Origin of IgA-secreting plasma cells in the mammary gland. Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine.


Plasma cell immunoglobulin secretion: arrest is accompanied by alterations of the golgi complex. Conditions influencing Ig secretion by plasma cells have been studied with suspensions of murine plasma cells and myeloma cells by determining the release of (3)H-Ig after a pulse of biosynthetic labeling with L- [4,5-(3)H]-leucine. Ig secretion is insensitive to a variety of hormones, mediators, cyclic nucleotide derivatives, extracellular calcium depletion, and agents acting on mierotubules or microfilaments; i.e., to a number of factors which are involved in the regulation of secretion by cells with a storage compartment. On the other hand, Ig secretion is markedly inhibited by conditions which (a) lower intracellular calcium levels (ionophore A 23187 in Ca(++)-free medium), (b) induce partial sodium/potassium equilibration (the ionophores monensin and nigericin and, in the case of myeloma cells, ouabain and incubation in K(+)-free medium) or (c) uncouple oxidative phosphorylation. The first two situations are accompanied by striking alterations of the ultrastructural appearance of the Golgi complex, different in each case. These ultrastructural observations, together with autoradiographic experiments after a short pulse with L-[4,5-(3)H]-leucine, have led to the following hypothesis: (a) under Ca(++) depletion (3)H-Ig passes to Golgi vesicles but these vesicles are incapable of fusion or migration and therefore accumulate in exaggerated numbers in the Golgi area; (b) under partial Na(+)/K(+) equilibration, (3)H-Ig passes to Golgi vesicles which have an exaggerated tendency to fuse with other Golgi elements, thereby generating large vacuoles which store increasing amounts of Ig; (c) under energy block, multiple membrane fission and fusion events are inhibited and there is therefore, little intracellular transport of (3)H-Ig or alteration of cell ultrastructure.


The genetic polymorphism of the fourth component of human complement: methodological aspects and a presentation of linkage and association data relevant to its localization in the HLA region. The C4 polymorphism in man has been studied by immunofixation electrophoresis, crossed immunoelectrophoresis, and functional detection after agarose gel electrophoresis. It has so far not been possible to reveal this polymorphism by isoelectric focusing and functional detection of C4 bands. Three common alleles and one less frequently occuring allele have been identified. In a small population sample studied by all the different techniques and verified by family segregation, the following gene frequencies have been found: C4F: 0.46, C4S: 0.32, C4F1: 0.20, and C4M: 0.02. By linkage and association studies in a family material it has been shown that a structural C4 locus is situated in the HLA region of chromosome 6 very close to the HLA-B and Bf loci.


Expression of a new cell surface antigen on activated murine macrophages. A macrophage cell-surface antigen associated with pyran and Corynebacterium parvum-activated macrophages and P388D1 cells but not detectable on normal or glycogen and thioglycollate-elicited murine macrophages has been described. The antigen was demonstrated both by complement-mediated cytotoxicity and immunofluorescence, using an appropriately absorbed rabbit antiserum to P388D1. This antiserum should enable the characterization of activated macrophage cell populations on an individual cell basis and should be a useful probe to study the interactions of macrophages with tumor cells and the relationship of activation to cell-surface changes.


Blocking of in vitro and in vivo susceptibility to mouse hepatitis virus. By pretreatment with concanavalin A (Con A) both in vivo and in vitro genetically susceptible mice and their cultured macrophages have been converted to animals and cells which are phenotypically resistant to mouse hepatitus virus (MHV). Con A at 1.0 mg/mouse decreased the mortality from 100% to less than 40% by inducing a prominent inflammatory response, increasing the number of macrophages in the virus inoculation site, and producing a population of macrophages not uniformly susceptible to the virus. In addition, mediators derived from Con A-treated spleen cells conferred resistance to normally susceptible syngeneic macrophages to 100 TCID50 of MHV.


Complement bridges between cells analysis of a possible cell-cell interaction mechanism. Different leukocytes (Raji, Daudi, Rael lymphoid cells; human peripheral blood lymphocytes, and guinea pig granulocytes), which had been coated with C3 by incubation of 37 degrees C for 20 min in a C3 solution, were demonstrated to form rosettes with erythrocytes coated with complement components (EAC142). The percentage of rosettes was dependent of the amount of C3 present on the cells. Loading of the lymphoid cells with C3 was a time- and temperature-dependent process. C3b was unable to serve the same purposes, although C3 and C3b occupied the C3 receptors on the lymphoid cells to a comparable degree. C3 functions in a similar manner. The C42 enzyme can be replaced by trypsin, so that bridging units may consist of C3 + C42, C5 + C42 OR C3 + trypsin, and C5 + trypsin. Bridging units can be constructed also from C4 + C1. It is suggested that enzymes on one cell liberate labile binding groups of complement components on adjacent cells, thus inducing coupling of the two cells. The possibility is raised that this type of cell interlinkage may play a role in vivo, since there is accumulating evidence that complement components are expressed in the plasma membrane of different cells.


Functional characterization of a stable, noncytolytic stage of macrophage activation in tumors. The state in which macrophages (Mphi) from regressing Moloney sarcomas could kill tumor target cells was a highly labile one which decayed rapidly in vitro. Thereafter, regressor Mphi were noncytolytic. Mphi from several different progressing sarcomas failed to kill, even when challenged with target cells immediately after explantation. Similarly, thioglycollate-induced peritoneal Mphi (TG-Mphi) did not kill. Noncytolygic Mphi derived either from progressing sarcomas or from long-term (up to 96 h) cultures of regressor Mphi were exquisitely sensitive to stimulation by bacterial lipopolysaccharide (LPS); picogram/milliliter amounts induced killing. Similar concentrations of LPS had no demonstrable effect on TG-Mphi. Thus, tumor Mphi generally appeared to have been primed in vivo, with those in regressing sarcomas having additionally acquired cytolytic activity. Inability of progressor Mphi to kill apparently stemmed from lack of, or failure to respond to, the signal needed in vivo to trigger cytolytic activity, rather than the total absence of activation.


Immunization of mice with syngeneic Moloney lymphoma cells induces separate antibodies against virion envelope glycoprotein and virus-induced cell surface antigens. Immunization of mice with heavily irradiated syngeneic Moloney lymphoma cells evokes antibodies against the major viral envelope antigen, gp71, and the Moloney virus-induced cell surface antigen (MCSA). A9HT cells, an L-cell subline, react with the antibodies against the viral envelope antigen only; this reaction can be completely inhibited by virus or purified gp71. Reactivity to Moloney lymphoma cells (YAC) was only partially inhibited (maximum 30%) or not at all. This can be attributed to the reaction of the YAC cells with antibodies directed against MCSA, a nonvirion cell surface component according to both biological and biochemical evidence. Antibody-induced capping of gp71 or p15(E) did not change the membrane distribution of MCSA or H-2, indicating that these antigens represent distinct entities on the cell surface. MCSA showed only minimal capping and thereby differed in behavior from both H-2 and virion antigens. gp71 could be capped by the mouse antiserum as revealed by subsequent staining with monospecific anti-gp71 antiserum. Under ordinary test conditions this reactivity is overshadowed by the reaction against MCSA. The lack of MCSA capping reflects a difference in anchorage of this antigen.


Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering. Using a specific and sensitive fluorometric assay, the H2O2 release from as few as 2 X 10(5) mouse peritoneal macrophages could be detected continuously and quantitated. It is emphasized that the assay measured H2O2 release, not production. Induction of H2O2 release required sequential application of two stimuli: the administration of an activating agent to the mice from 4 days to 10 wk before all harvest, and the exposure of the cells in vitro to a triggering agent. BCG was most effective as an activating agent, resulting in peritoneal macrophages which could be triggered to release H2O2 almost as copiously (8 nmol/10(6) macrophages per 5 min) as mouse peritoneal PMN (9 NMOL/10(6) PMN per 5 min). Casein and C. parvum could also serve as activators, but thioglycollate and FCS were ineffective after single injections. PMA was a potent triggering agent, resulting in a maximal rate of H2O2 release after a latency of about 40 s for cells in suspension. Other triggering agents included the ionophore A23187, concanavalin A in the presence of cytochalasin B, and phagocytosis. H2O2 release could be attributed to macrophages and PMN in peritoneal cell suspensions or in preparations of adherent peritoneal cells, but not to lymphocytes. Indirect evidence suggested that the H2O2 detected was formed from superoxide anion. These observations appear to justify renewed interest in the idea that H2O2 may be important in macrohpage antimicrobial and antitumor mechanisms.


[Binding of cortisol, fluocortolone and difluocortolone to human plasma proteins (author's transl)]. The binding properties of [3H]cortisol, [3H]fluocortolone and [3H]difluocortolone by human plasma, human albumin, human- beta- and gamma-globulins have been studied by equilibrium dialysis. Cortisol, in physiological concentrations (0,4 micromol/l), is 98% bound in human plasma at 25 degrees C, fluocortolone 96% and diflucortolone 85%. Uncer physiological conditions cortisol is mainly bound to the corticosteroid binding globulin (transcortin). 2/3 of fluocortolone is bound to transcortin and 1/3 to albumin and globulins, whereas difluocortolone is mainly bound to albumin and to globulins but not to transcortin. The binding affinities of beta- and gamma-globulins are -ery low for the corticoids investigated, but they are higher for fluocortolone and difluocortolone than for cortisol.


Influence of drugs on clinical chemical data for serum glucose, investigated with the automated glucose oxidase-perid method. Fifty drugs, applied in the therapy of internal diseases, were investigated for their effect on the clinical chemical determination of serum glucose by the automated GOD-Perid method. The results showed a statistically significant depression of the reported glucose value, by 7 drugs containing the pyrazolone group and its derivatives (Baralgin, Butazolidine, Analgin, Novalgetol, Analgocain, Irgapyrin, Aminopyrin) P less than 0.001; P less than 0.01. The influence depends on the quantity of drug and on the time interval between loading and glucose analysis.


