The cathartic colon: pathological findings and radiological/pathological correlation. Cathartic colon has been described radiologically, but the pathological characteristics have not been reported. The authors describe a case in which radiological/pathological correlation was possible, with emphasis on the pathology of the colon. The disease simulates chronic ulcerative colitis radiologically and pathologically.


Pneumatosis intestinalis in systemic lupus erythematosus. A benign episode of pneumatosis intestinalis developed in a 54-year old black woman with rapidly progressive systemic lupus erythematosus. This case illustrates that pneumatosis intestinalis in association with the various collagen diseases can have disparate prognostic implications.


Histological-venographic correlates in portal hypertension. Magnification hepatic wedge venography and manometry were evaluated in 40 patients with portal hypertension and in 6 normal individuals. Venography (alone or in combination with manometry) generally facilitated prediction of histology in cirrhosis, hepato-venular occlusive disease, periportal fibrosis, congenital hepatic fibrosis, and portal vein obstruction. The magnification wedge venograms demonstrated a number of histological features of cirrhosis that have not previously been described in vivo, including porto-hepatic vein shunts, micro- and macronodular regeneration, and obstructive changes which were more severe in hepatic than in portal veins.


Outpatient arteriography at a small community hospital. Most types of arteriographic procedures are performed on an outpatient basis at Knox County General Hospital. Four years of experience indicates no increased incidence of complications between the inpatient and outpatient groups. No patient had to be admitted to the hospital for delayed complications. Observation within the radiology department or short-stay recovery area for up to four hours seems adequate postarteriographic management and safely avoids routine overnight hospital admission.


Compartmental evaluation of osteoarthritis of the knee. A comparative study of available diagnostic modalities. The distribution and severity of osteoarthritis were investigated in 56 knees by history and physical examination, assessment of knee function, radiography with and without weight-bearing, double-contrast arthrography, and 99mTc-polyphosphate bone imaging. Compartmental involvement (medial, lateral, patellofemoral) was graded independently by 2 or 3 observers for each modality and was correlated with that observed during arthroscopy or direct surgical inspection. The more involved compartments were graded abnormal by all methods. In the less involved compartments, the gamma camera image was most sensitive to pathology, followed by arthrography. The choice of surgical technique and the prognosis depend upon accurate preoperative knowledge of the extent of disease.


Insufficiency and stress fractures of the long bones occurring in patients with rheumatoid arthritis. The occurrence of stress and insufficiency fractures in patients with long-standing rheumatoid arthritis has not been sufficiently emphasized. Osteoporosis due to rheumatoid arthritis and corticosteroid therapy, joint stiffness, contracture, and angular deformity of the extremity, and the unaccustomed exercise after reconstructive joint surgery combine to predispose to the occurrence of these fractures in these patients. The pain and disability caused by these fracture is often attributed to rheumatoid joint involvement. The fracture may not be visible on radiographs obtained near the onset of symptoms, and serial examinations may be needed for diagnosis.


Shoulder arthrography in rheumatoid arthritis. Arthrograms of the shoulder were evaluated in 10 patients with rheumatoid arthritis. The arthrographic findings common to all joints consisted of nodular filling defects, irregular capsular attachments, bursal filling defects and visualized lymphatic drainage. Findings unique to the shoulder joint consisted of rotator cuff tear, frozen shoulder, and biceps sheath dilatation. Since the agents used to treat patients with rheumatoid arthritis have profound side effects, it is important to exclude an associated rotator cuff tear and/or confirm the presence of glenohumeral rheumatoid involvement.


Trephine bone biopsy by radiologists: results of 73 procedures. Trephine bone biopsies were performed in 67 patients. Routine radiography, laminagraphy, and radioisotopic techniques were employed to determine areas of involvement and exact sites for biopsy. Sites were selected on the basis of accessibility, possible complications, and chances of recovering diagnostic material. The biopsy material was informative in 81% of patients. One controllable hemorrhage, one temporary sinus tract, a small pneumothorax requiring no therapy, and two benign vasovagal responses were the only complications. Widespread malignant disease and osteomyelitis, particularly disk-space infection, are the most suitable lesions for trephine biopsy.


Radiology of athletic injuries: baseball. The radiographs and medical records of 29 professional basebell players from several teams were reviewed. Each player had been selected because of radiographic abnormalities. Abduction views of the shoulder were employed in pitchers and outfielders who complained of shoulder pain. Upper extremity abnormalities predominated and accounted for 22 injuries including avulsion injuries of the origin of the long head of the triceps at the infraglenoid tubercle of the scapula and traction injuries at the origin of the pronator muscles at the medial epicondyle of the humerus. Trauma to the lower extremities was caused by collision with a fixed barrier in one man and by running and sliding in 13 others.


Rupture of the quadriceps tendon: diagnosis by arthrography. Arthrography revealed an abnormal tract of contrast agent dissecting from the suprapatellar bursa into the soft tissue anterior to the patella and downward to a level 9 cm beneath the tibial plateau in a patient with complete rupture of the quadriceps tendon. The bursal anatomy of the anterior portion of the knee is reviewed in relation to the capsule-forming structures of the quadriceps expansion. The use of knee arthrography for the assessment of quadriceps tendon injury is advocated.


Changes in the male urethra produced by instrumentation for transurethral resection of the prostate. Radiographic changes produced in the male urethra by instrumentation were studied by pre- and postoperative urethrograms in 50 consecutive men as well as in several hundred selected patients. All 50 patients showed postoperative changes in the urethra. Obvious findings developed in 30% without symptoms while 14% of the men suffered severe symptomatic strictures. In our total operated cases, patients who were entered through the urethral meatus showed a 17.2% rate of stricture formation, while those entered transperineally showed only an 8.5% stricture rate. We conclude that all transurethral instrumentation produces trauma as evidenced by varying degrees of radiographic change.


Metastatic melanoma of the adrenal: an unusual cause of adrenal calcification. A case of metastatic malignant melanoma to the adrenal gland is presented. The radiographic appearance mimicked a benign cystic adrenal lesion because of the presence of curvilinear calcification of its border.


Unusual local reaction to iodinated contrast medium. Injection of water-soluble contrast medium into a foot vein in a 5-month-old infant was complicated by intense edema and vesicle formation above the site of injection. This was due to local toxic effect of contrast medium entering the lymphatic system with backflow into the skin. The method by which the contrast medium entered the lymphatics could not be determined.


Radiographic contrast improvement by means of slit radiography. It is generally believed that properly constructed high ratio grids are very efficient in removing radiographic scatter. The authors show that grids inherently transmit substantial amounts of contrast-degrading scatter and suggest a better method of eliminating it. A system of moving paired slits produces radiographic images with higher contrast than do grids at the same tube voltage. The diagnostic implications are discussed.


Relapsing juvenile chronic subdural hematoma in adult life. Two cases of relapsing juvenile chronic subdural hematoma with late relapse in adult life are presented and the literature reviewed. Both patients contracted subdural hematoma early in life; its persistence resulted in characteristic skull deformitites. The patients led an asymptomatic life until a second head trauma caused rebleeding into the old hematoma sac with recurring symptoms and signs. The source of rebleeding is the outer subdural membrane. Radiographic features vary, depending on the location and size of the subdural hematoma. The significance of localized thickening of the cranium is stressed in refining the differential diagnosis.


Intraosseous leptomeningeal cysts of the posterior cranial fossa. Post-traumatic leptomeningeal cysts involving the occipital bone are intraosseous lesions which do not erode through the outer table, in contradistinction to leptomeningeal cysts elsewhere in the calvaria. In two of four reported cases, communicating hydrocephalus was associated with the intraosseous cyst. The clinical and radiological findings suggest that intraosseous leptomeningeal cyst of the posterior fossa represents a distinct entity. Resection of the cyst and closure of the dural defect may be less important than treatment of the communicating hydrocephalus.


The lateral angiogram in the differentiation of extracerebral hematomas. The pathophysiology of epidural hematomas is considerably different from that of subdural hematomas. Epidural hematomas are well-localized intracranial masses under high pressure, whereas subdural hematomas are more widespread collections of blood under lower pressure. The underlying small cortical vessels are normal in both acute and chronic subdural hematomas but are severely distorted in epidural hematomas. The appearance of these vessels, seen best in the lateral projection, can help differentiate the various types of extracerebral hematomas.


Intimal and medial calcifications of the carotid siphon and cerebrovascular disease. Skull films of 5,570 patients older than 40 years of age admitted to the neurological (4,308), ophthalmologic (1,151), and otorhinolaryngologic clinics (111) of the University of Milan over a period of 20 years were reviewed for carotid siphon calcification. The 485 positive findings were divided into intimal and medial calcifications on the basis of morphological criteria. Signs of cerebrovascular disease in the territory of the internal carotid artery were seen in 35.1% of the intimal group and 37.2% of the medial group. These findings suggest that the two types of calcification do not have different prognostic values as theorized previously.


The widened cervical intervertebral foramen. Widening of an intervertebral foramen in the cervical spine is a striking radiogical finding and generally denotes a patient with a dumbbell spinal tumor. Other, rare causes can also produce widening, such as expansion, tortuosity or elongation of the vertebral arteries, and congenital absence of a pedicle.


Reliability of gallium brain scanning in the detection and differentiation of central nervous system lesions. Both 99mTc-pertechnetate and 67Ga-citrate brain scans were performed in 93 patients with cerebral neoplasms and in 70 others with cerebral infarction or hemorrhage. Tumor detection was clearly better with 67Ga(96%) than with 99mTc(85%). Cerebral infarctions consistently either failed to concentrate 67Ga(67%) of revealed a much lower concentration than the 99mTc study (27%). In 6% of the infarction patients, gallium and technetium scans were equivalent.


Coronary angiographic and scintigraphic findings in experimental cardiac contusion. Clinical, angiographic, scintigraphic and pathologic observations in myocardial contusion were correlated. Radionuclide imaging of the injured heart with 99mTc-Sn-polyphosphate provides an accurate diagnosis in acute, even mild, myocardial contusion. The study can be carried out without danger to the critically ill patient. The coronary angiographic findings in this study explain what is occurring pathologically in the heart. Since arteriography is a more invasive technique than radionuclide imaging, its use is recommended only when the image is negative if it is neccessary to establish the clinical diagnosis for treatment or when more than one week has elapsed since the injury.


