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Biomedical subjects

A J Martinez

Publications and source records attributed to A J Martinez.

At least 19 recordsLinked to original sources

Lack of toxicity to adults of the Mexican fruit fly (Diptera: Tephritidae) of beta-exotoxin in Bacillus thuringiensis endotoxin preparations.

beta-Exotoxin (thuringiensin) was found in high titers in centrifugation supernatants and acetone/lactose powders produced from centrifugation pellets of strains Guat 1 and HD 2 of Bacillus thuringiensis (Berliner). Diets containing powders of either strain were toxic, diets containing Guat 1 supernatant were not toxic, diets containing HD 2 supernatant were slightly toxic, and diets containing powders or supernatants from uninoculated culturing medium spiked with beta-exotoxin were not toxic. Most mortality occurred within 3 d when flies fed on powders but not until 6-7 d when flies fed on HD 2 supernatant. These results indicated that the primary toxic principals of the powders were endotoxins/spores and that beta-exotoxin alone was not toxic to adult flies at the concentrations found in the supernatants or powders.

Adenosine↗

Beneficial effects of the radioprotectant 21-aminosteroid U-74389G in a radiosurgery rat malignant glioma model.

PURPOSE: To evaluate the radioprotectant effects of the 21-aminosteroid U-74389G on the rat C6 glioma model after stereotactic radiosurgery. Because radiosurgery causes both tumor cytotoxicity, as well as regional brain edema, we hypothesized that this drug might exhibit advantageous or deleterious effects on healthy and neoplastic tissue. METHODS: Rats were implanted with 10(6) C6 glioma cells into the right frontal brain and randomized to a Control Group (n = 18), radiosurgery on Day 14 (50% isodose = 35 Gy) (n = 15), or radiosurgery preceded by a single 15 mg/kg intravenous dose of 21-aminosteroid (n = 27). All animals were killed by 90 days and evaluated for survival, tumor size, the presence or absence of regional parenchymal edema, or radiation-induced vasculopathy. RESULTS: After tumor implantation, median survival in the Control Group was 23 days. Significant improvements in median survival were noted after RS alone (median, 31 days; p = 0.02), and RS plus 21-aminosteroid (median, 59 days; p < 0.0001). In the Control Group, mean tumor diameter was 5.4 mm. After RS alone, the mean diameter was 3.2 mm (p = 0.002), and after RS plus 21-aminosteroid, 2.9 mm (p = 0.0002). In the Control Group, the tumor grew as a hypercellular, compact mass. Only 3 of 18 animals had peritumoral edema. In contrast, 7 of 15 animals in the RS group had evidence of edema (p = 0.006), but rats that received 21-aminosteroid showed no increase compared to controls (p = 0.38). Similarly, 6 of 15 animals that had radiosurgery alone showed evidence of vasculopathy (p = 0.005) compared to no animals in the control group and only 2 of 27 aminosteroid-treated animals. CONCLUSIONS: The 21-aminosteroid U-74389G exhibits a radioprotectant effect on normal brain tissue, but does not appear to protect the tumor in an in vivo rat radiosurgery model. We believe that the observed beneficial effects on healthy brain led to significant prolongation of animal survival; perhaps, by limiting the adverse effects of high-dose radiosurgery. This radioprotectant should now be evaluated in randomized clinical trials in patients with malignant brain tumors.

Animals↗

Reductions in brain phosphatidylinositol kinase activities in Alzheimer's disease.

BACKGROUND: Converging lines of evidence suggest that alterations in the intracellular trafficking of the amyloid precursor protein, its derivatives, and other relevant proteins may contribute to the pathophysiology of Alzheimer's disease (AD). Since phosphatidylinositol (PI) kinase plays a pivotal role in the sorting and transport of newly synthesized proteins to their final destinations, we explored the hypothesis that AD is associated with alterations in the specific activities of these enzymes in postmortem brain tissue. METHODS: The specific activities of soluble and particulate pools of PI 3-kinase and PI 4-kinase from the frontal cortex were compared between 11 cases with histopathologically confirmed AD and 11 nondemented controls matched for sex, race, age at death, and postmortem interval. Potential associations of these activities with sociodemographic and clinical features were also explored. RESULTS: AD was associated with 43-59% reductions in the specific activities of the soluble forms of both lipid kinases; but no significant change in the specific activities of the particulate species. Associations of these specific activities with sex, age at onset or death, duration of illness, postmortem interval, or densities of morphologic lesions in the frontal cortex were not observed among the 11 AD cases. CONCLUSIONS: In addition to regulating protein sorting and trafficking, PI kinases participate in a wide range of cellular processes including protection from apoptosis, differentiation and cell growth, regulation of the cytoskeleton, and glucose metabolism. The results of this study suggest that one or more of these alterations in AD may result from a common abnormality in PI kinase regulation.

