Phytotoxicity induced in isolated zooxanthellae by herbicides extracted from Great Barrier Reef flood waters.

To date there has been limited evidence anthropogenically sourced pollution from catchments reaching corals of the Great Barrier Reef (GBR). In this study, freshly isolated zooxanthellae were exposed to polar chemicals (chiefly herbicides) extracted from water samples collected in a flood plume in the GBR lagoon. Photosynthetic potential of the isolated zooxanthellae declined after exposure to concentrated extracts (10 times) from all but one of the sampling sites. Photosynthetic potential demonstrated a significant positive relationship with the concentration of diuron in the concentrated extracts and a significant inverse relationship with salinity measured at the sampling site. This study demonstrates that runoff from land based application of herbicides may reduce photosynthetic efficiency in corals of inshore reefs in the GBR. The ecological impacts of the chemicals in combination with other potential stressors on corals remain unclear.

Increased functional cell surface expression of CFTR and DeltaF508-CFTR by the anthracycline doxorubicin.

Cystic fibrosis (CF) is a disease that is caused by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, DeltaF508, accounts for 70% of all CF alleles and results in a protein that is defective in folding and trafficking to the cell surface. However, DeltaF508-CFTR is functional when properly localized. We report that a single, noncytotoxic dose of the anthracycline doxorubicin (Dox, 0.25 microM) significantly increased total cellular CFTR protein expression, cell surface CFTR protein expression, and CFTR-associated chloride secretion in cultured T84 epithelial cells. Dox treatment also increased DeltaF508-CFTR cell surface expression and DeltaF508-CFTR-associated chloride secretion in stably transfected Madin-Darby canine kidney cells. These results suggest that anthracycline analogs may be useful for the clinical treatment of CF.

Functional enhancement of CFTR expression by mitomycin C.

Cystic fibrosis is caused by mutations in the CFTR gene. The most common of these mutations, DeltaF508, results in a protein that is not trafficked to the apical plasma membrane but instead is retained and degraded in the endoplasmic reticulum (ER) by the 26S proteosome. However, this protein is functional upon plasma membrane expression. It has been theoretically estimated that even a modest ( approximately 10%) increase in CFTR-associated chloride conductance can be beneficial in a clinical setting. Thus, understanding basic CFTR biogenesis is important, and identification of prototypical compounds that can increase CFTR expression and trafficking is potentially useful in the development of novel therapeutic strategies to treat cystic fibrosis. We report that mitomycin C (MMC) elicits such a response by increasing CFTR mRNA and protein expression in T-84 and HT-29 cells at very low, non-cytotoxic, pharmacologically relevant concentrations (0.1 microM) leading to enhanced chloride secretion. Thus, MMC may be a useful compound for understanding CFTR regulation and biogenesis.

Familial encephalopathy with neuroserpin inclusion bodies.

We report on a new familial neurodegenerative disease with associated dementia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State-a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei. These inclusions are distinct from any described previously and henceforth are identified as Collins bodies. The Collins bodies can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their predominant component. An affinity-purified antibody against neuroserpin specifically labels the Collins bodies, confirming their chemical composition. Therefore, we propose a new disease entity-familial encephalopathy with neuroserpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodies in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggests that FENIB is caused by mutations in the neuroserpin gene, resulting in intracellular accumulation of the mutant protein.

Solitary eosinophilic granuloma of the temporal lobe: case report and review of the literature.

A solitary eosinophilic granuloma of the central nervous system is an unusual manifestation of histiocytosis X. A unique case of a solitary eosinophilic granuloma of the right temporal lobe without osseous involvement is described. A 20-year-old man presented with a grand mal seizure. Magnetic resonance imaging demonstrated an intraaxial enhancing mass in the right temporal lobe with marked vasogenic edema. A right temporal craniotomy was performed for resection of the lesion and the diagnosis of an eosinophilic granuloma was confirmed by histopathology. Follow-up MR imaging obtained 5 years following resection demonstrated no recurrence. Solitary eosinophilic granuloma should be considered in the differential diagnosis of enhancing mass lesions affecting the central nervous system. Although the natural history of solitary eosinophilic granulomas remains poorly defined, surgical treatment still remains the mainstay of therapy for these unifocal cerebral lesions.

Familial dementia caused by polymerization of mutant neuroserpin.

Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases.

Recurrent intracranial Masson's vegetant intravascular hemangioendothelioma. Case report and review of the literature.

