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Although palliative sedation therapy is often required in terminally ill cancer patients, its efficacy and safety are not sufficiently understood. The primary aims of this multicenter observational study were to 1) explore the efficacy and safety of palliative sedation therapy, and 2) identify the factors contributing to inadequate symptom relief and complications, using a prospective study design, clearly defined measurement methods, and a consecutive sample from 21 specialized palliative care units in Japan. A sample of 102 consecutive adult cancer patients who received continuous deep sedation were enrolled. Physicians prospectively evaluated the intensity of patient symptoms, communication capacity, respiratory rate, and complications related to sedation. Symptoms were measured on the Agitation Distress Scale, the Memorial Delirium Assessment Scale, and the ad hoc symptom severity scale (0 = no symptoms, 1 = mild and tolerable symptoms, 2 = intolerable symptoms for less than 15 minutes in the previous one hour, and 3 = intolerable symptoms continuing for more than 15 minutes in the previous one hour). Inadequate symptom relief was defined as presence of hyperactive delirium (item 9 of the Memorial Delirium Assessment Scaleor=2) or grade 2 or 3 symptom intensity 4 hours after sedation. The degree of communication capacity was measured on the Communication Capacity Scale. Palliative sedation therapy succeeded in symptom alleviation in 83% of the cases. Median time elapsed before patients initially had one continuous hour of deep sedation was 60 minutes, but 49% of the patients awakened once after falling into a deeply sedated state. The percentage of patients who were capable of explicit communication decreased from 40% before sedation to 7.1% 4 hours after sedation, and the mean Communication Capacity Score significantly decreased to the level of 15 points (P0.001). The respiratory rates did not significantly decrease after sedation (18 +/- 9.0 to 16 +/- 9.4/min, P = 0.62), but respiratory and/or circulatory suppression (respiratory rateor= 8/min, systolic blood pressureor= 60mHg, or 50% or more reduction) occurred in 20%, with fatal outcomes in 3.9%. There were no statistically significant differences in patient age, sex, performance status, target symptoms, or classes and initial dose of sedative medications between the patients with adequate and inadequate symptom relief. Respiratory and/or circulatory suppression was significantly more likely to occur in patients receiving sedation for delirium and those with higher levels on the Agitation Distress Scale. Higher dose of midazolam was significantly correlated with younger age, absence of icterus, pre-exposure to midazolam, and length of sedation. Palliative sedation therapy is effective and safe in the majority of terminally ill cancer patients with refractory symptoms. However, a small number of patients experience fatal complications related to sedation. Comparison studies of different sedation regimens are needed to determine the most effective and safe sedation protocol.

The purpose of this study was to quantitatively assess cardiovagal, adrenergic and postganglionic sudomotor functions in a patient with chorea-acanthocytosis. We describe a 25-year-old woman with acanthocytosis, lip and tongue biting, chorea like movements and increased levels of serum creatine phosphokinase. The patient presented with orthostatic hypotension. The heart period response to deep breathing was moderately decreased and the quantitative sudomotor axon reflex test (QSART) was mildly abnormal in the lower extremities. The composite autonomic score (CASS) for this patient was 6 points which indicates moderate autonomic failure. Although a few previous reports have described autonomic dysfunction associated with chorea-acanthocytosis and have indicated that impairment is primarily sympathetic, our case study suggests that there is also parasympathetic dysfunction. We conclude that there is widespread autonomic involvement in chorea-acanthocytosis and that autonomic studies are useful in monitoring their course.

Six cases of normal perssure hydrocephalus (NPH) were found among 160 surgical cases of intracranial hematoma due to severe head injury, in the past 10 years. Out of the 160 cases, 80 were followed up. The incidence of post-traumatic NPH was 3.7%, or 7.5% in the followed-up cases. After a little improvement following the removal of intracranial hematoma, these cases showed prolonged disturbance of consciousness or a delayed recovery rate and a progressive enlargement of the ventricle without cerebral atrophy on CT scan. Diagnosis of post-traumatic NPH was made by the plateau level of clinical improvement accompanied by absence of intracranial hypertension and a progressive ventricular dilatation shown by an increased bicaudate cerebroventricular index on CT scan. Radioisotope serum albumin cisternography revealed disturbance of cerebrospinal fluid (CSF) circulation in all these cases and was a reliable tool for determining the indication for a shunting operation, which brought a marked improvement in five patients. The authors believe that the shunting operation should be tried on post-traumatic NPH patients who do not show cerebral atrophy. Presence of a subarachnoidal and a contusional hemorrhage on brain surfaces, noted in the operation, suggests the need to pay attention not only to the disturbance of the conventional extracerebral CSF pathway, but to that of the intracerebral pathway as regards the pathogenesis of post-traumatic NPH.

