Quantitative determination of 4-N-2-acetamido-2-deoxy-beta-D-glucopyranosyl-L-asparagine in the urine of patients with aspartylglycosaminuria by gas-liquid chromatography. A specific and sensitive method for the quantitative ;determination of glcNAc-Asn in the urine of patients with inherited deficiency of the lysosomal hydrolase N-aspartyl-beta-glucosaminidase is reported. The method is based on GLC assay of GlcNAc-Asn as its methylated derivative and requires 100 microliter of urine. The mean urinary excretion of GlcNAc-Asn in 14 AGU patients was 0.99 mmol/24 hr (range 0.15 to 1.88). Young patients had similar urinary levels of GlcNAc-Asn to those of the older ones when the results were calculated on the basis of creatinine excretion. Mass fragmentographic analysis revealed the presence of minimal amounts of GlcNAc-Asn in normal urine also. In four of the eight normal subjects studied, a rough quantitative estimation was feasible; the urinary output of GlcNAc-Asn in these subjects ranged from approximately 0.001 to 0.01 mmol/24 hr.


The effect of extremely high sodium intake on plasma renin activity, plasma aldosterone concentration, and urinary excretion of aldosterone metabolites. The effect of sodium intake on aldosterone production was examined in eight healthy men whose urinary sodium excretion approached their dietary sodium intake at levels of 10, 300, 800 and 1500 mEq sodium/day. Aldosterone secretion was estimated from the excretion rate of two aldosterone metabolites: Thaldo and aldosterone-18-glucuronide. Maximal suppression of aldosterone secretion appeared to have been reached when sodium intake was 800 mEq/day, since no further decrease in aldosteron metabolite excretion rates was observed at 1500 mEq/day dietary sodium. Both plasma renin activity and plasma aldosterone concentration were suppressed and approached or were below the detection limits of the respective radioimmunoassays when sodium intake reached 800 and 1500 mEq/day. Body weight and blood pressure significantly increased at each increment of sodium intake. Our findings show that when sodium intake is extremely high, aldosterone secretion does not decrease to zero but continues at a rate we estimate to be 10 to 30 microgram/day. We suggest that this nonsuppressible secretion of aldosterone may have contributed to the observed increases in weight and blood pressure.


Human plasma P component (protein AP): changes during growth and development and evidence for hepatocellular synthesis. A monospecific rabbit antibody to human plasma P component was used in a quantitative immunoelectrophoretic system. The assay readily detected levels as low as 0.3 microgram/ml, the equivalent of 0.008 U/ml of a normal plasma pool. he average coefficient of variation of duplicate determinations from five sets of nine dilution points of normal plasma was 6.6%. Among normal individuals, groups of 50 adults, 24 children, and 43 term and preterm newborns were each significantly different (p less than 0.001) and the level was positively correlated with age. Three fetal samples of approximately 20 weeks' gestation were near the lower limit of detection of the assay. P component levels in selected groups of patients demonstrated  a 1.5 fold elevation of the mean level in 15 patients with high erythrocyte sedimentation rates, no difference in the mean level of 23 patients on warfarin or 16 patients with plasma cell dyscrasia or chronic lymphocytic leukemia, and a depression of the mean level to one fourth of normal in 14 patients with alcoholic liver disease. Among the latter, the prolongation of the prothrombin time was correlated with the depression of P component (p less than 0.05). Conditioned media, even after 10-fold concentration, and lysed cell fractions of cultured adult fibroblasts, B and T lymphocytes, and endothelial and smooth muscle cells failed to demonstrate P component. Circulating levels of P component increase during growth and development to adult life and the hepatocyte is the most likely site of synthesis. Although homologous in structure, C-reactive protein levels are distinguished by their marked response to inflammation and their elevation in most of the patients with hepatocellular damage.


Metabolic studies in two families with hyperornithinemia and gyrate atrophy of choroid and retina. Studies on the metabolism of selected amino acids were carried out in five patients with gyrate atrophy of the choroid and retina and four obligate heterozygotes. Hyperornithinemia, hyperornithinuria, and hypolysinemia were found in all patients. In one of the patients, the condition was diagnosed as early as 4 years of age. Ornithine loadings in the affected individuals did not induce the expected elevation of plasma glutamic acid and proline. Oral lysine tolerance tests in patients resulted in (1) enhancement of the hyperornithinuria and hyperlysinuria and (2) elevation of plasma lysine levels, which were below values obtained from normal controls. Supplementation of the regular diet with lysine for a period of 1 month increased plasma lysine but had no effect on plasma ornithine concentration.


Regulation of fibrinogen biosynthesis: effect of fibrin degradation products, low-molecular-weight peptides of fibrinogenolysis, and fibrinopeptides A and B. Fibrinogen synthesis in rabbits was evaluated following intravenous infusions of stage 3 degradation products of homologous fibrinogen or fibrin, prepared in vitro. Fibrinogen production was measured by determining the rate of appearance of 75SeM into circulating fibrinogen. Fibrinogen synthesis increased threefold after the administration of stage 3 FDP (D and E), dialyzed to remove LMW digestion fragments,  In contrast, the fdp obtained by plasminolysis of crosslinked thrombin clots or of noncrosslinked ancrod or thrombin clots failed to enhance basal fibrinogen production. Accelerated fibrinogen production was not accompanied by alterations in haptoglobin concentration or by increased incorporation of 75SeM into haptoglobin. Fibrinogen synthesis was not increased after infusions of FPA and FPB.


Genetically determined deficiency of glucose 6-phosphate dehydrogenase (type-A-) is expressed in the liver. G6PD activity was determined in liver biopsy specimens from 31 patients (25 men and six women). The G6PD genotype of the patients was determined by carrying out on lysates of their red blood cells quantitative assays of the enzyme and starch-gel electrophoresis. In 21 subjects with normal G6PD activity in red cells, a relatively wide variation of G6PD activity was found in liver extracts. By contrast, in 10 subjects with G6PD deficiency, the activity of the enzyme in liver extracts was always low. The difference between the distribution of liver G6PD activity values of G6PD-normal and G6PD-deficient subjects was statistically significant (p less than 0.01). We conclude that G6PD deficiency of the African type is also expressed in the liver. These findings may have a bearing on hyperibilirubinemia, which cannot be entirely attributed to hemolysis, often encountered in G6PD-deficient patients.


Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. 1. Antigen-dependent inhibition and antigen-independent inhibition and enhancement of migration. The effects of DLE containing TFd activity from immune human donors on PBL, obtained from individuals nonresponsive to either PPD or Cocci antigen, were evaluated in vitro by the agarose LMl technique. Several different preparations of DLE were employed to evaluate the specificity and reproducibility of the effects: (1) from donors skin test positive to PPD but negative to Cocci, (2) from donors skin test negative to PPD but positive to Cocci, (3) from donors skin test positive to both antigens, and (4) from donors skin test negative to both antigens. With PBL from other human donors used as target cells in the direct agarose LMi technique, three types of effects were demonstrated for all preparations of DLE: (1) antigen-dependent specific LMl, (2) antigen-independent or nonspecific LMl, and (3) antigen-independent enhancement of migration. The demonstration of each activity was found to depend on the concentration of DLE used and the time allowed for migration. In experiments employing purified PMN and MNL as target cells and a two-step indirect LMl assay, it was shown that the antigen-independent effects resulted from the direct of components in DLE on PMN. The antigen-independent inhibition was shown not to result from toxic effects of DLE. It was produced by DLE but not by dialyzable liver or skin extracts when tested using an amount equivalent to DLE as judged by the absorbance at 260 and 280 nm. The antigen-dependent LMl was found to require secretion of a soluble mediator of molecular weight near 69,000, believed to be LMl. Our results indicate that the agarose LMl technique is a useful in vitro assay for studies of the mechanism of action of components in DLE which can specifically convert nonimmune lymphocytes to a measurable antigen-sensitive state (i.e., transfer factor). The antigen-independent effects of DLE may be responsible in part for previously reported nonspecific beneficial effects of DLE when used in immunotherapy.


Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. II. Separation and partial characterization of the components in DLE producing antigen-dependent and antigen-independent effects. Previous studies have shown that DLEs with TFd activity produce both Ag-dependent specific effects (mediated by TFd) and Ag-independent effects on CMl as demonstrated in vitro by agarose LMl. In the present study, Sephadex G-25 gel filtration provided a simple method for separating the DLE components responsible for each effect into distinct fractions. Ag-independent LMl was produced predominantly by Sephadex fraction l, of MW greater than 5000. The active components, further purified on Bio-Gel P-10, were shown to be of MW 14,000 to 17,000 and to contain both polypeptide and ribonucliotide material. The Ag-independent LMl activity was stable to heating at 56 degrees C for 30 min but was partially destroyed at 80 degrees C for 30 min, and the responsible components were shown to act on PMN directly. Ag-independent ELM was produced exclusively by material in Sephadex G-25 fraction V and also acted directly on PMN, whereas the Ag-dependent specific LMl activity was found predominantly in fraction lVb and to a lesser extent in fraction V and could not be detected in a direct assay using only PMN. In addition, a new activity, designated "Ag-dependent ELM activity," which caused increased migration in the presence of Ag, was found in Sephadex fraction lVa. This latter activity might mask the Ag-dependent LMl activity in fraciton lVb. Bio-Gel P-2 chromatography separated the components producing Ag-dependent and Ag-independent effects in fraction V into two separate subfractions (Va and Vb) of MW 1100 to 2000 and less than 900. The activity in fraction lVb eluted at a position identical to that of the components in fraction Va on Bio-Gel P-2. Fractions Va and Vb contained both polypeptide and ribonucleotide material. The Ag-dependent specific LMl or TFd activity was found to be partially inactivated at 56 degrees C and completely destroyed at 80 degrees C. The components responsible for this TFd activity were further purified by HPLC on ODS resin. The TFd activity was mediated by components with retention times much greater than that of adenosine 3'-monophosphate. The active fraction was composed of both polypeptide and ribonucleotide material but did not contain deoxyribonucleotides.


