Bilateral idiopathic inflammation of the optic nerve sheaths. Light and electron microscopic findings

Idiopathic perioptic neuritis is a term used to describe noninfectious inflammatory disorders of the optic nerve sheaths, the causes of which are unknown. In the following report, a 68-year-old woman with bilateral visual loss was found to have chronic inflammation with necrobiotic granulomas of her optic nerve sheaths. The patient, who had no systemic condition known to be associated with necrobiotic granuloma, lost vision from infarction of the optic nerve parenchyma and from compression due to thickened meninges. Although there are similarities between the inflammatory reaction in this case to the necrobiotic dermatoses, the pathogenesis of this condition remains obscure.     

Intrathecal synthesis of IgG subclasses in multiple sclerosis and in acquired immunodeficiency syndrome (AIDS)

Serum and cerebrospinal fluid (CSF) of 50 neurological patients (24 multiple sclerosis (MS), ten acquired immunodeficiency syndrome (AIDS) and 16 other neurological diseases (OND)) and ten controls were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgG subclass quantification and for the calculation of intrathecal synthesis (ITS). Total IgG was determined by two methods: electroimmunodiffusion (EID) and ELISA. A highly significant correlation was established between both methods. The existence of ITS was proved by the IgG/albumin ratio, the IgG index, Tourtellotte's formula, and Schuller's formula. In AIDS patients all IgG subclasses showed an increase in the CSF, whereas in sera only the IgG1 was significantly increased. CSF of MS patients showed a predominant increase of IgG1 whereas no significant modification of IgG subclasses was observed in sera. In most of the AIDS patients there was an ITS of IgG1, IgG3 and IgG4, but rarely (3/10) IgG2. In contrast, a polyclonal ITS of IgG was exceptional (1/24) in MS patients. No significant correlation could be established between clinical data and IgG subclass ITS in MS. The variations of each IgG subclass in serum and in ITS were not significantly correlated. Measurement of each IgG subclass and calculation of ITS seems essential in order to analyze any subclass antibody repertory inside the central nervous system.     

Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation

Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence.     

Anti-idiotypes in B-cell tumor therapy

Thirteen patients with B-cell lymphomas were treated with mouse monoclonal anti-idiotype antibodies. All but 1 of the patients in this study had received extensive prior treatment with conventional therapy for lymphoma. The treatment protocol initially included an escalating dose schedule which was intended to help us evaluate toxicity and pharmacokinetics and, eventually, to achieve appreciable levels of free mouse antibody in the circulation. The last 4 patients received substantial initial doses. Tumor sampling was performed before and during therapy for evaluation of tissue penetration by antibody. Patients received antibodies of gamma 1, 2a, or 2b isotype. None of the patients had serum paraproteins by routine clinical testing, but 6 had an idiotype protein detectable by a sensitive immunoassay at levels greater than 1 microgram/ml, two of which were greater than 200 micrograms/ml. These levels were temporarily reduced by plasma-pheresis. However, the presence of serum idiotype increased the requirement for mouse antibody to achieve tumor penetration. Another obstacle to treatment was immune response to mouse Ig that occurred in 5 of the 13 patients. Once an immune response had begun, further infusions of antibody failed to reach the tumor or induce tumor regression and were associated with toxicity. Our initial patient remains in an unmaintained complete remission 50 months after receiving antibody. Six of 12 additional patients have had objective remissions which also were clinically significant. However, these remissions were not complete. This therapy shows promise as an alternative modality for the treatment of B-cell lymphoma. We will need further studies to determine the mechanisms of the antitumor effect and to improve the clinical results.     

Natural evolution of moderate sleep apnoea syndrome: significant progression over a mean of 17 months