In the central nervous system, recurrence of intracranial Masson's vegetant intravascular hemangioendothelioma (MVIH) is rare. To the authors' knowledge, only three recurrent intracranial cases have been reported. The authors report the case of a 75-year-old woman with a recurrent left-sided cerebellopontine angle and middle cranial fossa MVIH. When the patient was 62 years of age, she underwent preoperative embolization and subtotal resection of the intracranial lesion followed by postoperative radiotherapy. She was well and free from disease until 9 years postoperatively when she became symptomatic. At 71 years of age, the patient again underwent preoperative embolization and near-gross-total resection of the lesion. Follow-up imaging performed 15 months later revealed tumor recurrence, and she underwent stereotactic gamma knife radiosurgery. At a 2.75-year follow-up review, the patient's imaging studies revealed stable residual tumor. This case report is unique in that it documents the clinical and pathological features, surgical and postoperative treatment, and long-term follow-up review of a patient with recurrent intracranial MVIH and suggests that this unusual vascular lesion is a slow-growing benign tumor rather than a reactive process. Because the pathological composition of the lesion may resemble an angiosarcoma, understanding this benign vascular neoplasm is crucial so that an erroneous diagnosis of malignancy is not made and unnecessary adjuvant therapy is not given.

Prevalence of anxiety and depressive illness and help seeking behaviour in African Caribbeans and white Europeans: two phase general population survey.

OBJECTIVE: To determine the prevalence of common mental disorders (anxiety and depression) and help seeking behaviour in African Caribbeans and white Europeans. DESIGN: Two phase survey in a general population sample. The first phase comprised screening with the 12 item general health questionnaire; the second phase was standardised psychiatric assessment and interview about help seeking. SETTING: People registered with four general practices in central Manchester. PARTICIPANTS: Of 1467 people randomly selected from family health services authority lists, 864 were still resident. 337 African Caribbeans and 275 white Europeans completed the screening phase (response rate 71%); 127 African Caribbeans and 103 white Europeans were interviewed in the second phase. MAIN OUTCOME MEASURES: One month period prevalence of anxiety and depressive disorders in each ethnic group. RESULTS: 13% of African Caribbeans (95% confidence interval 10% to 16%) and 14% (10% to 18%) of white Europeans had one or more disorder. Anxiety disorders were significantly less common among African Caribbeans (3% (1% to 5%) v 9% (6% to 12%) in white Europeans). Depressive disorders were significantly more common among African Caribbean women than white women (difference 8% (1% to 15%)). Medical help seeking was similar in the two groups, but African Caribbeans with mental disorders were more likely to seek additional help from non-medical sources (12/29 v 5/29, P=0.082). CONCLUSIONS: In an inner city setting the prevalence of common mental disorders is similar in these two ethnic groups.

Surgical management and seizure outcome in patients with tuberous sclerosis.

The authors report the results obtained in 11 patients with tuberous sclerosis (TS) who underwent cortical resection surgery for medically intractable epilepsy. Patients' ages at time of surgery ranged from 3 to 46 years (mean 19.6 years). Preoperative epileptiform electroencephalographic abnormalities were focal spike wave discharges in six patients (55%), multifocal in four patients (36%), and generalized in one patient (9%). In the multifocal and generalized groups, all patients (45%) were evaluated by means of subdural grid and strip electrode recordings, whereas electrophysiological localization in the remaining patients was derived from ictal and interictal scalp recordings. The seizure foci were found to be extratemporal in six patients (55%) and temporal in five patients (45%). Surgical intervention consisted of craniotomy and seizure foci resection guided by electrocorticographic monitoring and functional mapping in five awake (45%) and six asleep (55%) patients. Neuropathological examination of the resected seizure foci revealed cortical tubers in eight patients and diffuse gliosis in three patients. Follow up ranged from 8 to 127 months (mean 35 months). Six patients (55%) were seizure free, half of whom were not receiving antiepileptic drugs (AEDs); three patients (27%) had a greater than 70% reduction in seizure frequency, although they required AEDs; one patient (9%) had a 50% temporary reduction in seizure frequency during the initial 6-month postoperative period; and one patient (9%) was lost to follow-up study. From this small but adequately followed patient population with TS, the authors conclude that cortical resection of seizure foci tailored to electrocorticographic findings and functional mapping is encouraging for this difficult to manage patient population with medically intractable epilepsy.

Neuropathology of the limbic system.

The history and development of the fanciful terminology concerning the structures of the limbic system are discussed. The diseases involving the limbic system are divided into three groups; (1) diseases in which the limbic system is more or less selectively involved, such as limbic encephalitis, herpes simplex encephalitis, cerebral confusions by the falx and tentorium, and internal herniations through the falx and tentorium; (2) diseases in which the limbic system is predominantly involved, such as arhinencephalia, holoprosencephaly, cyst of cavum septi pellucidi, Pick's disease, Alzheimer's disease, hippocampal sclerosis, and vascular diseases of the hippocampal formation; and (3) diseases in which the limbic system is randomly involved, such as various types of neoplasms and vascular and inflammatory lesions. The relationship between destructive lesions of the hippocampus and memory also is emphasized.

