forms in Colorado cattle. Specimens from 15 cattle with naturally occurring malignant catarrhal fever and 5 cattle with induced disease were examined for cell-free and cell-associated viruses. Enteroviruses were isolated from leukocytes of 2 cattle with field cases of the disease. A herpesvirus with characteristics of the "Movar"-type, isolated from the spleen of another steer with a field case could be propagated optimally in bovine fetal spleen cells. A cell-associated virus, forming polykaryons, was isolated in adrenal and thyroid cells from 3 cattle with experimentally induced malignant catarrhal fever. It was cultured from leukocytes, ependymal tissue, spleen, lymph node, kidney and thyroid and adrenal glands of affected cattle and remained cell-associated in 48 subsequent passages. It was inactivated by freezing and thawing and by treatment with ultrasound; its polykaryon-forming activity was inhibited by 25 mug of 5 fluoro-2' deoxyuridine/ml. This viral agent replicated in bovine fetal adrenal, thyroid, and spleen cells, but not in primary kidney cells or in MDBK, HeLa, or L cells. A representative isolate was identified electronmicroscopically as an enveloped virus, 120 to 150 nm in diameter. Structural analysis indicated that it had properties of the bovine syncytial viruses. Attempts to induce MCF in cattle with 1 of the isolates failed. A parvovirus was isolated from the jejunal lymph node of calf 72-P-293, which had the experimentally induced disease and was also infected with the syncytial virus.


Experimentally induced bovine abortion with Mycoplasma agalactiae subsp bovis. Two pregnant cows aborted 11 and 18 days after Mycoplasma agalactiae subsp bovis was inoculated into the amniotic fluids. The placentas were retained. The fetuses (approx 100 and 150 days of age) were decomposed; M agalactiae subsp bovis was recovered from several tissues of the fetuses, the placentas, and fetal fluids. The same organism was given by intraperitoneal injection to 2 other pregnant (130 and 180 days, respectively) cows. At necropsy of the latter 36 days later, placentitis was severe; M agalactiae subsp bovis was recovered from the placentas of both cows and from the fetus of 1 cow. Control cows given sterile mycoplasma cultural medium by intraamnion or intraperitoneal injection did not abort and were not infected. When first recovered from the bovine placenta and fetus, M agalactiae subsp bovis grew slowly in liquid medium and assumed bizarre colonial morphology on solidified medium. Colonies were small (0.1 to 0.5 mm) and dark and lacked halos, but they reacted specifically in the direct fluorescent antibody test with equine M agalactiae subsp bovis antiserum. After 1 or 2 subcultures, the isolates grew at a normal rate and displayed their usual colonial morphology.


Conversion of chronic staphylococcal mastitis to acute gangrenous mastitis after neutropenia in blood and bone marrow produced by an equine anti-bovine leukocyte serum. A stock strain of Staphylococcus aureus of mastitis origin, characterized by alpha-, beta-, and delta-toxins, was used to produce chronic mastitis of 20 to 300 days' duration in 6 lactating mammary quarters of 4 cows. Early acute Streptococcus agalactiae mastitis was produced in 1 additional mammary quarter of 1 cow. Equine anti-bovine leukocyte serum (EABLS) was administered to all cows by continuous intravascular drip for 12 to 32 hours. Neutropenia in blood and partial depletion of neutrophil reserve in bone marrow were produced. Chronic subclinical staphylococcal mastitis in 2 quarters of 1 cow changed to gangrenous mastitis by the 40th hour after EABLS administration and led to death of the cow. The disappearance of neutrophil leukocytes from the milk was followed by uninhibited multiplication of S aureus. Probably, staphylococcal leukocidins accelerated the destruction of neutrophils in the milk as S aureus multiplication became intensified. In another quarter of the same cow that was infected with Str agalactiae, neutrophil leukocytes were present in milk as long as 3 days after their disappearance from blood and bone marrow. This may give some indication of the extravascular life-span of the neutrophil in the udder in mastitis. The 2nd cow died at the 16th hour from the start of EABLS administration and at a time when gangrenous mastitis was in the initial stages of development. The S aureus-infected quarters of the 2 remaining cows did not become gangrenous. Administration of EABLS to these 2 cows did not significantly reduce the numbers of neutrophil leukocytes entering the milk of the 3 S aureus-infected quarters. It is concluded that continuous diapedesis of neutrophil leukocytes into the milk in chronic staphylococcal mastitis protects the gland against the development of gangrenous mastitis in the presence of a strain of S aureus capable of alpha-toxin production.


Alkaline phosphatase activities in intestinal mucosa from calves infected with Cooperia punctata and Eimeria bovis. Thirty calves 12 weeks of age raised under essentially parasite-free conditions were used to determine the effects of Cooperia punctata and Eimeria bovis (in single and combination infections) on mucosal alkaline phosphatase activities at 8 locations in the small intestine. In experiment 1, 5 calves infected with C punctata 3 weeks previously had highly significant (P less than 0.01) reductions in mucosal alkaline phosphatase activities compared with those in 5 noninfected control calves. These reductions were greatest in the 2 locations of the intestine closest to the pylorus. Infected calves had a mean of 44,356 C punctata adults present. In experiment 2, 5 calves infected with E bovis 2 weeks previously had significant (P less than 0.05) reductions in mucosal alkaline phosphatase activities compared with those in 5 noninfected control calves. These reductions were present in the caudal half of the intestine. Numerous 1st-generation E bovis schizonts were present in the caudal third of the intestine. In experiment 3, 5 calves infected with C punctata and E bovis of the same durations as in experiments 1 and 2 had highly significant (P less than 0.01) reductions in mucosal alkaline phosphatase activities in the cranial half of the intestine compared with those in the controls. These reductions were much larger than in either of the monospecific infections (experiments 1 and 2). A mean of 31,968 adult C punctata were recovered from the infected calves, and numerous E bovis schizonts were observed in the caudal third of the intestine.