Deoxyhemoglobin S gelation and insolubility at high ionic strength are distinct phenomena. Deoxyhemoglobin S in solution forms a solid phase either in solutions of high ionic strength or in solutions of low ionic strength but a high hemoglobin concentrations. Presently, both techniques are in use to study various hemoglobin interactions which might occur during sickling of Hb S-containing red cells. When Hb S is treated with either nitrogen mustard or cyanate, there is no correlation between high-ionic-strength salting out and low-ionic-strength gelation studies. These results suggest that salting out studies are not equivalent to the assays that depend on the gelation of polymerization of Hb S.


Glucocorticoid-mediated inhibition of erythroid colony formation by mouse bone marrow cells. The ability of bone marrow cells, obtained from mice pretreated with the synthetic glucocorticoid dexamethasone, to form erythroid colonies in vitro was studied. The results show that these bone marrow cells form a reduced number of erythroid colonies in vitro in response to Epo. This effect is evident after single injection (1 mg, intraperitoneally) of dexamethasone (46% of control values) and is at a maximum after two to four consecutive treatments (12% to 17% of control values). In order to eliminate the influence of either influx or efflux of cells to or from the bone marrow, the effect of dexamethasone on erythroid colony formation in vitro was examined. In these experiments, bone marrow cells cultured in the presence of Epo (25 microU) and dexamethasone (2 X 10(-6)M to 2 X 10(-8)M) formed fewer erythroid colonies than cells cultured in the presence of Epo alone. The ability of the antiglucocorticoid, 17 alpha-methyltestosterone (2 X 10(-7)M) to reverse this dexamethasone-mediated inhibition of erythroid colony formation suggests that this phenomenon is mediated through a glucocorticoid receptor. These studies show therefore that dexamethasone, either in vivo or in vitro, decreases the number and/or functional capacity of adult murine bone marrow cells capable of forming erythroid colonies in vitro in response to Epo, although the precise mechanism of this inhibition remains to be established.


A new occult blood test not subject to false-negative results from reducing substances. A new stool occult blood test is described with improved sensitivity (more true positives) and specificity (fewer false negatives; more true negatives) than other clinically available procedures. The procedure chemically separates heme from globin and extracts heme into ethyl acetate, where a colorimetric reaction gives semiquantitative estimation of hemoglobin. The test is based on the retention of heme pseudoperoxidase activity in the ethyl acetate. Specifically, peroxide is degraded by heme to superoxide radicals which oxidize a chromophore to a colored compound. Various diamino and other chromogens are evaluated, and a new reagent, the noncarcinogenic diamino compound TMB is recommended for routine use. False positives may account for two thirds of all positives in routine screening. In addition, special diets and time delays due to dietary restrictions are avoided in this test. The test is also inexpensive and easy to perform. A technologist can perform 30 or more tests per hour.


Rhinitis caseosa in Nigeria.

Rhinitis caseosa in Nigeria. 13 cases or rhinitis caseosa in Nigerians are presented. A review of the literature was made to highlight the historical background and the aetiological factors responsible for the formation of the characteristic foul, malodorous, cheese-like mass of rhinitis caseosa. Even thought the clinical features of this unusual malady are unique, it has to be differentiated from carcinoma of the nose, ethmoids and maxillary antrum. The prognosis is excellent if treatment is undertaken early.


Iron deficiency in children undergoing adenoid-tonsillectomy. Following a preliminary study of peripheral blood values in 30 children undergoing tonsillectomy and adenoidectomy, a biochemical survey of the iron status of another 108 children also undergoing this operation was made utilizing an automated micro-method. It was shown that 8.4% of these children were frankly iron-deficient but there was no statistical relationship between the levels of serum iron and iron-binding capacity, the incidence of throat infections and the levels of the plasma immunoglobulins. Assessment of all children undergoing this operation for the presence of iron deficiency is advocated as a possible routine screening procedure.


Combined treatment of concurrent laryngeal and tracheal stenosis. This report describes a one-stage combined surgical procedure for laryngeal and tracheal stenosis presenting concurrently. The technique links together three new procedures. Autogenous hyoid bone transposition on a muscle pedicle for reconstruction of the larynx, together with implantation of a silicone T-tube in conjunction with a custom-carved silicone stent, for maintenance and resurfacing of both strictures. This technique has produced satisfactory results in four cases. In two of the patients there is sufficient follow-up to indicate the efficacy of this method.


An evaluation of the use of scanning and transmission electronmicroscopy in a study of the gentamicin-damaged guinea-pig organ of Corti. Scanning electronmicroscopy and transmission electronmicroscopy were used to study the normal and gentamicin-damaged guinea-pig organ of Corti. Scanning electronmicroscopy was principally used to locate the lesion and quantify the cell loss but also permitted and detailed study to be made of the degenerative surface changes. However, since consistent surface changes are not seen until intracellular degeneration has progressed to a great extent, scanning electronmicroscopy is not a suitable technique for identifying early degenerative changes in the sensory cells of the organ of Corti. Consequently, before conclusions may be drawn about the absence of pathological changes in the neuro-epithelium it also should be examined using transmission electron-miscroscopy.


Juvenile fibrous hamartoma of the pharynx. A case of juvenile fibrous hamartoma of the pharynx in a three-year-old boy is described. It is a rare tumour, mostly occurring in the subcutaneous tissues in the infant. A pharyngeal localisation has not been described before. Complete local excision appeared sufficient for cure.


Chronic stenosis of the larynx in children. Severe laryngeal stenosis in children can be corrected successfully with surgery. Re-canalization of the larynx allows for nasal respiration, reduces the danger of respiratory infections, contributes to improved tissue oxygenation, and stimulates the child's psychosomatic development. Contrary to prior otolarngeal approaches to laryngeal stenosis in children, it has been shown that surgery does not hinder the growth of the larynx, but rather stimulates the normalization of laryngeal function; and this function itself stimulates laryngeal skeleton. It is important that surgery be performed as soon as possible in order to avoid an erroneous functional mechanism which is difficult to correct later. This can also lead to chronic irreversible atrophic and fibrotic processes in the laryngeal mucosa.


Herpes zoster of the larynx--how common? Herpes zoster of the larynx is considered to be rare, but on reviewing the literature it is noted that some authors considered it to be more common than already acclaimed. Herpes may prove to be a common cause of cord palsies presently labelled as idiopathic and serological tests for herpes should be asked for. Of note is the fact that the cord palsy of a herpetic lesion can be short-lived and that earache is a common symptom. In this paper four cases of herpes laryngis are presented. It is advised that the larynx should be examined in all cases of herpes zoster of the head and neck.


Behçet's disease of the oesophagus.

Behçet's disease of the oesophagus. A forty-two-year-old man known to have Behçet's disease (two major and two minor symptoms) (Mason and Baines, 1969) presented with dysphagia, hoarseness and regurgitation of food. This was subsequently found to be due to a tracheo-oesphageal fistula consequent upon an area of Behçet's ulceration in the oesophagus. The fistula was excised, the defects in the trachea and oesophagues repaired, and the patient's recovery was uneventful.


A cochlear implant round window electrode array. This multiple-electrode array for round window cochlear implantation is a robust, reliable system for inserting 20 mm along the scala tympani with a minimum of trauma and can provide for bipolar stimulation.


Carbamazepine in the treatment of objective myoclonus tinnitus. Three patients have had objective clicking tinnitus which was demonstrated by using impedance audiometry. Additionally EMG studies to localize the contracting muscle were performed, and EEG recordings to find the possible focal cortical activity. One patient had central nervous degenerative lesions. Carbamazepine was given as the treatment. The results are encouraging: in all cases the clicks have almost totally disappeared, making normal living possible. When medication was discontinued, the symptoms reappeared.


Non-suppurative otitis media in children. (A retrospective study of 100 cases). This is a retrospective study of 100 cases of non-suppurative otitis media among children who presented to the E.N.T. Department at Poole General Hospital between 1975 and 1978. Their histories, investigations and management are reported, with special emphasis on the significance of surgical treatment, and its value in the prognosis of such cases.


Mucocele of the petrous apex.

Mucocele of the petrous apex. The first case of a primary mucocele of the petrous apex is presented and the differential diagnosis is briefly discussed. Since this area is unavailable for direct examination, a thorough radiographic evaluation is essential. A mucocele should be suspected when a lytic lesion has a multiloculated appearance and when the contralateral petrous apex is highly pneumatized. Even then, a biopsy may still be needed to make a definitive diagnosis. The appropriate treatment for these cystic lesions is fistulization into a radical mastoid cavity or an exteriorized sphenoid sinus.


Neurilemmoma of the vagus nerve: a case report. A CASE of an unusually big neurilemmoma arising from the vagus nerve in the neck is presented in this paper. The tumour was so big that it could not be removed until its size had been reduced by the removal of about 15 cc of its fluid contents. The patient had a cardiac arrest on removal of the tumour, denoting probable stimulation of the vagus nerve leading to vagal arrest. His heart started, however, after resuscitative measures and he has not shown any residual cardiac abnormalities, thus indicating that the main vagal trunk was undamaged.


Xanthoma disseminatum: its otolaryngological manifestations. The otolaryngological manifestations of xanthoma disseminatum are discussed. A case is reported in which the voice was recovered by a laryngofissure operation. The author believes that this is the first occasion on which this operation has been performed for this condition.


Olfactory neuroblastoma: long-term survival. Two cases of olfactory neuroblastoma have been described. A review of the aetiology, histopathology and radiological features has been undertaken. A regime of current treatment policy has been described.