The numbers of large and intermediate diameter myelinated fibers of 17 ventral lumbar (L3, L4 and L5) spinal roots (vsr) of man (ages 17-81 years) have been evaluated using the improved methods of histologic processing and morphometry now available, semi-automatic methods of measurement and programmed calculation and plotting. A population of small diameter myelinated fibers as found in thoracic (T11) vsr, which are presumed to be preganglionic sympathetic fibers, were essentially absent from L3, L4 and L5 roots. On the average, there were 5716 (70%) large diameter fibers and 2625 (30%) intermediate diameter fibers in the L3 ventral spinal root. Comparable figures for L4 vsr were 4900 (70%) and 2152 30%) and for L5 vsr were 5043 (75%) and 1559 (25%). On the assumption that these lumbar roots contain few if any small diameter myelinated pre-ganglionic sympathetic axons, the large diameter fibers correspond to alpha motoneuron axons and the small diameter fibers to gamma motoneuron axons. With age, a decrease in the number of myelinated fibers was estimated to be 350 fibers per decade (approximately 5% per decade).

Various classes of nuclear granules and inclusion bodies were observed in primary malignant lymphoma cells in the brain. In addition to the chromatin and the nucleoli, the perichromatin granules and the unusual dense granules were main granular structures. However, the most prominent features were clusters of interchromatin granules. The individual interchromatin granules were round or ovoid, sometimes filamentous in shape, and about 30 to 40 mμ in diameter. They were not extractable in enzyme digestion with pepsin, RNAase, or DNAase, and decreased markedly in electron density when both pepsin and RNAase were employed. It may be reasonably assumed that the interchromatin granules may be a complex of RNA and acidic proteins. Some nuclear bodies involved the interchromatin granules in formation. This study may suggest 2 possible processes of formation of nuclear bodies, which are derived (a) from the interchromatin substances or (b) from the inner nuclear membranes.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.

The diameter histograms of cell bodies (cytons) in motor neuron columns at the L5 segment of the spinal cord of adult man reproducibly yield three peaks of increasing height: small (Cs), intermediate (Ci), and large (Cl). Histograms of L5 myelinated axons obtained from the ventral root have two peaks of increasing height: intermediate (Ai) and large (Al). In histograms prepared from seven cases of amyotrophic lateral sclerosis (ALS), the Cl and Al peaks were decreased selectively and severely. This provides evidence for alpha, but not gamma, motor neuron vulnerability. The Cl peak of spinal ganglion neurons and the Al peak of dorsal roots were significantly reduced in number, without a concomitant increase in Ci, Cs, and Ai peaks. This, plus earlier reports of abnormal cutaneous sensation thresholds, abnormal rates of fiber degeneration in cutaneous nerves, and dorsal column demyelination, provides evidence that large afferent neurons are affected in ALS, but to a lesser degree than alpha motor neurons.

Three cases of acute epidural hematoma which developed on the opposite side during decompressive surgery for traumatic intracranial hematomas, such as, acute subdural hematoma, brain contusion or acute epidural hematoma, are presented. Each case had a skull fracture or a diastasis of the cranial suture contralateral to the decompressive craniotomy, which might have injured the dural artery. During or immediately after decompressive operations, sudden bulging of the brain was unexpectedly encountered. It was suspected that bleeding of the injured dural artery ensued from the abrupt release of the mass effect caused by the intracranial hematoma. Since deviation and distortion of the brain stem would be more rapid and more intense under such circumstances, operative evacuation of the contralateral epidural hematoma should be urgently carried out.

In recent morphometric studies of the cytons of lumbar motoneuron columns, it was possible to discriminate various populations by the criterion of size. It was felt that the use of celloidin embedding, optimal enlargement to increase the number of counting windows, and the use of improved morphometric analysis had been important to this discrimination. Employing the improved methods of histologic preparation and morphometry to a study of the L5 spinal ganglia of man, it has been possible to show tentatively that there are at least three populations of cytons by diameter. The average number of large, intermediate and small cytons were 11,429, 31,675, and 25,389 respectively. It should now be possible to test whether selective congenital absence or degeneration of any of these three populations of cell bodies is found in disorders affecting primary afferent neurons.

As compared to the diameter frequency distribution of myelinated fibers of L3, L4 and L5 ventral spinal roots (VSRs) which have two well developed peaks [large-diameter axons (AL) and intermediate-diameter axons (AI)] and a poorly developed or non-existent peak of small-diameter axons (AS), D11 VSRs contain small AL and AI peaks and a prominent AS peak. Because the ratio of AL to AI myelinated fibers of D11 VSRs is similar to that in L3, L4 and L5 VSRs and it is known that D11 VSRs contain many pre-ganglionic autonomic fibers it seems likely that AS is composed predominantly of preganglionic autonomic fibers. The mean diameter of the AS peak in D11 VSRs is approximately 2.4 micrometer. Average numbers of AS, AI and AL myelinated fibers for D11 VSRs are 3835, 738, and 1545 per root. These values should be useful as controls for morphometric studies of various neuropathies. The average diameter positions of the peak of AL, AI and AS of D11 VSRs as compared to those of L3, L4 and L5 are displaced to smaller diameter categoried which may reflect the smaller axon diameters of neurons which are shorter.

