Methylmethacrylate as an adjunct in internal fixation of pathological fractures. Experience with three hundred and seventy-five cases. In 323 patients with 375 pathological fractures or impending fractures, local tumor resection and internal fixation supplemented by intramedullary methylmethacrylate proved highly successful. One hundred and thirty-nine patients had metastases from breast carcinoma; 142, metastases from other tumors; and forty-two, myeloma or lymphoma. The mean survival for the 210 patients who had undergone operation two years or more before final evaluation was 15.4 months. Ninety-four per cent of the patients who were ambulatory before fracture regained the ability to walk. Eighty-five per cent had excellent or good pain relief and in only five was pain relief rated poor. There were four failures of fixation and six functionally poor results. Twenty patients died within four weeks of operation, but the remaining patients benefited from the procedure in terms of pain relief, improved mobility, and ease of nursing care.


Intramedullary fixation of pathological fractures and lesions of the subtrochanteric region of the femur. The Zickel intramedullary appliance was used without methylmethacrylate in forty-six patients to stabilize thirty-five fractures and eleven impending fractures associated with osseous lesions in the subtrochanteric region of the femur. Early mobilization or ambulation was possible in nearly all cases. The patients with actual fractures survived an average of 4.7 months, while those with lesions stabilized prophylactically survived an average of 13.8 months postoperatively. Fourteen of the thirty-five patients with fractures showed union after an average of 4.5 months.


Pathological fractures in the proximal part of the femur treated by Zickel-nail fixation. Twenty-one patients were treated with Zickel nail for neoplastic pathological fracture or impending pathological fracture: in the femoral neck in three, in the intertrochanteric region in three, and in the subtrochanteric region in fifteen. Nineteen patients were restored to bed-chain status by the third postoperative day, and twenty were able to walk. Failure of fixation did not occur and there were no infections.


Prophylactic internal fixation of the femur for neoplastic lesions. Prophylactic intramedullary nailing was performed in eighteen femora of fourteen patients who had neoplastic lesions in the femur and survived for from thirty-eight to 1309 days after nailing. The procedure enabled all but three patients to be ambulatory with a walker by four days after operation and to continue to walk until they became moribund shortly before death. The complications were: one postoperative infection, penetration of the nail through the femoral cortex in three femora before prebending of the nail became part of the procedure, and ectopic bone about the proximal end of the rod. The procedure is recommended for the prevention of pathological fracture and relief of pain.


The strength of the anterior cruciate ligament in humans and Rhesus monkeys. The mechanical properties of anterior cruciate bone-ligament-bone specimens from humans and rhesus monkeys were determined in tension to failure under high strain-rate conditions. The age range of the human specimens was from sixteen to eighty-six years. The values fro human specimens obtained from young adults with regard to elastic modulus, ultimate tensile stress, and strain energy to failure were approximately two to three times those for specimens from humans in the sixth decade and older. The major mode of failure was ligament disruption in the specimens from young adult humans and avulsion of bone beneath the ligament insertion site in the specimens from older humans. The difference in mode of failure correlated with histological observations of decreased bone mass at the site of ligament attachment in the specimens from older humans. Rhesus monkey specimens had higher values for elastic modulus, failure stress, and strain energy. Significant reductions in strength and stiffness properties of ligament units were shown to occur with advancing age to a greater degree than expected. All experiments in which specimens from older human cadavera are used should be interpreted with caution when the results are applied to mechanisms of ligament failure for younger or athletic individuals.


Cruciate ligament prosthesis: strength, creep, and fatigue properties. The mechanical properties of the Richards polyethylene ligament implant were studied and compared with the strength of human cruciate ligament preparations. The implant yields and plastically deforms at a force of 420 newtons (ninety-four pounds) and approximately 10 per cent elongation when tested at a strain rate of 100 per second. This is one-fourth the average tensile strength of the human anterior curciate ligament preparations. When tested at a strain rate of 1 per cent per second the implant's yield-point force was lowered by 15 per cent. The implant exhibits considerable viscoelastic  behavior and will progressively elongate under repetitive loads when insufficient time is allowed for it to return to its original length. In bending, the implant did not fail after eighty million stress reversals (forty million revolutions) when tested while immersed in saline solution at body temperature. The tests indicate that the tensile strength of the implant is low in comparison with both the strength of human preparations and estimates of actual in vivo functional loads. We conclude that caution is required in the use of this implant.


Hydroxychloroquine sulphate in prevention of deep venous thrombosis following fracture of the hip, pelvis, or thoracolumbar spine. One hundred and fifty-three patients, forty-eight to ninety-seven years old, were included in a double-blind placebo-controlled investigation of the usefulness of hydroxychloroquine sulphate for the prevention of deep venous thrombosis in patients with fractures of the hip, pelvis, or thoracolumbar spine. The results indicated that this drug can reduce the number of thrombeombolic complications significantly (p less than 0.005), a finding that corresponds to the results obtained with other drugs such as coumarin derivatives or  dextran 70.


Joint replacement surgery in patients under thirty. Forty-five patients, twenty-six of them with juvenile rheumatoid arthritis, had sixty-seven total hip arthroplasties. The patients' ages ranged from twelve to twenty-nine years. An over-all good result was demonstrated in 93 per cent of the patients had a poor result, in 6.9 per cent. The average follow-up period was 32.5 months. Careful planning in severely dysplastic joints should be done.


Treatment of ulnar fractures by functional bracing. Treatment of isolated fracture of the ulna by means of functional bracing was successful in seventy-two cases. No non-unions were encountered. There was minimum deformity and loss of pronation-supination, and no loss of motion at the elbow and wrist. The average time to healing was ten weeks.


Halo-pelvic distraction apparatus. An analysis of one hundred and fifty consecutive patients. One hundred and fifty consecutive patients on whom the halo-pelvic apparatus was used were analyzed. Sixty-six per cent had tuberculous kyphosis or paralytic scoliosis. The apparatus was of great value in holding and correcting spines with tuberculous kyphosis and the results were gratifying, even though the average correction of the kyphos was only 20 per cent. In paralytic scoliosis a 46 per cent correction was obtained, but presently Dwyer and Harrington instrumentation are used for the majority of such cases. The halo-pelvic apparatus was effective in holding and correcting severe congenital curves and kyphoscoliosis secondary to neurofibromatosis, especially when there were signs of cord compression. The complication rate was high early in the series, but has been lowered by strict patient selection and close adherence to specific guidelines in the application of the apparatus. The apparatus should be reserved for severe deformities when other means of correction or stabilization are inadequate.


Roentgenographic evaluation of vertebral rotation. To examine the accuracy of vertebral rotation determinations made from roentgenographic pedicle-shadow offset measurements, roentgenograms were made of fifteen cadaver vertebrae with different sagittal and frontal inclinations and longitudinal axis rotations ranging from 15 degrees left to 45 degrees right. It was found that significant uncertainties arise when vertebral rotation is evaluated from measurements of pedicle-shadow offset: true and apparent offsets in a single vertebra differ markedly; vertebrae from different spines have different offsets for the same degree of rotation and the same inclinations; and changes in the sagittal and frontal inclinations of a single vertebra alter its offset in the same manner as changes in rotation. From these results, it seems unlikely that precise measurements of rotation changes in spines with mild or moderate scolioses, for example, can be made from anteroposterior roentgenograms.


Complications of total hip-replacement arthorplasty in patients with rheumatoid arthritis. During the period 1969 through 1974, 716 total hip-replacement arthorplasties were performed. The results of the surgery in 275 cases of rheumatoid arthritis as regards complications were compared with those in 382 procedures in cases of osteoarthritis. In contrast to the reports of others,the incidence of deep would infection in the two groups was found to be equal. Patients undergoing total hip-replacement arthroplasty as a revision of a previous operation had a substantially increased risk of infection. Patients with rheumatoid arthritis, however, were more subject to certain other complication (intraoperative fracture, difficulties with anesthesia, and malposition of prosthetic components), in addition to the complications that were predictable because of the involvement of multiple joints and the systemic disease process.


Urinary infections in total hip arthroplasty. Influences of prophylactic cephalosporins and catheterization. We studied 359 patients retrospectively and 100 patients prospectively, all on cephalosporin prophylaxis. Urinary infections were eight times more frequent in catheterized patients; most were caused by Pseudomonas and Enterobacter. One patients had acute seeding in the arthroplasty site from a Pseudomonas urinary infection.


Boyd and Syme ankle amputations in children. The Syme and Boyd amputations at the ankle were compared in thirty-four children followed for three to sixteen years. Good results were found with both techniques. The best results occurred when the heel pad was aligned in the plantigrade position, which produced almost normal function of the heel pad. The Boyd technique was a surer method of obtaining such alignment but was technically more difficult. Both the Boyd and Syme techniques are recommended for ankle amputation in children, but a distinct advantage of one technique over the other could not be defined.


Oerative treatment of the plantar-flexed inverted foot in adult hemiplegia. From a population of 902 adult patients with acquired hemiplegia, thirty-two patients with extensor synergy were chosen for a reconstructive procedure designed to eliminate the need for an orthosis. Three additional patients underwent the procedure to eliminate severe spasticity which precluded orthotic fitting. The operative technique, first described by Mooney and associates, involved lengthening of the tendo achillis and tibialis posterior tendon, multiple toe-flexor tenotomies, and a split transfer of the tibialis anterior tendon. Satisfactory results were recorded for thirty-two patients. The three failures were ascribed to inappropriate selection of patients for surgery.


Squamous-cell carcinoma complicating chronic osteomyelitis. Treatment of carcinomatous degeneration in patients with chronic osteomyelitis requires differentiation between benign, penetrating epithelioma and invading, low-grade squamous-cell carcinoma. Although most lesions are low grade, analysis of the case histories of twenty-three patients treated at the Mayo Clinic indicates that these tumors do metastasize. When malignant-appearing epithelium invading bone is identified, ablative surgery is indicated. Inadequate surgical treatment resulted in the deaths of two patients in our series. Routine regional lymphadenectomy at the time of amputation seems unnecessary. Regional lymphadenopathy persisting for six to twelve weeks after amputation warrants surgical intervention. With prompt, aggressive surgical treatment, the prognosis for patients with squamous-cell carcinoma in an osteomyelitic cavity is good.


