Ca++-induced fusion of fragmented sarcoplasmic reticulum with artificial planar bilayers. Addition of fragmented sarcoplasmic reticulum (SR) vesicles to the aqueous phase of a black lipid membrane (BLM) causes a large increase in BLM conductance within 10 min. The conductance increase is absolutely dependent on three conditions: The presence of at least 0.5 mM Ca++, an acidic phospholipid such as phosphatidylserine or diphosphatidylglycerol in the BLM phospholipid mixture, and an osmotic gradient across the SR vesicle membrane, with the internal osmolarity greater than the external. These requirements are identical to conditions under which the fusion of phospholipid vesicles occurs. When the early part of the time course of conductance rise is examined at high sensitivity, the conductance is seen to increase in discrete steps. The probability of a step increases with the concentration of Ca++ in the medium, with the fraction of acidic phospholipid in the BLM, and with the size of the osmotic gradient across the SR vesicle membrane. On the other hand, the average conductance change per step is independent of the above parameters, but varies with the type and concentration of ions present in the aqueous phase. For a given ion, the mean specific conductance per step is independent of the ion's concentration between 10 and 100 mM. The probability distribution of the step-conductances agrees well with the distribution of SR vesicle surface areas, both before and after sonication of the vesicles. The evidence indicates that SR vesicles fuse with the BLM, thereby inserting SR membrane conductance pathways into it. Each discrete conductance jump appears to be the result of the fusion of a single SR vesicle with the BLM. This technique may serve as a general method for inserting membrane vesicles into an electrically accessible system.


Localization of 5-methylcytosine in human metaphase chromosomes by immunoelectron microscopy. Human metaphase chromosomes, fixed in methanol-acetic acid, were ultraviolet irradiated to produce single-stranded regions of chromosomal DNA and treated with anti-5-methylcytidine. Using an immunoperoxidase procedure, regions of antibody binding were readily visualized by light microscopy in the centromeric heterochromatin regions of chromosomes 1, 9, 16, the short arm of chromosome 15, and in the distal portion of the Y. Electron microscopic visualization of the same whole mount chromosome preparations transferred to formvarcoated grids revealed additional details of the distribution and arrangement of 5-methylcytosine. A helical arrangement of 5-methylcytosine residues was seen below the centromere of chromosome 1. The Y chromosome showed a concentration of 5-methylcytosine residues on the distal long arm, and in areas just below and slightly above the centromere. In all the above chromosomes, especially chromosome 15, additional 5-methylcytosine residues were detected as isolated foci along the arms. Our findings support the concept that clusters of similar purine or pyrimidine residues exist along the arms of condensed metaphase chromosomes, with the possibility that concentrations of 5-methylcytosine residues might have been enhanced at the surface of the chromosomes during the condensation process.


Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope. Human epidermal keratinocytes grow from single cells into stratified colonies. Cells in the upper layers of the colonies lose their ability to divide and begin terminal differentiation. In this process, there develops a cornified cell envelope that remains insoluble after heating in solutions of sodium dodecylsulfate and beta-mercaptoethanol. The insolubility of the cornified envelope depends upon proteins, since after treatment with proteolytic enzymes, the envelope becomes soluble in the detergent. Cells with cornified envelopes can be identified under the light microscope either in living colonies or following fixation and silver nitrate staining. Keratinocytes of the basal layer move in a characteristic way, but cornified cells do not move at all and form an immobile upper layer in the colonies. Keratinocytes disaggregated from growing colonies are of differing size and density, and can be separated on isopycnic gradients of Ficoll. The DNA-synthesizing cells are small (mean diameter 14 mum). The nonmultiplying cells are large and have a protein content proportionate to their size. Their final diameter may exceed 30 microns (volume increase greater than 10 fold). Cornified envelopes are found in some of the large cells but in none of the small. In growing colonies, usually 5-10% of the cells have cornified envelopes. The fraction is reduced in colonies growing in the presence of epidermal growth factor. Strain XB, an established keratinocyte line of mouse teratomal origin, also forms cornified envelopes, but the kinetics of the process are different, indicating that the program of terminal differentiation is not initiated at corresponding times in the two cell types.


In vitro studies of mouse embryos bearing mutations at the T locus: tw5 and t12 . Lethal mutations in the T region of chromosome 17 in the mouse cause death at specific stages of embryonic development. It is widely believed that death of homozygous mutant embryos occurs as a result of aberrant cell-cell interaction followed by disorganization and death of specific cell types within the embryo. In vitro culture of blastocysts homozygous for one of these mutations, tw5, has revealed that this mutation is lethal for all cells of the mutant embryo. In addition, measurements of beta-glucuronidase activity indicate that the lethal period of the tw5 mutation is the same in vitro as it is in vivo. Similar biochemical studies with t12 mutant embryos demonstrate that cessation of macromolecular synthesis occurs rather abruptly at the morula stage, the time at which those mutant embryos die in vivo. These results lead us to propose that all cells within the conceptus are directly and profoundly affected by early acting t mutations, and that failure of some cell types to organize properly is not an adequate explanation of the death of these mutants.


Genetic determination of the beta-galactosidase developmental program in mouse liver. The developmental program for beta-galactosidase in C57BL/6J and related strains of mice differs from that seen in most other mouse strains. Mice of the C57BL/6 group show a rise in liver enzyme activity during development that is not seen in mice of other strains. The developmental pattern of beta-galactosidase activity in heart and brain of C57BL/6 mice is similar to that in other strains. Physical, kinetic, and immunological tests indicate that the developmental increase in C57BL/6 enzyme activity is an increase in the number of molecules of the same species of enzyme protein that is present in other strains. In genetic crosses, the presence of the developmental rise in liver enzyme activity segregates as if determined by a single genetic factor showing additive expression in heterozygotes. This factor is closely linked to the beta-galactosidase structural gene on chromosome 9. The existence of a genetic variant with these properties is evidence that programmatic information capable of regulating the temporal expression of a structural gene can be encoded in DNA.


Characterization of single-stranded viral DNA sequences present during replication of adenovirus types 2 and 5. Replication intermediates of adenovirus DNA apparently contain extensive stretches of single-stranded DNA. Such single-stranded viral DNA sequences homologous to different regions of the viral genome present in adenovirus-infected cells during viral DNA replication have therefore been characterized by hybridization to the separated strands of restriction endonuclease fragments of 32P-labeled adenovirus types 2 and 5 DNA. Saturation hybridization experiments with infected cell DNA extracted at late times suggest that all regions of the adenovirus genome are represented in the single-stranded fraction, but at unequal frequencies. This nonuniform representation has been characterized in more detail with self-annealed, total cell DNA extracted 18 hr after adenovirus type 2 infection: the concentration of single-stranded sequences homologous to different regions of the viral genome was determined by comparing the rates of hybridization of 32P-labeled, single-stranded DNA probes with such self-annealed 18 hr DNA to the rates of hybridization of the same probes with equal concentrations of their complements. This approach allows the concentration of single-stranded viral DNA sequences in excess of their complements to be determined. Such sequences can be represented by two concentration gradients across the viral genome: those homologous to the r strand increase in concentration from 27.8-40.9 units toward the right end, whereas sequences homologous to the 1 strand increase from an area 27.8-40.9 units toward the left end. The time course of synthesis of single-stranded viral DNA sequences relative to accumulation of total viral DNA during the productive cycle and their behavior following a shift of H5ts125-infected cells in which viral DNA replication has begun from a permissive to a nonpermissive temperature support the contention that these sequences are indeed generated as adenovirus DNA is replicated. These results are therefore discussed in terms of current models of adenovirus DNA replication.


Monospecific immunoprecipitation of murine leukemia virus polyribosomes: identification of p30 protein-specific messenger RNA. A rabbit antiserum monospecific for the internal structural protein p30 of Moloney murine leukemia virus (M-MuLV) was prepared to immunoprecipitate the polyribosomes synthesizing this protein in producer cells. The antiserum was monospecific for p30 protein as judged by immunodiffusion analysis against purified p30 and total virus protein. In addition, it could specifically precipitate p30 from total virus protein in the presence of cell extracts. Less than 1% of the M-MuLV-specific messenger RNA (mRNA) could be precipitated from purified producer cell polyribosomes when the anti-p30 was used in conjunction with sheep anti-rabbit antiserum. However, considerably more virus-specific mRNA was precipitated when the anti-p30 was used in conjunction with inactivated Staphylococcus aureus, which has binding sites for the antibody. Conditions were obtained where approximately 7% of the virus-specific mRNA in purified polyribosomes was recovered by immunoprecipitation, while normal serum precipitated 10 fold less. The virus-specific mRNA in the immunoprecipitated polyribosomes was 30S-35S in size.


Methylated blocked 5' terminal sequences of sea urchin embryo messenger RNA classes containing and lacking poly(A). Sea urchin embryo mRNAs of three distinct classes--histone mRNA, nonhistone mRNA containing poly(A), "[+A] mRNA," and nonhistone mRNA lacking poly(A), "[-A]mRNA"--all contain blocked 5' terminal sequences in which 7-methylguanosine is linked 5'-5' via a triphosphate bridge to a 2'-0-methylated nucleotide. Only one general type of 5' terminal structure, 7mGpppXmpYp, is present. Additional 2'-0-methylation in the Y residue has not been found either in early or late stage embryos. A substantial proportion of the polyribosomal mRNAs in all three classes contain this blocked structure. Whereas both classes of nonhistone mRNAs have internal base methylations, histone mRNAs lack such modifications.


Methylated constituents of poly(A)- and poly(A)+ polyribosomal RNA of sea urchin embryos. We have examined the poly(A)- and poly(A)+ polyribosomal (Ps) RNAs of developing sea urchin embryos to see whether they contain the capped structures previously observed in the poly(A)+ cytoplasmic RNA (mRNA) of a variety of eucaryotic organisms. We have found that both classes of Ps RNA contain 7-methylguanosine linked to the RNA by a 5'-5' triphosphate bridge. Capped structures derived from either class of Ps RNA appear to be of the type m7G5'ppp5'NmpNp, with only a single sugar-methylated nucleoside per cap, and we have estimated that both classes of Ps RNA are capped to the same extent. The 5' terminal 2'-0-methylated nucleosides have been identified and quantitated. The relative amounts are Am = 78%, Gm = 14%, Cm = 5%, Um = 3% for poly(A)- Ps RNA, and Am = 78%, Gm = 15%, Cm = 5%, Um = 2% for poly (A)+ Ps RNA. In addition, both classes of Ps RNA contain 2-4 internal residues of N6-methyladenylic acid per molecule.


