An anatomic-arthrographic study of the relationships of the lateral meniscus and the popliteus tendon.

The anatomy of the posterior lateral knee joint is studied through photography and radiography of plastic corrosion casts of the knee joint. The images thus obtained are compared to in vivo arthrograms. This anatomic-arthrographic correlation  clearly demonstrates how the bursal extensions of the joint space about the popliteus tendon dictate the location and arthrographic appearance of the peripheral attachments of the posterior lateral meniscus. The casts also serve to illustrate a discussion of anatomic variation, embryology, and function of the popliteus apparatus. The largely unappreciated direct action of the popliteus muscle on the lateral meniscus is emphasized.


Comparison of radiographic abnormalities of the sacroiliac joint in degenerative disease and ankylosing spondylitis.

Degenerative disease of the sacroiliac joint is common in middle-aged and elderly patients. Its radiographic features simulate those of ankylosing spondylitis. Interosseous space narrowing, subchondral sclerosis, and osteophytosis are apparent. Although intraarticular bony ankylosis is generally absent, anterior paraarticular bridging osteophytes resemble true osseous fusion of the joint cavity on frontal radiographs. Focal sclerosis in degenerative disease is most common on the superior and inferior margins of the articular cavity and can usually be differentiated from that accompanying ankylosing spondylitis and osteitis condensans ilii.


Double-blind evaluation of glucagon and propantheline bromide (pro-banthine) for hypotonic duodenography.

The hypotonic effect of glucagon (2 mg) and propantheline bromide (Pro-Banthine, 30 mg) on the upper gastrointestinal tract was compared in a double-blind study in 12 healthy volunteers and 36 patients. The solvent solution for the two drugs was used as a placebo. Both drugs and placebo were administered intramuscularly. The time of onset of the hypotonic effect was similar for both drugs, with maximum effect achieved 10 min after injection. Effects of glucagon dissapeared rapidly after 30 min, while Pro-Banthine still retained 50% of its maximum effect 2 1/2 hr after injection. Side effects of Pro-banthine were related to the long duration of the hypotonic effect (4-6 hr). A significant placebo effect on the duodenal C loop was observed. Glucagon appears to be the drug of choice since its hypotonic and hypomotile effects on the gastrointestinal tract are comparable to propantheline bromide while having the advantage of shorter duration and practically no side effects.


Invasion of the duodenum by carcinoma of the stomach.

It has frequently been stated that extension to the duodenum occurs commonly in patients with gastric lymphoma but almost never in those with carcinoma of the stomach. We found radiographically detectable invasion of the duodenum in six of 111 consecutive patients (5%) with gastric carcinoma. The duodenum was involved microscopically in 18%. Radiographic abnormalities in the duodenum in 11 patients with proven transpyloric spread of tumor varied from irregularity of the base of the bulb narrowing and distortion extending well into the second portion of the duodenum. On the basis of these data and the reported frequency of transpyloric extension in gastric lymphoma, carcinoma appears to be the more likely diagnosis in a patient with duodenal involvement by an antral tumor.


Bacteremia and the barium enema.

To investigate the possible association of bacteremia with barium enema examinations, blood samples were obtained from 42 patients before and at 5, 10, and 20 min after administration of the enema. Patients with fever or symptoms suggestive of inflammatory bowel disease were not included in the study; neither were patients who had received antimicrobiotic medication during the preceding 3 months. Pour-plate blood cultures showed no bacteremia due to enteric organism in the 42 patients-a result at variance with previously published reports.


Gas-filled appendix: lack of diagnostic specificity.

Three patients with a gas-filled appendix in association with acute abdominal symptoms are described. In each case the gas-filled appendix was located in the right lower quadrant. None of the patients had appendicitis. It is emphasized that this combination of findings is not neccessarily diagnostic of appendicitis. Clinical evaluation is important in assessing the significance of this sign.


Double-blind comparison of meglumine iodamide and Renografin-60 for excretory urography.

A double blind comparison of meglumine iodamide and Renografin-60 in bolus intravenous pyelography, using 50 ml of contrast or less, was conducted in 78 patients. Meglumine iodamide produced more dense opacifications, but it also produced a greater number of laboratory abnormalities. All were transient and mild. No serious abnormalities resulted from the use of either agent.


The radiology of ex vivo renal perfusion and autotransplantation.

The radiologic findings in 16 patients subjected to ex vivo renal perfusion and autotransplantation are reviewed. Preoperative excretion urography and renal arteriography are essential to define ureteral and arterial anatomy; renal scintiangiography and renography are useful for baseline studies. Plain radiographs should be obtained during nephrolithotomy. Intraoperative renal arteriography should be reserved for patients who require more precise definition of vascular anatomy or verification of adequate repair after a difficult dissection. Postoperative scintiangiography is required on the first day to exclude arterial occlusion. Renography and urography to evaluate autotransplant anatomy and function should be deferred for about 3 weeks, unless there is clinical evidence of a complication.


Micro-balloon catheter for superselective angiography and therapeutic occlusion.

A miniature (0.5 mm) flow-directed balloon catheter with two different silastic balloon tips has been developed. One tip is used for perfusion; the other can be inflated and released to produce vascular occlusion. Examples of the developmental work in dogs and clinical use in patients are presented.


Polarized projection of stereo cerebral angiograms for audience viewing.

A simple and inexpensive method for producing stereo angiographic images for projection to large audiences is presented. Two 35 mm images are produced using a conventional reflex camera and direct positive film. When properly taken, these film chips can be mounted in stereo mounts and projected using a polarized light stereo projector.


Anatomic, clinical, surgical, and radiographic correlation of the zygomatic complex fracture.

Understanding the mechanisms by which clinical signs and symptoms are produced is a prerequisite to the correct appreciation of radiographic features. Radiographs of facial trauma are no different in this respect. This paper describes the specific clinical findings associated with each displaced bony fragment of the zygomatic complex fracture. Limitation of jaw movement and flattening of the cheek are produced by depressed fractures of the temporal process or zygomatic arch; unilateral epistaxis is a result of fractures of the zygomatic process of the maxilla or the floor of the orbit; paresthesia or anesthesia of the cheek results from fractures of the infraorbital process or orbital floor; unequal pupil heights is associated with fracture of the frontal process; and decreased extraocular muscle function with diplopia is caused by fractures of the orbital process, frontal process, or orbital floor. The clinical and radiographic findings are correlated with surgical management.


Cardiopulmonary dimensions: stability over a long period.

The transverse diameter of the heart, diameters of the basal arteries, lung height and width, and diaphragm level were measured from two radiographs obtained 10-34years apart in 100 normal subjects. No difference was found in basal artery diameters, lung height, or diaphragm level. Lung width increased slightly. Transverse diameter of the heart increased slightly (0.43 cm) but significantly. This increase was not related to the age of the subject and had a low linear correlation with the interval between radiographs. In eight subjects, the heart diameter increased by more than 1.5 cm. Age is not an important factor in judging heart size from the transverse diameter on chest radiographs.


Angiocardiography after total correction of tetralogy of Fallot using large homograft arteries.

Postoperative angiocardiographic findings were examined in eight patients whose pulmonary artery was reconstructed using an aortic or pulmonary homograft with valve. Apparent dilatation of the outflow tract of the right ventricle was seen in three patients. Only four showed valve mobility, with function judged almost normal in two of them. Calcification in a valve was not seen. The pulmonary trunk showed three directional patters, and stenosis was clearly observed in two cases. calcification of the pulmonary trunk was seen in only one case. The most difficult problem in the reconstruction of the pulmonary artery is the high incidence of pulmonary stenosis.


Angiocardiography of obstructing muscular bands of the right ventricle.

Two types of obstructing anomalous muscle bundle are described on the basis of right ventricular angiocardiographic analysis in 28 patients. In the low type the anomalous muscle bundle is located in the midsinus of the right ventricle; in the high type it lies at the subinfundibular level. Ocassionally, both forms of obstruction exist in the same individual. A ventricular septal defect was present in 24 of the 28 patients (85%). Serial catheterizations at a mean interval of 6.6 years demonstrated progession of the obstruction in eight of 15 patients. Differentiation of anomalous muscle bundle from tetralogy of Fallot is facilitated by clear angiographic delineation of the anomalous muscle and the position of the parietal band in most cases, but may not be possible when both anomalies occur together.


Single coronary artery from the right sinus of Valsalva: angiography, anatomy, and clinical significance.

A case of single coronary artery from the right sinus of Valsalva with a connecting branch passing between the aorta and right ventricular infundibulum is described. The anomaly was demonstrated at coronary arteriography and verified at surgery. This type of single coronary artery has been associated with sudden exertional death in young persons. The case prompted a review of the classification of single coronary artery with emphasis on clinical significance of the various subtypes and angiographic findings.


Effect of o-(beta-hydroxyethyl)-rutoside in lymphangiography.

In 30 patients who underwent lymphography of the retroperitoneal lymph nodes, the lymph vessels of one leg were pretreated with 5 ml of 10% o(beta-hydroxyethyl)-rutoside (HR) prior to administration of Lipiodol Ultrafluid. There were no untoward clinical effects associated with the pretreatment. Legs pretreated with HR showed significantly fewer extravasations of contrast material than those untreated. HR appears to reduce the permeability of the lymph vessels, thus preventing or diminishing the occurrence of extravasations.


Ultrasonic aortography: unexpected findings.

In a series of 125 patients examined ultrasonically for suspected abdominal aortic aneurysms, 15 patients (12%) had intraabdominal abnormalities unrelated to the aorta. In 12 of these patients, a retroperitoneal malignancy clinically mimicked an aneurysm. In the remaining three, other abnormalities were discovered in addition to an aneurysm. In one patient, a large uterine myoma was visualized; in another, large retroperitoneal lymph nodes subsequently proved to be lymphoma; in the third, enlarged lymph nodes in association with a carcinoma of the colon were discovered. Because of the high incidence of unsuspected findings, ultrasonography should become an essential part of the evaluation of this group of patients.


Gray scale ultrasound and isotope scanning: complementary techniques for imaging the liver.

Technical advances in gray scale ultrasound have led to better signal-to-noise ratios and improved resolution. A display of the texture of the liver is now possible, making ultrasound an important complementary technique to radioisotope scanning. In the positive radioisotope scan, ultrasound permits differentiation of isotopically cold areas into neoplasms, benign cysts, and abscesses. In addition, when the radioisotope scan is equivocal, ultrasound is invaluable in differentiating normal variants from disease states. Dilated intrahepatic ducts can also be identified. Examples of the use of ultrasound in defining radioisotope abnormalities are presented.