Influence of a progestogen on carbohydrate histochemical and histologic features of the ampulla of the bovine uterine tube. In the present experiment, study was made of the effects of melengestrol acetate given to heifers (0.5 mg for 14 days, starting at day 15 of the estrous cycle) on carbohydrate histochemical and histologic features of the ampulla of the uterine tube (oviduct). Melengestrol acetate-treated animals had significantly (P less than 0.5) fewer fertilized ova at 3 days after mating (50%) as compared with control animals (100%). Estrussynchronization treatment with melengestrol acetate reduced the amount of cytoplasmic and nuclear extrusions from the secretory cells of the uterine tubular ampulla, but did not alter the amount or types of mucosubstances within these cells.


Ultrastructural alterations in skeletal muscle of pigs with selenium-vitamin E deficiency. Light and electron microscopic studies were made of lesions which developed in skeletal muscles of 24 of 38 young growing pigs fed a semisynthetic diet deficient in selenium and vitamin E for 13 to 59 days. The major alterations in injured fibers progressed from hyaline degeneration, with subsequent macrophagic invasion and phagocytosis of disrupted sarcoplasm, to muscle fiber regeneration by myoblastic proliferation, fusion, and differentiation into fibers with mature myofibrils. The earliest electron microscopic alterations were myofibrillar lysis and disruption, with thick filaments persisting longest. Disruption of mitochondria, sarcoplasmic reticulum, and plasma membranes occurred in fibers with myofibrillar alterations. The basal lamina of the sarcolemma remained after destruction of the enclosed sarcoplasm and served as a scaffold for subsequent regeneration. Stages of regeneration included myoblastic proliferation, fusion into cords and myotubes, and, finally, fibrillogenesis to restore contractile material. The sequence of structural alterations in skeletal muscles of these affected pigs was discussed in terms of present theories of the biochemical role of these nutrients in maintaining cellular integrity.


Effect of experimentally induced hyperketonemia on glucose metabolism of ovine brain in vivo. The effect of high concentrations of circulating acetoacetate on the uptake and utilization of glucose-U-14C was investigated in brain of fed and 7-day fasted sheep. Uniformly 14C-labeled glucose and nonlabeled acetoacetate were infused via the jugular vein while blood samples were being taken from the carotid artery and dorsal sagittal sinus. Samples were analyzed for CO2 and its specific activity, glucose and its specific activity, ketone bodies, lactic acid, plasma-free fatty acids, and plasma-immunoreactive insulin. During 1 hour of infusion of 5 mM of acetoacetate/kg/hour, there was a significant decrease (P less than 0.05) in blood glucose concentration and a significant (P less than 0.05) decrease in the uptake of glucose by the brain. Significant (P less than 0.001) arteriovenous differences across the brain in ketone body concentration were observed in both fed and fasted sheep. Also, a significant increase in plasma-immunoreactive insulin and lactate and a decrease in plasma-free fatty acids were observed. These results indicate that hyperketonemia induced hypoglycemia and reduced the uptake of glucose. It also increased the uptake of ketone bodies and increased lactate production by the ovine brain.


Evaluation of selected compounds for estrus control in the bitch. Steroidal and nonsteroidal compounds were evaluated for estrus inhibition in the bitch. Mibolerone, an anabolic steroid, was effective and appeared to be safe. The remaining compounds lacked efficacy or had extensive side effects, or both.


Effects of melengestrol acetate on reproduction in the Beagle bitch. Melengestrol acetate orally given to bitches at dose levels of 200 mug or more each day effectively inhibited estrous activity for a treatment period of 243 days and a lapsed period of more than 400 days from the preceding estrous period. The 100-mug dose of the drug, given orally once a day, starting immediately after the bitches were bred or late in gestation, had no effect on conception, pregnancy, or parturition. Gestation was prolonged in bitches given melengestrol acetate starting 1 day after breeding. Drug-polymeric implants blocked reproductive activity, and the progestogen induced cystic endometrial hyperplasia.