Carcino-embryonic antigens, oestrogen receptors and androgen receptors in human breast tumours. Clinical evaluation of carcino-embryonic antigen, IV. This paper, the fourth in a series devoted to the study of the clinical usefulness of estimations of carcino-embryonic antigen (CEA), describes CEA levels in extracts of metastatic breast tumours. --Two groups can be distinguished, with CEA values higher or lower than 1.5 microgram CEA per g protein. The group of tumours with a CEA level  exceeding 1.5 microgram/g (CEA-positive) included a significantly larger percentage or oestrogen receptor-positive tumours than the group with lower CEA levels (CEA-negative). --It is stated that CEA-negative metastases are most likely to be found in patients who fail to respond to hormonal therapy. --No relation was demonstrable between the presence of androgen receptors and the CEA level. All the possible permutations of CEA, oestrogen receptors and androgen receptors were encountered in the tumours examined.


Determination of copper and iron in human blood serum by energy dispersive x-ray analysis. Human blood serum has been analyzed  by X-ray fluorescence spectroscopy utilizing the effect of background reduction by total reflexion of the incident X-ray beam on an optical flat as sample support. For sample preparation a drop of 10 microliter serum was pipetted onto the support and dried to a thin film. The minimum detectable limit was about 1.5 mmol/l in 1000 s and the precision in the 20 mmol/l range of the metals was 3-5%.


Comparison of control materials containing animal and human enzymes. Comparison of enzymes of human and animal origin, III. Highly purified enzymes of diagnostic interest from human and animal organs, dissolved in pooled human serum and in bovine serum albumin solution, were compared with respect to their response to alterations in routine clinical chemical assay conditions. Their response to changes in temperature, substrate concentration and pH-value was the same. In addition, the storage stability in each matrix was identical in the lyophilized and the reconstituted state, whereas some enzymes were remarkably less stable in the pooled human serum than in bovine serum albumin. This better stability, the better availability and decreased infectious nature of the material lead to the conclusion that animal enzymes in bovine serum albumin matrix are the material of choice for the quality control of enzyme activity determinations in clinical chemistry.


[Determination of urea with the Merckognost test strips, and a comparison with a photometric method (author's transl)]. The precision and practicability of the Merckognost-Urea Test Strips was tested in plasma, haemolysate, capillary and venous blood. The diacetylmonoxim method using an AutoAnalyzer II was taken as the reference method. The possibility of varying haematocrit values influencing the whole blood findings was taken into consideration in the investigations.


[A reagent-saving modification of the glucose dehydrogenase method for the determination of glucose in venous and capillary blood using the Autoanalyzer II (author's transl)]. A modification of the glucose dehydrogenase method for the Autoanalyzer II is described, which permits a considerable reduction in the quantities of enzymes and coenzyme, without affecting linearity. Using the new modification and a sample frequency of 80 per hour, glucose can be determined in venous blood and in diluted capillary blood haemolysates with no change in the construction of the apparatus.


Non-destructive neutron activation analysis of copper in liver samples and other biological materials. Neutron activation analysis via the short-lived radionuclide 66Cu was applied in the determination of the level of copper in tissues. With this procedure the samples are analysed non-destructively and can therefore be used for further histological tests. The applicability of the method in the analysis of biopsy samples is discussed.


[Biochemical data in the fluids of cystic degenerated euthyroid goiters (author's transl)]. Examinations of sera and cyst fluids in patients with cystic degenerated euthyroid goiters showed significant differences between the values of the cyst fluids and sera for almost all of the chemical substances. In the brown cyst fluids there are mostly higher values compared with the appropriate sera. Autolysis, diffusion and resorption, metabolic changes and, in the case of thyroid hormones, active incretion by wall-forming thyroid tissue, are the reasons for these differences in the concentrations.


[Hydroxyproline fractions in blood (author's transl)]. Modified methods for the determination of bound hydroxyproline in blood are presented. The fractionated and hydrolyzed samples are separated from interfering material by ion exchange chromatography. Internal standards are used to correct for recovery. After a several fold concentration of samples it is possible to work with reduced blood volumes. Up to 6.12 mumol/l of free and peptide-bound and 11.5 mumol/l of protein-bound hydroxyproline are detectable. Using the described methods hydroxyproline was determined in a pooled human plasma and in the sera of rats.


[A simple method for the radioimmunologic determination of sex steroids in plasma (author's transl)]. A simple method for the determination of plasma steroids by radioimmunoassay is described. Essential steps are: Dissolution of extraction residues in 20 microliter ethyl alcohol or direct addition of 20 microliter alcoholic plasma extract to the incubation tubes, addition of tracer solution with known tracer mass and antiserum dilution or gelatine phosphate buffer, incubation for 40 min and separation of free from bound radioactivity by charcoal-coated florisil. Plasma steroid levels are calculated by a simple equation, an immunologic equivalent to the tracer mass serves as the reference value.


Agarose gel electrophoresis of cerebrospinal fluid proteins and analysis of the pherogram profiles by analog computer. A micro-method of agarose gel electrophoresis requiring 1--3 ml of cerebrospinal fluid for quantitative analysis of cerebrospinal fluid proteins is described. After concentration of CSF to about 50 microliter by ultrafiltration and refractometric determination of protein, approximately 20--40 microgram of total protein are used for electrophoresis. Photometric scanning of the electrophoretic pattern at two different wavelengths permits quantitative evaluation. The pherograms are analysed by means of a modified DU-PONT analog computer. Factors which influence quantitative electrophoresis are examined. In cerebrospinal fluid of normal children 15 protein fractions are demonstrated: 2 prealbumins, albumin, 5 alpha-, 3 beta- and 4 gamma-globulins.


Acid phosphatase activity in lymphocytes from patients with Spielmeyer-Vogt-Batten's syndrome. The purpose of the investigation presented was to study whether the lymphocytes from patients with Spielmeyer-Vogt-Batten's syndrome deviate from normal with respect to acid phosphatase activity. The distribution of the activity seems to show that the patients with Spielmeyer-Vogt-Batten's syndrome can be divided into two groups, viz. one in which the values are concentrated around the normal level, and another with increased values.


Isolation of human urinary kallikrein by affinity chromatography. Determination of human urinary kallikrein, I. Human urinary kallikrein (EC 3.4.21.8) was purified to electrophoretically homogeneity by gel filtration on Sephadex G-100, followed by affinity chromatography on aprotinin-Sepharose. The molecular weight, estimated by gel filtration, is 64,000 Daltons, by dodecyl sulfate electrophoresis 45,000 Daltons and 29,000 Daltons, and it is microheterogeneous on electrofocusing, yielding isoelectric point values of 3.8, 3.9 and 4.05. The kinetic constants for hydrolysis of BZArgOEt, TosArgOMe, CbzTyrONp, and human HMW-kininogen were determined. Benzamidine and aprotinin are competitive inhibitors of human urinary kallikrein.


[Enzyme diagnosis in lipaemic sera before and after polyanion precipitation with heparin and magnesium chloride (author's transl)]. The method for the determination of enzymic activity in turbid, lipaemic sera, which involves clearing by polyanion precipitation with heparin and magnesium chloride, was critically reviewed. In the diagnosis of diseases of the liver and pancreas, which are frequently associated with hyperlipoproteinaemia, only residual enzyme activities are measured in the cleared serum after polyanion treatment. In the measurement of glutamate dehydrogenase and in the Phadebas test for alpha-amylase, the enzymes are inactivated by treatment with heparin and magnesium chloride. On the other hand, as a result of polyanion precipitation gamma-glutamyl transferase is transferred, together with lipoproteins and chylomicrons, to the lipid-rich supernatant. Acid phosphatase also exhibits only residual activity in cleared serum. The activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine arylamidase, cholinesterase, creatine kinase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase, and the activity of alpha-amylase in the Merckotest are not affected by polyanion treatment of the serum.


[Isolation and identification of some metabolites of phenyramidol (Cabral) from human urine (author's transl)]. The biological transformation of phenyramidol (I), some of which is also excreted unchanged, occurs by three main degradative pathways: 1. Hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI). 2. Cleavage of the ethanolamine chain with the formation of 2-aminopyridine (metabolite II) and presumably mandelic aldehyde. 3. Conjugation with glucuronic acid (metabolite III). Secondary reactions result in the production of: benzoyl carbinol (metabolite XV), benzoic acid (metabolite XI), mandelic acid (metabolite XII) and the glucuronides of V, VI, VII, XII and possibly II (metabolites VIII, IX, X, XIII and IV), all of which were also found as free, unconjugated compounds. A further, unusual reaction is the dimerisation of metabolite VI with the formation of a dipyridyl derivative (metabolite VII), which is excreted partly as the free compound, but mainly as the glucuronide (metabolite X). The occurrence of 2-(N-benzylamino)-pyridine (XIV) in the urine could not be explained. Four futher excretory products (metabolites XVI, XVII, XVIII and XIX) were not identified; XVI and XVII were extracted at an alkaline pH, whereas XVIII and XIX were extracted under neutral conditions. They could be detected both as free compounds, and after hydrolysis with HCl or alkali, but not after treatment with beta-glucuronidase.


[A fully enzymatic triglyceride determination in a continuous flow 12-channel analyzer (author's transl)]. A fully enzymatic triglyceride determination utilizing enzymatic hydrolysis with a lipase-esterase mixture and subsequent enzymatic glycerol determination, has been adapted for use in a continuous flow 12-channel-analyzer. The method is linear up to 7.9 mmol/l (700 mg/100 ml). The analytical precision in the concentration range of 1.5 to 5.4 mmol/l (133 to 478 mg/100 ml) is characterized by relative standard deviations of 0.8 to 4.8%. In the lower measuring range at concentrations around 0.7 mmol/l (62 mg/100 ml) a mean relative standard deviation of 7.2% is found for 1140 measurements under routine conditions. For triglyceride concentrations of 0.9 to 7.7 mmol/80 to 680 mg/100 ml) a mean relative coefficient of verspill Q = 2.0 is determined. Bilirubin caused no observable interference in the determination. In comparison with the manual method by Eggstein & Kreutz (1966) Klin. Wochenschr. 44, 262-267) the results from the fully enzymatic method on the 12-channel-analyzer were lower by approximately 16%, corrected by an additive factor of 0.029 mmol/l (2.59 mg/100 ml). The accuracy controls with controls sera showed a difference of 10%.


Inhibitory effect of histone on the peroxidase activity of the Hp/Hb complex. The human leukocyte nuclear histones can bind to haptoglobin (Hp), and thus interfere with subsequent binding of Hb. The Hp/Hb complex possesses peroxidase activity, but a Hp/histone complex does not. The inhibitory effect of histone molecules depends directly on the Hp and Hb, as well as the histone concentrations. The biological significance of the complex Hp/Hb as a measure of intravascular hemolysis and the interference of histones in this assay is briefly discussed.