A comparison of the structure of chicken erythrocyte and chicken liver chromatin. The structure of chicken erythrocyte and chicken liver chromatin has been studied by enzymatic digestion with micrococcal nuclease and DNAase I. Comparison of the fragments produced by brief digestion with micrococcal nuclease indicates that chicken erythrocyte chromatin has a longer nucleosome repeat than chicken liver chromatin, 212 base pairs as opposed to 200 base pairs (bp). More extensive digestion with micrococcal nuclease demonstrates that both tissues have 140 bp mucleosome cores. The difference in the length of the nucleosome repeat must therefore result from a difference in the length of the DNA linker between cores. Chicken erythrocyte chromatin is known to contain a tissue-specific, H1-like histone, H5, and to be genetically dormant. A model is presented to explain how changes in histone H1 could cause changes in the nucleosome repeat length and thereby alter the genetic activity of chromatin.


[Epithelial tumor-like changes, precancerous conditions and skin neoplasms (standardization study)]. A retrospective study of bioptic material was used to design the following outline of a histological classification of epithelial skin tumours tentatively compared with handbooks published by the WHO (1) and AFIP (2): I. Tumour-like changes: 1. senile verruca (mixed, acanthotic, melanoacanthotic, hyperkeratonic, reticular, inverted). 2. Virus verrucosities (v. vulgaris, v. plana, c. accuminatum, molluscom contagiosum). 3. Hamartogenic verrucosities (naevus verrucosus, n. comedonicus, fibroepithelial papilloma. 4. Genetically undefined verrucosities (acanthosis nigricans, light cell acanthoma, verrucous dyskeratosis). 5. Cysts (atheroma, epidermoid cyst, dermoid cyst, others). 6. Unclassified. II. Precanceroses: 1. Pseudoepitheliomatous hyperplasis, 2. keratosis senilis, 3. Radiation dermatosis, 4. Unclassified. III. Epithelial tumours A. From surface epithelium 1. Spinocellular carcinoma (basic type, anaplastic, adenoid, sarcomatoid, clear cell carcinoma, intraepidermal). 2. Basocellular carcinoma: a) varieties derived from surface epithelium (intraepithelial, superficial, solid, cystic, invasive), b) varieties with adenoid features (cylindromatous, fibroepithelia), c) varieties with trichoepithelial features (keratinizing, pigment-type, clear cell type), d) naevus varieties (basocellular naevi). 3. Spinobasocellular carcinoma. 4. Unclassifiable. B. Sweat gland tumours: 1. syringocystadenoma papilliferum, 2. hidradenoma papillare, 3. nodular hidradenoma (eccrine spiradenoma, eccrine acrospiroma, myxochondroepithelioma, myoepithelioma, mucinous epithelioma), 4. syringoma, 5. eccrine cylindroma, 6. hidrocystoma, 7. eccrine poroma, 8. carcinomas (so called extramammary Paget carcinoma), 9. unclassifiable. C. Sebaceous gland tumours: 1. adenoma sebaceum, 2. carcinoma sebaceum, 3. quasi tumours (naevus sebaceus, Pringle's hamartoma, steatocystoma multiplex, hyperplasia), 4. unclassifiable. D. Trichoepithelial tumours: 1. trichofolliculoma, 2. follicular poroma, 3. keratoacanthoma, 4. tricholemoma, 5. pilomatrixoma, 6. trichogenic adnexal tumour, 7. trichoepithelioma, 8l unclassifiable.


[Healing of skin wounds (electronoptic study)]. Tissue specimens of 46 skin wounds were taken on day 8 after a surgical operation to be given an electronoptic examination. The results were evaluated according to age groups. The best healing was the corium showing a prepondenrance of the epidermis had been regenerated with the corium showing a prepondenrance of the proliferation of fibroblasts most of them oriented across the wound direction. Nevertheless, there was a wrong neocolagen fibre orientation with the corium joined mainly by amorphous intercellular substance, probably non-fibrous soluble collangen. - Older subjects were found to have slowed down exudative and macrophagic reactions which were then seen interfering withe the proliferation of fibroblasts and their proteosynthetic activity. To a certain extent, a similar situation was also observed in children where, too, the precipitate exudative reaction was seen interfering in the fibroproliferative phase.


[Changes of articular cartilage in coxarthrosis]. In cases of advanced coxarthrosis indicated for total endoprosthesis [a total of 216 observations made] the most frequent changes included cases of lowering, defibration or even complete abrasion of cartilage in the most exposed segment of the articular head [196x]. Small patches of connective cartilage [133x] were found in the areas of abrasion. There were rare cases of chondrocyte nests as a manifestation of proliferation [25x]. The usual picture of coxarthrosis had exceptions in the form of flatly worn-out surface areas (34X) and pannus (7X). These may have been cases of secondary coxarthrosis accompanying some other, clinically overlooked, underlying process.


[Septic complications and atypical bacterial endocarditis in patients under hemodialysis]. In series of 68 patients who had been subjected to haemodialysis during life, septic complications were found in 16.2%. Bacterial endocarditis was observed in 8 of them. In 7 there occurred in abscess-like colliquation in the calcified attachment of the mitral valve. Lesioning by friction and an accelerated development of dystrophic valvular lesions are regarded the probable main etiopathogenic factors.


[Kinetics and morphology of immune reactive cells in the spleen as observed using the immune adherence method. IV. Primary response as influenced by total body irradiation in various intervals following administration of antigen]. The course of immunocytoadherence was followed in the mouse spleen during the primary immune response to intraperitoneal administration of sheep red blood cells at 24 hours, 72 hours and 6 days following a total body iradiation with a dose of 450 r after antigen administration. The number of RFC becomes reduced immediately after irradiation. The reduction thereof always correlates with a relative increase of macrophages. Small and medium-sized lymphocytes rapidly disappear from the population of rosette-forming cells. If the irradiation had been carried out before the radiation-uninfluenced reaction reached its maximum, the large lymphocytes relatively increase in number. In other cases their immunocytoadherent activity also shows a steadily decreasing tendency. During the primary reaction, irradiation always increases the total relative plasma cell count as related to the other RFC. In such cases the propurtion of the mature forms is larger than of the blastic ones. The values observer at the end of the studied postirradiation period in the sourse of the primary reaction are always characterized by a higher proportion of the plasma cell line at about 20 - 25.


The effect of dibromodulcitol on resting and dividing lymphoid cells. The effect of dibromodulcitol (DBD) on the incorporation of labelled precursors into DNA and RNA fractions of PHA-stimulated human lymphocytes and of P388F lymphoma cells at various stages of their growth was studied. Both cell systems showed sensitivity to the drug within the concentration rage of 1-10 mug/ml. When DBD was added before phytohaemagglutinin (PHA), h.han RNA. In contrast, by adding DBD after PHA, RNA labelling was much more inhibited than DNA. In the latter case, the decrease in DNA labelling occurred only 24 h after drug treatment whereas RNA labelling was decreased 1 h after treatment. Levels of DBD which normally produced 30% inhibition in plating efficiency of P388F lymphoma cells affected uridine-5-T incorporation to a different extent at different stages of growth of the culture. Enhanced RNA labelling occurred in early exponential stage while at later stages of growth, RNA synthesis was depressed.


Studies on proteins of animal ribosomes. XXIV. Localisation of proteins in ribosomal subunits of rat liver studied by chemical substitution with p-nitrophenyl acetate and methyl acetimidate. The reaction of [3H]p-nitrophenyl acetate (NPA) or [14C]methyl acetimidate (MAI) with amino groups of ribosomal pade between the reactivity of the proteins in situ in the ribosomal subunit with that of isolated protein mixtures. In the small subunit reactivity compared with the protein mixture was only 10-65% in the case of NPA but 45 to more than 100% in the case of MAI. In the large subunit reactivity to MAI was 10-60% that of the isas a denser structure than the small one. In agreement with earlier experiments with iodoacetamide the proteins S2, 5, 7, 8, 10 and 13 of the small subunit and L15, 17, 20, 24, 25, 27, 29, 33, 34, 35 and 38 in the large subunit are quite accessible while proteins S9, 14, 19, 20, 24, 25, 27, 29 and 30 of the small subunit and L1, 7, 8, 10, 11, 19, 28, 31, and 32 of the large one are relatively inaccessible.


In vitro acylation of the xi-amino group of L-lysine in calf thymus histones by the carcinogen, beta-propiolactone. We had previously reported that the carcinogen, beta-propiolactone (BPL) reacted in vitro with histones in whole mouse skin chromatin and that among the histone classes BPL was preferentially bound to the lysine-rich histones H1 and H1 degrees. In order to determine if in vitro reaction of BPL with calf thymus histones resulted in binding of BPL to L-lysine, we synthesized the model compounds XI-N-(3-hydroxypropionyl)lysine (HPL) and xi-N-(I-carboxyethyl)lysine (CEL) from BPL and L-lysine. The alpha-amino group of L-lysine was protected from reaction with BPL by the formation of a copper chelate. Structures were assigned on the basis of infrared spectra, pKa values and chemical analyses. BPL was reacted in vitro with calf thymus histones and the BPL-reacted calf thymus histones and control calf thymus histones were digested with trypsin followed by pronase. The respective digests were each chromatograhed on a column of AA-15 cation-exchange resin. The elution profiles of the two digests were very similar except for the appearance of a new ninhydrin-positive peak (NNPP) in the eluate of the trypsin-pronase digest of BPL-reacted calf thymus histones. When compounds HPL and CEL were added to the trypsin-pronase digest of control calf thymus histones and the mixture chromatographed on AA-15, both compounds were resolved from the other peptide (or amino acid) peaks. HPL was eluted in the same fractions as NNPP, HPL and NNPP exhibited identical RF values on silica gel TLC with acidic, alkaline and neutral solvents. CEL was not identified as a product of the reaction between BPL and calf thymus histones.


