Evaluation of the effect of training using auditory stimulation on rhythmic movement in Parkinsonian patients--a combined motor and [18F]-FDG PET study.

INTRODUCTION: A programme of rehabilitation using auditory cues has previously been shown to decrease movement variability in the gait of Parkinsonian patients. OBJECTIVE AND METHODS: We studied the temporal variability of finger-tapping and gait in 9 patients with Parkinson's disease (PD) before and after they undertook a physical rehabilitation programme. Positron Emission Tomography (PET) using 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) was performed in these subjects to look for changes in metabolic brain activity after completion of the rehabilitation program. RESULTS: The reduction of variability was seen not only in gait but also other repetitive movements such as finger tapping. Furthermore, here we show differences in resting regional cerebral glucose utilisation in these patients compared to healthy controls (significant hypometabolism-p < 0.001-for the PD group in the right parietal and temporal lobes, left temporal and frontal lobes and a hypermetabolism in the left cerebellum) and specific changes following the improvements in repetitive movement abilities (significant metabolic increment-p < 0.001-in the PD group in the right cerebellum and in the right parietal and temporal lobes). CONCLUSIONS: Although our study does not allow us to draw firm conclusions, it provides new information on the neural basis of auditory stimulation in PD. Our results extend those from previous studies to show improvement in the temporal variability of two types of rhythmic movements after participation by PD patients in a physical rehabilitation programme, along with changes in glucose uptake in several brain areas involved in sensorimotor processing.

Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves.

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.

The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons.

In acute spinal rats (C2-C3) the transvesical infusion of saline activates a vesico-vesical excitatory reflex (Brain Res., 380 (1986) 83-93). In bladders containing a subthreshold amount of fluid the topical application of capsaicin on the outer surface of the bladder dome activated this spinal reflex and also produced a transient rise in blood pressure and heart rate. The effects of systemic capsaicin desensitization (50 mg/kg s.c. 5 min, 60 days before) on the sensory (activation of the spinal vesico-vesical reflex) and 'efferent' (tetrodotoxin-insensitive capsaicin-induced contraction) functions mediated by the capsaicin-sensitive sensory fibers were correlated to changes in substance P-like immunoreactivity (SP-LI) content of the urinary bladder in adult rats. Blockade of both sensory and efferent functions was observed at a time (60 min from capsaicin administration) when the SP-LI content of the urinary bladder was unaffected. Four days after capsaicin desensitization the SP-LI levels of the bladder are almost depleted indicating that the neuropeptide(s) are entirely stored in sensory structures. At this time the sensory-efferent functions mediated by these fibers are still blocked. At 15-60 days from systemic capsaicin desensitization there was a progressive, time-related recovery of SP-LI levels in the bladder as well as of the sensory-efferent functions. These findings indicate a role of the capsaicin-sensitive innervation of the urinary bladder in activating the spinal vesico-vesical reflex. The present findings suggest that measurement of SP-LI levels in the rat bladder may be a useful biochemical index for monitoring the function(s) of the capsaicin-sensitive, peptidergic sensory neurons.

Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents.

Topical application of exogenous prostanoids (PGE2, TBX B2) on the serosal surface of the urinary bladder of urethane-anaesthetized rats activated reflex micturition. Likewise, intravesical instillation of PGE2 during the cystometrogram lowered the threshold for reflex micturition. Both effects were prevented by systemic capsaicin desensitization (50 mg/kg s.c., 4 days before). Indomethacin pretreatment and systemic capsaicin desensitization each increased the micturition threshold without affecting the amplitude of micturition contraction. However, the effect of the two treatments combined was not greater than the effect of either alone. These findings support the idea that endogenous prostanoids facilitate reflex micturition by stimulating or sensitizing, directly or indirectly, the subset of bladder mechanoreceptors which is capsaicin-sensitive in adult rats.

The effect of SC-19220, a prostaglandin antagonist, on the micturition reflex in rats.

