Apparent Central Nervous System Research Articles

FIVE‐YEAR RESULTS OF A PHASE 2 STUDY OF CNS‐ORIENTED THERAPY WITH R‐CHOP FOR UNTREATED INTRAVASCULAR LARGE B‐CELL LYMPHOMA: FINAL ANALYSIS OF THE PRIMEUR‐IVL STUDY

Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of extranodal large B-cell lymphoma characterized by selective growth of lymphoma cells in the lumina of small vessels. The prognosis of IVLBCL is typically poor without timely diagnosis. Based on the promising efficacy of rituximab-containing chemotherapy and a high incidence of secondary central nervous system (CNS) involvement after rituximab-chemotherapy, we conducted the PRIMEUR-IVL study to explore the efficacy of CNS-oriented therapy with rituximab-chemotherapy whose primary analysis demonstrated 2-year progression-free survival (PFS) of 76% and 2-year overall survival (OS) of 92% with a low incidence of secondary CNS involvement of 3%. Patients and Methods: The PRIMEUR-IVL study is a multicenter, single-arm, phase 2 trial at 22 hospitals in Japan for untreated histologically confirmed IVLBCL patients without apparent CNS involvement at diagnosis. The treatment regimen includes three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by two cycles of rituximab with high-dose methotrexate and additional three cycles of R-CHOP. Intrathecal chemotherapy including methotrexate, cytarabine, and prednisolone was administered four times during the R-CHOP phase. We present a preplanned final analysis of the PRIMEUR-IVL study including 5-year PFS, OS and secondary CNS involvement. Results: A total of 38 patients were enrolled, of whom 37 patients were eligible. One patient with a history of testicular lymphoma was excluded. As of July 2021, with a median follow-up of 7.1 years (interquartile range 5.6–8.7), 5-year PFS in all eligible patients was 68% (95% confidence interval [CI] 50%–80%) and OS was 78% (95% CI 61%–89%). Median PFS and OS were not reached. No additional secondary CNS involvement was observed after primary analysis with 3% of cumulative incidence. Severe adverse events after the primary analysis were grade 4 neutropenia (n = 1) and grade 4 myelodysplastic syndrome that did not require specific treatment (n = 1). During the observation period after enrollment, there were a total of eight deaths due to following reasons: primary disease (n = 6), sepsis (n = 1), and unknown sudden death (n = 1). Conclusions: In this 5-year, long-term follow-up analysis of the PRIMEUR-IVL study, frontline treatment of CNS-oriented therapy with standard R-CHOP for untreated IVLBCL patients without apparent CNS involvement provided durable response and clinically meaningful results for PFS, OS, and low incidence of secondary CNS involvement with manageable toxicity. Our result provides one of active treatment for untreated IVLBCL patients. The research was funded by: The Practical Research for Innovative Cancer Control, the Japan Agency for Medical Research and Development (AMED), Japan, JP19ck0106511 and the National Cancer Center Research and Development Fund, 23-A-17 and 26-A-4. The research was supported by the Center for Supporting Hematology-Oncology Trials (C-SHOT). Keyword: chemotherapy Conflicts of interests pertinent to the abstract K. Shimada Honoraria: AstraZeneca, Chugai, Eisai, Kyowa Kirin, Symbio M. Yamaguchi Honoraria: AbbVie, Bristol Myers Squibb, Chugai, Janssen, Kyowa Kirin, Meiji Seika, MSD, Nippon Shinyaku, SymBio, Takeda Research funding: AstraZeneca, Chugai Pharma, Genmab, Incyte, Eisai, Takeda, Nippon Shinyaku, Otsuka, Asahi Kasei, Kyowa Kirin, Chugai H. Nagai Honoraria: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Eisai, Novartis, Janssen, Mundi Pharma, Lilly, AstraZeneca, Ono, Meiji, AbbVie, Nippon Shinyaku, GSK, Sumitomo Pharma, Genmab, CSL Behring Research funding: Kyowa Kirin, Takeda, Chugai, Bristol Myers Squibb, Janssen, AstraZeneca, Ono, AbbVie, Nippon Shinyaku, Daiichi-Sankyo, Zenyaku Kogyo, Solasia J. Takizawa Honoraria: Chugai, Kyowa Kirin N. Fukuhara Honoraria: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, AstraZeneca, Meiji Seika, Ono, Janssen, Bristol-Myers Squibb, Eisai, Kyowa Kirin, Symbio, Novartis Research funding: Chugai, Genmab, AbbVie, Takeda, Eli Lilly, Incyte, Chordia Therapeu D. Ennishi Honoraria: Eisai, Kyowa Kirin, Chugai Research funding: Nippon Shinyaku, Chugai Y. Minami Consultant or advisory role: Takeda, Novartis Honoraria: Bristol-Myers Squibb, Novartis, Pfizer, Daiichi Sankyo, Astellas Research funding: CMIC, Bristol-Myers Squibb, Novartis, Takeda, Chugai, Ono Y. Atsuta Consultant or advisory role: Meiji Seika, JCR Pharmaceuticals, Kyowa Kirin Honoraria: Novartis, AbbVie H. Kiyoi Honoraria: Novartis, Astellas, AbbVie, Chugai Research funding: Zenyaku Kogyo, Nippon Shinyaku, Chugai, Astellas, Kyowa Kirin, Takeda, Sumitomo Pharma, Sanofi, Eisai, Ono, FUJIFILM, Kyowa Kirin, Otsuka, Perseus Proteomics, Daiichi Sankyo, CURED, Bristol-Myers Squibb, AbbVie

