A 2-year longitudinal evaluation of the impact of the COVID-19 pandemic on individuals with pre-existing anxiety disorders.

OBJECTIVES: To examine if the COVID-19 pandemic is associated with a differential effect over a 2-year time period in relation to its psychological and social impact on patients with established anxiety disorders. METHODS: Semi-structured interviews were conducted with 21 individuals attending the Galway-Roscommon Mental Health Services in Ireland with an ICD-10 diagnosis of an anxiety disorder. Interviews occurred at three time-points over a 2-year period to determine the impact of the COVID-19 pandemic and associated restrictions on anxiety and depressive symptoms, social and occupational functioning, and quality of life. RESULTS: No statistical difference in symptomatology was noted between the three time-points in relation to anxiety symptoms as measured utilising psychometric rating scales (Beck Anxiety Inventory (BAI), Hamilton Anxiety Rating Scale (HARS) or Likert Scale measures). The greatest impact of COVID-19 at all time-points related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted a tentative optimism for the future in the setting of vaccination and societal re-opening. Fear of re-emerging anxiety symptoms with the removal of societal restrictions was noted. CONCLUSIONS: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders, however variability was demonstrated, with some individuals describing ongoing anxiety, social isolation and concern for their future. A strong theme of hope for the future and less concern regarding the COVID-19 pandemic was evident; however tailored supports including the utilisation of tele-psychiatry is suggested, particularly for those experiencing increased anxiety with the removal of societal restrictions.

Dignity, coercion and involuntary psychiatric care: a study of involuntary and voluntary psychiatry inpatients in Dublin.

OBJECTIVES: There is a paucity of research about psychiatric inpatients' experience of dignity. Most of the limited literature on this topic is qualitative. Our study provides quantitative data about self-rated dignity among involuntary and voluntary psychiatry inpatients. We explore relationships between perceived dignity and legal status, coercion, level of insight, diagnosis, and therapeutic alliance, among other parameters. METHODS: We recruited 107 participants aged 18 years or over from two inpatient psychiatric units in Dublin, Ireland over a 30-month period. Interviews consisted of structured, validated assessment tools. Demographic and clinical data were obtained from patient charts. RESULTS: Patient Dignity Inventory (PDI) score was non-normally distributed (skewed to the right), with a median score of 63.0 out of 125 (inter-quartile range: 40.0-80.0). On multi-variable testing, lower self-rated dignity was associated with higher perceived coercion, better insight and more negative symptoms. There was no association between dignity and gender, employment status, marital status, ethnicity, age, admission status, diagnosis, working alliance, positive symptoms or cognition. CONCLUSIONS: Lack of dignity is linked with perceived coercion and negative symptoms, and is seen in patients with better insight. These links merit further study if we are to understand patient dignity in a more nuanced and useful way.KEYPOINTSWe interviewed psychiatric inpatients using the Patient Dignity Inventory and other structured assessment tools.There was no significant difference between voluntary and involuntary patient groups' self-rated dignity.Less self-rated dignity was seen in patients with higher levels of perceived coercion.Patients with better insight reported lower dignity.Dignity scores were not significantly associated with age, gender, ethnicity, diagnosis or length of stay in hospital.

A longitudinal evaluation of the impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders.

OBJECTIVES: To examine if the COVID-19 pandemic is associated with a differential effect over time in relation to its psychological and social impact on patients with established anxiety disorders. METHODS: Semi-structured interviews were conducted with 24 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases (ICD)-10 diagnosis of an anxiety disorder at two time points (six months apart) to determine the impact of the COVID-19 restrictions on anxiety and depressive symptoms, social and occupational functioning and quality of life. RESULTS: No statistical difference in symptomatology was noted between the two time points in relation to anxiety symptoms as measured by utilising psychometric rating scales (BAI and HARS) or utilising a Likert scale. The greatest impact of COVID-19 at both time points is related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted social isolation, concern for the participants' future and increased difficulty managing anxiety with ongoing restrictions. CONCLUSIONS: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders. Variability was, however, demonstrated between individuals, with some individuals describing ongoing anxiety, social isolation and concern for their future. Identifying those with ongoing symptoms or distress and providing multidisciplinary support to this cohort is suggested.