Tracheo-graft fistulae following pharyngo-laryngo-oesophagectomy. A cause and its prevention. Tracheo-graft fistulae developed in two patients who required intermittent positive pressure ventilation and intubation with conventional cuffed tracheostomy tubes following resection of post-cricoid carcinomata by pharyngolaryngo-oesophagectomy. Pressure necrosis of the posterior tracheal muscle and the anterior wall of the graft occurred as a direct result of compression of these structures between the tracheostomy cannula and air cuff, and the vertebral bodies at the thoracic inlet. This post-operative complication has not been encountered in subsequent resections since the introduction and routine use of a modified cuffed tracheostomy tube. The adjustable neck plate guards against trauma to the tracheostome, inadvertent intubation of one of the major bronchi in each individual patient and the siting of the cuff beyond the thoracic inlet. Unintentional over-inflation of air cuffs remains a hazard whereas only ambient air re-expands the foam cuff. This property of the cuff also ensures against surgical injury to the posterior tracheal wall during the operation. Pressure necrosis of the posterior tracheal wall by the main tracheostomy cannula is minimised by suitably modifying the curvature and length of the cannula for use in patients with end-tracheostomies.


Giant aneurysm of the internal carotid artery in the carotid canal. A case of giant aneurysm of the intrapetrous portion of the internal carotid artery, with intracranial and extra-cranial extension in an eight-year-old girl, is reported. Intracranial extension was demonstrated by the presence of a large sac projecting above the petrous shadow in a frontal carotid angiogram, and upward displacement of the middle cerebral artery in the post-ligation angiogram. Extracranial extension was shown clinically as a pulsating mass in the nasopharynx, and also radiologically as a widened medial coronoid space. Erosive destruction of the petrous bone and its neighbourhood produced palsies of the 6th, 7th, 8th, 9th and 10th cranial nerves. There was appreciable recovery in the cranial nerve palsies when the patient was assessed clinically two weeks after ligation of the internal carotid artery.


Benign solitary schwannoma of the cervical vagus nerve. A case report with a review of the literature. A case of benign solitary schwannoma of the cervical vagus nerve occurring in a 12-year-old girl is reported. Clinical and pathological problems connected with the neoplasm are discussed. From a review of the literature, the lesion seems to be less rare than is commonly believed. Treatment is also discussed, including the possibility of a surgical procedure which allows the restoration of function in the vagus nerve.


Serum concentrations of testosterone, oestrogens, luteinizing hormone and follicle-stimulating hormone in male and female rats during the critical period of neural sexual differentiation. Untreated male and female rat pups were killed 1--5 days post partum and the serum concentrations of testosterone, oestrogens, LH and FSH were determined by radioimmunoassay. At all five sampling times, the serum concentrations of testosterone in male rats were about three times higher than those in female rats, but serum levels of oestrogens did not differ between the sexes. Serum concentrations of LH and FSH were lower in male than in female pups. In another study, rats were decapitated 1--10 days after birth and serum concentrations of testosterone were determined with a different radioimmunoassay. Again, at all four sampling times, the concentration of testosterone was significantly higher in the male than in the female pups.


Seasonal fluctuations in the plasma concentrations of progesterone and oestradiol-17 beta in the female snapping turtle (Chelydra serpentina). Plasma concentrations of progesterone and oestradiol-17 beta were determined by radioimmunoassay procedures in the sexually mature female snapping turtle at four different stages of the annual ovarian cycle. The highest level of progesterone in the peripheral plasma was detected during the luteal stage (June), whereas the concentration of oestradiol was highest (280 pg/ml) in May, immediately before ovulation.


Immunological properties of synthetic human parathyroid hormone 53--84 fragment. The immunological properties of a synthetic peptide comprising the carboxyl-terminal 53--84 region of human parathyroid hormone (PTH) have been studied. The immunoreactivity of the synthetic human PTH-(53--84) peptide paralleled that of a 53--84 fragment of the native human hormone prepared by enzymic digestion, in both a standard radioimmunoassay, which was not region-specific, and also a radioimmunoassay specific for the carboxyl-terminal region of PTH. However, in both types of radioimmunoassay the synthetic human PTH-(53--84) peptide was four to five times more reactive than the native human PTH-(53--84) fragment.


International Reference Preparation of human prolactin for immunoassay: definition of the International Unit, report of a collaborative study and comparison of estimates of human prolactin made in various laboratories. As authorized by the World Health Organization 29th Expert Committee on Biological Standardization, the preparation of human prolactin in ampoules coded 75/504 has been established as the International Reference Preparation (IRP) of human prolactin for immunoassay. From the results of a collaborative study, to which 15 laboratories in nine countries contributed, with the agreement of the participants, the content of each ampoule is defined as 0.650 International Units (i.u.; 650 mi.u.) immunoassay. The results of this collaborative study show that the IRP is adequately stable and suitable for use as a standard for the determination of prolactin in human plasma and serum. Estimates of the prolactin content of human plasma and serum made in the various laboratories have been compared and show good agreement in ranking order, but only fair agreement in the numerical value of the estimates. Numerical agreement is poor between estimates of the human prolactin content of two samples identical except for coding; this shows the difficulty in achieving continuity of estimates when any laboratory calibrates a replacement standard.


Sex differences in the concentrations of glucocorticoid receptors in rat liver and thymus. The effects in rats of adrenalectomy, hypophysectomy, ovariectomy or combinations of these operations on the concentrations of glucocorticoid receptors in the cytosol of liver and thymus were measured. The concentrations of glucocorticoid receptors were lower in cytosols from liver and thymus of female than of male rats. After adrenalectomy, there was a significant increase in the concentrations of receptors measured in the cytoplasm from the liver and thymus of female rats and from the liver of male rats. After adrenalectomy or hypophysectomy, there was no sex difference in the concentration of glucocorticoid receptors in cytosols of liver or thymus. After ovariectomy, the concentration of receptors in cytosols from the thymus, but not from the liver, increased. Ovariectomized rats responded to adrenalectomy in the same way as intact male rats. The different responses shown by male and female rats to endocrine manipulation probably depend upon associated changes in plasma corticosterone concentrations which are influenced by the ovary. Differences in response between the liver and thymus probably reflect a preferential distribution of corticosterone to the liver rather than to the thymus.


Highly specific binding of 1,25-dihydroxycholecalciferol in bone cytosol. A method developed initially for the detection of high-affinity binding of glucocorticoids in the cytosol from foetal rat calvaria has been adapted for metabolites of vitamin D. Consistent displacement of [3H]1,25-dihydroxycholecalciferol ([3H]1,25(OH)2D3) by unlabelled 1,25(OH)2D3 was obtained with an apparent dissociation constant (Kd) of 2.3 x 10(-9) mol/l. The specificity of this binding was examined by competition experiments. Displacement of labelled 1,25(OH)2D3 by a 100-fold excess of unlabelled metabolites, expressing the fall with unlabelled 1,25(OH)2D3 as 100%, was as follows: 25-hydroxycholecalciferol (25(OH)D3), 61%; 24,25-dihydroxycholecalciferol, 29%; cholecalciferol, 3%. These are similar to results for the chick mucosa nuclear 1,25(OH)2D3 receptor. No displacement was obtained with corticosterone, testosterone, oestradiol or progesterone. When [3H]25(OH)D3 was used as ligand, a displacement curve with unlabelled 25(OH)D3 indicated only binding with a greater Kd (approximately 10(-7) mol/l). These data suggest a direct action of 1,25(OH)2D3 on bone which is similar to that of steroid hormones on their target tissues.


Variations in concentrations of prolactin, luteinizing hormone, growth hormone and progesterone in the plasma of broody bantams (Gallus domesticus). The concentrations of prolactin, LH, progesterone and GH were measured in the blood of broody bantam hens. The concentration of prolactin was at its highest when the birds began to incubate their eggs and in six out of nine hens it tended to remain raised until the eggs hatched. The increase in the concentration of prolactin was small: in incubating hens it was only 23% higher than in hens caring for their young and 14% higher than in laying hens (P less than 0.05 for both comparisons). The concentration of GH tended to be depressed in hens caring for young but otherwise was not related to reproductive activity. The concentrations of LH and progesterone decreased at the onset of incubation and remained depressed while the hens sat on their eggs (P less than 0.001) for both comparisons). After the chicks hatched, the level of LH began to increase slowly whereas the level of progesterone remained low. The hens stopped showing broody behaviour between 4 and 10 weeks after the chicks had hatched; this corresponded to the time when the concentration of LH had increased to values found in laying hens. These observations provide some evidence that prolactin secretion increases at the onset of incubation and support the view that the hormone is not secreted at an increased rate while hens are caring for their young.


Reduction of non-specific serum responses in human pituitary gonadotrophin radioimmunoassays. Serum and plasma from human and domestic animals contain variable amounts of non-specific material(s) which may be mistaken for hormone in assays for human LH and FSH, based upon antisera of high sensitivity and hormonal monospecificity. The non-specific response curves are generally, but not invariably, less steep than those of the hormone standards and endogenous homologous hormones. The levels of non-specific intrusion can be of sufficient magnitude to obscure specific estimations seriously, particularly at low hormone levels, unless the assays are designed to minimize this effect. The non-specific effects could be minimized (but not abolished) by careful optimization of the assays which involved making the response curve as sensitive as possible and incorporating the serum at a final dilution of 1 : 2, since further dilution increased the relative contribution of the non-specific substance(s). The optimized assays require only 48 h of total incubation and show a sevenfold increase in the mean concentration of LH between sera from prepubertal children and adults accompanied by a mean threefold difference in the concentration of FSH.


Metabolism of exogenous human chorionic gonadotrophin in men. The immunoreactivity of a commercial preparation of human chorionic gonadotrophin (HCG) was determined in a homologous double antibody radioimmunoassay for HCG using antisera to the beta-subunit of the hormone. The immunoreactivity of the commercial HCG was found to be 2.2 +/- 0.3 (mean +/- 2 S.D.) times the biological potency. Exclusion chromatography of the commercial HCG and then curve resolution of the elution profile derived from the radioimmunoassay revealed that on a molar basis, 21% of the immunoreactivity was attributable to beta-HCG. The rate of clearance of this preparation of HCG from the plasma after intravenous administration was determined as a function of the dose administered to ten normal men (age 36--64 years). The doses ranged from 10,000 to 300,000 i.u. immunological potency. The rate of clearance decreased significantly (r = 0.574, P less than 0.05) with increasing doses of HCG from a mean of 786 ml/h at the lowest dose to a mean of 298 ml/h at the highest dose. The renal clearance of administered HCG also decreased with increasing doses; the mean renal clearance of the 10,000 i.u. dose was 3.6 times the mean renal clearance after administration of 200,000 i.u. When the accumulated urinary HCG was expressed as a percentage of the dose administered, 14.1% of the 10,000 i.u. dose and 9.8% of the higher doses accumulated in the urine, suggesting that non-renal clearance increased with increasing dose.


