[Effect of sunlight penetration on the development of phototrophic sulfur bacteria in marine environment].

Bottles of medium were inoculated with both strains of Chromatiacea and Chlorobiaceae (mixed cultures) and immersed at differnt depths in the marine coastal waters of the Marseilles basin (France). After development, the in vivo absorption characteristics of the cells show the effect of the daylight penetration on the selective growth of photorophic sulfur bacteria. With depth, sunlight selects Chlorobiaceae rich in brown carotenoid pigments to the detriment of Chromatiaceae.


Denitrification by N2-fixing Sprillum lipoferum.

Forty-nine N2-fixing strains of Spirillum lipoferum isolated from a wide range of plant roots and soils were examined for reduction of NO3-. All strains reduced NO3-to NO2-. Thirty of the strains further reduced NO2-with production of gas. Examiniation of representative strains of the putative denitrifiers showed that they produced both N2O and C2H4 in the presence of 0.1 atm of C2H2. Strains which did not reduce NO2-with production of gas produced C2H4 but ont N2O in the presence of C2H2. This is the first report of a N2-fixing bacterium able to bring about denitrification of NO3.


An electrophysiological method for examining lumbosacral root compression.

The propagation velocities and conduction times of nerve impulses responsible for muscle F-waves were measured in the proximal segments of 60 normal posterior tibial nerves and of 41 normal peroneal nerves. The results were compared with those of 25 patients having confirmed lumbosacral root compression due to disc degeneration. Using the peroneal nerve, 65 per cent of patients had a prolonged proximal conduction time; a similar abnormality was found in 56 per cent of patients when the posterior tibial nerve was studied. The yield of positive results rose to 85 per cent and 76 per cent respectively when the M- and F-latencies in given individuals were compared. It was also shown that in normal subjects the F-response has a longer latency, and slower conduction velocity than the H-reflex when both are obtained using the same stimulating and recording sites. In patients in whom the ankle jerks and H-reflexes are absent, the F-waves may still be recorded indicating that the latter are mediated through motor fibers.


Parkinsonism--dementia complex, hydrocephalus and Paget's disease.

A 65-year-old female patient with Paget's disease displayed dementia, a bilateral Parkinsonian syndrome, gait ataxia, bilateral grasp reflex of the feet, urinary incontinence and a left hemicerebellar syndrome. She had a marked basilar impression; the radionuclide cisternogram was suggestive of a communicating hydrocephalus with ventricular dilatation. After a shunting procedure there was improvement in both neurological and mental function.


Intracranial aneurysms: a clinical, angiographic and computerized tomographic study.

Fifty-six patients with 63 aneurysms were selected from a larger group of patients because they had at least one angiographic and one CT scan study. A total of 102 CT scans and 136 angiograms were analyzed. In five patients the aneurysm was visualized on the CT scan. There was a tendency for the location of the subarachnoid hemorrhage and intracerebral hematomas visualized on the CT scans to correlate with the site of the aneurysm as seen on the angiogram. The CT scan was useful in demonstrating the evolution of hydrocephalus and in differentiating hematoma from edema. The patients with normal CT scans were more likely to have good neurological grades. No single angiographic or CT scan feature correlated significantly with survival at lower than the 5 percent level.


Early recognition of cardiac tamponade.

Nine patients with cardiac tamponade were seen in an 11-month period. Analysis of the clinical and laboratory data indicated that pulsus paradoxus was the most useful physical sign and echocardiography the most useful investigative technique. Three of nine patients died but in only one was the late recognition of tamponade a possible factor in the outcome. Pericardial fenestrations were required in four patients. Viral pericarditis accounted for the tamponade in three cases. There were two cases each of uremia and malignant disease and one case of tuberculous pericarditis. One other case followed pericardiectomy. In five patients tamponade was the initial manifestation of illness.


Subsittution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics.

The effect of inhaled beclomethasone dipropionate (dose, 400 mug daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14.


Emergency toxicology in a general hospital.

A study of all cases of attempted suicide by drug ingestion over a 6-month period was undertaken to evaluate the use of an emergency toxicology service and to establish the role of the emergency toxicology laboratory in the diagnosis and management of cases of attempted suicide. A total of 235 requests for emergency toxicologic analysis involving 259 specimens was received. Results of toxicologic screening were positive for 58% of all cases (range, 49% for patients who were drowsy to 90% for patients who were deeply unconscious). Barbiturate blood values did not correlate well with either the level of consciousness or the clinical state of the patient. In almost all patients who were drowsy or who were unconscious but had normal reflexes and vital signs there was no deterioration in the clinical state and no active treatment was required. The study demonstrated the need to educate all personnel involved in the care of patients with attempted suicide to limit laboratory investigations to the management of patients who benefit from such analyses. Quantitative drug analyses have a limited contribution to the management of such patients and should be performed only for patients with mixed drug overdosage and when the drugs require dialysis for their elimination from the body.


Colloid osmotic pressure: its measurement and clinical value.

Plasma colloid osmotic pressure (COP) is an important determinant in the appearance of edema. The development of a simple technique for COP measurement, based on an electronic pressure transducer and a semipermeable membrane system, has led to an appreciation of the value of COP determinations in clinical practice. In a steady state the measured COP replicates the value computed from serum proteins. In pathologic sera a derived value is unreliable. The normal human plasma COP averages 25.4 mm Hg. This value tends to decrease with age, is lower in females and is also lower in subjects at bed rest. As a clinical tool COP measurement represents an unduplicated contribution to the differential diagnosis of pulmonary edema. In critically ill patients COP measurement represents a reliable predictor of survival.


The renal pathology in clinical trials of cis-platinum (II) diamminedichloride.

The pathologic changes induced by Cis-platinum (II) diamminedichloride (CPDD) therapy in the kidneys are described in 12 patients with solid tumors and malignant lymphomas. According to dosage of CPDD the patients were divided into two groups: 1) low-dose group--.0.5-2 mg/kg daily, for 1 to 6 days; and 2) high-dose group--single injection of 3 or more mg/kg with concommitant mannitol-induced diuresis. Pathologic changes in the kidneys were essentially similar in both groups and consisted of focal acute tubular necrosis, affecting primarily the distal convoluted tubules and collecting ducts, dilatation of convoluted tubules, and formation of casts. These changes persisted as long as 29 days post CPDD therapy. In addition, the collecting ducts exhibited significant epithelial atypia. BUN and serum creatinine levels were elevated in both groups. The mean BUN/serum creatinine values were 54/2.2 mg/100 ml and 32/2.0 mg/100 ml for low and high-dose groups, respectively. Since the nephrotoxicity of CPDD is known to be dose-related, our findings suggest that mannitol-induced diuresis has considerably decreased the renal toxic damage of CPDD therapy in these patients.


Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer.

The effect of cyclophosphamide (CY) on ovarian function was studied in patients with breast cancer receiving prolonged daily administration of this agent (100 mg/day) after radical surgery. Out of 18 premenopausal patients that received 8.4-39.9 g CY, 15 developed permanent amenorrhea. The average dose given before the onset of amenorrhea was 5.2 g in patients in their 40s and 9.3  in their 30s. Urinary estrogens and serum progesterone were measured weekly for approximately 6 months postoperatively in six patients receiving CY. After the onset of amenorrhea, the levels of both hormones ceased to show their normal cyclic changes and remained low persistently, meanwhile serum FSH and LH were markedly elevated. No ovarian follicle was histologically found in three amenorrheic patients who underwent therapeutic oophorectomy after CY therapy. These findings indicate that CY induced primary ovarian failure.


Tumor-specific transplantation antigens in spontaneously transformed hamster cell lines.

Spontaneously transformed hamster cells were examined for the presence of TSTA by employing the tumor rejection test. It was demonstrated that each of the spontaneously transformed cell lines as well as cells derived from tumors induced by these cells possess an individual distinct antigen, capable of evoking a significant anti-tumor immunity. The immunizing potential of these antigens and their specificity were not affected by either in vivo or in vitro environment. The results suggest that the spontaneously transformed hamster cells undergo antigenic modification, which resembles the TSTA of chemical-carcinogen induced tumors.


Marker chromosome 14q+ in non-endemic Burkitt's lymphoma.

The chromosomal aberrations in tumor cells obtained by bone marrow aspiration from a patient with non-endemic Burkitt's lymphoma (BL) are reported. Twenty percent of the cells contained the marker chromosome 14q+ earlier described in endemic Burkitt's tumors. Other marker chromosomes were dound only in mitoses which did not contain the 14q+.


The proliferative patterns of human breast cancer cells in vivo.

The cell proliferation pattern in human breast cancer has been studied in eight patients in vivo using intravenously administered 3HTdR as a pulse and as a continous label. Two to 4% of the tumor cells were engaged in DNA synthesis in six patients, and 7% and 11%, respectively, in two others. From the composite percent labeled mitosis curve the estimated time for G1 + (M/2) was about 4 hours and for DNA synthesis about 24 hours. Many cells which entered the cycle spent longer intervals in DNA synthesis and in the post-DNA synthetic phase before entering mitosis. There was a wide range of intermitotic times among the tumor cells. These findings are of significance in the planning of drug therapy.


Melanotic neuroectodermal tumor of infancy: its histological similarities to fetal pineal gland.

Striking similarities between the pineals of 107 fetuses and infants and a pigmented neuroectodermal tumor occurring in the right orbital and right frontal regions in a 6-month-old Puerto Rican boy were found. Both the human fetal pineal and melanotic neuroectodermal tumors of infancy are characterized by pigmented (melanin) epithelial cells, small undifferentiated cells, and a fibrovascular stroma. Our findings suggest the fetal pineal may be a normally occurring precursor of the melanotic neuroectodermal tumor of infancy, or that melanin production may be a normal capability of differentiating neuroepithelial cells.


Plasma prostaglandins in hypercalcemic patients with neoplastic disease.

Peripheral plasma prostaglandin E (PGE) determinations were performed on a series of 79 patients with solid tumor neoplasms and correlated with their serum calcium levels. Fourteen patients were hypercalcemic and 11 of these had significant elevations in circulating plasma PGE. Ten of the hypercalcemic group had extensive metastases to bone. These findings support the recently developed hypothesis that prostaglandins are causally related to the genesis of hypercalcemia in malignancy.