Changes in the hexosamine content and swelling ratio of articular cartilage as functions of depth from the surface. The hexasamine content and swelling ratio of adult bovine articular cartilage were determined as functions of depth. Progressing from the surface downward, the hexosamine content increased rapidly to a depth equivalent to approximately 30 to 35 per cent of the total thickness of the uncalcified portion of the tissue, and thereafter decreased at a less rapid rate. The swelling ratio was relatively constant throughtout the first quarter of the tissue but diminished thereafter. At depths below 35 per cent, the curve for the decrease in swelling ratio with depth was similar in form to that for the decrease in hexosamine content. Considering the factors that determine the swelling ratio of polyelectrolyte gels, it is proposed that progressing down from the surface, the interaction between the macromolecular components of the tissue is increased to a depth equivalent to about one-third of the total thickness of the cartilage.


Fracture healing in the presence of chronic hypoxia. Recent studies have demonstrated that fracture healing normally takes place under hypoxic conditions. The present study evaluated the effect of a state of chronic systemic hypoxia on fracture healing in dogs. A significant delay in fracture healing was demonstrated in the hypoxic animals roentgenographically, histologically, and by strength-testing criteria. A further reduction in the available oxygen supply below that present during normal repair had an adverse effect on fracture healing.


Metabolic recovery of articular cartilage after intra-articular injections of glucocorticoid. The recovery of adult rabbit articular cartilage after nine weekly intra-articular injections of hydrocortisone acetate was investigated using biochemical, autoradiographic, and tracer methods. After the cessation of steroid injections, the rates of synthesis of proteoglycans and collagen increased by up to 900 per cent. The increase occurred because of accelerated metabolism of existing cells and an increase (caused by mitosis) in the number of functioning chondrocytes. The proteoglycan concentration only returned to normal values after six months.


Sickle-cell dactylitis.

Sickle-cell dactylitis. In order to define better the presentation, roentgenographic features, and clinical course of sickle-cell dactylitis, the records of nine children with sickle-cell anemia and acutely painful, swollen digits were reviewed. The average age of these children at the time of diagnosis was eighteen months, and in five instances the dactylitis occurred before the diagnosis of sickle-cell disease was established. The clinical signs, consisting of swelling, tenderness, fever, and leukocytosis, were self-limiting and resolved in five to thirty-one days. The roentgenographic features, characterized by periosteal new-bone formation or intramedullary densities, appeared in seven to fourteen days and resolved in two to three months. Incorrect diagnosis is frequent in this condition but can be avoided as familiarity with the syndrome increases.


Perturbation of mammalian cell division. III. The topography and kinetics of extrusion subdivision. If mitotic-arrested, cold-stored HeLa cells are incubated at 37 degrees C a proportion of the population divides by an aberrant process which we have called subdivision by extrusion. This process has been studied by time-lapse photography and shown to differ from normal cleavage in several respects. The cell surface becomes more generally mobile and, instead of producing the precisely localized furrowing activity of cytokinesis, gives rise to multiple surface protrusions. These protrusions enlarge at the expense of the parent cell and develop into a cluster of small daughter cells (mini segregants). The surface structure of the cell, as seen by scanning electron microscopy, also changes; the microvilli characteristic of interphase, metaphase and cleaving HeLa cells are lost during extrusion and the cell surface becomes smooth. Extrusion activity is much more variable than division by cleavage in terms of both topography and kinetics, and in general takes longer to complete. Some cells in the cold-treated populations divide by mixtures of cleavage and extrusion or by cleavage alone. The relative numbers of cells dividing in different ways vary with the conditions of pretreatment and incubation of the mitotic cells. The greater the perturbation (e.g. longer cold storage), the greater the proportion of extruding rather than cleaving cells. Human diploid cells can also be induced to subdivide by extrusion. Possible mechanisms underlying the different types of division activity are discussed.


Characterization of nuclear structures containing superhelical DNA. Structures resembling nuclei but depleted of protein may be released by gently lysing cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids sediment in gradients containing intercalating agents in a manner characteristic of DNA that is intact, supercoiled and circular. The concentration of salt present during isolation of human nucleoids affects their protein content. When made in I-95 M NaCl they lack histones and most of the proteins characteristic of chromatin; in 1-0 M NaCl they contain variable amounts of histones. The effects of various treatments on nucleoid integrity were investigated.


Lectin receptor sites on rat liver cell nuclear membranes. The presence and localization of lectin receptor sites on rat liver cell nuclear and other endomembranes was studied by light and electron microscopy using fluorescein and ferritin-coupled lectin conjugates. Isolated nuclei labelled with fluorescein-conjugated Concanavalin A (Con A) or wheat germ agglutinin (WGA) often showed membrane staining, which sometimes was especially bright on small stretches of the nuclear surface. Unlabelled nuclei and nuclei with a complete ring fluorescence were also seen. The nuclear fluorescence corresponded in intensity to that seen on the surface of isolated rat liver cells. Con A-ferritin particles were seldom detected on the cytoplasmic surface of the intact nuclear envelope. However, at places where the 2 leaflets of the envelope were widely separated or where the outer nuclear membrane was partly torn away, heavy labelling was seen on the cisternal surface of both the inner and outer nuclear membranes. Labelling with Con A-ferritin was also found on the cisternal side of rough endoplasmic reticulum present in the specimens. No labelling was seen on the cytoplasmic surface of mitochondrial outer membrane. The results demonstrate the presence of binding sites for Con A and WGA in nuclei and an asymmetric localization of these sites on the cisternal side of ribosome-carrying endomembranes in rat liver cells.


Evidence for a correlation between the number of marginal band microtubules and the size of vertebrate erthrocytes. In 23 species of vertebrates the dimensions of erythrocytes and the number of their marginal band microtubules were examined. A positive correlation was found between the size of erythrocytes and the number of microtubules. The absence of microtubules in diskoid erythrocytes of mammals-Camelidae-is discussed.


The preprophase band: possible involvement in the formation of the cell wall. Numerous vesicles were observed among the microtubules of the "preprophase" band in prophase cells from root tips of Allium cepa. The content of these vesicles looks similar to the matrix of adjacent cell walls, and these vesicles often appear to be involved in exocytosis. In addition, the cell walls perpendicular to the plane of (beneath) the preprophase band are often differentially thickened compared to the walls lying parallel to the plane of the band. Our interpretation of these observations is that the preprophase band may direct or channel vesicles containing precursors of the cell wall to localized regions of wall synthesis. The incorporation of constituents of the cell wall into a narrow region defined by the position of the preprophase band may be a mechanism that ensures unidirecitonal growth of meristematic cells.


Purification of gibberellic acid-induced lysosomes from wheat aleurone cells. Using isopycnic density gradient centrifugation, lysosomes were concentrated in a single region of a sucrose-Ficoll gradient (p = 1-10 g cm-3), well separated from most other cell organelles. Gibberellic acid-induced lysosomes were found to be rich in alpha-amylase and protease but not ribonuclease. The lysosomal band also contained a majority of the NADH2-cytochrome c reductase, a marker enzyme for endoplasmic reticulum, found in the gradient. Examination of electron micrographs revealed that a purified band of lyosomes contained at least 3 vesicle types, ranging in size from 0-1 to 0-5 mum. The significance of these findings to proposed mechanisms of action of gibberellic acid is discussed.


Freeze-fracture studies of frog atrial fibres. The freeze-fracturing technique was used to characterize the junctional devices involved in the electrical coupling of frog atrial fibres. These fibres are connected by a type of junction which can be interpreted as a morphological variant of the "gap junction" or "nexus". The most characteristic features are rows of 9-nm junctional particles forming single or anastomosed circular profiles on the inner membrane face, and corresponding pits on the outer membrane face. Very seldom aggregates consisting of few geometrically disposed 9-nm particles are found. The significance of the junctional structures in the atrial fibres is discussed, with respect to present knowledge about junctional features of gap junctions in various tissues, including embryonic ones.


Investigation of the index structure of Drugdoc and Ringdoc. A comparative study was performed on the index structure of Drugdoc and Ringdoc based on the output of both systems on the same nine articles. In both systems major and secondary indexing terms are used as descriptors for biomedical and pharmaceutical context, and alphanumeric codes for showing the concept and viewpoint of the article. Ringdoc is superior in coding of drugs and pharmaceutical information as its descriptors have hierarchical relations, multifacet coding is performed, and synonyms are selected. Medical term related descriptors are more abundant in Drugdoc, including synonyms and analogous words, but no hierarchy is seen. Ringdoc selectively chooses descriptors related to the main theme of the article, whereas Drugdoc chooses descriptors comprehensively throughout the article.


[Early and late results of choledoco-duodenal anastomosis during surgical treatment of biliary lithiasis. Apropos of a series of 62 cases]. The authors report a series of 62 choledoco-duodenal anastomoses carried out during surgical treatment of cholelithiasis and note the indications for this procedure, emphasizing the necessity for a wide common bile duct and a normal duodenum. Apart from complete obstruction of the common bile duct with gall stones, the main indication is organic obstruction of the terminal part and of the sphincter of Oddi. A 2 cm anastomosis is necessary. Duodeno-biliary reflux has no direct consequence in the absence of stenosis of the anastomosis and of pre-existing cholangitis. In the long term, the results are favourable in 95 p. 100 of cases.