False Positive Cerebrospinal Fluid NMDA Receptor Antibodies: A Single Center Case Series

Objective To report the presence of CSF NMDA receptor antibodies in four patients without NMDA receptor encephalitis encountered at a single tertiary care center. Background The diagnosis and confirmation of anti-NMDA encephalitis relies heavily on detection of IgG antibodies to the NR1 subunit of the NMDA receptor in cerebrospinal fluid. While this is generally considered a highly specific test for anti-NMDA encephalitis, there have been rare reports of false positive testing. Design/Methods A retrospective chart review of medical records for patients with positive CSF NMDA receptor antibody testing at University of Texas Southwestern Medical Center between 2011 to 2021 was performed. Results 40 patients were identified who had positive CSF NMDA receptor antibodies. Of these 40 patients, 4 (10%) were concluded to have false positive results. The false positive results consisted of 1 patient with refractory status epilepticus from suspected synthetic cannabinoid use, 1 patient with an anaplastic astrocytoma, 1 patient with fungal meningitis from Candida dubliniensis, and 1 patient with bifrontal cerebritis of suspected infectious etiology. Of the 4 patients with false positive antibody testing, 3 were immediately recognized as likely false positives while 1 patient was misdiagnosed and treated for an autoimmune encephalitis prior to a final diagnosis with tissue biopsy. Conclusions Although uncommon, false positive CSF NMDA receptor antibodies pose significant diagnostic and therapeutic challenges for clinicians. In our case series, false positive tests occurred in patients with apparent central nervous system disorders, including seizure, infection, and neoplasm. While antibody testing is an essential tool for the diagnosis of NMDA receptor encephalitis, caution should be exercised in interpreting positive results when the clinical and paraclinical data are not consistent with the well characterized phenotype of NMDA receptor encephalitis.

Favorable Outcomes of Newly Diagnosed Intravascular Large B-Cell Lymphoma Patients Treated with R-CHOP Combined with High-Dose Methotrexate Plus Intrathecal Chemotherapy: Results from a Multicenter Phase 2 Trial (PRIMEUR-IVL)

Favorable Outcomes of Newly Diagnosed Intravascular Large B-Cell Lymphoma Patients Treated with R-CHOP Combined with High-Dose Methotrexate Plus Intrathecal Chemotherapy: Results from a Multicenter Phase 2 Trial (PRIMEUR-IVL)

Acute encephalopathy with biphasic seizures and late reduced diffusion associated with Streptococcus sanguinis sepsis.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) develops in association with systemic as well as central nervous system (CNS) viral or bacterial infections. AESD is most often noted with influenza or human herpesvirus 6 infection in previously healthy infants. However, AESD has also been reported in an infant with developmental retardation and in a mentally and motor-disabled adolescent. Here, we report the case of a 4- year-old female with significant development delay due to spinal muscular atrophy, who developed AESD during Streptococcus sanguinis sepsis with no apparent CNS infection. Although the patient had extremely high serum procalcitonin (45.84 ng/mL, reference; <0.4) on admission indicating a poor prognosis, she was successfully managed for sepsis and AESD.