Primary leiomyosarcoma of bone.

A case of primary leiomyosarcoma of bone in the femur of an 18-year-old girl is described. Light and electron microscopy showed characteristic changes with cytoplasmic myofilaments, dense bodies, pinocytic vesicles and basal lamina fragments. Clinically, the patient is well and without evidence of tumor 9 months after the femur amputation without further treatment.


Intraductal papillary tumors of the breast: a study of 78 cases.

Seventy-eight intraductal papillary tumors of the breast were followed. The 14 papillary carcinomas were all treated by mastectomy. Metastases did not occur. In 64 patients with papillomas, six developed carcinoma--two in situ and four invasive. The incidence of cancer was higher in patients with multiple papillomas and with papillomatosis. The current experience (1949-1967) is discussed relative to the previous experience at the same institution from 1895 to 1941.


Posthypophysectomy taste abnormalities: their relationship to remote effects of cancer.

Abnormalities in taste sensation have been studied in 15 patients consisting of five normal controls, five patients with diffuse neoplasm and five patients post hypophysectomy. Threshold recognition for salt and HC1 in the three groups studied was the same. Sucrose and urea recognition was higher in patients with neoplasm as compared to normal controls. Patients post hypophysectomy had a lower threshold recognition for sucrose than both normal individuals and patients with neoplasm. The threshold recognition has markedly shifted for both sucrose (decreased) and urea (increased) post hypophysectomy. These observations are in support of previous findings and suggest that the pituitary plays at least a necessary permissible factor in the development of abnormalities in taste as observed in patients with disseminated cancer.


Hypophysectomy in the treatment of disseminated prostate carcinoma.

Seventeen patients suffering severe pain secondary to disseminated prostate cancer were subjected to hypophysectomy. Prolonged remission of pain and increased survival duration appeared to be consequent to obtaining objective signs of tumor regression. Patients who had only subjective improvement had significantly shorter periods of remission and survival. Patients  with hematocrits less than 30% and patients demonstrating evidence of liver involvement did not obtain objective remissions.


Tricuspid stenosis secondary to metastatic melanoma.

Cardiac metastases from malignant melanoma are frequent, usually asymptomatic and occur terminally. When responsible for symptoms, close evaluation of the patient is imperative for correct diagnosis and subsequent therapy. Surgical intervention where indicated in combination with chemotherapy and judicious use of irradiation constitutes optimal therapy.


Small cell carcinoma of the male breast: report of a case.

An uncommon type of breast carconoma in a male studied by light and electron microscopy, is reported. Light microscopy reveals histologic characteristics and a pattern similar to infiltrating lobular carcinoma in the female breast. The ultrastructural study, because of close similarities in cellular characteristics with previously published reports, gives firm support to the light microscope findings.


Blindness in a patient with malignant histiocytosis.

Malignant histiocytosis (MH) is a rapidly fatal systemic disease for which there is no adequate therapy. A case of MH with involvement of both eyes resulting in bilateral blindness is presented. Infiltration with malignant cells was seen in the ciliary bodies at autopsy. Attempts at treatment for this complication are discussed.


Diet and metabolism: large-bowel cancer.

Epidemiological data demonstrate that colon cancer incidence is associated mainly with high dietary fat consumption. Studies in metabolic epidemiology indicate that high fat intake influences both the amount and type of bile acids and neutral sterols and intestinal microflora acting on these compounds which may contain tumorigenic activity for the colon. This is compatible with the results of studies comparing populations with high or low risk for the colon cancer and patients with colon cancer.


Genetic markers and cancer epidemiology.

The study of potential associations between genetic markers and various cancers has a long history in cancer epidemiology. Such investigations are subject to serious problems of statistical significance and the choice of appropriate control populations. A promising future for the use of human population genetics in cancer epidemiology may be in the investigation of genetic markers (such as the HL-A complex) which code for proteins of potential immunological or physiological importance in susceptibility or resistance to cancer. The cerumen gentic marker has played a central part in a hypothesis formulated in our laboratory for the etiology of breast cancer. A second new development in this field is likely to be the investigation of genetic markers in families with high incidence of cancer. Such families permit the simultaneous study of genetic hypotheses of cancer inheritance and the association of marker genotypes with cancer through segregation and linkage analysis.


Mutation and cancer in man.

The risk of cancer can be increased by both genetic predisposition and environmental exposure. A common mechanism, mutation, may be involved in both. The rate of mutation in germ cells is the principal determinant of the incidence of genetically predisposed individuals, whereas the rate in somatic cells is the principal determinant in those not so predisposed. Many environmental carcinogens produce their effects via increased somatic mutation rates. The individuals of a population may be classified according to the operation of genetic predisposition, exposure to environmental carcinogens (mutagens), both, or neither. This last group reflects "background" somatic mutation rates.


Effect of 2-aminonaphthalene on glutathione content and cytochrome P-450 p-nitroanisole O-demethylation activity in mouse liver.

Four days after single i.p. administrations of 2-aminonaphthalene to C3H mice, the liver content of reduced glutathione and the liver microsomal cytochrome P-450 O-demethylation activity were decreased. No changes were observed in oxidized glutathione.


Interstrand cross-linking of DNA by 1,3-bis(2-chloroethyl)-1-nitrosourea and other 1-(2-haloethyl)-1-nitrosoureas.

Bifunctional alkylating agents are known to cross-link DNA by simultaneously alkylating two guanine residues located on opposite strands. Despite this apparent requirement for bifunctionality, 1-(2-chloroethyl)-1-nitrosoureas bearing a single alkylating function were found to cross-link DNA in vitro. Cross-linking was demonstrated by showing inhibition of alkali-induced strand separation. Extensive cross-linking was observed in DNA treated with 1-(2-chloroethyl)-1-nitrosourea, 1,3-bis-(2-chloroethyl)-1-nitrosourea, and 1-(2-chloroethyl(-3-cyclohexyl-1-nitrosourea. The reaction occurs in two steps, an intital binding followed by a second step which can proceed after removal of unbound drug. It is suggested that the first step is chloroethylation of a nucleophilic site on one strand and that the second step involves displacement of Cl- by a nucleophilic site on the opposite strand, resulting in an ethyl bridge between the strands. Consistent with this possibility, 1-(2-fluoroethyl)-3-cyclohexyl-1-nitrosourea produced much less cross-linking, as expected from the known low activity of F-, compared with Cl-, as leaving group. 1-Methyl-1-nitrosourea, which is known to depurinate DNA, produced no detectable cross-linking.


Intracellular localization of tumor-associated antigens in murine and human malignant melanoma.

Cross-reacting tumor-associated antigens have been demonstrated to be present in the cytoplasm of melanocytes in malignant melanoma. We have utilized both the leukocyte migration inhibition and the lymphocyte stimulation assays to determine the intracellular location(s) of these antigens in both human malignant melanoma and B-16 murine melanoma. The results of both assays indicate that this antigen(s) is associated with the membranous organelles, particularly the melanin granules, and is not found in the soluble components of the cytoplasm, as suggested by other studies.


Localization of GW-39 human tumors in hamsters by affinity-purified antibody to carcinoembryonic antigen.

With the paired-labeled antibody technique, the in vivo localization of radioiodinate, affinity-purified antibody to carcinoembryonic antigen (CEA) was studied in GW-39, a xenografted, CEA-producing tumor model. When compared to the whole immunoglobulin G fraction, a 4-fold greater tumor accumulation of radioantibody was obtained with affinity-purified specific CEA antibody. The degree of increased tumor localization of affinity-purified antibody was similar to its improved immunoreactivity as observed in radioimmunoassay and binding to CEA immunoadsorbent. Affinity-purified antibody cross-reactive with CEA and colon carcinoma antigen III was as equally effective in tumor localization as was specific CEA antibody prepared similarly. It thus appears that affinity-purified CEA radioantibody will provide a superior tumor-imaging agent for clinical use.


Histone phosphorylation and synthesis of DNA and RNA during phases of proliferation and differentiation induced in mouse epidermis by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate.

The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induces discrete waves of proliferation and differentiation when applied to mouse epidermis. The aim of this study was to elucidate the temporal relationship between histone phosphorylation and synthesis of DNA and RNA in mouse epidermis during the process of tumor promotion. This investigation as facilitated by choosing a low but nevertheless strongly tumor-promoting dose of TPA (0.002 micronmole/mouse), which induced the epidermal cells to go through only one round of DNA synthesis and cell division. Histones were isolated from mouse epidermis, and the rates of phosphorylation of the individual histone species were determined at different times after treatment with TPA. The results demonstrated that the phosphorylation of H1 histone was initiated at about the same time as the synthesis of DNA but continued past the S phase and reached a maximum simultaneously with the maximum in the epidermal mitotic rate. The only other histone that phosphorylated to any significant extent was Histone H2A. From the results obtained, it was concluded that histone phosphorylation in the epidermis is related to the processes of DNA replication and mitosis after stimulation with TPA. Positive evidence for the activation of specific genes, which has been proposed by other authors to be important in the promotion of epidermal tumors, was not found in this investigation.


Colony morphology and growth in agarose as tests for spontaneous neoplastic transformation in vitro.

Adherent fibroblast-like cells from paired lines, one non-neoplastic and the other "spontaneously" transformed neoplastic, were compared in simultaneous in vivo and in vitro assays. The in vivo assay was the i.m. implantation of 10(6) or 10(7) cells in irradiated syngeneic animals, and the two in vitro assays were the evaluation of colony morphology on plastic and the enumeration of colony growth in semisolid agarose. The percentage of colonies diagnosed from their morphology as neoplastic correlated with tumorigenicity as follows: 100% always indicated a tumorigenic cell population with tumor latent periods from 6 to 230 days and tumor incidence from 40 to 100%; 0% always indicated a nontumorigenic cell population; 1 to 32% indicated either a tumorigenic cell line with long tumor latent period (218 days) with 70% tumor incidence or a nontumorigenic cell line. Growth in agarose, as measured by colony number and size, correlated with tumorigenicity as follows: nontumorigenic cell lines produced no colonies; tumorigenic cell lines produced colonies, but not always larger than 0.1 mm in diameter. The number of size or colonies did not correlate with the tumor latent period or tumor incidence. Therefore, both in vitro tests were reliable qualitative assays of spontaneous neoplastic transformation, but they did not correlate directly with the tumor incidence or mean tumor latent period. The relative success of the agarose assay emphasizes the importance of decreased anchorage dependence for progressive growth of injected cells as a malignant neoplasm in vivo.


