Evaluation of aztreonam in the treatment of serious gram-negative infections in a university hospital in Saudi Arabia. The efficacy and safety of aztreonam were evaluated in an open trial at King Khalid University Hospital, Riyadh, Saudi Arabia. A total of 45 critically-ill adult patients were enrolled in the study. All patients with documented Gram-negative infection were treated with aztreonam as monotherapy. Antibiotics active against only Gram-positive and/or anaerobic organisms were allowed. Twenty cases were clinically evaluable. Eleven had lower respiratory tract infections (pneumonia), 3 had urinary tract infections, and 6 had septicemia. Clinical signs and symptoms, cultures and other laboratory profiles were assessed prior to treatment, at 4-6 days during treatment and within 2-3 days of the end of therapy (usually 7-15 days). Nineteen out of 20 (95%) had a satisfactory clinical response. All cases with septicemia and urinary tract infections were microbiologically cured. The overall microbiological response rate was 90%. Fifty-five percent of all infections were caused by Pseudomonas aeruginosa. Two patients with Gram-negative pneumonia due to P. aeruginosa did not respond microbiologically to aztreonam therapy. No serious adverse events requiring discontinuation of aztreonam therapy were reported. No mortality occurred.


Cost-effectiveness comparison of single and multiple-dose antibiotic treatment of lower uncomplicated urinary tract infections. This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in non-pregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 10-15 days was 86.4% for single-dose treatment with fosfomycin-trometamol (FT), and 81.8% for the multiple-dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treatment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slightly higher cost than for MDAG, which had a better cost/effectiveness ratio.


Influence of radiotherapy on intestinal microflora in cancer patients. We investigated in 15 patients with carcinoma of the uterine cervix or endometrium, who were undergoing postoperative radiation therapy, the effects of different fractionated radiation exposures on counts of fecal bacteria, on the growth of Clostridium difficile and Clostridium perfringens enterotoxin production. We observed a generally significant decrease in intestinal microflora after the first radiation exposure, whereas at the end of radiotherapy all bacteria increased and reached basal values except Enterococcus faecium 1, lactobacilli and total anaerobes. In some patients we observed an overgrowth of some Clostridium spp. which were potential pathogens associated with clinical symptoms. We did not observe an influence of multiple radiations on C. perfringens enterotoxin fecal contents. We conclude that patients receiving radiotherapy may benefit from the intake of oral bacteriotherapy, i.e. live beneficial bacteria such as Bacillus subtilis at the beginning of the irradiation exposure.


Carboplatin and radiation therapy for stage IV carcinoma of the head and neck. Preliminary results of a phase II study. 34 patients with head and neck cancer were treated with carboplatin and radiation therapy. Eligibility criteria included stage IV biopsy-proven squamous cell carcinoma with measurable disease and no distant metastases, Karnofsky performance status score of 60 or greater, age 18 years or more, no previous radiation therapy and adequate hematological, renal, and hepatic function. There were 27 males and 7 females. Ages ranged from 44-70 years with a median of 57 years. Follow-up ranged from 11-34 months with a median of 21 months. Total tumor doses ranged from 50-55 Gy with additional boosts of 15-20 Gy. Carboplatin was given in a dose of 100 mg/m2 once weekly (26 patients) and 200 mg/m2 once every 2 weeks (8 patients), during the radiation therapy course in all 34 patients. Each dose of carboplatin preceded irradiation. 25 patients responded while 9 did not. There were 19 complete responses (CR) and 6 partial responses. 4/19 CR recurred and 5/9 non-responding patients died of disease. Mild to moderate nausea and vomiting were seen in 52.3% of patients and mucositis was seen in 61.8% of patients. Moderate to severe hematological toxicity was seen in 35.3% of patients. Response rates and toxicity we observed during this study clearly show that the combination of carboplatin and radiation therapy is effective and suitable for the treatment of patients with stage IV head and neck cancer.


Treatment of elderly advanced gastric cancer patients with 5-fluorouracil and leucovorin combination. In September 1987 a phase II study was begun to verify if elderly symptomatic patients affected by advanced gastric cancer could benefit from a combination of 5-fluorouracil (5FU) and leucovorin (LV). We employed Machover's regimen: 5FU 370 mg/m2 i.v. infusion daily for 5 days; LV 200 mg/m2 i.v. bolus daily for 5 days; cycles were repeated every 3 weeks. 23 patients entered the study and 22 were evaluable for response and toxicity. We obtained only one partial response; 9 had stable disease and 12 progressed on therapy. The median duration of survival was 6 months. Symptoms were not affected by treatment. These data reflect the absence of significant improvement in the quality of life, which was further lessened by the presence of treatment side effects. Because of this we think that this regimen cannot be recommended for the treatment of elderly advanced gastric cancer patients.


Effect of intra-arterial versus intravenous cisplatin in addition to systemic adriamycin and high-dose methotrexate on histologic tumor response of osteosarcoma of the extremities. In neoadjuvant treatment of osteosarcoma of the extremities intra-arterial (IA) instead of intravenous (IV) administration of cisplatinum (CDDP) has been advocated to improve local response and consequently increase the percentage of limb salvages and the cure rate. Since the major local advantages from the IA use of CDDP have been recently questioned, a comparative prospective study was performed at the Rizzoli Institute between July 1990 and September 1991. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX), followed 6 days later by CDDP and adriamycin (ADM), HDMTX and ADM were delivered intravenously while CDDP was delivered according to previous randomization, either intra-arterially or intravenously. Of the 79 patients who entered the study 40 received CDDP IA and 39 CDDP IV. The percentage of clinical and radiological response of the tumor as well as the percentage of limb salvage procedures performed was the same in the two groups. However the rate of good histological response (tumor necrosis greater than 90%) was significantly higher in the group of patients who received IA CDDP than in the patients who received the drug intravenously (77.5% vs 46%: p less than 0.01). No differences in terms of local or systemic side effects were found in the two groups. A longer follow-up is necessary to establish if this improved good response rate achieved with IA CDDP will lead to an improved cure rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Recruitment of motor units in human forearm extensors. 1. Experiments were conducted on single motor units of two forearm muscles, extensor carpi radialis (ECR) and extensor digitorum communis (EDC) of human subjects. Our interest was whether or not task groups could be identified in these forearm muscles, and, if so, was there orderly recruitment within each task group. 2. To test for the presence of separate task groups within ECR, motor-unit recruitment was examined for two isometric contractions:wrist extension and radial deviation. Each of the ECR motor units tested repeatedly discharged during contractions in both directions, indicating the absence of separate task groups in ECR for contractions in these two directions. 3. Recruitment order between pairs of ECR motor-unit action potentials was examined for wrist extension and radial deviation. For 58 paired comparisons, the order of recruitment was the same in both directions. In terms of force output, plots of twitch torque versus recruitment threshold of ECR motor units showed a positive correlation for both directions, wrist extension and radial deviation, demonstrating size-ordered recruitment of ECR motoneurons for both contractions. 4. The EDC motoneuron pool exhibited two partially overlapping subpopulations of motoneurons on the basis of task, one subpopulation recruited for middle finger extension and the second one for ring finger extension. Contractions involving the index and little fingers were not examined. It is concluded that motor-unit task groups do exist within EDC motoneuron pool. Plots of twitch torque versus recruitment threshold showed positive correlations for each of these two task groups.(ABSTRACT TRUNCATED AT 250 WORDS)


PGO-related potentials in lumbar motoneurons during active sleep. 1. The present report describes the relationship that occurs during active sleep between ponto-geniculo-occipital (PGO) waves and changes in spinal cord motoneuron membrane potential. 2. These changes were characterized by the appearance of a complex pattern of motoneuron hyperpolarizing potentials, with a duration of approximately 300 ms, that were centered around the PGO wave. The first hyperpolarizing potential began before the onset of the PGO wave. Emerging from this hyperpolarizing potential was a second, larger-amplitude hyperpolarizing potential; it was followed by a succession of smaller-amplitude hyperpolarizations. 3. All potentials were present in conjunction with PGO waves during active sleep, but they were observed only in some motoneurons when PGO waves occurred during the transition period from quiet sleep to active sleep. 4. The potentials were reversed by chloride, demonstrating that they were inhibitory postsynaptic potentials (IPSPs). 5. These data, combined with the fact that these PGO-related IPSPs are blocked by strychnine, support the hypothesis that they are the result of the phasic enhancement of the activity of the same system that inhibits motoneurons during active sleep.