The biosynthesis of metallothionein rat liver and kidney after administration of cadmium. The biosynthesis of the cadmium-binding protein, metallothionein, was studied in rat liver and kidney after injection of cadmium chloride. A simplified procedure for the isolation of metallothionein from liver and kidney tissues was devised. It was found that the concentration of a subcutaneously injected dose of 30 mumoles of 109CdCl2/kg in the liver reached the maximum within 36 h. Thereafter, a slow decrease in the concentration of the isotope was noted during the 3 week period. In the kidney, the isotope was taken up in two phases. During the first phase the uptake was faster and lasted for about 4 days. The second phase of 109Cd accumulation showed a slower increase in the concentration oe 109Cd was associated with metallothionein. Amino acid incorporation studies revealed that active biosynthesis of metallothionein took place in the kidney as well as in the liver of cadmium-exposed rats. The turnover of 35S-labeled metallothionein was also investigated and the half-lives of the hepatic and the renal metallothionein were found to be 2.8 and 5 days, respectively.


Influence of dietary cadmium on the distribution of the essential metals copper, zinc and iron in tissues of the rat. The effect of long-term dietary cadmium treatment upon the distribution of the metals copper, iron and zinc has been compared in various organs of male and female rats. The renal accumulation of cadmium was similar in both sexes without a plateau being reached. In contrast, the hepatic accumulation of cadmium was higher in the female than in the male rat and a plateau was observed after 30-35 weeks of dietary cadmium treatment. Most of the cadmium which accumulated in these organs was recovered in the metallothionein fraction andthe concentration of hepatic cadmiumthionein in the female rat was correspondingly higher than in the male rat. Accumulation of cadmium was associated with an increased zinc concentration in the liver and an increased copper concentration in the kidney; these increases were correlated with increases in liver and kidney metallothioneins induced by cadmium. Uptake of cadmium into organs other than liver and kidney occurred to a small extent but was not associated with changes in the concentration of copper and zinc. Cadmium also accumulated in the intestinal mucosa where it could be recovered in a fraction corresponding to metallothionien. A loss of iron from the liver and kidney was also observed following dietary cadmium treatment and involved mainly a loss of iron from ferritin.


[Observations on the immediate and remote results of 112 internal biliary drainage operations]. The Authors report on the indications and result of 112 operations of internal biliary drainage performed in two distinct periods. In the first period (1960-1968) direct operations on the papilla were preferred (30 cases) as compared with biliary-digestive anastomoses (10 cases). From 1969 to 1974 the two types of operation were roughly equivalent. An analysis of post-operative mortality, complications and long-term outcome in 80 patients observed indicates a lower risk, a smaller possibility of relapse and, on the whole, better stable results for biliary-digestive anastomosis as compared with direct operations on the papilla, thus justifying the increasing favour accorded to them in the second period considered. The indications for the two types of operation are also analysed and stated, with stress on the importance of accurate intraoperative diagnosis.


[Anatomo-surgical aspects of peroperative cholangiography in biliary lithiasis]. Biliary anomalies and volumetric changes in the ductal system often make it difficult to identify individual structures during the course of operations for biliary lithiasis. The Authors reviewed 406 peroperative cholangiographies during the course of 1250 operations, evidencing some statistical data regarding the anomalies of greatest interest for surgical practice and stressing the significance and limits of dilation of the V.B.P. On the basis of their personal experience and the relevant literature the Authors conclude that peroperative cholangiography constitutes a useful method not only for diagnostic purposes, but also for correct definition of certain aspects of the extrahepatic biliary ducts.


[Value and limitations of telethermography in the diagnosis of peripheral arterial diseases (clinical contribution)]. Using a diagnostic technique allowing thermal variations of the body surface to be translated into pictures by remote recordings (telethermography), the Authors studied a group of patients suffering from peripheral arteriopathies. The patients were also subjected to other tests (oscillography, pletysmography, electrothermometry, arteriography). The diagnostic reliability of the telethermographic procedure in the cases studied was 80% (8 cases out of 10), with 20% of false negatives. Even in the two falsely negative cases, however, the investigation proved useful, since it allowed the improvement obtained with medical and surgical therapy to be evaluated. The Authors therefore conclude by asserting that telethermography is an effective diagnostic means because of the reliability of the results and its simplicity in use, as well as being non-traumatic and hence easily repeatable.


[Glucagon in the treatment of acute pancreatitis (clinical contribution)]. 16 patients suffering from acute pancreatitis were treated by intramuscular or intravenous administration of glucagon, with control of the amylasemia and amylasuria values at the start of treatment, the 12th hour and the 36th hour. By the 12th hour from the start of therapy they already observed a reduction in amylasemia and amylasuria to normal values, with disappearance of the symptomatology (pains, vomiting, shock) and complete cure of the patients in 94% of cases. On the basis of their own and others' experience, the Authors therefore believe that glucagon can advantageously be used in this disease, which is characterised by much higher mortality if treated with the traditional therapeutic means.


[Study of the behavior of gastric secretory function after proximal selective vagotomy for duodenal ulcer]. In 60 patients with duodenal ulcer subjected to S.P.V. operation, a study of gastric secretion (quantity of gastric juice, B.A.O., M.A.O., P.A.O., Hollander's test) and of gastrinemia before the operation, after one month and after one year was made. The results supplied by this study are: a marked reduction (over 50%) in the basal values and those after stimulation of the quantity of gastric juice and of acid secretion, with persistence of such reductions a long time after the operation. The finding of three cases with positive Hollander's test, which was negativised after administration of a beta-blocking drug, induced the Authors to a critical revision of the literature on the relations between sympathetic and parasympathetic innervation of the stomach in relation to gastric secretion.


[Critical considerations on the use in instrumental divulsion of the papilla in surgery of the bile ducts. Long-term results in 103 cases]. With a view to carrying out a critical review of the use of instrumental divulsion in surgery of the bile ducts, a long-term follow-up was made, from one to 12 years after performance of this operation, in 103 out of 157 cases. An examination of the immediate results which were favourable, in contrast with those found at long-term, led to the conclusion that this procedure was of little use and it has now been dropped both in diagnostics and, with greater reson, in treatment of benign papillary stenosis.


[Interesting changes in blood fibrinolysis following administration of acetylsalicylic acid in vascular diseases of the lower limbs]. After reference to the results of investigations reported in literature with regard to the effects of ingestion of acetylsalicylic acid on the blood biochemism in normal and pathological conditions, the Authors illustrate the results of their research on patients with chronic obstructive arteriopathy or with post-phlebitic syndrome of the lower limbs. An accurate evaluation was made of the variations induced in some important blood coagulation parameters by the said drug, which was found to cause a clear increase in fibrinolytic activity and which is moreover endowed with marked antithrombophilic therapeutic capacity.


[Postgastrectomy metabolic problems].

[Postgastrectomy metabolic problems]. A synoptic pattern is drawn up to synthesize the morpho-functional alterations and metabolic disturbances arising from total gastrectomy, while a comparison is made with those arising from massive resections of the small intestine (so-called short intestine syndrome). Emphasis is placed on the desirability of rebuilding the gastric reservoir and maintaining duodenal continuity through interposition of a loop. Among the various available techniques, preference is given to the Mouchet-Camey method, which seems to respond better than others to expectations of the patient's good metabolic recovery.


[Bacteriological studies on the bile in different conditions of surgical interest]. A bacteriological study was carried out on bile taken, during the course of surgery, from 235 patients suffering from a wide variety of diseases, both benign and malignant, concerning the bile ways. The investigation, initially directed to the aerobic bile flora, was afterwards extended to include germs growing in strict anaerobiosis. The highest incidence of bactibilia was found in repeat operations for post-operative stenosis of the hepatocholedochus, followed by neoplasias of the gall-bladder or main bile duct, and calculosis of the gall-bladder. For germs growing in compulsory anaerobiosis the responses to the cultural test were all negative, while in two cases microaerophilic streptococci were isolated. Finally the results of the antibiograms made on the isolated microbial species are reported.


Mephalan in the treatment of multiple myeloma. Seventy-three patients with symptomatic multiple myeloma at Memorial Sloan-Kettering Cancer Center were treated with melphalan from 1963-1967. All patients but one were followed for three years or until their death. Of the 60 evaluable patients, 31 obtained no benefit, 20 patients had objective and subjective responses consistent with clear clinical benefit; 6 patients had subjective responses in the absence of objective change, and 3 patients had stabilization of their disease. Toxicity was tolerable. It was not possible to predict which patients would respond, utilizing clinical status, hematological status or protein excretion patterns (i.e., which type of light chain was produced). In previously untreated patients, survival from time of diagnosis is 21 months. The median survival of the melphalan responders (39 months) is longer than that for the patients with no response (15 months). These data will provide useful baseline material for the evaluation of future therapeutic trials in patients with multiple myeloma at this Center.


Inhibition of conversion of thyroxine to triiodothyronine in patients with severe chronic illness. Many clinically euthyroid patients with severe, chronic, non-throidal illnesses (i.e. sick euthyroid patients) have very low circulating concentrations of total and absolute free triiodothyronine (T3), low-normal concentrations of total thyroxine (T4), elevated concentrations of absolute free T4, and circulating concentrations of thyrotrophin (TSH) that are either normal or subnormal. This study was undertaken to elucidate the mechanism of the low circulating T3 concentrations. The disappearance rate of 125 I-T3 from the circulation of five representative sick euthyroid patients was studied and found to be slower, but not significantly so, compared with three control subjects, thus excluding an increased destruction rate as the cause of the low T3 levels. A selective decrease of T3 secretion from the thyroid gland of these patients was also excluded by the results of TSH stimulation tests. Inhibition of extra-thyroidal conversion of T4 to T3 was suggested by studies of the thyroid function in a hypothyroid woman with a Grade IV lymphoma on T4 replacement therapy. When the lymphoma was in remission, her circulating T3 concentration was 2-55 nmol/l but when it relapsed it fell to 0-55 nmol/l. The T4 concentrations were 124-7 nmol/l and 126 nmol/1 respectively. Decreased monodeiodination of T4 to T3 in sick euthyroid patients was confirmed by paper chromatography of extracted serum obtained 48 h after an i.v. injection of 125 I-T4 into two severely ill patients from the intensive therapy unit and a control subject. Peaks of radioactivity corresponding to 125 I-T4 and 125 I-T3 were detected in the control subject, but only a single peak corresponding to 125 I-T4 was detected in the ill patients.


A system for the measurement of integrated concentrations of hormones in the blood. The study of integrated concentrations of hormones in the blood can be used to assess accurately the activity of endocrine diseases. A system for making such measurements is described, based on a new pump and double lumen catheter. The properties of this system are discussed and previous systems from the literature are reviewed.