Nucleic acid content of HeLa S3 cells during the cell cycle: variations between cycles.

The process of continuous resynchronization with excess thymidine provides sufficient cell material for accurate chemical determination of DNA and RNA in HeLa S3 cells at hourly intervals during the cell cycle. Total DNA is constant during the non-S phase portion of the cell cycle but varies widely among cycles of synchronous growth. Total cellular RNA content increases linearly in the G1 phase and  accelerates to a higher linear rate of accumulation, which remains constant during most of the S and G2 phases. The ratios of early and late cycle rates of RNA accumulation are not constant among cycles.


A stable isotope method for measurement of thymidine incorporation into DNA.

A method has been developed for the measurement of DNA synthesis in vivo using the incorporation of multilabeled, non-radioactive thymidine. Simultaneous intraperitoneal injection of hexalabeled thymidine and tritiated thymidine into a normal adult rat resulted in the incorporation of both labeled nucelosides into the DNA of cells undergoing replication. The DNA of several tissues and organs was analysed, including liver, thymus, spleen, bone marrow, and small intestine. Following extraction with hot trichloroacetic acid, acid hydrolysis, and thin-layer chromatography of the hydrolysates, the isotopic compositions of the thymine products were determined by field ionization mass spectrometry and by scintillation counting. The relative incorporation of radioactive and stable isotope-labeled thymidine was similar in all tissues, and corresponded to the ratio of the two labeled nucleosides in the injected material. These results indicate the feasibility of utilizing thymidine multilabeled with stable isotopes for measurement of cellular proliferation rates in conjunction with cancer therapy.


Regulation of bone marrow cell growth in diffusion chambers: the effect of granulocyte extracts.

Hysotonic lysis of mature human blood granulocytes yielded an extract which reduced granulopoiesis and enhanced macrophage formation of mouse bone marrow cells cultured for 7 days in diffusion chambers (DC). The low molecular weight fraction (MW less than 15,000-25,000 Daltons) obtained by Amicon filtration of the extract, reduced granulopoiesis without affecting macrophage formation. The high molecular weight fraction (MW greater than 15,000-25,000 Daltons) reduced the number of granulocytes and increased the number macrophages. Erythrocyte extract increased the macrophage formation in DC but did not alter the number of granulocytes. The spleen colony assay showed that the granulocyte extract increased the number of CFU-S in DC. It is suggested that the granulocyte extract contain an inhibitor of stem cell differentiation to myeloid cells thereby reducing the number of proliferative granulocytes in DC 7 days later. The inhibitor of differentiation may lead to an increased self renewal of the stem cell in the DC system.


The interaction of 1-anilino-8-naphthalenesulfonate with lipids: a nuclear magnetic resonance study.

The proton magnetic resonance (PMR) and phosphorus magnetic resonance (PhMR) spectra of egg phosphatidylcholine in the presence of 1-anilino-8-nahthalenesulfonate (ANS) have been studied. At low ratios of ANS to phospholipid, the spectra indicate that ANS molecules are in the lipid interface region where they interact with the head-group protons. ANS also penetrates into the hydrocarbon region to some extent. As the ANS/phospholipid ratio approaches one, a significant splitting of the head-group signal occurs. This splitting is associated with head-group signals from inner and outer molecules of the phospholipid vesicles. As the ANS/phospholipid ratio is further increased, a gel phase often occurs. The spectra for this gel phase suggest a highly mobile head-group. Further ANS addition results in a PMR spectrum suggestive of ANS-phospholipid micelle formation. The results for a phospholipid-cholesterol complex and for the total lipid extract from a cell membrane show that the ANS effect is more complicated in these cases.


Properties of mixed vesicles of lecithin: cholesterol up to a 1:2 molar ratio.

The cholesterol solubilizing capacity of lecithin vesicles was studied and some physicochemical properties of the resulting mixed vesicles were investigated. The maximum association of ultrasonicated cholesterol and lecithin was found to be a cholesterol/lecithin molar ratio of 2:1, with a limiting concentration of colloidal lipid of approximately 34 mg/ml. The 2:1 dispersions were found to be rather stable with no change in cholesterol/lecithin ratios for long periods. The mixed 2:1 cholesterol/lecithin vesicles were separated by Sepharose 4 B chromatography to obtain homogeneous preparations. The homogeneity was further tested by analytical ultracentrifugation and electron microscopy. Light-scattering measurements showed an increase in particle weight with increasing cholesterol proportion. 1H-and 13C-NMR studies demonstrated an additional broadening, especially of chain resonances, when going from a cholesterol/lecithin molar ratio of 1:1 to 2:1.


Role of prostaglandins in the control of renin secretion in the dog.

Infusion of indomethacin into anesthetized, salt-depleted dogs cuased an increase in mean arterial blood pressure (MABP), and decreases in heart rate (HR), urine flow rate (V), renal plasma flow (RPF), and renin secretion rate. MABP was 112.1 +/-5.4 mm Hg during control periods and was 147.7 +/- 5.6 mm Hg (P less than 0.005) 80 minutes after the infusion of indomethacin. V was 0.38 +/- 0.06 ml/min during control periods and was 0.08 +/- 0.01 ml/min (P less than 0.005) 80 minutes after the infusion of indomethacin. RPF was 126.3 +/- 13.3 ml/min and 41.5 +/- 7.5 ml/min, respectively (P less than 0.005), before and after 80 minutes of infusion. Renin secretion rate decreased from 1,194.1 +/- 353.9 U/min during control periods to reach 384.0 +/- 125.8 U/min (P less than 0.025) by 80 minutes of infusion of indomethacin. Subsequent infusion of prostaglandin E2 (PGE2) into the renal artery for 80 minutes caused increases of V to 0.53 +/- 0.13 ml/min (P less than 0.01), of RPF to 102.4 +/- 23.1 ml/min (P less than 0.01), and of renin secretion rate to 2,582.6 +/- 786.4 U/min (P less than 0.005). The decrease in renin secretion rate during the infusion of indomethacin persisted when renal perfusion pressure (RPP) was maintained relatively constant before and during the infusion of indomethacin. Furthermore, we found that infusion of prostaglandin E1 (PGE1) into the kidney gave the same pattern of response as PGE2. The data suggest that PGE1 and PGE2 play a role in the control of renin secretion.


Partition of xenon and iodoantipyrine among erythrocytes, plasma, and myocardium.

A new method was developed for determining directly the distribution of 133Xe between red cells and plasma in vitro without an air-fluid interface; the partitioning of 133Xe and 133-i-iodantipyrine between blood and myocardium was investigated in the dog in situ. The red cell-plasma partition coefficient for 133Xe (lambdacpX, unit: ml/ml) at 37 degrees C was 2.27 +/- 0.07 (mean +/- SD) for human blood and 3.31 +/- 0.06 for dog blood. The red cell-plasma partition coefficient for 131I-iodantipyrine (lambdacpI, ml/ml) was 0.75 +/- 0.04 for human blood and 0.97 +/- 0.03 for dog blood. lambdacpX and lambdacpI did not change significantly after the intravenous administration of sodium pentobarbital (30 mg/kg) into the dog. lambdacpX of dog blood varied inversely with temperature, whereas lambdacpI showed very little change with temperature. The blood-left ventricle partition coefficient for 133Xe (lambda'btX, corrected for trapped blood) varied directly with directly with red cell volume fraction (H): lambda'btX = 1.32 + 2.00 H. Blood-left ventricle partition coefficient for 131I-iodoanitpyrine did not vary significantly with H. The results support the concept of a three-compartment partition of the indicator among erythrocytes, plasma, and myocardium. The mean values (+/- SD) of the hematocrit-independent plasma-tissue partition coefficient in the left ventricle for 133Xe and 131I-iodoantipyrine were 1.08 +/- 0.16 and 1.54 +/- 0.20 g/ml, respectively.


The effect of ouabain, dinitrophenol, and lithium on the pacemaker current in sheep cardiac Purkinje fibers.

We studied the effect of ouabain and other inhibitors of the Na-K pump on the pacemaker current (IK2) in sheep cardiac Purkinje fibers. We found that exposure to ouabain (2 X 10(7) M) caused an apparent decrease in the amplitude of the IK2 activation curve. We also found that a similar effect was caused by exposure to dinitrophenol (DNP) or lithium-substituted Tyrode's solution. Our studies showed that after prolonged (more than 60 minutes) exposure to ouabain a characteristic current noise appeared and IK2 was replaced by an oscillatory inward current (IOS). The apparent threshold for IOS was -50 to -60 mV and the peak amplitude of this current increased with increasing levels of depolarization positive to threshold. These results suggest that (1) the apparent decrease in IK2 may be a consequence of ionic redistribution due to Na-K pump inhibition; (2) cardiac glycosides cause abnormal impulse generation by an ionic mechanism separate from IK2 and involving IOS.


New colorimetric method for quantitative determination of protein in urine.

Total urinary protein is rapidly precipitated at room temperature by tannic acid. The tannic acid/protein precipitate, dissolved in aqueous triethanolamine/ferric chloride solution, gives a purple-violet color of high absorptivity. Absorbance at 510 nm is linearly related to concentration from 0.05 to 1.50 A for a protein content of 0.05 to 1.50 g/liter, and less than 5 mg/liter can be detected. The CV and analytical recovery ranged from 0.5 to 1.8% and 98 to 103%, respectively. Nonprotein urinary constituents do not interfere.


Sequential-saturation-type assay for serum 25-hydroxyvitamin D.

We describe a method for measuring 25-hydroxyvitamin D in serum. The serum is denatured with ethanol, and the extract purified by chromatography on silicic acid to prevent potential interference from vitamin D and by other substances. 25-Hydoxyvitamin D is assayed by sequential saturation analysis in Tris-HCI buffer, pH 8.6, containing the surfactant Triton X-405 (2 ml/liter) to solubilize the steroid. Diluter, unpurifed normal human serum is used as the binder. The method is sensitive and precise. The dose-response curve is linear. The assay normally gives high count rates (12 000 to 20 000 cpm for the zero standard) and consequently 25-hydroxyvitamin D of low specific activity can be used if necessary. Serum 25-hydroxyvitamin D was determined in normal and osteomalacic subjects.