New trends in the treatment of breast cancer at the Cancer Institute of Milan.

Preliminary results from three trials on breast cancer treatment carried on at the National Cancer Institute of Milan are presented. In the first trial, radical mastectomy (105 patients) was compared to a more conservative procedure consisting of breast resection, axillary dissection, and radiation therapy (125 patients). Axillary metastases were found in 22% and 25% of the two groups, respectively. After 30 months, two local recurrences have occurred, one in each group. Four patients in the radical mastectomy group have developed distant metastases. In the second trial, carried out on patients with nodal involvement, radical mastectomy (179 patients) was compared to radical mastectomy followed by a prolonged combination chemotherapy using cyclophosphamide-methotrexate-fluorouracil (207 patients). After 27 months, recurrences have occurred in 24% of the patients treated only with radical mastectomy compared to 5.3% in those treated with radical mastectomy plus chemotherapy. In the third trial, 67 patients with inoperable breast cancer were treated with chemotherapy plus radiation therapy. Recurrences occurred at a lower rate than observed in a previous series of patients treated with radiotherapy alone.


The role of interstitial therapy in present day radiotherapy.

The role of interstitial therapy in the treatment of malignant tumors is discussed. With interstitial therapy, the tumor is accurately localized under general anesthesia, irradiation is limited to the tumor-bearing volume of tissues with minimal irradiation of normal structures, and treatment time is shorter than with external beam therapy. Disadvantages include its rather limited clinical application, more complicated dosimetry, the higher level of technical skill required in the surgical procedure, and radiation exposure of operator and personnel. Interstitial therapy is indicated for relatively small well differentiated primary tumors and in cases where the primary and lymph node metastases are in close proximity. A combination of interstitial and external beam therapy is recommended for advanced tumors and in cases of unsatisfactory implants. Seven illustrative cases are presented. It is recommended that improved afterloading techniques and surgical and nonsurgical procedures (e.g.,suspension laryngoscope) be developed so that this type of therapy can be extended to all cases requiring high doses and a small volume of radiation.


IgD myeloma with myelofibrosis and amyloidosis.

Two patients with IgD myeloma protein and lambda light chains are described. They had marked Bence Jones proteinuria, were treated with melphalan, prednisone, and allopurinol and died in less than one year. At autopsy, there was extensive myelofibrosis associated with neoplastic infiltrates of plasma cells in both cases. On electrophoresis, the serum and urine Bence Jones protein of one patient migrated in the alpha2 region, and the blood vessels of the other patient contained many nodular deposits of amyloid. Because these findings are rare in multiple myeloma, they may be unique to IgD myeloma.


Tuberculous infection in a vascular prosthesis: a case of aortic graft infection resulting from disseminated tuberculosis.

Insertion of an aortic prosthetic bypass graft in a patient with untreated disseminated tuberculosis resulted in graft infection with formation of a pseudoaneurysm. Microbiologic cultures implicated Mycobacterium tuberculosis as the causative agent, and a subsequent review of the literature indicated this report to be the first clinical demonstration of the susceptibility of vascular prosthesis to M tuberculosis infection to our knowledge.


Delayed perforation of the innominate vein during hyperalimentation.

Mechanical complications of central vein catheterization for hyperalimentation typically become manifest shortly after insertion. We present a case report describing a delayed innominate vein perforation by a central venous catheter. Use of the adult internal jugular vein for central venous catheterization should be limited to situations in which a subclavian vein is unavailable. Ongoing watchfulness and a vigorous diagnostic and therapeutic approach to such complications are mandatory in the treatment of patients receiving total parenteral nutrition.


Sodium valproate and clonazepam in the treatment of intractable epilepsy.

Of 88 patients with intractable epilepsy, 60 have been treated with clonazepam for up to three years and 60 have been treated with sodium valproate for up to 18 months. Each agent was used sequentially in an overlapping group of 32 patients. Both agents have proven effective in the control of petit mal absences and myoclonic jerks, although some patients responded to one and not to the other. Clonazepam has given better results than valproate in temporal lobe and other partial (focal) epilepsies, while valproate has given better results in grand mal seizures and atonic attacks. Both preparations were more effective in patients with spike and wave paroxysms in their EEG recordings, the correlation being more conspicuous with valproate. Both medications appear to be safe and useful additions to anticonvulsant therapy.


Regeneration of cartilage in the monkey auricle after subperichondrial resection.

Cartilage regeneration was histologically evaluated in vivo in the squirrel monkey pinnae. Only 2 of 11 ears exhibited evidence of cartilage regeneration (Movat stain) within the subperichondrial area, eight to nine weeks postoperatively. The present experimental results in squirrel monkeys contradict the previously reported high incidence of ear cartilage regeneration in young rabbits and may reflect a difference in surgical technique, animal species, or animal age.


Pericarditis in diabetic ketoacidosis.

A 25-year-old insulin-dependent diabetic man who was admitted to hospital with severe diabetic ketoacidosis and dehydration showed sequential electrocardiographic abnormalities of acute pericarditis. Though the patient had retrosternal chest pain, no pericardial friction rub was heard. None of the usual causes of pericarditis was found and the electrocardiographic abnormality may have been attributable to subepicardial injury caused by dehydration associated with the ketoacidosis. The abnormalities on the electrocardiogram were transient, returning to normal after 5 days. Whatever the exact underlying nature of the pericarditis, it is important to recognise that such transient changes may occur as, in the absence of other obvious causes of pericarditis, the condition is benign.


Effects of nitroglycerin, postextrasystolic potentiation, and pacing-induced ischaemia on wall motion in patients with ischaemic heart disease.

The influence of nitroglycerin, postextrasystolic potentiation, and rapid ventricular pacing on total and regional ventricular function was studied in 32 patients with normal ventricular function and in 44 patients with left ventricular asynergy caused by obstructive coronary artery disease. Total ventricular function was assessed by ventriculography and regional ventricular function was analysed by use of 7 hemiaxes. Nitroglycerin increased ejection fraction and decreased left ventricular systolic and end-diastolic pressures in the normally functioning ventricles; apical wall motion increased, while basal wall motion remained unchanged after nitroglycerin in these ventricles. Pressures fell significantly in ventricles with asynergy after nitroglycerin; ejection fraction decreased while wall motion in asynergic areas was inconsistently influenced. Postextrasystolic potentiation augmented ejection fraction by a powerful and homogeneous increase of wall motion in normally functioning ventricles. Asynergic areas and normal areas in diseased ventricles showed identical augmentation of wall motion after a premature beat. Rapid venticular pacing produced a significant increase in end-diastolic pressure and a fall in ejection fraction in patients with obstructive coronary artery disease. Wall motion in normal areas perfused by arteries with critical stenoses was dramatically depressed after pacing, while asynergic areas and normal areas perfused by normal arteries remained unchanged. The results show that normal contractile behaviour can be detected by postextrasystolic potentiation in asynergic areas, suggesting that some normally perfused muscle exists in these areas. Pacing stress does not further deteriorate function in asynergic areas, which suggests the presence of viable and well perfused muscle (within scar tissue) whose function may not profit from revascularization. Pacing-induced asynergy identifies the functional significance of coronary stenoses and suggests that bypass surgery might be beneficial.


Nitrite reductase system involved in the terminal oxidation of the Streptomyces griseus respiratory particle.

A nitrite reductase system which was associated with the electron transfer system of the respiratory particle in Streptomyces griseus was studied. The electron transfer pathway consisted of the cytochrome oxidase and the nitrite reductase systems under aerobic and anaerobic conditions respectively, and these systems showed the exact opposite response to 2-n-heptyl-4-hydroxyquinoline-N-oxide and azide. Azide inhibited specifically the nitrite reductase system. It seems that cytochrome d works as the nitrite reductase and the reduced cytochrome b works as an intermediate electron donor for cytochrome d respectively. The respiratory particle also had a hydroxylamine reductase activity and ammonia was identified as the product of hydroxylamine reduction by the respiratory particle. A terminal electron transfer pathway in Streptomyces griseus was proposed.


The purification and characterization of Dictyostelium discoideum plasma membranes.

A new procedure for the purification of plasma membranes of Dictyostelium discoideum is described. Cells are broken by vigorously stirring in the presence of glass beads, and plasma membranes are isolated by equilibrium sucrose density centrifugation. The purified membranes are considerably enriched in alkaline phosphatase and 5'-nucleotidase and contain very low levels of succinate dehydrogenase and NADPH-cytochrome c reductase. The purified membranes contain relatively high levels of phospholipid, sterol and carbohydrate. They appear as a relatively homogeneous population of membrane vesicles in the electron microscope. This new method of purification is compared to previously published procedures which have been found to be unsuitable for our purposes.


Evidence for cycloheximide acting as a glutamine analogue in plant tissue.

In growing maize root tissue [14C]asparagine formation in inhibited and [14C]glutamine accumulation stimulated by treatment with cycloheximide or glutamine analogs such as azaserine. In contrast, puromycin enhances the accumulation of [14C]asparagine but not [14C]glutamine. Cycloheximide and puromycin alone inhibit protein synthesis. This is interpreted to mean that the alteration in amide metabolism following cycloheximide treatment is a direct result of the antibiotic acting as a glutamine analog. While cycloheximide is often the cytoplasmic protein synthesis inhibitor of choice due to its potency and rapid action, its assumed specificity of action of eukaryotes is doubtful.


Poly(A)-binding RNAs from nuclei and polysomes of BHK-21 cells.

The presence in nuclei and cytoplasm of cultured BHK-21/C13 cells (baby hamster fibroblasts) of RNA species with high affinity for poly(A) was detected using either a Millipore-poly(A)-binding assay or columns of poly(A)-Sepharose 4B. The nuclear species which labels rapidly is metabolically unstable and appears to be a specific subclass of heterogenous nuclear RNA. Digestion with T1 RNAase gives rise to a low level (1%) of oligonucleotide fragments of a disperse size range which are relatively rich in uridylate residues. The cytoplasmic species with affinity for poly(A) is similar in size to polyadenylated messenger RNAs and also associates with polysomes. However it appears to be distinct from the polyadenylated messenger RNAs by virtue of an unusual base composition and relative metabolic instability.