[Thin layer chromatography screening test for semiquantitative detection of 4-hydroxy-3-methoxy mandelic acid (HMMA) in urine without extraction (author's transl)]. A thin layer chromatography (TLC) screening test is described, which allows the semiquantitative determination of HMMA in urine samples. From the collected 24 hour urine a measured sample is applied without extraction to a special TLC plate, which is developed in one dimension. In comparison to a series of graded standard solutions the daily HMMA output can be estimated semiquantitatively. In 102 patients over 18 years of age, suffering from high blood pressure, the daily HMMA output was estimated by both the Pisano method (Pisano, J.J., Crout, J.R. & Abraham, D. (1962), Clin. Chim. Acta 7,285--291) and the TLC method. Coincident results with both methods were obtained in 99 of these cases. The residual 3 cases show pathological results with the Pisano method and results in the normal range or the warning range, respectively, with the TLC method. These cases can probably be classified as false positive results of the Pisano method. The TLC method is recommended as a screening test for estimating the daily HMMA excretion.


Determination of the activity of aminotransferases: comparison of two buffer systems with and without supplementary pyridoxal-5'-phosphate. A comparison was made between the aminotransferase activities of a number of plasma or serum samples in 4 reaction media: phosphate buffer, phosphate buffer + pyridoxal-5'-phosphate, tris buffer and tris buffer + pyridoxal-5'-phosphate. The reactions were carried out in the various buffer systems on the same day at 35 degrees C on an automatic kinetic enzyme system (AKES, Vitatron, Dieren, the Netherlands). The highest enzymic activity of both aminotransferases is observed in tris buffer + pyridoxal-5'-phosphate. The activity is about 10--15% higher than in phosphate buffer + pyridoxal-5'-phosphate. Without supplementary pyridoxal-5'-phosphate the differences between both buffer systems are lower or absent. It appears necessary, therefore, to determine the activity of both aminotransferases in a buffer system with tris and to add pyridoxal-5'-phosphate, since assays should be carried out in the presence of optimal concentrations of any of the necessary factors.


Approaches to diagnosis and management of a lumg in the neck. Malignancies of the head and neck constitute 15 percent of the malignancies of all patients seen with cancer. Those individuals who present with neck masses deserve appropriate physical and diagnostic work-up before any surgical or therapeutic approaches are contemplated. In the series of patients presented here, only six percent had unknown primary lesions.


Family medicine approaches maturity.

Family medicine approaches maturity. During the past eight years, since its inception in 1969, the specialty of Family Medicine has gradually been developing toward maturity. With the specialty now firmly based in biomedical science, behavioral science, and patient management, it is prepared to accept a place of full responsibility in the spectrum of health care. This article explores the scope of family practice relating to the needs of a changing society and advocates a broad application of the skills and knowledge involved.


Family medicine: behavioral science contributions. The trend in medicine has been towards specialization which promotes a philosophy that extensive knowledge of a limited field is necessary for competence. Little emphasis has been placed on behavioral sciences as an important aspect for assisting the specialty physician in dealing with patients. Family medicine reverses this trend by emphasizing a breadth of medical knowledge with inclusion of behavioral sciences as a part of training. Behavioral sciences contribute heavily to the education of the family physician in the areas of character, culture, and counseling. The results is a humanistic physician with excellent skills in patient management. The inclusion of behavioral sciences in family medicine places this specialty at the forefront of a new direction in medicine and may well be emulated by other medical specialties.


The family practice resident as sexual counselor. Little research has been done on family practice residents and their sexual counseling attitudes, knowledge, and abilities. This study sought answers to five broad questions about family practice residents' perceptions of sexual counseling. Subjects were 132 residents and 21 faculty members from eight family practice training units in Minnesota, which were affiliated with the University of Minnesota. Residents regard sexual counseling as important and say they desire more training to deal with sexual problems encountered in family practice. They tend to raise the subject of sex with patients not routinely but only if there appears to be a psychosocial problem. Respondents indicate a lack of ability as well as discomfort with several areas of sexuality, notably frigidity and homosexuality. Family practice residents need to develop their skills in specific areas of sexual counseling. While these findings are most applicable to the eight units involved, the diversity in respondents' backgrounds and differences between units suggest that the results may be relevant to other residency programs.


A family practice rotation on a psychiatric service: the experiences, the opportunity, and the challenge. There is a considerable range of mutual interests between the disciplines of family practice and psychiatry. Each field has much to offer and receive from collaborative activities in teaching programs, particularly at the level of residency training. This paper describes the goals, content, methods, and initial experience of a one-month family practice rotation on a psychiatric service with a focus on Emergency and Consultation-Liason Psychiatry.


The pitfalls and perils of countersuits. The term "countersuit" is taking on an enchanting status to physicians, as if it were a miracle drug to cure the malpractice malady. Despite the fact that insurance industry studies show few nefarious malpractice suits, many physicans are convinced that there would be fewer claims if patients and their attorneys knew they might be back in court as defendants for instituting a nonmeritorious suit. Eliminating these few spurious suits, which are very difficult to establish at best, would have little impact on the overall problem. One countersuit may beget another. Although a few physician have been successful, a review of reported cases reveals that most countersuits have ultimately gone against the physician. Additional problems arise when medical societies attempt to alleviate the physician's financial burden by fostering countersuit funds. The funds may relieve the legal expenses, but in turn are fraught with formidable legal consequences, including conspiracy to intimidate prospective litigants and appearance of encouraging litigation. Physicians should proceed with deliberate caution in creating funds and undertaking countersuits.


Construction of an automated health problem inventory. An Automated Health Problem Inventory was designed to monitor resident exposure, provide access to subgroups of the patient population, allow for study of patient care patterns over time, and aid in health-care evaluation studies. Major design steps such as choosing data and codes are discussed. Data collection documents and data reports are described. Data were collected over a 12-month period in two clinical settings - a model clinic in a residency program and a private practice clinics. These data are displayed by categories of problems and frequency of individual problems. The authors comment on the human and procedural support needed to make a data system useful.


The use of computer generated patient profiles to evaluate resident performance in patient care. This paper describes the way in which data from a computer-based health information system are used to review the service experiences of family practice residents. First, it discusses the development of the patient profiles that provide a chronological account of a patient's visits, their purposes, diagnoses, laboratory procedures, treatments, and outcomes. Then, through four cases, it describes the way in which these computer-generated displays are used by faculty to conduct concurrent reviews of residents' performances, to select medical records for review, and to initiate feedback and instruction to residents as they care for their patients.


An integrated medical record and data system for primary care. Part 7: the encounter form: problems and prospects for a universal type. The importance of an encounter form for recording ambulatory patient information is stressed. Certain problems surrounding appropriate definition of the minimum basic data set (MBDS) are discussed as is the potential development of a uniform encounter form which would cover diagnostic information as well as items necessary for insurance companies and internal practice management.


The tired patient.

The tired patient. One of the most challenging diagnostic problems that comes into the physician's office is the patient who complains of "being tired." It can prove to be a frustrating experience for the physician (especially if the physician is also tired) and to the patient. This article will propose and describe a two-pronged systematic approach to the patient that can increase the probability of a satisfying outcome for both physician and patient. This approach assumes the "complaint" of every patient has both informational value ("I think there's something wrong.") and transactional meaning (Please take care of me."). Tiredness, fatigue, "exhaustion" need to be seen simultaneously as information and need. Both aspects require simultaneous work-up.


Serum thyroxine concentrations in larval and metamorphosing anadromous sea lamprey, Petromyzon marinus L. Thyroxine (T4) concentrations in samples of fresh sera taken from fed and unfed larval (ammocoetes) and metamorphosing anadromous sea lamprey (Petromyzon marinus) were measured by means of radioimmunoassay. T4 levels in unfed ammocoetes after a 1-month period were not significantly different from those of the fed ammocoetes. Nutritional state of ammocoetes therefore does not seem to affect their serum T4 levels. Serum T4 concentrations decreased abruptly at the onset of metamorphosis and declined to levels observed in spawing adults (Leloup and Hardy, '76; Packard et al., '76) by the middle (stage 3) of metamorphosis. No significant change in serum T4 levels occurred between stage 3 to the end of metamorphosis. The possible significance of decline in serum T4 levels to the metamorphic event in lamprey is discussed.


Inhibition of early postimplantation development of cultured mouse embryos by bromodeoxyuridine. Mouse embryos were treated with 5-bromodeoxyuridine (BrdUrd) for 24 hours at various preimplantation stages to determine its effect on early postimplantation development. The inhibitory effect of BrdUrd (10(-7) to 10(-6) M) on trophoblast outgrowth and inner cell mass (ICM) development was least severe when embryos were treated at the 2-cell stage and was most severe when they were treated at the morula stage. When embryos were treated at the blastocyst stage, the inhibitory effect on trophoblast outgrowth decreased, but that on ICM development remained severe. The severity of inhibition, particularly that on ICM development, appeared to be related to decreased cell numbers in BrdUrd-treated embryos. However, increasing the cell number by aggregating two ICM's isolated from BrdUrd-treated blastocysts did not increase their chance of survival or of forming two primary germ layers. This indicates that the decrease in cell numbers alone is not the cause of the failure of BrdUrd-treated embryos to develop. The mechanism of BrdUrd inhibition was studied by adding thymidine or deoxycytidine during BrdUrd treatments. A 10-fold excess of thymidine completely protected embryos from the inhibitory effect of BrdUrd. A 10-fold excess of deoxycytidine was less effective. Autoradiography indicated that both thymidine and deoxycytidine protected embryos by interfering with the incorporation of BrdUrd into the DNA.


The effects of temperature and season of collection on the onset and duration of diapause in embryos of the annual fish Nothobranchius guentheri. Annual fish are found in temporary bodies of water in habitats of alternating rainy and dry seasons. The populations survive the dry seasons in the form of embryos encased in the bottom mud. Several genera of annual fish have been reported to exhibit diapause (developmental arrest) at three specific stages of development and it has been proposed that through this adaptation the populations are able to survive the variable durations of the dry seasons. The effects of incubation ans spawning temperatures, and season of collection on the onset and duration of diapause in laboratory populations of the annual fish, Nothobranchius guentheri, were studied. At low incubation and spawning temperatures there was a prolongation of Diapause I and Diapause II. In addition, fish spawned at 25 degrees C during the short days of winter produced embryos that entered a prolonged duration of Diapause II, whereas embryos produced during the long days of summer bypassed Diapause II.