[Short common bile duct or high implantation. Apropos of 2 cases]. The authors report a case of so-called short common bile duct or highly implanted common bile duct, associated with double duodenal ulcer, with an unfavourable course in a very young girl. The pathological characteristics and the course suggested it was a congenital case of short bile duct, which is a rare disease, as 37 cases have been reported over a period of 25 years. 32 were associated with duodenal ulcer, which is often resistant to medical treatment, and becomes complicated in 33% of cases. The relationship between the two conditions remains hypothetical. Biliodigestive reflux was the first sign in 66% of cases. Retrograde opacification of the bile ducts under duodenoscopy should permit a diagnosis and precise pre-operative assessment. The abnormality has no special treatment, but the treatment of the associated disease, of the ulcer in particular, should be adapted to the ectopic bile duct to avoid serious injury. At operation, careful examination before dissection will determine the [site] of the papilla and of the opening of the biliary and pancreatic ducts. Vagotomy should be associated with a drainage operation, if possible, or gastrectomy may be performed with gastro-jejunal anastomosis leaving behind the posterior ulcer. Many precautions are necessary including the duodenal stump and details of these are given here.


[Post-traumatic sequestra of the liver]. The authors report 92 cases of trauma of the liver which survived initial operation and study the special problems linked to hepatic sequestration. They analyse the factors which favour the appearance of these sequestra and the methods of diagnosis using clinical, laboratory, arteriographic and scintigraphic data. Relatively frequent (8,4 p. 100), these complications require fairly early surgical treatment. They are commonly localised to the dome of the liver and this renders their approach difficult. A low postero-lateral thoracotomy with resection of the 10 th or 11 th rib, followed by sequestrectomy and drainage, seems to them ideal approach. The pleuropulmonary sequelae are minimal.


[Evaluation of the opening of the sphincter of Oddi]. Measurement of the activity of the sphincter of Oddi by the method of classical manometry did not reveal any significant difference before and after vagotomy. However, the existence after perfusion of residual pressure greater than initial pressure, suggests that a deformity of the duct during perfusion disturbs measurement of the opening of the sphincter. The mechanical properties of the duct were measured in vitro, as a first approximation it was suggested that the error due to a deformity of the duct, might be eliminated using several perfusion rates and calculating for each rate the opening R of the sphincter using the following formula: R equals (Perfusion pressure-Residual pressure) Flow rate. When the opening of the sphincter is calculated in this way, one may observe that vagotomy leads to definite reduction of the resistance of Oddi's sphincter.


Gas chromatography-mass spectrometry of some biologically important short chain acid butyl esters. Mass spectra of n-butyl esters of selected biologically important short chain fatty acids were obtained by using the technique of gas-liquid chromatography-mass spectrometry. The results indicate that simple cleavage is responsible for the primary fragmentation of the molecules. The mass spectral data are considered to be advantageous for the identification of unknown short chain acids.


Identification of gasoline contamination of ground-water by gas chromatography. Individual components that make up different grades of gasoline - or gasolines of the same grade produced by different manufacturers - are resolved and identified by gas chromatography using packed columns and a flame ionization detector. Contaminants at levels as low as 0.5 mu1/1 may be identified by the method if samples of gasoline from the source of contamination can be obtained for comparison. The uniqueness of this method is that it can be applied for routine analysis without the use of sophisticated complements for the gas chromatograph.


Simultaneous gas chromatographic analysis for the four commonly used antiepileptic drugs in serum. We describe a simple, sensitive method for the determination of phenobarbital, diphenylhydantoin, carbamazepine and primidone in serum, by use of gas-liquid chromatography with temperature programming. The methylated derivatives of these anticonvulsants were well resolved, as was 5-(p-methylphenyl)-5-phenylhydantoin, the internal standard. In this procedure we used an ion-exchange resin for separation of the drug from the serum. The proposed procedure requires only 1.0 ml of serum and can be done in less than 1 h. The lower limit of detection for each of the drugs is 0.5 mg/1. Analytical recoveries of drug from serum were excellent and peak height and concentration were linearly related up to twice the toxic concentration for serum.


Gas chromatographic analysis of dialkylbarbituric acids. A variety of procedures for the derivatization of barbituric acids for gas-liquid chromatography (GLC) are described and a convenient procedure for n-alkylation of barbiturates is reported. The gas chromatographic behavior of derivatives(methyl, ethyl, propyl, butyl, pentyl and hexyl) is discussed on the basis of the retention index. For the identification and quatitation of 23 barbiturates in biological fluids, use of the propyl derivatives allows a clear gas chromatogram to be obtained by using only one stationary phase. Alkylation with n-alkylating reagents gives only the N,N'-derivative, as confirmed by nuclear magnetic resonance (NMR) and infrared spectroscopy and gas chromatography-mass spectrometry (GC-MS). The fragmentation pattern by electron-impact mass spectrometry is discussed. Alkylation with branched alkylating reagents gives up to three peaks, the major peak being the N,N'-derivative; the other peaks identified by NMR and GC, correspond to the isomeric N,O-derivatives.


Simultaneous determination of methylated barbiturates and other anticonvulsant drugs by high-resolution gas chromatography. Several barbiturates and other anticonvulsant drugs can be analyzed simultaneously as dimethylated derivatives by high-resolution gas chromatography with a solid flash methylation injector. Quantitative determinations were performed on test serum during a quality control scheme. The sensitivity (+/- 0.1 mug/ml) and the accuracy are compatible with the measurement of therapeutic levels of barbiturates. The advantages of the method are discussed.


Improved technique for the analysis of amino acids and  related compounds  on thin layers of cellulose.XI. Direct, visual micro-method for investigating the primary structural sequence of collagen and other proteins. The present paper describes a new variation of the "finger printing" technique for examining the primary structure of proteins. It is based on the production of a reproducible, partial acid hydrolysate consisting of amino acids and small peptides which are separated into compact spots by bi-dimensional thin-layer chromatography. The spots are characterized by ther Rf values and colour reactions with a variety of reagents. The method was initially developed for collagen but has been applied to other proteins, with interesting results. It has developed logically from earlier, systematic studies on amino acids and peptides, and holds promise for the comparative investigation of normal and diseased human collagen.


A comparison of the determination of partition coeficients of 1,4-benzodiazephines by high-performance liquid chromatography and thin-layer chromatography. Relative partition coefficients (P) of 1,4-benzodiazepines were determined by a reversed-phase thin-layer chromatographic (RP-TLC) technique in the systemoleyl alcohol-water, and by high-performance liquid chromatography (HPLC) using several column packing materials. RMw values, obtained by RP-TLC, correlated well with log P values determined directly in the system oleyl alcohol-water and with the literature values for the  system 1-octanol-water. Th log k' w values from the HPLC experiments could be determined with greater precision, but the correlations of log k'w with log Poleyl alcohol and log Poctanol were not as good as those found for the Rmw values.


Determination of free fatty acids as pentafluorobenzyl esters by electron capture gas chromatography. A method for the determination of free fatty acids in minute serum samples has been developed. The acids are esterified by extractive alkylation, using tetrabutylammonium as a counter ion and pentafluorobenzyl bromide as alkylating reagent. The derivatization of palmitic acid required a reaction time of 25 min. The excess of pentafluorobenzyl bromide is removed by coupling it with a phenoalkylamine and extraction of the product into an acidic aqueous phase. Quantitation is carried out by gas chromatography with electron capture detection. The precision achieved in the determination of 6.2 mug of palmitic acid in 50 mul of mouse serum was 6.1% (S.D.).


Pyrolysis gas chromatography as an aid to the identification of Aspergillus species. Using pyrolysis gas chromatography it was possible to identify each of nine Aspergillus species. The effects of hyphal age and the non-differentiation with spores are discussed.


Comparative study on the derivatization of l-alpha-acetyl-methadol metabolites for electron capture gas-liquid chromatography. Six reagents-trichloroacetyl chloride, trichloroacetic anhydride, pentafluorobenzoyl chloride, heptafluorobutyryl chloride, heptafluorobutyric anhydride, and trifluoroacetic anhydride- were evaluated as potential derivatizing reagents for quantitating the metabolites of l-alpha-acetylmethadol (LAAM) -noracetylmethadol, dinoracetylmethadol, methadol, and normethadol-by electron capture gas-liquid chromatography. All of the reagents studied reacted quantitatively with all of the metabolites except methadol; however, trichloroacetyl chloride was found to be the most satisfactory general reagent for analyzing these metabolites in biological fluids. A gas-liquid chromatographic method is presented which combines both flame ionization and electron capture detection for quantitating plasma and urine levels of methadone, l-alpha-acetylmethadol and its metabolites.


Analysis of isomeric impurities in a synthesis of the novel anti-inflammatory drug, benoxaprofen. Gas-liquid chromatographic procedures are described for the determination of isomeric impurities in rho-chlorobenzoyl chloride and the intermediates, 2-(rho-nitrophenyl)-proprionitrile and 2-phenylpropionitrile, in a ten-stage synthesis of benoxaprofen, 2-(rho-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid.


General procedure for the isolation and identification of 6-alpha- and 6-beta-hydroxy metabolites of narcotic agonists and antagonists with a hydromorphone structure. In order to aid in the elucidation of the metabolism of drugs containing the hydromorphone structure, a method is described for isolation from urine, separation and identification of the 6-alpha- and 6-beta-hydroxy metabolites. The samples were acid-hydrolyzed, extracted, and separated by thin-layer chromatography. The zone containing the hydroxy metabolites was removed and the compounds were re-extracted and analyzed by gas-liquid chromatography (GLC). Silylation of the extract was necessary in most cases for optimum GLC resolution of the alpha- and beta-hydroxy epimers. To demonstrate application of this method, the urine of guinea-pigs and rats which had received a single 40-mg dose of naloxone subcutaneously was analyzed. Analysis indicated a alpha/beta ratio of 0.41 for the guinea-pig. In contrast, the amount of 6-alpha-naloxol found in the urine of the rat was negligible in comparison with the 6-beta-hydroxy metabolite, indicating a species difference in the stereospecificity of the drug-metabolizing enzyme.


Simultaneous quantification of procainamide and N-acetylprocainamide with high-performance liquid chromatography. A rapid, precise and specific method for the simultaneous determination of procainamide and N-acetylprocainamide (NAPA) in plasma using high-performance liquid chromatography is described. N-Formylprocainamide was utilized as internal standard. The coefficients of variation of the method for both procainamide and NAPA were 3.6% in the range of plasma levels to be expected clinically. The method is especially useful for rapid determination of acetylator phenotype in patients requiring procainamide for control of arrhythmias.