1-Phosphatidylinositol 4-Kinase↗

The neuropathology of intestinal failure and small bowel transplantation.

The aim of this study was to elucidate the neuropathological substrate of intestinal failure before and after small bowel transplantation (SBT). Retrospective analysis of complete autopsy or brain biopsy specimens of 17 patients with intestinal failure (12 children and 5 adults) were studied. Patients were divided into two groups. Group I (transplanted group; n = 13) included those patients who underwent intestinal transplantation under tacrolimus and steroids immunosuppressive therapy. Group II (control group) included 4 children with intestinal failure who were candidates for SBT and died while awaiting an intestinal allograft. Central nervous system (CNS) abnormalities were seen in 92% of the SBT recipients and in 100% of SBT candidates. The neuropathological lesions of SBT recipients included: (a) vascular lesions: global brain ischemia, infarcts, intracranial hemorrhage and edema (7 children/2 adults; 69%); (b) cerebral atrophy (6 children; 46%); (c) Alzheimer type II gliosis (5 children/4 adults; 69%); (d) infection (3 patients; 23%) due to cytomegalovirus (1 child), Aspergillus fumigatus (1 adult) and progressive multifocal leukoencephalopathy (PML)-like (1 adult); (e) Epstein-Barr virus-related cerebral post-transplant lymphoproliferative disorder (2 children; 15%); and (f) central pontine and extrapontine myelinolysis (1 child; 7.5%). The neuropathological lesions of SBT candidates were Alzheimer type II astrocytosis (4 patients), vascular changes (4 patients), brain atrophy (4 patients) and cerebral candidiasis (1 patient). CNS vascular, metabolic and infectious pathology are significant causes of morbidity and mortality in patients suffering intestinal failure, both before and after SBT. Brain atrophy was a frequent finding and may be related to nutritional and developmental inadequacy of long-term total parenteral nutrition.

Adult↗

Prospective study of risk factors for Alzheimer's disease: results at 7.5 years.

OBJECTIVE: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease and its relationship to the APOE epsilon4 genotype. METHOD: This report describes the results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. RESULTS: Nine incident cases of Alzheimer's disease were detected during the first 2,220 subject-years of the follow-up period. Age, increased platelet membrane fluidity, and the APOE epsilon4 allele made significant independent contributions to the risk of developing Alzheimer's disease, while sex and years of education did not. Increased platelet membrane fluidity was associated with incident Alzheimer's disease cases between the ages of 64 and 71, while the epsilon4 allele was associated with incident Alzheimer's disease cases from age 64 until at least age 80. CONCLUSIONS: These results indicate that increased platelet membrane fluidity is not produced by the APOE epsilon4 allele. Instead, increased platelet membrane fluidity and the epsilon4 allele appear to make significant independent contributions to the risk of developing Alzheimer's disease among the first-degree relatives of patients with this disorder. Moreover, the age ranges over which these risk factors operate appear to be different.

Adult↗

Use of cytological preparations for the intraoperative diagnosis of stereotactically obtained brain biopsies: a 19-year experience and survey of neuropathologists.

OBJECT: The goals of this study were to analyze the accuracy of cytological techniques, consisting of touch and smear preparations, for the intraoperative diagnosis of stereotactically obtained brain biopsy samples, and to determine the prevalence of the use of these methods among neuropathologists. METHODS: A survey regarding preferred methods for intraoperative diagnosis of stereotactically obtained brain biopsy samples was completed by 92 (62%) of 148 neuropathologists. Twenty-three percent of respondents chose frozen-section examination alone; 13% chose one or more cytological methods alone; and the remainder (64%) chose a combination of frozen-section examination and cytology. At the University of Pittsburgh, the neuropathology records for all stereotactic brain biopsies performed from May 1979 through May 1998 were retrospectively reviewed. Of the 946 stereotactic brain biopsies, 316 cases were excluded because the intraoperative neuropathological consultation was not recorded. Thirty-five cases were excluded because frozen-section examinations were performed. Therefore, a total of 595 cases were suitable for analysis. Intraoperative cytological investigation correlated with the final diagnosis in 90% of cases (52% complete correlation and 38% partial correlation). In 11% of cases there was no correlation between the intraoperative and final diagnoses. Intraoperative diagnoses were most accurate in cases of abscess, germinoma, lymphoma, metastasis, and malignant glioma. Overall, 91% of biopsy specimens were diagnostic when examined using the paraffin-embedded section technique. The sensitivity of cytological preparations in detecting a diagnostic specimen was 96% and the specificity in detecting a nondiagnostic specimen was 75%. CONCLUSIONS: Intraoperative cytological preparations correlated with the final diagnoses in 90% of stereotactic biopsies and had a 96% sensitivity in detecting diagnostic specimens. The highest rate of correlation was noted in cases of abscess, germinoma, lymphoma, metastasis, and malignant glial tumor.