Primary and Metastatic Central Nervous System Malignancies

About 13,000 deaths each year in the United States are attributed to primary central nervous system (CNS) malignancies. An estimated 20% of patients with cancer eventually develop clinically apparent CNS metastases, and an estimated 170,000 cases of brain metastases are diagnosed in the United States yearly. Autopsy studies suggest that as many as 50% of patients dying from advanced cancer may have metastasis to the CNS. This chapter provides an overview of primary and metastatic CNS malignancies with in-depth discussion of gliomas, primary CNS lymphoma, meningioma, brain metastases, leptomeningeal metastases, and metastatic epidural spinal cord compression. Discussions cover epidemiology, etiology, diagnosis, and treatment of gliomas, including surgery, radiotherapy, and chemotherapy for both newly diagnosed gliomas and recurrent gliomas. The epidemiology, diagnosis, treatment and prognosis for primary CNS lymphomas are reviewed, as well as the epidemiology, etiology, diagnosis, treatment, and prognosis for meningiomas. Epidemiology, diagnosis, and prognosis for brain metastases are briefly discussed, and the section on treatment includes surgery, stereotactic radiosurgery, and whole-brain radiotherapy for patients with three or fewer brain metastases. The sections on leptomeningeal metastases and metastatic epidural spinal cord compression cover diagnosis, treatment, and prognosis. This chapter contains 126 references.

Primary and Metastatic Central Nervous System Malignancies

About 13,000 deaths each year in the United States are attributed to primary central nervous system (CNS) malignancies. An estimated 20% of patients with cancer eventually develop clinically apparent CNS metastases, and an estimated 170,000 cases of brain metastases are diagnosed in the United States yearly. Autopsy studies suggest that as many as 50% of patients dying from advanced cancer may have metastasis to the CNS. This chapter provides an overview of primary and metastatic CNS malignancies with in-depth discussion of gliomas, primary CNS lymphoma, meningioma, brain metastases, leptomeningeal metastases, and metastatic epidural spinal cord compression. Discussions cover epidemiology, etiology, diagnosis, and treatment of gliomas, including surgery, radiotherapy, and chemotherapy for both newly diagnosed gliomas and recurrent gliomas. The epidemiology, diagnosis, treatment and prognosis for primary CNS lymphomas are reviewed, as well as the epidemiology, etiology, diagnosis, treatment, and prognosis for meningiomas. Epidemiology, diagnosis, and prognosis for brain metastases are briefly discussed, and the section on treatment includes surgery, stereotactic radiosurgery, and whole-brain radiotherapy for patients with three or fewer brain metastases. The sections on leptomeningeal metastases and metastatic epidural spinal cord compression cover diagnosis, treatment, and prognosis. This chapter contains 126 references.

A Pediatric Renal Lymphoma Case Presenting with Central Nervous System Findings

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis.Conflict of interest:None declared.

GABAB receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline

Peripherally restricted analgesics are desirable to avoid central nervous system (CNS) side effects of opioids. Nonsteroidal anti-inflammatory drugs produce peripheral analgesia but have significant toxicity. GABAB receptors represent peripheral targets for analgesia but selective GABAB agonists like baclofen cross the blood–brain barrier. Recently, we found that the CNS-impermeant amino acid, isovaline, produces analgesia without apparent CNS effects. On observing that isovaline has GABAB activity in brain slices, we examined the hypothesis that isovaline produces peripheral analgesia mediated by GABAB receptors. We compared the peripheral analgesic and CNS effect profiles of isovaline, baclofen, and GABA (a CNS-impermeant, unselective GABAB agonist). All three amino acids attenuated allodynia induced by prostaglandin E2 injection into the mouse hindpaw and tested with von Frey filaments. The antiallodynic actions of isovaline, baclofen, and GABA were blocked by the GABAB antagonist, CGP52432, and potentiated by the GABAB modulator, CGP7930. We measured Behavioural Hyperactivity Scores and temperature change as indicators of GABAergic action in the CNS. ED95 doses of isovaline and GABA produced no CNS effects while baclofen produced substantial sedation and hypothermia. In a mouse model of osteoarthritis, isovaline restored performance during forced exercise to baseline values. Immunohistochemical staining of cutaneous layers of the analgesic test site demonstrated co-localization of GABAB1 and GABAB2 receptor subunits on fine nerve endings and keratinocytes. Isovaline represents a new class of peripherally restricted analgesics without CNS effects, mediated by cutaneous GABAB receptors.