Computer-assisted quality control in clinical chemistry.

A MUMPS comuter program, which stores and retrieves quality-control data from all automated and manual work-station in the laboratory, has been developed as part of a laboratory information system. Tabular displays, Levey-Jennings charts, and summary statistics are available on a real-time basis. Significant economy over previous manual methods has been observed, and the total quality-control program in the laboratory has become a more active and timely process.


Interference by p-hydroxyphenobarbital in the 125I-radioimmunoassay of serum and urinary phenobarbital.

A radioimmunoassay for barbiturates is shown to be equally sensitive to phenobarbital and its major urinary metabolite, p-hydroxyphenobarbital, in serum and urine. Interference by the metabolite can be essentially eliminated by selectively extracting phenobarbital into chloroform. The extraction efficiency of the method for phenobarbital was 93+/-2% (SD) over the concentration range studied. Although cross reactivity between barbiturates and their metabolites may be less important in determining cases of barbiturates abuse or overdose, it may be extremely important if data on serum or urine are required for accurate estimates of drug disposition, or in establishing dose/response relationships.


An assessment of a reflectance meter system for measurement of plasma or blood glucose in the clinic or side ward.

The Reflomat System for rapid estimation of plasma or blood glucose concentration has been evaluated. The System gave a linear response throughout its analytical range and the recovery of glucose added to glucose-free plasma was 97-105%. Addition of sodium fluoride to plasma produced a 7-15% reduction in the estimated glucose concentration. Plasma glucose concentration estimated with the Reflomat agreed closely with results of a glucose oxidase and a hexokinase based method, and blood glucose concentration measured with the Reflomat agreed well with results of a glucose oxidase method.


Cerebrospinal fluid polyamine monitoring in central nervous system leukemia.

High-pressure chromatographic analysis of cerebrospinal fluid utilizing the o-phthalaldehyde-fluorescent detection system allows the reproducible detection of acid-soluble polyamines in this extracellular fluid compartment. Measurements made by this method in childhood acute lymphocytic leukemia appear to correlate with the remission-relapse status of the patient. The sensitivity of this analytic technique may allow much earlier detection of central nervous system disease. Studies are presently under way in our laboratories to define the usefulness of this technique to monitor successful chemotherapy of leukemia patients.


A study on the dimeric structure of creatine kinase (EC 2.7.3.2).

The generally accepted dimeric structure of creatine kinase (CK) is one in which M subunits and B subunits can occur. This paper reports the existence of three MM-bands and two MB-bands in human sera with increased CK-activity. These findings and supplementary data gathered from hybridisation experiments have led to the conclusion that there are two different M subunits, which can both occur in the enzyme in vivo. Further, findings are reported on the different CK-isozyme patterns of extracts from the cerebellum and from the cortex and the medulla of the cerebrum.


The measurement of serum free insulin by steady-state gel filtration.

A method for the separation of bound and free insulin in the serum of insulin treated diabetics by steady state gel filtration is described. The method meets the criteria which have been suggested for the validation of a method of separating bound from free ligand. The precision of the method is satisfactory, and the results compare well with those obtained by the methods of ethanol precipitation and polyethylene glycol precipitation.


Plasma cholinesterase variants in patients having lithium therapy.

The plasma cholinesterase variants of 190 mentally ill individuals having lithium prophylaxis have been examined. A significantly increased frequency of the E1f gene is reported. The effect of lithium nitrate and sodium nitrate on the plasma cholinesterase variants have been shown to be identical in the concentration range 25.0-50.0 mmol/l. The usual enzyme is slightly less sensitive to inhibition by either salt than the dibucaine resistant variant. The evidence suggest that the increased frequency of the E1f gene could be a genetic marker associated with some mental illness and not the result of lithium prophylaxis.


Serum creatine kinase isoenzymes in Duchenne muscular dystrophy.

Creatine kinase isoenzymes in sera of 51 patients with Duchenne muscular dystrophy were separated on a micro-column of DEAE Sephadex A-50. MB isoenzyme was detected in the sera of 32 cases (63%). MB percentage of total creatine kinase activity correlated significantly with urinary creatine/creatinine ratio in the early stages of the disease. No close relationship between MB levels and ECG findings was observed. The origin of serum MB in Duchenne dystrophy is discussed.


A gas-liquid chromatographic method for the quantitative determination of quinidine in blood.

A gas-liquid chromatographic method, using chloroquine as internal standard, for quinidine evaluation in serum is described. Prior to acidic delipidation, chloroquine is added to the serum sample and an alkaline extraction is used. Direct gas-liquid chromatographic analysis of unaltered forms using a nitrogen detector is performed. The sensitivity limit of this method is 0.5 microng/ml, i.e. sufficient for therapeutic quinidine blood level determinatin (1 to 5 microng/ml).


Chemical measurements of inulin concentrations in peritoneal dialysis solution.

Peritoneal inulin clearance during peritoneal dialysis is a useful indicator of efficiency of removal of larger solutes. Peritoneal dialysis solutions usually contain high glucose concentrations that interfere with the chemical measurements of inulin concentration. In these studies, inulin recoveries in simple glucose and peritoneal dialysis solutions with three chemical methods were compared; all methods reportedly were subject to minimal glucose interference. The findings showed one method subject to minimal and predictable glucose interference in all solutions tested. For two methods, interference in peritoneal dialysis solutions exceeded that predicted from glucose alone; this unexpected interference was shown to most likely result from carmalized glucose subsequent to the routine autoclaving of peritoneal dialysis solutions.


Linearization of data for saturation-type competitive protein binding assay and radioimmunoassay.

Most of the commonly-performed competitive protein-binding radioassay methods utilized in the clinical laboratory are based on the principle of saturation analysis. Although many different methods for linearization of saturation-type assays have been proposed, the algebraic equivalency of all of these methods has not been adequately documented. In this manuscript we have shown the physical and mathematical basis for various methods for linearlization of saturation type assays and the algebraic equivalency of these linearization methods. We have also shown that key parameters such as slope and intercept may be dependent on different components of the assays system with differnt linearization methods. An understanding of these key parameters can help the analyst to evaluate changes in these key parameters and to integrate these parameters in a complete quality control system.


Application of synchronous excitation spectrofluorimetry to drug analysis.

Among the analytical techniques available for the determination of toxic products, fluorimetry is, at present, one of the most frequently employed. But in many cases, measurements at low concentrations are interfered with by Rayleigh and Raman scattering. We propose to eliminate, in great part, this interference and hence increase the sensitivity of the method, by using the new synchronous excitation spectrofluorimetry. Application of this technique to the identification and determination of drugs during recent forensic investigations demonstrates its advantages over classical spectrofluorimetry.


Alkaline phosphatase isoenzyme in intestinal metaplasia of the stomach.

To investigate the relationship of intestinal metaplasia of the stomach and gastric carcinoma, isoenzymatic analysis of alkaline phosphatase (ALP) of the intestinal metaplasia was studied. Purified human intestinal ALP, and anti-human intestinal ALP antibody were used, and mucosa ALP of the other segments of human gastro-intestinal tract was studied simultaneously. Radioimmunoassay technique, and immunofluorescent staining using anti-human intestinal ALP antibody, were applied to the stomach resected for gastric carcinoma or peptic ulcer, ALP extracted from the mucosa of intestinal metaplasia, and from the mucosa of the other segments of human gastro-intestinal tract, was identical with intestinal ALP in its enzymological and immunological properties.


An evaluation of laboratory tests for the detection and differential diagnosis of Cushing's syndrome.

1. Results of tests for the diagnosis of Cushings syndrome of varoius aetiologies are discussed for twenty-five patients in whom the pathology was established by operation or autopsy. 2. Control values for the urinary excretion of free cortisol, 17-OHCS, Porter-Silber chromogens (P-SC) and 17-OS and plasma levels of P-SC are compared with those for normal subjects. 3. The results indicated that urinary values are within the normal range for some patients with Cushing's syndrome. 4. Plasma levels of P-SC in the morning were within the normal range for the majority and elevated for the rest. 5. Some patients showed day-night variation of plasma P-SC but evening values were above the normal range. 6. The expected response for low dosage dexamethasone was found in all patients tested but unexpected responses followed high dosage in some. 7. Plasma 11-OHCS in the five patients tested failed to respond to insulin induced hypoglycaemia. 8. Metyrapone administration and corticotrophin infusion tests had limited usefulness in establishing the aetiology of the disease. The 17-OHCS excretion became raised in the response to corticotrophin and the evaluation was prolonged beyond normal responsiveness.


DNA cytophotometry in pre-natal cytogenetic diagnosis.

DNA cytophotometry was used to resolve a cytogenetic ambiguity involving a possible deletion of part of the short arm of chromosome 18 in cells obtained by amniocentesis. Measurements of chromosomal DNA content were within normal limits. This is the first time that DNA cytophotometry has been used in cytogenetic diagnosis; it illustrates the potential of this new approach to cytogenetics.


Trisomy 9 mosaicism.

The first live-born female with trisomy 9 mosaicism is reported. This patient, like four others in the literature, has a characteristic face with narrowed temples, enophthalmus, large nose and pouched cheeks, as well as skeletal abnormalities of the extremities, including hip dislocation, limited joint mobility and bone hypoplasia.


The prone hip extension test: a method of measuring hip flexion deformity.

The "prone hip extension test" is described as a simple, convenient, and reliable method of measuring hip flexion contracture. The test may be performed on a padded examining table or bed, it is applicable to the spastic patient, and as the patient is examined prone, it provides a method of flattening the lumbar spine under visual control to avoid obtaining either a falsely high or low value. It, therefore, circumvents the problems commonly associated with the traditional "Thomas Test".


Osteotomy as an alternative to total hip replacement in young adults.

The young (under 50) patient with symptomatic osteoarthrosis of the hip from congenital hip dysplasia presents a difficult therapeutic problem. Although total hip replacement can be successful in such cases, the uncertaintly of a long-term result makes an alternative treatment attractive. A series of 15 patients with 17 involved hips were subjected to a carefully planned and executed valgus osteotomy combined with a selective muscle lengthening about the hip. Five years or more after this procedure 14 of the 17 hips of these patients were pain free. The other three hips caused mild pain only after exertion. No patient at final follow-up required external support. Sixteen of the 17 hips showed significant radiological regression of the osteoarthrosis.