Isoproterenol enhances a calcium-independent potassium current in mouse anterior pituitary tumor cells. 1. The patch-clamp technique was used to study the action of the beta-adrenergic agonist (-)-isoproterenol in anterior pituitary tumor cells of the mouse. 2. (-)-Isoproterenol induced an inward-rectifying potassium conductance with half-maximal stimulation at a concentration of approximately 67 nM. The isomer (+)-isoproterenol was less effective in stimulating the current. 3. The effect of (-)-isoproterenol was abolished by cholera toxin treatment, indicating the involvement of a Gs protein, whereas pertussis toxin treatment did not exhibit a current reduction. 4. We blocked or stimulated phosphorylation pathways in cells to test the involvement of adenosine 3',5'-cyclic monophosphate (cAMP). It was concluded that the current stimulation probably was not exclusively mediated by cAMP. 5. Activation of calcium-dependent potassium channels by an isoproterenol-induced calcium influx into the cell could be excluded. 6. Therefore it is suggested that the observed activation of a potassium current by isoproterenol could be directly mediated by a Gs protein.


Effects of OFF-BF tones on responses of chopper units in ventral cochlear nucleus. I. Regularity and temporal adaptation patterns. 1. We have recorded the responses of neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate-anesthetized cats to pure tones [either at the unit's best frequency (BF) or at another frequency (OFF-BF)] and to two-tone combination stimuli. 2. The effects of OFF-BF input (either alone or presented simultaneously with a BF tone in a two-tone stimulus) on the response patterns of choppers may include not only rate inhibition but changes in the discharge regularity and the temporal adaptation properties of the spike trains. 3. In the majority of cases we studied (119 of 146 frequencies examined in 45 units), the discharge regularity of a response to an OFF-BF or two-tone stimulus is comparable with that of a "rate-matched" BF tone response. In a minority of cases (27 of 146 frequencies examined), however, OFF-BF input (either alone or in a two-tone stimulus format) changed the regularity compared with that of a rate-matched BF tone response. 4. In the majority of cases studied (139 of 171 frequencies examined in 53 units), the initial pattern of rate adaptation ["temporal adaptation pattern" (TAP)] was the same in response to a short tone burst at BF, to an OFF-BF tone burst, or to a pair of tones. The TAP can, however, be significantly altered by OFF-BF input, although this is a comparatively infrequent occurrence in our data sample (32 of 171 frequencies examined), from the response to BF tone to the response to the two-tone or OFF-BF stimulus, are as follows: sustained to slowly adapting; slowly adapting to transiently adapting, and transiently adapting to slowly adapting. Changes in the TAPs of chopper unit responses have been recorded from both regular and irregular choppers and cannot be accounted for on the basis of changes in sustained firing rate. These changes in the discharge regularity and TAP in the small minority of cases suggest that (at least in these cases) the inhibitory effect of OFF-BF input is not simply the result of two-tone suppression at the level of the auditory nerve fiber input. 5. We have observed that regular choppers may be transformed into irregular choppers by OFF-BF (rate inhibitory) input.(ABSTRACT TRUNCATED AT 400 WORDS)


Organization of suppression in receptive fields of neurons in cat visual cortex. 1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS)


Neural responses to visual texture patterns in middle temporal area of the macaque monkey. 1. We studied how neurons in the middle temporal visual area (MT) of anesthetized macaque monkeys responded to textured and nontextured visual stimuli. Stimuli contained a central rectangular "figure" that was either uniform in luminance or consisted of an array of oriented line segments. The figure moved at constant velocity in one of four orthogonal directions. The region surrounding the figure was either uniform in luminance or contained a texture array (whose elements were identical or orthogonal in orientation to those of the figure), and it either was stationary or moved along with the figure. 2. A textured figure moving across a stationary textured background ("texture bar" stimulus) often elicited vigorous neural responses, but, on average, the responses to texture bars were significantly smaller than to solid (uniform luminance) bars. 3. Many cells showed direction selectivity that was similar for both texture bars and solid bars. However, on average, the direction selectivity measured when texture bars were used was significantly smaller than that for solid bars, and many cells lost significant direction selectivity altogether. The reduction in direction selectivity for texture bars generally reflected a combination of decreased responsiveness in the preferred direction and increased responsiveness in the null (opposite to preferred) direction. 4. Responses to a texture bar in the absence of a texture background ("texture bar alone") were very similar to the responses to solid bars both in the magnitude of response and in the degree of direction selectivity. Conversely, adding a static texture surround to a moving solid bar reduced direction selectivity on average without a reduction in response magnitude. These results indicate that the static surround is largely responsible for the differences in direction selectivity for texture bars versus solid bars. 5. In the majority of MT cells studied, responses to a moving texture bar were largely independent of whether the elements in the bar were of the same orientation as the background elements or of the orthogonal orientation. Thus, for the class of stimuli we used, orientation contrast does not markedly affect the responses of MT neurons to moving texture patterns. 6. The optimum figure length and the shapes of the length tuning curves determined with the use of solid bars and texture bars differed significantly in most of the cells examined. Thus neurons in MT are not simply selective for a particular figure shape independent of whatever cues are used to delineate the figure.


Discharge patterns of levator palpebrae superioris motoneurons during vertical lid and eye movements in the monkey. 1. We recorded single-unit activity in the caudal central nucleus (CCN) of the oculomotor complex in monkeys trained to make vertical saccadic, smooth-pursuit, and fixation eye movements. We confirmed that our recordings were from motoneurons innervating the upper lid, because small lesions placed at the sites of responsive units were recovered among neurons labeled by horseradish peroxidase (HRP) injections into the levator palpebrae superioris muscle. 2. For fixations above a threshold lid position, levator motoneurons discharged at a steady rate, which increased linearly with upward lid position. The average position sensitivity during fixation was 2.9 spikes/s per deg, and the average lid motoneuron was recruited into steady firing when the eye was looking 10 degrees down. 3. During upward saccades, levator motoneurons discharged a burst of spikes that began, on average, 7.3 ms before the lid movement if the saccade started from a straight-ahead position; the lead time decreased considerably as the initial eye and lid positions shifted downward. The firing rate usually reached its peak (130-280 spikes/s) at the very onset of the burst and declined gradually during the course of the saccade. The steady rate associated with the new fixation position was reached about halfway during the saccade. All units exhibited a pause in firing during the initial half of large downward saccades; during small saccades, the pause was inconspicuous or absent. 4. During vertical sinusoidal smooth pursuit, levator motoneurons exhibited a sinusoidal modulation in firing rate, which led eye position by an average of 23 degrees at 0.3 Hz. The average velocity sensitivity calculated from such data was 0.63 spikes/s per deg/s. 5. Although they exhibit a number of qualitative similarities, the discharge patterns of levator motoneurons and superior rectus motoneurons differ in several respects. First, during a blink, when the lid undergoes a large depression but the eye exhibits only a brief transient displacement, levator motoneurons cease firing completely, whereas superior rectus motoneurons continue to discharge. Second, for all types of coordinated lid and eye movements, levator motoneurons discharge at lower firing rates than do superior rectus motoneurons. Third, during saccades, levator motoneurons have less conspicuous and shorter-lasting bursts and pauses than do motoneurons involved in rotating the eye. 6. During upward gaze, the qualitative similarity of their burst-tonic discharge patterns suggests that levator and superior rectus motoneurons receive input signals that originate from a common source, but that the signals are processed differently to deal with the different loads facing these muscles.(ABSTRACT TRUNCATED AT 400 WORDS)


Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys. 1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)