Biopsy↗

Expression of retinoic acid, triiodothyronine, and glucocorticoid hormone nuclear receptors is decreased in the liver of rats fed a hypercholesterolemia-inducing diet.

Several studies have shown that dietary factors modulate cell signaling pathways. The aim of this study was to determine whether a hypercholesterolemia-inducing diet rich in saturated fat and cholesterol modifies rat liver expression of the nuclear receptors of retinoic acid (RAR), triiodothyronine (TR), and glucocorticoid hormone (GR), which are transcriptional factors. The experimental diet contained coconut oil 25 g/100 g as a source of lipids, cholesterol 1 g/100 g, and cholic acid 0.5 g/100 g, and the control diet contained olive oil 5 g/100 g. After 26 days of feeding the hypercholesterolemia-inducing diet, a lower binding capacity of the nuclear receptors and a smaller amount of their mRNA were observed. Moreover, the activities of malic enzyme (ME) and tyrosine aminotransferase (TAT), whose gene promotors contain a response element to TR and GR, respectively, were significantly decreased. These changes occurred in a cellular environment characterized by a high level of cholesterol and free fatty acids (FFAs). Thus, two nonexclusive hypotheses can be proposed to explain this decreased expression of nuclear receptors, one emphasizing the effect of lipidic components on the cellular amount of receptor ligands (retinoic acid [RA] and triiodothyronine [T3]), the other emphasizing a modification of the balance between nuclear receptors that could impede the upregulation of TR and RAR.

Animals↗

Death from a malignant cerebellopontine angle triton tumor despite stereotactic radiosurgery. Case report.

Malignant vestibular nerve tumors are rare: to date, only three cases have been reported in the literature. The authors report a case of an eighth cranial nerve tumor that progressed 5 years after stereotactic radiosurgery. The patient was a 44-year-old man who underwent stereotactic radiosurgery for a 27-mm cerebellopontine angle tumor that was discovered on investigation of tinnitus and hearing loss. He developed facial weakness after 5 years, and repeated imaging revealed tumor enlargement. Despite complete microsurgical excision, the tumor rapidly recurred locally and subsequently disseminated within the neuraxis. The patient died 1 year after tumor progression was detected. Histopathological analysis revealed a malignant spindle cell neoplasm with frequent mitotic figures. The presence of positive rhabdoid elements on immunohistochemical studies confirmed that it was a triton tumor. The authors review the relevant literature concerning the classification and management of malignant vestibular nerve tumors and discuss the implications of tumor progression after stereotactic radiosurgery.

Adult↗

Radiotherapy for nonfunctional pituitary adenoma: analysis of long-term tumor control.

OBJECT: The authors studied outcomes in patients who had undergone radiotherapy for nonfunctional pituitary adenoma to assess long-term tumor control and to identify factors affecting tumor control such as higher radiation doses, improved imaging, and histological characteristics of the tumor. METHODS: In this retrospective study, the authors evaluated 120 patients who received radiotherapy for nonfunctional pituitary adenomas between 1960 and 1991. The median follow-up period was 9 years (range 1 month-32 years). Radiation doses varied between 37.6 and 65.6 Gy (median 46.7 Gy). Tumors progressed in 15 of the 120 patients by 1 to 25 years after radiotherapy. Actuarial tumor control rates at 10, 20, and 30 years were 87.5+/-3.6%, 77.6+/-6.3%, and 64.7+/-12.9%, respectively. Tumor progression after radiotherapy occurred significantly more often (p=0.0397) in patients with oncocytoma than in patients with nononcocytic null cell adenoma. No other factors correlated significantly with tumor control. One case of optic and oculomotor neuropathy developed 4.5 years after a maximum dose of 50 Gy in 25 fractions. Radiation-induced neoplasms (meningioma and glioblastoma multiforme) developed at a rate of 2.7% at 10 and 30 years. CONCLUSIONS: The oncocytic variant of null cell pituitary adenoma appears less sensitive to control by radiotherapy than nononcocytic undifferentiated cell adenoma. A follow-up period extending beyond 20 years is needed adequately to assess the efficacy of radiotherapy for tumor control. Doses of 40 or 45 Gy in 20 or 25 fractions, respectively, appear optimal.

