Increased dopamine release in the human amygdala during performance of cognitive tasks.

Accumulating data support a critical involvement of dopamine in the modulation of neuronal activity related to cognitive processing. The amygdala is a major target of midbrain dopaminergic neurons and is implicated in learning and memory processes, particularly those involving associations between novel stimuli and reward. We used intracerebral microdialysis to directly sample extracellular dopamine in the human amygdala during the performance of cognitive tasks. The initial transition from rest to either a working memory or a reading task was accompanied by significant increases in extracellular dopamine concentration of similar magnitude. During a sustained word paired-associates learning protocol, increase in dopamine release in the amygdala related to learning performance. These data provide evidence for sustained activation of the human mesolimbic dopaminergic system during performance of cognitive tasks.

Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. Technical note.

Monitoring physiological changes in the brain parenchyma has important applications in the care of neurosurgical patients. A technique is described for measuring extracellular neurochemicals by cerebral microdialysis with simultaneous recording of electroencephalographic (EEG) and single-unit (neuron) activity in selected targets in the human brain. Forty-two patients with medically intractable epilepsy underwent stereotactically guided implantation of a total of 423 intracranial depth electrodes to delineate potentially resectable seizure foci. The electrodes had platinum alloy contacts for EEG recordings and four to nine 40-microm microwires for recording single-unit neuron activity. Eighty-six electrodes also included microdialysis probes introduced via the electrode lumens. During monitoring on the neurosurgical ward, electrophysiological recording and cerebral microdialysis sampling were performed during seizures, cognitive tasks, and sleep-waking cycles. The technique described here could be used in developing novel approaches for evaluation and treatment in a variety of neurological conditions such as head injury, subarachnoid hemorrhage, epilepsy, and movement disorders.

Mass isotopomer study of glutamine oxidation and synthesis in primary culture of astrocytes.

The metabolism of [1, 2-13C2] acetate via the tricarboxylic acid (TCA) cycle leads to the formation of a number of key mass isotopomers of glutamate. The distribution of these isotopomers which is a function of pyruvate carboxylase, pyruvate dehydrogenase and pyruvate recycling was used to determine the relative anaplerotic flux and glutamine oxidation of astrocytes in culture under different substrate conditions. Combinatory analysis of mass isotopomers formed from the condensation of labeled oxaloacetate with labeled acetyl-CoA was used to determine precursor enrichment and fractional glutamine synthesis. When glucose or glutamine was supplied in the medium, the effective anaplerotic flux (Y') was about 1.5 times that of the TCA cycle flux. Under substrate-limiting conditions, Y' and glutamine synthesis was significantly reduced. A unique feature of the use of [1, 2-13C2] acetate in this study is the formation of singly labeled isotopomer of glutamine in the C4 or C5 position when glutamine is irreversibly loss in net oxidation. We observed very little [4-13C] or [5-13C] glutamine either because of the lack of pyruvate recycling or the lack of pyruvate dehydrogenase activity. The lack of 13C recycling to the C4 and C5 position of glutamine suggests that less than 10% of the glutamine is oxidized into astrocytes for energy production. Therefore, glutamine is not a major energy substrate for astrocytes in culture.

Gastrointestinal tolerance, fat absorption, plasma ketone and urinary dicarboxylic acid levels in low-birth-weight infants fed different amounts of medium-chain triglycerides in formula.

This study was conducted to evaluate the effect of medium-chain triglycerides (MCT) in a formula for low-birth-weight (LBW) infants on gastrointestinal tolerance, fat absorption, plasma ketone levels, and urinary dicarboxylic acid (DCA) excretion. At the start of enteral feedings, 64 LBW infants (< or = 1500 g) were randomly assigned to one of four experimental formulas. The formulas contained either 0, 17, 34, or 50% of the total fat as MCT oil. The nonfat constituents of all four formulas were the same and identical to Similac Special Care 24 (SCF). Infants were studied from the start of enteral feeding until approximately 7 days after reaching full feeds. Growth and tolerance were assessed in all infants over the entire feeding period. A 48-h balance study was conducted after enteral intake exceeded 100 kcal/kg/day for 3 days. Stool fat, plasma D-(-)-3-hydroxybutyrate (3HB) and carnitine, serum glucose, and urinary DCA levels were determined. Groups did not differ in growth, formula intake, fat absorption (76-84%), serum glucose, or plasma carnitine levels. Gastrointestinal tolerance was excellent and did not differ among groups. Plasma 3HB was significantly different (p < 0.05) only between the 0 and 50% MCT groups, 50 +/- 10 versus 120 +/- 20 microM, respectively. The excretion of urinary DCAs increased with increasing amounts of MCT in the formula. In conclusion, fat absorption and gastrointestinal tolerance were not affected by different MCT levels (0 to 50% of the total fat), but higher levels of plasma 3HB and urinary DCAs were associated with higher levels of MCT in the LBW formulas studied.