Violations of Listing's law after large eye and head gaze shifts. 1. Kinematic constraints were examined in static eye and head positions after large gaze shifts to visual targets. Three-dimensional eye and head rotations were measured in six adult human subjects by the use of the magnetic field search coil technique. 2. Eye positions in space were found to obey Donder's law; i.e., for any given gaze direction there was a unique three-dimensional orientation. In other words, angular eye positions in space (expressed as quaternions) were constrained to a two-dimensional surface. 3. When only the eye moved (head stationary), the shape of this surface resembled a plane and thus the eye position in space obeyed Listing's law. However, after gaze shifts involving both the eye and the head, the eye in space surface became twisted and thus nonplanar. This twist was similar to that achieved by a Fick gimbal model of rotations in which the horizontal axis is nested within a fixed vertical axis. During oblique gaze shifts, the head made predominantly horizontal movements whereas the eye made predominantly vertical movements. This, combined with the fact that the eye is mounted within the head, causes the eye in space surface to resemble that of a Fick gimbal. 4. The angular position of the head in space was also constrained to a two-dimensional surface. This surface was also not planar (Listinglike) and twisted in a manner similar to that of the eye in space. 5. Whereas the angular position of the eye in head was found to obey Listing's law after head-fixed gaze shifts, violations of Listing's law occurred after head-free gaze shifts. These violations showed significant intersubject variation in their magnitude and character. 6. Given that the eye in space violates Listing's law after head movements, the supposition that Listing's law serves the perceptual purpose of maintaining radial constancy is untenable. The Fick gimballike behavior of the head in space and eye in space may hold several advantages over a Listing's system. When the head in space behaves like a Fick gimbal, a horizontal line through the eyes remains parallel to the horizon. By having the eye in space behave like a Fick gimbal, the work done against gravity may be minimized by having the eye contribute more to vertical gaze shifts than does the head.


Discharge patterns in nucleus prepositus hypoglossi and adjacent medial vestibular nucleus during horizontal eye movement in behaving macaques. 1. Monkeys were trained to perform a variety of horizontal eye tracking tasks designed to reveal possible eye movement and vestibular sensitivities of neurons in the medulla. To test eye movement sensitivity, we required stationary monkeys to track a small spot that moved horizontally. To test vestibular sensitivity, we rotated the monkeys about a vertical axis and required them to fixate a target rotating with them to suppress the vestibuloocular reflex (VOR). 2. All of the 100 units described in our study were recorded from regions of the medulla that were prominently labeled after injections of horseradish peroxidase into the abducens nucleus. These regions include the nucleus prepositus hypoglossi (NPH), the medial vestibular nucleus (MVN), and their common border (the "marginal zone"). We report here the activities of three different types of neurons recorded in these regions. 3. Two types responded only during eye movements per se. Their firing rates increased with eye position; 86% had ipsilateral "on" directions. Almost three quarters (73%) of these medullary neurons exhibited a burst-tonic discharge pattern that is qualitatively similar to that of abducens motoneurons. There were, however, quantitative differences in that these medullary burst-position neurons were less sensitive to eye position than were abducens motoneurons and often did not pause completely for saccades in the off direction. The burst of medullary burst position neurons preceded the saccade by an average of 7.6 +/- 1.7 (SD) ms and, on average, lasted the duration of the saccade. The number of spikes in the burst was well correlated with saccade size. The second type of eye movement neuron displayed either no discernible burst or an inconsistent one for on-direction saccades and will be referred to as medullary position neurons. Neither the burst-position nor the position neurons responded when the animals suppressed the VOR; hence, they displayed no vestibular sensitivity. 4. The third type of neuron was sensitive to both eye movement and vestibular stimulation. These neurons increased their firing rates during horizontal head rotation and smooth pursuit eye movements in the same direction; most (76%) preferred ipsilateral head and eye movements. Their firing rates were approximately in phase with eye velocity during sinusoidal smooth pursuit and with head velocity during VOR suppression; on average, their eye velocity sensitivity was 50% greater than their vestibular sensitivity. Sixty percent of these eye/head velocity cells were also sensitive to eye position. 5. The NPH/MVN region contains many neurons that could provide an eye position signal to abducens neurons.(ABSTRACT TRUNCATED AT 400 WORDS)


PII component of the toad electroretinogram. 1. The PII component of the electroretinogram (ERG) is comprised of the b-wave and the DC component and is thought to reflect bipolar cell activity. Although the b-wave is generated in large part by a K+/Müller cell mechanism, the origin of the DC component is unclear. In this paper we detail our investigation of the origin of the DC component. We hypothesize that the DC component is generated by a K+/Müller cell mechanism identical to that involved in b-wave generation. 2. We studied the ERG in the dark-adapted, isolated retina preparation of the toad, Bu fo marinus. We used K+ ion-sensitive microelectrodes (K+ISM), as well as conventional intra- and extracellular microelectrodes, to record [K+]o changes, the vitreal ERG, and Müller cell responses. 3. We used the excitatory amino acid receptor agonist N-methyl-DL-aspartate (NMDLA) to inhibit light responses of third-order neurons and thereby eliminate most of the ERG M-wave. In the absence of the M-wave, the ERG consisted of PII and PIII. We then superfused the retina with a solution containing both kynurenic acid (KYN) and 2-amino-4-phosphonobutyric acid (APB), which together inhibit all retinal responses proximal to the photoreceptors. In the presence of KYN and APB, the ERG consisted only of PIII. Using digital subtraction, we reconstructed PII. To our knowledge, this is the first report of the isolation of a PII component in the ERG of a nonmammalian species. 4. Using K+ISMs, we recorded the distal K+ changes in the outer plexiform layer (OPL).(ABSTRACT TRUNCATED AT 250 WORDS)


Serotonin-containing neurons in lobsters: their role as gain-setters in postural control mechanisms. 1. The electrophysiological properties of two pairs of identified serotonin-containing neurons in the fifth thoracic (T5) and first abdominal (A1) ganglia of the lobster, Homarus americanus, were studied with the use of intracellular recording methods. Intracellular dye injection combined with immunocytochemistry verified the neurochemical status of the recorded neurons. 2. The serotonin-containing neurons usually are spontaneously active at 0.5-1.0 Hz and produce large, overshooting action potentials with a prominent after-hyperpolarization. The action potentials appear to be generated by a pacemaking mechanism endogenous to the cells. Extracellular recordings from thoracic connectives and from second thoracic roots show that action potentials from the cells in A1 and T5 are propagated rostrally along their axons and invade axon collaterals that innervate neurohemal organs in the second thoracic roots and the pericardial organs. These observations suggest that these serotonin-containing cells may function in part as important neurosecretory cells in the lobster. 3. Members of the pairs of serotonin-containing cells are not synaptically connected. They receive prominent inhibitory inputs in the form of inhibitory postsynaptic potentials (IPSPs), which exhibit discrete size classes and probably arise from several sources. Most IPSPs are temporally synchronized among the two pairs of serotonin-containing cells. 4. The serotonin-containing cells respond to stimulation of postural command fibers, with flexion command fibers exciting and extension command fibers inhibiting the cells, suggesting that these cells are a part of the postural flexion circuitry. 5. Intracellular activation or inhibition of the serotonin-containing cells has no effect on the spontaneous readout of postural motor programs recorded from motor nerve roots. Coactivation of the serotonin-containing cells and command fibers, or inhibition of the serotonin-containing cells while activating command fibers, however, shows that the cells act as "gain-setters," modulating the interaction between command inputs and motoneuron outputs. 6. About 24% of the motor neuron units analyzed are influenced by the serotonin-containing cells. There is a bias toward facilitation of the readout of flexion motor programs, particularly with stimulation of strong and moderate flexion command fibers. 7. The serotonin-containing cells in T5 and A1 ganglia are hypothesized to serve two functions, one tonic and the other phasic, in modulating behavioral output in lobsters. Tonic firing of the cells should result in a sustained release of serotonin from central and peripheral sets of nerve terminals, which, in turn, could influence peripheral and central targets of the amine.(ABSTRACT TRUNCATED AT 400 WORDS)