Effect of staphylococcal alpha-toxin pancreatitis on glucose tolerance in the dog. Acute pancreatitis was experimentally produced in dogs to study the effect of the disease on glucose tolerance. The k value (glucose disappearance coefficient measured in percentage decrease of glucose/min) calculated from the high-dose intravenous glucose-tolerance test was used to evaluate the glucose tolerance of each dog. Thirty dogs were allotted to 3 groups of 10 dogs each as follows: group I--nonsurgical control dogs; group II--surgical control dogs; and group III--pancreatitis-affected dogs. To increase their susceptibility to diabetes, 50% partial pancreatectomies and ductal catheterizations were performed on group II and III dogs. Saline solution was infused into the ductal systems of group II dogs, and staphylococcal alphatoxin was infused into the ductal systems of group III dogs to produce pancreatitis. The results indicated that (1) high-dose intravenous glucose-tolerance test was an effective tool for determining decreased glucose tolerance in dogs; (2) glucose tolerance of group III dogs was markedly decreased compared with that of group I and II dogs; (3) staphylococcal alpha-toxin produced signs of moderately severe pancreatitis; and (4) 50% partial pancreatectomy and saline solution infusion produced clinical and clinicopathologic signs of mild pancreatitis. To determine if a simplified k value (calculated using 2 or 3 blood samples) could closely approximate the standard k value (calculated using 6 blood samples), simplified k values were derived from the 5- and 60-minute blood sample values. These values closely approximated the standard k values, indicating the simplified value may be used in the clinical situation. The standard k value, however, is preferred for investigative work.


Left ventricular diastolic stiffness in dogs with congestive cardiomyopathy and volume overload. Mean functional diastolic stiffness, an estimate of the left ventricular resistance to filling during diastole, was measured in 10 normal dogs, 7 dogs with diseases causing volume overload (patent ductus arteriosus and primary mitral valve insufficiency), and 4 dogs with idiopathic congestive cardiomyopathy. It was measured as the increase in pressure during diastole (deltaP), divided by the corresponding increase in volume (deltaV). The pressure was measured at cardiac catheterization, and the volume was derived by a cineangiocardiographic method. There was no increase in diastolic stiffness of the hearts with volume overload compared with the normal hearts, but those with cardiomyopathy had a large increase, although the end-diastolic volumes in cardiomyopathy were generally less than in volume overload.


Efficacy of different feeding levels of monensin in the control of coccidiosis in broilers. The feed level of monensin which gave maximal protection from coccidial infection in broilers reared in floor pens depended on the severity of the coccidial exposure and the criteria of infection studied. With indirect seeding of pens with coccidia (light coccidial exposure), 40 ppm was as efficacious as 100 ppm in improving weight gain, lesion score, and feed conversion. Statistical analysis with direct seeding (seeder birds; severe coccidial exposure) showed that feed levels of 84 and 102 ppm gave maximal improvement of weight gain and 4-week feed conversion, respectively. Further increasing the monensin level from 100 to 121 ppm did not improve weight gain and feed conversion at 8 weeks. Conversely, the relationship of plasma pigmentation and total lesion scores to monensin feed levels indicated that increasing the dosage of monensin from 100 to 121 ppm improved the performance of the broilers on the basis of these 2 infection indicators.


Feline urological syndrome: associations with some time, space, and individual patient factors. In the Veterinary Medical Data Program, 4,111 cases of the feline urological syndrome (FUS) were identified from the abstracted records for the period March, 1964, through December, 1973. Associations between FUS and some relevant factors were evaluated by a relative risk technique, referring to the characteristics of the population of all cats seen at the 13 contributing veterinary colleges. Significant differences existed in the rates of FUS for these institutions, whereas the seasonal variations in general were similar for all institutions and years, showing a peak in March and a decrease in July-August. There was an increase in the frequency of the FUS diagnosis over the 10-year period. Persian cats showed increased risk, and Siamese cats decreased risk relative to the other breeds, and castrated males and spayed females were found to have excess risk when compared with their respective unaltered sex category; interaction from age affected the degree but not the direction of these associations. The age factor per se had risks peaking at 2 to 6 years. Finally, heavy cats showed significantly higher risk of FUS than did less heavy cats.


Scleral contact lens electrodes for electroretinography in domesticated animals. Contact lens electrodes are necessary to produce a high quality electroretinogram. Comparison of the electroretinogram recorded with the contact lens electrode and a needle electrode showed a great difference. Contact lens electrodes showed a 50 percent or greater amplitude and less artifacts. This report details the procedure for construction of the contact lens electrodes for domestic animals.


Survival of Anaplasma marginale in Aedes albopictus cells. Bovine red blood cells infected with Anaplasma marginale were introduced into cell line cultures from the mosquito Aedes albopictus. The cultured mosquito cells phagocytized both infected and uninfected red blood cells. The parasite remained viable, as determined by calf inoculations, for 21 days.


Effect of temperature on survival of free-living stages of Haemonchus contortus. One percent or more unembryonated eggs of Haemonchus contortus survived in sheep fecal pellets less than 0.5 hour at -95 C, 2 hours at -28 C, 1 hour at -10 C, 4 days at 4 C, and 1 hour at 45 C. One percent or more embryonated eggs survived 1 hour at -95 and -28C, 12 hours at -10 C, 64 days at 4 C, and 12 hours at 45 C. Over half the unembryonated and embryonated eggs survived only 1 and 4 days, respectively, at 4 C. One percent or more 1st-stage larvae did not survive 0.5 hour at -95 C but did survive 0.5 hour at -28 C, 8 hours at -10 C, 16 days at 4 C, and 1 hour at 45 C. Less than 1% of 2nd-stage larvae survived up to 2 days at -95 C; all were dead by 4 days. Second-stage larvae survived 32 days at -28 C, 8 days at -10 C, 64 days at 4 C, and 2 hours at 45 C. One percent or more 3rd-stage larvae survived 256 days at -95 C, 16 days at -28 C, 32 days at -10 C, more than 256 days at 4 C, 128 days at 20 C, 64 days at 25 and 35 C, and 4 days at 45 C. Thus, the increasing order of survival was unembryonated eggs, 2nd-stage larvae, 1st-stage larvae, embryonated eggs, and 3rd-stage larvae.