Chromatographic separation of selenohypotaurine, selenotaurine, selenohomohypotaurine and selenohomotaurine. By either paper or ion-exchange chromatography the two seleninic compounds selenohypotaurine and selenohomohypotaurine, and the two selenonic compounds selenotaurine and selenohomotaurine may be all separated from each other. On paper chromatography seleninic derivatives may be separated from the corresponding sulphinic compounds, while selenonic compounds show RF values similar to those of the corresponding sulphonic derivatives. These two latter types of compounds may be differentiated, however, since selenonic compounds liberate iodine from HI, while sulphonic compounds do not. Also by automated ion-exchange chromatography seleninic derivatives are well separated from the analogous sulphinic compounds, while selenonic compounds are eluted together with the corresponding sulphonic compounds.


Identification and determination of phthalate esters in river water by high-performance liquid chromatography. The use of three separation modes (normal and reversed-phase adsorption chromatography and gel chromatography) with an ultraviolet absorption detector of variable wavelength provides the basis for a very sensitive method for the determination of phthalate esters in river water. Phthalates in river water were extracted with n-hexane and the extract was injected into three chromatographic systems [porous polymer beads-n-hexane (at 224 nm); porous polymer beads-methanol (at 224 nm); and polystyrene GPC gel-chloroform (at 243 nm)] without any pre-treatment such as clean-up concentration. Average concentrations of approximately 45 ppb of di-n-butyl phthalate (DBP) and 10 ppb of di-2-ethylhexyl phthalate (DOP) were found in a given river water. Phthalate concentrations as low as 2 ppb could be determined. The limit of determination could be lowered by the use of concentration process. The absolute detection limit was 2 ng of DOP at 224 nm.


Separation of polycyclic aromatic hydrocarbons by liquid chromatography on cross-linked polyvinylpyrrolidone. Polycyclic aromatic hydrocarbons (PAHs) can be separated by liquid chromatography on cross-linked polyvinylpyrrolidone (PVP) stationary phase using a polar solvent as eluent. The order of elution is determined primarily by the number of condensed aromatic rings Efficient separations were obtained with a column packed with 63-90 mum particles of PVP and isopropanol as eluent. Capacity factors (k') ranged from 0.3-10 for PAHS having from one to five aromatic rings, and theoretical plate heights were between 0.3 and 0.5 mm. This technique is being used to assist in the characterization of products from coal liquifaction processes.


Determination of beta-cetotetrine in plasma and urine using high-performance liquid chromatography with electrochemical detection. A sensitive and specific method for the determination of beta-cetotetrine in biological fluids has been developed using reversed-phase high-performance liquid chromatography and thin-layer electrochemical detection. The limit of detection for beta-cetotetrine was less than 0.25 pmoles, or approx. 100 pg injected on-column. beta-Cetotetrin could be analyzed in plasma at concentrations of 25ng/ml. Linear responses were observed up to 2.5 mug/ml, and the relative standard deviation of the procedure was +/-5%. The method was also employed for the determination of similar levels of beta-cetotetrine in urine.


Separation of chloramphenicol intermediates by high-performance liquid chromatography on micropak-NH2 columns. A column containing a chemically bonded phase, MicroPak-NH2, was used to seperate six components of a chloramphenicol-intermediate mixture. Two-component eluents comprising a non-hydrogen-bonding apolar solvent (cyclohexane) and a polar hydrogen-bonding solvent (dioxan, tetrahydrofuran or isopropanol) were tested. A correlation was found to exist between the values of the capacity factor (k') and the Hildebrand parameter (delta). Three-component eluents comprising cyclohexane and one of the binary mixtures dioxan-isopropanol or tetrahydrofuran-isopropanol were also studied. Optimum separation conditions with respect to analysis time, degree of resolution and detection limit were established. The system was successfully used to analyse production samples.


Fractionation of of proteolytic enzymes by affinity chromatography on sepharose aminocaproyl proflavin. The serine proteinases trypsin, chymotrypsin, elastase, and acrosin bind to the proflavin resin, the sulfhydryl proteinases ficin, bromelain, and papain are retarded by the resin, whereas most proteins and enzymes tested are not bound. Elution of the bound activities is accomplished NaCl or by variation from the pH optimum of the enzyme. Commercially available enzymes that are bound or retarded are easily further purified by the column. The acrosin activity of sperm acrosomal extracts is separated into bound and unbound activities. Acrosin is purified 120-fold from sperm acrosomal extracts in a single step, yielding a specific activity of 96.


Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents. Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.


Binding of progesterone by human uterine cytosol. Progesterone binding by 100,000 X g cytosols of human myometria from patients undergoing hysterectomy for various reasons was assayed using equilibrium dialysis or DEAE-cellulose filtration. The estimates of high-affinity porgesterone binding obtained by both techniques showed a significant correlation. Dialysis and filtration assays with cortisol competing with [3H]progesterone for binding indicated that the specific progesterone binding by the cytosols was the result of progesterone interaction with two high-affinity constitutents. Myometrial cytosols from tissues under progestin stimulation (secretory endometrium or pregnancy) had low concentrations of progestin binders. Cytosols from uteri with atrophic endometrium showed consistently high concentrations of progestin binders and those tissues under estrogen stimulation (proliferative endometrium or hyperplasia) and variable binder concentrations. No differences were detected between grouped observtions classified into 10 clinical categories. The DEAE-cellulose filtration is an effective method for evaluating progesterone binding which uses well-established statistical techniques and requires less tissue, less time for incubations, and fewer points for reliable analysis than does equilibrium dialysis.


The effects of diethylstilbestrol and medroxyprogesterone acetate on kinetics and production of testosterone and dihydrotestosterone in patients with prostatic carcinoma. Alterations in the metabolism of testosterone (T) and dihydrotestosterone (DHT) induced by diethylstilbestrol (DES) or medroxprogesterone acetate (MPA) could account for the beneficial therapeutic effect of these agents in prostatic carcinoma. To investigate this possibility we sutdied plasma kinetics of T and DHT in 17 elderly patients with prostatic carcinoma, before and after treatment with DES (1 or 5 mg/d) or MPA (10 or 30 mg/d) for 30 days. Metabolic clearance rates (MCR) were determined with the single injection technique and by use of two compartment model, plasma concentrations (PC) of T and DHT by radioimmunoassay, the per cent of T bound to plasma protein (T-binding) by charcoal adsorption of the unbound steroid. Production rate (PR) and PC of T were lower, PR and PC of DHT were higher in our patients than in normal men. With both DES regimens, PR, PC and MCR of either androgen declined; however, T was suppressed to a much greater extent than DHT. In either instance, the decrease may have been caused by direct suppression of testicular androgen synthesis and/or by decreased gonadotropin stimulation. Enhanced T-binding played an additional role in reducing the free testosterone index. High and low dose of DES were equally effective. The low dose regimen of MPA did not influence androgen metabolism. MPA in the higher dose suppressed PR and PC of T and DHT, possibly due to effects on testicular synthesis or by gonadotropin suppression as suggested for DES. In contrast to DES, MPA failed to cause profound changes in MCR of either androgen or in T-binding. When judged by its influence on the metabolism of T and DHT in prostatic carcinoma, MPA in higher doses is much less effective than either dose regimen of DES.


Cerebrospinal fluid prolactin: a reflection of abnormal prolactin secretion in patients with pituitary tumors. Cerebrospinal fluid prolactin levels were determined in 33 patients with pituitary disease, 3 pregnant women at term and 30 control subjects. Prolactin which was immunologically similar to the human prolactin standard was detected by radioimmunoassay in the CSF of most of these subjects. Elevated serum and CSF PRL concentrations were found in three pregnant subjects and in twelve patients with putuitary tumors. Ten patients with pituitary tumors had serum PRL concentrations greater than their corresponding CSF PRL levels. A significant correlation was noted between the elevated serum and CSF prolactin levels in the twelve hyperprolactinemic patients which suggested that the CSF prolactin concentration was influenced by the serum PRL level. Two patients with pituitary tumor however, had CSF prolactin concentrations higher than their serum levels, which suggested that direct secretion of prolactin from the tumor to the CSF can also occur. Three patients with chromophobe adenomas had normal serum PRL concentrations and elevated CSF prolactin levels which differentiated them from fifteen patients with the primary empty sella syndrome who had normal serum and CSF prolactin levels. The finding of normal CSF prolactin levels in the primary empty sella patients argues against the postulate that the diaphragma sellae significantly influences CSF pituitary peptide concentrations.


The circadian rhythm of renin.

The circadian rhythm of renin. The circadian rhythm of plasma renin activity during continuous recumbency was determined fifty-one times in thirty subjects who either slept at night or remained awake for 24 h. Both groups had maximum values between 2400 and 0800 h, despite absence of the expected early morning fall in blood pressure, pulse, and glomerular filtration rate in the awake subjects. Infusion of normal saline between 2300 and 0300 h initially suppressed renin, but did not prevent its subsequent rise regardless of the amount of sodium appearing in the urine. Of thirteen patients tested two to five times, twelve had recurrence of the zenith within a single 4 h period on retesting, despite differences in sodium intake, basal blood pressure, and mean plasma renin activity. Peaks of lesser magnitude were also frequently noted, most commonly at 1000 h and 1800-2000 h. Minimum PRA values were not restricted to a particular time of day and did not generally recur at the same time upon retesting. The mean ratio of maximum to minimum PRA in each study was 246% +/- 18.3% (+/- 1 SEM). The circadian rhythm of renin appears to be independent of known renal mechanisms responsible for regulating renin release. It is possible that this rhythm is controlled by the central nervous system.