Actuarial Analysis↗

Case of the month: September 1997--a 26 year old woman with new onset seizures.

A twenty-six year old, previously healthy nurse presented with new onset of seizures and was given a clinical diagnosis of herpes simplex encephalitis. After treatment with acyclovir there was incomplete resolution of the lesions by MRI scans and within a few months the patient's neurologic symptoms worsened, prompting a stereotactic biopsy. A diagnosis of progressive multifocal leukoencephalopathy (PML) was made using electron microscopy, and in situ hybridization studies. Subsequent to this biopsy, she was shown to be infected with human immunodeficiency virus (HIV) and had a CD4 T-cell count of 63. She had no known risk factors for HIV infections and had been tested as recently as eighteen months previously during her pregnancy. Neither the husband nor the child were positive for HIV. PML as a presenting sign of HIV infection is rare.

Adult↗

Proliferation index as a predictor of prognosis in malignant gliomas of childhood.

BACKGROUND: The prognosis for children with high grade gliomas remains somewhat unpredictable because histologic features alone provide an imperfect assessment of the biologic behavior of a given lesion. Whereas some patients experience prolonged disease control after surgery and adjuvant therapy, others with lesions that appear comparable exhibit rapid disease progression and death. METHODS: Because proliferative activity may provide a potential correlate of biologic aggressiveness, the authors examined the relationship between MIB-1 labeling index and outcome in a series of 29 archival pediatric malignant nonbrainstem gliomas from patients treated consecutively at the study institution between 1975 and 1992, in which clinical, histologic, diagnostic, and therapeutic parameters were previously defined. Three patients who died perioperatively were excluded from outcome analyses. All tumors were rereviewed by two neuropathologists and classified as Grade 3 or 4 lesions based on contemporary guidelines. RESULTS: Among the specimens from the 26 patients who survived the perioperative period, a striking difference in outcome was apparent between tumors with MIB-1 indices < 12 (n = 10) and those with indices > 12 (n = 16). Median progression free survival was >48 months in the low MIB-1 group compared with only 6 months in the high MIB-1 group (P = 0.014, rank-sum test). Median overall survival was >48 months in the low MIB-1 group compared with only 16 months in the high MIB-1 group (P = 0.012). MIB-1 index remained associated with survival after taking into account the effect of resection extent, which also correlated strongly with outcome in this cohort. Although MIB-1 index was associated with histopathologic grade (Grade 3: 11.9 +/- 9.7 vs. Grade 4: 27.3 +/- 19.0; P = 0.015, Fisher's exact test), it proved to be a much stronger predictor of outcome than histology. CONCLUSIONS: MIB-1 index may supplement routine histologic classification as a means for improving the accuracy of predicting the biologic behavior of childhood malignant gliomas and may provide a basis for stratifying patients in future malignant glioma studies and refining therapeutic decision-making.

Antibodies, Monoclonal↗

The relationship between TP53 mutations and overexpression of p53 and prognosis in malignant gliomas of childhood.