Impact of the COVID-19 pandemic on patients with pre-existing anxiety disorders attending secondary care.

OBJECTIVES: To examine the psychological and social impact of the COVID-19 pandemic on patients with established anxiety disorders during a period of stringent mandated social restrictions. METHODS: Semi-structured interviews were conducted with 30 individuals attending the Galway-Roscommon Mental Health Services with an International Classification of Diseases diagnosis of an anxiety disorder to determine the impact of the COVID-19 restrictions on anxiety and mood symptoms, social and occupational functioning and quality of life. RESULTS: Twelve (40.0%) participants described COVID-19 restrictions as having a deleterious impact on their anxiety symptoms. Likert scale measurements noted that the greatest impact of COVID-19 related to social functioning (mean = 4.5, SD = 2.9), with a modest deleterious effect on anxiety symptoms noted (mean = 3.8, SD = 2.9). Clinician rated data noted that 8 (26.7%) participants had disimproved and 14 (46.7%) participants had improved since their previous clinical review, prior to commencement of COVID-19 restrictions. Conditions associated with no 'trigger', such as generalised anxiety disorder, demonstrated a non-significant increase in anxiety symptoms compared to conditions with a 'trigger', such as obsessive compulsive disorder. Psychiatric or physical comorbidity did not substantially impact on symptomatology secondary to COVID-19 mandated restrictions. CONCLUSIONS: The psychological and social impact of COVID-19 restrictions on individuals with pre-existing anxiety disorders has been modest with only minimal increases in symptomatology or social impairment noted.

Precision Constraints for Three-Flavor Neutrino Oscillations from the Full MINOS+ and MINOS Dataset.

We report the final measurement of the neutrino oscillation parameters Δm_{32}^{2} and sin^{2}θ_{23} using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of 23.76×10^{20} protons on target producing ν_{µ} and ν[over ¯]_{µ} beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of ν_{µ} and the appearance of ν_{e} events between the Near and Far detectors yields |Δm_{32}^{2}|=2.40_{-0.09}^{+0.08}(2.45_{-0.08}^{+0.07})×10^{-3} eV^{2} and sin^{2}θ_{23}=0.43_{-0.04}^{+0.20}(0.42_{-0.03}^{+0.07}) at 68% C.L. for normal (inverted) hierarchy.

Neurocognitive disorder in hypertensive patients. Heart-Brain Study / Compromiso neurocognitivo en pacientes hipertensos. Estudio corazón-cerebro

The relation between hypertension and cognitive impairment is an undisputable fact. The aims of this study were to determine the prevalence of cognitive impairment in hypertensive patients, to identify the most affected cognitive domain, and to observe the association with different parameters of hypertension and other vascular risk factors. A multicentre study was carried out, and 1281 hypertensive patients of both genders and ≥21 years of age were included. Data on the following parameters were obtained: cognitive status (Minimal Cognitive Examination), behavioural status (Hospital Anxiety and Depression Scale), blood pressure, anthropometry, and biochemical profile. The average age was 60.2 ± 13.5 years (71% female), and the educational level was 9.9 ± 5.1 years. Global cognitive impairment was seen in 22.1%, executive dysfunction in 36.2%, and semantic memory impairment in 48.9%. Cognitive impairment was higher in males (36.8% vs. 30.06%) within both the 70-79-year-old and the ≥80-year-old (50% vs. 40%) age groups. Abnormal Clock Drawing Test results were related to high pulse pressure (p < 0.0036), and abnormal Mini-Boston Naming Test results to both high systolic blood pressure (p < 0.052) and pulse pressure (p < 0.001). The treated/uncontrolled hypertensive group showed abnormal results both in the Mini Mental State Examination (OR, 0.73; p = 0.036) and the Mini-Boston Naming Test (OR, 1.36; p = 0.021). Among patients without cognitive impairment (MMSE >24), 29.4% presented executive dysfunction, and 41.5% semantic memory impairment. Cognitive impairment was higher in hypertensive patients than in the general population. Executive functions and semantic memory were the most affected cognitive domains. High systolic blood pressure and pulse pressure were associated with abnormal results in cognitive tests