Techniques, indications and results of intraoperative radiotherapy of advanced cancers. After removing resectable lesions at operation, residual cancer nests were sterilized by irradiation before surgical closure. The great advantage of intraoperative radiotherapy lies in the treatment of lesions such as gastric cancers located near radiosensitive organs, and radioresistant tumors, such as soft-tissue sarcoma. Since the lesion is exposed directly to irradiation, a cancerocidal dose can be delivered without affecting normal structures. Clinical results have shown that cure can be expected following excision of the primary mass.


A modified Towne's view for radiography of the orbit and maxillary antrum. Routine radiographic examination of the paranasal sinuses and facial bones does not adequately demonstrate the posterolateral margin of the orbital floor. An anteroposterior projection with a 20 degrees cephalo-caudad angulation centered at the glabella adequately demonstrates the posterior and lateral orbital floor and the posterolateral margin of the orbital floor in all patients.


A treatment accessory for CNS irradiation in children. A treatment accessory for use in CNS radiotherapy of small children enables the head and spinal fields to be treated while the child lies supine. Children are not moved during therapy which minimizes the problem of gaps between the head and spinal fields.


An "air-cart" for scintillation camera positioning. An air-cart that operates on the laminar air flow principle was designed to permit easy movement of a scintillation camera detector by one operator. Air flow is obtained from the hospital main supply which is available to each room.


A projection system for effective utilization of ultrasound echogram information in radiation therapy. A system employing an opaque projector mounted on a steel-framed cart was constructed to provide full-scale enlargement of ultrasound echograms for use in radiation therapy planning. Anatomical outlines from the enlarged echograms are traced directly into a minicomputer. Life-sized isodose curves for a selected treatment plan are overlayed on the enlarged echogram to produce a permanent record for treatment field adjustments and retrospective analysis.


Intense transillumination for infant venipuncture. Transillumination of an extremity during venipuncture in infants or obese children is described. Transillumination facilitates accurate placement of the needle tip within the vein.


Extraction of an embolized central venous catheter using percutaneous technique. A method of intracardiac catheter fragment retrieval using a hook-shaped catheter and wire loop snare is described. A venous cutdown was not necessary for removal of the foreign body.


Statement on the use of diagnostic ultrasound instrumentation on humans for training, demonstration, and research: the American Association of Physicists in Medicine. Although no deleterious effects have been reported to date with the use of clinical ultrasound, the AAPM urges caution, especially regarding its prolonged use on any individual for research, training or commercial demonstration purposes. The development of suitable phantoms is suggested.


Diagnostic ultrasound exposure in man.

Diagnostic ultrasound exposure in man. In his review of the AAPM statement on ultrasound, the author feels that allowing "some" research or demonstration on normal persons in the face of cautionary statements on as yet unknown side effects is an inconsistent position.  The use of videotapes and the development of simulators hacked by data banks are offered in place of tissue phantoms.


Diagnostic ultrasound exposure: medical, educational and commercial. Rather than spending scarce research funds on the construction of ultrasonic tissue phantoms (as suggested in the AAPM statement), the author recommends the use of videotapes in place of live models for commercial sales demonstrations. While agreeing with AAPM safety standards, the author feels that an unduly conservative approach could impede the development of newer instrumentation.


Metabolism of prostaglandin f 1 alpha in the pulmonary circulation. 3-H5,6-Prostaglandin F1alpha is largely eliminated from the circulation during a single passage through the pulmonary vascular bed. Its elimination requires cellular uptake. The volume of distribution and the mean transit time of the radioactivity are greater than those of an intravascular marker, blue dextran. The lungs retain 25-30% of the radioactivity, most in the form of a metabolite less polar that PGF1alpha itself. The pulmonary venous effluent contains the same metabolite along with some unmetabolized PGF1alpha. The metabolite can be distinguished from prostaglandins of the A, B, D, E and F series. It is reduced on reaction with borohydride, but reduction does not yield PGF1alpha. NaOH has no effect on the metabolite, a finding that rules out the presence of a beta-hydroxy-ketone configuration of the ring structure. The chromatographic behavior of the metabolite and its reaction with borohydride are those expected of 9,11-hydroxy-15-ketoprostanoic acid.


Alpha-adrenergic stimulants, prostaglandins and catecholamine release from the adrenal gland in vitro. In rat adrenal glands incubated in Locke's solution in vitro norepinephrine and phenylephrine inhibited the release of epinephrine. PGE2 and PGE1 also inhibited the release of catecholamines but PGFalpha1 had no effect on the adrenal. Thus, catecholamine release from adrenal cells may be regulated by the same mechanisms as in adrenergic nerve endings.


Effects of crude and pure cholera toxin on prostaglandin. Investigations were made into the effects of crude and pure preparations of cholera toxin on the release of prostaglandin-like substances (PLS) from rabbit ileum. Perfusion of ileal loops in vivo with buffer containing crude toxin was followed by a release of PLS into the perfusate, in amounts up to 37.5 ng/30 min (PGE2 equivalents). In contrast, no detectable PLS was released when ileal loops were perfused with pure toxin. Similarly, pieces of ileum opened longitudinally released PLS in amounts up to 107 ng PGE2/g tissue when incubated with crude toxin for 1-4 hr, but no release of PLS was detected in the presence of pure toxin under comparable conditions. Treatment of rabbits with indomethacin, 1.6 mg/kg p.o., had no effect on the accumulation of fluid in ileal sacs injected with crude or pure cholera toxin. These results support the view that prostaglandins do not play an essential role in the action of cholera toxin.


Effectiveness of prostaglandin f 2 alpha in restoration of HMG-HCG induced ovulation in indomethacin-treated rhesus monkeys. Six mature female rhesus monkeys were treated with HMG-HCG in control cycles at doses adjusted to induce ovulation while avoiding superovulation. Occurrence of ovulation was determined by observation of fresh ovulation points at laparotomy 48 to 120 hours following HCG. In subsequent cycles animals were treated with indomethacin (treatment days 4 through 10) together with the established dose of HMG-HCG. In 8 cycles indomethacin 5 mg/kg was given i.m. once daily; in 9 cycles 10 mg/kg i.m. was administered in 2 divided doses. Following this, PGF2alpha (3 mg t.i.d. s.c.) was administered for 3 days together with indomethacin 10 mg/kg and HMG-HCG, beginning on the day prior to HCG. Determinations of progesterone were performed by RIA on treatment days 4, 7, 10, and 11. Eleven of the 13 control cycles were ovulatory. With indomethacin 5 mg/kg/day, 5 of 8 cycles were ovulatory but ovulation was delayed in 2 instances. Of 9 cycles using indomethacin 10 mg/kg/day only 1 was ovulatory. When PGF2alpha was administered in susequent cycles along with indomethacin (10 mg/kg) and HMG-HCG, ovulation occurred in 13 of 19 cycles. These data suggest that local ovarian PGF2alpha may be essential in the mechanics of follicle rupture in gonadotropin-treated rhesus monkeys.


Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm. Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E2 suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE2 suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE2 suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2 degrees F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last adminstration of PGE2. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE2 suppositories is a very effective abortifacient technque during the midtrimester, however the use of PGE2 in conjunction with a diaphragm did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE2 suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.


Contractility of rat testicular seminiferous tubules in vitro: prostaglandin  f 1 alpha and indomethacin-1,2. The frequency of spontaneous in vitro contractions of seminiferous tubules of the rat appeared to be increased in a dose-dependent manner by prostaglandin F1alpha. PGF1alpha treatment increased the tonus of the smooth muscle cells in the wall of the tubules as indicated by a reduction in the diameter of the tubules. When the tubules were rinsed successively with fresh Tyrode's solution, the contractile frequency was diminished. Returning the original bathing medium to the tubules restored their contractile frequency, as did treatment of the rinsed tubules with PGF1alpha (10(-7) M). Preinjecting ther rats with indomethacin tended to reduce the contractile frequency of the extirpated tubules. Treating the tubules with a solution of indomethacin for 90 min. in vitro was more effective than pretreatment in vivo in reducing contractile frequency, but a combination of these two procedures produced the greatest inhibition. PGF1alpha restored the contractile frequency of the indomethacin-treated tubules. Our results indicate that PGs modulate the in vitro contractility of the tubules.


Luteolysis induced in pigtail monkeys (Macaca nemestrina) with prostaglandin f 2 alpha, ICI 80996 and ICI 81008. Non-pregnant pigtail monkeys (M. nemestrina) were given ICI 80996 subcutaneously and ICI 81008 and PGF2alpha subcutaneously or intravaginally, once daily on days 20-30 inclusive, or two or three times on days 24 or 26 only. Doses of 50 mug/kg of ICI 80996, 100 mug/kg of ICI 81008 and approx. 1 mg/kg of PGF2alpha were used. In the majority of monkeys treated subcutaneously a rapid fall in circulating progesterone concentrations and earlier than normal menstrual bleeding occurred. When given per vaginam, ICI 81008 was as effective as when given subcutaneously, though PGF2alpha was less effective intravaginally than by the subcutaneous route.


Resolution of prostaglandin p-nitrophenacyl esters by liquid chromatography and conditions for rapid, quantitiative p-nitrophenacylation. The p-nitrophenacyl esters of a number of closely related and isomeric prostaglandins were resolved by HPLC on a microparticulate silica gel column (Zorbax-Sil, DuPont). Ten F-series prostaglandin analogs, eight E-series prostaglandin analogs, the isomeric 15(R)- and 15(S)-methyl prostaglandins of the E- and F-series and, lastly, PGA2 and PGB2 were chromatographed under conditions generating 2,000 to 7,000 theoretical plates. Conditions are described for quantitative conversion of prostaglandins to p-nitrophenacyl esters in less than 6 minutes at room temperature. Linear peak height and peak area plots were obtained for in-situ esterified PGE2 p-nitrophenacyl ester over the range of 0.4 - 3.1 mug. The lower limit of detection of this ester is about 1 ng. A linear relationship is observed between silica gel TLC 1/Rf values and HPLC retention times as predicted by theory.