Sbustrate specificity of the elastase and the chymotrypsin-like enzyme of the human granulocyte.

Human granulocyte elastase (EC 3.4.21.11) differs from hog pancreatic elastase in its specificity for synthetic substrates. Although hydrolyzing peptide bonds adjacent to the carboxyl group of alanine, the granulocyte enzyme prefers valine at the cleaved bond, in contrast to the pancreatic enzyme which prefers alanine. Peptide bonds involving the carboxyl group of isoleucine can be hydrolyzed by the granulocyte enzyme but are not hydrolyzed to any significant extent extent by pancreatic elastase. This difference in specificty could explain the lower sensitivity of the granulocyte enzyme to inhibitors containing alanine analogs, such as the peptide chloromethyl ketones and elastatinal. The human granulocyte chymotrypsin-like enzyme differs from pancreatic chymotrypsin by being able to cleave substrates containing leucine in addition to those containing the aromatic amino acids.


L-Asparagainases from Citrobacter freundii.

Three enzymes which catalyze the hydrolysis of L-asparagine have been identified in extracts of Citrobacter freundii. One of these (asparaginase-glutaminase (EC 3.5.1.1) also shows substantial glutaminase activity. This enzyme is extremely labile, is sensitive to inactivation by p-chloromercuribenzoate, and is not protected by dithiothreitol. A second enzyme (asparaginase B) is also sensitive to mercurials but is protected from inactivation by dithiothreitol. This enzyme has a relatively low affinity for L-asparagine (Km = 1.7-10(-3) M). The third enzyme (asparaginase A) is insensitive to inactivation by mercurials, is stable upon long term storage and has a relatively high affinity for L-asparagine (Km = 2.9-10(-5) M). This enzyme has been purified to homogeneity and has a molecular weight of approx. 140 000; the subunit weight being approx. 33 000. The C. freundii asparaginase A produced significant increases in the survival time of C3H/HE mice carrying the 6C3HED lymphoma tumor.


A calorimetric investigation of the growth of the luminescent bacteria Beneckea harveyi and Photobacterium leiognathi.

Direct calorimetric determinations of the rate of heat production along with simultaneous determinations of the rate of photon emission and the number of viable cells have provided insight into the growth of Beneckea harveyi and Photobacterium leiognathi. These experiments were performed with a Tronac isothermal microcalorimeter modified with a fiber optic light guide to allow in situ detection of light. Escherichia coli and a dark variant of P. leiognathi were also examined to provide points of reference. It is demonstrated that B. harveyi seems to pause in the rate of metabolic heat production at the same point in time that the enzyme luciferase begins to be synthesized. This effect is not removed if B. harveyi is grown in conditioned medium. The thermograms for all species are correlated with cell generation time. The heat production per cell indicates that uncrowded cultures produce more heat than older, more crowded cultures, supporting the original observation of Bayne-Jones and Rhees (1929). These observations reopen for examination the suggestion that living systems tend toward a state of minimum metabolism per unit mass.


Blood volume in monoclonal gammopathy.

The plasma volume, red cell volume, or both were measured in 170 normal, anemic, or polycythemic subjects. For anemic subjects without a serum protein abnormality or splenomegaly, the relationship between hematocrit and red cell volume was linear and predictable. In patients with a serum monoclonal globulin on electrophoresis, the plasma voluem was significantly increased for the hematocrit in 30%, and the total blood volume was increased in 45%. The frequency of an elevated plasma volume was higher in patients with a markedly increased level of monoclonal protein. Reductions of abnormal proteins with chemotherapy were associated with declines in plasma volume. For a specific concentration, the serum viscosity was highest in patients with IgM proteins and lowest in patients with IgG globulins. Marked elevations in viscosity were noted only in sera with macroglobulinemia or with more than 5 g/dl of IgG or IgA globulins.


Long-term haemodialysis and thyroid function.

Several indices of thyroid function were assessed in 74 patients with chronic renal failure. Sixty patients had undergone haemodialysis for varying periods. Within the first six months of haemodialysis treatment protein-bound iodine and total thyroxine (T4) levels rose, but after this T4 levels and the free thyroxine index fell progressively. Three out of the 12 patients who had undergone haemodialysis for longer than three years had subnormal T4 and supranormal thyrotrophin concentrations and a subnormal response to thyrotrophin stimulation. Lon-term haemodialysis may be a cause of biochemical hypothyroidism.


Thyrotoxicosis: relations between clinical state and biochemical changes during carbimazole treatment.

The relation between clinical and biochemical changes in thyrotoxicosis were studied in 12 patients with Graves's disease who were being treated with carbimazole. Clinical assessment (using the Crooks-Wayne index) was combined with the measurement of free thyroxine and triiodothyronine indices (FT4I and FT3I) and the assessment of two tissue markers of thyroid hormone action--sex-hormone-binding globulin (SHBG) levels and the thyrotrophin responses to TRH. In general the FT4I and FT3I fell rapidly once treatment was started, and returned to normal in one to four weeks, followed shortly by SHBG levels. The thyrotrophin response returned at this time in two patients, who still had borderline high levels of FT3I and SHBG. The clinical score fell more slowly and variably and was less closely related to any of the biochemical indices than these were to each other. During the early phase of treatment with antithyroid drug the clinical evaluation may be an unreliable indicator of persisting thyroid hormone excess, and when the patient seems clinically but not biochemically thyrotoxic the symptoms should be treated on their own merits with beta-blocking drugs and not with increased doses of antithyroid drugs.


Pattern discrimination thresholds after partial inferior temporal or lateral striate lesions in monkeys.

Ablation of inferior temporal (IT) cortex, particularly of the posterior region, produces severe impairment in pattern discrimination learning. The present study examined whether this impairment is associated with raised pattern discrimination thresholds. Groups of three monkeys each were given either anterior IT, posterior IT, or foveal striate lesions, or kept as controls. They were trained after surgery on a threshold task in which a 90 degrees white angle on a gray ground was the standard, and 15 angles ranging from 10 degrees through 88.5 degrees were the comparisons. As expected, monkeys with posterior IT lesions were the most severely impaired in learning the initial discrimination (90 degrees vs. 10 degrees). However, only the monkeys with foveal striate lesions showed significant impairment on the subsequent threshold determinations. The results indicate that raised pattern discrimination thresholds are not the cause of the pattern discrimination learning deficits produced by inferior temporal lesions. Data from additional visual discriminations presented after threshold testing was completed point, instead, to a loss of attention to stimulus features as the explanation for the learning deficit.


Subcellular distribution of thyrotropin-releasing hormone (TRH) in rat brain and hypothalamus.

TRH localization in rat brain and hypothalamic tissue was studied by determination of immunoassayable TRH in subcellular fractions prepared from homogenates of these tissues. In both hypothalamus and brain, most of the TRH was found in a crude mitochondrial fraction and its concentration was higher in the synaptosomal fraction isolated by density gradient centrifugation. Electron microscopy was used to verify the composition of the fractions. Exposure of the brain crude mitochondrial fraction to osmotic shock resulted in solubilization of TRH which then was sedimented by centrifugation at 96,000 X g. TRH added to brain homogenates in vitro was rapidly destroyed by incubation at 37 degrees C, but no endogenouse TRH was lost by such incubation. The localization of TRH of hypothalamic and brain tissue to subcellular fractions consisting largely of synaptosomes and synaptic vesicles is compatible with a neurotransmitter function for this substance.


Patients' compliance with follow-up after treatment of gonococcal urethritis.

By means of telephone tracing 96% follow-up was achieved in men treated for gonococcal urethritis. A large proportion (34.8%) of patients required one or more calls before follow-up could be obtained. Frequency of sexual re-exposure, proportion with persistent gonorrhea or reinfection, and interval between initial therapy and follow-up were greater in those who required telephone contact for follow-up than in the group who returned for follow-up. Failure to reappear for follow-up does not imply either bacteriologic cure or disappearance of symptoms. Control of gonococcal infection still depends largely upon aggressive methods of case finding, appropriate therapy and careful follow-up.


Plasma cell granuloma of the lung, response to radiation therapy: report of a single case.

A benign, inflammatory lung mass was discovered in a healthy 15-year-old boy who had no chest symptoms. A biopsy was performed, but total removal was not attempted. The histologic diagnosis was plasma cell granuloma of the lung. Because of progressive enlargement of the lung mass, radiation therapy was given and the mass has slowly regressed. Although surgery of these lung lesions is the preferred treatment, radiation therapy should be considered if there is no regression or if the mass continues to enlarge.


Monoclonal macroglobulinemia with osteolytic lesions: a case report and review of the literature.

A patient with monoclonal macroglobulinemia and osteolytic lesions was studied and 24 previously reported closely related cases were reviewed. Cases studied by ultracentrifugation without an immunoelectrophoresis were not considered. Patients presenting with a primary increase in monoclonal IgM molecules may be divided into three groups: typical Waldenstrom's macroglobulinemia, macroglobulinemia with osteolytic lesions resembling multiple myeloma, and a group displaying features of both diseases. At present, cell morphology is not helpful in separating these groups, and a bone survey is recommended. The authors underscore the clinical importance of the early recognition of these entities since procedures such as plasmapheresis for the management of hyperviscosity syndrome, mobilization and local radiotherapy to symptomatic lytic lesions may be necessary for optimal management.


Survival of patients with localized histiocytic lymphoma.

Twenty of 65 patients with diffuse histiocytic lymphoma were identified by staging laparotomy as being in pathologic stages (PS) I, I(E), II, II(E). Six of the 20 patients were treated with total nodal, 10 with extended mantle, and four with involved-field radiotherapy. The survival rate and relapse-free survival at five years were 71% and 78%, respectively. All relapses occurred within the first year and were confined to patients with PS II disease and four or more sites of involvement. Accurate pathologic staging identifies patients who are potentially curable with radiotherapy. Further studies are required to determine the treatment necessary to achieve cure in PS II patients with more than four sites of involvement.


The role of radiation therapy in localized resectable intestinal non-Hodgkin's lymphoma in children.