Patch-clamp study of postnatal development of CA1 neurons in rat hippocampal slices: membrane excitability and K+ currents. 1. The postnatal development of membrane properties and outward K+ currents in CA1 neurons in rat hippocampal slices was studied with the use of whole-cell patch-clamp techniques. 2. Neurons at all postnatal ages (2-30 days; P2-30) were capable of generating tetrodotoxin (TTX)-sensitive action potentials in response to intracellular injection of depolarizing current pulses. There was a gradual increase in the amplitude and a decrease in the duration of these action potentials with age. Stable values for spike duration were reached by P15, whereas spike amplitude increased until P20-25. In P2-5 neurons, the duration of action potentials was greatly prolonged by depolarization from the resting membrane potential, indicating a weak spike repolarizing mechanism at depolarized potentials. In contrast, the duration of spikes evoked in P20-30 neurons was not affected by similar changes in the membrane potential. 3. Application of tetraethylammonium (TEA, 10 mM) had no effect on the duration of spikes in P3-5 neurons, whereas application of 4-aminopyridine (4-AP, 2 mM) produced large increases in spike duration. In contrast, the duration of spikes in P26 neurons was greatly increased after TEA application, whereas 4-AP had smaller effects on spike duration in these neurons. 4. The input resistance and membrane time constant decreased with age from P2 to P15. The values for both parameters were considerably greater than those reported with conventional intracellular recording electrodes in the immature hippocampus. The resting membrane potential became more hyperpolarized with age. When the recording pipettes contained KCl (140 mM), the resting potential of P3-4 neurons was 34 mV depolarized compared with resting potentials observed with potassium gluconate-filled pipettes. Only a 13-mV change in resting potential was observed during similar comparisons in P27-28 neurons. 5. Outward currents activated by depolarization were examined with the use of voltage-clamp techniques in P2-30 neurons. In P2-5 cells, a small, slowly inactivating outward current was evoked with depolarizing commands from holding potentials near -50 mV. By preceding the depolarizing commands with a hyperpolarizing prepulse, an additional early transient outward current was evoked. The sustained and transient outward currents were separated by their kinetic properties and their sensitivity to cobalt (Co2+), TEA, and 4-AP.(ABSTRACT TRUNCATED AT 400 WORDS)


Time course of neural responses discriminating different views of the face and head. 1. Measurements of the magnitude and time course of response were made from 44 cells responsive to static head views at different levels of stimulus effectiveness. In this way responses to complex stimulus patterns evoking good, poor, and midrange responses could be compared across the cell population. 2. Cells exhibiting both good and poor initial discrimination between head views were found at short and long latencies; there was no correlation of any of the temporal response parameters measured with cell response latency. 3. The time course of the population response to the most effective stimuli showed a rapid increase to a peak firing rate (onset to peak, rise time, 58 ms) that was on average 115 spikes/s above spontaneous activity (S/A), followed by slower decay (decay time, 93 ms) to a maintained discharge rate (15% of the peak rate above S/A). 4. Discrimination between responses to different head views exhibited by the population showed a sharp rise and reached highly significant levels within 25 ms after the population's response onset. 5. On average, activity in a single neuron (the Average Cell) rises to 44% of its peak response rate within 5 ms of the response onset. 6. The Average Cell also showed exceptionally fast discrimination between views, significant within 5 ms of response onset. 7. It is argued that the fast rise in firing rate, followed by a decay to a lower rate and the very fast emergence of discrimination are features of pattern processing present in real neural systems that are lacking in many processing models based on artificial networks of neuronlike elements, particularly those where discrimination relies on top-down and/or lateral competitive inhibition. 8. It is concluded that the only way to account for the rapid discrimination is to consider a coding system in which the first spike from multiple sources is used to transmit information between stages of processing.


Bone scintigraphy following intravenous pamidronate for Paget's disease of bone. Pamidronate is one of several powerful bisphosphonates able to produce prolonged remissions of Paget's disease. This study examined to what extent bone scan changes parallel the clinical response and whether there is variability in the behavior of individual lesions. Twenty-five patients with pagetic bone pain for more than 2 yr were examined with bone scintigraphy before and on average 8 mo after six 30-mg infusions of pamidronate given weekly. Serum alkaline phosphatase and urinary hydroxyproline-to-creatinine ratios were measured before and 6 mo after treatment. A second course of pamidronate was given to 13 patients who had clinical or biochemical relapse. Of 136 pagetic lesions, 13 (10%) completely resolved, 90 (65%) improved and 33 (24%) remained unchanged. There was no significant difference in response between bony sites, although less active lesions were more likely to resolve completely. In conclusion pamidronate has a powerful effect on bone scan appearances in Paget's disease. Most lesions improve but complete resolution is uncommon. Less active lesions are more likely to resolve and are less likely to require further therapy.


Gallium imaging in metastatic and recurrent soft-tissue sarcoma. Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were 67Ga positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between 67Ga avidity and tumor grade with the exception of mesothelioma. No relationship was seen between 67Ga avidity and tumor cell type, disease site or lesion size. Following therapy, 67Ga correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy 67Ga avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma.


Significance of increased lung thallium uptake during adenosine thallium-201 scintigraphy. To determine the relationship of lung 201Tl activity during adenosine scintigraphy to the presence and extent of coronary artery disease, we investigated 132 subjects comprising 4 groups: 36 normal volunteers, 19 patients with angiographically normal coronaries, 29 patients with single-vessel (greater than 50% luminal stenosis) and 48 patients with multivessel coronary artery disease. Lung activity was quantified relative to maximal myocardial activity in both an early anterior planar image (pretomography) and the unprocessed tomographic image in the anterior projection. A good correlation was found for the lung-to-heart ratio assessed by planar and tomographic imaging (r = 0.83, p less than 0.0001), but the ratio was higher with planar imaging. The lung-to-heart ratio in the planar images was significantly higher in patients with multivessel disease compared to those with single-vessel disease (p less than 0.05) or volunteers and subjects with normal coronary arteries combined (p less than 0.001). A lung-to-heart ratio of greater than 0.45 in the planar images (upper 95% confidence limit for the normal subjects) was found in 6 (21%) single-vessel disease and 17 (35%) multivessel disease patients. Patients with elevated lung thallium activity during adenosine infusion had more hypoperfused myocardial segments (p = 0.007), more segments with redistribution (p = 0.04) and larger initial perfusion defect size (p = 0.04) than those with normal lung activity. Thus, evaluation of lung activity during adenosine thallium scintigraphy provides supplementary information regarding the severity of coronary artery disease and extent of myocardial hypoperfusion.


Bone mineral density of the axial skeleton in acromegaly. Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.


Dosimetry and biodistribution of an iodine-123-labeled somatostatin analog in patients with neuroendocrine tumors. A modified method for the preparation of a radiolabeled analog of somatostatin (123I-octreotide) is described. The pharmacokinetics and dosimetry of this analog were evaluated in patients with neuroendocrine tumors. Thirty patients had multiple blood and urine samples and sequential anterior and posterior whole-body scintigraphy up to 40 hr postinjection of 123I-octreotide. Region of interest analysis of the whole-body images was used to determine organ and tumor doses. The 123I-octreotide was rapidly cleared from the blood with a T 1/2 of 10 min by the hepatobiliary system. By 40 hr, approximately 55% was eliminated in the feces. The gallbladder wall received the highest dose (0.48 rad/mCi), with other organs receiving doses of 0.12 rad/mCi or less. Tumors were identified in 25 of 28 satisfactory studies. Tumor doses ranged from 0.1 to 0.6 rad/mCi. Calculations with 131I instead of 123I indicated that the gallbladder wall would receive 2 rad/mCi, while average tumor doses would range from 0.9 to 5.0 rad/mCi. Iodine-123-octreotide is a useful agent for the visualization of neuroendocrine tumors. The rapid washout of this agent from tumors precludes the possibility of radiotherapy with 131I-octreotide in these patients.


Unilateral voluntary hand movement and regional cerebral uptake of technetium-99m-exametazime in human control subjects. The study examines the sensitivity of a region of interest approach to detect functional changes in brain metabolism with SPECT and split-dose 99mTc-exametazime by replicating a simple hand movement experiment previously carried out with PET. Regional uptake of 99mTc-exametazime was determined in 12 healthy controls before and during a thumb-digit opposition task. Analysis of regional uptake was carried out blind to the hand used in the opposition task and showed a significant unilateral activation effect in a pericentral region of interest with opposite results in left- and right-handed activation. The maximum contralateral increase in tracer uptake was 16% before and 26% after correction for back diffusion. This is in good agreement with previous results employing absolute cerebral blood flow determination with PET and confirms the usefulness of 99mTc-exametazime SPECT for the examination of functional metabolic changes.


Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images. Preserved glucose metabolism in ischemically injured, dysfunctional myocardial tissue as demonstrated on PET imaging predicts functional improvement after revascularization. To characterize more precisely the relationship between regional myocardial blood flow, viability and extent and severity of flow and metabolism abnormalities, we developed a PC-based semiquantitative analysis technique using 13N-ammonia and 18F-deoxyglucose polar map displays. A data base for mean values (m) and standard deviations (s.d.) for relative 13N activities reflecting regional myocardial blood flow, relative 18F activities normalized to normal flow regions reflecting regional glucose utilization and the difference of normalized 18F and 13N activities as an index of a flow-metabolism mismatch was established in 11 normals. Parametric polar maps were derived by comparing patient data to a normal range defined as greater than m - 2 s.d. for relative myocardial blood flow and less than m + 2 s.d. for both relative glucose utilization and the difference between normalized 18F and 13N activities. Semiquantitative indices of extent and severity of blood flow defects, of relative increases in glucose utilization and of flow-metabolism mismatch areas are generated for the entire myocardium and the three coronary territories. The approach promises to be clinically useful to confirm presence and absence of flow and metabolic abnormalities and to assess their extent as a potential predictor of functional outcome after therapy.


Crossed cerebellar hypoperfusion in unilateral major cerebral artery occlusive disorders. We evaluated regional blood flow and oxygen metabolism in the cerebral and cerebellar cortices of 15 patients with unilateral major cerebral artery occlusive disorders with PET. These patients showed a cortical blood flow asymmetry in middle cerebral artery distribution. Only subcortical abnormalities were detected on computed tomography. Nine patients showed crossed cerebellar hypoperfusion, a reduction in contralateral cerebellar blood flow, while six did not. No difference in the degree of cerebral blood flow asymmetry existed between the two patient groups. However, oxygen metabolism asymmetry was more pronounced and was more closely matched to blood flow asymmetry in patients with crossed cerebellar hypoperfusion. These findings suggest that a major cause of cerebral cortical blood flow reduction is reduced metabolic demand in patients with crossed cerebellar hypoperfusion. Crossed cerebellar hypoperfusion may have clinical significance as a reflection of the cerebral metabolic state on blood flow images.


Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor. The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor.


Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer. Twelve patients with metastatic colon cancer were treated with 131I-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose.


Radiation dosimetry for indium-111-labeled anti-CEA-F(ab')2 fragments evaluated from tissue distribution in rats. Accurate dosimetric investigations are important to be able to fulfill the ambition of radiation protection in nuclear medicine and to minimize the radiation burden to the patient. This paper presents human radiation absorbed dose estimates following an administration of an 111In-labeled anti-CEA-F(ab')2 (BW431/31) based on detailed biodistribution and elimination data in a rat model. Animals were followed from the time of injection up to 28 days after injection. A significant initial uptake of 111In in the bone marrow, 25% of injected activity, was evident after 6 hr. The kidneys showed a maximal uptake of 20% at 24 hr. At the end of the study, 27% of the activity was still retained in the whole body. The estimated humans absorbed dose to the kidneys, testes, spleen and bone marrow was 2.27, 0.80, 0.51 and 0.37 mGy MBq-1, respectively. The effective dose was estimated to 0.27 mSv MBq-1. The tissue distribution in rats was comparable to that in humans, which was confirmed by whole-body scintigrams and human biopsies.


The effects of regional pulmonary blood flow on protein flux measurements with PET. We used PET to evaluate whether changes in regional pulmonary blood flow (PBF) or plasma volume (PV) affect calculations of the pulmonary transcapillary escape rate (PTCER) for 68Ga-labeled transferrin. We reduced PBF in five dogs by inflating a right atrial balloon. Regional PBF decreased 25% to 174 +/- 40 ml/min/100 ml lung without a change in PV or PTCER. In eight other dogs, we decreased PBF and PV via controlled arterial hemorrhage. PBF decreased 45% to 110 +/- 33 ml/min/100 ml lung and PV decreased 22% without a change in PTCER. We also used a series of computer simulations to evaluate the effect of even greater reductions in regional PBF on PTCER calculations. These simulations showed, in support of the experimental data, that if PBF was greater than 40 ml/min/100 ml lung, PTCER could be accurately measured. However, below this level, PV was increasingly under-estimated and PTCER overestimated. The results indicate the sensitivity of the PTCER calculation to errors in the PV measurement, especially in regions of markedly reduced regional PBF.


Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography. Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time-activity curve, and hence, noninvasive quantification of MBF without arterial cannulation.


Clinically important characteristics of maximum-likelihood reconstruction. SPECT images of a Jaszczak rod phantom, a single-slice Hoffman brain phantom and a uniform water-bath were acquired. Simulated noisy bar phantoms incorporating depth-dependent attenuation and blur were produced and compared to simulations with depth-independent attenuation and blur, as is the case in PET. Following iterative maximum-likelihood reconstruction, regularization was performed with use of Gaussian filters. While correction for attenuation is achieved in approximately 10 iterations, spatial resolution in the SPECT reconstructions, quantified by contrast in the bar simulations and by visual inspection of the real data, was highly nonuniform, being poorest at the center and improving toward the periphery. Image resolution continued to improve well beyond 50 iterations when regularization was applied that maintained a constant signal-to-noise ratio. Contrast in the simulated PET data also improved with increasing iterations, but the PET data showed uniform contrast throughout the transaxial slices at all numbers of iterations.


Copper-64-labeled antibodies for PET imaging. In the imaging of tumors using radiolabeled monoclonal antibodies, the use of PET gives increased sensitivity over conventional gamma camera imaging techniques. Copper-64, a positron-emitting radionuclide, has been labeled to 1A3, an anticolorectal carcinoma monoclonal antibody, and its fragments 1A3-F(ab')2 utilizing the bifunctional chelate Br-benzyl-TETA. The 64Cu-labeled intact 1A3 and 1A3-F(ab')2 have been evaluated as potential imaging agents for PET. Biodistribution studies of 64Cu-benzyl-TETA-1A3 and 64Cu-benzyl-TETA-1A3-F(ab')2 in tumor-bearing hamsters were compared with those of 111In-Br phi HBED-1A3, 111In-Br phi HBED-1A3-F(ab')2 and 125I-labeled intact 1A3 and 1A3-F(ab')2. Tumor uptake of 64Cu-labeled intact 1A3 and fragments in the hamster model was superior to both 111In- and 125I-labeled intact 1A3 and fragments. Human dosimetry data for 64Cu- and 123I-labeled 1A3 and 1A3-F(ab')2 were calculated from biodistribution data in rats. High kidney uptake of 64Cu-benzyl-TETA-1A3-F(ab')2 precludes clinical study at this time; however, the data shows that 64Cu-benzyl-TETA-1A3 would be suitable for positron tomography imaging of colorectal cancer in patients.


SPECT, magnetic resonance and angiographic features in a moyamoya patient before and after external-to-internal carotid artery bypass. Brain SPECT changes in a patient with cerebral vaso-occlusive disease caused by moyamoya disease are presented. Brain SPECT after a revascularization procedure demonstrated significant improvement of brain flow which was confirmed by angiography. Clinical and magnetic resonance features are reviewed.


Cerebral blood flow and glucose metabolism measurements in a patient surviving one year after carbon monoxide intoxication. A 29-yr-old woman was studied for 1 yr after acute carbon monoxide intoxication following an attempted suicide by inhalation of automobile exhaust fumes. The patient demonstrated impaired responsiveness to stimuli without any specific neurological deficits for 1 yr after carbon monoxide intoxication. Repeated brain magnetic resonance imaging consistently displayed only bilateral globus pallidus lesions, but no lesions in either deep white matter or cerebral cortex. Position emission tomography measurements of regional cerebral blood flow, and glucose utilization rate were made in this patient at 6 mo and 1 yr following carbon monoxide intoxication. Impairment of both blood flow and glucose metabolism were found not only in the basal ganglia but also in morphologically normal frontal cortex. The decrease in glucose utilization in the frontal cortex was greater than that in the basal ganglia. During the period of 6 mo to 1 yr, blood flow and glucose metabolism in the basal ganglia recovered to the normal range. In the frontal cortex, however, blood flow and glucose metabolism remained approximately 20% lower than the normal mean values. This prolonged dysfunction in the frontal cortex may therefore be responsible for the impaired responsiveness of the subject.