The antagonism by anti-inflammatory analgesics of prostaglandin f 2 alpha-induced contractions of human and rabbit myometrium in vitro. The anti-inflammatory analgesic drugs, aspirin, indomethacin, phenylbutazone, mefenamic acid ibuprofen and flurbiprofen are shown to inhibit in a dose-dependent manner the force of contraction of isolated human pregnant myometrial strips which have been stimulated to contract by adding prostaglandin (PG) F2alpha to the tissue bath. These drugs and also flufenamic acid and salicin show a similar antagonism of the action of PGF2alpha with isolated rabbit non-pregnant myometrium. The ratio of the inhibitory concentration in vitro to the maximum plasma level after a normal dose in vivo suggests that phenylbutazone and possibly ibuprofen may be capable of inhibiting human uterine contractions in vivo. Patients who were treated with aspirin during induction of abortion using PGF2alpha during the second trimester of pregnancy showed no significant change in the induction-abortion interval compared with patients not taking aspirin.


Prostaglandin synthesis by rheumatoid synovium and its stimulation by colchicine. The synthesis of prostaglandins by rheumatoid synovial tissue in organ culture was studied utilizing radioimmunoassay, with antisera to PGB1, PGF1alpha and PGF2alpha. It was established that PGE2 and PGF2alpha were the major prostaglandins formed by analyses of culture media with the two antisera to PGF, before and after alkali treatment. Indomethacin at 5 mug/ml suppressed prostaglandin synthesis, usually to less than 1% of control cultures. Colchicine, 0.1 mug/ml resulted in marked stimulation of prostaglandin synthesis, in some cases over 10 fold. It is suggested, because of the colchicine effect, that the state of the microtubules may regulate the rate of prostaglandin biosynthesis. It is possible that prostaglandin E2 produced by rheumatoid synovia may contribute to the pathogenesis of the inflammatory reaction and lead to destruction of juxta-articular bone in rheumatoid arthritis.


Prostaglandin-induced enhancement of the in vitro anamnestic response. The ability of various prostaglandins (PGs) to affect the in vitro anamnestic immune response of keyhole limpet hemocyanin (KLH)-primed rabbit popliteal lymph node cells was investigated. Of the four PGs studied (PGA1, PGE2 and PGF2alpha), PGE1 was found to have a stimulatory effect, whereas PGA1, PGE2 and pgf2alpha were ineffective in stimulating or inhibiting the in vitro anamnestic response. Under the conditions studied, a 3.5-fold increase in antibody production was obtained in PGE1-treated, KLH-stimulated cultures. Maximum enhancement was obtained when 0.2 mug of PGE1 were added at the time of culture initiation and were allowed to remain in contact with the lymph node cells for 24 hours.


The synthesis of prostaglandin analogs containing hydroxycyclohexenyl rings. The synthesis of prostaglandin analogs incorporating the 3-hydroxycyclohexenyl moiety in place of the natural C13-C20 side-chain has been accomplished via copper-assisted conjugate addition of the cycloalkenyllithium 2 to the cyclopentenous intermediates 4, 7 and 10.


Stereospecificity of enzymatic reduction of prostaglandin E2 to F2alpha. Antibodies directed toward PGF2beta were prepared in rabbits. The serologic specificity of the immune reaction was determined by inhibition of sodium borohydride-reduced (3H) PGE2 anti-PGF2beta binding by several prostaglandins. The antibodies to PGF2beta recognize the beta-hydroxyl configuration in the cyclopentane ring of PGF2beta. With the use of both anti-PFG2alpha and anti-PFG2beta, the product of PGE2 reduction by 9-ketoreductase purified from chicken heart was identified as PGF2alpha. Guinea pig liver and kidney homogenates were examined for PGE 9-ketoreductase activity. Although enzyme activity was present, no evidence of PGF2beta production was found.


Prostaglandin E2 effects on cation flux in sickle erythrocyte ghosts. Prostaglandin E2 has previously been shown to enhance the shape transformation of sickle prone erythrocytes (8) and to reduce the oxygen resaturation of Hemoglobin SS within intact sickle cell erythrocytes after deoxygenation (15). In view of the recent importance attributed to calcium transport in maintaining erythrocyte shape and viability (10) and the suggestion that prostaglandins may act via a calcium ionophore mechanism (9) on cell membranes, erythrocyte ghosts were prepared following the method of Lepke and Passow (12) from normal and sickle cell anemia erythrocytes. These two classes of ghosts are shown to display differing patterns of sodium and calcium transport, whith calcium influx being preferentially stimulated by prostaglandin E2 in sickle cell ghosts. It is suggested that in hypoxic, stasis conditions in vivo, prostaglandins may play a role in accelerating sickling of sickle prone erythrocytes via stimulation of calcium influx.


Effects of indomethacin and prostaglandins on ovulation of goldfish. A technique is described whereby elevated temperature and HCG injection yield a high percentage of ovulation in gravid goldfish. Indomethacin (10 mug/g; i.p. injection) completely inhibits ovulation if given within 6 hours following HCG (4 IU/g); the unovulated oocytes develop rapidly into corpora atretica. PGE1, PGE2, and PGF2alpha (5 mug/g; i.p. injection) induce ovulation in fish treated with indomethacin and HCG; PGE2 was most effective when given 11 hours after HCG. The results suggest that the ovulatory action of prostaglandins following HCG stimulation is at the level of the ovary and that it is restricted to a period between 7 and 12 hours after the gonadotropin injection.


Midtrimester abortion induced by single intra-amniotic instillation of two dose schedules of 15(S)-15-methyl-prostaglandin F2alpha. Midtrimester abortion was successfully induced in a series of 20 patient by intraamniotic instillation of 15(S)-15-methyl-prostaglandin F2alpha with a mean abortion time of 17.78 hours. The patients in this study was divided into two groups, Groups 1 received an initial dose of 2.5 mg 15-ME-PGF2alpha and aborted in a mean time of 16.26 hours. The patients in Group II received 3.0 mg 15-ME-PGF2alpha and aborted in a mean time of 18.94 hours. There was no significant difference in the abortion time, occurrence of side effects or the initiation of uterine activity between Group I and Group II. Parous patients aborted somewhat faster than nulliparous patients but this difference was not significant. In this study 80% of the patients aborted in 24 hours or less, and the intra-amniotic instillation of 15-ME-PGF2alpha was an effective abortifacient technique from the 15th to the 23rd week of gestation. The uterine response to intra-amniotic instillation of 15-ME-PGF2alpha was characterized by the gradual appearance of low amplitude, high frequency contractions accompanied by a rise in baseline intrauterine tonus. Uterine activity developed gradually and peaked at 1:50 hours after intraamniotic instillation of 15-ME-PGF2alpha. In this small series 15-ME-PGF2alpha administered via intra-amniotic instillation did not appear to have a distinct advantage over the naturally occuring PGF2alpha administered by the same method for the induction of midtrimester abortion; a large series in indicated to define the advantage of either technique.


Cervical dilatation with prostaglandin analogues prior to vaginal termination of first trimester pregnancy in nulliparous patients. Dilatation of the cervix with prostaglandin analogues prior to vaginal termination of pregnancy was attempted in 125 nulliparous women in the first trimester of pregnancy. The patients were divided into five groups (25 in each group) and given a single extra-amniotic dose of one of the following prostaglandin analogues 14-16 hours prior to the evacuation of the uterus by vacuum aspiration. (Group A) 15 (S) 15 methyl PGE2 (free acid); (Group B) 15 (S) 15 methyl PGE2 methyl ester; (Group C) 15 (S) 15 methyl PGF2alpha (free acid); (Group D) 15 (S) 15 methyl PGF2alpha methyl ester and(Group E) a mixture of 15 (S) 15 methyl PGE2methyl ester and 15 (S) 15 methyl PGF2alpha methyl ester. Evacuation of the uterus without mechanical dilatation of the cervix was possible in 111 (90%) of the patients. In an additional 10 patients (8%) there was some degree of cervical dilatation and further mechanical dilatation could be performed easily. With the combination of 15 (S) 15 methyl PGE2 methyl ester and 15 (S) 15 methyl PGF2alpha methyl ester the incidence of gastrointestinal side effects and pyrexia were considerably reduced.


The effect of indomethacin of HMG-HCG induced ovulation in the phesus monkey. The investigation was designed to study the influence of indomethacin on gonadotropin induced ovulation in the rhesus monkey. Six mature female monkeys were treated with HMG-HCG for at least 2 control ovulatory cycles at dosage levels adjusted to induced ovulation while avoiding superovulation. Ovulation was confirmed by observation of the ovaries for fresh ovulation points at laparotomy. Following establishment of an appropriate dosage schedule, treatment was begun with indomethacin (5 mg/kg/day) starting 5 days prior to HCG and continuing to the time of laparotomy. In a second treatment cycle, indomethacin was administered at a dose of 5 mg/kg b.i.d. together with the established dose of HMG-HCG. Ovarian inspection was carried out as in the control cycles. Venous blood was obtained on treatment days 4, 7, 10 and 11 for determination of serum estrone, estradiol and progesterone. Indomethacin administration resulted in ovulation inhibition at a dose of 10 mg/kg/day when ovulation inducing doses of gonadotropins were administered. Peripheral blood steroid levels suggest that follicle maturation and estrogen production was unimparied by indomethacin. These findings indicate that the ovarian synthesis of prostaglandin may be essential in the process of ovulation.


Quantitative electroencephalographic studies of the effects of ethanol in rabbits= I. Interaction between ethanol and reserpine. At a dose of 1 g/kg i.v. ethanol induced in the cortical EEG of rabbits a synchronization which lasted 2-3 hours. Thereafter a pronounced hyper-stimulation occurred which persisted up to 4 hours. Pre-treatment of the animals with reserpine reduced markedly the initial synchronization and abolished the delayed stimulant effect. These findings are discussed in terms of possible interaction between acetaldehyde and biogenic amines.


Separation and quantitative analysis of furosemide and 4-chloro-5-sulfamoylanthranilic adid (CSA) by high pressure liquid chromatography. After extraction by ether from acidified plasma or urine and concentration into basic phosphate buffer, furosemide and 4-chloro-5-sulfamoylanthranilic acid (CSA) were separated on a high pressure liquid ion-exchange system and measured fluorometrically. Sensitivity is 0.2 mug/ml of ether compound in plasma and 0.1 mug/ml in urine with an 8% coefficient of variation. Interference by porphyrins in urine was eliminated by subtracting a second fluorometric measurement at a different wave-length from that used for furosemide. No quenching at this wave-length is seen with concentrations of furosemide up to 50 mug/ml. Standard curves of furosemide and CSA are linear from 0.2 mug/ml to 50 mug/ml.