Embryological considerations of thyroid surgery: developmental anatomy of the thyroid, parathyroids and the recurrent laryngeal nerve. The surgeon planning a thyroidectomy must be prepared to find variations in three important structures in the neck. He must be prepared to find ectopic thyroid nodules above, below or lateral to the normally located thyroid gland. Any unattached nodule should be considered malignant until proved otherwise. He must identify and preserve parathyroid glands that may not lie in the typical location. He must be prepared to encounter recurrent laryngeal nerves that do not recur. The surgeon who remembers the embryology of the structures in the neck may occasionally be astonished, but never surprised.


The recurrent laryngeal nerve.

The recurrent laryngeal nerve. Nonrecurrence and variations in the ascending course of the recurrent laryngeal nerves make it essential to identify the nerve to avoid injury to it during thyroidectomy. We believe that visual identification of the nerve without undue handling is all that is necessary. The recurrent nerve is no more delicate than other similar nerves. Unilateral injury to the recurrent nerve may result in temporary hoarseness which will improve with time. Some restriction of the airway during exertion may be present. Bilateral injury to the recurrent nerves may produce initially a loss of voice without airway constriction. Later the voice may return, accompanied by serious respiratory embarrassment on exertion.


The superior laryngeal nerve.

The superior laryngeal nerve. Injury to the internal (sensory) branch of the superior laryngeal nerve during thyroidectomy is unlikely. Signs of injury are loss of sensation in the upper larynx, resulting in choking and aspiration of swallowed fluids. Injury to the external (motor) branch of the superior laryngeal nerve produces no problem of respiration, but may result in changes in the quality of the voice or even voicelessness. Injury to the external branch can be avoided if the anatomical variations are kept in mind during ligation of upper pole vessels.


Technique of parathyroidectomy.

Technique of parathyroidectomy. The goal of the surgical treatment of primary hyperparathyroidism is ablation of the proper amount of hyperfunctioning tissue. This paper presents our operative technique based on an experience in the treatment of 190 patients with primary hyperparathyroidism. The technique is based on a complete knowledge of the anatomy of the normal parathyroid gland as well as the pathology in primary hyperparthyroidism. We also propose a systematic and methodical search for possible abnormal locations incorporating a thorough knowledge of the specific embryology.


Complications associated with carotid endarterectomy. A discussion of some of the complications associated with carotid endarterectomy is presented. Accurate knowledge of anatomy is essential in preventing injury to nerves, blood vessels and other regional anatomical structures. Complications following carotid artery operation may be severe and must be avoided if possible. Indications for carotid endarterectomy are still controversial. The final decision for or against operation rests on the judgment of the vascular surgeon.


A fresh look at the intrinsic muscles of the back. The surgical anatomy of the intrinsic muscles of the back is easy to remember if the approach is systematic. There is a plan to the arrangement which can be easily learned. Without such a plan, the area will always remain a "no-man's land" for physicians and surgeons, even those who deal with many back problems.


Functional anatomy of the eyelids as related to reconstruction. Current information of eyelid anatomy and function is reviewed. This is a basis for an approach to repair of wounds and defects of the lacrimal system, medial canthal region and eyelids.


Vascular basis for a compound flap of the finger incorporating a bone graft. A defect of soft tissue and bone is closed by a primary arterialized flap. The flap was constructed to include a vascularized bone graft. The vascular anatomy of the hand permitting creation of this flap is reviewed.


An implanted electronic laryngeal prosthesis. The authors present a preliminary progress report on their investigations dealing with the development of an implanted electronic laryngeal prosthesis system. Their initial observations indicate success in the design and fabrication of the implantable, retropharyngeal transducer and secondary induction coil elements. The surgical procedure for implantation is described, and the complications encountered during the first thirteen procedures are reported. These complications included five seromas, one postoperative abscess, one partial wound breakdown secondary to animal-inflicited traumn, and two anesthetic deaths at the time of follow-up radiographic procedures. Additional observations are presented regarding the acoustical output of the transducer in air and after implantation. Projections are made concerning the use of this laryngeal prosthesis system in human patients for vocal rehabilitation after total laryngectomy.