Forty children with localized resectable intestinal non-Hodgkin's lymphoma were seen between 1948 and 1974. Survival was related to the extent of disease at presentation and to therapy. No deaths occurred after 15 months and no recurrences occurred after 13 months after diagnosis. Six of eight stage IE patients (75%) and nine of 29 stage IIE patients (31%) have survived a minimum of 2 years; one of the three stage IVE patients has survived 17 years. Unfavorable prognostic findings at surgery were serosal involvement, presence of tumor at the surgical margins, mesenteric nodal involvement, and the presence of abdominal fluid or blood. Paraortic nodal involvement or multiple primary foci were universally fatal. Eight of 11 patients (73%) treated with surgery and whole abdominal irradiation (greater than or equal 2000 rad) with or without chemotherapy have survived. Seven of 18 patients (39%) treated with surgery and low dose chemotherapy have survived. One of seven patients treated with surgery and localized or low dose radiation therapy with or without chemotherapy has survived. Four patients treated with surgery alone died. Bone marrow and central nervous system involvement occurred after previous disease relapse elsewhere.


Radiation therapy in the management of localized carcinoma of the prostate: a preliminary report.

Since 1970 a total of 107 patients has been treated radically with radiation therapy for carcinoma of the prostate. The local control with this form of treatment is over 90%. The five year actuarial survival is 74% and the disease-free survival 58%. Serious morbidity has been minimal. Survival is related to the extent of initial involvement and the histology of the tumor, but is not influenced by elevation of the acid phosphatase. Radical radiation therapy is an effective method of local control for carcinoma of the prostate and is potentially curative.


Epidermal ribosome accumulation during two-stage skin tumorigenesis.

The increase in interfollicular epidermal ribosomes on the backs of mice initiated with 7,12-dimethylbenz(a)-anthracene and promoted with 12-0-tetradecanoyl-phorbol-13-acetate was disproportionate to the increase in epidermal wet weight, protein, and DNA. Whereas ribosome numbers increased five- to sixfold 48 hr after the first, fourth, or eight application of 12-3-tetradecanoyl-phorbol-13-acetate, epidermal tissue increased only two- to threefold at these times. This disproportionate increase was due to the fact that, concurrent with the increased amount of interfollicular epidermal tissue and cells, ribosomes per g epidermis and per mg DNA increased two to three times normal. The tissue concentration and cellular content of ribosomes were also increased in the epidermal component of induced squamous papillomas. The work of others has demonstrated that, during growth of other tissues and organs, ribosome accumulation is proportionate to accumulation of tissue and/or cells. The results of our study indicate that the epidermis may have unique kinetics of ribosome accumulation during induced growth. Furthermore, these findings suggest the interesting possibility that other tumor-prone surface epithelia, such as the linings of the respiratory and gastrointestinal tracts, have similar kinetics of ribosome accumulation during induced growth.


Effects of serum concentration on the expression of carcinogen-induced transformation in the C3H/10T1/2 CL8 cell line.

The C3H/10T1/2 CL8 cell line (10T1/2) is being widely used as a quantitative assay system for chemical and physical carcinogens. 10T1/2 cells, but not their transformed counterparts, exhibit a decreased final saturation density with decreasing serum concentration. Exposure of carcinogen-treated cultures to 5% serum 8 days posttreatment led to a 2- to 6-fold enhancement in transformation frequency in comparison with cultures maintained in 10% serum throughout. Exposure 14,21, or 28 days posttreatment also caused enhancement of transformation frequency, provided a sufficient time for expression of the malignant phenotype was allowed. Exposure to 5% serum 1 or 2 days posttreatment did not lead to significant enhancement of transformation frequency. In contrast, exposure to 15 or 20% serum after 8 days virtually abolished the expression of malignancy; however, this inhibition could be reversed by 5% serum. Morphologically transformed foci isolated from cultures exposed to 5% serum produced clones in agarose with the same frequency as did foci isolated from cultures exposed to 10% serum. Reconstruction experiments, utilizing confluent monolayers of 10T1/2 cells overlaid with transformed cells, demonstrated that the growth of transformed cells decreased proportionally with the log of serum concentration. This effect was not caused by depletion of medium and was dependent upon the presence of 10T1/2 cells. It is concluded that the expression of malignancy in this system is governed by the serum-modulated cell density of the mass of non-transformed cells in the culture.


Destruction of experimental malignant melanoma by mediators of cellular immunity.

Listeria monocytogenes (LM) in admixture with B-16 melanoma suppresses local tumor development in syngeneic C57BL/6 mice. In vitro, LM-immune peritoneal and splenic cells are cytotoxic to B-16. Induction of cell-mediated immunity to LM antigens are required for the killing effect, since effector cells from LM-"immune" athymic nude mice are unable to kill tumor cells in vitro. Further, elimination of macrophages by a specific antiserum plus complement abrogates the cytotoxic effect of peritoneal cells. Peritoneal or splenic adherent or nonadherent cells are not cytotoxic, whereas combination of these two cell populations in the presence of the specific antigen can kill the B-16 target cells. A factor, probably lymphotoxin, released by the intact effector cells in the culture fluid mediates tumor cell destruction in vitro. Production of this factor requires cooperation of macrophages with specifically sensitized thymus-derived cells.


Separation of lymphocytes and mast cells from the Furth transplantable mast cell tumor in an isokinetic gradient of Ficoll in tissue culture medium.

Cell suspensions of the transplantable Furth murine mast cell tumor were separated both by velocity sedimentation in an isokinetic gradient and by isopyknic sedimentation. Prior to separation, the suspension of tumor cells contained 60.3+/-13.1% (S.D.) malignant mast cells, 9.8+/-10.4% lymphocytes, 4.3+/-2.1% granulocytes, 1.7+/-1.9% macrophages, 0.6+/-0.4% unidentified cells, and 22.8+/-8.5% red blood cells. After either isokinetic or isopyknic sedimentation, more than 97% of the nucleated cells in the purest modal fraction were malignant mast cells. Velocity sedimentation in the isokinetic gradient offered several advantages over isopyknic separation of this tumor; namely, in isokinetic sedimentation, the cells are exposed to a lower centrifugal force for a shorter period of time; a much larger proportion of mast cells were in the highly purified zone of the gradient following velocity sedimentation; and lymphocytes were more highly purified (88.9+/-10.1% of the nucleated cells) following velocity sedimentation. Granulocytes and macrophages were purified more than 8-fold over the nucleated cells in the starting sample suspension. The purified cells from this tumor offer the opportunity to study the interactions between highly purified, easily identified, malignant cells and cells that may participate in the defense of the host against cancer.


Inhibition of mammary cancer by retinyl methyl ether.

Daily feeding of the synthetic retinoid, retinyl methyl ether, beginning one week after the oral administration of 7,12-dimethylbenz(a)anthracene to female Sprague-Dawley rats, inhibited the incidence of mammary cancer and diminished the number of mammary tumors, both malignant and benign, caused by 7,12-dimethylbenz(a)anthracene. Retinyl methyl ether also markedly increased the latent period for appearance of mammary cancers. Retinyl methyl ether caused no evident toxicity and did not affect weight gain in these experiments. This synthetic retinoid was superior to the natural retinoid, retinyl acetate, for inhibition of mammary carcinogenesis.


In vivo sterol biosynthesis by pea aphid symbiotes as determined by digitonin and electron microscopic autoradiography.

Pea aphid primary symbiotes have previously been shown to synthesize cholesterol in vitro. Two electron microscopic techniques were used here to determine whether the symbiotes also synthesize cholesterol in vivo and whether this cholesterol is made available to the aphid. We also inquired into a possible role of secondary symbiotes in chosesterol biosynthesis. Treatment of aphids with digitonin resulted in significant alteration of ultrastructural sites in primary and secondary symbiote membranes. We concluded that these sites are areas of high cholesterol concentration in the symbiotes. Electron microscopic autoradiography with 3H-mevalonate precursor indicated that both primary and secondary symbiotes synthesize cholesterol; in both cases, the majority of grains were associated with the symbiote membranes. While the frequency of grains on the symbiotes remained constant, irrespective of incubation time in labelled media, the frequency of grains over surrounding tissues increased exponentially as the time of incubation was increased from 30 min to 8 h, indicating that symbiote cholesterol is transported to other tissues. High voltage electron microscopic autoradiography permitted thick section autoradiography, reducing the time of emulsion exposure from 54 days (thin section) to 12 days (0.5 mum sections).


Scanning electron microscopy of dissociated pancreatic acinar cell surfaces.

The pancreatic acinar cell surfaces have been studied by SEM with a dissection of technique and correlated with results obtained by TEM. The SEM results demonstrate characteristic arrangement of microplicae which in some areas are densely packed. In many areas, the microplicae are distributed in such a manner that they create zones with typical geometrical shapes and show a relatively smooth surface. These smooth areas may coincide, as indicated by correlated TEM results, with the limits of intimate contact between adjacent acinar cells which, in turn, represent part of the junctional complex.  Another aspect revealed by these SEM preparations concerns the presence of groups of densely packed microplicae, arranged in regular rows and distributed along some grooves and/or infoldings of the cellular surface. On the basis of SEM and TEM information, it is likely that these structures correspond to intercellular (and possibly, in some cases, intracellular) canaliculi which topographically form a kind of extensive microlabyrinthine arrangement running along all the cell sides. One final point revealed by fractured samples concerns the finding of spherical zymogen droplets within the vesicles of the Golgi complex. Because in many scanning images these vesicles appear connected by small openings, it is suggested that they may represent a system of intercommunicating chambers (vacuoles) through which the zymogen droplets can be continuously accumulated and discharged into the acinar lumen.


Sustained hemodynamic and antianginal effect of high dose oral isosorbide dinitrate.

Twenty-one patients with documented coronary atherosclerotic heart disease were studied to determine the effect of high dose oral isosorbide dinitrate (ISDN) on heart rate, blood pressure, and exercise time until angina pectoris. Patients were tested in two phases, initially with 0.4 mg of sublingual nitroglycerin and with sublingual placebo, and then with oral ISDN, mean dose 29 mg, and oral placebo. Both phases of the study were conducted in a randomized, double-blind, crossover manner. After ISDN was compared to oral placebo, heart rate increased at 30 to 300 min (P less than 0.01) (peak increase 18 beats/min at 60 min), and systolic blood pressure decreased from 45 to 300 min (P less than 0.005) (peak decrease 18 mm Hg at 60 min). Exercise time at 2 min after sublingual nitroglycerin increased 51% as compared to oral placebo, exercise time increased 54% at 1 hr (P less than 0.005), 37% at 3 hr (P less than 0.01), and 12% at 5 hr (NS). Twelve of 21 patients (57%) improved their exercise time until angina larger than or equal to 25% at 1 hr after oral ISDN. The exercise response to sublingual nitroglycerin was a good predictor of this response to oral ISDN.