Plasma testosterone and androstenedione levels during monitored induction of ovulation in infertile women with 'simple' amenorrhoea and with the polycystic ovary syndrome. Twenty-seven infertile patients with 'simple' amenorrhoea-oligomenorrhoea and eighteen with the polycystic ovary (PCO) syndrome were treated for induction of ovulation with clomiphene, human menopausal gonadotrophin and human chorionic gonadotrophin. The treatment was monitored by plasma oestradiol, testosterone, androstenedione and progesterone estimation. Women with PCO had significantly higher plasma androgen levels than women with 'simple' amenorrhoea (P less than 0--1 to P less than 0-001) both before treatment and during induction of ovulation. When  ovulation was induced the pregnancy rate for women with the PCO syndrome with elevated androgens was 21% while for those with uncomplicated amenorrhoea it was 75%. It is concluded that high levels of circulating androgens might be a factor preventing conception in some patients in whom ovulation is apparently successfully induced.


A radioimmunoassay for growth hormone release-inhibiting hormone: method and quantitative tissue distribution. A specific antiserum has been produced to haemocyanin conjugaed synthetic growth hormone release inhibiting hormone (GHRIH). This has allowed the development of a radioimmunoassay for GHRIH sensitive to 5 pg/tube. GHRIH content in 2 m acetic acid extracts of rat tissues have been measured and show the majority to be CNS-especially hypothalamus and septum and preoptic areas with substantial amounts in spinal cord and thalamus. Extra neurological localization in pancreas, gastric antrum, colon and thyroid have been demonstrated.


The radioimmunoassay of 3,3',5' - triiodothyronine (reverse T3) in unextracted human serum. A specific, sensitive and simple double antibody radioimmunoassay for total serum 3,3',5'-triiodothyronine (reverse T3, rT3) in small volumes of unextracted human serum is described. High titre antisera were raised in rabbits using dl=rT3 or l-rT3 conjugated to bovine serum albumin. The selected antisera cross reacted less than 0-003% with triiodothyronine (T3) and 0-14% with thyroxine (T4). A stable high activity rT3 tracer was prepared by iodination of 3,3"-diiodo-l-thyronine by the chloramine-T method, and purified by column chromatography on Sephadex LH-20. Binding of rT3 to endogenous serum proteins was blocked by including 8-anilino-1-naphthalene sulphonic acid (ANS) in the assay. Mean rT3 levels in healthy euthyroid adults are 0-27 nmo1/1 (range 0-21-1-18); in cord sera 3-67 nmo1/1 (range 2-30-7-45) and in amniotic fluid taken during the second trimester 4-70 nmo1/1 (range 2-22-8-00). In approximately half the hypothyroid subjects, rTO levels were undetectable ( less than0-05 nmo1/1) and in the remaining subjects the mean rT3 level was 0-10 nmo1/1 (range 0-05-0-25).


Prolactin levels during the menstrual cycle. The levels of prolactin, FSH, LH, oestradiol and progesterone were measured daily during fourteen ovulatory cycles. The behaviour of FSH, LH, oestradiol and progesterone was classical. Non-systematic changes occurred in prolactin levels during the course of the menstrual cycle with the highest level being either during the ovulatory period or during the luteal phase. However, the mean level of prolactin was significantly higher during the ovulatory and luteal phases than during the follicular phase. A direct relationship between oestradiol and prolactin levels was noted, although there was no correlation between prolactin on the one hand and FSH, LH and progesterone on the other.


Measurement of serum 3,3',5'-(reverse) T3, with comments on its derivation. A radioimmunoassay for the measurement of l-3,3',5'-triiodothyronine (reverse TO, rT3) has been developed for use with unextracted serum. The highly specific antiserum showed no cross-reactivity with l-3,3'5-triiodothyronine (T3) or tetradiodothyroacetic acid (T4A) and cross-reaction with L-thyroxine (T4) was low enough to be discounted for routine assay purposes. If a normal amount of rT3 was added to serum T4 cross-reactivity decreased considerably. Serial dilutions of hyperthyroid sera gave dose-response curves which were parallel to the rT3 standard curve. Serum concentrations of rT3 (mean+/- SEM) were 0-68 +/- 0-02 nmo1/1 in sixty-seven normal subjects, 0-19 +/- 0-02 nmo1/1 in twelve hypothyroid patients and 1-18 +/- 0-12 nmo1/1 in seventeen hyperthyroid patients. In sixteen patients with TO-toxicosis rTO was 0-42 +/- 0-04 nmo1/1 and eighteen patients with high circulating TBG had a mean rT3 of 0-54 +/- 0-03 nmo1/1.


Suppression of plasma growth hormone levels with glucose infusion in patients with acromegaly. Intravenous glucose infusion which increased blood glucose levels over 27-8 mmo1/1 suppressed plasma GH levels by 41-74% in five acromegalic patients with basal concentrations of less than 20 mu/1, but not in six patients with basal levels over 80 mu/1. Oral 100 g glucose loading had little suppressing effect in both groups. These results appear to indicate that the suppressibility with hyperglycaemia is partially retained or restored in some, if not all, patients of acromegaly with lower GH secreting activity.


Effect of metroclopramide on serum prolactin levels in humans. The effect of acute and chronic administration of metoclopramide on serum prolactin levels in normal subjects was studied. Metoclopramide 10 mg i.v. induced a prompt rise in serum prolactin levels in all subjects. At 180 min the levels remained high. Prolactin levels were markedly elevated during a 5 day course of treatment with metoclopramide in six subjects. It is suggested that metoclopramide could be used in the functional exploration of the hypothalamic-pituitary axis.


Specific antibody-dependent killing of Toxoplasma gondii by normal macrophages. The requirement for specificity of antibody-dependent inhibition or killing of intracellular Toxoplasma gondii trophozoites by normal mouse peritoneal macrophages was evaluated in vitro using light microscopy and autoradiography. Anti-toxoplasma antibody in the presence of 'accessory factor' rendered extracellular T. gondii trophozoites non-viable and non-infectious for cells, whereas exposure of extracellular trophozoites to heat-inactivated immune serum did not appear to damage the parasites. Although pretreatment of extracellular trophozoites with heat-inactivated immune serum neither diminished nor prevented infection of normal mouse peritoneal macrophages, it did confer upon macrophages the ability to inhibit or kill the organisms once they were intracellular. In contrast, pretreatment of trophozoites with either heat-inactivated normal or Besnoitia jellisoni immune serum did not enable normal macrophages to inhibit or kill T. gondii; rather, such organisms multiplied intracellularly in normal macrophages. Thus, pretreatment with specific antibody alone prepared T. gondii trophozoites for intracellular destruction by normal mouse peritoneal macrophages. These results suggest that spesific antibody acting in concert with normal macrophages may play a role in controlling infection with T. gondii.


Immune complexes and complement hypercatabolism in patients with leprosy. The occurrence of immune complexes in the serum and the level of the C3 breakdown product C3d in the plasma from patients with leprosy were studied by quantitative methods and the results were compared in various forms of the disease. These studies were performed on sixty-two samples from twenty-six patients. The serum 125I-C1q binding activity was found to be increased by more than 2 s.d., as compared to the normal values, in most of the sera from patients with erythema nodosum leprosum (ENL) (80%) and uncomplicated lepromatous leprosy (82%), but also in the sera from patients with tuberculoid leprosy (58%). In vitro studies suggested that immune complexes involving mycobacterial antigens were present in leprosy sera. An increased C3d level (greater than 2s.d.) was also found in most of the plasma from patients with ENL (70%), but rarely in the plasma from patients with uncomplicated lepromatous leprosy (18%) and never in tuberculoid leprosy patients' plasma. The absence of a significant correlation between the 125I-C1q binding activity and the C3d level in leprosy patients may suggest that extravascular immune complexes are involved in the complement activation occurring in ENL. The quantitation of C3d in plasma may be of some practical interest in the early diagnosis of ENL complications of leprosy.


Evidence for the involvement of IgE-basophil system in acute serum sickness. The role of the basophils in acute serum sickness of rabbits was examined by monitoring daily the absolute number of basophils before, during and after the disease period. After antigen (bovine serum albumin, BSA) elimination, levels of serum IgE and in vitro basophil degranulation in the presence of BSA were determined. The results showed that the onset of glomerular lesions depends upon the simultaneous occurrence of circulating immune complexes greater than 19 S and of an in vivo basophil depletion--probably equivalent to degranulation--reaching 70% of the pre-disease number. Post-disease antigen-dependent in vitro degranulation of the basophils and levels of serum IgE anti BSA did not prove to be good indexes of basophil sensitization. Our data suggest that basophils are instrumental at early stages of the deposition of immune complexes, most probably through their sensitization by membrane-bound IgE antibodies.


Leucocyte migration inhibition with inner and outer membranes of mitochondria and insoluble hepatocyte surface membranes prepared from rat liver in patients with chronic hepatitis and cirrhosis. Patients with chronic liver disease were tested for delayed hypersensitivity to the outer and the inner membranes of mitochondria (OMM and IMM) and the insoluble hepatocyte-surface membranes (IHSM), prepared from rat livers, by means of leucocyte migration inhibition technique. Positive reaction to OMM was found in  37% of patients with chronic persistent hepatitis and 35% of those with chronic active hepatitis and 43% of those with liver cirrhosis (P less than 0-05). That to IMM was 55%, 43% and 36% (P less than 0-05) and to IHSM was 37%, 47% and 45% respectively (P less than 0-05). IHSM was found to contain liver-specific components and patients with positive response to IHSM did not reveal at all a positive reaction to rat renal cell-surface membranes. The incidence of positive response to IHSM was significantly higher (54-2%) in patients with the present or previous infection with HBAg than in HBAg-non-infected patients (21-4%) (P less than 0-05). And there seemed to be a good correlation between a degree of cellular response to purified HBsAg and that to IHSM in these HBAg-infected patients. No correlation, however, was found between that to purified HBsAg and that to OMM or IMM in the same patients. This suggested that the cellular response to either HBsAg or IHSM, both related closely, may play a role in the perpetuation of chronic liver disease.


Binding of phytohaemagglutinin to serum substances and inhibition of lymphocyte transformation in Hodgkin's disease. Serum from eleven of fifty-four patients with Hodgkin's disease inhibited phytohaemagglutinin (PHA) stimulation of both autologous and homologous lymphocytes. The inhibitory effect resided in the macromolecular fraction of these sera. PHA was shown to bind to serum substances in inhibitory sera and the degree of PHA binding in the macromolecular fraction correlated directly with the extent of inhibition.