Referral of Asian patients to a GI clinic.

This study compared gastrointestinal (GI) symptoms and psychiatric morbidity in consecutive new out-patients presenting to a district general hospital. In a 6-month period 36 patients of South Asian origin were referred to the clinic. They were compared in terms of GI symptoms and psychiatric morbidity with white European controls, both with a large sample of clinic attenders, and with a subsample of 36 matched for age, gender, and diagnosis. A total of 72% (26 of 36) of Asian patients had functional GI disorders compared to 48% (42 of 88) of white patients (p < 0.05). However, comparisons of matched patients showed that Asian patients with functional GI disorders had less severe GI symptoms than the matched white patients, and fewer had psychiatric disorder (23% of Asians and 42% of white Europeans). These results suggest that the threshold for referral for Asian patients with functional GI disorders to hospital clinics is lower than for white patients. Detection and management of somatization in Asian patients in primary care need to be improved, and referral patterns of general practitioners need to be explored in future research.

Global cerebral dysplasia due to dysplasia and hyperplasia of periventricular germinal cells.

Complete obliteration of the cerebral ventricular cavities has not been previously described as an entity among central nervous system malformations. Markedly disorganized maldevelopment of the deep cerebral nuclei and moderately disorganized maldevelopment of the cerebral cortex were observed in the brains of two cases, a 3-year-old female and a male newborn infant. One showed complete and the other partial obliteration of the lateral and third ventricles. Both showed severe maldevelopment of the basal ganglia, which were represented by a large central mass consisting of randomly distributed multiple nodules of gray matter without any discernible differentiation into lenticulostriate nuclei, thalamus, or hypothalamus. Minor malformations involved the cerebral cortex, cerebellum, and mesencephalon to varying degrees. Each of the above two cases was thought to be unique and different until the brain of a fetus of 155 days' gestation was studied. This fetal brain showed exuberant and disorganized periventricular proliferation and migration of germinal matrix cells, with obliteration of the lateral and third ventricles. It was concluded that hyperplasia and disorganized migration of the periventricular germinal matrix early in gestation of whatever cause itself can result in severe maldevelopment of the deep cerebral nuclei and obliteration of the ventricular cavities.

Embarking upon a medical career: psychological morbidity in first year medical students.

This study was undertaken to measure the prevalence of psychological morbidity, and the nature and source of stress, in first year medical students. Two hundred and four first year medical students at a university in the north of England were sent a postal, self-report questionnaire. They were asked to complete the General Health Questionnaire (GHQ), the Stress Incident Record and to give details of their alcohol consumption. A total of 172 students (84.3%) replied. Thirty-six per cent of the students scored above the threshold of the GHQ, indicating probable psychological disturbance. There was no difference between men and women. Approximately half of the students described a stressful incident, the majority of which were related to medical training rather than to personal problems. Male students reported drinking significantly more alcohol than female students, but there was no relationship between levels of alcohol consumption and either psychological disturbance or reporting of stress. The findings suggest that even at the preliminary stages of medical training, many students find aspects of the medical course very stressful. The psychological well-being of medical students needs to be more carefully addressed, and closer attention paid to the styles of medical teaching that may provoke avoidable distress.

Radiation therapy for sarcoid of the thalamus/posterior third ventricle: case report.

There are a limited number of previously reported cases involving the use of radiation therapy for sarcoid of the brain. The case of a 22-year-old man with a thalamic/posterior third ventricle sarcoid mass that grew despite steroid medication is presented. The patient was treated with external beam radiation to a total dose of 20 Gy, with 2-Gy fractions over 14 elapsed days. A complete radiographic response was achieved 4 months after radiation was completed. Radiographic follow-up through 8 months postradiation shows no evidence of disease recurrence. Fractionated radiation therapy in low-to-moderate doses appears to be efficacious in steroid-refractory sarcoid of the brain.

Grading brain tumors other than astrocytomas.

In this article, a critique of the literature is presented concerning the correlation (or lack thereof) between the prognoses of patients with brain tumors other than astrocytomas and the histologic grades of their tumors. In general, the histologic "grade" is a shorthand description of the tumor type and should be understood only as a means of communication of a system of histologic classification and not as implying any indication of biologic behavior, because the "grade" is a relatively poor indicator of the patient's prognosis. Other biological factors (such as the age of the patient, the site of the tumor, and the extent of the surgical resection) are better correlates of subsequent behavior of the neoplasm. The authors suggest (without proof, however) that the determination of potential tumor-doubling times by measuring the percentages of tumor cells in S-phase (by flow cytometry) and in the cell cycle (by immunocytochemistry) may provide a better measure of the degree of malignancy (defined by the rapidity of growth) than can the histologic characteristics by themselves.