Developmental change in the apparent kinetic properties of drug-oxidizing enzymes in the human liver. When analyzing the effect of substrate concentration on the reaction rate of aminopyrine N-demethylation, aniline p-hydroxylation, and 3,4-benzpyrene hydroxylation by human fetal and adult liver samples we found that Lineweaver-Burk and Eadie-Hofstee analyses yielded mostly linear lines with fetal liver, but nonlinear lines with adult livermthis may be taken to indicate that a qualitative change in drug-oxidizing enzymes of the human liver occurs during ontogenetic development, of the human liver occurs during ontogenetic development, possibly so that during the fetal period liver contains one ana during the adult period two enzymes metabolizing aminopyrine, anilinw, and 3,4-benzpyrene.


A new simple and rapid method to monitor the renal function based on pharmacokinetic consideration of endogeneous creatinine=. Based on the linear single-compartment pharmacokinetic consideration of endogeneous creatinine a new equation is derived to estimate the true creatinine renal clearance and hence the renal function of a patient; By using this equation one can estimate clinically the creatinine renal clearance of a patient simply by measuring the creatinine serum levels at two different times without the necessity of urine collection. Almost a perfect prediction of the status of renal function in two anephric patients was demonstrated using this proposed methodmwith a sensitive assay technique for endogeneous creatinine, the proposed equation would enable on to monitor the creatinine clearance on an hourly basis= The method is especially valuable to monitor the rapidly changing (improving or deteriorating) renal function in all types of patients and also in certain groups of patients whose urine is difficult to ba accurately collected;


Treatment of tumour bearing mice with liponsome-entrapped actinomycin D prolongs their survival. The possibility of employing liposome-entrapped actinomycin D for the treatment of AKR mice inoculated with AKR-A cells was examined. It was found that injection of actinomycin D after its entrapment in liposomes prolonged the survival of such mice to a greater extent than did similar amounts of free actinomycin D. Data from in vitro experiments suggest that entrapped actinomycin D could localize in the nucleus of AKR-A cells presumably following endocytosis of the liposomal carrier and subsequent liberation of the drug in, and its diffusion from, the lysosomes.


Influence of phenobarbital pretreatment on tissue catecholamine content of various animal species. The influence of phenobarbital pretreatment on tissue catecholamine content was studied in various animal species. The results reported in this communication whow that such pretreatment increases the catecholamine content of the adrenal and the male accessory sexual tissues of the guinea-pig and the rabbit, while with the rat and hamster, only the adrenaline content of the adrenals was increased. In the female guinea-pig, there was an increase in the catecholamine content of the adrenals and the female accessory sexual tissues. It was concluded that the difference observed among species may be related either to the different type of adrenergic innervation or to a different influence of the adrenal gland on the sexual accessory tissues.


On the origin of desmethyl imipramine in rat brain. The formation of DMI after incubation of IP-C-14 with supernatant fractions prepared from brain and liver of male Wistar rats were studied to determine the sources of DMI in brain tissue. IP and its metabolites were isolated by thin layer chromatography, eluted and counted in a Geiger-Muller counter. A substantial amount of DMI was formed when the liver supernatant fraction was used, whereas the brain fraction did not form DMI even at low level. Under the incubation condition used, about 2.7% of IP was converted non-enzymatically to a DMI-like substance. Based on the results presented it appears that at least most of the DMI reported by other authors to be formed in rat brain after IP administration, reaches the brain via the blood stream.


Warfarin-phenylbutazone interaction in man: a long term multiple dose study. The effect of phenylbutazone on the disposition of warfarin was studied in a subject given warfarin daily for one month. During concomitant phenylbutazone administration, the total plasma warfarin concentration declined from 4.2 to 2.0 mg/L. In contrast, the unbound warfarin plasma concentration rose from 0.020 to 0.033 mg/L. The plasma concentration and daily urinary excretion of 7-hydroxywarfarin fell during phenylbutazone administration. Warfarin is administered as a racemate. Exclusive to and the major metabolic route of the more potent S-isomer is 7-hydroxylation. It is concluded that inhibition of S-warfarin metabolism can help explain the increased anticoagulation seen when phenylbutazone is added to the dosage regimen of a patient stabilized on warfarin.


Effects of various protein-modifying agents and the aminonucleoside of puromycin on dithioerythritol-reducible disulfide in glomerular basement membrane. Comparative study of dithioerythritol-reducible (DTE) disulfide bonds in glomerular basement membranes (GBM) isolated from normal rats and from similar groups of rats treated with the nephrosis-producing aminonucleoside of puromycin emphasize not only the importance of such linkages in the interaction and structural organization of the macromolecular GBM collagen-glycoprotein matrix but also suggest a modality by which GBM semi-permeability might be engendered. Although DTE-reducible disulfide is significantly reduced in GBM of rats as early as the fourth day after administration of a nephrosis-producing dose of the aminonucleoside it has not been possible to demonstrate an unequivocal in vitro or direct effect of the drug on DTE-reducible disulfide in normal GBM. Several-fold increases in DTE-reducible disulfide in GBM subjected to the denaturing action of guanidine-HCl or the proteolytic action of pronase indicates that most of the disulfide lies buried in the GBM. Location of disulfide crosslinks in the innermost regions or core of the GBM might be expected to not only stabilize the membrane but also to protect the GBM from a considerable array of disulfide cleaving (reductases) within the kidney cortex.


Australia antigen (HBsAg) carriers in a Greek community. Studies of transaminase (SGPT) levels. A study of SGPT levels in individuals with and without (HBsAG) was conducted in the village of Plati, Greece. The levels were higher in those with HBsAG  than without (p equals .007). The levels were higher in males than in females. From this and other studies it is concluded that at least some asymptomatic carriers had mild but detectable liver damage.


Terminal deoxynucleotidyl transferase and human leukemia. Terminal deoxynucleotidyl transferase activity is as much as several hundred fold greater in acute leukemic lymphoblasts than in unstimulated or phytohemagglutinin stimulated normal lymphocytes, and in leukocytes from other leukemias or from acute lymphoblastic leukemia patients in remission. On the other hand, acute leukemic lymphoblasts and myeloblasts  as well as phytohemagglutinin stimulated normal lymphocytes have DNA polymerase activity an order of magnitude higher than that in unstimulated normal lymphocytes, and in leukocytes from chronic leukemias or from acute lymphoblastic leukemia patients in remission. Terminal deoxynucleotidyl transferase thus appears to be a useful index for the detection of leukemic lymphoblasts.


Enhanced thyroxine metabolism following cutaneous application of microscope immersion oil. Microscope immersion oil, applied to the skin of rats or injected intraperitoneally, led to a substantial increase in the biliary excretion of intravenously injected 125-I-thyroxine (T4), elevated the bile: plasma 125-I ratio, enhanced the biliary clearance rate of plasma 125-I-T-4 and increased the proportion of biliary 125-I present as T-4-glucuronide. Immersion oil applied to the skin was at least as effective as injected intraperitoneally. Skin application also elevated bile flow, liver weight, thyroid 131-I uptake and Sephadex uptake of serum 125-I-triiodothyronine (indicating reduced binding of thyroid hormone to serum proteins) and depressed serum T-4 concentrations. These effects were similar to those previously observed after intraperitoneal injection of a polychlorinated biphenyl mixture.


Influence of PKa on the methylation of arylalkylamines by rabbit lung N-methyltransferase. Substitution of one or two fluorine atoms on the B carbon of phenethylamine progressively reduced the pKa of the amine and increased its rate of methylation by N-methyltransferase from rabbit lung. The methylation of other amines (amphetamine and benzylamine) was similarly increased by decreases in pKa. The results suggest that the neutral nonprotonated amine is the molecular species attacked or preferred by this enzyme.


Effect of prenatal administration of T-2 toxin to mice. T-2 toxin administered ip to mice at 1.0 and 1.5 mg/kg caused significant maternal mortality and decreased prenatal survival. Fetal weights were reduced on days 7, 10, and 11. Gross malformations involved the tail and limbs, exencephaly, open eye and retarded jaw development particularly in fetuses from females treated on days 9, 10, and 11. Ribs and vertebral malformations were seen in fetuses exposed on days 9 and 10.


Effect of pentoxifylline on energy rich phosphates in rat's erythrocytes. After an oral administration of 5 mg/kg pentoxifylline (3, 7-dimethyl-1-(5-oxo-hexyl)-xanthine, Trental -R) increases significantly total adenine nucleotides content, ATP and AMP, and decreases significantly ADP in rat's erythrocytes. This increased ATP level is likely partly responsible for the therapeutic effect of pentoxifylline in the disturbed peripheral circulation.


Decrease in rabbit lung microsomal cytochrome P-450 levels following ozone exposure. Exposure of Rabbits to 1.0 ppm ozone for 90 minutes results in a decrease in lung microsomal cytochrome P-450 levels.


Evaluation of altered blood-brain barrier permeability to amino acids. The blood-brain barrier (BBB) in one cerebral hemisphere of rabbit was damaged by the ipsilateral infusion of hypertonic (3 Molar) urea into the carotid artery. Using the indicator diffusion technique, the clearance of the glycine (by simple diffusion) and phenylalanine molecule (by facilitated diffusion) was enhanced in the urea infused cerebral hemisphere. The experimental methodology is a nondestructive and sensitive method for evaluating the integrity of the BBB.


Action of the anti-inflammatory agents, acetylsalicylic acid, indomethacin and fenoprofen on the gastric mucosa of dogs. Into the Heidenhain pouches of 3 dogs 30 ml of 0.1N HCl was instilled and removed at 30-minute intervals for 6 hours. During the 3rd and 4th periods the acid instillate contained 4.5 mg/ml or 12.4 mM of ASA, indomethacin or fenoprofen. All 3 agents affected the functional integrity of the mucosal barrier, but the characteristics of their actions were different. The H+ concentration was decreased by ASA and fenoprofen and increased by indomethacin when the instillate contained drug. All 3 drugs increased the net flux of Na+, K+, Ca++ and Mg++. Following initial augmentation of instillate volume and H+ concentration, indomethacin caused sustained back diffusion of acid from lumen to mucosa; this was accompanied by mucosal bleeding. Peak effects of ASA on the net flux of ions occurred during or immediately after drug infusion and were greater than those of indomethacin and fenoprofen. Fenoprofen at 12.5 nM had no effect on concentrations of Ca++ and Mg++ while both were significantly increased by equal molar dose of ASA or indomethacin. In onset of action indomethacin was slow but once disruption of functional integrity started, it continued for hours showing no signs of returning to normal condition. In this sense, the total disruptive action of an equal weight or molar dose of indomethacin was greater than that of ASA or fenoprofen. At pH 1, the absorption of ASA from the Heidenhain pouch was greater than that of indomethacin and fenoprofen; their respective concentrations in the plasma were 53.9, 14.2 and 13.7 mumol.