Dietary cholesterol and the origin of cholesterol in the brain of developing rats.

Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires.

Fatty acid oxidation and ketogenesis by astrocytes in primary culture.

The oxidation of the fatty acids octanoate and palmitate to CO2 and the ketone bodies acetoacetate and D-(-)-3-hydroxybutyrate was examined in astrocytes that were prepared from cortex of 2-day-old rat brain and grown in primary culture to confluence. Accumulation of acetoacetate (by mass) in the culture medium of astrocytes incubated with octanoate (0.3-0.5 mM) was 50-90 nmol C2 units h-1 mg of protein-1. A similar rate was obtained using radiolabeled tracer methodology with [1-14C]octanoate as labeled substrate. The results from the radiolabeled tracer studies using [1-14C]- and [7-14C]octanoate and [1-14C]-, [13-14C]-, and [15-14C]palmitate indicated that a substantial proportion of the omega-terminal four-carbon unit of these fatty acids bypassed the beta-ketothiolase step of the beta-oxidation pathway and the 3-hydroxy-3-methylglutaryl (HMG)-CoA cycle of the classic ketogenic pathway. The [14C]acetoacetate formed from the 1-14C-labeled fatty acids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. By contrast, the [14C]acetoacetate formed from (omega-1)-labeled fatty acids contained 90% of the label at carbon 3 and 10% at carbon 1, whereas that formed from the (omega-3)-labeled fatty acid contained 20% of the label at carbon 3 and 80% at carbon 1. These results indicate that acetoacetate is primarily formed either by the action of 3-oxo-acid-CoA transferase (EC 2.8.3.5) or acetoacetyl-CoA deacylase (EC 3.1.2.11) or both on acetoacetyl-CoA and not by the action of the mitochondrial HMG-CoA cycle involving HMG-CoA lyase (EC 4.1.3.4), which was readily detected, and HMG-CoA synthase (EC 4.1.3.5), which was barely measurable.

Ceftazidime in treatment of urinary tract infection in patients with spinal cord injury: comparison with moxalactam.

Ceftazidime was compared with moxalactam in the treatment of urinary tract infections in patients with spinal cord injury. Patients received ceftazidime or moxalactam, 500 mg twice daily for five days. Urine specimens were collected by urethral catheter. Adequate follow-up was obtained in 26 patients treated with ceftazidime and 13 patients treated with moxalactam. The infecting bacteria were not cultured in significant numbers from the urine of any patients after two to four days of antibiotics, except for 1 patient who had Pseudomonas aeruginosa persisting in the urine while receiving ceftazidime. At five to nine days after completing antibiotic therapy, the cure rate was 42 percent for ceftazidime and 15 percent for moxalactam. The rate of reinfection was significantly lower in the ceftazidime group than the moxalactam group.

Pseudomonas urinary tract infection in patients with spinal cord injury.

Serum antibodies to P. aeruginosa were measured in 28 patients with spinal cord injury before and after the development of bacteriuria during their hospital rehabilitation. Serum IgG, IgA and IgM were measured against the infecting strain of P. aeruginosa isolated from the urine of each patient. After bacteriuria was detected, a significant increase (fourfold or greater) in IgG and/or IgA antibodies was found in nine patients (33%). This increase was significantly associated with leucocytosis. These observations indicate that bacteriuria with P. aeruginosa in patients with spinal cord injury is associated with a serum antibody response in a significant number of patients, indicating tissue invasion by this microorganism.

Lipogenic potential in liver of the preweanling rat: influence of dietary cholesterol.