La relación entre la hipertensión y el deterioro cognitivo es un hecho indiscutible. Los objetivos de este estudio eran determinar la prevalencia de deterioro cognitivo en pacientes hipertensos, identificar el dominio cognitivo más afectado y observar la asociación con diferentes parámetros de hipertensión y otros factores de riesgo vascular. Estudio multicéntrico donde fueron incluidos 1.281 pacientes hipertensos de ambos sexos ≥ 21 años. Se evaluó el estado cognitivo (examen cognitivo mínimo), el estado conductual (escala hospitalaria de ansiedad y depresión) y se midió la presión arterial, la antropometría y el perfil bioquímico. La edad promedio fue de 60,2 ± 13,5 años (71% mujeres) y el nivel educativo de toda la muestra fue de 9,9±5,1 años de estudio. El deterioro cognitivo global fue del 22,1%, el compromiso de la función ejecutiva del 36,2% y de la memoria semántica del 48,9%. El deterioro cognitivo fue mayor en varones (36,8 vs. 30,06%), en los grupos de edad de 70 a 79 años y > 80 años (50 vs. 40%). El resultado anormal del test del reloj se relacionó con la elevación de la presión sistólica (p < 0,052) y la presión de pulso (p < 0,001). El grupo de hipertensos tratados/no controlados mostró resultados anormales tanto en el Mini Examen del Estado Mental (OR: 0,73; p = 0,036) como en el Test de Denominación Mini-Boston (OR: 1,36; p = 0,021). Entre los pacientes sin deterioro cognitivo (Mini Examen del Estado Mental > 24), 29,4% presentó disfunción ejecutiva y 41,5% de deterioro de la memoria semántica. En conclusión, el deterioro cognitivo fue mayor en los pacientes hipertensos que en la población general. La disfunción ejecutiva y la memoria semántica fueron los dominios cognitivos más afectados. La presión sistólica y la presión de pulso elevadas se asociaron con resultados anormales en pruebas cognitivas

Neurocognitive disorder in hypertensive patients. Heart-Brain Study.

The relation between hypertension and cognitive impairment is an undisputable fact. The aims of this study were to determine the prevalence of cognitive impairment in hypertensive patients, to identify the most affected cognitive domain, and to observe the association with different parameters of hypertension and other vascular risk factors. A multicentre study was carried out, and 1281 hypertensive patients of both genders and ≥21 years of age were included. Data on the following parameters were obtained: cognitive status (Minimal Cognitive Examination), behavioural status (Hospital Anxiety and Depression Scale), blood pressure, anthropometry, and biochemical profile. The average age was 60.2±13.5 years (71% female), and the educational level was 9.9±5.1 years. Global cognitive impairment was seen in 22.1%, executive dysfunction in 36.2%, and semantic memory impairment in 48.9%. Cognitive impairment was higher in males (36.8% vs. 30.06%) within both the 70-79-year-old and the ≥80-year-old (50% vs. 40%) age groups. Abnormal Clock Drawing Test results were related to high pulse pressure (p<0.0036), and abnormal Mini-Boston Naming Test results to both high systolic blood pressure (p<0.052) and pulse pressure (p<0.001). The treated/uncontrolled hypertensive group showed abnormal results both in the Mini Mental State Examination (OR, 0.73; p=0.036) and the Mini-Boston Naming Test (OR, 1.36; p=0.021). Among patients without cognitive impairment (MMSE >24), 29.4% presented executive dysfunction, and 41.5% semantic memory impairment. Cognitive impairment was higher in hypertensive patients than in the general population. Executive functions and semantic memory were the most affected cognitive domains. High systolic blood pressure and pulse pressure were associated with abnormal results in cognitive tests.