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. It has remained unclear whether or not it is progressive. The evolution of OSA was examined in a retrospective case note study of 55 unselected patients of mean (SD) age 55.8 (10) years with mild to moderate disease untreated by interventional methods such as continuous positive airway pressure (CPAP) or surgery. Correlations between clinical and functional variables, upper airway anatomy, and change in disease severity were also investigated. METHODS: Patients underwent full polysomnography on two occasions (T0 and Tx) at a mean interval of 77 (50) weeks (range 17-229). In addition, upper airway imaging with computed tomographic scanning or cephalometry had been performed in 43 patients at T0. Morbidity before, during, and after the study period was assessed by questionnaire, as was smoking history and alcohol and sedative intake. RESULTS: The apnoea hypopnoea index (AHI) for the group as a whole increased from 21.8 (11.5) to 33.4 (21.3) (p = 0.0001). Using a 25% change in AHI to divide patients into worsened, stable, and improved groups showed that, although most of the patients deteriorated, 25 patients improved or remained stable. The change in AHI was not correlated with body mass index which remained stable at 29.7 (5.4) kg/m2 versus 29.7 (5.6) kg/m2. There was a trend for apnoea duration to increase. No patient reported increased alcohol consumption and only one patient reported increased use of sedatives between T0 and Tx. No correlation was found between change in AHI and age, time between recordings, anatomical measurements of the upper airway, respiratory function, oximetry, or arterial blood gas tensions. Total cardiovascular and cerebrovascular morbidity was high: hypertension (26 patients, 46%), cardiac arrhythmia (17 patients, 33%), angina (12 patients, 23%), myocardial infarction (10 patients, 19%), and stroke (10 patients, 19%). Twenty nine patients (52%) were prescribed CPAP after Tx, two of whom went on to have maxillofacial surgery. These 29 treated patients had significantly higher values of AHI at T0 and Tx and greater change in AHI than the untreated patients. CONCLUSIONS: This study shows that mild to moderate OSA has a tendency to worsen in the absence of significant weight gain and that upper airway anatomy and clinical variables do not appear to be useful in predicting progression. It follows that mild to moderate OSA justifies systematic follow up. Deterioration in AHI over a mean of 17 months led to interventional treatment in over 50% of patients in the study.


     

Carcinoma of the lip: observations on its frequency in females

Seventy-three patients with lip carcinoma were treated from 1970 to 1988 in the Otolaryngology Department of the Beilinson Medical Center. The most common histological type was squamous cell carcinoma which occurred in 68 patients; four tumours were basal cell carcinoma and one acinic cell carcinoma. Carcinoma of the lip is more frequent in males. Nevertheless, the frequency of carcinoma in females in our series was substantially higher than the average reported in the literature. Forty-nine patients were treated surgically and 24 patients were treated by irradiation. Analysis of the results among those treated by surgery and those treated by irradiation shows a difference in tumour local control which was statistically significant (p = 0.025). Surgical treatment is recommended because of the advantage of tumour margin assessment, avoidance of radiotherapy complications and rapid rehabilitation. Two rare cases of carcinoma of the lip in young patients (age under 20 years) are presented.     

Apathy and the basal ganglia

Journal of Neurology - We should like to emphasize the following points: 1. Apathy is defined here as a quantified and observable behavioral syndrome consisting in a quantitative reduction of...     

Kinetics of drug action in disease states. XXIX. Effect of experimental nephrotic syndrome on the pharmacodynamics of heptabarbital: implications of severe hypoalbuminemia

The purpose of this investigation was to determine the effect of nephrotic syndrome (NS) on the pharmacodynamics of a barbiturate. NS was induced in male rats by puromycin aminonucleoside; it caused hypoproteinemia, increased liver and kidney weight and elevated serum creatinine and urea nitrogen concentrations. Serum albumin concentration decreased from 3.5% in controls to 0.90% in NS animals. The rats were infused i.v. with heptabarbital, 1 mg/min, until they lost their righting reflex. The total dose (mean +/- S.D.) required by rats with NS, 40.2 +/- 4.2 mg/kg, was substantially lower than that required by normal animals (68.6 +/- 6.2 mg/kg, P less than .001). Serum protein binding of heptabarbital was reduced from 49% in controls to 26% in NS rats. However, the drug concentration in cerebrospinal fluid (CSF) at the pharmacologic endpoint was not significantly different in controls and NS rats (18.9 +/- 1.5 vs. 18.3 +/- 1.4 mg/l). Serum, CSF and the brain contained appreciable concentrations of a metabolite of heptabarbital. To determine if the metabolite contributes to the pharmacologic effect of the parent drug, rats received an i.v. injection of 46, 60 or 100 mg/kg of heptabarbital. Concentrations of heptabarbital in CSF at return of righting reflex (which occurred after 15, 25 and 50 min, respectively) were independent of dose whereas metabolite concentrations increased with increasing dose. Thus, the metabolite of heptabarbital in male rats is pharmacologically inactive.(ABSTRACT TRUNCATED AT 250 WORDS)