Etiology of bilateral abductor vocal cord paralysis: a review of 389 cases. The etiology of 389 cases of partial or complete bilateral abductor vocal cord paralysis has been determined and classified. One hundred and forty-nine were infants and children 12 years of age and under; 240 were adults, age 13 and older. In the infants and children the paralyses were congenital in 82 cases, of which 43 were associated with other congenital anomalies, and 39 were without associated anomalies. Fifty-nine cases were considered acquired, most being secondary to underlying congenital anomalies, particularly the associated findings of meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. Eight cases of paralysis in this age group were of undetermined etiology. Of the 240 adult cases of bilateral vocal cord paralysis. 138 followed thyroidectomy. Fifty-two cases were associated with various neurologic disorders, including poliomyelitis, Parkinson's disease, cerebrovascular accident, Guillain-Barré syndrome, multiple sclerosis, neoplasms and other miscellaneous neurologic conditions. Sixteen cases were due to malignant neoplasms of the neck and mediastinum. The remaining 34 cases constitute a miscellaneous group which includes foreign bodies, bilateral neck dissection, infection, congenital lesions, trauma, and idiopathic paralyses. The characteristic symptoms of bilateral abductor vocal cord paralysis include normal or near normal phonation with inspiratory stridor which may progress to complete respiratory obstruction. These symptoms are due to the stationary but flaccid midline position of the vocal cords which places them in a phonating position, where they both obstruct the airway and produce a faily clear voice or cry. This paradoxical combination of symptoms was frequently found to be responsible for a failure or delay in diagnosis.


Experience with vocal cord injection.

Experience with vocal cord injection. For 14 years investigators accredited by the FDA have been injecting a Teflon - glycerin mixture into lateral-lying, paralyzed vocal cords. This paper represents a summary of the work of this author, including successes, failures, and complications; it is the largest reported series, plus that of accredited investigators. The method described is exceptionally useful; it has restored voices, laughter, the ability to strain, and has prevented aspiration. A new surgical technique involving the injection of sterile glycerin into comparable vocal cords in acute new situation is also described. This is done by direct or indirect laryngoscopy, and has been used to eliminate some tracheotomy surgery by virtue of the immediately improved cough effectiveness.


Recurrent laryngeal nerve section for spastic dysphonia. Spastic dysphonia is a severe vocal disability in which a person speaks with excessively adducted vocal cords. The resulting weak phonation sounds tight, as if he were being strangled, and has also been descrived as laryngeal stutter. It is often accompanied by face and neck grimaces. In the past it has been regarded as psychoneurotic in orgin and treated with speech therapy and psychotherapy with disappointing results. Because of laboratory and clinical observation that recurrent nerve paralysis retracts the involved vocal cord from the midline, it was proposed that deliberate section of the recurrent nerve would improve the vocal quality of patients with spastic dysphonia. In 34 patients the recurrent nerve was sectioned after Xylocaine temporary paralysis showed significant improvement in vocal quality. Several patients have been advised against this operation because of the type of voice they developed with one vocal cord temporarily paralyzed. With nerve section plus postoperative speech therapy, approximately half of the patients have returned close to a "normal" but soft phonatory voice. The rest had varying degrees of improvement, but all, so far, have been pleased with the improvement in ease and quality of phonation and reduction or elimination of face and neck grimaces. Two men have a breathy component in their phonatroy voices, and one woman has variable pitch.


Fiber components of the recurrent laryngeal nerve in the cat. Experimental neuroanatomical methods were employed in 21 adult cats to determine 1) the number and size of myelinated motor and sensory fibers in the recurrent laryngeal nerve (RLN), and 2) the fiber components originating in the nucleus ambiguus (NA) and retrofacial nucleus (RFN) of the brain stem. Intracranial transection of the X and XI cranial nerves and selective destruction of the NA or RFN were the experimental lesions inflicted in order to obtain the following results. About 55% (312) of the right RLN  (565 fibers) is composed of myelinated motor nerve fibers which measure 4 mu - 9 mu in diameter. Nine percent come from the RFN and are smaller (4-6 mu) than the 46% which emanate from the NA and measure 6-9 mu in diameter. The remaining 45% of the RLN is made up of sensory neurons which can be divided into three groups. 1) The largest numerical group (32%) is very small in caliber (1-3 mu) and supplies extralaryngeal regions (trachea, esophagus). 2) The intermediate size fiber group (4-9 mu) comprises 11% of the RLN and probably supplies the subglottic mucosa. 3) The smallest group (2%) of sensory fibers is the largest in diameter (10-15 mu) and may represent either the innervation of muscle spindles or afferents from the superior laryngeal nerve coursing down into the chest.


Otolaryngological manifestations of arthrogryposis multiplex congenita. The important otolaryngological manifestations of arthrogryposis multiplex congenita (AMC), which heretofore have not been described in otolaryngological and other specialty journals, are reviewed. Thirty-seven patients with AMC were studied. Nine of these patients with neurogenic AMC, had otolaryngological manifestations. Six of these had Pierre Robin-like syndromes. Seven patients had severe dysphagia and aspiration pneumonitis. Five patients had voice changes, and three of these required tracheotomy to relieve laryngeal obstruction and prevent aspiration. Two of these patients were aphonic and had laryngeal paralysis. Three of the nine patients who had laryngeal examination showed supraglottic narrowing similar to laryngomalacia. Six patients with otolaryngological problems were autopsied, and two had pharyngeal biopsies. The histological examination demonstrated normal laryngeal and pharyngeal musculature. The cricoarytenoid joints were found normal in all the larynges examined. Central nervous system dysfunction rather than simple muscle weakness, caused the dysphagia and respiratroy difficulties in patients with neurogenic AMC. Dysphagia with aspiration was the single most important cause of death in approximately 20% of patients with AMC. A tracheotomy and feeding gastrostomy appears essential for successful management of the otolaryngological complications of AMC.