Stress fractures associated with osteosarcoma of the lower limb. Three patients with osteosarcoma of the femur developed abnormal radiopharmaceutical uptake in the bones of the contralateral leg. This uptake was not due to metastases. The histology in one patient, the form of the lesion and the disappearance of the abnormal uptake without treatment in the other two, indicated that the uptake was probably due to stress fractures. Changes in weight bearing and walking in the normal leg as a result of the osteosarcoma in the other leg could have been the cause of the stress fractures. It should be recognized that new abnormal uptake on bone scintigraphy in patients with osteosarcoma of the leg may not necessarily indicate metastasis. It may be caused by a stress fracture and disappears after rest.


Gallium-67 distribution in a man with a decrease in both transferrin and hepatic gallium-67 concentration. A patient with reduced transferrin concentration had a 67Ga scintigram that showed uptake in a peritoneal abscess, pericarditis and pleural effusion but only faint liver uptake. Gallium-67 activity was measured in liver, lung, muscle and plasma samples obtained at autopsy. The percent injected dose/kg for liver and plasma samples was considerably lower than previously reported while that in muscle and lung tissues values were comparable to prior data. In this patient, sites on transferrin available to bind 67Ga were reduced from the normal 40 microM to 5.2 microM; this in turn increased the concentration of radiogallate from 1% to 7%. This elevated free activity increased 67Ga excretion and reduced the amount of 67Ga*transferrin species. These results and those of previous studies suggest that liver uptake is slower than abscess uptake and more sensitive to concentration of 67Ga*transferrin. Iron status is an important facet of the interpretation of 67Ga scintigrams.


Necrotizing tracheobronchitis identified on an indium-111-white blood cell scan. The clinical entity of necrotizing tracheobronchitis (NTB) is well described in the pediatric literature. The incidence of NTB in neonatal autopsies varies from 4% to 44%. More than 3 hr of assisted ventilation may be necessary for the development of NTB in neonates. A similar clinical problem was described as "hemorrhagic tracheitis" in two adults during high frequency jet ventilation and as a complication of conventional mechanical ventilation in an adult. We present here a rather unusual case of NTB in an adult on mechanical ventilation, in whom tracheobronchitis was diagnosed incidentally with an 111In white blood cell scan obtained for other purposes.


Fast maximum-likelihood reconstruction.

Fast maximum-likelihood reconstruction. A significant problem in application of maximum-likelihood reconstruction to SPECT and PET studies is the very long computation time required for this iterative algorithm. An approach is presented in which the basic calculations involved in projection and backprojection are performed only once and stored in computer memory, thus significantly reducing the computation time.


The technetium-99m-DTPA renal uptake-plasma volume product: a quantitative estimation of glomerular filtration rate. An image-based method for estimating quantitative renal glomerular filtration rates (GFR) by calculating the product of the renal uptake rate and plasma volume is presented. By using the relationship GFR = F.PV/t, F represents renal 99mTc-DTPA uptake after bolus injection, PV is the plasma volume and t is time. This GFR evaluation was carried out on 96 patients and compared to GFR values determined in the same patients using radiotracer blood clearance techniques relying on two venous blood samples. When estimating patient plasma volumes using patient's weight and measured hematocrit values, the image-based method for calculating GFR accurately approximates the values obtained from blood samples (linear regression slope = 1.03; y-intercept = -2.81 ml/min). The two techniques correlate with a value of r = 0.89.


Orienting foreign nurse graduates through preceptors. Many staff development departments have difficulty orienting foreign nurse graduates. Some of the difficulties foreign nurses themselves have are described in this article, as are difficulties American nurses have in orienting them. Nursing preceptors trained to understand and solve the problems of foreign nurse graduates may make orientation more successful for the nurse and the unit.


Rejuvenating orientation to increase nurse satisfaction and retention. The current nursing shortage has forced nursing managers to examine the reasons for nurse turnover and to evaluate institutional programs and policies that may strengthen staff nurse retention. For the past two decades, the nursing profession has concluded that nurse retention is linked to job satisfaction. Accordingly, employers have attempted to improve job satisfaction by permitting self-scheduling, nurse selection of unit assignment, and bonus pay for less desirable shifts. In spite of these and other efforts designed to retain nurses, the turnover rate generally has remained high.


Helping staff help students.

Helping staff help students. Nurses in a variety of health care settings work with nursing students. Staff development educators can help the nurses create a successful student affiliation while protecting the agency and patients. By teaching staff what to ask and what to tell, educators help students learn without compromising care. Positive student experiences also may help recruit new graduates to the agency. Teaching the staff to share information will help staff help students.


Using self-studies to meet JCAHO requirements. Using self-studies to provide mandatory information for hospital employees is both cost effective and time effective. Time invested in writing and distributing these programs is well worth it provided learning is verified through testing. Records of mandatory information can be kept either by hand on education cards or by computer. Periodic updates of material keep the self-study process fresh and interesting for participants and educators alike.


Investigating the effectiveness of self-learning packages in staff development. The nursing shortage and high patient acuity levels make it difficult for nurses to attend traditional inservice programs. Time and financial constraints affect the staff educator's ability to teach needed topics to large numbers of nursing staff. This study suggests that the use of self-learning packages can be a viable alternative or adjunct to traditional inservice programs for nursing staff development.


Dentine hypersensitivity--the effect of toothbrushing and dietary compounds on dentine in vitro: an SEM study. Dentine hypersensitivity occurs when dentinal tubules are open on the dentine surface and patent to a vital pulp. There has been limited interest in the aetiology of dentine hypersensitivity. In particular, little is known about agents that remove the dentine smear layer to expose tubules. Toothbrushing certainly may expose dentine, but whether a toothbrush per se has the effect of opening tubules has not been established. The aim of this study in vitro was to determine whether a toothbrush could remove or create a smear layer. In addition, the combined effects of toothbrushing with dietary fluids on dentine was assessed. Toothbrushing was observed, by scanning electron microscopy, both to remove and to recreate a smear layer on dentine specimens. However, the processes took a considerable time, and under conditions of normal toothbrushing it is unlikely that the latter plays a direct aetiological role in opening tubules. Indeed, together with toothpaste it is more likely that brushing has a therapeutic action by mechanically forming a smear layer. Conversely, and importantly, toothbrushing in the presence of dietary acids enhanced smear layer removal. This finding raises the question of whether the dental profession should be advising that teeth be brushed before meals rather than after, as is often the case.


A systems approach to capillary blood glucose monitoring. A joint nursing/patient education effort. Capillary blood glucose monitoring was successfully instituted on the nursing units at a small community hospital using a systematic, goal-directed process. Through the efforts of the diabetes educator and the coordinator of nursing education, nursing staff are now able to detect fluctuations in patient blood glucose levels rapidly and to provide prompt treatment. The system was implemented on the nursing units with preceptors serving as instructor-trainers. The implementation required the close cooperation and collaboration of multiple hospital departments. The nurse educator and the diabetes educator conduct ongoing monitoring using data collected from the patient, the nurse, and the multidisciplinary team.


The antimicrobial effect of an iron-binding agent on Streptococcus mutans. The antimicrobial activity of 2,2'-bipyridine, an iron-binding agent, was investigated by incorporating this agent into Scotchbond dental adhesive resin. The growth of Streptococcus mutans on the surface of resin, media and culture vessel was determined by optical density measurements. It was observed that 2,2'-bipyridine exhibited excellent antimicrobial properties.


Stresses generated by luting resins during cementation of composite and ceramic inlays. The present study used the finite element method to model the stresses generated by a composite luting cement around a class I composite restoration and a ceramic inlay. In many cases maximum tensile stresses of greater than 20 MPa were found, and failure of the restoration-dentine and restoration-glass ionomer interfaces was predicted.


Age and maintenance of removable dentures in Finland. The age and maintenance of dentures, and denture-cleaning habits, were studied by an interview survey. The material represented nation-wide the Finnish population aged greater than or equal to 15 years old, and there were 957 interviewees, of whom 328 were denture wearers. In total, 45% of the upper and 40% of the lower dentures were over 10 years old. More than one-third of the dentures more than 5 years old had never been maintained during that time. Individuals whose dentures had been made and fitted by dental technicians visited dentists less frequently than individuals whose dentures had been made by dentists. Over 80% of the denture wearers reported cleaning their dentures by brushing at least once a day, and women cleaned them more frequently than men. The present findings suggest that denture wearers should be a special target group for dental health education, for the development of the latter, and for the development of dental health care services in the future.