Some serum protein studies in Crohn's disease and ulcerative colitis. An auto-immune origin was postulated previously for ulcerative colitis. The present results do not support this hypothesis. Crohn's disease has been compared to sarcoidosis and lymphogranuloma venereum. Crohn's disease may be a virus infection coming from the bowel content. The virus may multiply, for instance, inside the submucosal lymphocytes.


Effects of prostaglandin E2 and indomethacin on responses of the isthmus of rabbit oviduct to norepinephrine and transmural stimulation. The effects of prostaglandin E2 and of indomethacin on the responses of the circular muscle of the isthmus of rabbit oviduct to (-)-norepinephrine and to transmural stimulation were determined. At 26 degrees C, 10 ng/ml prostaglandin E2 significantly reduced responses to transmural stimulation but had little effect on responses to (-)-norepinephrine. At 26 degrees C, 5.6 x 10(-5)M indomethacin slightly reduced responses to both transmural stimulation and to (-)-norepinephrine. At 37 degrees C, spontaneous desensitization to both stimulation and to (-)-norepinephrine occurred but transmural stimulation was more inhibited. Addition of 2.8 x 10(-6)M indomethacin prevented this desensitization. These results suggest that responses of the isthmus of rabbit oviduct to (-)-norepinephrine were not dependent on prostaglandin generation. Adrenergic transmission to the oviduct was, however, inhibited by prostaglandin E2. Evidence was also obtained for the spontaneous liberation at 37 degrees C of prostaglandins that inhibited the contractility of the oviduct.


The growth-inhibiting effect of sodium pentobarbital on the body weight of the chick embryo. A single dosage of sodium pentobarbital (5.0 mg/0.1 ml) given during the embryonic period inhibited the body weight of the chick embryo from 10 through 18 days of incubation. The mean wet and dry weight of the barbiturate-treated embryos were lowered significantly. This weight-decreasing effect was not observed in the hearts or livers of the barbiturate-treated specimens.


Analgesic activity of substituted benzylidinohydrazines. Sixteen substitued benzylidinohydrazines were evaluated for morphine-like analgesic activity by mouse tail-pinch test while aconitine-induced writhing test in mice was used to determine their ability to possess aspirin-like analgesia. All benzylidinohydrazines exhibited analgesic activity where protection against tail-pinch and aconitine-induced writhing response ranged from 16.7-83.3% and 16.7-66.7%, respectively.


Increased survival of mouse ependymoblastoma hosts previously treated with dehistonized tumor chromatin. Half of the mice treated with dehistonized chromatin (protein-DNA complex) from a transplantable mouse ependymoblastoma before subcutaneous challenge with the syngeneic tumor survived twice as long as untreated animals.


Lipid peroxidation: a possible mechanism for paraquat toxicity. The toxicity of the herbicide paraquat in mice, measured by the single dose lethal to 50 per cent of the animals after 7 days, was significantly enhanced by prior exposure to diets deficient in selenium or vitamin E and by pretreatment with diethyl maleate. These data suggest lipid peroxidation to be an important in vivo biochemical mechanism of paraquat toxicity as both selenium and vitamin E have antioxidant functions.


Age differences affecting induction of hepatic drug metabolizing enzymes by methaqualone and phenobarbital in the rat. Methaqualone pretreatment for 3 or 6 days caused an induction of hepatic enzymes in the young male rat as measured by a reduction in hexobarbital-hypnosis. However, methaqualone pretreatment had no effect on the hexobarbital-hypnotic response in older male rats. Phenobarbital was a more potent enzyme inducer than methaqualone, and caused induction of liver enzymes in both age groups.


Palytoxin: effects on contractility and 45Ca2+ uptake in isolated ventricle strips. Palytoxin (PTX) inhibited phasic tension production and initiated tonic contracture in isolated paced ventricle strips at concentrations greater than 10(-10) M. PTX-induced contracture was associated with increased 45Ca2+ uptake. PTX-induced additional 45Ca2+ uptake was completely blocked by 2 mM La3+. All observed PTX effects were enhanced by elevation of [Ca2+] o from 1.9 to 6 mM and this threefold increase in [Ca2+] o resulted in a threefold increase in isotope-determined Ca2+ uptake in presence of 10(-8) M PTX. It is concluded that the observed effects of PTX could be mediated by an increase in calcium permeability of myocardial cells.


Studies on the role of dopaminergic systems in morphine-induced motor activity. Comparison with noradrenergic and cholinergic systems. The role of dopaminergic, noradrenergic and cholinergic systems in morphine-induced motor activity was investigated in mice using both blockers and stimulators of the receptors of the respective systems. The dopaminergic blocking drugs, spiroperidol and clothiapine, significantly reduced while stimulating dopaminergic receptors with amantadine significantly increased morphine-induced motor activity. Blockade of noradrenergic receptors with phenoxybenzamine and cholinergic receptors with atropine significantly reduced morphine activity whereas stimulation of either of these systems with DOPS and physostigmine respectively, had no effect. These data suggest that a dopaminergic system mediates morphine-induced motor activity and that this can be modified by interrupting either noradrenergic or cholinergic systems.


Regulation of succinic dehydrogenase activity of heart mitochondria by anti-arrhythmic drugs. It was observed that either propranolol or iproveratril could increase the succinate oxidation activity by rat heart mitochondria to 444% and to 371% respectively. Both drugs decreased the respiratory control coefficient and ADP/O ratio. No effect on mitochondrial succinic dehydrogenase, succinic dehydrogenase-Co Q-reductase and malic dehydrogenase was observed. It was pointed out that these drugs would act preventing the reoxidation of NADH+ + H+ through the respiratory chain.


The pharmacokinetics of procainamide in normal subjects using a specific gas chromatographic assay. Previous procainamide pharmacokinetic studies have involved the use of colorimetric and fluorimetric methods for the determination of drug concentrations in plasma and urine. However, recent evidence shows that N-acetyl procainamide, the major metabolite in humans, is hydrolyzed during these assay procedures. As a result, a specific gas chromatographic method has been developed for the determination of procainamide in biological fluids. Using this assay procedure, the pharmacokinetics of procainamide were studied in 7 normal subjects following intravenous administration of the drug. The values of half-life (2.08 +/- 0.52 hr), volume of distribution (4.3 +/- 0.6 1/Kg) and total body clearance (1344 +/- 238 ml/min) found in this study differed from those previously reported. These discrepancies could be understood in terms of differences in assay specificity.


Recovery of procaine from biological fluids. A published method for the recovery of procaine from human plasma using 5M NaOH gave very poor recoveries. Investigation showed that under the recommended extraction conditions procaine was rapidly hydrolysed. Extraction into benzene of samples buffered to pH 9.0 with borate buffer allowed essentially 100% recovery of procaine from equine plasma and urine.


The involvement of methysergide-sensitive receptors and prostaglandins in the hyperthermia evoked by 5-HT in the cat. In the unanesthetized cat, an injection of 0.01 or 0.03 M 5-hydroxytryptamine into the rostral hypothalamus produced an immediate, short-lasting increase or decrease in body temperature. A delayed and long-lasting hyperthermia often followed the initial response. When indomethacin, 10 mg/kg, was administered intraperitoneally 3 hours prior to an injection of 5-hydroxytryptamine at sites which produced an initial increase in body temperature, the secondary hyperthermia was reduced or abolished but the immediate response remained undiminished. Pretreatment with methysergide, 2 mg/kg i.p., attenuated or abolished the initial temperature increase but did not reduce the delayed hyperthermia. The results suggest that the initial rise in body temperature produced by 5-hydroxytryptamine is mediated by activation of methysergide-sensitive 5-HT receptors and that the response is independent of prostaglandin release. The secondary hyperthermia, on the other hand, is apparently mediated by a sustained release of prostaglandins.


Carbamazepine-10,11-epoxide metabolites in rat urine. The metabolism of carbamazepine-10,11-epoxide, after administration of the epoxide to rats has been studied. The iminostilbene epoxide and the 10,11-dihydrodiol of the iminostilbene have been identified as metabolites of carbamazepine-10,11-epoxide by means of gas chromatographic and gas chromatographic-mass spectrometric techniques.


Comparative bioavailability of anhydrous griseofulvin and its chloroform solvate in man. Using a crossover experimental design, the absorption profile of griseofulvin was assessed in human volunteers after oral administration of a 500 mg dose of the antifungal antibiotic as capsules of the anhydrous (nonsolvated)-and monochloroform solvate forms of the drug. The maximum body level of drug and the rate and extent of griseofulvin absorption (or bioavailability) were significantly increased after administration of the chloroform solvate as compared to that observed after administration of the nonsolvated form of the drug. The enhanced absorption of griseofulvin chloroformate correlated well with its enhanced solubility and dissolution rate at 37 degrees C in simulated intestinal fluid (20 mM sodium deoxycholate, pH 7.5). This is the first demonstration of a drug-organic solvate displaying improved gastrointestinal absorption characteristics over the anhydrous form of a drug.


Microassay of an arylamidase in needle biopsies of human liver. A method is described for determination of liver arylamidase activity in homogenates of the small amount of human as well as experimental animal tissues (approx. 5-15 mg wet wt.) obtained by needle biopsy. One milligram of human liver contains 90-130 mug protein. The arylamidase activity in normal liver was 0.2 to 0.6 nmoles benzylhydrazine formed/mug protein/hr. The microdetermination of an arylamidase described in this paper is worth in the diagnosis of hepatic injury because of the use of biopsy sample.


Study of periodontal disease and coenzyme Q. A 25-year old Caucasian with uniquely severe and chronic periodontal disease, requiring extraction of all teeth, was treated with hexahydrocoenzyme Q4 which functions like naturally occurring coenzyme Q10 in gingival tissue. During the fourth and fifth examinations after the seventh and eighth weeks of treatment, three dentists separately and independently scored clinical improvements of five symptoms by significances of essentially P less than 0.01 to P less than 0.001. The initial benefit of the treatment was observed at the second examination after three weeks of treatment. The administration of coenzyme Q could be an important therapeutic adjunct to periodontal therapy for certain patients.