Primary and Metastatic Central Nervous System Malignancies

About 13,000 deaths each year in the United States are attributed to primary central nervous system (CNS) malignancies. An estimated 20% of patients with cancer eventually develop clinically apparent CNS metastases, and an estimated 170,000 cases of brain metastases are diagnosed in the United States yearly. Autopsy studies suggest that as many as 50% of patients dying from advanced cancer may have metastasis to the CNS. This chapter provides an overview of primary and metastatic CNS malignancies with in-depth discussion of gliomas, primary CNS lymphoma, meningioma, brain metastases, leptomeningeal metastases, and metastatic epidural spinal cord compression. Discussions cover epidemiology, etiology, diagnosis, and treatment of gliomas, including surgery, radiotherapy, and chemotherapy for both newly diagnosed gliomas and recurrent gliomas. The epidemiology, diagnosis, treatment and prognosis for primary CNS lymphomas are reviewed, as well as the epidemiology, etiology, diagnosis, treatment, and prognosis for meningiomas. Epidemiology, diagnosis, and prognosis for brain metastases are briefly discussed, and the section on treatment includes surgery, stereotactic radiosurgery, and whole-brain radiotherapy for patients with three or fewer brain metastases. The sections on leptomeningeal metastases and metastatic epidural spinal cord compression cover diagnosis, treatment, and prognosis. This chapter contains 126 references.

Multiple-year experience in the diagnosis of viral central nervous system infections with a panel of polymerase chain reaction assays for detection of 11 viruses.

Polymerase chain reaction (PCR) is becoming more common in diagnostic laboratories. In some instances, its value has been established. In other cases, assays exist, but their beneficial use has not been determined. This article summarizes findings from 3485 patients who underwent testing over a 6-year period in our laboratory. A panel of PCR assays was used for the detection of a range of viruses associated with central nervous system (CNS) infections. PCR results were analyzed in conjunction with information about patient age and sex, the time between onset and specimen collection, and other variables. Medical chart review was conducted for 280 patients to gain diagnostic and epidemiologic insight with regard to cases of unresolved encephalitis. A total of 498 PCR-positive samples (14.3%) were detected. Enteroviruses accounted for the largest number (360 [72.3%]) of positive PCR results, followed by herpes simplex virus (76 [15.3%]), varicella-zoster virus (29 [5.82%]), and West Nile virus (WNV) (18 [3.61%]). Of 360 patients who tested positive for enterovirus, only 46 met the Centers for Disease Control and Prevention's encephalitis definition. It resulted in the greatest decrease (87.2%) in positive PCR results. Overall, the PCR positivity rate for specimens collected within 5 days after illness onset was 17.2%, compared with 8.6% for specimens collected > or =6 days after onset. The value of PCR in the diagnosis of viral infections has been established. PCR is of lower value in the detection of WNV in CNS, compared with serological testing, but is of greater value in the detection of other arboviruses, particularly viruses in the California serogroup. Medical chart reviews indicated that apparent CNS infection resolves in approximately 50% of cases.

Benign Angiopathy of the Central Nervous System

Apparent central nervous system vasculitis could have a benign course in a subset of patients and is referred to as benign angiopathy of the central nervous system (BACNS). This is mostly is seen in young women and presents with acute onset of neurologic symptoms, usually in the form of severe headache and/or a focal neurologic event. Cerebrospinal fluid analysis could be normal or nearly normal. Brain angiogram typically shows segmental narrowing, ectasia, or beading in multiple vascular territories on brain angiogram. Like in all cases of CNS vasculitis, exclusion of other systemic diseases or its mimickers associated with cerebral involvement is important.BACNS could respond favorably to treatment with corticosteroids alone or in combination with a calcium channel blocker, thereby avoiding unnecessary and prolonged treatment with other immunosuppressants like cyclophosphamide with their side effects. Little is published in the literature about BACNS, but is a rapidly emerging concept. It is thus important to recognize. We report a patient with classic presentation of BACNS to highlight the significance of distinguishing benign angiopathy from the more aggressive form of CNS vasculitis, because the treatment and response varies in these 2 entities.