SC-19220 (5-20 mg/kg i.v.), a competitive receptor antagonist of PGE, increased the bladder capacity and reduced the voiding efficiency of micturition (elicited by slow transvesical filling) of urethane-anesthetized rats. The effect of SC-19220 was prevented by indomethacin pretreatment, whereas indomethacin per se mimicked the effects of SC-19220. SC-19220 produced a competitive rightward shift of the dose-response curve for the contractile effect induced by PGE2 on strips of rat detrusor muscle in vitro, whereas the amplitude of nerve-mediated twitches was unaffected. These findings support the hypothesis that endogenous PGE2 is physiologically involved in the regulation of vesicourethral motility in this species by facilitating attainment of the micturition threshold during the collection phase of the cystometrogram.

The effects of baclofen on spinal and supraspinal micturition reflexes in rats.

1. The effect of (+/-)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A 'low' dose of (+/-)-baclofen (0.5 mg/kg i.v.) barely affected the early phase of the transurethral cystometrogram (CMG) which involves activation of a spinal vesico-vesical excitatory reflex. 2. At a higher dose (2.5 mg/kg i.v.) (+/-)-baclofen suppressed both the spinal and supraspinal components of the bladder response to transurethral saline filling. 3. When the bladder was filled by the transvesical route a series of regular voiding cycles was obtained which are due to activation of a supraspinal vesico-vesical excitatory reflex. In this model, voiding efficiency of the rat bladder was markedly reduced even after a low dose of (+/-)-baclofen (0.5 mg/kg) and almost suppressed at 2.5 mg/kg. 4. (+/)-Baclofen reduction of voiding efficiency was mainly ascribable to an inhibitory effect on the expulsive phase of the voiding cycle which, in rats, depends critically upon the activation of a reflex which induces a twitch-like contraction of urethral/periurethral skeletal muscles. 5. (+/-)-Baclofen produced a small inhibition of the pinching-induced somatovesical excitatory reflex. (+/-)-Baclofen (2.5 mg/kg i.v.) produced also a marked but transient inhibition of bladder contractions induced by preganglionic nerve stimulation. However the time course of this effect was markedly shorter as compared to the long lasting suppression of voiding cycle observed with this same dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of Pneumocystis carinii pneumonia in patients with AIDS and other conditions: experience in a Philadelphia University Teaching Hospital.

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty-three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP-SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP-SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.

Experimental procedure to favor an otherwise undetectable potential rat muricidal behavior.

We hypothesized that variation in mouse aggressiveness could, at least in part, affect muricidal attitude of rats, therefore we introduced a sedated (diazepam 50 mg/kg/PO) instead of a normal (nonsedated) mouse into a cage with a rat. Rats were challenged with sedated or nonsedated mice for two-four days. It was found that a) the percentage (40-60%) of rats which killed a sedated mouse was higher than that (about 10%) of those which killed a nonsedated mouse; b) rats trained to kill a sedated mouse did not kill a nonsedated mouse and c) rats which did not kill a nonsedated mouse did not kill a sedated mouse. The present results indicate that the first experience in the presence of a sedated mouse uncovers a muricidal behavior which persists upon exposure to subsequent similar experimental conditions. This behavior undergoes seasonal variations, reaching a maximum in September-October and a minimum in February-March.

Intracisternal glycine activates the micturition reflex in urethane-anaesthetized rats.

Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.

Determinación de antígeno carcinoembrionario en los exámenes rutinarios de salud realizados desde Atención Primaria / Carcinoembryonic antigen as a cancer screening marker by primary care physicians

No disponible

Treatment of infectious complications of acquired immunodeficiency syndrome.