Long-lasting effect of oral molsydomine on exercise performance: a new antianginal agent.

This study examines whether the beneficial effects of molsydomine, a recently introduced antianginal agent, on exercise performance of patients with angina pectoris are long lasting. The hemodynamic effects are known to persist for several hours. The effects of molsydomine on the duration of exercise and the time to the onset of ST depression were compared to those of placebo during two hours after oral administration. Molsydomine prolonged the duration of exercise in all eight patients (average 2.8 min, P less than 0.001) and delayed the onset of ST depression (average 2.2 min, P less than 0.001), while the placebo failed to alter these measurements. The increment of the duration of exercise produced by 2 mg of molsydomine in two hours following oral administration was comparable to the increment produced in a few minutes after 0.3 mg of nitroglycerin given sublingually. The results indicate that molsydomine offers prophylasis for angina pectoris that lasts at least two hours after oral administration.


Erythrocyte porphobilinogen synthase (delta-aminolaevulinate dehydratase) activity: a reliable and quantitative indicator of lead exposure in humans.

We assessed optimal conditions for assay of porphobillinogen synthase (EC 4.2.1.24) activity in human blood containing abnormally high concentrations of lead. Zn2+and -SH, both required for complete activation of the enzyme, had additive effects. Using a modified method based on these studies, we found blood lead concentration to be strictly proportional to ln(activated/nonactivated) enzyme activity. One brand of commercially available "lead-free" tubes contained a substance that interfered with this relationship. In vitro studies, with the modified assay, showed ALAD to be activated by low concentrations but inactivated by high concentrations of Hg2+, Cd2+, and ethylenediaminetetraacetate. We fouund no genetically influenced differences among unexposed individuals when in(activated/nonactivated) enzyme activities were compared. The technique is suitable for use in screening for lead poisoning in humans.


A simple ligand-binding assay for thyroxine-binding globulin on reusable Sephadex columns.

A method for the assay of thyroxine-binding globulin on reusable Sephadex G-25 (fine) columns is described. It depends upon elution by diluted iodothyronine-free serum of protein-bound [125 I]thyroxine from the columns under conditions where binding to thyroxine-binding prealbumin and albumin are abolished. It is simple, rapid and precise and permits determinations in large numbers of samples. Values (mg/l; mean +/- S.D.) were: normals 31.6 +/- 5.4, hyperthyroid 28.3 +/- 4.8, hypothyroid 40.6 +/- 7.5, oral contraceptives 40.1 +/- 6.8, pregnant 50.3 +/- 5.4, cirrhotics 20.7 +/- 4.3. Concentrations were reduced in serum heated at 56 degrees C, while the uptake of [125 I]triiodothyronine was increased. There was a significant negative correlation between thyroxine-binding globulin concentration and triiodothyronine uptake in the heated serum samples and in euthyroid subjects.


A study of enocrine function in protein-energy malnutrition.

Serum concentration of cortisol, growth hormone, thyroxine, thyroid stimulating hormone, follicle stimulating hormone and luteinising hormone, together with triiodothyronine uptake have been measured in Nigerian children with kwashiorkor and marasmus and compared with controls. In both types of malnutrition the cortisol and growth hormone concentrations are raised, whereas those of thyroxine and thyroid stimulating hormone are lowered compared with the controls. Triiodothyronine uptake is lowered in malnutrition but there is no apparent effect on follicle stimulating hormone or luteinising hormone in this age group.


A patient with purine nucleoside phosphorylase deficiency: enzymological and metabolic aspects.

1. Enzymological and metabolic data in a patient with nucleoside phosphorylase (NP) deficiency are described. 2. Incubation of intact NP-deficient red cells with [14C]adenosine showed a rapid uptake and conversion to inosine. Almost no radioactivity was incorporated in the adenosine nucleotides and no hypoxanthine labeling could be detected. 3. Incubation with [14C]inosine resulted in a rapid conversion to IMP in the normal intact red cells but in an accumulation of inosine in the medium with the erythrocytes of the patient, proving again that a NP deficiency is present. 4. The high PRPP level found may result from impaired consumption due to lack of substrates for the salvage enzyme HGPRT. 5. Incubation with [14C]hypoxanthine and [14C]adenine showed that normal HGPRT and APRT activities were present in the NP-deficient red cells. 6. In serum and urine of the patient the levels of inosine and guanosine were considerably increased, while the serum and urinary levels of uric acid were very low. In the two deceased sisters NP deficiency was also strongly suggested by analyses of the serum purines, of stored deep frozen samples.


Fenoprofen, aspirin, and gold induction in rheumatoid arthritis.

Fenoprofen calcium (2,400 mg/day) or aspirin (3,900 mg/day) was administered in double-blind fashion to 20 rheumatoid patients during 6 months of gold induction therapy, and to 20 rheumatoid patients not receiving gold. Among both the gold-treated and nongold-treated patients, the fenoprofen and aspirin groups improved equally in all but one parameter of disease activity. Fenoprofen and aspirin did not differ significantly in the observed prevalences of abdominal discomfort, guaiac-positive stools, or peptic ulcers. Aspirin was associated with significantly higher mean serum glutamic oxaloacetic transaminase (SGOT) levels than fenoprofen, but only among patients undergoing gold induction. Comparison of efficacy parameters between patients treated with gold and patients treated with oral drugs alone revealed significant differences favoring gold.


Evolution of bacterial sensitivity to fosfomycin in the Cindad Sanitaria 'Francisco Franco' in Barcelona.

A revision was done of the sensitivity of isolated germs in urine cultures and various other cultures to fosfomycin from 1972 to the present in the Ciudad Sanitaria 'Francisco Franco' in Barcelona. The results obtained were analyzed. The general observation was that of a fairly uniform behavior in the majority of germs that had shown an increase in resistance in 1973, and a clear tendency to a decrease in resistance in 1974 and 1975 with the exception of P. rettgeri (Lact.+) and P. morganii.


Susceptibility to fosfomycin of hospital strains isolated in Nantes (France). Frequency of mutation to resistance.

Susceptibility of 760 bacterial isolates to fosfomycin has been determined by the agar dilution method. The MICs of 364 strains have been determined by comparison of agar alone and agar plus glucose-6-phosphate. This later enhances the activity of fosfomycin. Lastly, we studied frequency of mutation toward resistance for 109 susceptible strains. We obtained 88 stable mutants.


R plasmids coding for gentamicin, tobramycin, and carbenicillin resistance in Serratia, Klebsiella and Escherichia coli strains from a single clinical source.

Serratia marcescens, Klebsiella sp. and Escherichia coli strains bearing transferable resistance to aminoglycoside antibiotics, namely, gentamicin, tobramycin, kanamycin, streptomycin, lividomycin, and carbenicillin, as well as to a series of more classical drugs, began to emerge in materials from the Frankfurt University Hospital. Plasmids from Serratia, Klebsiella, and E. coli exhibit a broad host range in that they are transferable to E. coli, Proteus mirabilis and Salmonella typhimurium receipients. They are not transferable to Pseudomonas aeruginosa, although in that species plasmids of gentamicin and tobramycin resistance, was well as of resistance to further drugs, were detected in that area as early as in 1973. High-level carbenicillinase has been identified in Serratia and Klebsiella plasmids associated with drug resistance to aminoglycoside antibiotics.


The action of fosfomycin on the growth of Pseudomonas aeruginosa.

A study was made of the effect of the inoculum size and the culture conditions on the MIC of a strain of Pseudomonas aeruginosa that was sensitive to fosfomycin. The increase of the inoculum and the conditions which favour the cellular multiplication considerably increase the MIC. Phosphates inhibit the action of the antibiotic. Fosfomycin produces a logarithmic decrease in the number surviving 1 h after being added; the bacterial lysis measured by the decrease in the OD depends on the medium and is hardly noticeable in ordinary broth. In a minimum medium the antibiotic does not affect the growth. The determination of the variation in the consumption of oxygen is a rapid and accurate method of evaluating the effect of fosfomycin. A spontaneous mutant glpT was isolated which was more than 128 times more resistant than the isogenic parental strain. The growth curves of this mutant, the sensitive parental strain and a naturally resistant strain that was isolated in a patient were similar to each other in complex media. In synthetic media the naturally resistant strain shows shorter phases of latency, but the generation times are analogous. This would seem to indicate that the resistance to fosfomycin in P. aeruginosa has no influence on the speed of growth.


Bacteraemia by P. aeruginosa associated with nephrotic syndrome after shunt operation for hydrocephalus.

One patient of sepsis by P. aeruginosa after the implanting of a ventriculoatrial valve following extirpation of an expansive intracranial process is studied. During the evolution of the septic process there appeared as associated nephrotic syndrome with histologic lesions corresponding to an acute exudative glomerular nephritis. The germ became resistant to the antibiotics used, carbenicillin plus gentamicin, being later sensitive only to fosfomycin with which finally complete cure was achieved.


Fosfomycin, antimicrobial activity in vitro and in vivo.

Antibacterial activities of fosfomycin were investigated both in vitro and in vivo for the purpose of comparative evaluation on its fundamental properties with other antimicrobial agents. The MIC was determined with nutrient agar (Difco) inoculated with one loopful of 1,000-fold dilution (about 10(6) cells/ml) of bacterial suspension cultured overnight in nutrient broth. This substance showed antibacterial activity to most gram-positive and gram-negative bacteria, being strongest to Enterobacteriaceae with a peak of the MIC at 1.56 mug/ml in Salmonella. It was also active against P. aeruginosa with a peak of the MIC at 6.25 mug/ml in its sensitivity distribution. Intravenous and subcutaneous fosfomycin Na salt and oral fosfomycin Ca salt were given to 5-week-old ddN strain male mice challenged with clinical isolates of P. aeruginosa, E. coli and P. mirabilis. Therapeutic effect was observed in all these test organisms. In P. aeruginosa, it was more effective than carbenicillin.


Evolution of sensitivity to fosfomycin at Jimenez Diaz Foundation.