Intratumoral hemorrhage after remote subtotal microsurgical resection and gamma knife radiosurgery for vestibular schwannoma.

Our report describes the occurrence of intratumoral hemorrhage in a vestibular schwannoma, which was treated with microsurgical resection thirteen years and gamma knife surgery (GKS) more than two years prior to the event. Although rare, it is apparent that bleeding into a vestibular schwannoma remains a possibility, even after the tumor has responded favorably to GKS. Long-term followup of patients with vestibular schwannoma who have been treated with GKS is advisable to assess treatment response and to detect adverse events (e.g. hemorrhage) suspected on clinical grounds.

IgG4 as the predominant IgG subclass in pemphigoides gestationis.

BACKGROUND: Pemphigoides gestationis (PG) is a blistering disorder of pregnancy caused by antibodies against basement membrane proteins. They are directed against the 180 kD bullous pemphigoid antigen (BPAg2), towards the epitopes within the NC 16A domain. There are many similarities between pemphigoid gestationis and bullous pemphigoid (BP), but the literature so far indicated different immunofluorescence results in regards with C3 and IgG, and IgG subclasses (IgG4 vs. IgG1). METHODS: We evaluated staining patterns and IgG subclasses, as well as C5b-9 membrane attack complex (MAC) in 10 pregnant patients with PG, using sandwich double antibody immunofluorescence (SDAI) and direct immunofluorescence (DIF). RESULTS: All ten specimens stained with C3 by DIF, but only five had trace amount of IgG reactants by this method. By SDAI, 100% were positive for the IgG4 and C5b-9 MAC, 70% for IgG2, 50% for IgG1, and 40% for IgG3. CONCLUSION: IgG4 was the predominant IgG subtype identified. This finding has not been reported for PG, but it mimics results reported for BP. One explanation is prolonged disease course, as well as blocking of antigenic domains by IgG4. Understanding this completely will help develop therapies and prevention strategies for immunobullous and other autoimmune diseases, and perhaps aid in an exact classification.

Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

Syngeneic central nervous system transplantation of genetically transduced mature, adult astrocytes.

Advances in the development of highly infectious, replication-deficient recombinant retroviruses provide an efficient means of stable transfer of gene expression. Coupled with ex vivo transduction, surrogate cell populations can be readily implanted into the brain, thus serving as vehicles for delivering selected gene products into the central nervous system (CNS). Here we report that rat astrocytes can be routinely and safely isolated from brain tissue of a living donor by use of short-term gelatin sponge implants. The mature, nontransformed astrocytes were easily expanded, maintained in long-term tissue cultures and were efficiently transduced with an amphotropic retrovirus harboring a heterologous, fused transgene. In vitro retroviral infection rendered the nontransformed cells essentially 100% viable after exposure. The level of efficiency of infection (30-50% effective genome integration of provirus and expression of transgene in target cell populations) and minimal cell toxicity obviated the need to harvest large numbers of target cells. Cultured transduced astrocytes were resilient and exhibited select peptide expression for up to 1 year. Subsequently, transduced astrocytes were used in a series of experiments in which cells were transplanted intracerebrally in syngeneic animals. Post-implantation, astrocytes seeded locally and either insinuated into the surrounding parenchyma in situ or exhibited a variable degree of migration, depending on the anatomic source of astrocytes and the targeted brain implantation site. Transduced astrocytes remained viable in excess of 8 months post-transplantation and exhibited sustained transgenic peptide expression of green fluorescent protein/neomycin phosphotransferase in vivo. The sequential isolation and culture of nontransformed, mature, adult astrocytes and recombinant retrovirus-mediated transduction in vitro followed by brain reimplantation represents a safe and effective means for transferring genetic expression to the CNS. This study lays the foundation for exploring the utility of using a human autologous transplantation system as a potential gene delivery approach to treat neurological disorders. Prepared and utilized in this manner, autologous astrocytes may serve as a vehicle to deliver gene therapy to the CNS.