Surface electromyographic estimates of recruitment/rate coding of masseteric motor units. Surface electromyographic (EMG) recordings were obtained from the masseter muscles in healthy subjects performing brisk maximum voluntary teeth clenching (MVC) for about 1 s. During the onset (0-600 ms) of ballistic MVC activity, the peak amplitude of the EMG interference patterns showed a consistent and significant increase, on examination for 0-200 ms, 200-400 ms, and 400-600 ms of MVC activity. The peak (maximum) and median (centroid) frequencies of power spectrum density functions of the raw surface EMGs (interference patterns) showed an absence of consistent and significant changes during 0-600 ms of ballistic MVC activity. However, the estimated total energy contents (peak amplitude x peak frequency) of the surface interference patterns showed a consistent and significant increase from 0 to 600 ms of ballistic MVC activity, and this was interpreted as global recruitment/rate coding of masseteric motor units.


Use of shell crowns in Hong Kong dental hospital attenders. In 1984 an oral health survey of Hong Kong adults aged 35-44 years revealed that 15% of subjects presented with metal shell crown restorations, often as components of fixed-bridge reconstructions. The aim of this study was to describe the patterns and means of use of shell crowns, and to describe the patterns of tooth loss in patients who presented with such restorations, attending for treatment at the dental teaching hospital in Hong Kong over a 2-year period. A total of 1563 such patients attended. The records, which included radiographs, of 165 of these patients aged 35 years and above, obtained by means of a systematic sampling frame, were studied by one trained examiner. On initial presentation each patient was found to have a mean of 4.0 shell crowns, 77% of these being components of bridge restorations. The bridges involved a mean of only 3.9 units (retainers and pontics). The tooth type most commonly replaced by a bridge of this type was the first molar. It was concluded that most shell crowns used in this patient group are abutment retainers for predominantly short-span bridge restorations.


Number and intensity of occlusal contacts following surgical correction of mandibular prognathism. The aim of the present investigation was to study the changes in the number and intensity of occlusal tooth contacts in the intercuspal position following surgical correction of mandibular prognathism. The study sample consisted of 33 adults with mandibular prognathism whose management included bilateral vertical ramus set-back osteotomy and combined orthodontic treatment. Measurement of the number and intensity of occlusal tooth contacts was performed by means of the photocclusion technique. Recordings of the number and intensity of occlusal contacts were made 1 day before operation and 6 months post-surgery. Testing of the differences of the means for both the number of occlusal contacts and their intensity between the two phases was achieved by means of a paired t-test. The results of the study showed that the combined orthodontic and surgical treatment produced a significant increase (P less than 0.001) in the number and intensity of occlusal contacts (4.54 and 160 kg mm-2 respectively). However, whether this increase in occlusal contacts resulted in an overall improvement in craniomandibular functional status cannot be answered by the present study.


Bond strength and rupture properties of some soft denture liners. The bond strength and rupture properties of three soft acrylic liners (Coe-Soft, Coe Super-Soft and Vertex Soft) and two silicone liners (Molloplast-B and Flexibase) were tested immediately after processing and following immersion in water at 37 degrees C for 7 and 90 days. The bond test gave variable results, as some materials partly peeled and then stretched until rupture occurred. After saturation the acrylic liners exhibited an increase in tear resistance, whilst silicone materials deteriorated, in the case of Flexibase to approximately 25% of its original value. Vertex Soft was the exception, as tear resistance decreased as water sorption increased. Scanning electron microscopy revealed indefinite demarcation between soft acrylic resins and hard denture base, which was not altered after saturation in water. On the other hand, the interface between denture base and silicone liners was clearly visible before and after saturation. The results indicated that denture soft liners had variable water sorption values depending on their basic structure, and some properties changed after immersion in water, a finding that is of relevance to prosthodontic practice.


A novel lamina lucida component of epithelial and endothelial basement membranes detected by LH39 monoclonal antibody. The murine monoclonal antibody, LH39 was characterized in this study and appeared to bind to a novel basement membrane epitope. This antigen was expressed in the epithelial basement membrane of human tissue derived from all three germ cell layers and in basement membranes surrounding small blood vessels within the stroma of all organs examined. LH39 antigen could be first detected in fetal skin at the dermo-epidermal junction at 7 weeks estimated gestational age but was not present in the dermal vasculature until 16 weeks. When tested against tissue from a range of lower mammalian species, LH39 antigen appeared to be primate-specific. The epithelial basement membrane zone in organotypical cultures, where there is de novo synthesis of basement membrane components, contained abundant LH39 antigen in contrast to other basement membrane components, type IV collagen, laminin, and type VII collagen. Ultrastructural localization of LH39 epitope, using immunogold electron microscopy on unfixed freshly frozen tissue, was to the lamina lucida. No cross-reactivity could be detected between LH39 and laminin, fibronectin, and collagens I, III, IV, and V using the ELISA assay. In vitro studies with a range of proteolytic enzymes suggested that the antigen was non-collagenous in nature. LH39 precipitated a polypeptide with a molecular weight of 185 kD from extracts of metabolically labelled cultured keratinocytes, and polypeptides of 185 and 200 kD from the culture medium. The tissue distribution of LH39 antigen suggested that it may be an epitope within anchoring filaments. Potential applications of this antibody include the study of benign and malignant human vascular disorders, diseases and tumours associated with angiogenesis, epithelial neoplasms, and conditions of tissue regeneration and repair, such as wound healing.


Sequential dermal microvascular and perivascular changes in the development of scleroderma. It has been previously proposed that there is a primary microvascular abnormality in patients with systemic sclerosis. In this study using conventional light and electron microscopy, immunohistochemistry, and labelled adenosine uptake techniques, changes in the dermal microvasculature have been related to the various clinical stages of skin disease in systemic sclerosis. The earliest pathological changes are seen in clinically normal skin. They constitute changes in endothelial cell function and their consequences. Perivascular oedema is an early feature. With progression in the clinical disease, there is, at first, an inflammatory cell infiltrate into the dermis, particularly the papillary and mid-dermis, and platelet aggregation within vessels. Further clinical progression is associated with increasing dermal fibrosis, loss of adnexae, and vascular effacement. It is postulated that the recruitment of different types of mononuclear cells into the dermis is causally linked with the preceding endothelial cell dysfunction and the subsequent induction of fibroblast proliferation and collagen synthesis.


Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material. The objective of this study was to test the hypothesis that excessive severity of ischaemic heart disease in diabetics is due, in part, to capillary inadequacy. Sections from autopsied hearts of diabetic patients with and without myocardial infarction as well as from those of patients with infarcts and no diabetes were used for morphometric studies of intramural microvessels in areas without infarction. Normoglycaemic patients with normal hearts were also examined. Two to five transverse sections from each of 44 hearts (stained with methenamine silver) were examined for capillary numerical density, capillary to myofibre ratios, and myofibre diameters. Averages for each case and totals for each group were calculated and compared. Normoglycaemic patients with infarcts had increased morphometric values. Diabetics with infarcts had significantly lower capillary densities than the other groups. In conclusion, it is suggested that in diabetes there is an inadequate ischaemia-induced, reactive angiogenesis. This may contribute towards increased myocardial vulnerability in further ischaemic injury and perhaps to diabetic cardiomyopathy.


A tumour promoter induces alterations in vinculin and actin distribution in human renal epithelium. Loss of cell-substratum adhesion is an important factor during tumour progression. We have previously described reduced focal contact components and poorly organized cytoskeletal actin in renal cell carcinomas. In this study, we have used the potent tumour promoter TPA on cultured human renal epithelium to mimic neoplastic transformation. The morphological changes induced by TPA were examined by phase contrast and fluorescence microscopy. TPA treatment caused rounding up of cells and loss of adhesion to either fibronectin or laminin substrata. Cytoskeletal actin was redistributed from orientated stress fibre bundles to a perinuclear circumferential arrangement. This was accompanied by a progressive reduction in the number of vinculin-containing contacts with accumulation of vinculin in punctate spots in the perinuclear region. These altered membrane-cytoskeletal interactions induced by TPA are entirely reversible and mimic epigenetic changes which occur during tumour progression.


Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis. The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.


Apposition of fibroblasts to mast cells and lymphocytes in normal human lung and in cryptogenic fibrosing alveolitis. Ultrastructure and cell perimeter measurements. The perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (-19.6, 25.1); P = 0.65). The PPAF range overall was 3.8-94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung. The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung.


Myoendothelial contacts in the thoracic aorta of rat fetuses. There is increasing documentation of the presence of endothelial-smooth muscle communication in both small and large arteries. We have found that morphological evidence of these contacts appears early in development. Intimate contacts between endothelial and muscle cells in the thoracic aorta of normal rat fetuses have been studied with transmission electron microscopy. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the elastic lamellae. Most of these cell processes seem to arise from the muscle cells and they usually have a club-shaped configuration. The specific nature of the cell-cell contact was predominantly via simple appositions with an intercellular space of 6-15 nm. Myoendothelial contacts are potential sites for electrical and metabolic communication between elements of the intima and media, ensuring that the vessel wall works as a unit. The demonstrated necessity of intact endothelium for smooth muscle cell response to load may depend on this type of contact.


X-ray microanalysis of bulk hydrated specimens of neoplastic and non-neoplastic human urothelium. Specimens of neoplastic and non-neoplastic human urothelium were rapidly frozen against a copper block immersed in liquid nitrogen, planed in a cryoultramicrotome and then examined by low-temperature scanning electron microscopy (LTSEM) following coating by aluminium. Energy dispersive X-ray microanalysis (XRMA) was performed on the superficial urothelial cells and on gelatin blocks mounted in parallel which had known concentrations of sodium, potassium, chloride, and phosphorus. The neoplastic urothelial cells had significantly less phosphorus (P less than 0.05) than non-neoplastic cells and the ratios K+/P,K+/Na+, and K+/Cl- were significantly higher in neoplastic cells than in non-neoplastic cells (P less than 0.00001). These results are consistent with those expected in cells with a sustained increase in intracellular pH caused by stimulation of Na+/H+ ion membrane exchange.


Macrophage and perisinusoidal cell kinetics in acute liver injury. Perisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride-induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear-incorporated bromodeoxyuridine. The results showed an expansion of the desmin-positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.


Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963-1972 (N = 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P less than 0.01). Inter-observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Borders' grading of the whole biopsy had no prognostic value (P less than 0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis.


Image analysis in the discrimination of verrucous carcinoma and squamous papilloma. Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in these two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P less than 0.001) by an uncorrelated t-test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 microns 2 and the latter 184 microns 2. Squamous cell carcinomas differed from the other two neoplasms by their large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 microns 2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 microns 2 supports a diagnosis of squamous papilloma.


Degranulation of cystic fibrosis nasal polyp mast cells. The ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non-CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non-CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non-CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non-CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non-CF specimens. Although eosinophils were observed in the non-CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non-CF nasal polyps with mast cell degranulation, a salient feature of CF specimens.


Improve your hospital autopsy rate to 40-50 per cent, a tale of two towns. In the light of medical audit, all pathology departments are scrutinizing their hospital autopsy rate. In most countries, the rate has fallen over the last few decades to between 10 and 20 per cent. However, it is still possible to achieve a much higher rate. We compare two neighbouring District General Hospitals (DGHs): Northampton, with the more usual autopsy rate of 11 per cent, and Kettering, with a higher rate of 40-50 per cent. These hospitals are comparable in almost every way except for the system used to request permission for an autopsy. These differences were evaluated and the following factors were found to be of importance in achieving a high rate: (1) centralization of death certificates within the mortuary and personal contact between the certifying doctor and the relatives within the bereavement room; (2) mortuary pathology technicians are designated as bereavement officers and act as coordinators between relatives, clinicians, and pathologists; and (3) regular clinico-pathological meetings and a positive attitude to autopsies by clinicians.


The fractal dimension may be a useful morphometric discriminant in histopathology. The hypothesis is presented that fractal geometry, and the fractal dimension in particular, is likely to be a more useful method of image analysis in histopathology than the use of regular Euclidean geometry. The concept of the fractal dimension is described and it is suggested that many human tumours have a fractal structure over a wide range of scales. It is postulated that the fractal dimension will be useful in discriminating between different diagnostic categories and may also allow more precise prognostic stratification within single diagnostic groups.


A two-colour technique for chromosome in situ hybridization in tissue sections. By extending non-isotopic in situ hybridization of DNA probes (targeted to metaphase chromosomes or interphase nuclei) to hybridization using tissue sections, additional topological information on the DNA structure and specific alterations can be obtained. We have established a method for the application of two different, chromosome-specific probes labelled with two colour dyes allowing simultaneous detection of two-colour signals. This method was tested in and is applicable to tissue sections of various origins. To demonstrate its sensitivity, prostate carcinomas (either as cryosections or as sections from paraffin blocks) were investigated for the presence or absence of chromosomes 1 and Y. The technique presented here, comparable to immunohistochemical staining, is particularly useful for routine application in diagnostic laboratories and testing of fresh or archival material.


Parathyroid hormone-related peptide: expression in fetal and neonatal development. Hypercalcaemia frequently complicates the clinical management of cancer. Many factors have been implicated in the pathogenesis of this humoral hypercalcaemia of malignancy, the most recent candidate being parathyroid hormone-related peptide (PTHrP). Until now, this peptide has been detected only in some normal and transformed adult tissues. In recent years, it has become apparent that tumours are capable of expressing and secreting factors previously elaborated only during fetal life. Many of these factors act to stimulate the growth of both tumour and fetal cells in an autocrine manner. The data presented here demonstrate that PTHrP is expressed in the human and rat fetus throughout gestation. Immunocytochemistry reveals a gestationally related, changing pattern of expression which is paralleled by changes in mRNA transcription. These data support the hypothesis that PTHrP may function as a fetal growth factor.


Seminal vesicle amyloid: the first example of exocrine cell origin of an amyloid fibril precursor. Amyloid fibrils have been extracted from seminal vesicles, and a dominant 14 kD amyloid fibril protein has been identified. An antiserum to this protein reacted both with amyloid and with epithelial cells in some normal seminal vesicles. These reactions were blocked with seminal vesicle secretion and seminal vesicle amyloid fibril protein, but not by degraded amyloid fibrils or fibril protein from other types of amyloid. It is concluded that seminal vesicle amyloid is derived from secretory proteins of the seminal vesicles. As such, it is the first amyloid described which appears to be the product of an exocrine secretory cell.


'Pleural' and pulmonary carcinosarcomas. The histological distinction between carcinosarcoma and mesothelioma has received little attention. The object of this study was to describe the histology and immunohistochemistry of two carcinosarcomas presenting as pleural tumours. These were compared with 12 carcinosarcomas from sites within the lung, and with the established features of mesothelioma. Histologically and immunohistochemically, these 'pleural' carcinosarcomas are similar to conventional pulmonary carcinosarcomas but accurate recognition is hindered by their gross appearance and biphasic histology which closely mimic mesothelioma. They may exhibit features such as neutral mucin, expression of carcinoembryonic antigen, squamous differentiation, and neuroendocrine differentiation which, when present, are evidence against mesothelioma. These tumours are rare and have passed unnoticed until now.


Immunopathological changes in the skin following recombinant interleukin-2 treatment. The systemic administration of the cytokine recombinant interleukin-2 (rIL-2) is associated with a number of toxic effects, including dermatological complications. The clinical, histological, and immunopathological changes occurring in the skin of six patients receiving rIL-2 for metastatic colorectal carcinoma have been studied. All of the patients developed a diffuse erythema shortly after initiation of the treatment. In one patient, generalized erythroderma and photosensitivity developed. The initial biopsy revealed patchy spongiosis, focal exocytosis, and focal basal layer damage with a perivascular chronic inflammatory cell infiltrate. With further treatment there was progressive thickening of the epidermis. Immunohistochemistry revealed changes in the expression of CD1, CD3, CD4, and CD25, particularly on perivascular cells. Additionally, there was an increase in the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes in the basal and mid-layers of the epidermis, endothelial cells, and perivascular cells. It is hypothesized that the expression of ICAM-1 by the epidermal keratinocytes may be the important event in initiating the cutaneous manifestations associated with rIL-2 administration.