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Biomedical subjects

J B Posner

Publications and source records attributed to J B Posner.

At least 145 records · Page 8Linked to original sources
PubMed1987

Back pain and epidural spinal cord compression.

Back pain, one of man's most common afflictions, can be caused by a wide variety of disorders ranging from exercise-induced lumbar strain to spinal cord compression by metastatic tumor. A rational approach to the diagnosis and management of the patient with back pain allows the physician to treat self-limited disorders without excessive workup while identifying those patients with malignant disease sufficiently early to prevent permanent neurological damage.

Adrenal Cortex Hormones↗
PubMed1987

Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration.

Autoantibodies directed against neuronal proteins have been identified in some patients with paraneoplastic cerebellar degeneration. To identify the molecular targets for these autoantibodies, we constructed a lambda gt11 cDNA expression library from human cerebellum and screened the library with IgG from a patient with paraneoplastic cerebellar degeneration. A single clone, pCDR2, produced a fusion protein that reacted strongly with the patient's IgG. The isolated pCDR2 clone was used to identify six overlapping cDNA clones. Sequencing of the pCDR clones revealed a distinctive pattern consisting of a unit of 18 nucleotides (6 amino acids) repeated in tandem along the entire cDNA sequence. This sequence is unlike any previously described eukaryotic gene. Southern blot analysis was consistent with single-copy representation of the CDR (cerebellar degeneration-related) gene in the human and mouse genome. RNA blotting studies with normal tissues showed expression of the CDR gene to be largely restricted to brain. Expression of the CDR message was also noted in cell lines derived from cancers of neuroectodermal, kidney, and lung origin.

Adenocarcinoma↗
PubMed1987

Detection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid.

To evaluate the diagnostic utility of flow cytometry (FCM) as compared to cytology, DNA and RNA content of cells were measured in 233 samples of cerebrospinal fluid (CSF) from 147 patients with solid tumors or lymphomas and 17 controls with nonmalignant disorders. All control specimens were normal. Twenty-eight samples were abnormal: 20 showed an aneuploid peak and 8 an increased number of cells with DNA content in the S and G2M phases of the cell cycle. Of these 28, cytologic results were positive in 18, suspicious in 3, and negative in 7. All but one of the suspicious and negative cases had confirmatory laboratory and/or radiographic evidence of leptomeningeal metastasis within one week of FCM examination. Cytologic results were positive in eight samples negative by FCM. Compared with cytology, the sensitivity of FCM was 69% and the specificity 95%. Abnormal DNA content by FCM can be a useful adjunct to cytologic examination.

Adolescent↗
PubMed1987

Primary CNS lymphoma: managing patients with spontaneous and AIDS-related disease.

Primary central nervous system lymphoma, especially that associated with AIDS, is increasing in frequency. CT scan is virtually diagnostic when it shows multiple, hyperdense, diffusely enhancing periventricular lesions. Treatment often results in a complete remission, but the overall prognosis is poor. Surgery is important diagnostically, but resection is not helpful. Corticosteroids can produce significant shrinkage, and even disappearance, of PCNSL, but cranial radiation is still the cornerstone of therapy. The addition of chemotherapy to RT is promising in non-AIDS patients but still investigational.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Autoimmune pathogenesis of paraneoplastic neurological syndromes.

"Remote effects" of cancer on the nervous system (paraneoplastic syndromes) are disorders of the nervous system of unknown cause that occur almost exclusively, or with greatly increased frequency, in patients with identifiable or occult cancer. There are several hypotheses concerning the pathogenesis of these rare disorders. One hypothesis is that the underlying tumor and portions of the nervous system share antigens and that an autoimmune response generated against the tumor causes the nervous system disorder. Evidence supporting this hypothesis includes the ability to transmit the Lambert-Eaton Syndrome (a paraneoplastic syndrome involving the neuromuscular junction) to experimental animals by infusing IgG from patients with the disorder, the presence of autoantibodies against Purkinje cell neurons in some patients with paraneoplastic cerebellar degeneration, and the presence of autoantibodies against many neurons in patients with sensory neuronopathy and encephalomyelitis. Other evidence supporting the hypothesis is presented in this review.