Leucocyte aggregation in subjects with nickel dermatitis. The effect of nickel sulphate on leuco-aggragation in whole blood buffy coat layers was studied in nickel-sensitive and control subjects. At concentrations of 150 mug and 200 mug nickel sulphate per ml a significant increase in the numbers of leuco-aggregates was noted in the nickel sensitive as compared with the control subjects.


Synergistic effect of cortisol and prostaglandin E2 on the PHA response. Relation to immunosuppression induced by trauma. Surgical and thermal trauma in man are followed by depressed immunological responses in vivo and reduced lymphocyte reactivity in vitro. The possibility that these are related to trauma-induced rises in tissue levels of cortisol and prostaglandins was examined by studying the effect of a wide range of concentrations of cortisol and prostaglandin E2 (PGE2), separately and together on the phytohaemagglutinin (PHA) response of human peripheral blood lymphocytes. These effects were plotted on two-dimensional dose:effect graphs; the shapes of the curves connecting combinations of equal effect (isoboles) showed that these agents acted with marked synergy in suppressing the response, provided they were present while the response was taking place. Synergy was also shown by using a simple equation relating the concentrations of the agents producing a given effect when used in combination to the concentrations needed to produce the same effect when used separately. Cortisol at concentrations reached in the peripheral blood after trauma in man (1-4 X 10(-6)M) and PGE2 at concentrations to be expected in traumatized tissues (up to 4 X 10(-7)M) each suppressed the response only slightly. The former reduced the response to 0-7 of controls and the latter 0-5 (means of seven subjects). When both were present together at these concentrations, the response was markedly depressed (mean 0-06, range 0-02--0-13 of controls). However, when lymphocytes were incubated at 37 degrees C with cortisol  and PGE2 for 20 hr and then washed before exposure to PHA, the response was not inhibited, even by substantially higher concentrations than the above, and was usually moderately enhanced. Therefore, these in vitro experiments do not explain the depressed PHA response observed in peripheral blood lymphocytes after trauma. It is possible, however, that raised cortisol and prostaglandin levels depress the reactivity of lymphocytes while they remain in the traumatized region and its lymph drainage area.


The modified anaphylaxis hypothesis for cot death. Anaphylactic sensitization in guinea-pigs fed cow's milk. Guinea-pigs on a normal diet, but given cow's milk to drink instead of water, very soon became anaphylactically sensitive to cow's milk and may be fatally shocked following either i.v. injection or intratracheal inhalation of cow's milk.


Adenosine deaminase activity in thymus and other human tissues. Adenosine deaminase activity (ADA) has been estimated in human tissues. Levels in the thymus during childhood were very much higher than in any of the other 6 tissues studied. Intermediate activities were obtained from spleen and lymph nodes and also skin. Cerebral cortex, liver and kidney had relatively low levels. ADA activity in lymphocytes from peripheral blood was significantly increased after antigenic stimulation by TAB immunization. The available evidence appears to be consistent with T-lymphocyte growth and development in the thymus being dependant on ADA.


A third dipeptide carrier system typified by l-prolyl-lhydroxyproline and independent of l-leucyl and beta-alanyl dipeptides in rat gut loops. 1. The intestinal transport of L-prolyl-L-hydroxyproline (10 mmol/l) was investigated in rat small gut loops in vivo under pentobarbitone anaesthesia. Osmolality of test solutions was adjusted to eliminate any positive effect of solvent drag on disappearance of solutes from the lumen. 2. L-Leucylglycine and beta-alanyl-L-histidine (carnosine), representative members of two distinctly different dipeptide transport groups previously delineated, were tested for competitive action on L-prolyl-L-hydroxyproline uptake at ten times equimolar concentration (100 mmol/l), but were found to have no effect on the carrier system. 3. L-Prolyl-L-hydroxyproline uptake was markedly blocked by other L-prolyl dipeptides, indicating that they shared a common carrier system. Disappearance of L-prolyl-L-hydroxyproline from the gut lumen was reduced from 48% 15 min-1 10 cm-1 (control, containing 70 mmol/l mannitol) to 11% or 20% in the presence of L-prolylglycine (100 mmol/l) or L-prolyl-L-leucine (25 mmol/l), respectively. 4. It was concluded that at least three separate dipeptide carrier protein systems exist in the rat small gut, the disappearance of L-prolyl-L-hydroxyproline from the gut lumen being inhibited by two other L-prolyl dipeptides but not by L-leucyl or beta-alanyl dipeptides.


The influence of coumarin on tissue levels of radio-labelled plasma protein and povidone (polyvinylpyrrolidine) in normal and thermally injured rats. 1. The administration of coumarin resulted in a two-fold increase in the entry of 51Cr-labelled rat plasma protein into otherwise normal tissues. 2. Prior treatment of rats with coumarin allowed about 50% more radio-labelled protein to enter the tissues immediately after thermal injury than occurred with thermal injury in untreated rats. 3. In coumarin-treated rats, 30 min or more after thermal injury, tissue levels of 125I-labelled povidone (polyvinylpyrrolidine) were significantly elevated or showed no change compared with tissue levels in rats which received only thermal injury. 4. Conversely, tissue levels or radio-labelled protein in coumarin-treated rats, 30 min or more after thermal injury were significantly reduced to between 20 and 30% of those in untreated, thermally injured rats. 5. These results were attributed to enhanced proteolysis of the radio-labelled protein caused by coumarin. Other results have shown that normal protein is similarly affected. 6. The products of proteolysis may then rapidly leave the tissues, freeing the osmotically-held fluids and reducing the oedema.


Familial interstitial nephritis.

Familial interstitial nephritis. We report a family in whom sixteen members in three consecutive generations have died or currently suffer from chronic renal failure. Histology revealed an interstitial nephritis. One patient also had medullary cysts. The condition appears to be similar to familial juvenile nephronophthisis.


Urine concentrating capacity in women: the results of a screening method in a population study. Urine concentration tests were performed as part of a population study in 1405 women in age strata between 38 and 60 years. The measurement of urine osmolality from the 13th hour of fluid deprivation overnight was adopted as a screening test. If an osmolality of 600 mOsm/kg H2O was not attained, a second test was performed and if this was abnormal a pitressin tannate test was carried out (54 women). Among women with a low urine concentration after pitressin tannate (less than 700 mOsm/kg H20) all but one suffered from chronic renal disease. The urine concentration capacity decreased with age illustrating the inadequacy of using the same "normal" limits at different ages. The outcome of the study raises the question of whether one simple fluid deprivation test discriminates tubular damage sufficiently satisfactorily to justify its application to the screening of large groups of people.


Inhibition of excitation-contraction coupling in the ventricular myocardium of the dog by SKF 24260. 1. The effects of SKF 24260 on the coronary vasculature and on the electrical and mechanical activities of the ventricular myocardium were studied by the use of papillary muscle preparations of the dog. The preparation was cross-circulated from a donor dog through the anterior septal artery, and driven at a rate of 120 beats/min. Drugs were injected into the anterior septal artery. 2. SKF 24260, in doses of 0-01-100 mug, caused a dose-dependent increase in the rate of blood flow through the anterior septal artery; the mean dose producing a 100% increase in blood flow rate was about 0-7 mug. 3. SKF 24260 in doses of 0-01-0-03 mug produced a slight increase in developed tension of papillary muscles. With 0-1-0-3 mug of SKF 24260 the increase was preceded by a transient decrease, and with doses larger than 1 mug the drug caused a dose-dependent decrease. The mean dose producing a 50% decrease in developed tension was about 2-8 mug. 4. SKF 24260 failed to affect the amplitude and shape of bipolar electrograms even in doses of 39-100 mug which completely abolished the developed tension. 5. The decrease in the developed tension caused by SKF 24260 was overcome by exogenous calcium; the increase in the developed tension in response to exogenous calcium was antagonized by SKF 24260. 6. These results indicate that the dilator action of SKF 24260 on the coronary vasculature is more prominent than the negative inotropic action on the ventricular myocardium, and suggest that the negative inotropic action is probably due to antagonism of the role of calcium in excitation-contraction coupling.


Effects of propranolol on development and maintanance of severe renal hypertension in rats. 1. The effect of chronic administration of propranolol on the development and maintenance of severe renal hypertension in rats subjected to unilateral renal artery constriction was studied in relation to possible changes in peripheral PRA and the blood and tissue levels of propranolol. Propranolol was administered s.c. twice daily in doses of 1, 10 and 25 mg/kg, starting 2 days before operation. 2. Contrary to expectations, not only did the initial rise in systolic blood pressure become accelerated, but the established level of hypertension attained in the propranolol treated rats was of the same severity as that attained in placebo treated rats. Moreover, the progressive rise in peripheral plasma renin activity following unilateral renal artery constriction was not affected by propranolol administration. 3. The same doses of propranolol were also administered daily for 8 days to rats with established severe hypertension. A slight further rise in blood pressure occurred initially, followed by a moderate decrease of 15-25 mmHg. Propranolol failed to exert this minor hypotensive effect in hypertensive rats treated concomitantly with furosemide. No suppressive effect on the markedly increased levels of plasma renin activity was observed in these severely hypertensive rats in the presence or absence of furosemide administration. 4. These results indicate that in severely renal hypertensive rats propranolol has only a minor hypotensive effect and no blocking action on renin release under the conditions of study.


Whole-blood thrombin time: a bedside method for determination of heparin activity. A bedside method of measurement of the whole-blood thrombin time for the determination of heparin activity was used in 300 dialyses. It was easily performed by the whole staff despite the absence of previous training in laboratory work. This test, using a clot timer with an automatic pipette device, gives a minimum risk of exposure to hepatitis virus. An increase of the thrombin time of 50-100 per cent above the starting value (3.7-6.6 sec) was aimed at during the heparin infusion. Bleeding complications, which were minor, were seen only on 18 and fibrin formation only on 26 occasions out of 1500 observations. Within the 50-100 per cent limits bleeding complications were observed on 2 and fibrin formation on only 13 occasions. No protamine was given.


Renal responses to slight elevations of renal arterial plasma angiotensin II concentration in dogs. 1. Angiotensin II was infused into the renal artery of intact kidneys of slightly volume expanded anaesthetized dogs at rates of 125, 250, 500, and 1000 pg/kg body weight per min, resulting in elevations of the calculated renal arterial plasma angiotensin II concentration of 16.9 (s.e.m. =2.1), 35.0 (s.e.m.=4.3), 73.3 (s.e.m.=8.8), and 159.8 (s.e.m.=20.4)pg/ml...