Transfer of matching performance in pigeons. Three pigeons were given extensive training on three-key simultaneous matching problems using geometric-form and hue stimuli. After acquisition of matching, the birds were tested with pairs of stimuli involving one or both novel members. Matching during the test stimuli occurred less often than during the later stages of the acquisition phase, but more often than would occur if no transfer had taken place. Greater positive transfer was observed for problems that involved one, rather than two, novel stimuli. In the second phase of the experiment, previously trained birds were shifted to problems that required symbolic matching, i.e., the pigeons had to associate a particular center-key stimulus with a particular side-key stimulus. On each trial, one of two simuli was presented on the center key, and two other stimuli, different from those used on the center key, were displayed on the side keys. When the problem shift was introduced, correct responding was impaired, but remained considerably above chance level and quickly recovered in following sessions. The results were interpreted as favoring a stimulus-response-chaining account of matching behavior.


Effects of cocaine and d-amphetamine on the repeated acquisition and performance of conditional discriminations. The acute and chronic effects of cocaine and d-amphetamine on food-reinforced behavior were investigated in pigeons responding on a two-component multiple schedule. In one component, the behavioral task consisted of the same chain of conditional discriminations each session (performance). In the other component, the chain of conditional discriminations was changed from session to session (learning). In comparison to control sessions, both acute cocaine and d-amphetamine increased errors in each component of the multiple schedule. Responding in the learning component, however, was generally disrupted at lower doses than those that affected responding in the performance component. At high doses, both drugs produced pauses in responding in each component in three of the four subjects. Pausing engendered by d-amphetamine was approximately twice as long as that under cocaine. Upon chronic administration, both the pausing and error-increasing effects of each drug diminished. Drug-induced changes in timeout responding, however, did not decrease during chronic administration. Redeterminations of the d-amphetamine dose-effect curves following chronic cocaine administration suggested the existence of cross-tolerance between cocaine and d-amphetamine. Both the acute and chronic data are consistent with the view that conditions of stimulus control may modulate the behavioral effects of drugs.


Pentobarbital and d-amphetamine effects on concurrent performances. The effects of pentobarbital and d-amphetamine were studied in pigeons responding under several concurrent fixed-ratio variable-interval and concurrent fixed-ratio fixed-interval schedules of food presentation. Drug effects were compared with different fixed ratios, fixed and variable intervals, changeover delays, and with the schedules operating singly. Doses of d-amphetamine that increased or did not affect responding under the interval schedules decreased responding under the fixed-ratio schedule, whereas doses of pentobarbital that increased responding under the fixed-ratio schedule decreased or eliminated responding under the interval schedules. These effects depended both on the schedule of food delivery and the parameters of schedules arranged concurrently. Pentobarbital increased responding under the fixed-ratio schedule with 4-minute and 10-minute interval schedules arranged concurrently, but not with 1.5-minute schedules. d-Amphetamine decreased concurrent ratio and interval responding with the 1.5-minute interval schedules, but either increased or did not affect responding with the longer intervals. Changes in the parameter of one schedule altered responding controlled by that schedule and also other concurrent performances. As a consequence, the effects of drugs on each behavior were altered.


Reinforcement contingencies as discriminative stimuli: II. Effects of changes in stimulus probability. Three pigeons were trained on a matching procedure involving a sample component and a choice component. Responding in the sample component, according to either a differential-reinforcement-of-low-rate schedule on some trials or a differential-reinforcement-of-other-behavior schedule on other trials, produced access to the choice component in which each of two keys was illuminated with a unique color. The correct choice response was defined by the contingency that was met to produce the choice. The food hopper operated for 1.5 seconds following an appropriate sample response and for 3 seconds following a correct choice response. A signal-detection analysis showed that variations in the probability of presentation of the different contingencies systematically affected response bias but not sensitivity to the contingencies as stimuli. Substitution of a blackout for food at the end of the sample component did not differentially affect performance, but elimination of the delay between sample and choice components generally increased the sensitivity measure. The findings suggest a role for reinforcement contingency discrimination in schedule-controlled responding.


Schedule-induced locomotor activity in humans. In two experiments, humans received tokens either on a fixed-interval schedule for plunger pulling or various response-nondependent fixed-time schedules ranging from 16 to 140 seconds. Locomotor activity such as walking, shifting weight, or pacing was recorded in quarters of the interreinforcement interval to examine the induced characteristics of that behavior in humans. While performance was variable, several characteristics were present that have counterparts in experiments with nonhumans during periodic schedules of food reinforcement: (a) first quarter rates, and sometimes overall rates, of locomotor activity were greater during intervals that terminated in a visual stimulus and token delivery than those without: (b) overall rates of locomotor activity were greater during fixed-time 16-second schedules than during fixed-time 80- or 140-second schedules; (c) rates of locomotor activity decreased during the interreinforcement intervals; (d) locomotor activity was induced by response-dependent and response-nondependent token delivery. These results showed that the rate and temporal pattern of locomotor activity can be schedule-induced in humans.


Genetically determined, interferon-dependent resistance to influenza virus in mice. The genetically determined resistance towards orthomyxoviruses exhibited by mice homozygous (A2G) or heterozygous (A2G X A/J) for the gene Mx was abolished or greatly diminished by treatment with anti-interferon globulin (AIF). AIF induced increased susceptibility to challenge with hepatotropic, neurotropic, and pneumotropic strains of influenza A virus. Hepatotropic virus titers in blood and livers of AIF-treated, Mx-bearing mice were higher by a factor of 10(3)--10(6) than those in untreated mice of the same genotype, and were comparable to those in genetically susceptible (untreated or AIF-treated) mice. Peritoneal macrophages from Mx-bearing untreated mice were resistant to challenge with a macrophage-adapted strain of influenza A virus even in the presence of AIF. However, when macrophages were taken from resistant mice injected with AIF and also cultivated in the presence of AIF, they were as susceptible to the virus as macrophages taken from susceptible mice. We conclude that interferons is an important factor in resistance to orthomyxoviruses governed by the gene Mx.


DR (Ia-like) antigens on human melanoma cells. Serological detection and immunochemical characterization. 11 cultured human melanoma cell lines were tested for the expression of DR antigens by using specific allo- and xenoantisera in an indirect rosette microassay. Four of these melanoma cell lines expressed DR antigens, but in lower amounts than expressed on cultured human B-lymphoid cells. Rabbits injected with the DR-positive melanoma cells produced antibodies that were serologically and immunochemically reactive with B-cell-derived DR antigens. Immunochemical studies indicate that melanoma cell-derived DR antigens have a two-chain structure with 34,000 and 27,000 mol wt components. The melanoma cell-derived DR beta-chain at 27,000 mol wt is slightly smaller than that of the Victor cell DR beta-chain whose mol wt is 29,000.


The tumor dormant state. Comparison of L5178Y cells used to establish dormancy with those that emerge after its termination. The tumor dormant state established in L5178Y immunized and challenged mice is characterized by a prolonged period of clinical normalcy followed by rapid tumor outgrowth. The tumor cells which emerged after termination of the tumor dormant state had abnormal marker chromosomes identical to those in the L5178Y cells used in the original challenge inoculum, indicating that the emergent tumor cells were progeny of the challenge inoculum. Original and emergent L5178Y cells had equivalent in vivo growth rates, when inoculated into normal DBA/2 mice. The emergent L5178Y cells were less susceptible than original cells to in vitro lysis by tumor dormant PC. Original and emergent L5178Y cells expressed common tumor-associated target antigens for cytolytic effector cells. Both modulation and masking of these target antigens were ruled out as mechanisms for decreased susceptibility to cell-mediated cytolysis. Immunofluorescence revealed heterogeneity in tumor-associated antigen expression within both original and emergent cell populations, with a decreased intensity of staining in the emergent population. Both populations were equally susceptible to lysis by alloimmune cells, alloantiserum, and anti-Thy 1.2 serum, but emergent cells were less susceptible to lysis by serum directed against L5178Y TAA. Quantitative absorption revealed that the emergent L5178Y cells expressed eightfold less serologically detectable TAA than the original cells. These findings indicate that the host immune response developing during establishment of the tumor dormant state selects a stable tumor cell subpopulation which expresses decreased amounts of surface tumor-associated target antigens.


Relation between structure and correcting activity of bovine high molecular weight kininogen upon the clotting time of Fitzgerald-trait plasma. Bovine high molecular weight kininogen (bHMWK) partially corrects the activated plasma thromboplastin time (aPTT) of Fitzgerald trait plasma which is congenitally deficient in HMWK. The relationship between the structure and activity of HMWK was clarified by studying the effects of different fragments of bHMWK on the aPTT of Fitzgerald-trait plasma. The peptides studied were lys-bradykinin-free HMWK, bradykinin-fragment 1-2-free HMWK, heavy chain, fragment 1-2-light chain, and light chain. All fragments were tested in equimolar concentrations. Bradykinin-fragment 1-2-free HMWK, heavy chain, and light chain have little or no correcting activity upon Fitzgerald-trait plasma aPTr. Fragment 1-2 light chain has the same correcting activity as intact bHMWK, while that of lys-bradykinin-free HMWK appears to be higher. Both fragment 1-2 and fragment 2 inhibit the clotting time of normal human plasma. When compared on a molar basis, fragment 2 is a more active inhibitor than fragment 1-2. When the effects of bovine plasma kallikrein upon bHMWK and hHMWK were studied, it was found that it released kinins from both kininogens. However, while the correcting activity of bHMWK was completely destroyed after 60 min of incubation, that of hHMWK was fully retained. These data suggest that: (a) the active part of bHMWK is comprised of the fragment 1-2 light chain portion; (b) fragment 1-2 or fragment 2 is the binding site to negatively charged surfaces, while the light chain interacts with other components of the surface-mediated reactions; and (c) bovine plasma kallikrein releases kinins, but probably does not cause the release of fragment 1-2 from human HMWK.