Congenital laryngeal defects in the adult. Two types of congenital laryngeal defects in the adult are presented. The first case is a patient with a laryngeal cleft who became symptomatic at 42 years of age. Dysphagia, dyspnea, hoarseness and aspiration progressed in severity until surgery was necessary at the age of 48 years. The second case presented is a 21-year-old male with nonfusion of the thyroid laminae. He was asymptomatic except for persistence of a high-pitched voice after puberty. The case histories and radiographic studies are reviewed, emphasizing that the diagnosis of these defects was more difficult than their management. The surgical repair is described and illustrated. Briefly, this involved repair of the laryngeal cleft using techniques similar to those of a hernoiorrhaphy. The nonfusion of the thyroid laminae and resultant defective anterior glottis was repaired using bipedicled muscle flaps and a silicone keel.


Granular cell tumors of the larynx.

Granular cell tumors of the larynx. Granular cell tumors of the larynx are relatively uncommon, always benign, and most commonly located in the posterior portion of the larynx. They are easily identified and should be differentiated from other lesions. A possible problem in the differential diagnosis is the presence of pseudoepitheliomatous hyperplasia, which overlies the granular cell tumor and which may mimic squamous cell carcinoma. Careful histopathologic differentiation is important because the laryngeal granular cell lesion should be managed conservatively, with transoral local excision usually being adequate. The histogenesis of these lesions remains in doubt, with a neural or epithelial derivation being the most likely possibility.


Recurrent respiratory papillomatosis: management with the CO2 laser. Recurrent respiratory papillomatosis is most common in childhood but it affects all age groups; it represents a diathesis of the aerodigestive tract so that lesions amy develop at various sites - the nares, lips, pharynx, nasopharynx, larynx, tracheobronchial tree, approximately one-third of patients for one year or more; since relapses amy occasionally occur 2 to 20 years later, cure can never be assumed. At the present time, management is directed towards total ablation of all visble papilloma consistent with preservation of the airway and voice; reduction of the tumor burden to minimal proportions is thought to allow the maximum opportunity for remission. As the host-papilloma relationship is unraveled, it may be possible in the future to provoke an immune response so that remissions can be predicted and produced consistently.


Dinitrochlorobenzene skin sensitization and peripheral lymphocyte count: predictors of survival in head and neck cancer. Dinitrochlorobenzene (DNCB) is a simple chemical useful to evaluate both afferent (sensitizing) and efferent (reacting) limbs of the delayed, cell-mediated immune system. This system invokes the small lymphocyte (T cell) and is apparently part of the host defense against cancer. Severnty-two patients with new primary squamous cell carcinomas of the larynx, hypopharynx and oropharynx were sensitized to DNCB by contact application, and delayed cutaneous hypersensitivity tested. The T cells were also assessed in this study by lymphocyte count. All patients were treated for cure. Ninety-one percent of DNCB reactors were alive and tumor-free at two years. Forty-five percent of negative reactors had recurrent tumor and died of carcinoma. Cases grouped by site among glottic, supraglottic and inferior hypopharynx showed identical results. Lymphocyte counts showed a trend in the same direction. On statistical analysis, all differrences were significant. Eighty-five percent of recurrent tumors occurred in patients who were nonresponders. The present data suggest DNCB reactivity is helpful in predicting outcome after surgery, or combined radiation and surgery, for mucosal squamous carcinoma of the head and neck.


Laryngeal suspension and epiglottic flap in laryngopharyngeal trauma. Physicans treating laryngeal trauma are still looking for ways to improve results. Severe disruption of the supporting structures between hyoid and trachea may allow stretching and narrowing of the laryngeal lumen during the healing period. This can easily be prevented by placing wires across the disrupted zone. In addition, loss of the epithelial lining of the larynx is a serious cause of stenosis. By dissecting out the epiglottic cartilage, one can create a sizeable, useful flap of mucous membrane based in the vallecula to use in relining of the anterior larynx.


Osteoplastic frontal sinusotomy: an analysis of 250 operations. The operative approach and findings of 250 osteoplastic frontal sinusotomy operations performed from 1956 through 1972 at the Massachusetts Eye and Ear Infirmary are reviewed. Indications for surgery were symptomatic and/or complicated disease of the frontal sinus, including primary chronic sinusitis and osteoma or trauma with or without associated infection. Immediate postoperative complications were minor. Follow-up of at least three years was obtained in 83% of the patients, and 93% of these have no significant symptoms to date. A distressing problem of persistent postoperative frontal pain is discussed in detail. Revision surgery has been performed in 6% of patients due to recurrent frontal sinus infection. The reasons for failure are anlyzed, and recommendations are made to minimize the possibility of recurrence.


Verrucous carcinoma of the larynx management by radiotherapy and surgery. Verrucous carcinoma is an unusual and distinct variant of well differentiated squamous cell carcinoma, and accounts for approximately 1 to 2% of all primary squamous cell carcinomas of the larynx. There has been considerable controversy regarding the role of radiotherapy in the managment of these tumors as they are said to be radioresistant, and in a number of instances "anaplastic transformation" has apparently occurred following such therapy. We have reviewed 18 patients with verrucous carcinoma of the larynx in which eight received surgical therapy alone, eight received radiotherapy alone, and two received combined therapy. We conclude that radiotherapy and surgery are equally effective in eradicating the disease. "Anaplastic transformation" of these tumors represents a small but nevertheless real risk following radiotherapy. Accordingly, our current therapeutic policy is to treat by surgical excision those smaller tumors which can be removed by conservation laryngectomy procedures, reserving radiotherapy for those large tumors which would require total laryngectomy if treated surgically.