Studies on phenolic studies in human subjects. XX. In vivo conjugation and metabolism of estradiol-17beta in the human kidney. Labeled estradiol-17beta (E2) was injected into one of the renal arteries of two human subjects. At the same time, an equimolar amount of differently labeled E2 was injected into a peripheral vein. The urinary metabolites were analyzed by DEAE-Sephadex A-25 column chromatography, countercurrent distribution (CCD) and enzyme hydrolyses. Identification was made by statistical analysis of data from CCD, thin layer chromatography (TLC) and co-crystallization upon admixture with authentic compounds. The major urinary metabolites were E2-17glucosiduronate (E2-17G), E2-3G and estriol-16G (E3-16G). The E2-17G was excreted immediately following injection of 14C-E2 into the renal artery of subject no. 1, at a rate which decreased gradually with time; whereas 3H-E2-17G did not appear in the urine until 5 min after injection of 3H-E2 into a peripheral vein. The excretion of 14C-E2-17G was very prominent as opposed to that of 3H-E2-17G; however, the excretion of both 14C- and 3H-E2-17G terminated within 30 min. 14C-E2-3G was excreted immediately following injection, whereas 3H-E2-3G did not appear until 5 min after the injection. Also, the excretion of 14C-E2-3G was more prominent as opposed to that of 3H-E2-3G. The excretion of these compounds was rapid in the initial 15 min after injection and then continued slowly for 1 h. On the other hand, 14C- and 3H-E2-16G appeared at 30 min after injection and the 3H/14C ratio was almost the same as that of the injected compounds. When subject no.2 was injected with the labeles reversed, the results were very similar to those described above. The results indicate that E2 is conjugated directly in the human kidney to form the 17G and 3G and excreted into the urine, whereas the conversion of E2 to E3 occurs systematically rather than in the kidney. In contrast of E3, the kidney appears to play a minor role (no more than 10% of the total E2 is involved) in the conjugation and/or metabolism of E2 in the human.


Plasma prostaglandin E in patients with cancer with and without hypercalcemia. Circulating levels of immunoreactive (i) PGE, calcium and parathyroid hormone (iPTH) were examined in 21 patients with neoplasia and 3 patients with primary hyperparathyroidism. Plasma iPGE was elevated in 4 of 11 hypercalcemic cancer patients; all extracts of liver metastases obtained from 3 of these 4 patients had elevated iPGE levels (metastases = 19.43 +/- 3.43, n = 11; normal liver = 2.04 +/- 0.23; ng/g tissue, x +/- SE, P less than .001). In contrast, only one of 10 normocalcemic cancer patients and none of 3 hyperparathyroid patients had elevated plasma iPGE. There were no apparent relationships between the presence of metastases and either hypercalcemia or elevations of plasma iPGE. Serum iPTH levels were undetectable or below the mean of the normal range in 19 of 21 cancer patients; only the three hyperparathyroid patients had elevated levels. Seven hypercalcemic patients were treated with indomethacin; plasma iPGE decreased in 6 (-34 +/- 10% decrement, n = 6, P less than .01). Decreases in serum calcium occurred only in those patients (2 of 6) who had abnormally elevated plasma iPGE prior to the therapy. It is concluded that plasma iPGE elevations are found in some cancer patients, especially those with hypercalcemia, and that this marker may identify those patients who will respond to indomethacin treatment.


Regulation of renin release by calcium and ammonium ions in normal man. The effect of infusing calcium chloride, magnesium sulfate, sodium lactate, and ammonium chloride on renin secretion was compared to equimolar infusions of hypotonic and normal saline in sodium-deplete normal subjects. The infusion of 75 mEq of ammonium chloride for 60 min in 6 normal, sodium-deplete subjects suppressed plasma renin activity significantly (P less than 0.01) from 4.4 +/- 0.8 to 2.1 +/- 0.2 ng/ml/h, an effect comparable to that produced by normal saline. Sodium lactate (75 mEq sodium/hr) also significantly reduced renin levels at 20-30 min (P less than 0.01). The infusion of 1/3 normal saline (25 mEq sodium/h for 2 h) produced a significant reduction (P less than 0.01) in plasma renin activity (from control levels of 5.2 +/- 0.8 to 3.1 +/- 0.6 ng/ml/h at 90 min). On the other hand, comparable infusions of 50 mEq of magnesium sulfate over 2 h had no effect on renin release (4.6 +/- 0.8 to 4.6 +/- 0.9 ng/ml/h at 2 h), while the infusion of calcium chloride produced an intermediate reduction (5.2 +/- 1.2 to 3.7 +/- 0.8 ng/ml/h at 2 h (P less than 0.05). The observed effects of the hydrogen and calcium ions on suppressing renin release may be secondary to their known actions on renal sodium excretion. Since the infusions of calcium and hydrogen ions both result in an increased delivery of sodium to the distal segment of the nephron, the results may reflect the regulation of renin by the macula densa, a sensitive intrarenal sensor of renal tubular sodium.


Restoration of plasma testosterone levels in uremic men with clomiphene citrate. Five men with chronic renal failure and symptoms suggestive to androgen deficiency were treated with clomiphene citrate (Clomid) at a dose of 100 mg/day for a period of 5 to 12 months. The treatment resulted uniformly in increased libido, sexual potency, and a general sense of well-being. Circulating testosterone rose from mean basal value of 223 +/- 164 to 879 +/- 171 ng/dl (SD), representing a mean increment of 290%. Mean serum lutenizing hormone (LH) and follicle-stimulating hormone (FSH) values before treatment were 76 +/- 40 and 143 +/- 85 ng/ml (SD). During treatment, both LH and FSH increased dramatically to 518 +/- 302 and 787 +/- 291 ng/ml (SD), respectively. Both serum gonadotropin values are expressed as ng/ml of LER 907. The effect of clomiphene on spermatogenesis in these subjects was inconclusive as either improvement or deterioration occured. In these five patients, serum prolactin was not related in any way to testicular function as its values were consistently in the normal range throughout the entire study period. Serum total estrogen, however, was elevated in all; the significance of this high circulating estrogen in relation to gonadal dysfunction in uremia is not clear at the present time. However, we found that normalization of circulating androgen was beneficial to our patients and that long-term clomiphene treatment achieved this goal by increasing pituitary gonadotropin secretion and secondarily stimulating testicular hormonogenesis.


Growth hormone and prolactin release in acromegalic patients following metergoline administration. In six acromegalite patients oral administration of 4 mg of metergoline, an antiserotonin agent, produced a fall in plasma growth hormone (GH) and prolactin (PRL) concentrations. In the same patients this inhibitory effect was observed after administration of dopaminergic drugs, L-Dopa and 2-Br-alpha-ergocryptine. Both GH and PRL levels remained suppressed during a 6 day course of treatmnt with metergoline. These results are consistent with the hypothesis that the inhibitory effect of netergoline on GH and PRL release is determined by inactivation of serotonin receptors in the hypothalamus or at the pituitary.


Spironolactone stimulation of gonadotropin secretion in boys with delayed adolescence. Spironolactone (Aldactone) acts as an antiandrogen by blocking testosterone synthesis and competing with testosterone for the androgen receptor. These properties of the mineralcorticoid antagonist were used in an attempt to interrupt the gonadal-pituitary-hypothalamic negative feedback axis and thereby stimulate LH and FSH in 7 boys with delayed puberty. Following administration of aldactone (5 mg/kg) daily for one week, there was a significant (P less than .01) mean increase in serum LH of 60%. In all 7 boys an absolute rise in LH was observed, but these changes were statistically significant in only 5 individuals. While mean FSH levels increased by 60% in this group of boys, the individual responses were variable. No rise in gonadotropin levels occurred in 2 patients with Kallmann's syndrome, who also received 5 mg/kg of spironolactone daily for 1 week. Large doses of the drug appeared necessary to stimulate gonadotropin secretion since a dose of 3 mg/kg per day did not cause LH or FSH increments in 2 additional patients with delayed puberty. Progesterone and 17alpha-hydeoxyprogesterone levels increased to a greater extent than LH and FSH in response to spironolactone, reflecting either adrenal or testicular enzyme inhibition. Spiornolactone is the first drug shown to be capable of stimulating gonadotropin secretion by interrupting negative feedback inhibition in boys with delayed puberty.


Overnight follicle stimulating hormone (FSH) and luteinizing hormone (LH) excretion in normal males. FSH and LH in acetone precipitates of timed overnight urine collections were measured by radioimmunoassay. FSH and LH urinary excretion extrapolated to 24 h was determined in 147 boys 3-16 years and 20 normal men. FSH and LH (2nd IRP-HMG) progressively increased with age from 1.8 +/- 1.1 (FSH) and 2.1 +/- 1.2 (LH) IU/24 h for the 3-4 year age group to 8.6 +/- 3.2 (FSH) and 18.8 +/- 9.0 (LH) IU/24 h for the 15-16 year age group. FSH and LH excretion increased progressively with stage of sexual development. The integration of several hours of FSH and LH secretion and the accuracy, simplicity and convenience of collecting a single urine sample are advantages of the timed overnight urine collection which should make this technique extremely useful in the evaluation of gonadotropin function.


Urinary progesterone as an index of ovulation and corpus luteal function. Urinary excretions of progesterone (P) during normal menstrual cycle have been measured by radioimmunoassay. The excretion pattern mimics that of plasma P. Measurements of P in a single voided urine may be a reliable substitute for plasma analyses in the evaluation of ovulation and corpus luteal function.


Human puberty: 24-hour estradiol in pubertal girls. Plasma luteinizing hormone, follicle-stimulating hormone, and estradiol were measured at 20-minute intervals for 24-hours in seven pubertal premenarchal girls whose sleep was monitored polygraphically. A circadian variation in plasma estradiol was demonstrated with the highest values occurring during the day (1400-1600 hours) and lowest values during sleep, a time when gonadotropin secretion was augmented.


Prevalence of hepatitis B surface antigen and antibody in white and black patients with diabetes mellitus. The prevalence of hepatitis B surface antigen (HBSAg) and antibody (anti-HBS) was determined in 531 white and 519 black diabetic outpatients and in appropriate white and black control populations. There was no difference between the prevalence of either HBSAg or anti-HBS in either the white or black diabetics and that in the white and black controls. These findings make it unlikely that the vast majority of patients with diabetes mellitus have either an increased susceptibility to infection by the hepatitis B virus or an impaired ability to clear the virus once they are infected.