The sensitivity to fosfomycin of more than 8,000 strains of bacteria isolated from products recevied by the laboratory between 1972 and 1974 has been studied. Some were studied by the dilution technique in a solid medium and the remainder was studied by diffusion. A single 50-mug disc was used and the strains inhibited by concentrations of less than 64 mug/ml or with inhibition halos of 15 mm diameter or more were considered sensitive. It is clear from this study that there are no significant changes in the sensitivity of the bacteria studied during the above-mentioned time, with the exception of a decrease in that of indole-positive Proteus, Providentia and Klebsiella.


Potentiation of sulphamethoxazole by trimethoprim in Neisseria gonorrhoeae strains.

Quantiative determinations of the sensitivity of 322 Neisseria gonorrhoeae strains to sulphamethoxazole (Su), trimethoprim (Tr) and a combination of Su and Tr in a ratio of 5:1 are described. Data are also given on the potentiation of Su by tr. It was striking that the Su-sensitive N. gonorrheoeae strains showed no potentiation of Su by Tr when a Su/Tr ratio of 5:1 is used. The sensitivity to combinations of Su and Tr in various ratios was determined for seven N. gonorrhoeae strains with known senstivity to Su and Tr. On the basis of these data, the rules according to which Su is potentiated by Tr. could be formulated.


Sensitivity of Neisseria meningitidis to sulfonamides and antibiotics. In vitro trials on 302 strains isolated during the Brazilian epidemic of 1974.

During the recent epidemic of meningitis in Brazil, 1974, bacteriological and antibiotic sensitivity investigations were performed on 302 strains of Neisseria meningitidis, isolated from meningitis patients from the São Paulo and Rio de Janeiro districts in the first half of 1974. The experiments have shown that 58% of the strains belong to the serological type A, 25% belong to type C and the remaining 17% to a group designated 'untypable' in that they did not react with the diagnostic antisera A, B, C, and D. Antibiotic sensitivity tests in vitro have made evident that, independently of the serological type, 89.8% of the 302 strains were inhibited by 10 mug/ml of a long-acting sulfonamide (sulfamethoxypyrazine, SMP), that is, by levels easily reached in the CSF during a normal prophylactic or therapeutic treatment.


[Histomorphology of the sacroiliac joint in ankylosing spondylitis and relevance to treatment (author's transl)].

The sacro-iliac joint of a patient who had been ill with ankylosing spondylitis for half a year was investigated histologically at necropsy. Two basic histological phenomena were apparent: inflammation and aggressive proliferating chondroid metaplasia at the chondro-osseous junction and in the subchondrium. Joint cartilage degeneration, joint cartilage fusion, capsule ossification and subchondral bone apposition were observed as epiphenomena at the sacro-iliac joint. Both basic morphological phenomena are due to the same cause which has not yet been clarified. They progress independently of each other with varying intensity. This assumption explains differing opinions and the relation of inflammation and pathological ossification of the skeletal axis as well as the unsatisfactory objective results of treatment. Only a combination therapy directed against both morphological basic phenomena will result in an objective therapeutic success and not only in a symptomatic improvement of ankylosing spondylitis.


Drug interactions with oral sulphonylurea hypoglycaemic drugs.

The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.


The difficult asthmatic.

The most common reason why asthma presents difficulties in management is the failure to treat it with drugs which are appropriate and taken in adequate dosage. An understanding of the pathophysiology and aetiology of asthma is essential if full advantage is to be taken of the wide range of drugs now available for treating it. Airflow obstruction due to bronchial muscle constriction is usually readily reversible by bronchodilators, whereas that due to the inflammatory component of asthma is refractory to the latter and can only be reversed by steroids. Refractory airflow obstruction is liable to be confused with irreversible obstruction which occurs in those patients whose asthma is complicated by chronic obstructive bronchitis or other lung disease. The choice between symptomatic, preventive and suppressive forms of treatment should be made only after a careful assessment has been carried out with objective measurement of airflow obstruction. The Wright peak flow meter is unsurpassed for this purpose. By its means it should be possible to estimate how much of a patient's airflow obstruction is readily reversible, how much is refractory and how much is irreversible. In general, the aim of treatment is to relieve airflow obstruction rather than to counteract supposed aetiological factors. Both doctor and patient must understand the purpose, limitations and possible dangers of any drug which is prescribed. Steroids are the only form of treatment which is effective in persistent refractory asthma. Prejudice against steroids has resulted in many patients being deprived of their benefit, but this situation may change with the recent introduction of steroid aerosols.


Prolactin release following electrical stimulation of the brain in ovarectomized and ovariectomized estrogen-treated rhesus monkeys.

Selected areas in the medial basal (MBH) and rostral (RH) hypothalamus and in the amygdala (AMYG) of long-term ovariectomized rhesus monkeys were electrically stimulated for 30 min through permanently implanted bilateral stainless steel electrodes. Stimulation of an area in the MBH extending from the dorsal part of the ventromedial nucleus through the arcurate nucleus to the upper median eminence resulted in a 200 to 400% increase within 5 min in 8 monkeys. In one monkey the elevated serum prolactin levels persisted after termination of stimulation and in 2 monkeys prolactin remained unchanged during the 30-min stimulation but increased after stimulation was discontinued. Stimulation of the paraventricular-dorsomedial nuclear area in one monkey had no effect on prolactin release. Prolactin responses to stimulation in the RH varied. In 2 monkeys the electrode tips extended into the optic chiasm but part of the uninsulated tips remained in contact with the RH; only one of these monkeys released prolactin in response to stimulation. In 4 monkeys the electrode tips were located in the suprachiasmatic-anterior hypothalamus area. Serum prolactin increased by 200 to 300% in response to stimulation in 2 of these monkeys but increased only slightly in the remaining 2 monkeys. Prolactin responses to stimulation of the AMYG varied with the location of the electrodes. Stimulation in the corticomedial region produced no change in serum prolactin but stimulation in the basal or basolateral area produced marked elevations. An increase in circulating levels of estradiol-17beta (E2) to 100 pg/ml by SC implantation of E2 capsules 72 h before stimulation had no significant effect on basal prolactin levels, but markedly enhanced the prolactin release induced by stimulation in both the MBH and RH. Sham-stimulation did not affect serum prolactin. We conclude that prolactin release in rhesus monkeys can be triggered by electrical stimulation of selected hypothalamic and amygdaloid areas and that stimulation-induced prolactin release in the RH and MBH can be enhanced by E2 pretreatment.


Delayed hypersensitivity in Graves' disease and exophthalmos: identification of thyroglobulin in normal human orbital muscle.

Patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity to antigens present in extracts of certain normal human tissue; namely,thyroid gland and retroorbital tissue. The delayed hypersensitivity can be assayed in vitro by quantitating the amount of a lymphokine, migration inhibition factor (MIF), which is produced when T lymphocytes of patients with Graves' disease and exophthalmos are exposed to these antigens. In the present report, a partial purification is described for the retro-orbital tissue antigen which is responsible for the positive leucocyte migration inhibition factor assay (MIF assay) exhibited by a sensitized lymphocytes of these patients. The purified retro-orbital tissue antigen preparation demonstrates a 50- to 150-fold higher specific activity over crude homogenates in its ability to act as an antigen in the MIF assay of exophthalmic patients. Immunodiffusion, ultracentrifugation, and disc electrophoretic data indicate that this purified antigen preparation, obtained from normal human, retro-orbital tissue, contains thyroglobulin or a derivative of thyroglobulin; immunofluorescence studies localize the anti-thyroglobulin reactive material to the plasma membranes of extraocular muscle fibers of normal individuals. On the basis of these data it is concluded that thyroglobulin or a derivative of the thyroglobulin molecule is present in the orbital muscle of normal individuals. Since thyroglobulin purified from normal human thyroid glands and the purified retro-orbital tissue preparation are nearly equivalent as antigens in the MIF assay of exophthalmic patients, we conclude that thyroglobulin or an antigenic component of the thyroglobulin molecule is one of the antigens to which patients with Graves' disease and exophthalmos demonstrate delayed hypersensitivity.


Prolactin release in response to blockade of dopaminergic receptors and to TRH injection in developing and adult rats: role of estrogen in determining sex differences.

Female rats released more prolactin in response to blockade of dopaminergic receptors with Pimozide (P) than males at all ages studied (from day 15 to day 75). Testosterone propionate (Tp) administered during the neonatal period did not change the female response to P. The male response to P was not faciliated by neonatal orchidectomy, orchidectomy at day 21 or "feminization" of male fetuses, but it was enhanced by an injection of estradiol benzoate (Eb; 5 mug, SC, 48 h before P). Ovariectomy of adult androgenized or normal female rats blunted the prolactin response to P and an estrogen injection facilitated it. Pituitary prolactin reserve was evaluated by injecting TRH and measuring the resulting plasma prolactin levels. Adult males released less prolactin in response to TRH than females on proestrus or on diestrus day 1. The response of adult females to TRH varied during the cycle, being maximal on proestrus and minimal on diestrus day 2. In both sexes, castration suppressed the prolactin response to TRH and a single Eb injection restored it. Pituitary prolactin content was lower in males than in females and decreased following castration in both sexes. Eb partially restored it. The results indicate that a) the prolactin response to blockade of DA receptors is more pronounced in females than in males, b) this difference is not determined by a process of neonatal or fetal hypothalamic sexual differentiation, but rather is a consequence of a modulating action of estrogen at the hypothalamic-hypophyseal level during the coruse of sexual development, and c) the main site of action of estrogen in determining this sex difference appears to be the pituitary gland.


Gonadotropin-sensitive progesterone production by rhesus monkey luteal cells in vitro: a function of age of the corpus luteum during the menstrual cycle.

Progesterone production in vitro, in the presence and absence of exogenous gonadotropin, was examined in suspensions of luteal cells, isolated by collagenase digestion of rhesus monkeys corpus luteum at various stages of the menstrual cycle. Cells isolated during mid-luteal phase (days 15-19) of the cycle secreted progesterone for up to 6 h in vitro. Mid-luteal phase cells were responsive to physiologic concentrations of human chorionic gonadotropin (hCG), with progesterone production significantly (P less than 0.05) enhanced by as little as 0.1 ng hCG/ml. Maximal stimulation was obtained with 100 ng hCG/ml. Both macaque chorionic gonadotropin (mCG) and human luteinizing hormone (hLH) significantly (P less than 0.01) increased progesterone production, while human follicle stimulating hormone (hFSH) did not. Under control conditions, in the presence of nutrient medium alone (no exogenous gonadotropin), the progesterone synthetic activity of mid-luteal phase cells was significantly (P less than 0.01) greater than that of cells from late luteal phase (days 22-28) of the cycle. Moreover, progesterone production by mid-luteal phase cells was consistently stimulated (P less than 0.01) by the presence of 100 ng hCG/ml, whereas late luteal phase cells were less sensitive or unresponsive to exogenous gonadotropin. The progesterone synthetic activity of luteal cells in vitro correlated positively with both the wet weight of the excised corpus luteum (r = 0.82, P less than 0.01) and the peripheral serum progesterone concentration immediately preceding luteectomy (r = 0.66, P less than 0.01). These findings suggest that freshly isolated luteal cells reflect the functional capability of the corpus luteum in vivo. It is apparent that the age of the rhesus monkey corpus luteum of the non-fertile menstrual cycle is an important factor governing luteal cell progesterone synthetic capability and luteal cell responsiveness to gonadotropin in vitro.