Activity of sulfamethoxazole and trimethoprim against Bacteroides fragilis. Minimum inhibitory concentrations (MICs) of sulfamethoxazole (SMX) and trimethoprim (TMP), alone and in three combinations, 20:1, 1:1, and 1:20, were determined on Diagnostic Sensitivity Test (DST) and Mueller-Hinton (MH) agars containing lysed blood for various inocula of 91 strains of Bacteroides fragilis from the U.S.A. and U.K. MICs of SMX were high with large inocula and higher on MH than DST, but results for TMP were less affected by these two factors. True SMX resistance was rare: 10 U.S.A. strains previously reported as resistant appeared to be susceptible. Maximum potentiation of MICs was observed when SMX and TMP were combined in ratios close to those of the ratios of their MICs, that is, SMX/TMP 20:1 for large inocula and the reverse for small inocula for determinations on DST and usually 20:1 for all inoculum sizes on MH. These observations explain some of the discrepancies in reports, but defer the problem of potential usefulness of the drugs in the treatment of infection with anaerobes to future study.


Cefuroxime: human pharmacokinetics..

Cefuroxime: human pharmacokinetics.. Single doses of cefuroxime, a new parenteral cephalosporin, were given to 44 normal male subjects. Doses of 0.25, 0.5, 0.75, or 1.0 g were given intramuscularly to 33 volunteers. Mean peak serum concentrations of 14.8, 25.7, 34.6, and 40.0 mug/ml were assayed at 29 to 45 min, and measurable levels were present 8 h after the 0.5-g and higher doses. Single intravenous bolus doses of 0.25, 0.5, or 1.0 g were given to nine volunteers, and mean levels of 39, 66, and 99 mug/ml were assayed at 3 min. The antibiotic has a mean ultimate serum half-life of 70 min, a mean serum protein binding of 33%, a metabolic stability of greater than 95%, an apparent distribution volume of 11.1 to 15.8 liters/1.73 m(2) depending on dose, and a mean urinary recovery of at least 95% for all parenteral doses. The cefuroxime/creatinine clearance ratios for all volunteers indicated that 43 to 54% of the antibiotic is secreted through the kidney tubules, and this was confirmed in some volunteers who received probenecid simultaneously. The injections by both routes were well tolerated, and the slight pain experienced after intramuscular injection disappeared within a few minutes. Physical and laboratory investigations in the volunteers showed that administration of cefuroxime had had no adverse effects. There was no evidence of absorption after oral administration.


Ribonucleic acid synthesis dependent on exogenous triphosphates in nystatin-treated cells of of Kluyveromyces latis. Kluyveromyces lactis cells treated with nystatin became permeable to ribonucleoside triphosphates. Although not viable, nystatin-treated cells were capable of sustaining ribonucleic acid synthesis. The system depended on the presence of divalent ions and the four nucleoside triphosphates, and was strongly stimulated by ammonium sulfate. The system utilized endogenous deoxyribonucleic acid as template. Synthesis of ribonucleic acid was associated with the cells and probably occurred internally.


Active immobilized antibiotics based on metal hydroxides. The water-insoluble hydroxides of zirconium (IV), titanium (IV), titanium (III), iron (II), vanadium (III), and tin (II) have been used to prepare insoluble derivatives of a cyclic peptide antibiotic by a facile chelation process. Testing of the antibacterial activities of the products against two gram-positive and two gram-negative bacteria showed that in the majority of cases the water-insoluble antibiotics remained active against those bacteria susceptible to the parent antibiotic. The power of the assay system has been extended by the novel use of colored organisms to aid determinations where the growth of normal organisms could not be distinguished from the appearance of the supporting material. Insoluble derivatives of neomycin, polymyxin B, streptomycin, ampicillin, penicillin G, and chloramphenicol were prepared by chelation with zirconium hydroxide, and these derivatives similarly reflected the antibacterial activities of the parent compounds. Several of the metal hydroxides themselves possess antibacterial activity due to complex formation with the bacteria. However, the use of selected metal hydroxides can afford a simple, inexpensive, and inert matrix for antibiotic immobilization, resulting in an antibacterial product that may possess slow-release properties. The mechanisms by which the metal hydroxide-antibiotic association-dissociation may occur are discussed.


Antibacterial activity of selected beta-lactam and aminoglycoside antibiotics against cephalothin-resistant Enterobacteriaceae. The in vitro antibacterial activity of four beta-lactam antibiotics (cefatrizine [BL-S640], cefamandole, cefoxitin, and carbenicillin) and three aminoglycosides (amikacin, gentamicin, and tobramycin) was determined against 197 strains of cephalothin-resistant Enterobacteriaceae. Eighty strains were found to be gentamicin-sensitive, and 117 were found to be gentamicin-resistant. Carbenicillin was the most active beta-lactam antibiotic against gentamicin-sensitive Serratia marcescens and Enterobacter spp. Cefoxitin was the most active beta-lactam antibiotic against the remaining gentamicin-sensitive and -resistant Enterobacteriaceae, including Providencia stuartii and indole-positive Proteus spp. Cefatrizine exhibited little activity against the organisms studied. Cefamandole was less active than cefoxitin and carbenicillin. Amikacin was the most effective agent in vitro. With the exception of S. marcescens, cefoxitin appeared to be the next most promising agent in vitro against gentamicin- and cephalothin-resistant Enterobacteriaceae.