We examined the effect of a lower dietary cholesterol load on hepatic lipogenic capacity and plasma cholesterol concentrations during the normal suckling period in artificially reared preweanling rats. The artificially reared rats were fed a milk formula that contained low or normal concentrations of cholesterol during the period from the 5th to 17th day after birth. The activities of HMG-CoA synthase and HMG-CoA reductase in livers of 17-day-old rat pups reared on the low-cholesterol diet were enhanced three- to five-fold over those observed in the age-matched rats in the normal cholesterol and mother-reared control groups. The concentration of cholesterol in plasma of rats reared on the low-cholesterol milk was about 20% lower than that for mother-reared controls. In contrast, rats reared on milk with normal cholesterol content exhibited plasma cholesterol levels about 25 and 50% higher than the mother-reared and low cholesterol groups, respectively. The long-term metabolic consequences of rearing rats on milk formulations without adequate cholesterol remains to be determined.

Klebsiella pneumoniae colonization in patients with spinal cord injury.

Klebsiella pneumoniae colonization of 53 patients with spinal cord injury was studied. Cultures of multiple body sites from patients, the environment, food, and hospital personnel were obtained. K. pneumonaie was cultured from one or more body sites in 46% of male patients. Significant bacteriuria was found in 10% of male patients. Positive cultures of the urethra and perineum for K. pneumoniae were significantly associated with the use of the external condom catheter (p less than 0.05, Fisher's exact test). K. pneumoniae colonization increased with length of stay in the hospital. Serotype 64, the predominant serotype found, was isolated only from patients who had been in the hospital for at least 4 wk and primarily in those patients using the external condom catheter. Urinary drainage bags were frequently colonized with K. pneumoniae at a time when the patients did not have significant bacteriuria. Colonized male patients were found to be the primary reservoir of K. pneumoniae and may serve as the major source for cross-contamination.

Cefsulodin in treatment of Pseudomonas urinary tract infection in patients with spinal cord injury. Comparison with aminoglycosides.

Male patients with spinal cord injury and urinary tract infection with Pseudomonas aeruginosa were treated with cefsulodin (1.0 or 1.5 Gm) every six hours or an aminoglycoside (amikacin 5 mg/Kg or tobramycin 1 mg/Kg) every eight hours for seven days. The study was discontinued after treating 6 patients with aminoglycosides because of the poor results with these antibiotics. At five to nine days after completing treatment P. aeruginosa was eliminated from the urine of 12 to 15 patients (80%) treated with cefsulodin and 3 of 6 patients (50%) treated with an aminoglycoside. When examined at four to six weeks 5 of 15 (33%) of the cefsulodin group had persistent infection or relapse, while 5 of 6 (83%) infections treated with an aminoglycoside either persisted or relapsed. Cefsulodin was discontinued in 1 patient, known to be allergic to penicillin, because of hypersensitivity resulting in periorbital edema and rash. No other serious side effects were noted with cefsulodin or the aminoglycosides. These results indicate that cefsulodin is an effective antibiotic in the treatment of urinary tract infection with P. aeruginosa in patients with neurogenic bladder resulting from spinal cord injury and confirmed previous observations of a poor response of Pseudomonas urinary tract infection to aminoglycosides in this group of patients.

Incidence of temperature elevations after a full mouth dental rehabilitation under general anesthesia.

Fifty-seven patients underwent a full-mouth dental rehabilitation under general anesthesia at Texas Scottish Rite Hospital for Crippled Children. Thirty-eight subjects had complete data collected to monitor for temperature elevation. Nineteen subjects were discarded from the study due to incomplete data. The results showed 45 percent (seventeen subjects) had a significant temperature elevation to 38 degrees C or above. Sex of the subject made no difference. The significance temperature elevations occurred in the younger age-groups, especially in the one- to-five-year age-group. In the subjects with a significant temperature elevation after surgery, no definite pattern was evident as to when it would occur or how long it would last. The study population was divided into two groups, one with a significant temperature elevation to 38 degrees C or above, and the control group with temperatures below 38 degrees C. These groups were then compared to see whether their preoperative Oral Hygiene Index, Gingival Index, and soft tissue trauma or extraction of teeth showed a difference. No significant difference was found. This study is the first designed specifically to monitor temperature. It reported the highest percentage of subjects (45 percent) to have a postoperative temperature elevation, in comparison to other studies. Although no single factor could be found as the cause of the postoperative temperature elevation, combinations of the factors mentioned or the effects of anesthetic may have caused the elevations.

The fibrous skeleton of the corpora cavernosa and its probable function in the mechanism of erection.