The appearance of transition forms between monocytes and Kupffer cells in the liver of rats treated with glucan. A cytochemical and ultrastructural study. A massive accumulation of mononuclear phagocytes in the rat liver was found after the injection of glucan, a beta-1,3-polyglucose. Portal vessels and central veins contained large numbers of rounded and elongated cells which were adherent to the endothelium. By scanning electron microscopy most of these cells exhibited prominent lemellopodia, raised ridge-like profiles and blebs, the typical features of mononuclear phagocytes. Peroxidase cytochemistry revealed that whereas most cells in portal vessels were monocytes with peroxidase positive and negative granules, the majority of cells in central veins were macrophages exhibiting peroxidase activity in nuclear envelope (NE) and endoplasmic reticulum (ER). In sinusoids monocytes and macrophages were seen side by side. The major finding of the present study was that some cells, adherent to the endothelium or portal vessels or to the lining of sinusoids, exhibited a peroxidase pattern intermediate between monocytes and Kupffer cells, i.e. strong peroxidase activity in cytoplasmic granules, as well as a weak to moderately positive peroxidase reaction in NE and ER. These intermediate cells also contained peroxidase-negative granules with halo, which are usually seen in monocytes. Furthermore, examination of serial ultrathin sections of typical Kupffer cells revealed numerous peroxidase-positive granules and peroxidase-negative granules with halo in their cytoplasm. Finally, dividing Kupffer cells with positive peroxidase reaction in ER were found. These in vivo observations provide ultrastructural and cytochemical evidence in support of the concept of derivation of Kupffer cells from monocytes, demonstrating in addition that Kupffer cells are capable of self-replication in situ.


Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes. The effect of surface-bound immune complexes on the secretion of neutral proteases by human peripheral monocytes was examined. Monocytes cultured on 125I-fibrin secreted plasminogen activator in a continuous fashion. Monocytes incubated on 125I-fibrin with surface-bound immune complexes displayed a burst of plasminogen-independent fibrinolytic activity, whereas no release of plasminogen activator was observed through 21 h. The plasminogen-independent fibrinolytic enzymes were derived from monocytes and not from lymphocytes or contaminating polymorphonuclear neutrophils. The effects of various protease inhibitors on the secretion of plasminogen-dependent and independent enzymes were determined. Chymostatin selectively inhibited the monocyte-derived plasminogen activators. Similar effects of chymostatin were observed on human urokinase in the absence of cells. The predominant protease producing plasminogen-independent fibrinolysis exhibited responses to inhibitors characteristic of leukocyte elastase. When monocytes were cultured on 125I-fibrin with adherent immune complexes approximately equal to 40% of the solubilized radioactivity represented deiodination and not proteolysis. It was concluded that culture of human monocytes on surface-bound immune complexes stimulates the secretion of plasminogen-independent fibrinolytic proteases, primarily elastase, and of deiodinating enzymes. Under these conditions, plasminogen activator secretion is inhibited. Neutral proteases secreted from newly recruited monocytes may contribute to tissue injury in human diseases characterized by the presence of adherent immune complexes.


Three types of blood group I specificity among monoclonal anti-I autoantibodies revealed by analogues of a branched erythrocyte glycolipid. Blood group I activities of the purified glycosphingolipid lacto-N-iso-octaosyl ceramide (Fromula: see text) and 8 of its analogues have been evaluated with 11 anti-I sera including 5 anti-I sera previously tested. All but one of the antisera were inhibited by the lacto-N-iso-octaosyl structure. Three types of I-specificity could be distinguished although none of the anti-I sera was identical in its inhibition patterns with the nine glycophingolipid analogues. The anti-I sera Ma and Woj represent the first type and require an intact Galbeta1 leads to 4GlcNAcbeta1 leads to 6 chain, the anti-I sera Step, Gra, Ver, and Ful represent the second type which requires Galbeta1 leads to 4GlcNAcbeta1 leads to 3 chain with branching, and the anti-I sera Phi, Da, Sch, and Low belong to the third type which requires both branches to be intact. Anti-I antibodies varry in their ability to react with their antigenic determinants in the presence of external substitutions with alpha-linked galactose or sialic acid.


Structural studies on the murine Ia alloantigens. V. Evidence that the structural gene for the I-E/C beta polypeptide is encoded within the I-A subregion. The E/C alpha- and beta-subunits of intra-I-region recombinants were analyzed for primary structural variation by comparative tryptic peptide mapping. The E/C alpha-polypeptides from B10.A, B10.A (3R) and B10.A (5R) showed complete coincident elution of peptides; the E/C beta-chains from B10.A and 3R (or 5R) were approximately 40% different. This suggests that the structural gene for the E/C beta-polypeptide is within the I-A subregion.


Follow-up on the problem of increased incidence of thyroid carcinoma from the effects of childhood irradiation. There has been widespread concern in both the medical and lay community on how to deal with the problem of the increased incidence of thyroid cancer in patients irradiated in the head and neck during childhood, including the difficult question of whether all of these patients should be recalled and screened. Such an approach is not deemed logistically feasible and the desired benefits of the program which hinge on treatment through early detection are nullified by the protracted nature of the disease. The iatrogenic nature of the problem has raised ethical questions concerning professional duty and responsibility. The principle of "similar treatment for similar cases" seems fairest and most justifiable in pursuit of the goal of equal access to health care. The most effective plan appears to be a carefully devised public education campaign. Informing practicing physicians not already aware of the problem should be an important part of this effort. The responsibility for seeking treatment would be left to the patient who would see his personal physician or be recommended to a previously designated physician in his area.


Varicella pneumonia during pregnancy.

Varicella pneumonia during pregnancy. Varicella pneumonia during pregnancy may be relatively mild or rapidly fatal. Diagnosis is based on the usual criteria for varicella in association with signs and symptoms of respiratory distress: dyspnea, tachypnea, cough, chest pain, and hemoptysis, with characteristic x-ray findings. Treatment should be directed toward maintaining blood oxygen saturation at as near normal as possible (monitored by serial blood gas determinations). The occurrence of congenital varicella is unpredictable, but an infant born within four days of the mother's development of the varicella skin rash is at high risk, with the outcome being fatal in five percent of cases.


Mycosis fungoides: clinical and therapeutic review. Mycosis fungoides is a cutaneously-derived malignant lymphoma which, without effective treatment, may run an unrelenting, rapidly lethal course. Often beginning as a nonspecific skin eruption, easily misdiagnosed as a common eczema or psoriasis, the disease progresses through a plaque stage to the tumor stage with the appearance of the mushroom-like growths for which the entity was originally named. Because of the dismal outlook in uncontrolled cases, newer, more aggressive approaches to therapy are being developed and are being instituted earlier in the course of the disease.


Documentation of inpatient clinical experience of family practice residents: a manual system. A simple, efficient, and inexpensive system for quantitatively documenting the range of clinical experience of individual residents on inpatient rotations is described. Information provided by this system can be used by program faculty to make informed educational decisions concerning both the design of rotations and individual resident program planning. The data are also useful to residency graduates to document their clinical experience when applying for hospital privileges.


Behavioral science and family practice: a status report. The purpose of this study was to assess the current status of behavioral science instruction in family practice residency training programs. The primary areas of interest were: (1) characteristics of those who teach behavioral science (number of persons teaching behavioral science by discipline and academic degree, number and percent of time behavioral science personnel employed, work responsibilities, academic unit responsible for instruction, description of those who provide inservice training in behavioral science ), (2) the relative importance of various behavioral science topics as perceived by faculty/staff (21 topics), and (3) preferred methods of instruction. The data revealed a wide variety of persons involved in behavioral science instruction, a strong emphasis placed on communication and counseling skills, and similar, but not innovative, teaching methods used for behavioral science instruction.


Teaching interpersonal skills in family practice: results of a national survey. The increasing recognition of the importance of a well-developed set of interpersonal skills to the competent family physician has resulted in a rapid growth in the formal teaching of interpersonal skills within family practice residencies. Of the 168 programs responding to a national survey of family practice residencies, 88 percent indicated that they have formal programs in interpersonal skills. It is estimated that there are well over 500 family practice faculty members who have special responsibilities in teaching interpersonal skills. While most programs address the component skills of the interpersonal process (eg, demonstrating empathy, information gathering, information giving, and psychological intervention), it is of concern that only about half offer explicit training in patient education (53 percent), specific types of counseling (eg, family counseling, 55 percent), or some of the specific interpersonal skills important in team practice and practice management (eg, supervisory skills). One of the most striking findings was that 88 percent of the reporting programs use videotechnology, with 77 percent of these planning to increase their use. Although most programs evaluate their interpersonal skills training using both indirect and direct assessment methods, only 25 percent attempt to use patient outcome as a measure of teaching effectiveness.


The nature and management of telephone utilization in a family practice setting. Study of the telephone practice in four family practice settings reveals a complex interaction between patients, physicians, and receptionists. Patients present a limited number of complaints--80 percent of complaints represent 25 common chief complaints, and 95 percent represent 50 chief complaints. Little difference was observed between the symptoms reported by patients to the physicians as compared to those received by the receptionist staff. Physicians are more likely to use the telephone contact to treat  the patient's complaint with home care advice or a prescription. Receptionists are more likely to use the telephone contact for scheduling an office visit.


An approach to locating a family practice office in a metropolitan area. A simple, economically feasible approach to locating a family practice office within a metropolitan area is presented. The Grand Rapids area serves as the population base for this investigation. An Office Location-Population Profile is determined from census tract population data and known physician office distrubution. Based on this information, a subsegment of the total area is delineated as a possible neighborhood for an office location and a physician-opulation ratio for this subsegment is determined. This is compared with recommended ratios. A statistical profile of the population, within the area considered as a possible site location, is developed using information available through census bureau statistics. Finally, a direct survey of a random sample of households within the selected area is performed. This format provides an objective approach to facilitate rational decision making in locating a family practice office in a metropolitan area.