Mecillinam, a novel penicillanic acid derivative with unusual activity against gram-negative bacteria. The in vitro activity of mecillinam, a 6 beta-amidinopenicillanic acid derivative, was investigated. Mecillinam is not active against most gram-positive coccal or bacilliary forms. Many members of the Enterobacteriaceae are inhibited, with 86% of Escherichia coli, 71% of Klebsiella, 62% of Enterobacter, 75% of Salmonella, 69% of Shigella, and 70% of Citrobacter inhibited by 6.3 mug/ml. Indole-positive Proteus and Serratia were generally resistant as are Pseudomonas strains. Although mecillinam is hydrolyzed by gram-negative beta-lactamases, the compound inhibits beta-lactamase-producing organisms, particularly E. coli. The conductivity of medium used to determine minimal inhibitory concentration and inoculum size produce markedly different values. In medium of high conductivity, 10 mS, mecillinam is inactive against many strains of bacteria. In all media there is a great difference between the minimal inhibitory and minimal bactericidal levels.


Cefatrizine (SK&F 60771), a new oral cephalosporin: serum levels and urinary recovery in humans after oral or intramuscular administration--comparative study with cephalexin and cefazolin. Cefatrizine (SK&F 60771), a new broad-spectrum cephalosporin, was administered in a 0.5-g dose either orally or intramuscularly to volunteers in a crossover study. After oral administration, the average peak serum levels were 5.6 and 22.1 mug/ml for cefatrizine and cephalexin, respectively. The serum half-life of cefatrizine appeared to be more extended than that of cephalexin. Urinary recovery of cefatrizine (35%) was approximately half that of cephalexin (68%) after oral administration. After intramuscular injection of 0.5 g, the average peak serum level of cefatrizine (12.0 mug/ml) was approximately one-fourth that of cefazolin (44.0 mug/ml). The serum half-life after intramuscular injection was 86 min for cefatrizine and 118 min for cefazolin. Urinary recovery was 45% of the intramuscularly administered dose, as compared with cefazolin, which was 74%.


Comparison of direct and standardized disk diffusion susceptibility testing of urine cultures. A comparison between direct and standardized disk diffusion tests was made on a total of 300 urine specimens containing >/=10(5) organisms/ml. Of these, 246 represented pure cultures and 54 represented mixed cultures. The number of major discrepancies per organism tested in pure culture was 18 (7.3%) and in mixed cultures it was 23 (42.6%). The percentage of major discrepancies per total number of antimicrobial drug comparisons made was 1.4%. Although this procedure may be of value in selected cases with pure cultures of organisms present in quantities >/=10(5)/ml, its use on a routine basis is not recommended.


Nephrotoxicity of cephalosporin-gentamicin combinations in rats. TO STUDY THE POSSIBILITY THAT CEPHALOSPORINS AUGMENT THE NEPHROTOXICITY OF GENTAMICIN, GROUPS OF RATS WERE GIVEN FOUR HOURLY SUBCUTANEOUS DOSES OF: gentamicin (5 mg/kg), gentamicin plus cephalothin (100 mg/kg), gentamicin plus cefazolin (20 mg/kg), gentamicin plus cefazolin (50 mg/kg), gentamicin plus cephaloridine (50 mg/kg), or saline diluent for 15 days. Periodic measurements were made of urine volume, urine osmolality, urine protein excretion and lysosomal enzymuria, as well as blood urea nitrogen, creatinine clearance, and drug concentrations in renal cortex and medulla. Tissue was examined by light and electron microscopy. Enzymuria and proteinuria increased early in the course of all treatment groups, whereas urine osmolality declined. No distinct patterns of these variables were discernable among the groups. Gentamicin alone, gentamicin plus cephalothin, and gentamicin plus cefazolin (20 mg/kg) caused the same significant fall in glomerular filtrate rate from control values by day 15 (P < 0.05). Gentamicin plus cefazolin (50 mg/kg) and gentamicin plus cephaloridine failed to cause a decline in glomerular filtration rate compared with controls (P > 0.05). Gentamicin concentrations in renal cortex were 5 to 10 times higher than those in medulla in all groups. Cephaloridine and cefazolin (50 mg/kg) also displayed a gradient pattern in renal cortex, whereas cephalothin and cefazolin (20 mg/kg) did not. Cytosegrosomes with myeloid figures were characteristic ultra-structural changes seen in all groups; however, they tended to be smaller with less numerous myeloid bodies in the groups receiving gentamicin plus cephalothin, cefazolin (50 mg/kg), or cephaloridine. Cephalosporins did not augment gentamicin toxicity. High doses of cefazolin and cephaloridine protected kidneys from gentamicin nephrotoxicity. The protection may involve intracellular drug interaction within the renal cortex.