The infectious complications of the acquired immunodeficiency syndrome (AIDS) are discussed, and the conventional and nonconventional therapies used for these infections are reviewed. The infections most commonly encountered in patients with AIDS are Pneumocystis carinii pneumonia (58%), Candida esophagitis (31%), toxoplasmosis (21%), cytomegalovirus infections (15%), and herpes-simplex virus infections (12%). Pneumocystis carinii pneumonia is the most common life-threatening process in these patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the drug of choice for its treatment. Oral candidiasis often indicates the progression to AIDS in the high-risk populations of homosexual or bisexual men, intravenous drug abusers, and individuals with hemophilia. Nystatin suspension is commonly used to treat oral candidiasis, while Candida esophagitis demands systemic therapy with ketoconazole. Toxoplasmosis most commonly manifests itself in patients with AIDS as a cerebral mass lesion. The recommended therapy includes sulfadiazine and pyrimethamine. AIDS patients frequently experience protozoal invasion of the intestinal tract with Giardia lamblia, Isospora belli, and Cryptosporidium muris. Various drugs have been tried for these infections, including quinacrine hydrochloride, metronidazole, TMP-SMZ, and spiramycin. Cytomegalovirus (CMV) infections commonly involve the lungs, gastrointestinal tract, eyes, brain, and nervous system. Attempts to treat these disseminated CMV infections with antiviral agents, including acyclovir, have not been successful. However, acyclovir has been found beneficial in the treatment of herpes-simplex virus infections. Multiple infectious complications may occur in patients with AIDS as a result of the cellular-immune deficiency associated with this disease. Until more research is done with AIDS patients, therapy must be based on the data available from the treatment of these infections in immunosuppressed patients without AIDS.

The effect of cyclooxygenase inhibitors on the low filling rate cystometrogram in urethane anesthetized rats.

The effect of two widely used cyclooxygenase inhibitors (indomethacin and ketoprofen) on the low filling rate cystometrogram was investigated in urethane anesthetized rats. Both indomethacin and ketoprofen significantly increased volume threshold to elicit neurogenic bladder contractions without affecting their amplitude. Also the pressure threshold was unaffected by both drugs while the volume/pressure relationship was significantly flattened compared to controls. These findings indicate that acute suppression of arachidonic acid metabolism along the cyclooxygenase pathway increases the micturition threshold without affecting bladder muscle contractility and/or neurotransmission along the efferent pathway of the micturition reflex.

Dual effects of clonidine on micturition reflex in urethane anesthetized rats.

The effects of clonidine (CLO) on reflexly activated bladder motility have been examined in urethane-anesthetized rats and compared to its effects on field stimulation-induced contractions of isolated urinary bladder. Intravenous CLO suppressed micturition reflex transiently in a yohimbine-sensitive manner. The suppressive effect of i.v. CLO was greater after surgical sympathectomy (bilateral section of the hypogastric nerves). Intracisternal CLO was more effective than topical (on the bladder dome) or intracerebroventricular CLO in suppressing micturition. When tested in experimental conditions involving activation of both excitatory and inhibitory reflexes to the bladder CLO produced either inhibitory and/or excitatory effects on bladder motility in dependence of factors such as dose, route of administration and integrity of the sympathetic (inhibitory) innervation to the bladder. CLO suppressed bladder contractions produced by dimethylphenilpiperazinium, a ganglionic stimulant, and reduced those produced by postganglionic nerve stimulation. CLO inhibited, in a yohimbine-sensitive manner, amplitude of field stimulation-induced contractions of isolated rat bladder, and its effectiveness was inversely related to the frequency of stimulation. Our findings are suggestive that the inhibitory action of CLO on micturition reflex is counteracted, in normal animals, by a negative feedback on sympathetic inhibitory influences carried out through the hypogastric nerves.

Sampling for airborne fluorouracil in a hospital drug preparation area.

Fluorouracil content was studied in air samples from a hospital pharmacy work area where a vertical laminar-airflow biological safety cabinet (BSC) vented into the work area was used for the preparation of antineoplastic drugs. The BSC was run 24 hours per day and used approximately 6 hours per day. During one 56-hour period and one 95-hour period, a portable pump delivering room air at 2 L/min was positioned 12 inches outside the BSC. Fluorouracil content in extracts from 0.5-micron Teflon filters housed in the pump was assayed by high-performance liquid chromatography. The assay's lower limit of fluorouracil detection was 0.2 ng/cu m air. In the 56-hour sampling period and the 96-hour sampling periods, 25.4 g and 25 g, respectively, of fluorouracil were prepared. No fluorouracil was detectable in the filter extracts. Use of an appropriate biological safety cabinet in conjunction with good aseptic technique and the recommended procedures for safe handling of antineoplastic drugs may reduce the potential for dispersal of drug into the pharmacy workroom environment.