Antibodies, Monoclonal↗
PubMed1986

Hydrocephalic dementia and spinal cord tumor. Report of a case and review of the literature.

A 68-year-old woman presented with an 18-month history of low back pain followed by leg weakness, dementia, and incontinence. Myelography revealed an intradural, extramedullary block from L-2 to L-4, and cranial computed tomography demonstrated ventriculomegaly. Excision of a benign schwannoma resulted in rapid relief of back pain and more gradual normalization of mental function and hydrocephalus. Five similar cases of dementia and hydrocephalus complicating spinal cord tumor have been reported. A variety of mechanisms have been proposed to explain the association but the pathophysiology is still unclear. Spinal tumor should be considered in the differential diagnosis of dementia and of communicating hydrocephalus.

Aged↗
PubMed1986

Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: the effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow.

Using quantitative autoradiography, we investigated the effect of intracarotid infusions of hyperosmolar mannitol solutions on capillary permeability and blood flow. Capillary permeability, expressed in terms of a blood-to-tissue transfer constant (K), was determined in two rat brain tumor models by measuring the entry of 14C-alpha aminoisobutyric acid into brain tumor, into brain tissue adjacent to tumor, and into cortex. Cerebral blood flow was determined by measuring the uptake of 14C-iodoantipyrine in one rat brain tumor model. Blood flow was examined in the same regions as K, as well as in the corpus callosum. Before mannitol administration, K values in both Walker 256 (W256) carcinosarcoma and C6 gliomas were much higher than those in cortex. C6 gliomas were about three times more permeable than were W256 tumors. There was a direct correlation between tumor size and increased capillary permeability. Mannitol at a concentration of 1.37 M did not increase the K values for either tumor or adjacent tissue. At 1.6 M, mannitol increased the K values for both tumors (1.7-fold in C6 glioma and 13-fold in W256) as well as for adjacent tissue. At both concentrations, mannitol markedly increased cortical K values in all groups: by 48- to 72-fold at 1.37 M and by 90- to 105-fold at 1.6 M. The net effect of the mannitol was to reverse the tumor-to-cortex permeability relationship. Cortical blood flow increased modestly after intracarotid mannitol administration on both sides of the brain. These data provide little justification for using intracarotid mannitol during chemotherapy of human brain tumors.

Animals↗
PubMed1986

Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor.

An autoantibody highly restricted to the nuclei of neurons was found in four patients with subacute sensory neuronopathy and small cell carcinoma of the lung. The antibody was not found in normal subjects or patients with or without cancer who did not have subacute sensory neuronopathy. One- and two-dimensional immunoblotting analysis of nuclear extracts of rat and human brain identified an antibody reactive with a 35-38 kilodalton (kd) basic nucleoprotein. An identical protein lacking the 38 kd peptide was identified in tumor extract of one of the patients. All four patients' serum reacted with the same antigen in the brain and the tumor. In the postmortem study of one of the patients, IgG was found within the neurons of the dorsal root ganglia by direct immunofluorescence. These findings support the hypothesis that the subacute sensory neuronopathy is caused by an antibody that cross-reacts with a tumor cell antigen and a brain nucleoprotein.

Aged↗
PubMed1986

Single brain metastases: surgery plus radiation or radiation alone.

We reviewed the records of patients treated for single brain metastases from non-small-cell lung cancer for 1978 through 1982. Forty-three patients received surgical treatment, including 37 who had surgery plus postoperative whole-brain radiation therapy and 6 patients who had surgery after failing to respond to radiation therapy. The surgically treated patients were matched with 43 patients treated with radiation therapy alone. The combined therapy group had significantly longer survivals than those treated with radiation therapy alone (19 months versus 9 months). The rates of local recurrence and neurologically related deaths were significantly higher in the radiation therapy-alone group. Patients treated with combined therapy survived longer, and the increased survival was due to lower recurrence of brain metastases after surgery and fewer neurologically related deaths.