Quantitation of Friend spleen focus-forming virus by a nine-day 59Fe assay. A previously described 3-day 59Fe assay for quantitation of Friend spleen focus-forming virus has been modified to produce a 200-fold more sensitive 9-day 59Fe assay. A characterization of this assay is reported here. Male BALB/c mice received intravenous injections of appropriately diluted Friend polycythemia virus (FVP); control mice received virus diluent. All mice were allowed food and water ad libitum for 6 days, and on day 6 after virus injection were fasted by removal of food but not water. On day 3 of the fast (the 9th day after virus injection) each mouse received an intraperitoneal injection of 1 muCi of 59Fe. Six hours later the mice were sacrificed and the splenic radioactivity was determined. The percent splenic incorporation of 59Fe was directly related to the logarithm of spleen focus-forming units (SFFU) of FVP injected in a range of approximately 25 to 1,000 SFFU. Using a standard FVP preparation in a dose range of 25 to 1,000 SFFU, it was possible to determine the SFFU titers of unknown samples by extrapolation of the percent splenic 59Fe incorporation to the logarithm of SFFU. SFFU titers obtained by the 9-day 59Fe assay were similar to those obtained by the enumerative-response assay. Advantages of the 9-day 59Fe assay over the enumerative-response assay include a 50-fold greater virus dose range, an easier and a more objective counting procedure, and a reduced coefficient of variation.


Cellular fatty acids and metabolic products of Pseudomonas species obtained from clinical specimens. The cellular fatty acid composition of 112 reference strains and clinical isolates of Pseudomonas species was determined by gas-liquid chromatography (GLC). The presence and relative amounts of cyclopropane, hydroxy, and branched-chain fatty acids were distinguishing features of these strains. Determination of short-chain fatty acids extracted from spent growth media provided an additional means for identifying some strains. Our results show that clinical isolates of pseudomonads can be divided into eight distinct GLC groups. The procedures were especially useful for distinguishing glucose-nonoxidizing pseudomonads, which are difficult to identify by conventional criteria. Since the GLC procedures are simple, rapid, and highly reproducible, they are useful in diagnostic laboratories that process large numbers of cultures. Coupled with selected conventional tests, the analysis of short-chain and cellular fatty acids can be very useful for rapid screening of clinical isolates of Pseudomonas species.


Serum dilution neutralization test for California group virus identification and serology. The serum dilution neutralization test was evaluated for serological diagnosis of California group arbovirus infections and identification of virus isolates. The technical advantages and the degree of subtype specificity of the serum dilution neutralization test over the hemagglutination inhibition test and the complement fixation test were demonstrated with paired specimens from human cases, single human survey sera, and sentinel rabbit sera. Twenty-one virus isolates from various geographical areas of the United States were also used to evaluate the efficacy of the serum dilution neutralization test for specific virus identification.


Long-chain fatty acids of peptococci and peptostreptococci. The long-chain fatty acids extracted from the whole cells of 12 clinically significant species of peptococci and peptostreptococci were characterized by gas-liquid chromatography. The resulting methylated fatty acid profiles (and some unidentified compounds) of 82 strains allowed the 12 species to be separated into four groups. Fifteen strains of Peptostreptococcus anaerobius were placed in group I because they had a unique, prominent compound that occurred in the area where a C8 to C10 fatty acid would be expected. Group II, consisting of Peptostreptococcus intermedius, Peptostreptococcus micros, Peptostreptococcus parvulus, Peptococcus morbillorum, and Peptococcus constellatus, produced C14, C16:1, C18:1, and C18 fatty acids. Peptococcus prevotii, Peptococcus variabilus, Peptococcus magnus, Peptococcus asaccharolyticus, and Peptostreptococcus productus were placed in group III because they contained three to six additional, unidentified compounds that strikingly differentiated them from group II. Peptococcus saccharolyticus was the single species assigned to group IV because it yielded C14, C16, C18:1, C18, and C20 fatty acids and a prominent unidentified peak that occurred between C14 and C16 fatty acids. This study indicated that cellular long-chain fatty acids may be an important tool in clarifying the taxonomy of the peptococci and peptostreptococci.


Abnormal responses to rubella infection. Two cases of rubella are described which caused initial problems in laboratory diagnosis due to abnormal features in the immune response. One patient presented with thrombocytopenic purpura and associated circulating immune complexes. The other patient, who was in early pregnancy, had an unusually prolonged rash and a delayed humoral immune response. The possible reasons for the difficulties in serological confirmation are discussed.


Characteristics of a strain of Clostridium carnis causing septicaemia in a young infant. Clostridium carnis is a species which is only rarely isolated from man or animals and is occasionally found in the soil. This paper is an account of a single isolate found in blood cultures obtained from an 8-week-old boy who was suffering from gastroenteritis.


Marine vibrios associated with superficial septic lesions. Three cases are reported in which a marine vibrio, Vibrio alginolyticus, was isolated from superficial septic lesions. All cases had been exposed to sea-water. The possible significane of these findings and the need for further investigations are discussed.


Adenosquamous carcinoma of the endometrium. An adenosquamous carcinoma of the endometrium is one which contains both malignant glandular and malignant squamous components; such tumours are considered rare in Britain but are thought to account for nearly one-third of all endometrial neoplasms in the United States. A survey of 675 cases of endometrial cancer seen during the period 1956-75 showed that the incidence of adenosquamous carcinoma was 5%, an incidence that remained static during this 20-year period. The principal difficulties encountered in the diagnosis of these neoplasms are in identifying the squamous component as such and in differentiating it from benign metaplastic squamous epithelium. The prognosis for patients with an endometrial adenosquamous carcinoma is very much worse than for women with a pure adenocarcinoma, and because these neoplasms are often wrongly identified it is possible that the currently accepted prognoses for both pure adenocarcinoma and adenoacanthoma of the endometrium may have to be revised. There appears to be a true variation in the incidence of this neoplasm between Britain and the United States.


A case of primary lymphoma of the liver. A case of primary malignant lymphoma of the liver is described. Presenting with epistaxis, he died in hepatic encephalopathy with an intractable bleeding post-bulbar duodenal ulcer.


Factor VII as a marker of hepatocellular synthetic function in liver disease. Factor VII levels have been measured in 100 patients with liver disease following parenteral vitamin K1 therapy. There was good agreement between specific factor VII measurements and the one-stage prothrombin time apart from six patients with compensated cirrhosis in whom the prothrombin time was prolonged despite the presence of normal factor VII levels. A mean activity of 58% was found in patients with cirrhosis. Cirrhotic patients with features of hepatic decompensation had a significantly lower mean level of activity (40%) than the "contrast" patients with surgical obstruction of the major bile ducts (93%). Patients with chronic active liver disease had moderate depression of factor VII levels and those with non-cirrhotic liver damage had mean activities similar to the contrast group. Factor VII levels could not be correlated with BSP retention but there was a correlation with serum albumin concentration. It is concluded that the prothrombin time using Quick test with a standardized thromboplastin showing good sensitivity to factor VII, eg, the Manchester reagent (BCT), provides a reliable index of coagulability in chronic liver disease, and specific factor VII assays are not indicated.


An interpretation of the serum alkaline phosphatase isoenzyme patterns in patients with obstructive liver disease. Earlier studies have identified two main isoenzymes of alkaline phosphatase in the sera of patients with obstructive liver disease. This paper reports on a study of these isoenzymes in specific types of liver disease where the pathology in relation to bile duct obstruction is known. The results have been used to support the theory that in biliary obstruction the increase in serum alkaline phosphatase is in part due to regurgitation of the biliary isoenzymes.


Biochemical indices of osteomalacia in pregnant Asian immigrants in Britain. Serum calcium, phosphate and alkaline phosphatase, and urinary calcium excretion were examined during the second trimester of uncomplicated normal pregnancy in Asian immigrants to Britain and in local Caucasians. The mean serum calcium was significantly lower in Asians than in Caucasians, and the mean serum alkaline phosphatase was significantly higher in Asians. The geometric mean of the urinary calcium excretion was highly significantly lower in Asians than in Caucasians. The variances of the serum calcium, serum alkaline phosphatase, and urine calcium excretion did not differ significantly in the two populations. This indicates that there is a shift in values of immigrant Asians as a group compared with Caucasians. A comparison with figures obtained on normal nonpregnant persons of both suggests that the shift is not an inherent feature of the Asian population.


Clinical and immunochemical study of the serum IgG fraction not precipitated in a zinc-sodium salicylate reagent. A reagent made of zinc sulphate (0-08 M) in a 0-4 M sodium salicylate solution at pH 7-3 precipitated most of the IgG when a small volume of human serum was added. Sera with normal IgG levels or polyclonal hyperglobulinaemia showed a close correlation between total IgG and zinc-precipitated IgG (r = + 0-95). In clinical material, not including IgG myeloma, zinc-soluble IgG varied between 0 and 6 mg/ml and was independent of the IgG serum concentration. In 31 normal subjects the average IgG concentration, as determined by the Technicon immunonephelometric method, was 10-2 +/- 1-7 mg/ml for total IgG and 2-2 +/- 1-0 mg/ml for the soluble fraction. Among 173 sera, including 24 from cord blood, 16 from pregnant women, and 133 from patients with miscellaneous diseases, no pathological conditions except three cases of IgG myeloma were found with a zinc-soluble IgG definitely above the normal values; zinc-soluble IgG levels were often low in patients with hyperglobulinaemia, and the difference was highly significant in liver disease. kappa and gamma light chains as well as the four IgG-Hp chain subclasses were found in both zinc-soluble fractions of normal IgG. A study of myeloma monoclonal IgG showed that globulins of classes 1, 3, and 4 could be either soluble or insoluble in the zinc reagent. One, G2, was mainly insoluble. Hexose and antistreptolysin contents per milligram normal IgG were not significantly different in either fraction. It is suggested that zinc-soluble IgG consists of the recently synthesized molecules, the zinc-solubility of which has not yet been decreased by protein association, lipid interaction, antigen binding, or enzymatic denaturation. Within this hypothesis, a low level of soluble IgG would mean either an increased precatabolic protein or a decreased synthesis.