The capsaicin-sensitive innervation of the rat urinary bladder: further studies on mechanisms regulating micturition threshold.

The functional role of the capsaicin-sensitive innervation of the rat urinary bladder in regulating micturition has been investigated by means of the transvesical cystometrogram which allows study of the effects of drugs on the various phases of the bladder voiding cycle in urethane-anesthetized rats. Capsaicin desensitization (50-125 mg./kg., 4 to 60 days before) significantly increased both the volume and pressure threshold for micturition, indicating functional impairment of the mechanisms which transmit volume information from the bladder to the central nervous system. On the other hand the parameters related to the expulsive phase of the voiding cycle of the rat bladder are unaffected by capsaicin pretreatment. In capsaicin-desensitized rats the bladder weight remained within the limits of controls up to 60 days from the treatment although at this time the volume threshold was still elevated. In capsaicin-desensitized rats an increase of infusion rate above the physiological range produced micturition cycles having a normal volume and pressure threshold. These findings suggest that at high values of volume/pressure threshold micturition could be initiated through capsaicin-resistant sensory mechanism(s); in effect, multiple sensory systems, having different thresholds, relay volume/pressure information from the detrusor to the CNS.

Spinal and supraspinal components of GABAergic inhibition of the micturition reflex in rats.

The effect of gamma-aminobutyric acid (GABA)ergic drugs on micturition reflexes was investigated in urethane-anesthetized rats. Intracisternally administered GABA or homotaurine inhibited, in a bicuculline-sensitive manner, the supraspinal micturition reflex. Bicuculline or picrotoxin increased the amplitude and duration of the micturition contractions of supraspinal origin, suggesting the existence of a tonic GABAergic inhibitory mechanism. Neither diazepam nor bicuculline or picrotoxin had any significant effect on threshold of the spinal vesico-vesical micturition reflex. Aminooxyacetic acid, an inhibitor of GABA catabolism, increased threshold of the spinal but not of the supraspinal vesico-vesical reflex in a bicuculline-sensitive manner. Volume threshold for eliciting the supraspinal reflex was increased by diazepam and decreased by picrotoxin. Neither picrotoxin nor aminooxyacetic acid modified amplitude of bladder contractions elicited by pinching of the perineal skin (spinal somato-vesical reflex) nor of that produced by preganglionic nerve stimulation of the excitatory nerves. It is concluded that endogenous GABAergic mechanisms involving the activation of GABA A receptors modulate both the spinal and the supraspinal vesico-vesical micturition reflexes. These endogenous GABAergic mechanism(s) are operating tonically in inhibiting micturition at supraspinal but not spinal level.

Further studies on mechanisms regulating the voiding cycle of the rat urinary bladder.

1. The effect of transection of pudendal or hypogastric nerves and of various pharmacological pretreatments on the bladder voiding cycle elicited by saline filling was investigated in urethane-anesthetized rats. 2. Sectioning of pudendal nerves reduced efficiency of the expulsive phase of the voiding cycle while sectioning of hypogastric nerves enhanced voiding efficiency and reduced residual volume. 3. An increased voiding efficiency was also observed in 6-hydroxydopamine-treated rats. 4. Atropine and physostigmine decreased and increased voiding efficiency, respectively. Indomethacin pretreatment produced a marked increase in residual volume. 5. These findings indicate that the autonomic innervation of the bladder and urethra as well as production of local factors such as prostanoids regulates not only the collecting phase of the cystometragram but also influence markedly voiding efficiency.

Neurocutaneous melanosis, neurofibromatosis and spinal meningioma: an unusual association.

The case of 38-year-old woman bearer of a congenital giant naevus "en pélerine" with numerous neurofibromas and other satellite naevi was reported: the patient was afflicted by spastic tetraparesis, more pronounced on the right side. MRIscan of the spine revealed the presence of a cervical spinal tumor shown histologically to be a psammomatous meningioma. The skin picture was consistent with neurocutaneous melanosis; the rarity of its association with neurofibromatosis and spinal meningioma is discussed in the light of embryologic arguments.