The stimulation of lymphocytes by nucleus pulposus in patients with degenerative disk disease of the lumbar spine.

Being avascular the nucleus pulposus is not normally in contact with the immune mechanisms. Rupture out of its confines may result in an inflammatory reaction and contact with immunocompetent cells. Using the lymphocyte transformation test we incubated lymphocytes of 25 patients and 43 controls with an extract of nucleus pulposus. Ten patients with sequestrated or large herniated disks had a mean transformation index of 16.6 compared to controls whose mean index was 3.6. Nine patients with negative myelograms had an idex similar to controls. These results suggest an auto-immune response to nucleus pulposus in patients with sequestrated disks.


The gluteus maximus femoral insertion: a guide in surgery about the hip.

The proximal portion of the gluteus femoral insertion consistently lies at the level of the lesser trochanter, a common reference point in many surgical procedures about the hip. The advantages of using the tendinous insertion of the gluteus maximus into the femur over that of the lesser trochanter is that it is easy to palpate and visualize through the standard lateral and posterolateral approaches to the hip and proximal femur.


Extracellular matrix-cell interactions and chondrogenesis.

Extracellular matrix macromolecules are capable of complex interactions. Recent studies demonstrate that extracellular matrix macromolecules can regulate the synthesis of chrondroitin sulfate by chondrocytes. Extracellular chondroitin sulfate stimulates chondroitin sulfate synthesis, whereas external hyaluronic acid inhibits chondroitin sulfate production. Other matrix macromolecule-cell interactions are reviewed. An hypothesis is proposed to account for the interaction between the cell and its extracellular matrix macromolecules.


Condylocephalic nailing for pathologic subtrochanteric fracture.

Pathologic subtrochanteric fracture in a femur rarefied by fibrous dysplasia of bone was successfully treated with condylocephalic nailing and bone grafting. This procedure is recommended not only for traumatic fractures but also for pathologic fractures secondary to bone tumor.


Fracture healing in the presence of anemia.

In experimental fractures in rabbits, a decrease in blood volume associated with anemia delays healing, but uncomplicated normovolemic anemia has no adverse effect. For the purpose of stimulating the repair process in normovolemic anemia individuals blood transfusions would be ineffectual.


Histocompatibility determinants in idiopathic scoliosis.

The HLA antigen distribution in 64 random scoliosis patients has been determined. Of the surgical group (greater than 50 degrees), the specificity W19 was increased. In the nonsurgical group (less than 45 degrees) the W19 specificity was also increased; however, the only specificity significantly increased was A29 (X2=11.64, P=less than .02). These observations are preliminary and more extensive work is needed to establish the relevance of the major histocompatibility system in the etiology and progression of idiopathic scoliosis.


Diagnosis of ostechondritis dissecans of the femoral condyles: the value of the lateral x-ray view.

The lateral X-ray view of the knee is more likely to yield the diagnosis of osteochondritis dissecans of the femoral condyles if the examiner is aware that most cases are located in the subarticular bone of the medial femoral condyle between two lines: The first extended anteriorly from the density of the roof of the intercondylar notch, and the second, extended distally from the posterior cortex of the distal femoral diaphysis.


Morphology and crystal composition of chondrocalcinosis after osteochondritis dissecans.

Three patients, who in their youth had been operated upon for osteochondritis dissecans in the femoral condyles, and who had developed gonarthrosis and chondrocalcinosis 30 years later, were investigated by arthrotomy. Tissue was obtained from the semilunar cartilages, the joint cartilages and the synovialis, for crystal analysis and morphological studies. The calcium deposits were with X-ray diffraction and polarization microscopy, The compound found was mainly calcium pyrophosphate dihydrate. Crystals were seen in all the tissues studies and the deposits could also be seen in micro-radiography. The histological examination demonstrated mainly degenerative, but also regenerative changes in the articular cartilage. On the site of the osteochondritis lesion the fibrous tissue was very rich in crystals. In the semilunar cartilages and the synovialis crystals were also seen.


Percutaneous biopsy of the iliac crest.

By use of a percutaneous trephine, a relatively large (7.5-mm diameter), full-thickness bone sample can be obtained from the iliac crest under local anesthesia. Such a specimen can be used for histologic evaluation as well as small-volume, bone-grafting procedures. Patient acceptance has been excellent.


Pubic symphysis diastasis treated by open reduction and internal fixation.

Pubic symphysis diastasis usually can be treated by nonoperative means. Nevertheless, there is the unusual patient for whom surgical intervention is required to establish and/or maintain a permanent reduction.


Angiographic assessment and control of potential operative hemorrhage with pathologic fractures secondary to metastasis.

Two cases are reported, which demonstrate the contribution of angiography to the operative management of neoplastic, pathologic fractures. The degree of fracture site neovascularity was assessed by pre-operative arteriography. Selective trans-catheter gelatin-foam embolization was then employed to markedly reduce or obliterate the arterial supply to lesions shown to be richly vascular. Open reduction and internal fixation was subsequently accomplished with minimal operative hemorrhage.


A new technique of open amputation: use of the rolled flap.

In patients with extensive skin, soft tissue or bone loss and chronic osteomyelitis, or vascular disease, one feature in common is a source of potential infection in that limb. An amputation is often advisable but primary closure frequently results in complications. The above described method of open amputation enables us to retain the optimum bone length and skin flaps without basing the level of the amputation upon the apparent proximal level of normal skin. This method is expecially useful in the acutely traumatized and unsalvagable limb with gross contamination, and can produce early primary healing.


Principles of exposure for extremity surgery.

Extremity surgery requires sound anatomical knowledge and adherence to principles of exposure: (1) Position of patient should be optimal for surgery and compatible with adequate and safe anaesthesia; (2) Provide access to the involved areas for suitable surgical procedure; (3) Avoid damage to functional important structures; (4) Produce as little tissue damage as possible; (5) Be adaptable to enlargement or change; (6) Be so done that functional continuity can be restored and the possibility of complications minimized; (7) The healed surgical wound should produce as acceptable cosmetic appearance as possible.


Osteotomy for "delta-phalanx" deformity.

A "delta phalanx" is often not triangular but may be trapezoidal. A "delta phalanx" may be present without a supernumerary digit. It is a form of complex syndactyly. Correction of the deformities of "delta phalanz" is obtained by open wedge osteotomy with excised bone fragments used as a graft and Z-plasty of the skin on the ulnar side of the finger.


The nasal spine.

Although not a frequent occurence, when present a prominent nasal spine contributes to unpleasing septolabial and columella-alar angles which detract from the overall aesthetic quality of the face. It is important to recognize and correct this deformity. In some patients the necessity for spine resection may be subtle. Resection of the nasal spine must be conservative.


The surgical correction of the non-Caucasian nose.

Repairing the non-Caucasian nose can be satisfying to both patient and surgeon. Goals should be directed towards restoring balance and accent--not the elimination of racial characteristics. Careful technique, adhering to a group of principles, leads to exciting results with minimal morbidity and complications.


Scar prognosis.

Scar prognosis is a matter of great natural interest to patients. It is important to realize that the nature of the injury is the most important consideration in the final result. The orientation of the wound in relation to the normal lines of skin tension, its location and pattern, and peculiarities of the individual are all determining factors in the final appearance. Good surgical technique is quite well understood, if not always practiced. The final assessment must always await full maturation of the scar. When discussing either the prognosis or the evaluation of a scar, it must be remembered that the view of the patient is influenced by many subjective factors and will not always coincide with the objective evidence. A knowledge of the factors in scar prognosis is invaluable in establishing and maintaining the rapport and confidence of patients.


Radiation osteitis following irradiation for breast cancer.

Radiographs of the shoulder girdle were examined in 180 women who attended the breast follow-up clinic at the Department of Radiotherapy, Edinburgh. These comprised 52 controls who had been treated by radical mastectomy alone and 128 patients who had received post-operative X-ray therapy. The significance of osteoporosis as a sequel to irradiation is doubtful as it occurred in a substantial proportion of the control cases. Osteitis of severe degree occurred in 13.3% of patients who had been irradiated and was present in a mild form in a further 8.6%. The development of severe osteitis requires an NSD of 1650 rets or more. Estimates of the frequency of radiation osteitis are of no value unless detailed information is also provided about the techniques and quality of radiation.


Problems and limitations of bone scanning with the 99Tcm-phosphates.

99Tcm-phosphate bone scans are being increasingly used in the detection of bony metatases. The sensitivity of the bone scan and the non-specific nature of the isotope image, when compared with radiographs, make it important to be aware of the problems and limitations of the technique. This paper describes and illustrates some of the diagnostic problems encountered by the author over the past 3 years.


Drug abuse proficiency testing.

Concerning drugs in general, proficiency testing has undoubtedly been a major contributing factor to improved detection. Some of the improvement may be due to advances in technology, and this is possibly the case with improvement in the detection of morphine and methadone. The improvement in the determination of methamphetamine within three surveys over six months can clearly be attributed to proficiency testing. In drug screening for cocaine abuse, the poor results in proficiency testing for the detection of the primary metabolite, benzoylecgonine, has clearly demonstrated that laboratories are not proficient in this screening.


Studies on protein and nitrogen metabolism in nephrotic syndrome using 15N-labelled glycine and urea.

Administering 15N-labelled glycine, 15 N incorporation into serum albumin and its excretion into urine and feces, together with nitrogen balance were investigated in 3 nephrotic and 2 normal adults. Furthermore, 15N-labelled urea was injected into a nephrotic adult and a glomerulonephritic adult, both advanced in azotemia and treated on low protein diet, and a normal subject on a normal diet, to examine the amounts of 15N incorporation into serum albumin. In the 3 nephrotic patients whose nitrogen balance was almost maintained, incorporation of 15N-glycine into serum albumin has been proved greater than in the normal subjects. In any of the above patients, 15N excretion into urine was less than in the normal subjects. Fecal 15N excretion was 2.0--2.5 % of the doses, indicating that approximately 98 % of 15N-glycine was absorbed. In the nephrotic patients, 15N incorporation into serum albumin examined by 15N-labelled urea administration was more accelerated than in the glomerulonephritic patients and was negligible in the control subject on a normal diet.