Evidence against gene expression after meiosis in the male mouse. Isozyme patterns in homogenates from various testicular cell types from mice were examined in an effort to ascertain whether the haploid genome is expressed during spermiogenesis. Male mice heterozygous for electrophoretic variants of several glycolytic enzymes were analyzed by starch gel electrophoresis. The enzymes examined were isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, and glucosephosphate isomerase. The isozyme patterns produced by these dimeric enzymes reflect the relative activity of genes in each cell type. These patterns reveal the presence or absence of the transcription of specific genes during spermiogenesis. We found that the genes encoding these enzymes continue to increase during spermiogenesis. Synthesis of these enzymes most likely continues in spermatids, but this synthesis must depend upon premeiotically produced mRNA. These data provide biochemical evidence for the hypothesis that the phenotype of the haploid mammalian gamete depends upon the preceding diploid genome and that a mechanism must exist for the long term post-transcriptional regulation of gene expression during spermiogenesis.


Termination of photorefractoriness in golden hamsters-photoperiodic requirements. The photorefractory period of golden hamsters is characterized by the failure of short daylengths (less than 12.5 hours per 24) to induce gonadal regression. Photorefractoriness is terminated by prolonged exposure to long daylengths (greater than 12.5 hours per 24). This study was designed to determine the precise duration of long day (LD 14 hours light/24) exposure necessary to terminate refractoriness. The data indicate that 11 weeks of LD 14:10 terminate refractoriness in nearly every hamster. Exposure for fewer than 11 weeks is less effective whereas exposure for more than 11 weeks is no more effective. The data show that hamsters begin measuring long days to terminate photorefractoriness irrespective of the physiological state of the reproductive system, and, therefore, that photorefractoriness is induced some time during the period of testicular regression (during the first 10-12 weeks of short day exposure).


Genetic and experimental studies on three associated mutant genes in the Mexican axolotl: st (for stasis), mi (for microphthalmic) and h (for hand lethal). Three mutant genes, st, mi, and h, were discovered in an axolotl male received from Mexico City. All three are recessive to their normal alleles, and appear to segregate independently. Larvae homozygous for st (for stasis) suffer blockage of the circulation at hatching or shortly after, and the majority soon die; any surviving live only a few weeks at most. The mi/mi (microphthalmic) can be identified at the feeding stage. None survives more than a few days. The h/h (hand lethals) live until the digits have appeared on the forelimb. They may then be recognized by the thumb-like orientation of digit 1. Transplants from st/st embryos into normal produce normal structures which persist indefinitely. Those from mi/mi and h/h donors do not survive. The structures (forelimb, gills) derived from h/h donors grow for a relatively long time, and their final death and degeneration result in defects leading to death of most of the recipients. Parabiosis is of no benefit to st/st or h/h mutants and leads to the death of the normal twin; mi/mi mutants undergo a gradual absorption by the normal twin.


Chemotactic behavior of the sperm of chitons (Mollusca: Polyplacophora). Observations of sperm behavior in the vicinity of gradients of egg-water or alcohol extracts of whole freshly-spawned eggs of several chitons reveal what appear to be directed movements of sperm up the gradient, resulting in the aggregation of motile sperm at the gradient source. Plots of the tracks of the sperm approaching the gradient source show that the cells increase the time during which they move toward the source and decrease the time spent moving away. Although this resembles the kinesis behavior shown by bacteria in a gradient, the path directions are markedly non-random. The reorientation behavior of thigmotactic sperm involves enlargement of the normal circular path diameter in the direction of the source and an alternation of tight loops and wide circular arcs, with the latter made in the direction of the source. The form of the path of attracted chiton sperm is like that observed during chemotaxis of the sperm of the hydroid Tubularia and the tunicate Ciona and resembles the behavior of Ciona sperm in that there is no increase in velocity as the cells move up the gradient. However, unlike the cnidarian and urochordate cases, the attracting substances extracted from chiton eggs do not act species-specifically.


Nuclear decondensation of mammalian spermatozoa: changes during maturation and in vitro storage. Swelling of the spermatozoan nucleus and decondensation of the chromatim occur soon after penetration of spermatozoa into the egg cytoplasm. This decondensation was duplicated in vitro by incubating pre-ejaculatory ram, rabbit and bovine spermatozoa and also stored post-ejaculatory bovine spermatozoa in 1% sodium dodecyl sulfate and 2.0 mM dithiothreitol. Spermatozoa obtained from the testis and epididymal caput, corpus and cauda showed a progressive resistance to nuclear decondensation, while no change was evident in the decondensation time of spermatozoa obtained from the epididymal cauda, vas deferens and ejaculated semen. There was also a significant increase in decondensation time after the spermatozoa had been stored in vitro at 25 degrees C. This increased resistance to nuclear decondensation in the in vitro stored spermatozoa, reflecting an increase in cross-linking within the spermatozoan histones by formation of disulfide bonds, may account for part of the increased embryonic mortality observed when spermatozoa are stored in vitro prior to insemination.


The effect of light on forelimb regeneration in the newt. The forelimb of the newt, Triturus (Notophthalamus) viridescens, was bilaterally amputated and the animals subjected to different photoperiods during the period of regeneration, namely (1) continuous light, (2) 15 hours of light/day and (3) total darkness. Animals exposed to continuous light reached the palette regeneration stage four to five days before those kept in total darkness with the 15 hours of light/day animals being intermediate. The difference in regeneration rate was first evident in the moderate early stage (blastema accumulation stage); it then increased during subsequent stages and the difference persisted during the observation period. In an attempt to determine whether the retina was the receptor of light affected, some animals were blinded at the time of amputation and subjected to continuous light. Their rate of regeneration was similar to sighted animals subjected to continuous light but greater than sighted animals in total darkness. The pineal is discussed as the likely mediator of the photo effect.


Timing of sperm penetration, pronuclear formation, pronuclear DNA synthesis, and first cleavage in naturally ovulated mouse eggs. Timing of development of naturally ovulated mouse eggs from sperm penetration to first cleavage, including that of DNA synthesis, was established. In an attempt to limit variability, partial synchronization of ovulation was accomplished by shortening the length of the dark period to five hours, and partial synchronization of sperm entry was attempted by mating the females soon after the ovulated eggs reached the ampulla and by limiting the period at which mating could occur to only 20 minutes. Evidence of sperm penetration (presence of one or more sperm in perivitelline space or inside the vitellus) was found beginning 1.75 hours after the end of the mating period. Pronuclei were formed three to four hours after sperm entry. Pronuclear DNA, synthesis began about eight hours postmating, 3.25 to 4.5 hours after pronuclear formation, or about 6.25 to 8.5 hours after sperm entry; it was completed in almost all zygotes by 16 hours postmating. The first completed cleavage division was found 17 to 18 hours postmating, and almost all eggs had cleaved by 20 hours.


The effect of nerve growth factor and limb regeneration on the spinal and sympathetic ganglia of Triturus. In Triturus administration of NGF causes hypertrophy of neuronal perikarya of third dorsal root ganglia and post-subclavian sympathetic ganglia. Two classes of neurons were characterized cytologically in the third dorsal root ganglia. Some evidence is presented which indicates that Class I neurons respond more vigorously to NGF. It is suggested that Class I neurons are similar to the medio-dorsal neuroblasts of chick embryos in their response to NGF. Forelimb amputation did not cause neuronal hypertrophy in either third dorsal root ganglia or post-subclavian sympathetic ganglia. The incorporation of (3H)-uridine increases to a highly significant extent in third dorsal root ganglia following NGF treatment or limb amputation. When NGF treatment and limb amputation were combined, no further increase in (3H)-uridine incorporation was noted. This suggests that RNA synthesis is maximally stimulated by either NGF treatment alone or limb amputation alone.


The presence of sperm-specific surface isoantigens on the egg following fertilization. Sperm surface isoantigens can be detected on the surface of fertilized eggs by using cytotoxic (complement dependent) sperm-specific isoantisera. These isoantigens cannot be detected on unfertilized eggs. This may indicate their transfer from sperm to egg during fertilization.


Low Na+ concentration: a factor contributing to diminished uptake and incorporation of amino acids by diapausing mouse blastocysts? Uptake and incorporation of 14C amino acids by normal and diapausing blastocysts was found to be Na+ dependent with one exception. Delayed embryos preincubated 25 h in medium containing 124 mM Na+ had labeling characteristics independent of the Na+ concentration present during labeling. Since diapausing embryos preincubated 25 h in low Na+ medium (55mM) retained their Na+ dependent labeling characteristics, delayed blastocysts may be in a low Na+ environment in situ. Low Na+ may explain why delayed blastocysts are unable to utilize radioactive methionine in vivo (Weitlauf and Greenwald, '68).


Threonine catabolism in Trypanosoma brucei. L-Threonine is catabolized by Trypanosoma brucei to give equimolar quantities of glycine and acetate. The pathway, which involves the two enzymes L-threonine dehydrogenase (EC 1.1.1.103) and aminoacetone synthase (acetyl-CoA:glycine C-acetyltransferase, EC 2.3.1.29) and subsequent hydrolysis of the acetyl-CoA, is most active in cultured trypanosomes but is also present in bloodstream forms. L-Threonine dehydrogenase from both culture and bloodstream forms of trypanosomes has an apparent molecular weight of between 28 000 and 38 000, and is sensitive to a wide range of sulphydryl reagents.


Effects of oxygen on Propionibacterium shermanii grown in continuous culture. Growth yields, enzyme activities, cytochrome concentrations and the rates of product formation were determined in Propionibacterium shermanii cultures grown in a chemostat with lactate as the energy source at various concentrations of oxygen. Oxygen was toxic when its partial pressure in the inflowing gas was just sufficient to give measurable dissolved oxygen concentration in the culture, when it inhibited lactate oxidation and NADH oxidase activity. Below this oxygen concentration, P. shermanii behaved as a facultative anaerobe. The adaptation from anaerobic metabolism to aerobic metabolism, however, was complex. Low partial pressures of oxygen led to decreased cytochrome and membrane-bound dehydrogenase activities and molar growth yield. Above an oxygen partial pressure of 42 mmHg in the inflowing gas stream, these changes were reversed, leading to an aerobic type of metabolism. At the highest subtoxic concentration of oxygen used (330 mmHg in the input gas), lactate was oxidized mainly to acetate and carbon dioxide and the rate of propionate formation was very low. The high molar growth yield obtained under these conditions suggested that lactate and NADH oxidation via the cytochrome electron transport system was coupled to ATP synthesis.