The prognosis for children with high-grade gliomas remains somewhat unpredictable. Although prolonged disease control is sometimes achieved after surgery, radiotherapy, and chemotherapy, most patients exhibit rapid disease progression. Because p53-dependent apoptosis mechanisms are involved in the cytotoxic effects of irradiation and chemotherapy, we questioned whether p53 status might be associated with outcome in childhood malignant gliomas. Therefore, we examined p53 status, both immunohistochemically and by direct sequencing of exons 5-8, in a series of 29 archival pediatric malignant non-brainstem gliomas treated consecutively at our institution between 1975 and 1992. Eighteen tumors had dense p53 staining in the majority of cells, although only 11 had mutations of the p53 gene (TP53). On univariate analysis, there was a significant association between p53 overexpression and a shorter progression-free survival (PFS) and overall survival (OS; P = 0.019 and 0.013, respectively; rank sum test). In addition, there was a significant association between TP53 mutations and a poorer PFS (P = 0.04), and a strong trend toward a shorter OS among patients with TP53 mutations (P = 0.06). Median PFS and OS for patients with TP53-mutated tumors were 6 months and 16 months, respectively, and for those with p53 overexpression 5.5 months and 14 months, respectively, versus 16 months and 25 months, respectively, for those without TP53 mutations and 25 months and >4 years, respectively, for those without p53 overexpression. The percentage of patients in this series with TP53 mutations (37.9%) was substantially higher than in previous studies of childhood gliomas and comparable to the frequency of mutations noted in adult gliomas. However, both TP53 mutation and p53 overexpression were significantly less frequent in tumors from children younger than 4 than from older children (P = 0.02 and 0.01, respectively). These results indicate that p53 mutation and expression status may be associated with prognosis in childhood malignant gliomas, and thus may provide a basis for stratifying patients biologically in future malignant glioma studies.

Adolescent↗

Spinal cord astrocytomas: long-term results comparing treatments in children.

Technology enabling radical resection has expanded treatment options for children with spinal cord astrocytomas. Comparison of long-term survival and neurological function after complete tumor removal with more conservative treatment may determine whether radical surgery can improve outcome in well-differentiated and anaplastic spinal cord astrocytomas. In all, 18 children with spinal cord astrocytomas were initially treated between 1976 and 1992 with biopsy in 6, subtotal removal in 7, and complete resection in 5. Seven had anaplastic tumors. Nine children treated before 1988 received radiotherapy. Survival after a median follow-up of 11 years was 82% (9/11). Five patients with anaplastic tumors are alive between 12 and 18 years after treatment. No patient relapsed after total resection, whereas more than two-thirds treated with other than complete resection relapsed within 3 years (P = 0.029). All but 1 patient with symptomatic relapse received radiotherapy (P = 0.059). Magnetic resonance imaging more than 3 years postoperatively showed no recurrences in 13 of the 15 survivors and asymptomatic progression in the other 2. Although excellent long-term survival was seen, frequent relapse was associated with either incomplete resection or radiotherapy. Prolonged relapse-free survival was observed in all patients treated with complete resection, including 3 with anaplastic tumors.

Adolescent↗

Anti-aflatoxin mutagenic factors in corn.

Extracts, isolated through sequential fractionation and partition procedures described previously (Martinez et al. 1994) from aflatoxin-free corn and aflatoxin-contaminated corn with and without ammonia treatment, were investigated for mutagenic potential using the Ames test (TA 100 tester strain). 2-Aminofluorene (2-AF) and pure aflatoxin B1 (AFB1) were used as positive controls. Although TA100 showed mutagenic response to pure AFB1 at a dose of ca 10 ng/plate, all isolates tested from ammonia-treated aflatoxin-contaminated corn containing 7500 ng AFB1/g did not exhibit positive results in the Ames test. Additionally, isolates from non-ammonia-treated aflatoxin-contaminated corn failed to give positive mutagenic potentials. These results indicate that differences between the mutagenic potentials of pure aflatoxins and of aflatoxins in naturally-contaminated corn exist. CH2Cl2 extracts (the fractions containing aflatoxins) obtained from aflatoxin-contaminated corn with and without ammonia treatment were applied to preparative thin layer chromatography (TLC) in an effort to separate aflatoxins and/or ammonia/aflatoxin reaction products from the "unknown interfering materials' existing in the corn matrix. Each of the fractions separated by TLC was tested by the Ames test with S9 activation and none of them gave a mutagenic response to TA100. CH2Cl2 extracts in dimethylsulphoxide (DMSO) obtained from non-ammonia-treated aflatoxin-free corn were spiked with pure AFB1 and tested by TA100 with S9 activation. Again, no positive responses were observed. These findings provide further evidence of "unknown interfering materials' in corn which may bind with aflatoxin and/or can be extracted by CH2Cl2 together with aflatoxin, and, therefore, block the mutagenic activity of aflatoxin in the Ames test. Those materials were not separated from the aflatoxins by the TLC technique used in the present study. Possible reasons and further studies required to evaluate this phenomenon are discussed.

Aflatoxins↗

Toxicity of an isolate of Bacillus thuringiensis subspecies darmstadiensis to adults of the Mexican fruit fly (diptera: (Diptera:Tephritidae) in the laboratory.