Linear IgA bullous dermatosis in one of two piroxicam-induced eruptions: a distinct direct immunofluorescence trend revealed by the literature.

BACKGROUND: The report focuses first on two patients with piroxicam-induced bullous eruption, one whose disease was diagnosed as linear IgA bullous dermatosis (LABD) and the other with no disease-specific immunologic findings using immunofluorescence methods. A review of the literature points to a distinctive direct immunofluorescence feature of drug-induced LABD cases. OBJECTIVE: Our purposes were to focus on divergent piroxicam reactions and to compare immunofluorescence findings in our and other reported drug-induced LABD cases to randomly occurring LABD cases. METHODS: Direct and indirect immunofluorescence methods were used to study biopsy and serum samples from both cases and biopsy specimens of 40 other LABD cases. RESULTS: Tense blisters developed in two patients medicated with piroxicam. Immunofluorescence studies demonstrated deposits of IgA at the basement membrane zone (BMZ) in case 1 and only non-disease-specific fibrin deposits at the BMZ in case 2. Within 1 month of discontinuation of piroxicam, all lesions were gone in both patients. CONCLUSION: In LABD cases proven by direct immunofluorescence, (1) the index of suspicion of drug induction should be higher in cases with only IgA and no IgG in the BMZ; (2) possibly up to two thirds of all LABD cases may be drug induced; and (3) the negative immunofluorescence findings in case 2 and other cases reported in the literature suggest that LABD is one of several host responses in drug-induced blistering diseases.

Simultaneous presence of mucous membrane pemphigoid and pemphigus vulgaris: molecular characterization of both autoantibodies.

There are several reports in the literature describing the coexistence of features of pemphigus vulgaris and pemphigoid in the same patient. We describe 15 patients with clinical, histological, and immunopathological features of mucous membrane (cicatricial) pemphigoid at the time of initial diagnosis. All 15 patients failed to respond clinically to conventional systemic agents over a mean period of 7.2 years. Hence, IVIg therapy was used. Prior to initiating IVIg therapy, features of mucous membrane pemphigoid and pemphigus vulgaris were demonstrated by various serological tests. Different assays were performed to identify molecular characteristics of these two autoantibodies. Twenty-five healthy normal individuals, 22 patients with mucous membrane pemphigoid, 17 patients with pemphigus vulgaris, and 12 patients with pemphigus foliaceus served as controls for comparison of serological studies. On indirect immunofluorescence, using monkey esophagous as substrate, sera of all 15 patients had demonstrable levels of anti-intercellular cement substance (ICS) or anti-keratinocyte cell surface antibody. Sera of 14 patients on salt split skin bound to the epidermal side of the split, which was consistent with mucous membrane pemphigoid. Sera of all 15 patients demonstrated binding to a 205-kDa protein (human B4 integrin) and a 130-kDa protein (desmoglein 3) on immunoblot. In a sample of sera from each of the 6 patients with mucous membrane pemphigoid and pemphigus vulgaris, the anti-ICS antibody was of the IgG4 subclass. The IgG4 subclass is a characteristic feature associated with pathogenic autoantibodies in pemphigus vulgaris. Hence, in such patients, a dual diagnosis should be considered and confirmed by various serological assays. It is possible that the presence of two pathogenic autoantibodies in these patients could have contributed to the lack of response to conventional immunosuppressive therapy.

2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) in a nude rat glioma model: implications for photodynamic therapy.