Binding of prolactin by fetal rhesus cell membrane fractions.

Interest in possible physiologic roles of prolactin in the developing fetus led to the present study of affinity of human prolactin to fetal rhesus cell membrane fractions. The fractions were prepared by ultracentrifugation and their composition confirmed by electron microscopy. The cell membrane preparations were derived from the fetal placenta, liver, lung, myocardium and brain. Kinetic studies showed apparent binding affinity constants for 125I-labeled human prolactin (hPRL) of the order of 10(9)M-1 and capacities of from 3 ng to over a microgram per organ in late pregnancy for all of these tissues except brain. The calculated binding capacities, although probably underestimated, were found sufficiently high to insure that a portion of maternal and fetal prolactin exists in bound form to fetal tissues, consistent with possible roles in the regulation of fetal tissue cellular function, and provided they have access to circulating PRL.


Amniotic prolactin control over amniotic and fetal extracellular fluid water and electrolytes in the rhesus monkey.

Administration of 1-10 mg ovine pituitary prolactin (oPRL) into the amniotic fluid of 10 rhesus monkeys in the last third of gestation consistently caused a decrease in amniotic fluid volume not seen when saline, vasopressin, or bovine serum albumin were injected into 9 other monkeys. The effects lasted for 24 h. Intraamniotic injection of 10 mg oPRL prevented or reversed a doubling of water and electrolyte content of the fetal extracellular fluid (ECF) volume in the face of hypertonic amniotic fluid. Efflux of these substances from the fetal ECF in the face of hypotonic amniotic fluid was similarly prevented or reversed by intraamniotic prolactin injection. Ovine PRL had no effect on fetal ECF water and electrolytes in the face of isotonic amniotic fluid. Possible sites of these oPRL effects were amnion, placenta, fetal lung and/or fetal gastrointestinal tract.


Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolactin; response to LH-releasing hormone and thyrotropin-releasing hormone.

Adult male Sprague-Dawley rats averaging 300 g each were subjected to complete food removal for 7 days (acutely starved), 7 days complete food removal followed by 2 weeks of 1/4 ad libitum food intake (chronically strved), 7 days complete food removal and 2 weeks of 1/4 ad libitum intake followed by ad libitum feeding for 7 days (refed), or fed ad libitum throughout (controls). Serum LH, FSH, TSH, PRL, and GH levels were measured by radioimmunoassays for each group of rats. The in vivo response to the combination of synthetic LHRH and TRH also was tested in each group of rats. Circulating LH, TSH, GH, and PRL were significantly depressed in acutely and chronically starved rats, and FSH was lowered only in acutely starved rats. After 7 days of refeeding, serum levels of LH and FSH were significantly greater than in ad libitum fed controls, PRL returned to control levels, and TSH and GH increased but were still below control levels. After LHRH + TRH injection serum LH and TSH were increased significantly in all groups of rats, FSH and PRL rose in acutely but not in chronically starved rats, and GH was not elevated in any group. The increases in serum LH, FSH, TSH and prolactin in response to LHRH + TRH injection in acutely or chronically starved rats were equal to or greater than in the ad libitum fed controls. These data indicate that severe reductions in food intake result in decreased release of at least 5 anterior pituitary hormones, and this is due primarily to reduced hypothalamic stimulation rather than to inability of the pituitary to secrete hormones.


The treatment of intractable diarrhea by the method of "Baustein" principle using a casein hydrolisate.

Ten infants with intractable diarrhea, celiac disease and small bowel resection were treated with a special dietetic regimen called "Baustein" principle. The three major food constituents were added to the formula stepwise: first glucose and maltodextrin followed by protein and vegetable oil or MCT oil. The protein source was a newly developed casein hydrolisate also containing minerals, trace elements and vitamins.


Behaviour of glibenclamide on repeated administration to diabetic patients.

Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating "deep" compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.


Integration of cerebral and peripheral inputs by interpositus neurons in monkey.

The patterns of convergence of cerebral and peripheral nerve inputs onto interpositus neurons were studied in cebus monkeys. The strongest inputs to interpositus neurons are from motor and somatosensory cortex, with weaker inputs from peripheral nerves and cerebral area 6. The neurons in the anterior portion of interpositus receive cerebral and peripheral inputs primarily representing the hindlimb, while inputs to neurons in the posterior division represent forelimb or mixed forelimb and hindlimb. The hindlimb neurons integrate signals principally from motor cortex, somatosensory cortex, nerves, supplementary motor and medial pre-motor areas, while forelimb neurons receive inputs from motor, somatosensory, lateral premotor cortical areas and nerves. The results from this study are compared with those from studies of interpositus and dentate neurons in cat and monkey in order to determine the role of n. interpositus in movement. It is suggested that the inputs integrated by interpositus neurons are consistent with a role in up-dating skilled movements.


Current concepts of prolacting physiology in normal and abnormal conditions.

Currently the physiology and pathophysiology of pituitary prolactin secretion are under intensive investigation. Development of sensitive, specific radioimmunoassays for hPRL and improved roentgenographic techniques have increased the diagnostic acumen for incipient pituitary microadenomas. Several modalities of treatment are available at the present time which can result in improvement in the clinical symptoms of the amenorrheagalactorrhea syndromes. Eponymic classification of amenorrhea-galactorrhea syndromes should be discarded and appropriate diagnostic studies initiated to determine the etiology of the inappropriate breast secretion and/or elevated serum hPRL level.


Influence of vasopressin on colon blood flow in monkeys.

Inferior mesenteric arterial blood flow was measured with an electromagnetic blood flowmeter in five anesthetized rhesus monkeys. The effects of vasopressin on this vasculature were determined to evaluate the optimal, safe concentration of this agent during its clinical application in the management of hemorrhagic lesions of the colon. Control flow was 29 +/- 3 (SE) ml min-1; aortic pressure was 124 +/- 4 mm Hg. Intraarterial injections of vasopressin, in doses ranging logarithmically from 5 X 10(-5) to 5 X 10(-2) U kg-1, caused dose-dependent decreases in flow. At the highest dose, vasopressin reduced flow by 50% and increased arterial pressure by 9 mm Hg. When infused, at a rate of 5 X 10(-3) U kg-1 min-1, vasopressin produced a significant and sustained reduction in inferior mesenteric arterial blood flow. Autoregulatory escape was not observed. At this rate, vasopressin increased arterial pressure 10 mm Hg, by the 6th minute of infusion. This hypertension was unaccompanied by significant bradycardia. After cessation of the infusion, flow gradually returned to control values over a period of minutes. These observations indicate that vasopressin is a potent constrictor in the inferior mesenteric arterial circulation of the monkey, and support the use of this agent to control lower intestinal bleeding in man. At a dose of 5 X 10(-3) U kg-1 min-1, vasopressin causes a significant reduction in flow without adverse systemic side effects.


Parenteral nutrition at home for 5 years via arteriovenous fistulae. Supplemental intravenous feedings for a patient with severe short bowel syndrome.

On March 26, 1970, a 33-year-old male suffered intestinal infarction which required total enterectomy and duodeno-transverse colostomy. Nutrition was maintained in the hospital by daily parenteral feeding for 2 months postoperatively, after which parenteral feedings were decreased and stopped for long periods. Various oral dietary regimens failed to provide adequate nutrition, and the patient lost 40 kg and became severely malnourished during the next 13 months. In June 1971, supplemental home parenteral nutrition (PN) via an arteriovenous fistula was instituted on a 3 or 4 nights per week basis. The patient's weight and strength increased markedly after institution of the home supplemental PN program. The first fistula became occluded after 9.5 months of home PN use and subsequent successive fistulae have remained patent for 31.3, 8.8, and 5.5 months of use. The patient prepares his own PN fluids at home, using a commercial device for filling plastic intravenous fluid bags. Although several different types of fluid have been used, the current mixture of 25% glucose and 2.75% amino acids with added vitamins, potassium, calcium, magnesium, and insulin plus simultaneously administered lipid emulsion has proven most effective. Only when the patient's low fat, low oxalate diet is supplemented with this parenteral mixture 4 nights each week is he in positive nitrogen, phosphorus, and magnesium balance. However, his negative calcium balance is only partially corrected. There has been no sepsis, embolism, or fistula infection during 5 years of home PN.


A quantitative analysis of the organization of a group of captive talapoin monkeys (Miopithecus talapoin).

Grooming and avoiding scores were used as measures of the attractive and repulsive forces operatinc in a group of eight monkeys. The results revealed: (1) three unisexual grooming subgroups; (2) two focal monkeys (one female and one male) which were each avoided by five animals, one female avoided by three animals, the rest avoided by one or none; (3) that each monkey was 'friendly' with one to three others and was 'antagonistic' toward all the rest; (4) that males were socially inactive, ranked below most females, associated primarily with each other, and, in this study, were killed by females during the mating period. The social organization of talapoins seem to differ from that of other Old World monkeys and may be similar to that of the New World squirrel monkeys.


Factors influencing nursing in Macaca fascicularis.

Nursing by two mother-infant pairs in a caged colony of Macaca fascicularis was monitored at 1-min intervals for 8 h beginning 8:30 a.m. BST, once a week for 3 months in the summer of 1973. Nursing occupied about 210 min in 8 daylight hours for the infants at 10 weeks of age, and the time spent nursing decreased at the average rate of 9.4 min per week until the infants were about 6 months old. The time spent nursing by the infants studied here resembles closely the times spent nursing by some other macaques and by baboons. In the course of a day the amount of time spent nursing varies significantly with a diurnal peak. If nursing by one mother-infant pair is independent of nursing by the other pair, then the time the two pairs spend nursing together would be a function of the product of the frequencies of nursing by each pair. The expected times for the pairs nursing together based on the hypothesis of independent events were significantly less than the observed times the pairs nursed together. Nursing, therefore, involves a positive influence or imitation of one nursing pair by the other. Nursing sessions involving both mother-infant pairs were longer on the average than sessions involving only one pair.