Glomerulonephritis in late-onset cystinosis. Report of two cases and review of the literature. This paper describes the clinical history of two male nontwin siblings with late-onset cystinosis, a variant of cystine storage disease. The diagnosis was established clinically and confirmed by measurement of cystine concentrations in leucocytes and skin-fibroblasts. Both patients presented with an incomplete nephrotic syndrome and renal biopsy showed, in addition to lesions of polykaryocytosis, a picture of focal and segmental glomerular hyalinosis. Renal function was stable in one patient over a follow-up period of two years; the other patient progressed toward terminal renal failure and was successfully transplanted.


Comparative study of the action of antiarrhythmic drugs on sinoatrial nodal pacemaker activity and contractility in the isolated blood-perfused atrium of the dog. 1. The effects of five antiarrhythmic drugs (quinidine, procainamide, lignocaine, phenytoin and propranolol) were studied on pacemaker activity in the sinoatrial node and on contractility in twenty-three isolated, blood-perfused atrium preparations of dogs. Each drug was administered directly into the cannulated sinus node artery of an isolated atrium over a period of 4 s. 2. Quinidine produced negative chronotropic and inotropic effects. Occasionally, higher doses induced a biphasic inotropic effect, an initial negative phase being followed by an increase in contractility. 3. Three response patterns to procainamide were observed: negative chronotropic and inotropic effects; biphasic effects, initially negative chronotropic and inotropic effects being followed by positive effects; a biphasic inotropic effect and a negative chronotropic effect. The third pattern was most frequently produced by relatively high doses. 4. Lignocaine, phenytoin and propranolol induced dose-related negative chronotropic and inotropic effects. 5. All five of the antiarrhythmic drugs used caused sinus arrest in high doses. 6. Procainamide-induced positive chronotropic and inotropic effects were significantly inhibited by treatment with alprenolol or nadolol, but not by tetrodotoxin or desipramine. 7. These results indicate that procainamide-induced positive chronotropic and inotropic effects may involve an adrenergic mechanism.


Mineralocorticoid receptors in sheep kidney and parotid: studies in Na+ replete and Na+ deplete states. 1. As an adrenalectomized sheep becomes progressively more Na+ deplete, its salivary electrolyte secretion becomes increasingly sensitive to exogenous aldosterone administration. 2. Alteration in mineralocorticoid receptor affinity or concentration is a possible mechanism whereby this sensitivity could be expressed at a molecular level. 3. Bonding sites with a high affinity for aldosterone (Kd 37 degrees C approximately 5 x 10(-10) M) have been demonstrated in sheep kidney and parotid. 4. Renal binding sites were examined in detail, and shown to have affinity characteristics appropriate for mineralocorticoid receptors (aldosterone greater than deoxycorticosterone greater than dexamethasone greater than cortisol greater than progesterone greater than oestradiol greater than dihydrotestosterone). 5. No difference in mineralocoticoid receptor affinity or concentration could be shown between Na+ replete and Na+ deplete sheep, in either kidney or parotid gland. 6. Accordingly, the molecular mechanisms whereby parotid sensitivity is mediated remain as yet undefined.


Stimulation of sodium and water secretion without inhibition of glucose absorption in the rat jejunum by vasoactive intestinal peptide (VIP). 1. Infusion of vasoactive intestinal peptide (VIP) into the arterial blood supply of the small intestine in anesthetized rats did not alter either the perfusion pressure in the superior mesenteric artery or the active absorption of glucose from the jejunum, but did produce a large net secretion of Na+ and water into the lumen of the jejunum. 2. The results are compared to the effects of prostaglandin E1 which stimulates Na+ and water secretion and inhibits glucose active absorption in the rat jejunum.


Arteriosclerosis, heredity, and some previous infections in the etiology of Parkinson's disease. A case-control study. A case-control study was performed to investigate the significance of arteriosclerosis, heredity and some infections in the etiology of Parkinson's disease. The study group consisted of all traceable patients with Parkinson's disease living in a defined area, a total of 444 patients, and of control subjects for each patient, matched in sex and age, chosen from among the general population residing in the same area. No significant differences were found between the patients and the controls concerning the occurrence of cardiac insufficiency, coronary heart disease, or stroke. The Parkinsonian patients, however, had a significantly lower incidence of clinical arterial hypertension when compared with the controls. In addition, the patients more often had low systolic blood pressures and more rarely high pressures than the controls. Even the mean systolic blood pressure was significantly lower in the patients than in the controls. The low blood pressure seems to be an effect of Parkinson's disease itself with a minor contribution of levodopa therapy. The observations above are considered to indicate that arteriosclerosis and Parkinson's disease are probably only concurrent disorders and not in etiological relationship with each other. There was no statistically significant difference in the proportion of the patients and the controls with relatives with Parkinson's disease or essential tremor, which suggests that genetic factors do not have a significant role in Parkinson's disease and on the other hand that essential tremor and Parkinson's disease are two separate disease entities. No other encephalitis than a lethargic one was found to precede Parkinson's disease and the occurrence of meningitis was rare both among the patients and the controls. The history of Spanish influenza was found to be as frequent in the patients as in the controls, thus not supporting the idea that influenza has etiological importance in Parkinson's disease.


Purulent osteomyelitis of the cervical spine with epidural abscess. Operative treatment by means of dorsal and ventral approach. The present case concerns an acute purulent osteomyelitis with an epidural abscess, located particularly in the intervertebral foramen between C5 and C6, which led to infection by staphylococci of the adjacent vertebral arches and vertebral bodies. An obstruction of the CSF passage was discovered by myelography at the level between C5 and C6. The bony tissue changed by inflammation was removed as far as possible by laminectomy. After irrigation of the epidural space with antibiotics and after control of the severe inflammation, the vertebral bodies C6 and C7 which were destroyed by the spreading inflammatory granulations, could be removed by a ventral approach 4 weeks later. The defect was filled with spongiosa chips. After immobilisation in a plaster shell and Crutchfield extension for 8 weeks the patient was slowly mobilized. A fusion of the vertebral bodies C5 and C6, C6/C7 and C7/C1 was achieved. A dislocation of the cervical spine did not occur and the patient recovered completely except for a paresis of the right hand. Treatment of this very rare and severe case was only possible by a combined dorsal and ventral procedure on the cervical spine.


Tests of the hypothalamic-pituitary-ovarian axis. The availability of RIA to measure the pituitary gonadotropins and ovarian sex steroids has greatly helped in the development of tests of hypothalamic-pituitary-ovarian function. The use of estimates of basal gonadotrophin and sex steroid hormones together with dynamic tests such as the LH-RH test, oestrogen provocation test, clomiphene tests and exogenous gonadotrophins can now test the integrity and functional capacity of each of the components of the HPO axis. Figure 4 demonstrates how these tests can be used in a logical sequence to investigate patients with a disorder of the HPO axis after having first excluded any other endocrine abnormality. Screening of serum for elevated levels of gonadotrophins, prolactin and progesterone is an important  initial step. Interpretation of the oestrogen provocation and clomiphene tests requires a normally functioning pituitary gland and hence the response to an LH-RH test also plays a ket role. The flow chart also demonstrates the points at which specific ovulation induction treatment can be instituted and should be useful in saving patient and doctor investigative time. Using these types of tests it should be possible to reclassify disorders of the HPO axis on the basis of their underlying pathology.


A computer program for the generalized chi-square analysis of categorical data using weighted least squares (GENCAT). GENCAT is a computer program which implements an extremely general methodology for the analysis of multivariate categorical data. This approach essentially involves the construction of test statistics for hypotheses involving functions of the observed proportions which are directed at the relationships under investigation and the estimation of corresponding model parameters via weighted least squares computations. Any compounded function of the observed proportions which can be formulated as a sequence of the following transformations of the data vector--linear, logarithmic, exponential, or the addition of a vector of constants--can be analyzed within this general framework. This algorithm produces minimum modified chi-square statistics which are obtained by partitioning the sums of squares as in ANOVA. The input data can be either: (a) frequencies from a multidimentional contingency table; (b) a victor of functions with its estimated covariance matrix; and (c) raw data in the form of integer-valued variables associated with each subject. The input format is completely flexible for the data as well as for the matrices.


Automatic treatment of assay data by competitive protein binding and radioimmunoassay. A method is devised for the automatic computation of data obtained from a series of determinations by radioimmunoassay or by competitive protein binding. The input data is introduced by means of an automatic paper tape punch attached to the sample counter. A series of programs is set up for a Hewlett Packard computer, model 2116B with 16K, which calculates bound and free fractions with control processes for varying possible errors. From experimental data, by linear least squares regression, a standard curve of best fit is derived and is considered in three different ways. The curve of best fit is selected by comparing the correlation  coefficients obtained and by calculating the unknown sample concentrations. The program presents the results graphically together with a list of results which is for use within the Radiochemistry laboratory. Individual reports are also prepared for sending to those departments that requested the test.


Period analysis of the electroencephalogram. A program is described which utilizes the Digital Equipment Corporation LINC-8 computer with 4K of memory to process the electrical activity of the brin into a set of meaningful statistics. The program provides an efficient methol of obtaining spectoral information concerning the EEG without the associated cost or complexity of conventional power spectrum techniques. The combination of utilization of a small laboratory computer with an easily programmable method provides an approach for automated EEG analysis which is within the financial and technical scope of most small hospital EEG laboratories;


Recovery from unilateral visuo-spatial neglect? Patients who had demonstrated unilateral visuo-spatial neglect on a simple drawing and copying task three to four weeks after a right hemisphere stroke were reassessed five months later. Although the incidence of neglect as defined had dropped markedly in that period, they remained impaired on tests of spatial analysis and visual perception relative to a group of right hemisphere patients without neglect. The measurement of neglect is discussed in the light of both these results and the stability of the neglect group's abnormal position preference on one of the tests administered.


A modified card sorting test sensitive to frontal lobe defects. Milner's (1963) report of impaired performance on the Wisconsin Card Sorting Test (WCST) in a group of patients with frontal lobe lesions suggested that this test might be a useful one in the investigation of individual patients with suspected brain lesions. However, for many of our older hospital population the WCST was found to be too difficult and distressing, and also the inherent ambiguities associated with certain responses limited the test's usefulness for research purposes. Therefore, a simpler and less ambiguous modification was devised (MCS) and a new method of measuring perseverative errors proposed. In a group of 53 patients with unilateral cerebral lesions, those with frontal lobe lesions performed less well with the MCST and made a higher proportion of perseverative errors than those with lesions elsewhere: there were no laterality effects in either frontal or non-frontal groups. The usefulness of the MCST for detecting frontal lobe lesions in individual patients was established, and the use of cut-off scores briefly discussed.