Specificity of sodium-dependent electrogenic sugar transport in amphibian kidney proximal tubule.

Microelectrode studies were performed to examine the specificity of the electrogenic sugar transport by Triturus proximal tubule. Two types of carriers could be distinguished, one having an affinity for D-mannose but not for D-xylose (M type), and the other having the reverse characteristics (X type). D-Glucose and alpha-methyl-D-glucoside had a relatively high affinity for both types of carriers, but D-galactose, D-fructose, 3-O-methyl-D-glucose, D-mannitol and L-glucose had no affinity for them. The observed structural requirements of renal sugar transport were different from and stricter than those of intestinal sugar transport observed in the same animal.


A scanning electron microscope study of the human Bowman's epithelium.

The parietal epithelium of the Bowman's capsule in normal human kidney was studied by scanning electron microscopy. Stereoscopic scanning electron microscopy showed clearly that the Bowman's capsule, cut in half by a razor blade, was depressed hemispherically and coated with a flat layer of polygonal epithelial cells. The epithelial cell had a round, slightly elevated, and eccentrically located nuclear portion, and extended flat cytoplasmic layer from it toward the periphery. Tiny cytoplasmic projections, microvilli, were seen in varying degrees on the surface. One or two thin and long cilia were occasionally present around the nuclear portion.


Chromosome analysis in the Kruger National Park: the chromosomes of the bushbuck (Tragelaphus scriptus).

Chromosome studies in the male and female bushbuck (Tragelaphus scriptus) are discribed. The male has a diploid chromosome number of one fewer than the female, and the Y-to-autosome fusion. The configuration of a quadrivalent observed in meiotic preparations from the male confirmed the presence of a fusion between a Y chromosome and an autosome. All other members of the tragelaphine tribe so far studied chromosomally show the presence of a Y-to-autosome fusion. It is postulated that the fusion observed in all present-day species of the tribe studied to date arose as a single event in a common ancestor.


Respiratory status of Los Angeles firemen. One-month follow-up after inhalation of dense smoke.

A standardized respiratory questionnaire and detailed pulmonary function tests were administered to 21 Los Angeles firemen one month following exposure to the combustion products of polyvinylchloride, which had produced transient hypoxemia in 19 of the firemen. The results of these studies were compared with those obtained in a sample of nonfiremen residing in the Los Angeles area who were matched by computer with the firemen for anthropomorphic characteristics and smoking status. The frequency of respiratory symptoms, the results of spirometric and plethysmographic studies, and the single-breath nitrogen washout were similar in the firemen, compared with the matched sample, whereas closing volume was higher in the matched controls. These findings suggest that although fighting fires may result in acute pulmonary injury secondary to discrete episodes of inhalation of smoke, it does not appear to predispose to the development of chronic respiratory symptoms or chronic functional respiratory impairment.


Pseudo left axis deviation and the S1S2S3 syndrome in chronic airway obstruction.

Pseudo left axis deviation (not true left axis deviation and the S1S2S3 syndrome are infrequently reported electrocardiographic findings in chronic airway obstruction. One hundred fifty-eight patients with severe chronic airway obstruction documented by pulmonary function testing were evaluated for these electrocardiographic findings. Pseudo left axis deviation was found in 23 patients (15 percent), and the S1S2S3 syndrome was found in 14 patients (9 percent). The electrocardiographic and vectorcardiographic findings are illustrated.


Relationship between the electrical (electrocardiographic) and mechanical (echocardiographic) events in Wolff-Parkinson-White syndrome.

Studies using epicardial mapping on patients with Wolff-Parkinson-White syndrome have demonstrated that the delta vector of the electrocardiogram is a detector of the location of at least one bypass tract. In order to relate the electrical activities (preexcitation) with the mechanical activity (septal and ventricular wall motion), echocardiographic strip-chart recordings were obtained in 22 patients with Wolff-Parkinson-White syndrome. Our studies indicated that in the majority of patients with Wolff-Parkinson-White syndrome, left ventricular and septal contraction is normal, suggesting that normal activation predominates and that the determinants of abnormal septal wall motion are (1) the location (right ventricular free lateral wall or septrum) and (2) the degree (duration of the QRS complex greater than 130 msec) of ventricular preexicitation.


"Acute" granulomatous pericarditis. clinical and hemodynamic correlate.

Ten cases of acute constrictive pericarditis from southern Iran are presented. They differed from chronic constrictive pericarditis by the absence of ascutes and edema of the lower extremities, the presence of cardiomegaly on posteroanterior chest x-ray film, the lack of calcification of the pericardium on fluoroscopic examination, and the presence of sinus rhythm in all cases. If tuberculosis is the etiologic agent, early pericardiectomy should be considered. This is especially important in areas where close follow-up of patients is difficult or impossible, since all patients in this series ultimately developed clinically significant constriction.


Pertussoid eosinophilic pneumonia. Pulmonary infiltrates with eosinophilia in very young infants.

This presents four new cases of pertussoid eosinophilic pneumonia in young infants. The 19 previously reported cases have been young infants with bilateral intersitial infiltrates and eosinophilia. The cause of this syndrome is unknown. Cultures from the four patients were negative; however, studies of immunoglobulin levels suggest that the disease has an infectious etiology. The cause of the eosinophilia is also unknown; however, it appears to be associated with a favorable prognosis in young infants with severe bilateral pneumonitis.


Validation of therapeutic bronchoscopic bronchial washing in cystic fibrosis.

Validation of rigid-tube bronchoscopy with small-volume (5-ml increments not to exceed 300 ml) bronchial washing as a therapeutic adjunct was performed on six patients with cystic fibrosis, using serial tests of pulmonary function as a yardstick for assessment of efficacy. Two patients did not undergo the procedure and served as control subjects. All patients were characterized as having varying severity of pulmonary involvement. Large central airways were severely obstructed, and older patients had more trapped gas in their lungs. Hypoxemia and large alveolar-arterial oxygen pressure differences [P(A-a)O2] were due to inhomogeneity of alveolar ventilation. Results indicated that up to ten days to two weeks, bronchoscopic bronchial washing may in some instances improve maximal expiratory flow-volume curves and specific airway conductance and decrease P(A-a)O2 towards normal. Distribution of alveolar gas P(A-a)O2 towards normal. Distribution of alveolar gas became more homogeneous. We conclude that bronchoscopic bronchial washing may be effective in the management of patients with cystic fibrosis, by augmentation of their inadequate cleansing function of the conducting airways.


Paradoxic acceleration of ventricular rate after therapy with lidocaine and ajmaline. Findings in two patients with supraventricular tachyarrhythmia.

In two patients with supraventricular tachyarrhythmias with atrioventricular block, therapy with lidocaine and ajmaline decreased the atrioventricular block and caused paradoxic acceleration of the ventricular rate. Appropriate treatment of this hazardous result of therapy with antiarrhythmic drug is reviewed.


Clinical pulmonary tuberculosis in an asthmatic patient using a steroid aerosol.

A patient who was receiving a steroid aerosol for treatment of asthma developed clinical pulmonary tuberculosis. Continued administration of the steroid aerosol along with antituberculosis chemotherapy did not adversely influence healing of the pulmonary lesion.


False-positive echocardiographic diagnosis of pericardial effusion. Result of tumor encasement of the heart simulating constrictive pericarditis.

A 46-year-old man had advanced squamous cell carcinoma of the lung and apparent constrictive pericarditis. Echocardiographic studies twice demonstrated apparent pericardial effusions, but pericardiocenteses were unsuccessful. Tumor encasement of the heart was diagnosed clinically and at necropsy. This entity is yet another cause of a false-positive echocardiographic diagnosis of pericardial effusion.


A nosocomial outbreak of influenza A.

During the first week of March 1974, a hospitalized patient being evaluated for hyperproteinemia and hypertension experienced fever, chills, and myalgia and showed pulmonary signs consistent with diffuse pneumonia. Subsequently, the findings from serologic tests confirmed that the patient had viral influenza. Seven other compromised hosts on the same ward developed symptoms of pneumonic influenza, and serologic data on three of the seven confirmed influenza A2. Additionally, a previously healthy young adult admitted with acute respiratory distress died of nonbacterial complications and was shown to have community-acquired influenza. The unusual features of the epidemic were the intrahospital localization of the epidemic in compromised hosts, the high rate of pneumonic complications, the low rate of secondary bacterial infection, and the severity of the viral pneumonia in the community-acquired case.


Short-duration treatment of pulmonary tuberculosis.

In this study, pulmonary tuberculosis was treated on an ambulatory basis, with the patients engaging in their usual activities and with a shortened period of chemotherapy. During the first year of the study, patients with pulmonary tuberculosis were randomly included in one of the following two groups: (1) group 1 received isoniazid (5 to 6 mg/kg of body weight), ethambutol (25 mg/kg), and rifampin (rifampicin, 10 mg/kg) daily for a total of six months; and (2) group 2 received the same therapy as group 1, but treatment was continued for a further six months with only isoniazid (5 mg/kg three days per week). At the beginning of the second year of the study, all subsequent patients included in the study were placed into group 1. Of the 163 patients who started the study, 136 patients (99 from group 1 and 37 from group 2) completed the treatment and converted their bacteriologic findings. There was one relapse in group 1. Adverse reactions were observed in six patients, but they did not have to interrupt treatment.


Cardiac metastases in lung cancer.

Cardiac metastases from bronchogenic carcinoma are not commonly diagnosed prior to death. This study isolates factors associated wtih the development of cardiac involvement. Four hundred eighteen consecutive patients with lung cancer who had autopsies were studied. Twenty-five percent of these patients had cardiac involvement. Factors associated with cardiac metastases were (1) histologic cell type of the tumor, (2) aggressive therapy, (3) extent of disease, and (4) tumor differentiation. The presence of cardiac metatases was not related to the length of survival. Clinical signs of cardiac involvement included an enlarging heart on the chest x-ray film, development of congestive heart failure, or electrocardiographic changes. Suspicion of cardiac metastases in high-risk individuals, prompt diagnostic evaluation, and rapid institution of therapy may improve the outlook for many patients, since reaccumulation of fluid was generally slow.