Improved antibody detection by the use of range expansion and longer filter wavelength in a low ionic strength-protamine sulphate Auto-Analyzer system. Range expansion, achieved by insertion of a variable resistance between the colorimeter and the recorder together with the use of 550 nm colorimeter filters, has resulted in markedly improved sensitivity for antibody detection, and improved sample identification, in a low ionic strength-protamine sulphate (LISPS) system. Range expansion also permits a lower concentration of red cells to be used, thus economizing on fully typed cells. Glycerol stored frozen cells were found to be only slightly less sensitive than fresh cells in this system.


Removal of non-specific serum inhibitors of haemagglutination of rubella virus by treatment with dodecylamine-gel. The suitability of using dodecylamine-gel for removing the serum non-antibody-like inhibitors of haemagglutination by rubella was studied. Compared with kaolin and MnCl2/heparin treatment this new procedure appears to have a higher specificity since it removes the non-antibody-like inhibitors from serum without affecting the immunoglobulin level significantly. The potential application of this procedure in routine serological analysis for rubella virus infection is discussed.


Staphylococcal protein A; its preparation and an application to rubella serology. Good yields of staphylococcal protein A are obtained by growing the staphylococcus Cowan type 1 on cellophane agar. The activity of these preparations in removing immunoglobulin G (IgG) from human serum can be readily measured by the Mancini radial-diffusion technique and the correct in-use dilution determined. Treatment with protein A of sera from women with a history of rubella may help in the identification of those having specific antibody in the IgM and IgA fractions. This relatively simple procedure may have worthwhile application in the diagnosis of rubella.


The use of time-expanded speech as an aid in the diagnosis of articulation disorders. The recordings of 20 speech defective speakers' readings of a standard prose passage were presented to 36 student speech clinicians under three listening conditions: (1) unaltered; (2) time expanded to 150% of the original recording time; and (3) time-expanded to 200% of the original recording time. Results of their evaluations indicate that the expanded versions of the recordings elicited more accurate evaluations by the student clinicians. Implications of these findings concerning the possible usefulness of time-expanded speech as an aid in the training of listening skills in student speech clinicians are discussed.


Perceptions of auditory components of stuttered speech. Two student groups, one of speech pathology majors and one a class of mixed background fulfilling a humanities requirement, listened to the same set of sentences spoken first in nonstuttered and then in stuttered form. Subjects rated each replication along a set of 114 semantic differential-type adjectives but on 10-point unipolar scales. These scales had previously been factor analyzed and represented 31 positive and 29 negative perceptual factors. The results indicate that all college students react favorably to stuttered speech. However, six factor differences significant at the 0.05 level or above emerged between the two groups when evaluating the stuttered version. These results suggest that pathology students do not perceive stuttered speech as do nonpathology students; they are more favorably disposed on every dimemsion.


Therapist habituation and purported client progress in articulation therapy. Ten graduate student clinicians, in their final year of training, evaluated the tape recorded pretherapy performances of 10 /s/-defective children on the 68 /s/ items of the McDonald Deep Test of Articulation (1964). Five of the 10 clinicians were randomly selected and assigned one of these /s/-defective children as part of their regular case load. The children were seen for 1 hr per week for a 5-week period. The clinicians were not informed as to the nature of the study or that the composition of their case load was in any way connected with the tapes that they had previously evaluated. The five remaining clinicians and children did not participate in therapy during this 5-week period. Immediately following this 5-week period, an additional tape recording was made of all 10 children's responses to the /s/ items of the McDonald Deep Test (1964). Both pre- and posttreatment tapes were then evaluated by all 10 clinicians in independent listening sessions. Significant between-tape differences, indicative of both habituation and sensitization to client errors within the in-therapy clinicians only, are discussed in terms of their clinical applications.


Perseveration in brain-injured adults.

Perseveration in brain-injured adults. Despite the acceptance of perseveration as a characteristic sign of disturbed CNS functioning, objective data relative to its nature and occurrence are noticeably lacking. Data obtained in this study, not unexpectedly, indicate that perseverative responses occur more often in brain-injured than in normal subjects. The brain-injured subject most likely to evidence perseveration appeared to be one who (1) had suffered a CVA (2) less than 6 months ago that (3) resulted in aphasia. Two types of perseveration, repetitious and continuous, were noted in the responses of the brain-injured with higher incidences of the repetitious type occurring. It was felt that the behavioral definitions used to differentiate between repetitious and continuous perseveration allowed for reliable judgments between observers.


The recovery process of a bilingual aphasic. The recovery process during the first year poststroke in an English-Japanese bilingual aphasic is analyzed with special emphasis on the effect of language therapy. The patient initially manifested equally severe impairment in both English and Japanese involving all language modalities with moderate impairment of reading and auditory comprehension and severe impairment of oral production and writing. Language therapy was conducted in English in a community where Japanese was the only language in the environment. In the course of language therapy, auditory and reading comprehension improved almost simultaneously in both English and Japanese. In contrast, oral language production and writing abilities improved markedly only for the treated language (English). The results are discussed in terms of their implication for the effect of language therapy on aphasia.


Effects of task difficulty on sentence comprehension performance of aphasic subjects. Twenty aphasic subjects participated in an auditory comprehension task in which they were asked to point to pictures named by the examiner. The spoken commands delivered to each subject were either "easy" or "difficult," as determined by the subject's performance in a preexperimental session. Difficulty was determined by the number of items that the subject was asked to point to in sequence. Each subject performed in two conditions. In the Low Error Condition, a small number of difficult commands (as determined in the preexperimental session) was interspersed in a larger number of easy commands (as determined in the preexperimental session). In the High Error Condition, a small number of easy commands was interspersed in a larger number of difficult commands. Analysis of the results indicated that presentation of a series of difficult commands interfered with subject's subsequent performance to commands that would ordinarily be very easy.


Concurrent modification of incorrect responses and off-task behaviors occurring during articulation instruction. Incorrect articulation responses and inappropriate off-task behaviors occurring during programmed articulation instruction were concurrently modified by the presentation of an identical punishing stimulus for both groups of behaviors or by the presentation of different punishing stimuli for each group of behaviors. Results indicated that both procedures were equally effective in reducing both groups of undesirable behaviors. The nature of the relationship between articulation responses and off-task behaviors is discussed in detail, especially in terms of behavioral covariation.


The influence of task presentation and information load on the adaptation effect in stutterers and normal speakers. Fourteen stutterers and 14 normal speakers read two passages differing in information value under two different conditions. Condition I provided subjects with a priori knowledge regarding the experimental limits and requirements. Condition II withheld such knowledge. Results indicate that adaptation curves for both stutterers and normal speakers were influenced by the information value of the reading passage. Less adaptation was observed with the high information than with the low information passage. The task presentation variable differentiated stutterers from normal speakers. When a priori instructions were provided to stutterers, the adaptation curve assumed a smooth, decelerating course. When a priori instructions were withheld, the curve deviated from the expected course. For normal speakers, identical adaptation trends were observed whether or not a priori instructions were provided. Stuttering adaptation is a function of both linguistic and situational variables; normal nonfluency adaptation is primarily a function of linguistic variables. Theoretical, experimental, and clinical implications are offered.


Access to usual source of care by race and income in ten urban areas. In terms of less access to private sources of care (as distinguished from hospital-public clinics) and longer travel time to usual source of care, poverty areas are at a disadvantage. Within the ten areas studied, the poor have less access than the nonpoor, with access differences even greater between the races than between income groups. Blacks generally have less than whites when income differences are taken into account. Both the type of usual source of care and travel time appear to be related to differential utilizations of ambulatory care resources: persons reporting private sources of care and persons with shorter travel time to their usual source of care tend to make more physician visits in a year. Mechanisms for public financing of health care will not likely alleviate the problems of inaccessibility presented by poverty areas. It is in these areas of low access that public responsibility to organize and locate facilities will continue even after the advent of a fairly comprehensive payment mechanism for health care among the poor.


Health services, health status, and work loss. The numbers of workdays lost because of illness, coupled with records of health service utilization patterns, were studied to establish possible links between health status and different forms of prepayment coverage. The records of industrial workers at four branches of the same company were analyzed. Records of employees with broad-benefit coverage were compared with those who had less-comprehensive indemnity coverage. A free choice of providers was available to the study population. Data for workers covered by the broader plans revealed fewer medical admissions to hospitals, more surgical admissions, and more outpatient physician visits. As hypothesized, their number of days absent from work were lower. Because few of these results were statistically significant, caution is necessary in their interpretation. Some aspects of the project warranting further consideration are discussed. Data suggest a positive correlation between breadth of health plan coverage and health status, with possible economic benefits to be derived from such coverage. The data also indicate the desirability of additional investigations to be based on employers' and health plan records, that involve other types of populations and other benefit options.


Interpreting legislative voting patterns on health issues: a method and rationale. Crucial decisions affecting the health field are increasingly being made in the political arena. To interpret and effectively influence these political events, the health specialist must become acquainted with the political decision maker's perspective on health issues. This report presents a method for analyzing legislative voting patterns to determine the issue structure within which health-related legislative decisions are made. Once this issue structure has been determined for a given legislative body, relevant strategies for influencing the decision-making process can be designed.


Bridging the gaps between departments on community and family medicine: the Calgary experience. Current emphasis on innovation in primary care has revealed conflicts between generalist clinicians and professionals in community medicine. Several problems are now evident in the combination of community medicine and family medicine. Three elements of a planned institutional approach to overcome problems in primary health care education at the University of Calgary, Faculty of Medicine, are discussed: the introduction of an integrated curriculum, de-emphasis of departments, and a center for ambulatory care.