Adenocarcinoma↗
PubMed1986

Neurologic complications of carcinoid.

We reviewed the records of all patients treated for carcinoid tumors at Memorial Sloan-Kettering Cancer Center from 1974 through 1984. Of 219 patients, 90 developed metastatic complications, and of these, 36 developed neurologic complications. Metastases, the most common neurologic complication, included epidural spinal cord compression (14 patients), intracranial metastases (13 patients), leptomeningeal metastases (1 patient), and peripheral nerve lesions (5 patients). Nonmetastatic complications were hepatic encephalopathy (six patients), herpes zoster infection (two patients), cerebral infarction due to septic emboli (one patient), superior sagittal sinus thrombosis (one patient), and carcinoid myopathy (one patient). The carcinoid syndrome was seen in eight patients (4%). Response of neurologic metastases to conventional radiation therapy was usually favorable. We conclude that (1) the frequency and type of neurologic complications associated with carcinoid tumors are similar to those seen with other systemic cancers; (2) CNS metastases are relatively common in patients with metastatic carcinoid (29%); and (3) the carcinoid syndrome is less common than CNS metastasis.

Adolescent↗
PubMed1986

Partial characterization of the Purkinje cell antigens in paraneoplastic cerebellar degeneration.

Serum from seven patients with paraneoplastic cerebellar degeneration contained anti-Purkinje cell antibodies. The samples were examined by immunoblotting to determine whether they recognized common antigens in isolated human Purkinje cell neurons. Two groups of antigens were detected by all seven sera with Mr 62/64 kd and 34 to 38 kd, both of which contributed to the Purkinje cell antigens detected immunohistochemically. These reactivities were absent from all controls tested. These antibodies may play a role in the pathogenesis of paraneoplastic cerebellar degeneration.

Antibodies↗
PubMed1985

Evolution of computed tomographic abnormalities in leptomeningeal metastases.

We obtained serial cranial computed tomographic (CT) scans from 25 patients with documented leptomeningeal metastases in order to correlate the course of clinical symptoms and cerebrospinal fluid abnormalities with the evolution of CT abnormalities. In almost one-third of patients, relatively specific CT findings such as enhancement of the meninges, obliteration of cisterns or sulci, and hydrocephalus with transependymal edema preceded clinical symptoms. By the time patients became symptomatic, 10 of 25 (40%) had specific abnormalities, and 4 more became specifically abnormal with time. The first scan after cerebrospinal fluid tumor cells were discovered showed specific abnormalities in only 6 patients, but 7 more became specifically abnormal with time. Ventriculomegaly occurred in 18 of 25 patients (72%) and was associated with sulcal and/or cisternal obliteration in one-half of the patients. In 4 patients sulcal and cisternal obliteration developed prior to ventricular enlargement. Multiple small, enhancing cortical nodules were detected prior to symptom onset and discovery of leptomeningeal tumor in 5 patients.

Arachnoid↗
PubMed1985

Autoimmune response of patients with paraneoplastic cerebellar degeneration to a Purkinje cell cytoplasmic protein antigen.

Sera from 6 of 12 patients with paraneoplastic cerebellar degeneration (PCD) contained anti-Purkinje cell antibodies, as determined by indirect immunofluorescence on frozen sections of normal human cerebellum. Samples of cerebrospinal fluid from 2 of the patients with serum antibodies were tested, and both specimens contained anti-Purkinje cell antibody. The anti-Purkinje cell antibodies were polyclonal, fixed complement, and were present in all patients at serum dilutions of 1:1,000 or greater. Antibody activity could not be suppressed by preabsorption of sera with human or animal brain and tissue powders or with fresh crude human cerebellar extracts. No anti-Purkinje cell antibodies were detected in control sera from 167 neurologically normal cancer patients, 32 normal volunteers, 10 patients with other causes of cerebellar degeneration, or 8 patients with other paraneoplastic neurological diseases. Preliminary evidence suggests that the Purkinje antigen is a protein that is often concentrated in the periphery of the cytoplasm in disc-shaped structures. Patients with antibodies often developed signs of PCD near the time of detection of the tumor and had relentless progression of neurological disease. Patients without antibodies frequently had cancer for months to years before PCD developed, and often had spontaneous stabilization of neurological disease with time. Four patients without and 3 patients with antibodies underwent plasmapheresis without response.