Tail carriage in baboons (Papio cynocephalus): relationship to dominance rank and age.

Several metric and categorical variables were used to assess tail carriage in 717 photographs of 54 yellow baboons (Papio cynocephalus) of known identity, sex, dominance rank, and estimated or known age. Analyses of these data demonstrated that age was the primary factor, influencing tail carriage of baboons not engaged in social interaction. Specifically, the proximal segment of the tail was carried increasingly close to the vertical with increasing age; other changes in tail angles and segment curvature were also correlated with age. There was no relationship between dominance rank and neutral tail carriage in adult male or female baboons, nor was the neutral tail carriage of the first-ranking male or female either distinctive or characteristic. The morphological basis of ontogenetic changes in neutral tail carriage in baboons is also discussed.


Why did the strepsirhine tooth comb evolve.

The hypothesis that the original strepsirhine tooth comb evolved for scraping gum is examined. The comparative morphology of the anterior dentition does not corroborate this view, and our study suggests that the primitive tooth comb, which was 6-toothed, evolved for the maintenance of the five, evenly distributed narrow spaces in between them. Unlike the incisors of other groups, platyrrhines or catarrhines, for example, the apical extremities in the primitive condition are not closer to one another than the basal portions of these teeth. The biological role responsible for the evolution of the function of the original tooth comb is believed to be fur-combing. Subsequent modifications in numerous lineages altered both morphology and function as a result of new roles, and this tended to obscure the cause of origin of this character complex.


[Educational goals during the internship for general medicine].

The student is to be taught a wide spectrum of nonstationary practical care of sick and healthy people of every age and genus. He is to experience all daily events of a general practice and shall also become acquainted with the doctor, his assistants, and the doctor's family. The student ought to experience by his assistance in practice the increasing responsibility, the burden, and also the fulfillment of medical profession. General Medicine contributes to the education of the student by the famulature. Who chooses the medical profession, declares his readiness to help fellow-creatures and to accept medical responsibility for them. Medical education should intensify the readiness to help.


[Assessment of the therapeutic effect of Trental 400. Double-blind study in geriatric patients with circulatory disorders].

A double blind trial was performed in a geriatric unit in order to evaluate efficacy and tolerability of Trental 400 (400 mg Pentoxifylline per tablet) against a comparative formulation (2,4 mg adenosine per tablet) in 36 patients displaying signs of peripheral vascular disease and in 16 patients with symptoms of cerebrovascular disorders. 3 tablets were administered daily over a period of three months. Trental 400 proved to be significantly more effective in either indication group. Based on the observed good tolerability and pronounced efficacy Trental 400 can be considered as an easy to handle therapeutic tool for the long term treatment of symptoms resulting from peripheral and cerebral vascular disorders.


[The practicability of vaccinations].

Up to now there has been paid not much notice to the practicability of vaccinations: however, its influence on vaccination-participation should not be neglected. Examples for optimal and insufficient practicability are shown.


In vivo distribution of Pseudomonas aeruginosa slime glycolipoprotein: association with leukocytes.

Intraperitoneal injection of slime glycolipoprotein (GLP) from Pseudomonas aeruginosa induced leukopenia and death of mice, similar to the effect of infection with viable organisms. Differential counts established that the leukopenia was characterized by a decrease in the number of polymorphonuclear leukocytes, followed by death of mice. Mice immunized with GLP survived challenge and responded with a leukocytosis that had a substantial increase in circulating polymorphonuclear leukocytes. Leukocytes from GLP-injected mice were agglutinated by anti-GLP serum, indicating an association between GLP and leukocytes. Other results indicated that 14C-labeled GLP is deposited mainly in the liver. Normal leukocytes labeled with 51Cr were injected intravenously into mice receiving an intraperitoneal injection of GLP. As with GLP, the 51Gr-labeled leukocytes were sequestered in the liver. These results indicate that GLP enters the blood stream and becomes associated mainly with neutrophils, and that the neutrophil-GLP complex is deposited in the liver, possibly accounting for the leukopenia in mice.


Experimental scrub typhus immunogens: gamma-irradiated and formalinized rickettsiae.

Scrub typhus immunogens were prepared by exposing infected yolk sac suspensions of Rickettsia tsutsugamushi to various doses of gamma radiation. Mouse lethality was abolished at doses greater than 200 krads, whereas immunogenicity of the suspensions, as shown by mouse protection tests, was diminished relatively little by radiation doses in the 200- to 400-krad range. Using a 300-krad gamma dose to provide a safety factor, immunogens were prepared and their protective capacity was contrasted with formalinized scrub typhus immunogens prepared by conventional techniques. Formalinized suspensions afforded mice only partial protection against intraperitoneal challenge with 1,000 50% mouse lethal doses of the virulent homologous strain and no significant protection against similar challenge with an equally virulent heterologous strain. Using the same strains, radiation-inactivated preparations provided 100% protection against 10,000 50% mouse lethal doses of the homologous strain and 70% protection against challenge with the same doses of a heterologous strain. Neither immunogen was a potent stimulator of antibody production as measured by the complement-fixation test. Cell-transfer studies using inbred mice indicated a role for cell-mediated immunity after vaccination with gamma-irradiated immunogens, but no cell-mediated protection could be demonstrated after vaccination with formalin-inactivated rickettsiae.


Hemagglutinating activity of Fusobacterium nucleatum.

Gingival isolates of oral Fusobacterium nucleatum strains (gram-negative anaerobic fusiform bacilli) have shown the characteristic ability to hemagglutinate a variety of erythrocytes (RBC) of human and animal origin. Other members of the genus tested (F. necrophorus, F. varium, and F. mortiferum) displayed little if any ability to hemagglutinate RBC. The hemagglutination (HA) activity could be observed in the F. nucleatum strains with the whole cells and in most instances with sonicated preparations of the organisms. The HA activity was observed in cell wall preparations of the organism and appeared dependent upon a heat-labile protein component of the cell wall. In decreasing order, the RBC that would hemagglutinate with the smallest concentration of HA preparations were rabbit, monkey, human, sheep, horse, and ox. No differences in HA activity of the preparations with cells from the various human blood types were noted. Absorption of the HA preparation of one strain with human cells removed HA moiety was bound to the cells via a Ca2+ binding site interaction since ethylenediaminetetraacetic acid and ethylene glycol-bis-N,N'-tetraacetic acid inhibited binding, and HA could be reestablished by the addition of Ca2+ but not Mg2+. Rabbit antisera to the F. nucleatum strains inhibited HA activity when tested with the HA preparation in the standard test, whereas anti-Leptotrichia buccalis sera or normal rabbit sera had no effect. A tanned-cell passive HA test with rabbit anti-F. nucleatum sera displayed reactivity between the homologous strains but little reactivity with the other Fusobacterium species tested.


K99 surface antigen of Escherichia coli: purification and partial characterization.

K99, a presumed colonizing factor of enterotoxigenic Escherichia coli of calf origin, has been purified. K99 was removed from K99+ bacteria by salt extraction and subsequently purified by ammonium sulfate precipitation and column chromatography on diethylaminoethyl-Sephadex. The purified material was homogenous in size, having an s20,w of 13 to 15 S. It was composed of two subunits: a major component with a molecular weight of 22,500 and a minor component of 29,500. When observed in the electron microscope, K99 appeared to be rod-shaped, with a strong tendency for self-aggregation. At concentrations where aggregation was minimized, individual rods were observed with diameters of 8.4 nm and mean lengths of 130 nm. Based on the subunit structure, exterior location, and rod-like shape of K99, it is concluded that K99 is a pilus or pilus-like structure. Chemically, K99 is composed primarily of protein and has an isoelectric point of greater than 10. Purified K99 did not hemagglutinate guinea pig erythrocytes.


Genetic association of the humoral and cellular immune responses of rats to Moloney sarcomas.

Brown Norway (BN), Lewis (Le), F1 hybrids of LexBN (LBN) and parent-to-LBN backcross rats were tested for cellular and humoral responses to a BN Moloney sarcoma. Regardless of AgB phenotype, BN backcrosses produced low levels of cell-mediated cytotoxicity (CMC) that were comparable to those of BN parents. Le backcrosses developed high levels of CMC similar to those produced in Le parents. An inverse relationship between levels of CMC and serum antibodies (cytotoxic for tumor cells and anti-p30 of MuLV) was observed; BN parents and backcrosses produced high levels of serum antibodies whereas levels in Le parents and backcrosses were low. LBN hybrids developed relatively high levels of CMC and serum antibodies. An additional finding was that the CMC response in Le parents and back-crosses was directed primarily against tumor-associated antigens rather than histocompatability antigens expressed on the tumor cells. The results suggest that humoral and cellular responses to Moloney sarcoma in rats are not determined solely by the major AgB histocompatibility locus but do have a genetic association. This genetic association was detected with a 51Cr release assay which detects T-cells, suggesting that select populations of effector T-cells may be genetically regulated.


Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey.

In cynomolgus monkeys, intracameral infusion of 0.2 to 5.0 mug of cytochalasin B caused an increase in outflow facility, as measured by two-level constant pressure perfusion. Cytochalasin B had its full effect in eyes which had undergone surgical disinsertion of the ciliary muscle from the scleral spur, and were therefore insensitive to pilocarpine. The cytochalasin effect was apparent in less than 20 min. and was largely reversible over a few hours. Thirty to 50 days after the infusion, facility was normal, and a second reaction could be elicited. No early or late damage to anterior segment structures was apparent by routine biomicroscopy during or after the single administration.


Pathogenesis of corneal damage from pseudomonas exotoxin A.

Pseudomonas aeruginosa exotoxin A was injected into rabbit corneas. Death of epithelial, endothelial, and stromal cells resulted, and necrosis of the cornea followed. Control eyes with exotoxin neutralized by specific antitoxin showed minimal damage. A dose-response pattern was evident. Antitoxin neutralization of pseudomonas exotoxin A in corneal ulcers may have possible therapeutic implications.