Screening high-risk populations: a challenge to primary medical care. The organizational, educational, and policy implications of screening high-risk populations are considered for five selected conditions: (a) the role of pregnancy-risk indices for the identification of high-risk women as it relates to the efficient use of perinatal and neonatal intensive care centers; (b) screening school-age children for conductive hearing loss, with emphasis on the role of complete otologic examination, threshold testing, and tympanometry in children with a history of recent or recurrent middle ear disease; (c) the efficacy of Pap smears in reducing mortality from cervical cancer; (d) the current status of clinical examination and mammography for detecting breast cancer; and (e) the problems inherent in diagnosing and treating hypertension. Because of the increasing costs of new technology that have not yet been adequately tested, health professionals bear an increasing obligation to require scientific evidence of the efficacy of the screening procedures before instituting large-scale programs.


Central projections of the chorda tympani nerve in the mallard, Anas platyrhynchos L. The central projections of the chorda tympani nerve in the duck were studied by means of the Fink-Heimer technique. Following section of the VIIth nerve proximal to the geniculate ganglion terminal projections of the CT are found in the sensory nucleus N VII (sVIId) on the dorsum of the descending trigeminal root, the n. presulcalis anterior solitarii, the n. sulcalis anterior solitarii p. dorsalis and p. ventralis, and the n. ventrolateralis anterior solitarii (Vla). Small quantities of terminal degeneration are also found in the n. intermedius anterior and the lateral substantia gelatinosa of the solitary complex. A number of fibers decussate to terminate contralaterally in corresponding portions of the opposite solitary complex. Comparison with data of the pigeon reveals a limited overlap of projections of the chorda tympani nerve and of the nodose ganglion, respectively, in the dorsal and ventral parts of the n. sulcalis anterior. We suggest that the regions sVIId and Vla alone may convey gustatory information.


Growth of lobster giant axons: correlation between conduction velocity and axon diameter. The conduction velocity and axon diameter of medial and lateral giant axons in lobsters was followed during growth from early juvenile (13 mm) to adult (250 mm) forms. In both axons, conduction velocity increased more than 4-fold in the growth period examined. Correlated with the increase in conduction velocity is an increase in axon diameter and the relationship between these two parameters is expressed by the equation CV = krX, where X equals 0.5 for the lateral and 0.7 for the medial giant axons. The sheath surrounding the giant axons also increases in size during growth with that of the medial giant axon being considerably thicker than that of the lateral giant axon. The significance of the increase in axon diameters is to increase conduction velocity and thereby reduce the latency of the escape response mediated by these giant axons.


Patterns of cell and fiber distribution in the neocortex of the reeler mutant mouse. In the neocortex of the reeler mutant mouse, there is inversion in the normal relative positions of polymorphic and pyramidal cells and of large with respect to medium-sized and small pyramidal cells. Granule cells are concentrated at a near-normal mid-cortical level in the mutant. As in the normal animal, and despite cell malposition in reeler, the principal tangential fiber system lies in the zone of polymorphic cells. Large fiber fascicles, known from experimental studies to be principally thalamo-cortical afferents, enter the tangential fiber system in the polymorphic cell zone of both reeler and normal neocortex. In the mutant these fascicles must traverse the full width of the cortex to reach this fiber system in its superficial location. In both normal and mutant animals single fibers, again principally thalamo-cortical afferents, pass from the principal tangertial fiber system to ramify in a fiber feltwork in the zone of granule cells. In the mutant these descend whereas in the normal animal they ascend. Also, as in the normal mouse, single fibers pass radially between all levels of the mutant cortex and the central white matter. Regional variations in the character, the pattern of distribution and the relative prominence of homologous cell and fiber elements are closely parallel in reeler and normal. This suggests that cell differentiation and the tangenital organization of reeler neocortex are normal despite cell malposition in the mutant.


Electron microscopic observations of nodes of Ranvier in the external cuneate nucleus. During the course of an investigation of the synaptic organization of the external cuneate nucleus (ECN) in the Sprague-Dawley albino rat, the ultrastructural morphology of nodes of Ranvier in the neuropil has been studied. The majority of nodes observed have the basic morphological features of conventional central nodes but there is individual variation with regard to length, surface area and cytoplasmic organelles. In addition, nodes with multiple myelinated branches are observed. Some nodes of Ranvier were observed to form specialized synaptic boutons. Two types of nodal synaptic boutons were present; a simple type and a complex type. Simple nodal boutons were observed more frequently. These nodes usually synapse upon a single dendritic element; the portion of the node opposite the presynaptic area has a morphology similar to conventional nodes. Complex nodal boutons are of greater dimension than simple nodal boutons and are usually in contact with several neuronal elements. They may be presynaptic to dendritic shafts or spines and are occasionally observed to be postsynaptic to small axonic profiles, a synaptic relationship which, until this report, has not been demonstrated in the central nervous system (CNS). The possible functional significance of these observations is discussed.


An anatomical study of some somesthetic afferents to the intercollicular terminal zone of the midbrain of the opossum. Following lesions of the dorsal column nuclei, spinal cord and sensorimotor cortex, anterograde degeneration was traced to a common target in the central midbrain; the intercollicular terminal zone. Although not all the midbrain projections of the three pathways are contained within this zone, it receives overlapping projections from each of the three body-related somesthetic pathways studied. The intercollicular terminal zone covers the entirety of the external nucleus of the inferior colliculus and the intercollicular nucleus of Mehler, spilling over into adjacent parts of the central gray and deep layers of the superior colliculus. Little evidence of somatotopy in the somesthetic projections was disclosed, and bilateral input was found in each experimental case, regardless of the type of lesion. Golgi-stained material was examined to explore the basis of the extensiveness of the terminal zone. These materials showed that the dendritic spread of neurons in the external nucleus of the inferior colliculus and the intercollicular nucleus, taken together, covers the entirety of the intercollicular terminal zone. That is, the dendrites invade the same portions of the central gray and deep layers of the superior colliculus which are covered by the terminal field. We conclude that a tripartite division of the sensory midbrain may be justified: with the somesthetic modality being represented anatomically in a fashion at least roughly analogous to that of vision and audition.


Cutaneous nerve lesions in prurigo nodularis. Electron microscopic study of two patients. Skin biopsies from two patients with pruirgo nodularis were studied with the electron microscope. Lesions were found in the cutaneous myelinated and unmyelinated nerves. Schwann-cell cytoplasm showed large, irregular, membrane-bound, electron-lucent vacuoles. Umyelinated axons were distended and devoid of neurotubules and neurofilaments. Myelinated nerves showed various degrees of demyelination. Onion-bulb formations with a centrally located myelinated fibre were also observed and numerous mast cells were found in the cellular infiltrate. All these findings indicate the presence of a chronic peripheral neuropathy, the etiology of which remains to be determined.


Cell renewal in discoid lupus erythematosus. Cell proliferation has been evaluated in four patients with discoid lupus erythematosus after in vivo incorporation of tritiated thymidine. Numerous epidermal cells are in S phase or in mitosis. The acceleration of cell renewal is paralleled by a shortening of the transit time of completely differentiating keratinocytes. Remodellings of the vascular belt are evidenced by the labeling of many endothelial cells. There is no sign of lymphoblastic transformation in the dermis since the mononuclear infiltrate remains unlabeled.


Lobomycosis. Report of the eighth Colombian case and review of the literature. The eighth Colombian case of lobomycosis and the one hundredth in the world literature is reported here. The patient was a 38-year-old female who showed a bilobed mass on the left forearm which had appeared at the site from where a similar lesion had been excised 19 years previously. She had always lived in a rural area, located in the humid subtropical forest. The tissue reactions to the fungus as well as the fruitless attempts to culture it are described. An analysis of the relevant literature is made and suggestions for experimental animal models are given in the text.


The epidermal component of melanocytic naevi. Two hundred moles were examined histologically and the degree and type of epidermal change was recorded and correlated with the arrangement, density and type of naevus cells present and with the clinical presentation. Resemblances to the epidermal architecture of seborrhoeic warts were noted in 49% of the moles studied (this type of change was mainly seen in younger patients). In these there was a predominance of epithelioid cells, mainly in the junctional and upper dermal zones. Thirty-five per cent of moles possessed an epidermis with an overall appearance of being stretched, beneath which was a relatively clear zone followed by a uniform distribution of predominantly "lymphocytoid" naevus cells and large numbers of naevus cells of the giant type. These were found mainly in the older age groups. A third group (11%) was characterized by the presence of bulbous epidermal rete ridges and many junctional nests of naevus cells. This group was found mainly in younger age groups and there was often a history of recent change in the mole. It is concluded that the epidermal component of moles might itself be a naevoid disorder or result from the dermal disturbance induced by the mole cells.


Solitary keratoacanthoma of the nipple in a male. Case report. A heretofore undescribed localization for solitary keratoacanthoma, namely the skin of the nipple, is reported. The tumor developed in a 69-year-old man who had suffered a trauma in the thorax near the left nipple 5 months before. A possible origin in mammary ducts, considering the breast as a modified sweat gland, is discussed.


Dermal vessels in acrodermatitis chronica atrophicans. An ultrastructural investigation of two patients suffering from acrodermatitis chronica atrophicans revealed in the small dermal vessels swelling of the endothelial cells, material of probably plasmatic origin accumulated in the subendothelial area, and sleeves of basement membrane-like material on a concentric perivascular layout.


Effects of positive and negative feedback on behavior control in hyperactive and normal boys. The hypothesis that hyperactive boys have relatively less response to negative feedback than to positive feedback was studied. Sixteen hyperactive boys and 16 controls were compared on two tasks under different feedback conditions. Feedback conditions were no feedback, positive feedback, and negative feedback. Tasks were symbol encoding and correcting spelling words. Hyperactives and controls were compared in amount of time on-task and amount of work correctly completed. Hyperactives were on-task significantly more under conditions of negative feedback than under positive feedback, but negative feedback significantly increased errors on the spelling correction task. Controls were equally responsive to positive, negative, or no feedback. Hyperactives accomplished significantly less than controls on the coding task, but performed as well as controls on the spelling correction task, which was administered to each boy at his own level of spelling ability. The results imply that while consistent negative feedback can reduce off-task behavior for hyperactives, it can also decrease the accuracy of the work they are doing.