Ocular and systemic side effects of brimonidine 0.2% eye drops (Alphagan®) in children

Brimonidine 0.2% (Alphagan) is a topical alpha-2 agonist widely used as an antihypertensive. There have been occasional reports of systemic adverse effects in children including apparent central nervous system depression. There are few data available on the overall safety of brimonidine 0.2% in children. Computerised pharmacy records were used to identify all children who had been prescribed brimonidine 0.2% in our eye department between August 1999 and June 2001, and their notes were reviewed. In all, 23 patients were identified from pharmacy records and 22 sets of notes were recovered and reviewed. The mean age at commencement of treatment was 8 years (range 0-14 years). In all, 10 (46%) were treated in one eye and 12 (54%) in both. Brimonidine 0.2% was taken for a mean 14 months (range 1 day-75 months). A total of 14 (64%) patients were already taking a topical beta-blocker when brimonidine 0.2% was commenced and a further four (18%) were being treated with another topical hypotensive agent. Of the 22 patients, six (27%) had to stop brimonidine 0.2% because of adverse side effects (two because of local irritation/allergy, two because of tiredness, and two because of fainting attacks). Many topical hypotensive agents are not licensed for use in children and few safety data are available. In this study, 18% of children had systemic adverse effects sufficient to necessitate stopping the drug. It is possible that educational impairment may have passed unnoticed in others. Larger studies are required to investigate this further.

Hypotension and bradycardia in infants after the use of topical brimonidine and beta-blockers

Brimonidine is a selective alpha-2 adrenergic agonist used to treat glaucoma. There have been several reports of central nervous system depression after its use in infants. 1 Berlin R.J. Lee U.T. Samples J.R. Rich L.F. Tang-Liu D.D. Sing K.A. et al. Ophthalmic drops causing coma in an infant. J Pediatr. 2001; 138: 441-443 Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar , 2 Carlsen J.O. Zabriskie N.A. Kwon Y.H. Barbe M.E. Scott W.E. Apparent central nervous system depression in infants after the use of topical brimonidine. Am J Ophthalmol. 1999; 128: 255-256 Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar , 3 Walters G. Taylor R.H. Severe systemic toxicity caused by brimonidine drops in an infant with presumed juvenile xanthogranuloma. Eye. 1999; 13: 797-798 Crossref PubMed Scopus (21) Google Scholar , 4 Korsch E. Grote A. Seybold M. Soditt V. Systemic adverse effects of topical treatment with brimonidine in an infant with secondary glaucoma. Eur J Pediatr. 1999; 158: 685 Crossref PubMed Google Scholar We observed rapid-onset bradycardia and decreased blood pressure in addition to central nervous system depression in 2 infants who received concomitant topical brimonidine and beta-blockers.

The role of the brain in metamorphosis of the olfactory epithelium in the frog, Xenopus laevis

Retrograde signaling from the brain to the olfactory sensory epithelium is important for neuronal survival, but the importance of the olfactory bulb in retrograde signaling during the naturally-induced, neuronal plasticity occurring during metamorphosis is unclear. The olfactory system of the African clawed frog ( Xenopus laevis) undergoes dramatic rearrangements during metamorphosis, making this an ideal system in which to examine interactions between the brain and the olfactory sensory epithelium. The main olfactory epithelium of larvae, located in the principal cavity (PC), changes at metamorphosis in function, receptor neuron morphology, biochemistry, and axon termination sites. A new, “middle”, cavity forms during metamorphosis that assumes all the characteristics of the larval PC. Using a combination of bulbectomy and olfactory transplantation, we investigated changes in expression of a marker protein (E7) and in apical ultrastructure in olfactory receptor neurons either (1) connected to the olfactory bulb, (2) connected to non-olfactory brain regions, or (3) with no apparent central nervous system (CNS) connections. We find that neurons in the middle cavity (MC) lacking connections with the CNS appear mature but neurons in the PC do not. Supporting cells in the PC undergo the changes normally observed during metamorphosis. Neurons connected to non-olfactory brain regions, either after bulbectomy or transplantation, appeared normal with regard to the changes normally expected after metamorphosis. These results suggest that influence from the brain is necessary for metamorphic changes in the X. laevis olfactory epithelium, but that these signals are not confined to the olfactory bulb; non-olfactory brain regions can also support these metamorphic changes.