BACKGROUND AND OBJECTIVE: In this study, we evaluated 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor) as a photosensitizer for the treatment of malignant gliomas by photodynamic therapy (PDT). STUDY DESIGN/MATERIALS AND METHODS: We performed in vivo reflection spectroscopy in athymic rats to measure the attenuation of light in normal brain tissue. We also studied HPPH pharmacokinetics and PDT effects in nude rats with brain tumors derived from stereotactically implanted U87 human glioma cells. Rats implanted with tumors were sacrificed at designated time points to determine the pharmacokinetics of HPPH in serum, tumor, normal brain, and brain adjacent to tumor (BAT). HPPH concentrations in normal brain, BAT and tumor were determined using fluorescence spectroscopy. Twenty-four hours after intravenous injection of HPPH, we administered interstitial PDT treatment at a wavelength of 665 nm. Light was given in doses of 3.5, 7.5 or 15 J/cm at the tumor site and at a rate of 50 mW/cm. RESULTS: In vivo spectroscopy of normal brain tissue showed that the attenuation depth of 665 nm light is approximately 30% greater than that of 630 nm light used to activate Photofrin, which is currently being evaluated for PDT as an adjuvant to surgery for malignant gliomas. The t1/2 of disappearance of drug from serum and tumor was 25 and 30 hours, respectively. CONCLUSION: Twenty-four hours after injection of 0.5 mg/kg HPPH, tumor-to-brain drug ratios ranged from 5:1 to 15:1. Enhanced survival was observed in each of the HPPH/PDT-treated animal groups. These data suggest that HPPH may be a useful adjuvant for the treatment of malignant gliomas.

The impact of age and sex on the incidence of glial tumors in New York state from 1976 to 1995.

OBJECT: In this study the authors describe secular trends in the incidence of three glial tumors--glioblastoma multiforme (GBM), astrocytoma not otherwise specified (ANOS), and anaplastic astrocytoma (AA)--in New York state from 1976 through 1995. They also describe the effect of age and sex on the relative risk (RR) for these tumors, specifically GBM. METHODS: Crude, age-, and sex-specific incidence rates were calculated for each tumor type from 1976 to 1995 by using data from the New York State Cancer Registry. Age-adjusted incidence rates were calculated by the direct standardization procedure, in which the 1970 United States Census Population Standard Million is used. The RR of GBM for the female population was calculated and plotted. Statistical comparisons were made using Pearson's correlation coefficient and regression analysis with the coefficient of variation. CONCLUSIONS: The age-adjusted incidence of these three glial tumors increased during the study period. Increases in age-specific incidence of GBM were primarily limited to patients 60 years of age or older. The reasons for these increases cannot be fully explained with the data. Those in the female population had a lower risk of developing these tumors than those in the male. For GBM, the protective effect of sex was first evident at the approximate age of menarche, was greatest at the approximate age of menopause, and decreased in postmenopausal age strata. The overall protective effect of female sex and the described trend in RR for GBM in the female population suggests that sex hormones and/or genetic differences between males and females may play a role in the pathogenesis of this tumor.

A case of dermatitis herpetiformis with IgA endomysial antibodies but negative direct immunofluorescent findings.

A patient with clinical findings of dermatitis herpetiformis (DH), negative direct immunofluorescent (DIF) findings for junctional IgA deposits in 2 biopsy specimens, and positive for IgA endomysial (AEmA) and tissue transglutaminase (tTG) antibodies responded initially to dapsone. After dapsone had to be discontinued because of side effects, a gluten-free diet and supportive therapy controlled the disease; the AEmA and tTG antibodies became negative. Our data on 10 consecutive DH cases examined by DIF and by serum studies for AEmA and antibodies to tTG, point to frequencies of 90% DIF positive and 70% AEmA and tTG positive cases. The use of both DIF and serum tests for AEmA and tTG reveals DH cases not detected by DIF alone that respond to gluten-free diet. Findings on autoantibodies to tTG, an enzyme that metabolizes gliadin, points to a role of tTG in the immunopathology of gluten-sensitive enteropathy and helps to explain the need for a gluten-free diet in the management of DH cases.