Thoracocentesis of loculated pleural effusions using grey scale ultrasonic guidance.

Six patients with either malignant pleural effusion or empyema, in whom multiple conventional attempts at thoracocentesis were unsuccessful, were evaluated by ultrasound. In each case, a subsequent thoracocentesis guided by ultrasound produced sufficient fluid to enable a diagnosis to be established. In no case was pneumothorax produced.


Decortication after 35 years.

A 66-year-old white woman had a paraffin plombage performed in 1940 for tuberculosis. In 1975, she had decortication for terminal respiratory insufficiency, with return to an active life. Thirty-five years of pulmonary compression does not produce irreversible changes in the pulmonary parenchyma.


Psychiatric hospitalization. I. Comparison of public and private delivery systems.

The effect of financial requirements for admission on the delivery of psychiatric treatment services was studied by comparing all patients admitted to the psychiatric services of a public and a private general hospital, serving geographically similar areas. Patients admitted to these two services (both staffed by the same Department of Psychiatry) were compared in a variety of factors relating to admission determinants, diagnosis, length of hospitalization, and type of treatment. The two patient groups differed in a number offactors, including presenting problems, diagnoses, and.psychological concept of their illnesses. The public hospital patients were less likely to receive somatic treatments (especially psychotropic drugs) and more likely to be hospitalized for longer periods than were the private hospital patients. These findings, although inconclusive because of social class, age, and sex variables, suggest that financial requirements for admission affect the intensity and expeditiousness of the treatment.


A suicide epidemic in a psychiatric hospital.

There were 3 suicides on one ward of a psychiatric hospital in 6 months, and no others in the hospital in 10 years. Statistics demonstrate that this was probably not due to a chance change in the patient population, and deteriorating therapy conditions may have been responsible. The hospital staff was very uncertain about treatment goals and techniques at that time, and resident supervision suffered. Associated specific treatment errors are revealed in the 3 case histories. The epidemic ended after the re-institution of firm supervision of basic psychiatric care directed toward clearly-defined treatment goals.


Mood elevating effect of trihexyphenidyl and biperiden in individuals taking antipsychotic medication.

The author calls attention to mood-elevation as a side effect of Biperiden HCL and Trihexyphenidyl HCL, two anticholinergic antiparkinsonian agents. This is of significance because of the despondency and anergy often seen in schizophrenics taking antipsychotic medication and because of the difficulty discerning the origin of affective changes in the face of polypharmacy.


Munchausen's syndrome with a psychiatric presentation.

An unusual case of Munchausen's Syndrome is presented, in which the patient feigned a psychiatric history, complained of emotional symptoms and sought admission to a psychiatric unit. This variant of the usual somatic presentation is discussed in terms of the problem of motivation in Munchausen's Syndrome. Munchausen's Syndrome is a behavioral complex in which patients feign history and symptoms of illness and seek hospital admissions. Such an unusual pattern of behavior is clearly within the province of psychiatry, yet these patients, presenting most commonly with somatic symptoms, are often reluctant to see a psychiatrist and flee before being interviewed. Of 38 cases in one series, only 16 had a psychiatric consultation. The purpose of this paper is to describe an unusual case of Munchausen's Syndrome, a patient who, rather than fleeing from psychiatrists, sought admission to psychiatric units. While the genetic material available in this case is sparse, the phenomenon itself of psychiatric complaints and history in such a patient may further our understanding of, and spur futher interest in, a perplexing disorder.


[Oral anticoagulants and platelet function in hypolipemic therapy using a new clofibrate analog (BM 15.075) (author's transl)].

When testing the effect of a new clofibrate analogue (BM 15.075) on oral anticoagulation and blood clotting in 15 patients for over four weeks it was demonstrated that, depending on the dose of the drug, there was an increase in anticoagulation. The dose of phenprocoumon had to be reduced by 20.6 or 28.7%, respectively, when BM 15.075 was given at a dose of 450 or 600 mg. There was an inhibition of collagen-induced platelet-aggregation. In parallel there was an increase in bleeding time. Fibrinogen concentration was slightly but statistically not significantly decreased. Euglobulin lysis was shortened, especially if previously abnormally long. There was no direct influence on other plasmatic clotting factors.


[Endoscopic diagnosis of oesophagitis: problems of differentiation from normal (author's transl)].

The diagnostic significance of endoscopically early signs of oesophagitis in the absence of macroscopic evidence of epithelial abnormalities has been studied prospectively. Changes from the usually observed shininess, pale-pink colour, smooth texture, regular capillaries, sharp Z-line and a decreased mechanical resistance of the mucosa to mechanical damage do not indicate oesophagitis. Nor should one infer gastro-oesophageal reflux from these endoscopic findings. They are presumably ageing changes in the oesophagus.


[Longterm results of mitral valve replacement (author's transl)].

210 patients were followed up by the actuary method for over 5 years after isolated mitral valve replacement or a double valve replacement. After isolated valve replacement the one month survival including the operative mortality was 92+/-2%. The survival after one year was 83+/-3% and after 5 years 66+/-7%. The five year survival of patients in preoperative class III (according to the NYHA) was 73+/-8% and of class IV 57+/-8% (P less than or equal to 0.1). A comparison of valve replacements for pure mitral stenosis or mitral insufficiency showed no statistically significant differences. In the 37 patients who had a double valve replacement the survival risk was not increased in comparison with those patients who had had a single valve replacement. Age above 45 years and a preoperative markedly raised pulmonary arteriolar resistance reduced the chances of survival.


[Results of embolectomy in massive pulmonary embolism (author's transl)].

In ten patients successful embolectomy after acute massive pulmonary embolism was performed. Clinical symptoms included circulatory arrest and shock as well as collaps, syncope and dyspnoe. Pulmonary angiography regularly showed massive, bilateral emboli. In 9 patients more than one half of the pulmonary artery system was involved (perfusion defect more than 50%). Right heart catheterization demonstrated pulmonary hypertension in all cases. In 8 patients the pulmonary artery mean pressure (PAm) exceeded 30 mm Hg. In 9 patients there were signs of right heart failure (RVEDP more than 11 mm Hg). At recatheterization 6 to 30 (mean 19) days after operation using cardiopulmonary bypass there was a marked improvement of pulmonary angiograms, which were normal in 3 cases. PAm decreased from 34.3 mm Hg to 14.6 mm Hg postoperatively and RVEDP from 14.4 to 5.1 mm Hg (p less than 0.001). These results confirm, that pulmonary embolectomy leads to a good functional results.


[Revascularisation after lower-leg arterial block. Report of 115 femoro-crural reconstructions (author's transl)].

Revascularisation after arterial block in the lower leg is a low-risk procedure which is definitely superior to lumbar sympathectomy in stage III and IV. In 110 patients 115 femorocrural reconstructions were performed in almost 9 years. Four weeks after the operation the revascularisation was open and showed free flow in 93.3%. In 64.4% an open revascularisation with largely painless walking ability was found 2-9 years post-operatively.


Ribonuclease H levels during the response of bovine lymphocytes to concanavalin A.

Several enzymes with ribonuclease H specificity have been identified in bovine lymphoid tissue. Their nomenclature and some of their properties have been reported previously. In this study the time course of the induction of the different ribonuclease H activities during the stimulation of resting bovine lymph-node cells with concanavalin A was investigated. The activity of one of these enzymes (ribonuclease H IIb) increases in parallel with the induction of uridine incorporation and is well separated from the induction of ribonuclease H I, which increases together with DNA synthesis. These data indicate that the different ribonuclease H activities serve different physiological functions. They suggest that ribonuclease H I belongs to the set of enzymes which are involved in DNA synthesis.


The purification, characterization and partial sequence determination of a trout testis non-histone protein, HMG-T.

A specific non-histone chromatin-associated protein, having a high content of both acidic and basic amino acids has been isolated from the chromatin of rainbow trout (Salmo gairdnerii) testis cells. The protein has been prepared by the extraction of chromatin with 0.35 M sodium chloride and purified by chromatography on carboxymethyl-cellulose with a gradient of lithium chloride at pH 9.0. The amino acid sequence of the first 29 residues of the amino-terminal region has been determined using an automatic protein sequencer. The primary structure of this protein differs from that of any of the histones yet sequenced and, therefore, cannot be a degradation produce of any of them. Moreover, the N-terminal amino acid sequence shows considerable similarity to the HMG-1 and HMG-2 chromosomal proteins described by Goodwin et al. [Eur. J. Biochem. 38, 14-19 (1973)] whose-N-terminal sequences were also determined in this laboratory.


Least-squares analysis of circular dichroic spectra of proteins.

It is shown that the method proposed by Baker and Isenberg [Biochemistry, 15, 629 (1976)] for estimating secondary structure composition of proteins from circular dichroic spectra is a least-squares fitting technique. Estimates obtained by this method for myoglobin, lysozyme, lactate dehydrogenase, papain, and ribonuclease are not substantively different from those obtained using unconstrained linear least squares.


The superhelical density of nuclear DNA from human cells.

Structures resembling nuclei may be released by gently lysing human cells in solutions containing non-ionic detergents and high concentrations of salt. These structures, which we call nucleoids, sediment in sucrose gradients containing the intercalating agent, actinomycin D, in the manner characteristic of superhelical DNA. We have determined the concentration of actinomycin that minimises the rate of sedimentation of nucleoids. At this concentration, we have determined the amount of drug bound per base pair of DNA by means of a double-labelling procedure. Assuming that each molecule of actinomycin bound to nucleoid DNA unwinds the double helix by 26 degrees, we calculate that there is one supercoil every 90-180 base pairs in nucleoid DNA. These values lie within the range found for the circular DNA molecules of plasmids and viruses.


Paramyotonia congenita without cold paralysis and myotonia levoir. A genetic and clinical study.

A family with myotonia congenita without cold paralysis in 26 affected members is described. Cold paralysis never occurred spontaneously in this family and could not be provoked by immersion in ice water or by K+ load. The findings confirm the existence of paramyotonia without cold paralysis as a separate genetic entity.


Effect of thalamotomy and levodopa therapy on the speech of Parkinson patients.