Apparent central nervous system depression in infants after the use of topical brimonidine

PURPOSE: To report two cases in which topical brimonidine resulted in apparent central nervous system depression and unresponsiveness in an infant. METHODS: Review of two patients. An 11-day-old infant became lethargic and apneic after a single drop of brimonidine. These symptoms were reproduced after a second administration of brimonidine. A 5-month-old infant became lethargic and poorly responsive after receiving 1 drop of brimonidine in each eye. RESULTS: The first patient required admission to the hospital for medical stabilization. He recovered without sequelae. The second patient recovered spontaneously approximately 2.5 hours after administration of brimonidine. CONCLUSIONS: Topical brimonidine may be associated with central nervous system depression in infants. The use of brimonidine is not recommended in these patients until further data are available.

Improvement of P300 latency by treatment in non-insulin-dependent diabetes mellitus.

P300 event-related potentials were investigated in 24 cases of non-insulin-dependent (Type II) diabetes mellitus (NIDDM) without apparent central nervous system (CNS) symptoms and without cerebrovascular diseases on head magnetic resonance imaging, and in 16 age-matched healthy control subjects. N200 and P300 latencies were significantly prolonged and N200 and P300 amplitudes were significantly smaller in the NIDDM group than in the healthy control group. P300 latency was significantly shorter after the treatment than before. N200 and P300 waves have been recognized as useful indicators of cognitive function. The present study suggests that cognitive function is impaired in NIDDM patients and may improve with treatment of hyperglycemia.

Increased Human Immunodeficiency Virus (HIV) Type 1 DNA Content and Quinolinic Acid Concentration in Brain Tissues from Patients with HIV Encephalopathy

Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS.

Pancytopenia and vacuolation of marrow precursors associated with necrotizing encephalopathy

Subacute necrotizing encephalopathy (SNE) or Leigh disease is an autosomal recessive disorder associated with various defects of oxidative phosphorylation. Two reports have described the concurrence of SNE with pancytopenia and vacuolation of bone marrow precursors, and have raised the possibility that this symptom complex may be part of a spectrum of diseases which includes Pearson's syndrome (vacuolation of bone marrow precursors, sideroblastic anaemia, exocrine pancreatic dysfunction). We describe a case of Pearson's syndrome in which haematological manifestations antedated progressive neurological deterioration by several years. Cytogenetic studies showed an inverted duplication of chromosome 9 (qh) [inv dup (9) (qh)]. We suggest that cytopenia associated with vacuolation of bone marrow precursors even without clinically apparent central nervous system pathology should prompt consideration of SNE, or related diseases. Conversely, a diagnosis of SNE should prompt evaluation of other organ system functions including bone marrow. Cytogenetic evaluation of other patients with SNE may determine whether the 9 (qh) findings are pathogenetic.

Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass

The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL · kg −1 · min −1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity-duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation ( p < 10 −6), excessive blood loss in the ICU ( p < 10 −4), need for vasopressors before cardiopulmonary bypass ( p < 10 −4), postoperative myocardial infarction ( p < 10 −3), emergency reoperation ( p < 0.002), excessive postoperative transfusion ( p < 0.02), and chronic renal disease ( p < 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit ( p < 10 −6), intracardiac thrombus or valve calcification ( p < 0.02), and chronic renal disease ( p < 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations.

Effect of low‐dose butorphanol on halothane minimum alveolar concentration in ponies

Minimum alveolar concentration (MAC) for halothane was measured before and after administration of intravenous butorphanol (0.022 and 0.044 mg/kg in bodyweight in nine yearling Shetland ponies. Arterial blood pressure, heart rate, respiratory rate, expired CO2 and rectal temperature was also measured. Even though mean MAC values decreased 10 and 9 per cent after the low and high doses respectively, they were not statistically different from those measured prior to butorphanol. Halothane MAC values increased after butorphanol in two ponies, both animals increasing locomotor activity and demonstrating apparent central nervous system stimulation. No significant differences were seen in any variable measured after butorphanol administration.