The Dienes phenomenon: identification of the determinants of compatibility. Two hundred and four isolates of swarming strains of Proteus species which had been typed for their ability to produce bacteriocin (proticine) and also their proticine sensitivity (P/S typing) were tested in all combinations for their Dienes compatibility with each other. Ninety-eight distinct Dienes compatibility groups were found. Physiological and genetic experiments supported the evidence of typing results that, irrespective of species, both the type of proticine a strain produces (P type) and the sensitivity of the strain to proticine (S type) were determinants of Dienes compatibility. Strains showing compatibility in the Dienes test were of the same P/S type, whereas those of different P/S types were incompatible.


A technique for the rapid selection of drug-sensitive and auxotrophic mutants of Phycomyces blakesleeanus. An auxotroph enrichment procedure has been developed for Phycomyces blakesleeanus which has proven useful in obtaining both auxotrophs and drug-sensitive mutants. The technique is based on the differential heat sensitivity between ungerminated auxotrophic spores and germinated prototrophic spores. Germinated spores and mycelia die when left at temperatures higher than about 35 degrees C for 16 to 24 h but ungerminated spores survive this treatment and subsequently germinate if transferred to complete medium. With the dwarf colonial strain, replica plating permits the rapid characterization of these newly selected auxotrophs.


Genetic relationship between an influenza A and a B virus. The base sequence homology between all eight 32P-labelled RNA segment of fowl plague virus (FPV) and the complementary RNA (cRNA) of an influenza B virus (B-mass), and between segment 8 of virus N and the cRNA of the same influenza B strain has been determined. All segments of FPV and segment 8 of virus N show a significant base sequence homology, ranging from 18 to 50% suggesting that influenza A and B viruses have a common ancestor. The conserved regions in segments 4,6 and 8 of the influenza A strains are identical to corresponding regions of the influenza B virus tested.


Antagonism by locally applied dopamine into the nucleus accumbens or the corpus striatum of alpha-methyltyrosine-induced disruption of conditioned avoidance behaviour. Male Sprague-Dawley rats were trained to avoid an electric shock in a two-way shuttle-box. The local application of dopamine into the nucleus accumbens or the corpus striatum was found to antagonize the suppression of conditioned avoidance behaviour induced by systemically administered alpha-methyltyrosine, emphasizing the importance of these dopamine-rich brain structures in mediating conditioned avoidance behaviour.


Brain-noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's syndrome. 1. Significantly reduced values of noradrenaline in Parkinson's disease were observable in all brain areas which were studied. 2. A topographic distribution of free 3-methoxy-4-hydroxyphenylglycol (MHPG) can be demonstrated in the human brain. As MHPG in the various brain areas shows a different pattern of concentration it seems that this metabolite of noradrenaline is of physiological significance and is able to reflect noradrenaline turnover. The highest values of free MHPG were found in the hypothalamus, n. accumbens, thalamus and n. ruber. 3. In a limited series of patients with Parkinson's disease post mortem analysis indicated lower values of MHPG in caudate n., putamen, s. nigra, red nucleus and n. accumbens. All other brain areas did not show significant alterations. 4. Parkinsonian patients who died during Madopar therapy demonstrated a significant increase of MHPG in caudate n., putamen, s. nigra, n. ruber, n. amygdalae and n. accumbens when compared to the untreated group, indicating an enhanced turnover of noradrenaline in these areas. 5. Bound MHPG has been estimated in various brain areas as to be in the range of 13--38 percent of free MHPG.


The influence of bromocriptine on serotonin neurons. Bromocriptine (CB-154) is regarded as a dopamine agonist, hence is used in the treatment of Parkinson's disease. In the paper presented a possibility of the influence of bromocriptine on central serotonin neurons has been studied. It was demonstrated that CB-154, like tryptophan, 5-hydroxytryptophan, LSD or fenfluramine in previous experiments, potentiates the flexor reflex of the spinal rat, and this effect of CB-154 is prevented by serotonin antagonists--cryproheptadine and danitracen. CB-154, like fenfluramine used as a comparative serotonergic agent, rises the body temperature in rabbits. The hyperthermic effect of CB-154 is prevented by cyproheptadine, danitracen and mianserin. Haloperidol prevents the hyperthermia caused by a lower dose of CB-154 or on fenfluramine-induced hyperthermia. The results obtained indicate that CB-154, besides a dopaminomimetic action, possesses central serotonin actions as well.


The effect of 4-aminopyridine on acetylcholine release. The effect of 2-, and 4-aminopyridine (4-APYR) on the release mechanism of acetylcholine (ACh) from the nerve terminals of the Auerbach plexus-longitudinal muscle preparation of the guinea-pig ileum, suspended in eserinized Krebs' solution, was investigated. 2- and 4-APYR increased the release of ACh from the nerve terminals at rest and at both low and high frequency stimulation. The enhanced ACh release was found to be due to increased volley output. At lower frequency of stimulation, potentiation of ACh release was much higher than at higher rate of stimulation. 4-APYR was able to increase ACh release in the absence of [Ca2+]o. However, when a Ca-chelating agent, EDTA, was also added to the Ca-free Krebs' solution, 4-APYR was entirely ineffective. The depression of ACh release induced by Mg-excess was completely antagonized by 4-APYR. Tetrodotoxin (TTX) prevented augmentation of ACh release by 4-APYR. It is suggested that 4-APYR lowers the demand of nerve terminals for [Ca2+]o required for the excitation-secretion coupling process. The presence of a low concentration [Ca2+]o, however, is essential for the action of 4-APYR.


Brain monoamines in metabolic (endotoxic) coma. A preliminary biochemical study in human postmortem material. Spectrofluorometric assays of DA, 5-HT and 5-HIAA were performed in different areas of postmortem brains of humans who died in hepatic and uremic coma. Brain DA showed a mild general decrease, the average reduction being 20 to 30 percent of the controls. By contrast, 5-HT and 5-HIAA were markedly increased in most brain areas, most significantly in the reticular and raphé nuclei of the brainstem and in some parts of the limbic system. Despite individual and regional differences, the monoamine changes had similar patterns in both hepatic and uremic coma. These data in human brain which confirm previous clinical and experimental studies in hepatic encephalopathy suggest some common disorders of central monoamine metabolism in endotoxic coma of different origin. Brain edema, a constant feature in toxic coma, is probably due to increased 5-HT content in the brain, the pathophysiologic effect of 5-HT on the blood-brain barrier being well established. The prominent changes of indoleamine metabolism in the reticular brainstem and limbic systems may be related to disorders of consciousness.


Electrophoresis of unconcentrated natural cerebrospinal fluid. A rapid and simple method to perform protein electrophoresis for natural unconcentrated cerebrospinal fluid is described. Hereby, pherograms with technically incontestable separations are acquired with a running time of 70 min at 180 V.


Multiple sclerosis in Coloured South Africans. Detailed case histories of seven Coloured South Africans with multiple sclerosis are presented; the summary of one South African-born Indian is included. Apart from an isolated case report in 1947, this is the first time that multiple sclerosis has been reported in detail in this South African racial group. All the Coloured patients presented for the first time during the last 12 years.


Hydrocephalus as a cause of dementia: evaluation by computerised tomography and intracranial pressure monitoring. To identity those patients with hydrocephalus as a basis for their presenile dementia it is suggested that such patients be screened non-invasively by CT scan. If there is ventricular dilatation and small cortical sulci, intracranial pressure should be monitored for 48 hours to detect `B' waves. Patients with significant `B' waves (10 mmHg) for at least two hours in the day might benefit from a shunt.


Monoamine metabolites in cerebrospinal fluid in multiple sclerosis. The concentrations of homovanillic acid (HVA), 5-hydroxyindolylacetic acid (5-HIAA), and 4-hydroxy, 3-methoxyphenylethylene glycol (MHPG) were estimated in the lumbar cerebrospinal fluid (CSF) of control subjects and in some patients who probably, and others who definitely, suffered from multiple sclerosis (MS). In the control group, the concentration of HVA was lower in people who underwent lumbar puncture having fasted and been recumbent for 12 hours before the procedure than in those from whom CSF was obtained under non-standardised conditions. These studies demonstrate that a standardised procedure for lumbar puncture is required in order to obtain meaningful results. In patients suffering from MS the CSF 5-HIAA concentrations were significantly lower than in comparable controls but the HVA concentrations did not differ. There was no relationship between metabolite concentrations, site of lesion, the duration of the disease, gamma-globulin levels nor the occurrence of relapse within the previous month.


Effect of nicergoline on cerebral blood flow. Cerebral blood flow (CBF) was measured before and after intravenous injection of the cerebral vasodilator nicergoline in 13 patients with cerebrovascular disease. CBF increased in seven. The possibility that the effect of the drug in the remainder may have been masked by a fall of CBF which occurs during sequential measurement of patients at rest is discussed.


Electroencephalographic variants and genetic predisposition to schizophrenia. Schizophrenic patients (249) were divided into those with and those without a family history of major functional psychosis. The same patients were then divided into those with entirely normal electroencephalograms and those whose traces contained some variant of normal. Traces were interpreted without knowledge of the patients' identities, and the question of the presence or absence of positive heredity had been decided without knowledge of the patients' electroencephalographic status, so that the discovery that normal electroencephalograms correlated highly significantly with positive heredity, and vice versa, commands attention. It is considered in the setting of previous work on psychoses and organic and electroencephalographic findings.


Benign fibrillation potentials in normal muscle and their correlation with endplate and denervation potentials. Fibrillation potentials in normal muscle are identical in origin with the 'spikes' in the endplate zone. The difference in shape is due to the site of the electrode. Both potential types are characterised by a high average maximal frequency and a very irregular discharge pattern. These properties distinguish them from the typical fibrillation potentials of the denervated muscle which show lower maximal discharge frequency, very small differences between consecutive time intervals, and slow up and down drifts in the discharge frequency. Less commonly, irregularly discharging fibrillation potentials are also observed in denervated muscle, which are exactly the same as those in the normal muscle, and which, therefore, may be assumed to have the same origin. It is only the rhythmically discharging fibrillation potentials which indicate a denervating process. The irregular fibrillation potentials, on the other hand, are of no pathological significance. The term benign fibrillation potentials is suggested for the latter.


Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance. It has been argued theoretically and confirmed experimentally that conduction velocity (theta) should be proportional to nerve fibre diameter for myelinated fibre tracts, such as normal peripheral nerve, exhibiting 'structural' similarity'. In some axons, however, the nodes of Ranvier are more closely spaced than in normal peripheral nerve. Analytic arguments have suggested that when internodal distance (L) alone is changed, the plot of theta versus L should have a relatively flat maximum. This was confirmed by several previous computer simulations of myelinated axons, but internode lengths of less than half the normal case were not examined. In order to gain insight into impulse propagation in myelinated and remyelinated fibres with short internodal lengths, the present study examines the conduction velocity and spike configuration for a wide range of internodal lengths. As L becomes large, theta falls and finally propagation is blocked; as L becomes small, theta decreases more and more steeply. From this, it is predicted that for fibres with very short internodal lengths, small local changes in L should affect substantially the conduction velocity.


Acute fulminant myoglobinuric polymyositis with picornavirus-like crystals. Myoglobinuria was found in an 11 month old girl suffering from fever, dyspnoea, and muscle hypotonia. Muscle biopsy showed focal degenerative necrosis of the muscle fibres. Electronmicroscopically, picornavirus-like crystals were demonstrated in the muscle fibres. These and other findings strongly suggest that she suffered from acute myositis with myoglobinuria probably caused by Coxsackie B6 virus infection. The causal relationship of viral infection (Coxsackie, influenza, or myxo-viruses) and acute or chronic polymyositis with or without myoglobinuria is discussed.


Cephalic tetanus: demonstration of a dual lesion. A clinical and electrophysiological study of 15 cases of cephalic tetanus is reported. This condition is a form of local tetanus which commonly follows an injury to the face or head. It is characterised by muscle paralysis which is maximal close to the site of injury, while spasm is evident at mroe distant sites. As muscle paralysis improves with time it is succeeded by spasm. It is argued that paralysis is due to high local concentrations of toxin in the brainstem while lesser concentrations cause spasm by abolishing inhibition. Electrophysiological studies indicate that paralysis is of lower motor neurone type with denervation potentials, hyperirritability, loss of motor units, and marginally increased distal latencies being the features recorded.


Giant cell tumour of the sphenoid bone with dural extension. A case of giant cell tumour of the sphenoid bone is reported. Besides the familiar presentation with headaches, ocular manifestations, and upper cranial nerve lesions, this case showed previously undescribed features such as grand mal seizures, hemiparesis with facial palsy, and dural extension. The reported high incidence in females is questioned. The tumour histologically showed some cartilage.


Ulnar nerve tumours of the hand in childhood. Two examples are presented of non-traumatic lesions of the deep motor branch of the ulnar nerve occuring in children. The clinical and histological features of solitary neurofibroma and neurilemmoma are compared and contrasted.


Peripheral nerve conduction in Miller Fisher syndrome. Two cases of acute ophthalmoplegia, ataxia, and arreflexia with high CSF protein are reported (Miller Fisher syndrome). Detailed EMG and nerve conduction studies showed abnormal conduction in peripheral sensory fibres from the initial stages of the illness in both patients. Careful review up to 10 months after the onset was required to document the sensory conduction abnormality properly in one of them. The electrical findings did not differ from those that can be seen in the Guillain-Barré syndrome and provided no clues as to the mechanism of the ataxia.


Diencephalic epilepsy in a patient with agenesis of the corpus callosum confirmed by computerised axial tomography. A case of diencephalic epilepsy is described in whom stereotyped attacks of spontaneous hypothermia and diaphoresis occurred over a 20 year period. No abnormality of the hypothalamo-pituitary-adrenal axis was found, and there was no evidence of an intracranial mass lesion. Pneumoencephalography and computerised axial tomography (EMI scan) demonstrated agenesis of the corpus callosum.


Gaze-induced laughter.

Gaze-induced laughter. Pathological laughter was stimulated by pursuit eye movements with a large extramedullary brainstem tumour. Laughter was also evoked by intense direct light. The mechanism by which visual stimuli could induce pathological laughter is discussed.


Myocardial creatine kinase isoenzyme in serum after subarachnoid haemorrhage. The myocardial isoenzyme of creatine kinase (MB CK) has been demonstrated in the serum of seven of 16 patients presenting with acute subarachnoid haemorrhage. All patients with elevated MB CK levels exhibited at some stage either intracranial arterial spasm as demonstrated by cerebral angiography, or a focal reversible neurological deficit not due to direct pressure by either intracranial haematoma or aneurysm. The presence of MB CK isoenzymes in sera of patients with subarachnoid haemorrhage may be an index of cerebral ischaemia, and may thus be of value in determining optimal timing of surgery or, ultimately, the long-term prognosis. Changes in the sympathetic nervous system may be a common factor producing both MB isoenzyme release from the myocardium and intracranial arterial spasm.


Hypothalamic and myocardial lesions after subarachnoid haemorrhage. The hypothalamus and myocardium of 12 patients who had died after a subarachnoid haemorrhage, and of six patients who had died from other intracranial pathology were examined. Only in the patients who had died from subarachnoid haemorrhage were histological lesions found in both the hypothalamus and myocardium. The possible significance of these findings is discussed with particular reference to the sympathetic nervous system.


Radionecrosis of the brain presenting as a mass lesion: a case report. A case of radionecrosis of the brain in a patient previously treated for squamous cell carcinoma of the scalp is presented. Cerebral angiography revealed a mass effect primarily in the right frontal area. Computed tomography showed extensive hemispheric oedema. A frontal lobectomy was performed, and the recovery was excellent. The lower limit for brain tolerance for irradiation is about 5000 rads given in five weeks. This dose should not be exceeded when extracranial lesions are treated. Although computed tomography cannot diagnose brain necrosis, specifically, it should, along with the clinical history, be very helpful.


Cerebrospinal fluid pressure in mannitol-treated rabbits. Equations describing the response of cerebrospinal fluid (CSF) pressure to a rapid intravenous injection of mannitol were developed by combining equations of membrane transport with equations of CSF hydrodynamics. The physiologic variables appearing in these equations were measured in anesthetized rabbits as brain water volume = 7.9 cm3, plasma osmolality = 308 mmol/kg, fractional total body water content = 0.62, time constant of blood-brain osmotic flow = 32 min, resistance to CSF absorption = 1.92 TPa-s/m3 and brain compliance = 0.173 mm3/Pa. Mannitol (5.5-27.5 mmol/kg) was administered intravenously to anesthetized rabbits while Elliott's B solution was infused (0.13-1.27 mm3/sec) into a lateral ventricle to simulate formation of CSF. Measured CSF pressure changes corresponded closely with those predicted by theory.


Spinal cord limb motor neurons in dystrophia myotonica. The total numbers of limb motor neurons have been counted in 20 micron sections of the lumbosacral spinal cord obtained a autopsy from 5 control subjects who showed no evidence of neuromuscular disease and from 5 patients with dystrophia myotonica ranging in age from 42 to 64 years. No significant reduction in the total number or distribution of such neurons was found in the cases of myotonic dystrophy and the quantity of lipofuscin present in the cells was similar to that in controls. Glial cell numbers were, however, significantly increased in the cases of dystrophia myotonica and this increase was not due to shortening or "crowding" of the relevant cord segments; in 2 patients with dystrophia myotonica the cell body area of the motor neurons was reduced by comparison with normal controls.


The numbers of limb motor neurons in the human lumbosacral cord throughout life. Forty-seven spinal cords from subjects between 13 and 95 years of age have been examined; in the majority death occurred suddenly or rapidly from a state of previous good health. The limb motor neurons in the lumbospinal segments have been estimated by counting nucleoli in characeteristic cells in every fifth group of 10 serial sections from the entire lumbosacral cord. No evidence exists of loss of motor neurons up to the age of 60 years, but beyond that age, although individual counts vary considerably, there is increasing evidence of a diminishing motor neuron pupulation; above 60 years, several cases showed motor neuron counts of only 50% of the counts in early adult life or middle age. Cell loss appeared to be uniform throughout all the segments and was unaccompanied by any other striking morphological change.


Fatty acid composition of myelin isolated from the brain of a patient with cellular deficiency of co-enzyme forms of vitamin B12. Myelin fractionation and subsequent lipid isolation have been carried out on a brain from a patient who suffered from a cellular deficiency of the adenosylcobalamin and methylcobalamin co-enzyme forms of vitamin B12. Examination of the fatty acid composition of choline and ethanolamine glycerophospholipids indicated a relative enrichment of odd-chain fatty acids which were identified by gas-liquid chromatography-mass spectroscopy as C15, C15:1, C17 and C17:1. A mixture of methyl branched C17 fatty acids was also identified. Odd-chain fatty acids accounted for 9.8% of the total fatty acid in the myelin choline phospholipid conpared to control values of 1.2%. The affected brain myelin phospholipids had a lower unsaturated fatty acid content. Examination of the myelin sphingolipids, sphingomyelin, cerebroside and sulfatide, yielded abnormal fatty acid profiles. The sphingomyelin contained only small amounts of C24:1 fatty acid. Both normal and hydroxy fatty acid containing cerebroside and sulfatide had reduced levels of C24 fatty acid. Determination of the relative hydroxy and normal fatty acid content of the galactolipids indicated an abnormally high hydroxy fatty acid level. Abnormal fatty acid profiles of brain cerebral sphingolipids have not been previously described in cases of vitamin B12 deficiency. Whether or not these alterations are characteristic will only be established by estimating sphingolipids in other such cases.


Global spatial disorientation. Clinico-pathologic correlations. Two patients presenting with the acute onset of bilateral parietal lobe damage showed initially the features of Balint's syndrome. After most of its manifestations had cleared, both patients exhibited severe disorders of spatial orientation: acoustic ataxia, inability to localize objects in space. In addition, 1 patient showed a topographical disorientation and abnormalities of whole body movements. This patient came to post-mortem examination, which revealed bilateral and fairly symmetrical old and recent infarctions of the superior parietal lobules. In the light of these observations and previous reports, it is suggested that the reported abnormalities of whole body movements can be explained on the basis of a visuo-motor intrahemispheric disconnection due to the bilateral lesion of the dorsal parietal lobe. In addition, the global spatial disorientation is analysed and is thought to be the manifestation of a derangement of a specific function centered in the parietal lobe. Moreover, it is pointed out that topographic disorientation does not require the concomitant failure of oculomotor mechanisms for its production. The topography of the anatomical lesion is considered in relation to current concepts on brain damage after severe hypotension and cardiac arrest. It is concluded that this group of patients is most likely at risk of developing behavioural abnormalities akin to the ones here reported.