Bioenergetics in clinical medicine. Studies on coenzyme Q10 and essential hypertension. The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs.


Inhibition of epidermal DNA synthesis by cycloheximide and other inhibitors of protein synthesis. Cycloheximide, pactamycin and tenuazonic acid inhibit protein synthesis in eukaryotic cells. It is the purpose of these studies to determine whether these agents would be effective in vivo inhibitors of epidermal DNA synthesis. Single I.P. administration of 1.5 mg/kg cycloheximide, 0, 1 or 3 hours prior to a 45 minute pulse of thymidine-3H inhibited epidermal DNA synthesis by 68%, 63% and 88%, respectively. This response was dose related at 3.75 hours after cycloheximide with no effect at 0.375 mg/kg and maximal inhibition at 1.5 mg/kg. Epidermal DNA synthesis was inhibited 18, 29 and 62% at doses of 1.5, 3.0 and 6.0 mg/kg pactamycin administered 3 hours before thymidine-3H. Similarly, at doses of 70 and 140 mg/kg tenuazonic acid, epidermal DNA synthesis was inhibited by 50% and 60%, respectively. These data suggest the possible use of protein synthesis inhibitors in epidermal disorders.


Indomethacin release from silicone rubber: a suggested method for continuous inhibition of prostaglandin synthesis. Indomethacin was vulcanized in dimethylpolysiloxane, an inert silicone suitable for tissue implantation. The drug is released from this polymer matrix gradually in amounts that can inhibit endogenous prostaglandin synthesis. The method is simple, rapid and inexpensive and eliminates repetitive administration in studies where prolonged inhibition of prostaglandin synthesis is desired.


Comparative effects of kanamycin and amikacin on aortic blood pressure, cardiac rate and surface electrocardiogram in the conscious dog. Intravenous infusion in conscious beagle dogs of either kanamycin or amikacin to doses of 30 mg/kg resulted in little or no detectible dose related effects on mean aortic blood pressure, cardiac rate, the surface electrocardiogram or gross behavior. Increasing doses of kanamycin and amikacin resulted in dose-related increases in the plasma levels of the two antibiotics. These results indicate that in the conscious dog high plasma levels of kanamycin (64 mug/ml) and amikacin (78 mug/ml) were not associated with depression of systemic blood pressure.


Growth hormone and liver mitochondrial protein synthesis effect of cortisol and estradiol. The effect of cortisol and estradiol on the stimulation by growth hormone of liver mitochondrial protein synthesis in hypophysectomized rats has been studied by measuring radioactive leucine incorporation in vivo and in vitro. Estradiol inhibited the stimulatory effect of growth hormone on incorporation into mitochondrial and microsomal proteins. Cortisol blocked the stimulatory effect of growth hormone on mitochondrial protein synthesis. The stimulatory effects of cortisol and growth hormone on microsomal incorporation were not additive. Gain in body weights corresponded with their effects on mitochondrial and microsomal protein synthesis. These results show that steroid hormones may act as regulators of the growth hormone effect.


Inhibitory effect of nickel and chromium upon antibody response of rats to immunization with T-1 phage. Nickel and chromium significantly depressed the circulating antibody response of rats immunized with a viral antigen (T-1 phage). Consistent suppression of antibody was observed in all metal-treated animals; the greatest decrease in antibody titers was noted in animals receiving metals two weeks prior to the initial antigen dose.


Plasma cannabinoids measured by radioimmunoassay in rabbits after intravenous injection of tetrahydrocannibinol, 11-hydroxy-tetrahydrocannabinol, cannabinol and cannabidiol. An antiserum raised in sheep against a conjugate of tetrahydrocannabinol with bovine serum albumin has been used as the basis of a radioimmunoassay for cannabinoids in the blood of rabbits given tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, cannabinol or cannabidiol by rapid intravenous injection. In the case of both 11-hydroxy-tetrahydrocannabinol and cannabinol plasma cannabinoid concentrations fell exponentially from an initial peak plasma level attained immediately after the completion of intravascular distribution of the injected bolus. In the case of tetrahydrocannabinol itself, however, there was a progressive rise in plasma cannabinoid concentration between five and fifteen minutes after the rapid intravenous injection. The reasons for this rise in plasma cannabinoid concentration are discussed.


Transformations of cannabinol in the mouse. The in vivo transformations of cannabinol (CBN) in the mouse have been studied and a pattern of metabolism established. As with other cannabinoids, the 7 position and the side chain are hydroxylated followed by further oxidation to acidic metabolites. Two of these CBN metabolites have been isolated previously as metabolites of delta1-tetrahydrocannabinol (THC) suggesting that CBN may be a transformation product of delta1-THC.


Brain and blood levels of ethanol and acetaldehyde in strains of mice with different preferences for ethanol. The ethanol level in brain and blood and the blood level of acetaldehyde upon waking from an anesthetic dose of ethanol were found to be significantly higher in C57BL/6J mice which prefer to drink ethanol solution over water than in DBA/2J mice which avoid the drinking of an ethanol solution. The brain level of acetaldehyde did not differ significantly between the two mouse strains. Possible explanations for the difference in brain sensitivity toward ethanol are discussed.


Methadone plasma levels in maintenance patients: the effect of dose omission. The stability of methadone plasma levels during steady drug intake and the effects of a single dose omission on the methadone plasma level, were studied in 3 reliable patients (Group I) and in a nonselected group of 11 clinic patients (Group II). The plasma levels of methadone were determined by gas-liquid chromatography. In Group I patients receiving an average dose of 1.13 mg/kg (range 0.45-1.6 mg/kg) little day to day variation was seen: the average plasma level was 0.358 ug/ml with a variance of +/- 3.6% measured in 4 different days. Forty-eight hours after the last dose (after omission of a single dose), methadone plasma levels declined on the average by 0.179 ug/ml which represents a 50% decrease form the preomission average level. In Group II patients during the presumed steady methadone intake (average dose 1.25 mg/kg, range 0.57-1.75 mg/kg), the average plasma level of methadone was 0.377 ug/ml with a variance of 48.5% measured in 4 different days. A fall in methadone plasma levels occurred mainly after weekends in some of the Group II patients suggesting possibly nonconsumption of the prescribed dose of medication. The rapid and substantial decline of methadone plasma levels following a single dose omission is apparently a parallel to the observed rapid loss of methadone induced cross tolerance.


Verapamil and diazoxide antagonism of agonist-induced contractions of aortic strips from normal and spontaneously hypertensive rats (SHR). The vulnerability of aortic strips from 50-52 week old Spontaneously Hypertensive Rats (SHR) and normotensive Wistar-Kyoto (WKY) controls to the inhibitory or relaxing effects of the calcium antagonists verapamil and diazoxide was studied. Verapamil produced concentration-dependent inhibition (antagonism) of KCl, PGE2, and methoxamine-induced contraction of aortic strips from SHR and WKY. KCl and PGE2-induced contraction of SHR tissue were less readily antagonized by verapamil compared to WKY preparations. The reverse was seen with methoxamine-induced contraction. The slope of the verapamil inhibition curve of KCl-induced contraction was significantly steeper for aortic strips form WKY. Verapamil and diazoxide also produced concentration-dependent relaxation of KCl-induced contraction of aortic strips, no significant differences being noted in SHR and WKY responses. Results are compatible with the hypothesis that arterial smooth muscle from SHR is characterized by a more tightly bound pool or source of activator Ca++ which is released by certain agonists. Failure to observe a significant difference in verapamil or diazoxide induced relaxation of KCl contracted tissues from SHR or WKY suggests that in the tonic phase of KCl contraction, transmembrane fluxes of Ca++ in SHR and WKY are equally vulnerable to the Ca++ channel inhibitory effect of the antagonists.


Preparation of deuterium-labeled cocaine and benzoylecgonine. The preparation of deuterium-labeled cocaine and benzoylecgonine by a site-specific method is reported. This method involves the reductive dehalogenation of appropriately substituted derivatives by a NaBD4 - PdCl2 system. By the judicious choice of halogen-substituted aromatic systems, a wide variety of specifically deuterated compounds of biological interest can be prepared.


Rapid onset of salt induced hypertension in rats with hereditary hydronephrosis. Rats with hereditary hydronephrosis and littermates with normal kidneys were given 1% saline solution instead of drinking water, and renal excretory function, blood pressure, fluid volumes, and plasma renin activity were monitored. A marked increase in blood pressure and positive correlation between blood pressure and plasma volume were found in hydronephrotic rats after five weeks of salt loading, while animals with normal kidneys remained normotensive. No involvement of the renin-angiotensin system could be demonstrated in the observed phenomenon. It is suggested that the impairment of renal excretory function along with the deficiency of antihypertensive reno-medullary factors are responsible for the greater sensitivity of the hydronephrotic rats to the hypertensive stimulus of salt overload.


Liver regeneration as influenced by the structure of aromatic and heterocyclic compounds. The effect of aromatic hydrocarbons and derivatives and heterocyclic agents administered s.c. daily for the first 7 days or as dietary supplements was ascertained on the extent of liver regeneration in partially hepatectomized male rats over a period of 10 days. The monoalkylbenzenes proved ineffective by injection except for ethylbenzene and possibly n-propylbenzene and the introduction of the double or triple bond in the side-chain as exemplified by styrene and phenylacetylene, led to little change over the respective controls. A number of noncarcinogenic hydrocarbons accelerated the regenerative process but much higher s.c. dosages were required as compared to the carcinogenic hydrocarbons. As tested by the dietary route, the optimum effect among the phenylmethanes was reached with diphenylmethane, toluene, tri- and tetraphenylmethanes and the Sn analog, tin tetraphenyl being inactive. With the diets, carcinogens as BP or DBA at 0.10% were without effect whereas acenaphthene or fluoranthene at this level accelerated the regeneration. Although diets supplemented with anthracene or octahydroanthracene led to little change in liver increment, 9,10-dihydroanthracene, anthraquinone and anthrone comprised liver stimulants, an activity which did not extend to phenanthraquinone. Aniline and triphenylamine did not alter the control increment but diphenylamine was active as was also the case with o- and m-terphenyls, the p-isomer being ineffective. Although naphthalene lacked activity by either route, 1- and 2-phenylnaphthalenes proved stimulatory by injection and 1- and 2-naphthylamines, by diet. Among other derivatives, phenyl sulfide and its sulfoxide and sulfone were quite stimulatory in addition to heterocyclic S compound as benzothiophene, phenothiazine, phenoxathiin and thianthrene but not thianaphthene at the dietary levels screened. Several series were conducted with intact rats under the above conditions; ethyl-benzene and phenathrene injected s.c. at high levels did not alter the control dry- or wet liver-body weight ratios. The findings are summarized in Table 4.