Stereotactic neurosurgical biopsy is an underutilized modality.

The objective of this study was to ascertain if stereotactic neurosurgical biopsy (SNB) optimizes the therapy of undefined CNS masses. The design was of retrospective treatment and outcome analysis and the setting was a large general hospital. We studied a total of 141 patients with undefined, space-occupying CNS lesions detected between 1991-1997, with whom we used SNB to define the lesions. We sought to correlate empiric and histological diagnostics and their impact on medical management. The stereotactic biopsy produced a diagnostic yield for each patient. Management was altered in 57 cases (40%) due to histology and, of these, malignancy was found in 39. Morbidity was ten asymptomatic hemorrhages on post-biopsy CT scans and two cases of clinical deterioration. Our conclusions were that SNB produces high yield with low morbidity. In the community setting, a wide variety of diagnoses can be made with improvements in medical management. SNB should be employed to guide therapy of CNS lesions where complete excision is not possible or when diagnostic questions arise.

Hormonal effects on glioblastoma multiforme in the nude rat model.

OBJECT: The authors studied the effect of gender and hormonal status on survival in nude rats implanted with human glioblastoma multiforme (GBM) cell lines. METHODS: Nude rats received intracerebral implants of either wild-type U87MG cells or U87MG cells transfected with the gene for endothelin-1 (U87/ET-1). In the initial study, survival was compared in males and females for each of the two cell lines. The six second-phase study groups were composed of: 1) males; 2) females; 3) ovariectomized females; 4) sham ovariectomized females; 5) ovariectomized rats given 10 microg/day estradiol benzoate for 21 days; and 6) ovariectomized rats given 20 mg/kg/day progesterone for 21 days. All rats in the second phase were implanted with U87/ET-1 cells. Animals were killed when they exhibited initial signs of neurological deterioration. Female nude rats survived longer than male rats implanted with either U87 or U87/ET-1 cells. In the second phase, ovariectomized, male, and progesterone-treated rats died at approximately 19 days, whereas the female, sham-treated, and estrogen-treated animals died 23 to 25 days after tumor cell implantation. CONCLUSIONS: The authors demonstrate that female nude rats implanted with human GBM cells have a survival advantage over male rats and that estrogen provides the advantage.

Intratumoral infusion of topotecan prolongs survival in the nude rat intracranial U87 human glioma model.

Topotecan is a topoisomerase (topo) I inhibitor with promising activity in preclinical studies. We hypothesized that low-dose intratumoral delivery of topotecan would be highly effective for gliomas. Human glioma cell lines (U87, U138 and U373) displayed different sensitivities to topotecan (IC50 range: 0.037 microM to 0.280 microM) in cell culture. The most resistant of the glioma cell lines (U87) was implanted stereotactically into the brains of nude rats. Twelve days later, at which time tumor diameter measured 2 to 2.5 mm, animals were randomized to three groups: group I, intratumoral topotecan infused via osmotic pump (n = 12); group II, intratumoral saline infusion (n = 7); and group III, no treatment (n = 10). Animals were sacrificed when signs of deterioration developed, or at 60 days. Animals in group I had a mean survival time (MST) of > 55 days (range = 40-60); whereas, those in groups II and III had MST of 26.1 (range = 21-31) and 26.5 (range = 20-30) days, respectively. The differences in survival between group I and each of the other groups were statistically significant (p < 0.0001; Logrank Mantel-Cox). None of the animals that survived 60 days had histological evidence of residual tumor at sacrifice. Measurement of topotecan levels in normal brain revealed cytotoxic concentrations up to 4.5 mm from the site of infusion. This study demonstrates that intratumoral topotecan delivered via an osmotic pump prolongs survival in the U87 human glioma model.