Aged↗
PubMed1985

Positron emission tomographic measurement of blood-to-brain and blood-to-tumor transport of 82Rb: the effect of dexamethasone and whole-brain radiation therapy.

Unidirectional blood-to-brain and blood-to-tumor transport rate constants for rubidium 82 were determined using dynamic positron emission tomography in patients with primary or metastatic brain tumors. Regional influx rate constants (K1) and plasma water volume (Vp) were estimated from the time course of blood and brain radioactivity following a bolus injection of tracer. Eight patients were studied before and 24 to 72 hours after treatment using pharmacological doses of dexamethasone, and 6 additional patients with metastatic brain tumors were studied before and within 60 to 90 minutes after 200- to 600-rad whole-brain radiation therapy. Steroid treatment was associated with a 9 to 48% decrease in tumor K1 and a 21% mean decrease in tumor Vp. No consistent changes in K1 or Vp were observed in control brain regions. Tumor K1 and Vp did not increase in patients undergoing whole-brain radiation therapy, all of whom were taking dexamethasone at the time of study. These data suggest that corticosteroids decrease the permeability of tumor capillaries to small hydrophilic molecules (including those of some chemotherapeutic agents) and that steroid pretreatment prevents acute, and potentially dangerous, increases in tumor capillary permeability following cranial irradiation.

Adult↗
PubMed1985

Cerebrovascular complications in patients with cancer.

In an autopsy study of patients with cancer, 14.6% had pathologic evidence of cerebrovascular disease (CVD), and in 7.4% clinical symptoms of CVD had been present in life. The usual risk factors for CVD were overshadowed by pathophysiologic abnormalities related to the neoplasm, including direct effects of the tumor, coagulation disorders, infections and diagnostic or therapeutic procedures. In patients with leukemia, hemorrhages (72.4%) were much more common than ischemic infarcts. In lymphoma patients, the incidence of cerebral bleeding was lower (36.3%). In both groups, the leading causes of ischemic infarction were septic thrombi and intravascular coagulation. In patients with carcinoma, cerebral infarctions (54.1%) were more frequent than hemorrhages. NBTE (18.5%) and intravascular coagulation (9.6%) were the most common etiologies. Hemorrhages other than intratumoral bleeding in patients with melanoma or germ cell tumors were unusual. The clinical presentation of CVD in patients with cancer is more often a diffuse encephalopathy, with or without localizing signs, than the typical acute onset of a focal deficit. This was particularly true with intravascular coagulation, septic infarction and subdural hematoma. Our study suggests that by knowing the clinical setting, neurologic features and laboratory findings, one can, in many instances, make an accurate clinical diagnosis that, in some cases, leads to effective treatment.

Arteriosclerosis↗
PubMed1985

Neuronal antinuclear antibody in sensory neuronopathy from lung cancer.

We found an antinuclear antibody highly restricted to nuclei of neurons in two patients with subacute sensory neuronopathy complicating oat cell carcinoma of the lung. Serum was tested by indirect immunofluorescence and immunoperoxidase staining. At low concentrations of antibody, only the nuclei of the neurons were stained. At high concentrations, there was also staining of the nuclei of glial cells and fetal nonneural tissues. The cytoplasm of most neurons was stained with the immunoperoxidase method.

Antibodies, Antinuclear↗
PubMed1985

Neurologic complications of systemic cancer.

Patients with cancer commonly suffer neurologic disabilities. These neurologic disorders can be either metastatic to the brain, spinal cord, leptomeninges, or peripheral nerves or nonmetastatic including infections, vascular problems, metabolic abnormalities, side effects of therapy, or paraneoplastic syndromes. Careful diagnostic evaluation of patients with cancer and neurologic symptoms often indicates effective therapy.

Arachnoid↗