Stability of mixed function oxidases in frozen rabbit liver. Little information is available on the effect of storage on hepatic mixed function oxidases. Livers from male New Zealand White rabbits were excised, frozen and maintained at -74 degrees C. Assays were conducted immediately on samples of unfrozen liver (day 0) and on thawed samples of the frozen liver at days 49, 92, 142, 181, and 221. Influence of storage on microsomal protein content, aniline hydroxylase activity, cytochrome P-450, and metabolism of digitoxigenin were determined at each time point. After day 92, homogenates gradually began losing the ability to metabolize digitoxigenin to 6beta-hydroxy-3-epidigitoxigenin, with 50% of the original activity at day 221. The amount of 3-epidigitoxigenin increased after day 92 in an amount equal to the loss of formation of 6beta-hydroxy-3-epidigitoxigenin. Microsomal protein content, aniline hydroxylase activity, and cytochrome P-450 content did not significantly change over the course of 221 days.


Renin activity solid phase radioimmunoassay. A solid-phase radioimmunoassay for measurement of generation angiotensin I (renin activity) in plasma is reported. The angiontensin I antisera were attached to diazotized arylamine and N-hydroxy succinimide controlled pore glass, and reacted with labelled and unlabelled angiotentin I for saturation analysis before and after one hour incubation. Chelating agents were used to inhibit the conversion of angiotensin I to angiotensin II in vitro. The assay is accurate, rapid and reproducible.


Some effects of the behaviorally active drug, phenitrone, a purported hashish and LSD antagonist, on brain noradrenergic and serotonergic systems. Phenitrone, (3-hexahydro-1H-azepin-yl)-3'-nitropriophenone HCl) had no effect on brain norepinephrine levels but decreased serotonin levels and serotonin turnover rate.


The effects of different atmospheric pressures of room air on the lethality of methamphetamine and pentobarbital. Mice were used to obtain LD50's for methamphetamine and pentobarbital at 282, 380, 760, 1520, 3040, 3800 and 4560 mm Hg of room air. The animals were allowed to stabilize at the test pressure 15 min. prior to drug injections. The lethality of both methamphetamine and pentobarbital was significantly increased over sea level determinations only at 282 mm Hg. Most previous research in this area has utilized drug injections given prior to ascent or descent. The relative lack of increased toxicity under conditions of altered atmospheric pressure observed in this study compared to previous research suggests that the temporal relationship between drug administration and pressure changes is important.


Some physiological changes in pregnant sheep and goats before, during and after surgical insertion of uterine catheters. Corticosteroid concentrations in maternal plasma from pregnant sheep and goats increased during the preoperative starvation period, anaesthesia and surgery, and reached maximum values when the animals regained consciousness. During the operation the vaginal temperature fell 2-3 degrees C. Postoperatively, corticosteroid levels took two to four days, while glucose concentrations took five to seven days in sheep and 10-12 days in goats to return to prestarvation levels. Feed intakes returned to prestarvation levles three to four days after operation in sheep and five to seven days after operation in goats.


The anthelmintic efficacy of fenbendazole against a mixed nematode infection in sheep. Fenbendazole (methyl-5-(phenylthio)-2-benzimidazole carbamate) at dose rates of 5 mg/kg and above was 100 per cent effective in eliminating a naturally acquired Dictyocaulus filaria infection in sheep. The drug was 100 per cent effective in eliminating concurrent infections of adult Trichostrongylus axei, Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagii, Cooperia oncophora, Cooperia mcmasterii, Nematodirus spathiger, Neumatodirus filcollis, Oesophagostomum venulosum and Chabertia ovina. Fenbendazole was 93 per cent and 97 per cent effective at doses of 5 and 10 mg/kg respectively in removing infection with adult T colubriformis, and post-treatment worm-egg production was completely suppressed in surviving female worms. No adverse side-effects were observed in treated sheep at either of the two dose rates used.


Phagocytosis of Trypanosoma (Nannomonas) congolense by circulating macrophages in the African buffalo (Syncerus caffer). Nineteen African buffalo were short in the Mara region of Kenya. Leucocytes were separated from the buffalo samples by sedimentation and centrifugation. In leucocyte smears of six buffalo, trypanosomes were detected and in two of them, high levels of phagocytosis of Trypanosoma (Nannomonas) congolense by circulating macrophages were demonstrated.


The effect of ageing on the antigenicity of Haemonchus contortus larvae. Viable Haemonchus contortus larvae used as a source of antigen in complement fixation tests showed a decrease in antigenic potency following storage for approximately two months at 5 degrees C. In contrast, larvae killed by freezing and stored at --15 degree C showed no such decline over a similar period. It is suggested that this loss of potency with ageing may be partly responsible for increased worm populations in sheep in spring.


Experimental chronic copper toxicity in sheep. Changes that follow the cessation of dosing at the onset of haemolysis. Eight sheep were given daily oral doses of copper sulphate until haemolysis occurred. Three of the sheep developed further periods of haemolysis after dosing ceased. Serum enzyme and urea levels were measured throughout the experiment and compared to those obtained from three undosed control sheep. Serum enzyme levels rose prior to haemolytic crises and urea levels rose subsequent to haemolysis in animals that died or were killed in extremis. Severe morphological changes were seen in liver, kidney and brain. Tissue levels of copper and iron were markedly elevated. It is concluded that tissue damage continues even after the cessation of ingestion of copper and that the damage can be severe enough to lead to repeated haemolytic crises.


Morphological studies on the fetal membranes of the normal singleton foal at term. Of 211 consecutive thoroughbred foalings, 145 satisfied a set of criteria for normal parturition and foal viability. The fetal membranes from these and from 10 pony foalings have been systematically examined morphologically and quantitatively and the findings compared to those of other authors. Five sites on the allantochorion were consistently devoid of villi. Expulsion usually occurred with the non-villous side outermost. In 24 per cent of allantochorions the non-pregant horn was of equal length or longer than the pregnant horn. These placentae tended to be shed with the villous side outermost. All membranes contained a hippomane in the allantoic cavity. Remnants of the yolk sac placenta and extra-embryonic coelom were always present. Large vestigeal yolk sacs have previously been confused with anomalous twins. In most cases the endometrial cup sites were site recognisable, usually arranged around the umbilical cord attachment. This attachment was found on the dorsal aspect of the uterine cavity either at the junction of the horns or within the pregnant hor; rarely, it was in the non-pregnant horn. A degree of twistng of the umbilical cord is normal. In 6.2 per cent of cords small urachal dilatations were noted, resulting from flight stenosis of the urachal luman at the site of a twist. Ninety-five per cent of cords measured between 36 and 83 cm.


Mandibular cheek tooth development and its relationship to age in young Friesian cattle. The oral and intra-osseous development of each of the six manidibular cheek teeth found in the permanent dentition of cattle was studied. The animals used were all British Friesians, of varying sex, and slaughtered at different weights at ages between 13 and 22 months. The various stages of development observed in each tooth together with the mean age and age range at which they were seen are recorded. Significant differences were found between the ages at which several of the developmental stages were seen in most of the teeth and indicated that tooth formation in the Friesian cattle studied tended to fall within well defined age limits.


Acquired immunity to Fasciola hepatica in splenectomised rats. Significant resistance to a second infection with Fasciola hepatica was obtained in splenectomised and sham operated rats (P less than 0.001, 78 and 76 per cent respectively) when compared with singly infected splenectomised or sham operated control groups. For both the stimulating and challenge infections, there were no significant differences in the number of flukes recovered from rats that had been splenectomised as compared to those receiving the sham operation. Thus, splenectomy did not significantly affect the ability of rats to develop an acquired immunity to F hepatica, nor were fluke recoveries from a particular schedule of infection significantly affected by the presence of absence of a spleen. It is concluded that the presence of a spleen is not necessary for the development of acquired immunity to F hepatica in the rat.


Renal biopsy in the pig.

Renal biopsy in the pig. In the pig, needle renal biopsy proved a safe and simple procedure which caused little discomfort to the animal. It proved a valuable method for following serial changes in renal histology and can therefore be applied to the study of both spontaneous and experimental renal diseases in pigs.


Carbohydrate absorption by chicks affected with the fatty liver and kidney syndrome. Chicks with fatty liver and kidney syndrome (FLKS) were given oral doses of one of the following test solutions: water, glucose, maltose, starch. Plasma glucose concentration was measured during the four subsequent hours. All FLKS-affected chicks were hypoglycaemic before treatment. Although in some cases plasma glucose concentration increased slightly in the FLSK-chicks given water alone, significantly greater increases were invariably observed following the administration of carbohydrate to sick birds. Results obtained from dietary experiments in which starch was replaced by glucose in a ration causing high mortality from the syndrome revealed no beneficial effect due to the substitution. It was concluded that FLKS does not involve any major impairmant of carbohydrate digestion or absorption.


The response of the immature fowl to multiple injections of adrenaline. Chicks were injected, from one to 21 days of age, with either L-adrenaline (500 mug/kg) or the solvent three times a week. Birds treated with adrenaline showed an imparied growth rate. Relative (mg/kg0.75), but not absolute (mg) adrenal weight was significantly increased. No changes in adrenal cholesterol content or concentration were noted.


The corticosteroid content of cattle skin washings. In vitro techniques have been developed to study the invasive processes of Fasciola gigantica. The conditions necessary for excystment were identical with those required by F hepatica. The ability of larvae to penetrate mouse gut in vitro was influenced by the composition of the fluid within the gut, and by the region of gut wall to which the larvae were exposed. Larvae remained viable on spleen cell monolayers for at least 60 days.


Methods for in vitro study of the invasive processes of Fasciola gigantica. In vitro techniques have been developed to study the invasive processes of Fasciola gigantica. The conditions necessary for excystment were identical with those rquired by F hepatica. The ability of larvae to penetrate mouse gut in vitro was influenced by the composition of the fluid within the gut, and by the region of gut wall to which the larvae were exposed. Larvae remained viable on spleen cell monolayers for at least 60 days.