Error patterns in auditory comprehension of adult aphasics. The error patterns of normal and aphasic adults on a sentence comprehension test were studied. For position of error, both normals and the three aphasic groups performed consistently with the expected error distribution. Neither sentence half was experienced as more difficult to process. All groups, both aphasic and normal, demonstrated error patterns for grammatical class and for surface structure linguistic constituent which were consistent with the expected error distributions. Exceptions were noted for the normals on the verb class and for the Wernicke's aphasics on the NP and VP linguistic constituents. Rank orderings of error proportions were similar across groups for both grammatical form class and linguistic constituent. The general findings lend support to the notion that, for auditory comprehension of sentences, aphasic patients differ quantitatively from normal adult speakers, but behave qualitatively similar to them.


Development of hemispheric specialization for speech perception. When lists of word pairs were presented simultaneously in a dichotic monitoring task to three groups of right-handed subjects aged 5, 7 and 11 years, more target words were responded to, and reaction times was shorter, when these occurred in the right rather than the left ear. The magnitude of the effect did not change with age. A signal detection analysis showed that the right ear advantage was due to greater sensitivity of the right ear, rather than a response bias. Hand effects were assessed separately by using binaural stimulation in which each ear received two inputs, one in a male voice and the other in a female voice. The right hand responded to target words in one voice, and the left hand to target words in the other voice. The contribution of a right hand superiority to the ear effect was found to be minimal. The effects of language acquisition and attention strategies on the right ear advantage are discussed. It was concluded that at 5 years of age the left hemisphere is specialized for the analysis of speech signals. This produces a right ear advantage in competitive verbal listening.


Cerebral dominance and visual similarity judgements. Visual similarity judgements among rectangles varying in form and area were investigated in control subjects and in patients with lesions confined to either cerebral hemisphere. While an overweighing of form with respect to area was found in both control subjects and right brain-damaged, left brain-damaged patients equally weighted the two relevant dimensions. Beyond revealing differential processing rules related to the side of the injury in the brain, the findings lend themselves to some speculation about cerebral dominance.


Sinistrad mirror writing and reading after brain concussion in a bi-systemic (oriento-occidental) polyglot. The problem of mirror writing and reading is discussed in the light of a clinical case, where this disturbance appeared after an apparently minor head injury. Mirror writing and reading in this polyglot individual affected only the sinistrad (Hebrew) writing and reading system, leaving the dextrad (Latin) system unimpaired. This disturbance appeared together with dyscalculia, left-right disorientation and slight temporal confusion, suggestive of parieto-occipital lobe pathology. The clinical picture also showed apparently "conversional" traits, such as are sometimes seen in incomplete parietal lobe syndromes. The relevant literature is reviewed and patho-physiological mechanisms of mirror reversal are discussed.


Phonemic behavior of aphasic subjects without dysarthria or apraxia of speech. Thirty adult aphasic subjects without apraxia of speech or dysarthria were tested for their ability to produce phonemes in single test words and in spontaneous contextual speech. Results indicated that 75% of the total phonemic errors were due to a whole-word phenomenon apparently associated with faulty processing of the word rather than faulty production of the phoneme. True phonemic errors comprised 25% of the total errors or about 2% of all responses. Phoneme substitutions were by far the most frequent error (61%). Of the 30 subjects, 28 made no phonemic errors in spontaneous contextual speech. Aphasic behavior is not characterized by significant breakdown of articulatory performance. Observed patterns of error do not clearly support a phonemic regression hypothesis.


The cerebral laterality of "minimal brain damage" children. "Minimal brain damage" children and controls matched for age, sex and intelligence were assessed for lateral preference, unimanual motor speed, reaction time to lateralised stimuli and dichotic ear advantage. "Minimal brain damage" children were found to be less extreme and stable in their lateral preferences, slower, and less lateralised in their motor performance. This suggests a deficit of interhemispheric integration, although the groups did not differ in dichotic listening performance, the normal group failing to show the expected ear advantage. "Minimal brain damage" children may be suffering from a partial disconnection syndrome.


Aphasic disorders in matching tasks involving conceptual analysis and covert naming. Aphasic, non-aphasic brain-damaged, schizophrenic and normal Ss were required to select which of two pictures in each item was indicated by a third picture. The latter was related to the referent not through direct associations but only through a mediator: a homonym -- the name for clue and referent --, a situational association, or a perceptual feature common to both. The availability of these mediators was to be tested. Aphasics were as good as normals when the task could be solved via situational associations (e.g. guitar/violin -- bullfight; mediator: "Spain"). They showed poorer performance than all the control-groups not only when the solution depended on the availability of a word but also when it was necessary to identify analytically a perceptual feature characteristic for clue and referent (e.g. swan/turkey -- snowman; mediator: "white"). This result is seen as possibly corresponding to the specific deficiency of both non-fluent and fluent aphasics in the Token Test which might be characteristic of left hemisphere dysfunctions in the analytical decomposition into separate features of what presents itself perceptually and experientally as a unit or Gestalt.


Response to delayed auditory feedback in patients with hemispheric lesions. The effect of delayed auditory feedback (DAF) on the performance of verbal and nonverbal tasks at two levels of difficulty by patients with left or right hemispheric lesions and non brain-damaged controls was compared. All subjects showed DAF effects, as measured by increases in response duration and intensity. While controls showed an increase in DAF effects as a function of increased task difficulty, the brain-damaged patients failed to show such an increase on tasks on which they were presumably impaired (verbal tasks for lefts, nonverbal for rights). Findings suggest a clear dissociation between DAF effects in unilateraly lesioned patients due to the nature of the stimulus material and its difficulty level.


Effect of immunotherapy in bronchial asthma: treatment with mite extract absorbed on tyrosine. A trial was carried out in 18 asthmatic patients to assess the effectiveness of a vaccine of house dust mite extract (Dermatophagoides pteronyssinus) absorbed on tyrosine. Patients were initially given 6 graduated doses of the vaccine subcutaneously at 7-day intervals. Maintenance injections were then given at 2-week intervals, the total dose being determined by clinical response. About 60% of the treated patients showed a significantly beneficial response to immunotherapy as assessed by symptomatic improvements. Seventy-two per cent of the patients required less oral anti-asthmatic therapy and 50% of the patients had a demonstrable increase in blocking antibodies. Local reactions were not severe and occurred infrequently. None of the patients developed systemic reactions to immunotherapy. Clinical response was found to depend to some extent on the dosage of antigen administered and rise in blocking antibodies of the patient's serum.


Clinical investigation of a very low dosage oral contraceptive combination: 0-75 mg lynestrenol and 0-0375 mg ethinyl oestradiol. A trial was carried out in 3 clinics to test the efficacy of and cycle control obtained with a very low dosage oral contraceptive combination of lynesternol (0.75 mg) and ethinyl oestradiol (0.0375 mg). A total of 134 healthy, fertile women, ages ranging from under 19 years to over 40 years, participated and completed 1144 treatment cycles. No pregnancies occurred. Then length of the treatment cycle compared to the cycle length before treatment was unchanged in 79.3% of cases. Withdrawal bleeding occurred in 93.1% of all treatment cycles, and in 78.9% of cases the duration of the withdrawal bleeding corresponded to that of the bleeding before treatment. The proportion of irregular bleeding in the first treatment cycle was 51.4% but by the 12th treatment cycle this was reduced to 12.5%. Side-effects, when they did occur, were very slight; existing complaints clearly decreased during the treatment.


Intravenous administration of erythromycin: serum, sputum and urine levels. Eight patients requiring antibacterial therapy were given a continuous infusion of erythromycin lactobionate, using 5% dextrose solution as the infusant, at the rate of 1 g per 12 hours over a period of 5 days. Serum, urinary, and sputum levels of the antibiotic were measured at regular intervals. The results of the assays showed that after the initial 8 hours the levels of erythromycin produced were sufficient to inhibit a wide range of aerobic and anaerobic pathogens. There was no evidence of clinical or biochemical deterioration of renal or liver cell function during the treatment period.


The use of pindolol in the treatment of essential hypertension: a multi-centre assessment. A multi-centre general practitioner assessment of pindolol, a beta adrenergic blocking drug, was carried out in 464 patients with essential hypertension. The average daily dose was 21 mg and the average period of observation was 15 weeks. Pindolol was shown to be a safe, effective and well tolerated hypotensive agent. In 227 new cases of hypertension, 148 (65.2%) were controlled on pindolol alone, and in 237 previously treated cases of hypertension 91 (38.4%) were subsequently controlled on pindolol alone. In the remaining cases the addition of a diuretic or other antihypertensive agent was necessary to achieve satisfactory control. The mean blood pressure was lowered from 190/111 mmHg to 154/90 mmHg, a mean fall of 36/21 mmHg. Side-effects were not of a serious nature.


Comparative chiasma analysis using a computerised optical digitiser. A new computerised technique has been devised for measuring the distribution of chiasmata along diplotene bivalents. The method involves the introduction into the field of view of the microscope, of a fine light spot which can be accurately manipulated along the chromosomes of each bivalent. The data recorded include (a) the positions of the chiasmata along the bivalent in terms of their relative distances from the centromere and (b) the individual bivalent and cellular chiasma frequencies. -- The method has been applied to the analysis of chiasma distribution patterns in the two known species of the genus Caledia, C. species nova 1 and C. captiva and in two chromosomal races of the latter. Statistical tests indicate that within bivalents at least 40% of the comparative distribution patterns of chiasmata between races and species are significantly different. Similar comparisons between populations within races reveal only 18% significant differences. -- The observed distribution patterns of chiasmata in this genus suggest that chiasma formation is sequential from centromere to telomere. -- The variation in the frequency and distribution of chiasmata between races and species suggests that the interference distances between successive chiasmata are, at least partially, independent of chiasma frequency and position. -- The interracial and interspecific differences in chromosome structure are correlated with changes in chiasma pattern.