Electrocorticography in patients with medically intractable temporal lobe seizures. I. Quantification of epileptiform discharges prior to resective surgery.

We studied retrospectively the intraoperative preresection electrocorticograms (ECoGs) of 72 patients undergoing surgery for medically intractable, mostly complex partial, temporal lobe seizures (TLS). Quantification of interictal epileptiform discharges (EDs) detected visually at each electrode location in 2 min recording epochs included computations of ED rates (EDs/min) and cumulative voltages (CuVs) (microV/min). Of 6388 EDs, 81% involved the infratemporal surface, 18% the lateral temporal surface and 1% the orbital frontal area. Forty-eight patients (67%) demonstrated multiple (up to 5 or more), temporally independent foci. Dominant foci in medial and lateral infratemporal locations were about equally common and were significantly more frequent than in lateral temporal locations. Rankings of ED CuVs and rates at individual cortical locations defined 4 areas of "relative interictal cortical epileptogenicity." These were arranged in an orderly pattern with the anterior parahippocampal gyrus and the inferomedial surface of the temporal tip displaying the highest and the lateral temporal and posterior infratemporal cortices showing the lowest propensity to the interictal epileptiform discharge. Individual areas were not characterized by distinct clinical seizure manifestations. Preresection ECoGs provide information on the epileptogenic dysfunction that involves most of the temporal lobe of patients with medically intractable TLS.

Electrocorticography in patients with medically intractable temporal lobe seizures. II. Quantification of epileptiform discharges following successive stages of resective surgery.

We quantified retrospectively the interictal epileptiform discharges (EDs) detected visually in the electrocorticograms (ECoGs) of 42 patients undergoing successive stages of anterior temporal lobectomy for medically intractable temporal lobe seizures (TLS). Following first resection sparing the hippocampus (H) and the parahippocampal gyrus (PHG), EDs were recorded on both structures in all patients and by far exceeded in amount those on residual lateral infratemporal and lateral temporal cortices. Frequently, EDs occurred apparently simultaneously but with opposite polarities on the H and the PHG, but more complex relationships were also evident in most individuals. These features likely reflected abnormal post-synaptic activity generated at different locations and cortical depths within the H, PHG, or both. Quantification of epileptiform activity and the effects of selective anterior hippocampectomy or parahippocampectomy suggested that both the H and PHG had remarkable epileptogenic potential. Levels of epileptiform activity were not significantly different in the H and PHG and in the H of subjects with and without H sclerosis. After final resection, including the amygdaloid nucleus (AN), anterior H and PHG, interictal EDs were present, although markedly diminished, in 35 patients. Postresection foci were significantly less numerous and extensive, and attained smaller maximal voltages, than did foci before and after first resection.

Pituitary oncocytomas: clinical features, characteristics in cell culture, and treatment recommendations.

To determine whether there are significant differences between oncocytomas and pituitary adenomas, we evaluated clinical features, treatment regimens and outcome in 23 males and 9 females (average age 64 years, range 43-81 years) with the histologic diagnosis of pure pituitary oncocytomas (> 95% oncocytes). Symptom duration was six to twelve months in 6 cases (19%) and more than one year in 19 cases (59%). Three patients presented with sudden onset of symptoms, and were found to have hemorrhage within their tumors. Visual loss (69%) and symptoms of hypopituitarism (44%) were the most common presenting complaints. Preoperative endocrine profiles revealed abnormalities in most cases, including pituitary insufficiency in 56% and hyperprolactinemia in 59%. The tumors were typically large at presentation; all but one had suprasellar extension. 28 patients underwent transsphenoidal tumor resections; 4 underwent subfrontal craniotomies. Gross dural invasion was found at surgery in 11 cases. At a mean followup of 31 months (range 2-68 months), recurrent tumor was identified in 4 patients (12.5%). Tumor size, dural invasion, preoperative endocrine profile, and postoperative radiotherapy did not correlate with recurrence. Among seven oncocytomas grown in culture, five demonstrated two distinct cell types consisting of oncocytes and typical adenoma cells, respectively. Oncocytomas often have a different clinical presentation than functional pituitary adenomas.

Intraventricular fat from a ruptured sacral dermoid cyst: clinical, radiographic, and pathological correlation. Case report.

The authors report a unique case of a dermoid cyst that ruptured into the lumbosacral subarachnoid space following trauma, resulting in dissemination of cyst contents into the ventricles and cerebrospinal subarachnoid spaces. An intraspinous source should be considered when intraventricular fat is identified without a clear intracranial source.