Sixty-two cases of acute subdural hematoma were clinically analyzed with special reference to such prognostic factors as age, Glasgow Coma Scale (GCS) score on admission, pupillary signs, decerebration, and initial computed tomography (CT) findings. Intraparenchymal lesions demonstrated by CT were evaluated according to Yamaura's classification. In 19 cases, serum fibrin and fibrinogen degradation products (FDP) were measured at the time of admission. Emergency surgery was performed in 46 cases, and the remaining 16 patients were treated conservatively. The final outcome was judged according to the Glasgow Outcome Scale, and patients were divided into a “good outcome” group (good recovery or moderate disability) and a “poor outcome” group (severe disability, vegetative state, or death). In general, the outcomes proved to be unsatisfactory. Forty-four patients (71%) had a poor outcome, with 32/62 (52%) mortality, and only 18 (29%) had a good outcome. The clinical factors associated with a poor outcome were age over 64 years, a GCS score on admission of less than 7, decerebration, and absence of pupillary reaction to light. Initial CT scans showed brain damage in 46 patients (74%), 39 (85%) of whom had a poor outcome. This indicates that the outcome was significantly related to brain injury complicating the acute subdural hematoma. A high serum FDP level was similarly related to a poor outcome, which suggests that the serum FDP level reflects the degree of both primary and secondary brain injury. Thus, measurement of serum FDP may be valuable both in assessing clinical status and in evaluating the extent of brain injury in acute subdural hematoma.

Using a methodology which corrects for split cell error, and for the linear relationship between diameter of nucleolus and of cell body (cyton) and using semi-automatic methods of counting and sizing and programmed calculation and plotting, the number and diameter histograms of cytons of L-3, L-4, and L-5 motoneuron columns of 18 reference spinal cords of man (ages 17 to 82 years) have been evaluated. The number and frequency distribution of diameters (diameter histograms) of myelinated fibers of L-3, L-4 and L-5 ventral spinal roots (VSRs) had been determined in a preceding study as a control to validate the estimated number of alpha and gamma motoneuron cytons determined in this study from the same segment of spinal cord. The diameter histograms of cytons of motoneuron columns consistently contain three discrete peaks: a large-diameter peak (CL), an intermediate-diameter (CI) and small-diameter peak (CS). To illustrate, on the average, there were 4874 ± 585 large cytons and 1700 ± 564 ← intermediate cytons in the L5 segment of spinal cord. A reasonably close concordance was found between the average number of large cytons of spinal cord segments and the number of large-diameter myelinated fibers of ventral spinal roots (VSRs) (0.91, 0.94, and 0.98 for L3, L4 and L5 spinal cord segments and ventral spinal roots, respectively). For the ratio of the number of intermediate cytons to the number of intermediate axons the concordance was not as good (0.77, 0.85, and 1.14 for L3, L4 and L5 segments, respectively). Assuming that a cyton provides only one axon to VSR it is reasonable to infer from our studies that most large-diameter cytons are those of alpha motoneurons and that most of the intermediate-diameter cytons are those of gamma motor neurons. The greater number of axons than of cytons for the intermediate diameter group may be from a spurious inclusion of small-diameter axons (possibly pre-ganglionic autonomic fibers) with the intermediate-diameter group. On the average, the range of diameters of large-diameter cyton population in motoneuron columns was found to be 33 to 59 µm and for intermediate-diameter cytons was 24 to 33 µm. The total number of cytons per L3, L4 and L5 segments fell at a rate of ∽260, 175 and 200 per decade, respectively.

Motor, spinal ganglion, intermediolateral and sympathetic trunk neurons were reconstructed by morphometric sampling of their cell bodies at L5 and T7 segments and at various levels of spinal roots and peripheral nerves in a 31-year-old patient with dysautonomia and compared to reference cases. The patient had strikingly fewer intermediate motoneuron column neurons and intermediate ventral root axons (probably gamma motoneurons), spinal ganglion neurons, preganglionic autonomic neurons and sympathetic trunk neurons that did controls (approximately 10--30% of reference values). The striking agreement between selective absence of intermediate-diameter cytons (Ci) and of intermediate diameter myelinated fibers (Ai), which are thought to be gamma efferent, of L5 motoneuron columns provides further confirmation to our previous suggestion that the Ci peak of motoneuron columns are somas of gamma efferent neurons. The number and size of alpha motoneuron cell bodies and their proximal axons were like those of controls but their distal axons were probably atrophic. This finding probably explains the small reduction in maximum conduction velocity of motor nerve fibers found in this disorder. The brunt of the pathologic process in this disorder has been borne by intermediate and small neurons preferentially.

Lesions in the frontal base have been conventionally approached extra- and intradurally through a bilateral frontal craniotomy. However, when the lesion is large or deeply situated, wider retraction of the bilateral frontal lobes is required to obtain a sufficient operative field. The authors describe a new operative approach to dumbbell-shaped tumors in the frontal base, consisting of en bloc osteotomy of the bilateral orbital roofs and frontal sinus. This procedure, which is a modification of the transbasal approach described by Derome, is termed the "extensive transbasal approach." Successful applications of this procedure in three patients with frontal base tumors, two with frontal base fractures, one with a frontal arteriovenous malformation, and one with a frontal sinus mucocele are described. Also, the advantages of this approach over other, conventional operative approaches are discussed.