Muscle carnitine levels in neuromuscular disease. The production of energy in muscle from long-chain fatty acid oxidation is dependent upon the presence of carnitine. An abnormally low level of muscle carnitine, as seen in patients with the carnitine deficiency syndrome, results in marked muscle weakness. Muscle from 83 consecutive patients undergoing diagnostic muscle biopsy  was assayed for carnitine. Carnitine levels (mean +/- SEM, expressed as nmoles carnitine per mg noncollagen protein) in muscle from patients with Duchenne dystrophy (8.1 +/- 1.7) and possible Becker dystrophy (10.6 +/- 3.0) were significantly (P less than 0.001) different from histologically normal muscle (24.0 +/- 1.4). Carnitine levels in patients with limb-girdle dystrophy (16.1 +/- 3.1) and polymyositis/dermatomyositis (16.6 +/- 3.2) were also low, although not as low as in Duchenne dystrophy. Carnitine levels from patients with denervation atrophy (22.1 +/- 3.6), nonspecific fiber atrophy (21.3 +/- 1.3), and a group of miscellaneous neuromuscular diseases (20.4 +/- 1.4) were not significantly different from histologically normal muscle. The low values of carnitine seen in Duchenne dystrophy and a group of possible Becker dystrophy patients may be a nonspecific effect, related to severe muscle damage.


Histocompatibility types and measles antibodies in multiple sclerosis. The relationship between HLA antigens and measles antibody titers was investigated in 105 multiple sclerosis (MS) patients. HLA antigens were determined serologically by a micro-lymphocytotoxicity test and measles antibody titers were determined by the hemagglutination inhibition test. There was an increased frequency of HLA-B7 and HLA-Bw35 antigens and a decreased frequency of HLA-A2, HLA-B12, and HLA-Bw40 antigens in MS. Measles antibody titers were significantly higher in MS than in control cases. In the MS patients, the chi-square test for homogeneity did not show any significant difference between the presence or absence of antigens HLA-A3, HLA-B7, HLA-B8 HLA-A2 or HLA-B12 when compared with measles antibody titers. The chi-square test for association did not show any significant difference between the presence or absence of these antigens compared with measles antibody titers above 1:64 or 1:128 or 1:256. However, there were significantly higher measles antibody geometric mean titers in MS patients with HLA-A3 antigen or lacking HLA-A2 antigen. In the case of HLA-A3, this was reflected in the female but not in the male patients. The increased measles HI antibody titer in MS may be related to the increased frequency of HLA-A3, or the decreased frequency of HLA-A2, or both.


Complex oligodendroglial invaginations within myelinated nerve fibers of the central nervous system during axonal degeneration. Ultrastructural studies of spinal cord in rats subjected to hyperbaric oxygen exposure and experimental spinal cord trauma have resulted in frequent degeneration of axons. In both experimental situations central nervous system myelinated fibers containing complex cytoplasmic interdigitations of electron lucent, normal appearing cytoplasm, and dense cytoplasm, interpreted as degenerative, were observed. In some of the complex profiles the electron lucent cytoplasm could be traced back to the inner mesaxon, where its relation to the latter indicated a glial origin. Cytochemical evaluation of acid phosphatase activity in the complex cytoplasmic interdigitations revealed that both components contain significant lysosomal activity. The complex structures are interpreted as being sequestrations of degenerating axoplasm by distal adaxonal oligodendroglial processes, possibly representing an unusual form of heterophagocytosis.


Toxic effects of adriamycin on the ganglia of the peripherial nervous system: a neuropathological study. Rats were injected intravenously with 10 mg/kg of adriamycin (doxorubicin). All the treated animals developed severe posterior limb ataxia on days 11 and 12 following the injection. Mild ataxia of the forelimbs was noted later. The animals were killed between days 10 and 50. Light microscopy revealed changes in ganglion cells of the peripheral nervous system with sparing of neurons in the central nervous system. In the spinal, paravertebral and trigeminal ganglia, necrosis of neurons was followed by mild lymphocytic infiltration, and ultimate loss of ganglion cells, and a marked proliferation of nerve sheath cells. Electron microscopic study revealed increased numbers of neurofilaments and the presence of membrane-bound cisterns in the affected dorsal root ganglion cell bodies. It is concluded that adriamycin, an important anticancer therapeutic agent, has neurotoxic properties and that it selectively damages the ganglia of the peripheral nervous system.


Biochemical and behavioural effects of inhalation exposure to tetrachlorethylene and dichlormethane. The exposure of adult male rats to 200 ppm of tetrachlorethylene t hours daily for 4 days resulted in a marked sequestration of solvent in perirenal fat 17 hours after the last exposure period. Similar exposure of similar rats to 500 ppm of dichlormethane led to a lesser accumulation of the solvent in fat as studied at the same time. Further exposures on the fifth day increased promptly the solvent contents of various organs. The exposure to tetrachlorethylene caused a diminished brain RNA content on the fifth day with simultaneous increase in the activity of non-specific cholinesterase. Similar changes in the RNA content were not seen in experiments with dichlormethane while the activity of acid proteinase increased above the control level in brain. Observations on the performance of the same animals in an open-field situation revealed that ambulation was affected in experiments with tetrachlorethylene immediately after exposure while preening pattern was changed after exposure to dichlormethane. Analysis on liver microsomal cytochrome P-450 content displayed slight increases in the hemochrome content in both experiments. The present data indicated that a rather modest exposure to both solvents could cause significant solvent accumulation in the fat and brain with marked effects on rat behaviour and protein metabolism in brain while changes in liver cytochrome P-450 content might not reflect the magnitude of these changes.


Lumbar motoneurons of man: III. The number and diameter distribution of large- and intermediate- diameter cytons by nuclear columns. In a recent study we estimated the number and frequency distribution of the diameters of the cytons of all of the combined motoneuron columns of L3, L4 and L5 ventral horn of the spinal cord of man. In the present study we have estimated the number and frequency distribution of the diameter of motoneuron cytons in the lateral (L) and the medial (M) groups of the ventral horns of L3, L4 and L5 spinal segments and of the three motoneuron columns [antero-lateral (AL), central (C), and combined postero-lateral and post-postero-lateral )PL + PPL)] of the L group in the L5 segment in the same 18 reference spinal cords of the earlier study. These reference morphometric values are needed to be able to determine whether the number and size of motoneuron cytons are abnormal or not, and in what way are they abnormal, in various neuromuscular diseases.


Hemochromatosis associated with brain lesions--a disorder of trace-metal binding proteins and/or polymers? A 68-year-old man, after having been diagnosed as having hepatic disease at about the age of 41 years, had been hospitalized frequently until his death. Blood sugar, iron, and copper had not increased during his illness. Although the diagnosis of liver cirrhosis had been made and he had been receiving therapy, various neurologic symptoms without disturbances of consciousness appeared six months before his death. Autopsy revealed hemochromatosis, liver cirrhosis, and pancreatic fibrosis. A large amount of iron had accumulated in the liver, the pancreas, and the thyroid gland, while considerable numbers of ceroid and lipofuscin pigment granules had accumulated diffusely in the brain. Abnormal astrocytes of the Alzheimer II type were diffusely distributed in the brain and contained no intranuclear glycogen which stained positive with the carmine stain. No spongy changes were seen in the deeper layers of the cerebral cortex. Chemical analyses for trace metals in the brain, liver, and kidneys revealed a large amount of iron and increased copper in the liver, and considerable quantities of copper, manganese, calcium, and mercury in the brain. Because of changes in the erythrocyte sedimentation rate and marked thymol turbidity seen before and after the occurrence of the neurologic symptoms, this man was suspected of having disorders of the trace-metal binding proteins and/or of their polymers.


Suppression by elevated calcium of black widow spider venom activity at frog neuromuscular junctions. Frog neuromuscular junctions were treated with both concentrated black widow spider venom (BWSV) and elevated extracellular calcium (5-50 mM). This procedure causes a dramatic increase in the frequency of spontaneous miniature endplate potentials (mepps) which persists for only a few minutes. In contrast, BWSV-induced mepp activity, the venom effect (VE), continues for 20 min-1 h at junctions in elevated calcium Ringer solutions treated with doses of dilute venom or at junctions in normal calcium (1.91 mM) Ringer solution treated with concentrated venom. Following the disappearance of the VE in elevated extracellular calcium, only a few normal amplitude mepps and a few giant amplitude mepps are observed. The disappearance of the VE in these preparations is irreversible and occurs whether exposure to elevated extracellular calcium precedes or follows exposure to BWSV. Electron microscopy indicates that the major structural alterations produced by exposure to concentrated BWSV and 20 mM calcium Ringer solution are the swelling of nerve terminal mitochondria and the clumping of synaptic vesicles, large numbers of which remain in the terminals. Exposure to 20 mM calcium Ringer solution alone produces no ultrastructural modifications in these preparations. These observations can best be explained if one of the effects of BWSV is to increase the permeability of the nerve terminal membrane to calcium. Only doses of concentrated venom can sufficiently elevate intracellular calcium to a concentration at which synaptic vesicles clump together, thus interruping the transmitter release process.