The corpora cavernosa contain a fibrous skeleton composed of tunica albuginea with its fibrous columns, periarterial and perineural fibrous sheaths, and an intraparenchymal fibrous framework attached to all fibrous elements of the corpora cavernosa. This anatomical arrangement probably plays an important part in the firmness of the corpora cavernosa during erection. The fibrous framework, due to its numerous attachments to the deep surface of the tunica albuginea and its columns, when stretched during erection, prevents bending and deformation of the corpora cavernosa.

Specificity of plasma cells in the rheumatoid synovium. I. Immunoglobulin class of antiglobulin-producing cells.

Plasma cells synthesizing rheumatoid factors (RF) were identified by fluorescent staining of sections of synovium and macrophage-depleted cells from dispersed synovial tissue. The latter avoided problems related to sampling errors in studying tissue sections and in the uncertainty raised by the staining of macrophages with intracellular complexes. Plasma cells producing IgG predominated, and seropositive patients had a higher proportion of IgM producers than seronegative subjects. None the less, in both groups of patients more than 90% of the IgM plasma cells were synthesizing RF, whereas the corresponding figure for IgG was between 50% and 60%. Only around 10% of IgA plasma cells were positive for RF. The high percentage of IgM plasma cells making RF would tend to argue for an IgG-specific response and against direct polyclonal activation as the stimulus. The percentage of IgG-producing cells positive for RF is also consistent with a dominant response to IgG. Accepting the difference in the relative proportion of total IgM- to IgG-producing plasma cells in seropositive as against seronegative patients, the close similarity between the two groups in the fraction of cells making RF favours the view that the two groups have a comparable underlying immunopathology dependent on IgG autosensitization. From the technical standpoint, the dispersed cell method gives results in line with those obtained with sections but which are easier to read, whereas the fluorescent techniques described give clear and reproducible results for the detection of RF of different heavy-chain isotype.

Special microanatomical features surrounding the intracorpora cavernosa nerves and their probable function during erection.

The nerves of the corpora cavernosa have anatomical characteristics different from other nerves. The intracavernous nerves are located in fibrous tunnels into which numerous fibrous bundles establish attachments. These bundles are part of the fibrous meshwork included in the corpora cavernosa. We suspect that during erection, when the corpora fill with blood and high intracavernous pressure develops, the aforementioned meshwork of fibrous bundles attached to all fibrous elements of the corpora, including the tunica albuginea and the perineural fibrous tunnels, stretches and prevents compression of the intracavernous nerves.

Pseudomonas aeruginosa colonization in patients with spinal cord injuries.

The prevalence of Pseudomonas aeruginosa colonization of patients with spinal cord injury was studied annually from 1976 to 1980. The urethra, perineum, rectum, drainage bag, and urine of patients on the spinal cord injury service were cultured. A total of 224 men and 32 women were studied. Most patients were managed with an external urinary collection system or padding, with or without intermittent catheterization. P. aeruginosa was cultured from one or more body sites (urethra, perineum, or rectum) in 65% of men and 18% of women. Drainage bags on the beds were frequently colonized with P. aeruginosa (73%). Significant bacteriuria with P. aeruginosa was present in 19% of the men and 13% of the women. P. aeruginosa colonization of body sites in men was closely associated with the use of an external urinary collection system. Significantly greater urethral and perineal colonization was found in men using an external urinary collection system. P. aeruginosa serotype 11 was the predominant serotype for the first 3 years, and the number of patients colonized with serotype 11 increased with length of hospital stay. The prevalence of serotype 11 significantly decreased in the last 2 years. The antibiotic susceptibility of the strains of P. aeruginosa isolated from these patients did not change in the 5 years, except that there was increasing susceptibility to carbenicillin in later years. This increasing susceptibility to carbenicillin was a reflection of a decreased prevalence of serotype 11 in these patients, since serotype 11 was more resistant than other serotypes to carbenicillin.

Effects of bathing on Pseudomonas and Klebsiella colonization in patients with spinal cord injuries.

This study of Pseudomonas aeruginosa and Klebsiella pneumoniae colonization in humans with spinal cord injuries who were using the external urinary collection system showed that meticulous bathing with the bar soap issued by the hospital did not eliminated colonization and was frequently associated with the shifting of these bacteria to adjacent sites on the body. Bacterial counts of the skin showed that bathing did reduce the numbers of P. aeruginosa and K. pneumoniae found on the skin surface and temporarily eliminated these bacteria from some sites. The persistence of these organisms for long periods, even when patients were meticulously bathed, indicates that P. aeruginosa and K. pneumoniae may become part of the resident flora in these patients.