Emergency room misuse by medical assistance patients in a family practice residency. Four hundred individual Emergency Room records were retrospectively reviewed. Demographic data, complaint, diagnosis, and treatment were tabulated and analyzed by computer assistance. Judgment was not made regarding the necessity of physician consultation, but whether an Emergency Room visit was warranted considering the duration of the presenting complaint. During a time period when 29 percent of the total outpatient visits to the Family Practice Center Model Office were made by recipients of Medical Assistance, the same population accounted for 53 percent of the Emergency Room visits reviewed. Twenty-five percent of the 400 visits were judged to be unnecessary according to the pre-established criteria. Sixty-four percent of the unnecessary visits were by Medical Assistance patients. Of 304 total families represented, 73 were responsible for multiple visits. Thirty-one percent of these visits were unnecessary, whereas 21 percent of the visits made by families with single visits were unnecessary. In this family practice setting, it is concluded that Medical Assistance patients have a greater tendency toward inappropriate use of the Emergency Room when compared to non-Assistance patients.


Health action alliance: a consumer approach to improving ambulatory care in a family practice residency clinic. "The Health Action Alliance for Family Practice Clinic--St. Marys" is a group of physicians, patients, and clinic personnel who meet regularly for the purpose of providing a forum for interaction between health care personnel and patients. The group deals with patient training for effective participation in general clinic activities, participation in decision making processes of the clinic, health education, and other topics as the group decides. This paper discusses the formation of the group, its purposes, accomplishments, and plans for the future.


The depressed patient.

The depressed patient. SAdness and normal grief are distinguished from pathological grief and depression by intensity, duration, precipitating events, and the quality of psychopathological features. Depression is evaluated as a final common pathway of potential psychodynamic, genetic, psychosocial, physiological, and personality characteristics or events. The clinical entity of depression is diagnosed by describing some of each of the affective, behavioral, and cognitive changes concomitant with depression. The clinical entity of depression is further differentiated for purposes of treatment into the categories of bipolar depression (manic-depressive illness), unipolar depression (psychotic depressive reaction or involutional melancholia), neurotic depression, and secondary depression (secondary to somatic disease, drugs, or to other psychiatric disorders). The immediate treatment depends on the type of depression diagnosed. Unipolar and bipolar depressions respond to specific pharmacologic therapy and supportive care. Neurotic and characterologic depressions respond to supportive or insight psychotherapy with possible brief adjunctive anti-anxiety or hypnotic medication. All of the treatment modalities, with the possilbe exception of insight psychotherapy, can be effected very adequately by the primary care physician who is given clear diagnostic and assessment guidelines with specific treatment approaches.


Fracture management by family physicians and guidelines for referral. Family physicians are now receiving more formal training in orthopedics, preparing them to deal with common orthopedic problems. Core curriculum objectives for orthopedics are being developed in family practice programs. Family physicians should have guidelines as to which fractures and dislocations they themselves can manage and which fractures should be managed by orthopedists. General guidelines for consultation and referral are presented, and the management of specific common fractures in adults and children is outlined. Many fractures can be cared for by the family physician with appropriate consultation and advice from the orthopedist.


A study of hysterectomy in a family practice. This paper reports on a study of women in a family practice who have undergone hysterectomy as compared with a group of matched controls. Significant differences were found in the greater number of major surgical procedures (other than hysterectomy) and the reporting of chronic and recurrent symptoms for the study group. Study group women were also found to have a greater number of identified intrapersonal and family problems. There was no significant difference, however, in the number of identified chronic organic problems. Differences which did not reach statistical significance suggest that women in the study group may be more likely to be living without a male partner, to be using long-term medication, and to be smokers. A most important finding was that the group of women who had undergone hysterectomy had also had 2.6 times the number of major surgical operations than the controls, excluding the hysterectomy. There were no differences between the two groups with respect to a number of other factors studied, eg, education, religion, history of psychiatric admission, obesity.


The content of physician/patient communication in family practice. Observation of a series of office visits by patients to family physicians provide information on physician-patient communication. During interaction on medical matters, the physicians instigated 80 percent of the interview. By way of contrast, when discussion of matters beyond the strictly medical situation occurred, 70 percent of the conversation was initiated by the patients. Irrespective of diagnoses, there were significant differences in the overall content of communications for patients from different socioeconomic groups, with more verbal exchange occurring with upper social class patients than with lower social class patients. Other patient factors which led to an increase in verbal interaction were chronic illness, emotional disorders, and ill-defined conditions. The analysis of categories of verbal interaction between physicians and patients proved to be a practical method of studying the physician-patient relationship, and provided guidelines for those seeking to make objective measurements of communication in family practice.


Orthopedic problems in family practice: incidence, distribution, and curricular implications. The spectrum of orthopedic problems encountered by family physicians in everyday practice has received little study in the past. This paper presents and analyzes the incidence and distribution of orthopedic problems in general/family practice based on four sources of secondary data. These sources include the National Ambulatory Medical Care Survey, a Family Practice Service in a large military teaching hospital, a state wide study in Virginia, and two community-based family practice settings in Washington State. Orthopedic problems constitute about ten percent of all office visits in family practice. Over one half of these involve chronic, nontraumatic musculoskeletal problems. Major differences are noted in the distribution of sprains, strains, and fractures in adults and children. Fractures of the hand, foot, forearm, lower leg, and clavicle comprise between 50 and 80 percent of fractures seen in the settings under study. This kind of information should be helpful in better defining goals and methods for graduate training of family practice residents in orthopedics.


A structured experiential curriculum in community medicine. In order to provide experimental training in community medicine, a structured curriculum has been developed. Specific methodological skills in community medicine are identified and nine content areas are presented in seminar form during the three-year training program. Each resident is expected to participate in a community health care project and demonstrate one or more of the methodological skills identified. The experiences of two residents are reported. One involved a community health needs assessment and one, the development of a mechanism to ensure continuing consumer/provider communication.


Some principles of epidemiologic studies. The use of epidemiological evidence is frequently involved in clinical decision making. Usually epidemiological investigation seeks to determine the extent of the association between a suspected factor and the occurrence of a disease. When the data are collected retrospectively then rates of exposure to the factor are compared for a group of cases of the disease and a group of controls. If the study is prospective then incidence rates of the disease are compared for a group exposed to the factor and an unexposed group. Although the retrospective approach is often more feasible it is also more vulnerable to bias. The possible influence of bias and chance must be taken into consideration when interpreting the results of any study. Relative risk serves as a useful index for expressing the strength of the association between the factor and the disease.


Failed appointments: a review.

Failed appointments: a review. Failed appointments disrupt office operations. Most studies involved hospital clinics with low socioeconomic populations, which have shown fail rates between 19 and 28 percent. Family practice centers report fail rates which vary from 5 to 11 percent. Young adults, adults with young children, and patients in low socioeconomics groups tend to increase the fail rate. Sex and race are probably not a factor. Reasons for failing appointments include communication problems, the absence of a sense of urgency for keeping the appointment, and the lack of a personal physician. An interval greater than two weeks between appointment scheduling and the appointment date places patients most at risk for failing the appointment. Mail and telephone reminders significantly reduced the fail rate and are cost efficient. Incentives are also used in reducing the fail rate. By examining the process, the patients, the provider, and the environment with respect to appointment keeping behavior, a more quantitative approach to research on the subject can be effected.


A method for determining patients' perceptions of their health needs. Success or failure in establishing a meaningful relationship between physician and patient depends to a large extent on how fully the patient communicates, and the physician understands, his/her health needs. Return visits, compliance with the physician's prescribed regimen, and the effectiveness of the treatment and rehabilitation are also closely related to the disclosure and assessment of the patient's health needs. A model of how health needs are determined is presented. Various behavioral outcomes which follow the identification of a health problem and assessment of health needs by a patient are discussed. A Health Needs Assessment Questionnaire is presented in English and Spanish to be used and tested as an aid to the family physician in assessing patient's health needs at the first encounter.


Bacteriocin, plasmid and pectolytic diversity in Pseudomonas cepacia of clinical and plant origin. Pseudomonas cepacia strains of plant and clinical origin were compared with the type strains of P. cepacia, P. kingii and P. multivorans. Conventional biochemical tests and antibiotic sensitivity patterns supported the previous proposals of synonymy between P. cepacia, P. kingii and P. multivorans. However, bacteriocin production patterns, onion maceration tests and hydrolysis of low pH pectate agar clearly differentiated strains of clinical and plant origin into two distinct groups; these tests may therefore be helpful in epidemiological studies. In contrast, plant and clinical strains were of equal lethality to mice. Agarose gel electrophoresis indicated the presence of one or more plasmids (molecular weights 9 X 10(6) to 120 X 10(6)) in 15 out of 16 strains of both types examined.


Productive influenza virus infection of synchronized chick embryo fibroblast cells. The effects of cell metabolic activity on the outcome of influenza virus infection were studied in partially synchronized chick embryo fibroblast cultures. There was no evidence to show that the time in the cell cycle at which cells were infected had any significant effect on the final virus yield. However, some differences were detected in the length of the latent period between infections established in synchronized or in stationary cells. Influenza virus could replicate in synchronized or normal cell cultures in which DNA synthesis was inhibited with 9-beta-D-arabinofuranosyladenine (ara-A).


Effects of leukocyte and fibroblast interferon on events in the fibroblast cell cycle. Serum-depleted human foetal skin fibroblasts were stimulated by addition of 10% foetal calf serum to proliferate synchronously for at least one cell cycle. This proliferation was suppressed by leukocyte or fibroblast interferon (IF), which prolonged the G1 phase and diminished the rate of DNA synthesis during the S phase in a dose-dependent manner. When used in identical concentration, as judged in terms of units of antiviral activity, fibroblast IF had more pronounced effects on cell cycle events than leukocyte IF. Interferon exerted its effect in early G1, before the cells were irreversibly committed to DNA synthesis.