The speech of three groups of Parkinson patients--nonsurgical, postunilateral and postbilateral thalamotomy--was evaluated. Dysarthria, bulbar motility and pyramidal tract indexes were determined for each patient. There was a statistically significant greater impairment in dysarthria and pyramidal tract indexes of patients with thalamotomy. L-Dopa and carbidopa therapy failed to significantly improve speech in any group.


Scleroedema (Buschke). A case report.

A case of scleroedema is reported in a 28-year-old man with severe neuromuscular involvement. Failure in neural conduction as well as muscular degeneration and necrosis were seen. Histopathological study showed resorption and formation of scar tissue probably secondary to ischaemia. In addition there was increase in neutral, sulphated and non-sulphated mucosubstances in the dermal and endomysial connective tissue.


Comparative Doppler directional sonographic and ophthalmodynamographic study in the occlusion of the internal carotid artery.

In the occlusion of the internal carotid artery, the change occurring in the internal-external carotid pressure gradient may cause flow reversal within the ophthalmic artery and its branches. Ophthalmodynamographic, Doppler directional sonographic and angiographic investigations were performed in 21 cases (11 total occlusions, 6 severe and 4 moderate stenoses of the internal carotid artery). The authors compare the results of these investigations and discuss the practical importance of Doppler directional sonography and the significance of flow reversal in the ophthalmic artery.


Paget's disease with spinal cord compression. Favourable course after decompression and calcitonin treatment in two cases.

Two cases with spinal cord compression due to Paget's disease (osteodystrophia deformans) are reported, which were treated with calcitonin (Salmon Calcitonin) during 12 and 24 months after decompressive laminectomy. Both presented a favourable clinical course with improvement of sensory and bladder disturbances, paraparesis and pain. Diagnostic criteria as X-ray investigation, scintigraphy of bones, biochemical parameters and the long-term treatment whith calcitonin, are discussed.


Refractory period of human sural nerve action potential related to age in healthy probands.

150 sural nerves from 150 probands 10-70 years of age were investigated by applying supramaximal paired electric stimuli and recording the action potentials with needle electrodes. The responses to the first and second stimulus were evaluated with respect to latency and amplitude. Correlation of the electrophysiological findings with the age of the probands gave the following results: (1) Slight but statistical insignificant reduction of conduction velocity with advancing age up to 70 years. (2) Statistical significant decrease of amplitudes and prolongation of potential duration with advancing age. (3) No significant relationship between refractory period (latency and amplitude of the test response) and advancing age up to 70 years. The results are discussed in terms of their clinical meaning.


Cortical and cervical somatosensory evoked responses in demyelinating diseases.

In six patients suffering from a multifocal neurological disease of the demyelinating type, a somatosensory evoked response was analyzed in the cortical and cervical are after stimulating the right index finger and the right nervus suralis. The results of the investigation with this method indicate that localization of the central nervous system pathology seems to lie within the realms of possibility, in which case this method will be a useful addition to the tools used to evaluate quantitatively the results of different treatments in this type of disease.


Plasma levels of phenobarbital and phenytoin in epileptic outpatients.

In a group of 65 epileptic outpatients the reliability of intake of prescribed medication was evaluated according to two criteria. The following results were obtained: the number of patients with no or irregular intake of antiepileptic drugs in the whole group was 28%; the relationship between dose and observed plasma levels in patients reliable to intake could be verified; physicians were more often aware of unreliable intake by their patients than could be expected by chance.


The role of cerebral perfusion pressure as origin of brain edema in acute arterial hypertension.

In a series in 8 cats, cerebral perfusion pressure (CPP) was evaluated over a period of 5 min after production of an acute arterial hypertension. The mean percentual increase of blood pressure, CPP and ICP equalled 100%. the fact, that ICP does not play any role in acute hypertension, indicates that an abrupt elevation of filtration pressure within the capillaries must be the decisive factor leading to edema.


A study of the activity of platelet monoamine oxidase in patients with migraine headaches or with 'cluster headaches'.

The results of the study of the activity of platelet monoamine oxidase (MAO) in patients with migraine headaches or with 'cluster headaches' are presented. In both types of headaches, MAO activity is lower than in normal subjects. We suggest that the low MAO activity is due to a primary constitutional defect.


Renal revascularization after splenic artery implantation into the kidney. Consecutive serial angiographic study in the dog.

29 mongrels were subjected to splenic artery implantation into the left kidney. Consecutive angiographies showed that this procedure regularly was followed by an initial thrombus formation in the implanted artery and an early recanalization of this thrombus. After creation of stenosis and eventually occlusion of the left renal artery, newly formed intrarenal vessels could be demonstrated next to the implanted artery. These vessels formed communications between the splenic and intrarenal arteries. At angiography of the implanted splenic artery the constrast medium was seen to pass over to the newly formed vessels and to intrarenal arteries followed by contrast medium opacification of the renal parenchyma and the renal vein and excretion to the pelvis and ureter. The experimental animals survived contralateral nephrectomy and ligature of the ipsilateral renal artery provided that a slowly progressing stenosis of this artery was created.


Profound reflex bradycardia produced by transient hypoxia or hypercapnia in man.

A quadraplegic patient was able to breathe adequately for the first 3 days after his cervical spinal cord was transected by a bullet. However, for several days thereafter spontaneous ventilation became inadequate, most likely due to edema of the cord, and mechanical ventilation was required. When the ventilator was disconnected for required tracheal aspiration, before there was any tracheal stimulation, profound bradycardia, hypotension and syncope occurred within a few seconds. The bradycardia could be diminished by atropine and its onset delayed by prior ventilation with oxygen. Because of the rapid onset of the hemodynamic changes and their correlation with relatively small changes in PaO2 and PaCO2, it is suggested that this vagally mediated bradycardia represents the primary cardiac reflex response to peripheral chemoreceptor stimulation, which, although extensively studied in experimental animals, has not before been described in man. Just as in animals, it seems likely that the inability to hyperventilate permitted the primary cardiac reflex to occur rather than the usual response of tachycardia to chemoreceptor stimulation which is prepotent with spontaneous ventilation. An understanding of this reflex was important in the clinical mangement of this patient.


Ex vivo vascular perfusion of the isolated rat small bowel. Importance of the intestinal brush border enzyme-release in basal conditions.

The vascular perfusion of the whole isolated intestine of the rat with homologous non-diluted blood is compared with classical in vivo experiments. During a 2 1/2-hour perfusion procedure no significant difference was noted between the two experimental schedules as far as haemodynamic, histological, mechanical and/or electrical activities of the gut are concerned. However, striking changes in the intestinal brush border enzyme output within the lumen appear between ex vivo and in vivo experiments. The early increase of intraluminal intestinal sucrase, already after the 95th min of perfusion indicate clearly the existence of a subcellular damage even not detectable by other tests of viability. Therefore, it is suggested that release of brush border enzymes might represent an interesting criterion of viability of in vitro or ex vivo preparations.


Evaluation of implanted faulty demand pacemakers by magnet waving and electrical chest wall stimulation. A report of clinical experience.

15 different models of implanted demand pacemakers (61% Cordis models) in 156 patients were scrutinized owing to an announcement that had identified 3 faulty Cordis series and, as a consequence, had provoked considerable uncertainty among all pacemaker patients in the community. Malfunctions of the sensing, and reed switch mechanisms as well as changes in pacers' refractory periods were excluded by the electrical chest wall stimulation (ECWS), magnet waving (MW) or a combination of both. That those models suspected of malfunction show merely a drop in rate was verified. Established patterns of early rate drop guided the exchange for new units: no abrupt or complete rate drop occurred and no patient was lost. The application of indirect overdrive revealed that the blocking capacity for rapid rates was in Omni-Ectocor units less reliable than in Ectocor units. The characteristic reactions to MW and ECWS of the 15 demand pacemaker models were determined. Because both methods proved to be as easy to apply as they were beneficial for the follow-up, also in the uncommon situation created by the Cordis announcement, the application of both of these methods on a routine basis in pacemaker clinics is advocated.


Acute coronary events in some Dutch countryside communities.

Incidence of, mortality from and fatality of acute myocardial infarction (AMI) and fatal attack of presumed coronary origin (FCA) were registered between July 1970 and March 1974 in a well-defined Dutch countryside population. Patients with a documented previous AMI or aged 70 or older were excluded. AMI (431 cases) and FCA (124 cases) were considered separately. No differences in coronary history profile, age or sex distribution could be demonstrated. However, the period of premonitory symptoms preceding FCA was at a 5% level significantly shorter than in AMI, provided that the unstable angina was the first symptom of IHD. The combined fatality rate of AMI and FCA, counting death during the first 28 days only, was 25% under age 55 and 32% in age group 55-69 yr. None of the 171 cases under age 55 who survived the first 24 h died in the following 4 weeks, whereas 20 out of 384 in the older age group did: a significant difference at a 5% level. The incidence and mortality rates are presented for both AMI and FCA, subdivided in the age groups 35-44, 45-54, 55-64, and 65-69, per 1000 person years. The incidence was 1, 5, 10, 14 in males, and 0, 1, 2, 6 in females, respectively. Mortality was 0, 1, 3, 5 in males, and 0, 0, 1, 3 in females. The set-up of the survey, the diagnostic criteria and the comparability with recent studies are discussed.


Plasma concentrations of propranolol in patients with essential hypertension.

Sixteen patients with essentialy hypertension were treated with propranolol 160 to 640 mg daily for three months. Significant decreases both in recumbent and standing blood pressure were observed after three days treatment and subsequently. Reduction of blood pressure was more pronounced when the dose of propranolol was increased. However, neither the mean dose nor the plasma concentration of propranolol could be correlated with the mean decrease in blood pressure. There was great interindividual variation in the plasma concentrations of propranolol produced by the same daily dose. The initial stimulation of plasma renin activity and the therapeutic response to propranolol could not be correlated.


Elimination of canrenone in congestive heart failure and chronic liver disease.

The elimination half-life (T1/2) of canrenone, the principal unconjugated metabolite of spironolactone, was 59 h (range 32-105 h) in 5 patients with chronic liver disease and 37 h (range 19-48 h ) in 7 patients withcongestive heart failure. In comparison the T1/2 in normal subjects was 13.5-24 h in previous reports and 20.5 h in the present study, However there was no evidence of greater cumulation of canrenone in the plasma of those patients with a prolonged T1/2.