The effect of somatostatin on the rise of growth hormone and glucagon secretion induced by arginine and L-dopa in diabetic patients. The growth-hormone-release-inhibiting hormone somatostatin was infused in seven juvenile diabetic subjects during an arginine infusion test and in six juvenile diabetic subjects during an L-dopa stimulation test. The plasma growth hormone response to arginine and L-dopa was completely inhibited by somatostatin. The plasma pancreatic glucagon response to arginine was also inhibited by somatostatin. The plasma pancreatic glucagon level was not changed by L-dopa, but somatostatin induced a significant fall in this level. The plasma glucose increase after arginine and L-dopa administration was slightly inhibited by somatostatin. The arginine-induced fall in free fatty acids was prevented by somatostatin, and the L-dopa-induced rise in free fatty acids was enhanced by somatostatin. The growth hormone- and glucagon-surppressive effect of somatostatin may prove useful in controlling the metabolic state and in preventing the development of angiopathy in diabetic patients. A somatostatin preparation with prolonged activity is needed for lifelong administration, but the presently available compound may be of value as an adjunct in the standard treatment of diabetic ketoacidosis and coma.


Breakdown of 5'-adenine nucleotides in ischaemic renal cortex estimated by oxypurine excretion during perfusion. The catabolism of 5'-adenine nucleotides in the cortex of the rabbit kidney was studied during normothermic and hypothermic ischaemia. Changes were found in the cortical content of ATP, ADP, AMP, and SAN (the sum of 5'-adenine nucleotides) during ischaemia; those changes were delayed by hypothermia. The loss of SAN was found to be significantly correlated to the duration of normothermic as well as hypothermic ischaemia. The oxypurines hypoxanthine and xanthine and the nucleoside inosine were shown to be the final products of the catabolism of 5'-adenine nucleotides. An accumulation of hypoxanthine-xanthine and inosine in the tissue and a corresponding excretion in the perfusion fluid occurred simultaneously with the catabolism of 5'-adenine nucleotides, in equivalent amounts. It is concluded that determination of the amount of oxypurines excreted during kidney preservation is an indirect measure of the loss of SAN in the tissue, and a reflection of the changes in the metabolic state.


Effective renal plasma flow (ERPF) of the individual kidney and renal venous renin activity (RVRA) determined simultaneoulsy before and after the administration of dihydralazine in renovascular hypertension. Effective renal plasma flow (ERPF) and renal venous renin activity (RVRA) were determined for the two kidneys separately before and after intravenous administration of dihydralazine in 50 cases of suspected unilateral renovascular hypertension. A ratio above 1.4 between the ERPFs of the two kidneys and an RVRA ratio above 1.5 were used as signs of lateralization. The two procedures showed agreement about presence or absence of lateralization in 36 cases before and 44 after dihydralazine administration. Eleven patients underwent surgery. ERPF and the changes in ERPF induced by dihydralazine gave important prognostic and preoperative information. Data on renin release rates are presented.


Extraction of endogenous plasma triglycerides by the working human forearm muscle in the fasting state. The extraction of triglycerides (TG) by the working forearm was determined in eight healthy fasting men, both by the measurement of chemical arterial-deep venous (a-dv) TG differences and by the a-dv differences in TG radioactivity after endogenous labeling with tritiated palmitate. Measurements were made before and then during nicotinic acid infusion. Correction for plasma water shift in the forearm vasculature was made by estimating the (125I)albumin activity after an intravenous injection. The overall mean value +/- S.E.M. without and with nicotinic acid was for TG arterial concentration (mumol/1) 713 +/- 153 and 695 +/- 140, TG a-dv concentration difference (mumol/1)-14 +/- 7 and -6 +/- 4, TG arterial radioactivity (cpm/ml) 1650 +/- 469 and 1471 +/- 342, TG a-dv radioactivity difference 12 +/- 24 and -2 +/- 13. The average standard errors for the determinations of triglycerides were 0.85% and 1.5% for the chemical and the isotope methods, respectively. In conclusion, no significant average a-dv difference in TG concentration as determined by either the chemical or the isotope method was detected. With the standard errors achieved, however, a-dv differences of less than around 20 mumol/lcould not be discovered. Such an extraction of endogenous plasma TG could, if oxidized, account for about 25% of the oxygen extraction by the eercising forearm.


Ultrasensitive radioimmunoassay for direct determination of free triiodothyronine concentration in serum. Free triiodothyronine (T3) in serum has been measured directly in dialysates of serum, using a wick chromatographic radioimmunoassay. Adequate sensitivity was attained by the use of [1251]T3 with very high specific activity (2,000 to 3,000 muCi/mug). Sera were dialysed against a Krebs-Ringer bicarbonate buffer modified so as to be similar to plasma water. Dialysis took place under carefully controlled circumstances. The influence on the equilibrium of total to free T3 of temperature, serum dilution, and dialysis time was studied. By the present method, free T3 in serum from groups of subjects including 20 men, 10 women taking oral contraceptives, and 20 women with normal menstrual cycles were identical, averaging 5.2 pg/ml. A chromatographic radioimmunoassay of total T3 using high specific activity [1251]T3 and very small test samples is also described.


Adenine nucleotide content of human liver. Normal values and fructose-induced depletion. A method is described for the determination of metabolites in liver biopsy samples. Normal values of lactate, pyruvate, and adenine nucleotide content of human liver are presented. Infusion of D-fructose, 5.9 mmol9kg-minus l.h-minus l, for 70 min resulted in a 22.5 per cent decrease of the adenine nucleotide pool (mainly by ATP depletion), increased content of fructose 1-phosphate, lactate, and pyruvate. The extent of adenine nucleotide depletion varied greatly between subjects and appeared related to the degree of increase in plasma urate. Infusion of glucose at the same rate did not affect the hepatic content of adenine nucleotides.


A continuous-flow method for the determination of the activity of serum alkaline phosphatase in diethanolamine buffer. A procedure for determination of serum alkaline phosphatase activity (EC 3.1.3.1) in diethanolamine (DEA) buffer with an AutoAnalyzer II apparatus was designed. The buffer used was 1.0 mol/l DEA-HC buffer, pH 9.8 at 37 degree C, containing 0.5 mmol/l of MgCl2 and 10 mmol/l of substrate 4-nitrophenyl-phosphate. The reaction time was about 3 min at 37 degree C. The enzyme activity (U/l) was calculated by determining the amount of 4-nitrophenol formed in reaction. A sampling rate of 70 samples per hour can be used with good linearity up to 1000 U/l. The results obtained by the new continuous-flow system were compared with those measured by the kinetic method according to the Scandinavian recommendation (10). A close correlation between the two methods was observed.


Activities of aspartate and alanine aminotransferases and alkaline phosphatase in sera of healthy subjects. The activities of serum aspartate aminotransferase (EC 2.6.1.1, L-aspartate: 2-oxoglutartate aminotransferase, ASAT) and alanine aminotransferase (EC 2.6.1.2, L-alanine: 2-oxoglutarate aminotransferase, ALAT) were determined in the sera of 1484 apparently healthy subjects using kinetic methods according to the Scandinavian recommendation (33). In the adult sera the mean activity of ASAT was 21.4


The degree of mineralization in normal bone tissue estimated as the phosphorus to hydroxyproline ratio. The degree of mineralization can be evaluated from the phosphorus to hydroxyproline ratio in bone biopsies. A small but significant rise in the ratio with increasing age was observed in 137 persons without bone diseases, aged from 20 to 89 years. No significant difference between men and women was found with regard to the phosphorus to hydroxyproline ratio. The study indicates that with increasing age, in addition to senile osteopenia, there is also a change in the form of an increase in the degree of mineralization.


Blood flow distribution in the stomach of cats with gastric ulcer. Ulcer was induced in the anterior wall of the antrum by a subserous injection of 0.3 ml of a 20% acetic acid solution. Carbonized microspheres 15 plus or minus 5 mu in diameter and labelled with 169Yb were used to measure blood flow in different regions and layers of the stomach. Approximately 2-3 million microspheres were injected into the left ventricle of the heart. Simultaneously a blood sample was drawn from the distal aorta at a flow of 1 ml/min. Standardized tissue samples were punched from the lesser curvature and the anterior and posterior walls of the antrum, corpus, and fundus. In each sample the mucosa was separated from the muscularis. The radioactivity of the blood and tissue samples was determined, and the blood flow was calculated for each tissue sample. Three groups of animals were examined: 1) anaesthetized control animals, 2) animals laparotomized one week before examination, 3) animals with a one-week ulcer. In the control animals the blood flow was found to be the same in corresponding regions of the anterior and posterior walls of the stomach. The flow was slightly lower in the antrum than the fundus. The flow was similar in the different regions of the muscularis. The muscularis flow was markedly lower than the mucosa flow. In the laparotomized animals the blood flow was found to be increased in the muscularis of the corpus. In the ulcer animals the mucosa flow was increased in the anterior wall of the antrum, and the muscularis flow was increased in the antrum and the anterior wall of the corpus.


Effects of fasting and feeding and pilocarpine on paneth cells of the mouse. The effects of fasting and feeding and pilocarpine on Paneth cells (PC) of the mouse were studied by labelling the secretory granules of PC with dopamine and by counting the number of granules. Pilocarpine stimulated the extrusion of granules from the cytoplasm of the cells and significantly decreased their number, whereas fasting for 2 days significantly increased the granule count of cells. Standard food did not have any effect on PC of the duodenum, whereas in the jejunum resuming eating after 2 days fasting significantly decreased the number of granules when compared with the mice deprived of the food.


Gastroscopic observations related to bioptical histology in healthy medical students. The examinations were performed on 10 medical students, 22-23 years old, of whom 5 were women. Directed biopsies were taken from the antral mucosa and the mucosa of the greater and lesser curvatures, average number being 6.7. Gastroscopy showed a normal mucosal folding in all students. None had mucosal reddening or mucus covering of more than slight grades. The examination concluded with a normal gastric mucosa in 4 and probably normal in 2 students. In 4 students a superficial gastritis was supposed to be present. Bioptical histology showed a normal mucosa in the antrum in 6 students, at the lesser curvature in 7, and at the greater curvature in 8 students. In the others a slight superficial gastritis in the antral mucosa. There was a fairly good correlation between the gastroscopic observations and the findings by histology on directed biopsy in 6 of the students.