A comparison of polypeptides in measles and SSPE virus strains. The polypeptide patterns of twelve subacute sclerosing panencephalitis (SSPE) and measles viruses have been compared by slab gel electrophoresis. The polypeptide patterns of nine strains of SSPE and measles virus were identical. Differences in the NP protein and the HA protein of the Oddo strain, the P protein of the large plaque variant of the Lec strain of SSPE and in the M protein of the Hu 2 measles strain could not be correlated with biological characteristics such as plaque morphology, origin or haemagglutination properties.


Togavirus interference in Culex annulirostris mosquitoes. Culex annulirostris mosquitoes infected with SFV-S, a temperature-sensitive, small-plaque mutant of Semliki Forest virus isolated from cultured Aedes albopictus cells, could not be infected later with wild-type virus (SFV-W). Interference occurred as soon as 24 h after infection with SFV-S. In mosquitoes infected with a mixture of the two viruses, both replicated normally.


Requirement of adenovirus type 12 gene 401 function for initiation of virus DNA synthesis. The highly oncogenic human adenovirus type 12 temperature sensitive mutant. H12ts401, is unable to maintain the growth characteristics of transformed cells at the non-permissive temperature. In lytic infection, the 401 gene function is required to produce virus DNA. In the present study, virus DNA synthesized in ts401-infected human cells after temperature shift-up was characterized. No apparent suppression of DNA chain elongation or ligation occurs at the non-permissive temperature, but, as shown by density labelling, new initiation of virus DNA replication is inhibited under this condition. The results indicate that the 401 gene function is involved in the initiation of virus DNA synthesis in the lytic cycle.


Increased calcium-activated neutral protease activity in muscles of dystrophic hamsters and mice. A Ca2+-activated neutral protease activity was examined in muscles of normal and dystrophic hamsters and mice. Light grey and golden brown strains of normal and B10 14.6 strain of dystrophic hamsters were used. Normal and dystrophic mice were of the Bar Harbor 129 ReJ strain. Enzyme activity was measured in the post myofibrillar fraction (homogenate) and in the 75,000 x g pellet (particulate fraction) and supernatant using purified myofibrils. In normal and dystrophic hamsters or mice, the Ca2+-activated neutral protease was most active in the supernatant followed by the homogenate and particulate fractions. As compared to fractions from normal muscle, enzyme activity was significantly elevated in all 3 fractions from dystrophic muscles of hamsters and mice. Both homogenate and supernatant fractions from muscles of normal hamsters had significantly higher enzyme activity than those of normal mice. Enzyme activity was similar in the particulate fraction. Similarly enzyme activity in the 3 fractions from dystrophic hamster and mouse muscles showed no significant difference. It is suggested that the Ca2+-activated neutral protease may be involved in muscle fibre necrosis in muscular dystrophy.


Inhibition by polyunsaturated phospholipids of experimental allergic encephalomyelitis in the guinea pig. This paper reports the effect of polyunsaturated phospholipids (Lipostabil, Nattermann, Cologne) on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. A dose of 100 mg/kg of Lipostabil solution, containing about 50 mg of unsaturated fatty acids (UFA), was inoculated i.v. beginning on the 3rd day after sensitization with 100 microgram of basic protein (BP) in complete Freund's adjuvant (CFA). A series of 7--14 daily injections either completely inhibited EAE or reduced its severity. The production of anti-BP antibodies, detected by indirect immunofluorescence and radioimmunoassay, was not affected, whereas cellular reaction as measured by a skin test was markedly reduced. These findings confirm previous reports on the immunoregulative effect of UFA, even if a potentiating effect of additional components of Lipostabil (vitamin B6, nicotinic acid and adenosine-5-monophosphoric acid) cannot be excluded. Serological findings support the assumption that the regulative effect mainly influences the cellular response. In this way deviation in the immune reaction leading to cellular immunopathology might be prevented or decreased.


Decrease of muscle extensibility and reduction of sarcomere number in soleus muscle following a local injection of tetanus toxin. Slow soleus muscle in guinea pig developed within 4--6 days after local injection of a sublethal dose of tetanus toxin and 2--4 days after the first signs of local tetanus, a myostatic contracture characterized by a change in the passive tension--lengthening curve associated with a considerable decrease of the sarcomere number. It was demonstrated by clinical and EMG investigations that the soleus did have a tetanic spasm at least within the 2--4 day period of observation. When local tetanus was confined to slow soleus by functional suppression of rapid gastrocnemius and ankle flexor muscles, the decrease of the sarcomere number still persisted. This decrease failed to occur after section of the nerve supplying the soleus when associated with an injection of the tetanus toxin, and was much greater than when the soleus was passively shortened for the same period of time by plaster cast.


Benign intracranial hypertension. A retrospective and follow-up study. Thirty-six patients with benign intracranial hypertension (BIH) were reviewed. Follow-up was obtained on 33 patients (91%) after a mean period of 7 1/2 years. Precipitating factors were found in 27 patients (75%). On admission, 5 patients had retro-ocular pain, especially on eye movements, a complaint not yet described in BIH. Seven patients had nystagmus, two of them horizontal positional nystagmus. It is questionable whether all signs in BIH are caused by the raised CSF pressure. The general outcome was good. Only two patients sustained severe ultimate visual impairment. Both presented with retro-ocular pain and sudden loss of vision on admission. Papilloedema can persist for years in BIH without serious visual impairment. Sometimes "causal" treatment is possible. No symptomatic treatment which is free from complications has been proved to prevent visual failure.


Clinical data and the identification of special forms of multiple sclerosis in 1271 cases studied with a standardized documentation system. In a multicenter study the clinical data of 1271 patients with multiple sclerosis (MS) were recorded in a standardized manner and analysed by a computer program. Some of the retrospective data are compared with previous reports. The frequency of optic nerve involvement in the present series was close to the Japanese figures. The development of signs and symptoms during the course of MS was given for the 1271 patients and differences in the reversibility of symptoms are presented. In this study, one of the chief purposes was the selection of groups of MS patients with particular symptomatology and course of the disease for prospective, detailed study. The following groups were selected and are under further investigation: 109 patients with an exclusively spinal symptomatology throughout the course of their disease; 441 patients with optic neuritis as initial symptom; 110 patients with early brain-stem involvement; 64 benign cases (duration of the disease more than 14 years and disability not more than 3 according to Kurtzke), 35 malignant cases (duration of the disease under 5 years and disability grade of 7 or more); 83 families with more than one member with MS; 289 females with a history of pregnancy, childbirth and/or use of oral contraceptives. In 339 patients a lumbar puncture was performed at the present examination. The parameters determined constitute a pathognomonic pattern highly indicative of the diagnosis of MS.


Adrenoleukodystrophy brain cholesteryl esters and other neutral lipids. Further examination of the neutral lipid fractions derived from brain tissue of two patients afflicted with adrenoleukodystrophy has demonstrated the presence not only of free cholesterol and cholesteryl ester, but also of appreciable free fatty acid and triglyceride. Using a gas--liquid chromatographic system normally employed for the analysis of long-chain fatty acids of galactolipids and spingomyelin, it was possible to establish the presence of long-chain (greater than C20) fatty acids in the cholesteryl ester, free fatty acid and triglyceride fractions. Long-chain fatty acids were most abundant in the cholesteryl esters. Fatty acids identified by gas--liquid chromatography and gas chromatography--mass spectroscopy included normal saturated and monounsaturated fatty acids as large as C34. Several unknown fatty acyl compounds, of as yet undetermined structure, were also observed. All investigations thus far would indicate that the pathogenesis of adrenoleukodystrophy is closely related to the aberrant metabolism of these long-chain fatty acids.


Magnesium and inorganic phosphate content in CSF related to blood-brain barrier function in neurological disease. In normal controls and in a large number of neurological patients divided into certain disease groups both Mg and PO4 were determined in cerebrospinal fluid (CSF) and serum. For both Mg and PO4 there was a marked concentration gradient between CSF and serum in normals where Mg was higher and PO4 content lower in CSF. Comparison of CSF values with serum values of patients showed pathological changes only in CSF, serum values always being within the control range. A number of disease processes associated with a disturbance of blood-brain barrier (BBB) function such as inflammatory CNS disease or CNS tumors showed significant alterations of PO4 concentrations in CSF which are interpreted as an approximation of serum values. A similar decrease of Mg did not reach statistical significance. Both Mg and PO4 in CSF showed a correlation with CSF protein concentrations, but no relationship with cells in CSF. Patients with cerebrosvascular disease were not significantly different from controls as regards their Mg and PO4 in CSF, but a small subgroup consisting of patients with an intracranial hemorrhage showed elevation of both Mg and PO4 which could signify cell necrosis rather than BBB dysfunction. Patients with disc protrusion or peripheral neuropathy did not demonstrate any abnormality of CSF Mg and PO4. In the multiple sclerosis group individual patients had elevated CSF concentrations of PO4 but the group as a whole is not different from the controls.


Multi-infarct dementia.

Multi-infarct dementia. Fifty-two patients presenting with dementia were divided into a group in whom clinical features suggested an ischaemic basis (multi-infarct dementia) and a group in whom a primary degenerative process seemed more likely. Focal EEG changes and angiographic evidence of ischeamic areas and atheromatous disease of intracranial vessels were more common in the "ischaemic" than in the primary degenerative group. CBF was significantly reduced in the former but the regional pattern was equally distorted in the two groups. These findings strengthen the belief that the ischaemic score can identify those patients whose dementia is associated with vascular disease.


An experimental model for cerebral metastasis: preliminary light and ultrastructural studies. An experimental model for hematogenously spread cerebral metastases by injection of a suspension of M3 fibrosarcoma cells into the carotid artery of C57 BL/6 mice was developed. Intracerebral metastatic tumor nodules were consistently produced by this method with subsequent death of the animals. Development of extracerebral metastatic disease was minimal. Light and electron microscopic studies were carried out at various time intervals postintracarotid injection of tumor cells to observe the morphologic events during the development of the brain metastases. Tumor cells were observed arrested in the cerebral capillaries from 15 minutes to 4 days post-injection. From 1 day to 4 days post-injection, individual tumor cells were also observed in the pericapillary spaces in the brains of the injected animals. From 5 days post-injection on, tumor cells were seen to be proliferating in peri-capillary spaces displacing the brain parenchyma and eventually formed tumor nodules with resulting death of the animals. Morphological changes were observed in the endothelial cells of the blood vessels which were surrounded by the growing metastatic tumors. This model, and modifications thereof, should prove to be valuable in the study of cerebral metastatic disease.