Descending inputs to the cat dorsal cochlear nucleus: an electron microscopic study. This experimental study provides identification of several types of terminals in the fusiform cell layer (FCL) of the cat dorsal cochlear nucleus (DCN). Eight types of synaptic terminal were defined in control animals. 22 experimental cats were then subjected to unilateral lesions of the superior olivary complex or SOC (Groups I and II), the inferior colliculus or IC (Groups III and IV), or the IC plus the dorsal nucleus of the lateral lemniscus or DNLL (Groups V and VI). After one to 14 days, animals were killed by perfusion-fixation and brain stems prepared for light and electron microscopic study of degeneration. After SOC lesions, the ipsilateral FCL showed degeneration of small (type 2a) endings on small dendritic shafts; the contralateral FCL showed degeneration of larger (type 5) endings mostly on fusiform cell somata and on some primary dendrites. Both sides showed mild degeneration of large, glomerular (type 1a) endings. After small IC lesions, the ipsilateral FCL demonstrated degenerating type 1a glomerular endings but the contralateral FCL showed severe degeneration of type 5a terminals (axodendritic to fusiform cells) and mild degeneration of both glomerular (type 1a) and axosomatic (type 5) endings. Combined IC-DNLL lesions caused extensive degeneration in a pattern similar to that following IC lesions. In addition retrograde degeneration of fusiform cells occurred bilaterally. These studies showed that: (1) type 2a endings originate in the ipsilateral SOC; (2) type 5 endings on fusiform cell bodies originate from the contralateral SOC; (3) type 5a endings on fusiform cell dendrites originate from the contralateral IC; and (4) type 1a glomerular endings probably arise from several sources, including the IC, the SOC and (possibly) the DNLL of both sides.


Penetration of systemically injected horseradish peroxidase into ganglia and nerves of the autonomic nervous system. HRP given intravenously to rats and guinea-pigs passes within 5 minutes into the extracellular spaces of the superior cervical and coeliac ganglia, reaching the spaces between neurons and their associated satellite cells and the equivalent spaces between neuronal processes and satellite cells. The sympathetic nerve trunks have a blood-nerve barrier. The myenteric plexus does not contain blood vessels, but is permeable to tracer from the extracellular spaces of the adjacent muscle layers.


Reversed visuomotor behavior mediated by induced ipsilateral retinal projections in goldfish. 1. When one optic lobe of a goldfish is removed and the optic nerve from the contralateral eye is deflected ipsilaterally, the nerve innervates the intact, previously foreign side. When the control eye is left intact, the animal shows normal swimming and coordination of head and eyes. In some cases, however, optokinetic nystagmus evoked through the experimental eye is reversed, indicating a functional ipsilateral projection which was apparently outweighed by the normal projection during swimming. 2. When the same surgical procedure is accompanied by partial or complete destruction of the control eye, the animals show overt reversal of visuomotor behavior soon after the ipsilateral projection is established. They make a spontaneous nystagmus and circle continuously. The nystagmus and the circling persist in total darkness for days before they are extinguished. They resume as soon as the animal returns to light. 3. The vestibuloocular reflex is biased differently from normal, but the sign of the gain is normal. 4. We conclude that the neurological reversal of vision triggered the nystagmus and the circling, and that the many months with reversed vision resulted in some longer lasting change in the nervous system such that the behaviors persisted even in the absence of moment-to-moment visual stimulation.


Optical recording of neuronal activity in an invertebrate central nervous system: simultaneous monitoring of several neurons. 1. Using an optical method for measuring membrane potential, we have been able to monitor action-potential activity simultaneously in 14 neurons of the supraesophageal ganglion of the barnacle. 2. Under favorable conditions, 4-mV synaptic potentials could also be detected optically.


Cerebral arterial blood flow and aneurysm surgery. Part 1: local arterial flow dynamics. Cerebral arterial blood flow was monitored in 22 patients undergoing surgery for intracranial saccular aneurysms. An electromagnetic flow probe was used to record the internal carotid artery (ICA) flow in the neck or intracranially in seven patients. The ICA flow ranged between 100 and 175 ml/min (average 144 ml/min). Intracranial flow measurements with specially designed probes were made in 17 patients. The middle cerebral artery (MCA) showed flow values between 75 and 120 ml/min (average 97 ml/min). Flow figures recorded from the proximal anterior cerebral artery (ACA) were lower (average 65 ml/min), and had a wider range from 30 to 110 ml/min. Test occlusion of the terminal ICA showed a retrograde flow in the proximal ACA to the MCA ranging from 15 to 125 ml/min (average 78 ml/min). This test was used to investigate the collateral potential of the anterior portion of the circle of Willis, which is essential to the decision of whether to undertake trap ligation procedures in this location. Flow monitoring in the parent vessel was also of use in some patients to assess flow conditions after the clipping of the aneurysm neck.


Cerebral arterial blood flow and aneurysm surgery. Part 2: Induced hypotension and autoregulatory capacity. A study of 21 patients was conducted to clarify the autoregulatory capacity in patients subjected to induced hypotension during intracranial surgery for saccular aneurysms. Trimethaphan camsylate (Arfonad) was used for induced hypotension and arterial blood flow was measured with an electromagnetic flow probe on the internal carotid artery or one of its main intracranial branches. In Grade I and II patients the control arterial blood pressure (ABP) ranged from a mean of 90 to 135 mm Hg (average 110 mm Hg), with a lower level of autoregulation (LLAR) from 35 to 85 mm Hg (average 62 mm Hg). Grade III patients had a control ABP of between 105 and 145 mm Hg (average 124 mm Hg) and the LLAR was found to be between 60 and 95 mm Hg (average 76 mm Hg). There was a significant difference between the two groups with regard to both the control ABP and the LLAR. A surprising result obtained from these data was that the average lower autoregulatory range (the difference between control ABP and LLAR) is practically the same in the two groups. A systematic investigation of the upper limit of autoregulation was not possible for ethical reasons. In those few patients in whom spontaneous increase in the ABP made such observations possible, upper limits up to 150 mm Hg with a total autoregulatory capacity of about 75 mm Hg were observed. In some patients, however, lower limits and cing that the upper limit of autoregulation is markedly influenced by several factors.


Reinforcement with gauze wrapping for ruptured aneurysms of the middle cerebral artery. A 2- to 15-year follow-up study is presented of a series of 35 consecutive patients treated for ruptured aneurysms of the middle cerebral artery by reinforcement with gauze wrapping. Only one patient suffered early recurrent hemorrhage in the postoperative period, and none had a late hemorrhage. The procedure carried a relatively low mortality rate (8.6%). Morbidity was the direct sequel of preoperative conditions. Wrapping is an effective and safe treatment of these aneurysms, with a low mortality and morbidity, and freedom from occlusive infarcts.


Does dexamethasone inhibit the growth of human gliomas? Dexamethasone (10-(4)M) was shown to inhibit the growth of human gliomas in culture. This was indicated by the inhibition of incorporation of radioactively labeled thymidine into the deoxyribonucleic acid (DNA) of the cells, and by the increase in the generation time of cells exposed to the drug in vitro. On the other hand, tumors obtained from patients who had received dexamethasone before craniotomy grew considerably faster in vitro than tumors from patients who had not been given the drug before operation.


Genetic perspectives on craniosynostosis and syndromes with craniosynostosis. Thirty-seven syndromes in which craniosynostosis is a feature are presented in tabular form, allowing the clinician to rapidly identify a given syndrome and gain immediate access to the pertinent literature. A plea is made to delineate unknown genesis syndromes with craniosynostosis as rapidly as possible. As an unknown genesis syndrome becomes delineated, its phenotypic spectru, its natural history, and its inheritance pattern or risk of recurrence become known, allowing for better patient care and family counseling.


A pressure-balanced radio-telemetry system for the measurement of intracranial pressure. A preliminary design report. A fully implantable radio-telemetric differential intracranial pressure sensor is described with a zero-point calibration that can be confirmed repeatedly. Intracranial pressure (ICP) is measured with the device by the principle of applying a known external pressure to the scalp above the sensor and simultaneously detecting by radio-telemetry the zero-point of the sensor corresponding to a balance of pressures across it. The radio-telemetry is implemented by a resonant circuit in the sensor of which the resonant radiofrequency is detected outside the body. The sensor is passive, has built-in barametric compensation, negligible permeability of temperature drift, no calibration ambiguities, and fast dynamic response. The implanted sensor has been used successfully for short-term as well as long-term ICP monitoring. It has been implemented primarily for intermittent ICP measurements, but also adapted to continuous recording. Preliminary clinical experience with the system indicates that it is effective, safe, and simple to operate.


The true sagittal diameter of the cervical spinal canal and its diagnostic significance in cercical myelopathy. A method is presented for measuring the true sagittal diameter of the cervical spinal canal on routine lateral radiograms by the use of a midline perforated ruler. Sagittal measurements were made in 92 normal adults to establish a range of normal values. The lower and upper limits were 10 mm and 17 mm, respectively, at the levels of C-3 to C-7. Comparison of the results with the anatomical measurements of dried specimens showed good agreement. Four cases of cord compression were presented and the diagnostic significance of the method in cervical myelopathy was discussed.


Pancreatitis following spinal cord injury. Six cases of pancreatitis following spinal cord injury are presented. No single, etiologically accepted mechanism already postulated to cause pancreatitis can account for all the cases reported. The authors hypothesize that spinal cord disruption may produce pacreatitis by sympathetic-parasympathetic nervous system imbalance resulting in over-stimulation of the sphincter of Oddi. This may lead to stasis of secretions with absorption of amylase into the systemic circulation, and structural pancreatic damage. Pancreatitis in those with cord injuries is easily overlooked because abdominal pain is usually absent and fever is usually attributed to more frequently occurring pulmonary or urinary tract infections. Recognition of this complication is important in order to decrease the morbidity and mortality that follows spinal cord damage.


Embolism to the central nervous system from cardiac myxoma. Report of two cases. Two cases of left atrial myxoma are reviewed, both presenting as embolic phenomena. Neither patient gave a history compatible with pre-existent cardiac dysfunction. Sudden collapse and subsequent right hemiplegia resulted in one patient when an embolus lodged in the left middle cerebral artery. The second patient presented with headache and transient visual obscuration in the left eye. She showed evidence of embolism to the central retinal artery, and particulate matter could be seen within the retinal arterioles. Attention is drown to the fact that echocardiography now constitutes a simple, noninvasive, and highly reliable method of making this diagnosis. The propensity for embolic tumor fragments to grow and invade cerebral arterial walls is discussed along with its possible neurosurgical significance.


Focal eosinophilic granuloma of the temporal lobe. Case report. The authors describe the clinical, pathological, and therapeutic aspects of a case of focal temporal lobe eosinophilic granuloma, presenting with otitis media and meningitis, and evolving subsequently into a temporal lobe mass. This triad, otitis media, meningitis, focal cerebral lesion with systemic manifestations of inflammation, eosinophilia of blood and cerebrospinal fluid, should suggest eosinophilic granuloma in the differential diagnosis. The lesion is sensitive to relatively small doses of radiation.