Disjunction types and their frequencies in two heterozygous reciprocal translocations of Blattella germanica (L.). Adjacent-1, alternate-1, adjacent-2, and alternate-2 disjunction configurations were observed cytologically at metaphase I in heterozygotes from two reciprocal chromosome translocations in the German cockroach, Blattella germanica (L.). T(7; 12) shows random disjunction and the frequencies of the above four types were in a ratio of 2:1:1:2 (p greater than 0.90). T(3; 12) has directed disjunction (about 70% alternate) which is attributable to a heavy preponderance of alternate-2. No interpretable ratio occurs here except for the equality of alternate-1 and adjacent-2 types. These observations confirm the existence of two types of alternate disjunction, and provide insight into the basis for random vs directed disjunction.


A possible active segment on the inactive human X chromosome. An idic(Xp--) in which the two X chromosomes are attached short arm to short arm, and which thus has two b regions (the Q-dark segment next to the centromere on Xp) between the inactivation centers, assumed to be situated on the Q-dark region next to the centromere on Xq, showed 63.8% bipartite Barr bodies as compared with 22.2% formed by idic(Xq--). In addition, the mean distance of the two parts of the Barr bodies in the fibroblasts of a patient with idic(Xp--) is significantly greater than in the cases with one or no b region. Contrary to the other patients with abnormal X chromosomes, the buccal cells of a woman idic(Xp--) showed a number of bipartite Barr bodies. -- To explain these observations we have put forward the hypothesis that the b region on the Xp always remains active and thus, when the rest of the chromosome forms a Barr body, this segment is extended, allowing the two parts of the X chromatin to get farther apart and at the same time increasing the percentage of bipartite bodies.


Chromosomal distribution of rDNA in Pan paniscus, Gorilla gorilla beringei, and Symphalangus syndactylus: comparison to related primates. Hybridization in situ was used to identify rDNA in chromosomes of the pygmy chimpanzee, mountain gorilla, and siamang gibbon. In contrast to other Pongids, and man, the gorilla has only two pairs of rDNA-containing chromosomes. The single pair in the siamang bears no resemblance to the nucleolar chromosome of the closely related lar gibbon. Pan paniscus and P. troglodytes have the same rDNA distribution, and similar karyotypes except in the structure of chromosome 23p. Grain counts over unbanded preparations show that the human, orangutan, and both chimpanzees have about the same total rDNA multiplicity.


Solid tissue model for the standardization of the echo-ophthalmograph 7200 MA (Kretztechnik). After discussion of the biologic basis of echographic tissue differentiation and of the required standardization of the ultrasonic diagnostic device by means of tissue models (citrated blood), a technical standard is presented. This solid tissue model, which can be used an unlimited number of times, enables the investigator to determine or check the tissue sensitivity of his instrument at any time easily and quickly. The model consists of a synthetic resin (Wacker Silgel 504) to which a certain number of microbeads (glass beads S-100) are added before it hardens. The acoustic properties of this technical standard correspond to those of the biologic standard (citrated blood) including all important factors such as reflectivity, degree of scattering and sound attenuation.


[Cavity structures in the peripheral retina]. 1. Lange's fold of the ora frequently found at autopsy in fetuses and infants is a purely postmortal change. 2. The 'honeycomb ora' occurring in infants and small children may sometimes be present in vivo. The extensive and larger cavities however may well have appeared only postmortally here too (they are not seen in older children). 3. Both the typical or external and the reticular or internal cystoid degeneration of the peripheral retina increase in frequency and extent with increasing age. Both occur in vivo. Biomicroscopically cystoid degenerations apparently can be demonstrated in any living eye after indentation of the ora. Basal membrane fragments and microfibrils have sometimes been shown by staining in the cyst walls (when cyst and vitreous body are connected) and mucopolysaccharides in the cystoid cavities. But there are also cystoid degenerations occurring postmortally. The picture of internal cystoid degeneration can also be seen as a fixation artefact (only) in fetuses in not yet vascularised sections of the retina. In the cystoid cavities one finds histologically sometimes reaction-free cell debris, torn fibres and isolated cell nuclei of the granular layers. Whereas the biomicroscopically found cystoid degenerations almost always end (well) in front of the equator of the eyeball, the histologically found cystoid degenerations are seen relatively often considerably behind the equator. Scotomas to be expected in vivo in these cases have not been observed so far. The periphery of the retina is histologically often torn off the ora without any reaction and displaced far forward. The picture of cystoid degeneration can also be produced quite artificially by bulging of the retina due to fixation in histology (different treatment of the two halves of the eyeball). Even without any tissue participation a picture like cystoid degeneration below the peripheral retina, between it and the pigmented epithelium, may develop in celloidin itself if too quickly hardened. 4. Retinal cysts found relatively often histologically are predominantly extensive cystoid degenerations. Exceptionally these are apparently identical with the rare cysts or retinoschisis cases visible ophthalmoscopically. 5. Small to large-cystic retinal degenerations are mostly secondary reactive changes. The situation of Lange's fold, honeycomb ora and especially cystoid degenerations depends postmortally (but also apparently in vivo) on the pull of the zonule and vitreous body fibrils as regards extent and direction. The intravitally present cavities in (honeycomb ora and) cystoid degeneration are considerably increased postmortally and apparently still more by histological preparation. In addition there seems to be an age-specific alteration in the ratio of the pull of zonule-vitreous body fibrils on the one hand and the (age-dependent) tearability of the retina on the other: in fetuses and infants we get Lange's fold, in infants and small children honeycomb ora and in later childhood increasingly extensive cystoid degenerations.


[Effect and complications of Vogt perforating cyclodiathermy in various forms of glaucoma]. In 178 eyes 223 perforating cyclodiathermies (PCD) have been performed. The technique described by Vogt was modified by additional coagulations around the insertions of the recti-muscles. This procedure was done if one or repeated glaucoma procedures (fistulas, iridectomies or trabeculotomies) were not successful of if these surgical methods were not reasonable because of the morphological conditions of the iris and the chamber angle. If one compares in this retrospective study the average diurnal curves of 60 eyes preoperatively and 7 days postoperatively the PCD has lowered the curve and removed the morning peak that was visible preoperatively. In 153 eyes (86%) the intraocular pressure could be lowered at least for some time. A new increase was seen in most cases during the first 6 months postoperatively. 116 eyes had a postoperative follow-up of 6 months up to 3 years. 45 (39%) of these eyes were controlled without and another 31 eyes (27%) with additional medical therapy (single measurement or average of the diurnal curve less than or equal to 21 mmHG). In some eyes a repetition of the PCD was necessary to be successful. The best results had been achieved in primary glaucoma, in secondary glaucoma after uveitis and in aphacic eyes. In congenital glaucoma only 12 out of 25 eyes could be controlled and this was similar in secondary glaucoma of the vascular type. There is no influence of the preoperative pressure level on the rate of success. But the effect correlates with the preoperative visual acuity: the worse the visual function, the lower the percentage of controlled eyes. The intra-operative complications are not important. The most important postoperative complication is a phthisis bulbi which was seen in at least 10 out of 178 eyes. Most of these eyes were suffering from a secondary glaucoma of the vascular type with high preoperative pressure. All eyes had a visual acuity of 1/50 or less. To repeat the PCD after a few weeks is another factor that facilitates this serious complication. After at least 3 months the repetition of a PCD seems to be without a special risk of phthisis bulbi.


Human psychophysical analysis of receptive field-like properties: IV. Further examination and specification of the psychophysical transient-like function. In this paper we examine several key properties of the moving 'windmill' target used in evaluation of the psychophysical transient-like function. Magnitude of the transient-like function, herein defined as the difference in threshold-determining background field luminance between stationary and moving windmill conditions, was greatest for a rate of approximately 6-8 on-off transitions/second for the moving windmill. Increasing the light/dark ratio of the windmill also augmented the magnitude of the transient-like function. The one-, two- and four-section 'windmill' targets exhibited essentially similar results, indicating that the number and length of borders do not influence this response. In conjunction with previous stationary windmill results (Enoch and Johnson, 1976), these data define the relevant transient-like function properties and provide a basis for comparison with findings in the companion paper (Enoch, Johnson & Fitzgerald, 1976a) which describes the application of these properties to clinical populations for diagnostic purposes.


The blood-retinal barriers.

The blood-retinal barriers. The Blood-Retinal Barrier (BRB) is a situation of restricted permeability which is present between the blood and the retina. This barrier has a well defined anatomic substrate, particular permeability characteristics and appears to play a role of major importance in the pathophysiology and therapeutics of retinal disease. The BRB phenomenon operates fundamentally at two levels, retinal vessels and chorioepithelial interface, forming which may be better called an inner BRB and an outer BRB. The main structures involved are, for the inner BRB, the endothelial membrane of the retinal vessels, and for the outer BRB, the retinal pigment epithelium. 'Zonulae occludentes' are present in these membranes forming complete belts around the cells, sealing off the spaces between them. Other structures appear to play an accessory role. Both barriers show an apparent predominance of processes of active transport over mechanisms of passive transfer, these being extremely restricted. Much information on the pathophysiology of the BRB mechanism has been obtained from studies of its experimental breakdown. In this way, a breakdown of the inner BRB may be induced by acute distension of the vessel walls, ischaemia, chemical influences, defects in the endothelial cells and failure of the active transport system, whereas experimental ischaemia, mechanical distension of the pigment epithelial membrane, defects in the pigment epithelium and failure of the active transport systems can cause a breakdown of the outer BRB. The increased permeability of the inner BRB, and of the outer BRB, appears to be related to changes in the vascular endothelial membrane and retinal pigment epithelium, respectively. In clinical ophthalmology there are two methods for the diagnosis of breakdown of the BRB, fundus fluorescein angiography and vitreous fluorophotometry. Vitreous fluorophotometry being capable of detecting functional alterations of the barrier before any pathological changes are apparent. There is evidence of an intimate relationship between breakdown of the BRB and almost every retinal disease, particularly the vascular retinopathies and the pigment epitheliopathies. Diabetic retinopathy, hypertensive retinopathy, retinal vein obstruction, blood diseases, trauma or surgery to the eye, temporary arterial obstruction, perivasculitis, Behçet's and Coats' diseases, retinoblastoma, hemangioblastoma and retinal neovascularization are examples of situations where a breakdown of the inner BRB has been demonstrated. On the other hand, examples of breakdown of the outer BRB include situations of choroidal ischaemia, detachment of the pigment epithelium, choroidal neovascularization, photocoagulation, retinal detachment, Koyanagi's disease, central serous choroidopathy, multifocal inner choroiditis and acute placoid pigment epitheliopathy.