Acoustic response characteristics of neurons in nonspecific areas of cat cerebral cortex. 1. Acoustic properties of single neurons in pericruciate, anterior lateral, and medial suprasylvian "association" areas were studied in chloralose-anesthetized cats using sealed stimulating systems incorporating probe microphone assemblies. 2. A total of 652 cells were isolated. Approximately 70% of the cells in each area were responsive to acoustic stimulation, and the majority of these cells were also driven by visual and/or somatosensory stimulation. 3. Association cortex neurons responded to tone- or noise-burst stimulation with an onset response of 16--50 ms latency. The onset response was found to be followed by a long period of suppression in those cases in which spontaneous activity was sufficiently high for this to be detected. 4. The majority of 56 units for which detailed frequency-tuning data were obtained had broad, irregular tuning curves extending over 5--6 octaves or more. A small proportion of association cortex cells exhibited sharp tuning comparable to that obtained in control recordings from cells in primary auditory cortex (AI). Although a number of broadly tuned units were rather insensitive, many cells--both broadly and sharply tuned--were of comparable sensitivity to AI cells. 5. Of the association cortex cells examined for binaural properties, 95% received excitatory input from each ear, and the dominant mode of binaural interaction in these cells was one of occlusion. The occurrence of occlusion at suprathreshold intensities reflected a tendency for monoaural and binaural intensity functions to asymptote at the same level. 6. The broad tuning, lability, and polysensory convergence exhibited by association cortex cells are similar to those of the so-called auditory lemniscal adjunct system. However, the binaural properties of association cells differ significantly from those of both the lemniscal line and adjuct components of the auditory pathway. 7. The homogeneity of acoustic and polysensory input to the three association fields is compatible with their input being derived from the single subcortical nonspecific projection system (reticular formation and medial/intralaminar thalamus) postulated by previous investigators. However, both neuroanatomical and neurophysiological evidence suggest that the lemniscal adjunct system and certain areas of periauditory cortex might also contribute to this input.


Importance of corpus callosum for visual receptive fields of single neurons in cat superior colliculus. 1. Section of the posterior two-thirds of the corpus callosum eliminates almost completely the response of superior colliculus (SC) neurons to stimulation of the contralateral eye in split-chiasm cats. On the contrary, the responsiveness of SC neurons to stimulation of the contralateral eye is not abolished by a transection of the posterior and tectal commissures leaving the corpus callosum intact. The callosal section also reduces the number of SC receptive fields abutting the vertical meridian in the ipsilateral eye of split-chiasm cats. 2. In cats with intact optic pathways, a similar callosal section abolishes the SC representation of the ipsilateral visual field in the ipsilateral eye and also reduces the number of receptive fields adjoining the vertical meridian in the same eye. In the contralateral eye, the SC representation of the ipsilateral visual field is reduced in extension to about one-fifth of that seen in cats with intact commissures. 3. The results suggest that the corpus callosum is the main pathway for cross-midline communication of visual information at not only the cortical, but also the midbrain level. The corpus callosum may subserve this function because it contains uninterrupted crossed corticotectal projections or because it transmits visual information from one hemisphere to contralateral cortical areas projecting ipsilaterally to SC. The latter hypothesis is more likely but, in any case, the findings imply that the lack of interhemispheric transfer of visual learning in cats with a chiasmatic and callosal section may depend on a midline disconnection of both subcortical and cortical visual centers. 4. The corpus callosum is also responsible for the representation of the ipsilateral visual field of the ipsilateral eye in the cat SC. The SC representation of the ipsilateral visual field in the contralateral eye is due, in minimal part, to direct retinotectal connections from temporal retina and, for the largest part, to the corpus callosum. 5. Finally, the corpus callosum contributes to the representation of the contralateral visual field near the vertical meridian of the temporal retina in both split-chiasm and normal cats. This is probably due to the scarcity of direct retinotectal projections from this part of the retina and to their supplementation by corticotectal neurons influenced by the callosal afferents.


Triggering of lordosis reflex in female rats with somatosensory stimulation: quantitative determination of stimulus parameters. 1. Pressure on the skin of the tail base and perineum of female rats in the range of 40--440 millibars, following bilateral contact with the flanks, was adequate to elicit the lordosis reflex. Hair deflection alone or noxious stimulation was neither sufficient nor necessary for lordosis behavior to occur. 2. For a given pressure, increasing the area of stimulation increased the effectiveness for evoking lordosis; inputs from mechanoreceptors at different skin locations can be summated to trigger the behavioral response. 3. During mating behavior, increased pressure from the male rat on the skin of the female, in the range of 50--450 millibars, was associated with increased probability and strength of lordosis. 4. Increasing the dose of estrogen increased the probability of lordosis to a given pressure stimulus. The hormone effect can be characterized as a facilitation of the throughput from low-threshold pressure receptors on tail base and perineum to motoneurons for the lumbar vertebral dorsiflexion of lordosis.


Responses of single units in sixth lumbar dorsal root ganglion of female rats to mechanostimulation relevant for lordosis reflex. 1. The activity of single units (n = 312) was recorded from dorsal root ganglion L6 in female rats; 84% received input from cutaneous mechanoreceptors. 2. Among cutaneous mechanoreceptive units (n = 263), 22% responded to individual guard hair movement, 18% to down hair, 11% to clitoral hair, and 14% to stimulation of tylotrich hair-haarscheibe (type I) receptors, 5% responded to punctate skin deformation, but not hair movement of pressure, and 18% responded to pressure. 3. No significant differences between estrogen-treated and untreated ovariectomized rats were observed in receptive-field size, or von Frey hair, or pressure threshold of any given type of unit. 4. The lordosis reflex of female rats is triggered by pressure, but not hair deflection, on skin regions innervated by dorsal root L6 (10). Stimulation from the male rat mounting would cause a barrage of action potentials from most of the unit types identified here, but only pressure units and type I units gave sustained responses to a lordosis-triggering type of pressure stimulation.


Interlimb coordination during stepping in the cat: an electromyographic analysis. 1. Simultaneous electromyographic (EMG) records were obtained from a single-joint extensor muscle of each of the four limbs of intact cats during repeated overground stepping trials. 2. In each limb, the temporal spacing of step cycles was determined by measurements of the intervals between consecutive terminations of EMG activity, since this occurs in a consistent relationship to the removal of the limb from the ground. By measuring the latencies between step cycles so determined, the temporal spacing of step cycles between limbs was determined. Each latency was expressed as a function of step duration or as a phase interval. 3. Analysis of the cooordination of step cycles of both homologous limb pairs (the forelimbs and hindlimbs), both homolateral limb pairs (the fore- and hindlimb on the right and left sides), and both sets of diagonal limbs suggest that the step cycles of the four limbs are coordinated according to a few frequently occurring patterns. However, the representation of a large number of phase intervals between these preferred patterns indicates a substantial amount of variability in interlimb coupling. 4. Analysis of the interaction of different interlimb-coupling patterns indicates that during alternate coordination of hindlimbs, coupling of the other limbs is fairly predictable. The step cycles of the forelimbs and hindlimbs are spaced according to a trotting form of coupling. During in-phase coordination of hindlimbs, the patterns of coordination of the other limbs are more diffuse. Forelimbs step cycles are coupled via a number of different modes, as are those of the forelimbs and hindlimbs. 5. It is concluded that the step cycles of different limbs are coordinated, but the association of observed patterns of coordination with any known neural pathways or the interaction of neural pathways should be approached with caution. The variability about the frequently occurring patterns is interpreted as an expression of the faculatative capabilities of the neural mechanisms controlling locomotion. Thus, these data favor a model of interlimb control during stepping, which recognizes preferred patterns of coordination and the variability about these patterns.


Phrenic motoneurons in the cat: subpopulations and nature of respiratory drive potentials. 1. Intracellular recordings were made from 78 phrenic motoneurons (PM) in anesthetized, paralyzed, artificially ventilated cats that were slightly hypercapnic. 2. Three subpopulations of PM (types A, B, and A/B) were identified on the basis of their membrane potential trajectories during expiration (E). Type A cells exhibited wholly linear trajectories. These were rapidly hyperpolarized at the onset of E followed by a slow ramp of increasing hyperpolarization observed in 51 of 59 type A cells. Types B (13 cells) and A/B (6 cells) had nonlinear trajectories in E. Type B cells approached their end-expiratory potential levels more slowly. 3. Measurements of axonal conduction velocity, expiratory phase input resistance, initial depolarization rate, and initial spike onset during inspiration revealed that type B cells had significantly slower axonal conduction velocities, higher input resistances, greater initial depolarization rates, and earlier initial spike onsets than type A cells. The properties of type A/B were intermediate between the other cell types. These results support the hypothesis that the PM pool is not homogeneous. 4. Active E-phase inhibition of all types of PM was directly demonstrated by reversal of the increasing hyperpolarizing wave to a depolarizing wave with hyperpolarizing current injection using a bridge circuit. Thus hyperpolarization of PM during E is not merely due to a central disfacilitation. 5. During hyperpolarizing current injection the inspiratory phase membrane potential trajectory of all PM became a ramp depolarization similar to that seen during control conditions in type A cells. These results support the conclusion that all cells within the PM pool are receiving a similar central excitatory synaptic input during inspiration. The rapid initial depolarization of type B and their concomitant early spike onset is a consequence in part of a rebound excitation from their expiratory phase inhibition as well as a higher input resistance, probably due to a smaller cell size. 6. Expiratory related neural activity was recorded within the phrenic motor nucleus. It is suggested that these expiratory related neural elements, based on the temporal pattern of their activity, may be responsible for the active inhibition of PM.