Centrifugation pellets obtained from an isolate of Bacillus thuringiensis subspecies darmstadiensis (Guat 1) cultured from a Guatemalan soil sample were found to be toxic to Anastrepha ludens (Loew) adults in the laboratory. We developed a bioassay diet that consisted of a mixture of the bacterium, a protein source, and sugar. A pH of 4.1 of the mixture was needed to obtain maximum adult mortality. One meal of the diet, which lasted from 30 s to 4 min, was enough to cause > 70% mortality of both fed or starved adults. Mortality of fed adults was 70-75% following a feeding period of 60 min and mortality of starved adults was 80-90% following a feeding period of 30 min. The isolate was toxic to adults from 1 to 21 d old.

Animals↗

Radioprotective effects of the 21-aminosteroid U-74389G for stereotactic radiosurgery.

OBJECTIVE: Future improvements in the results of stereotactic radiosurgery will be related to better patient selection, dose planning, radiosensitization of the target, and, possibly, protection of the brain surrounding the target. 21-Aminosteroids may provide protection against brain radiation injury by inhibition of lipid peroxidation and a selective action on vascular endothelium. We hypothesized that the 21-aminosteroid U-74389G would reduce radiosurgery-related brain injury without attenuating the target volume response. METHODS: One hundred and forty-five rats were divided into four experimental groups before undergoing radiosurgery: control (n = 47); low-dose U-74389G (5 mg/kg of body weight, n = 30); high-dose U-74389G (15 mg/kg, n = 20); and methylprednisolone (2 mg/kg, n = 48). The drug was administered 1 hour before radiosurgery (4-mm gamma knife collimator) of the normal rat frontal lobe (single-fraction maximum doses of 50, 100, or 150 Gy) was performed. All brains underwent histological examination at 90 or 150 days to evaluate the diameters of necrosis and the findings of radiation-induced vasculopathy, brain edema, and gliosis. RESULTS: None of the animals that received 50-Gy radiation developed histological changes, whereas all of the animals that received 150-Gy radiation developed radiation necrosis without drug-induced protection from vascular changes or edema. In animals receiving 100-Gy radiation, high-dose aminosteroid reduced radiation-induced vasculopathy at 90 days (P = 0.06) and at 150 days (P = 0.02) and prevented regional edema at 90 days (P = 0.01) and at 150 days (P = 0.03). Low-dose aminosteroid and corticosteroid provided no protection. CONCLUSION: The 21-aminosteroid U-74389G provided protection after a single intravenously administered dose of 15 mg/kg against radiation-induced vasculopathy and edema. High-dose 21-aminosteroids seem to have optimal properties for radiosurgery, surrounding brain protection without reducing the therapeutic effect desired within the target volume.

Animals↗

Free-living, amphizoic and opportunistic amebas.

Amebas belonging to the genera Naegleria, Acanthamoeba and Balamuthia are free-living, amphizoic and opportunistic protozoa that are ubiquitous in nature. These amebas are found in soil, water and air samples from all over the world. Human infection due to these amebas involving brain, skin, lung and eyes has increased significantly during the last 10 years. The epidemiology, immunology, protozoology, pathology, and clinical features of the infections produced by these protozoa differ strikingly. Infection by the pathogenic Naegleria fowleri is acquired by exposure to polluted water in ponds, swimming pools and man-made lakes. Raised temperatures during the hot summer months or warm water from power plants facilitate the growth of N. fowleri. N. fowleri is a thermophilic ameba that grows well in tropical and subtropical climates. The CNS infection, called Primary Amebic Meningoencephalitis (PAM), produced by N. fowleri is characterized by an acute fulminant meningoencephalitis leading to death 3-7 days after exposure. Victims are healthy, young individuals with a history of recent water-related sport activities. The portal of entry is the olfactory neuroepithelium. The pathologic changes are an acute hemorrhagic necrotizing meningoencephalitis with modest purulent exudate, mainly at the base of the brain, brain-stem and cerebellum. Trophozoites can be seen within the CNS lesions located mainly around blood vessels. Thus far 179 cases have been reported; 81 in the USA alone. Balamuthia mandrillaris and several species of Acanthamoeba are pathogenic "opportunistic" free-living amebas which cause Granulomatous Amebic Encephalitis (GAE) in humans and animals. GAE is an infection, usually seen in debilitated, malnourished individuals, in patients undergoing immunosuppressive therapy for organ transplants and in Acquired Immunodeficiency Syndrome (AIDS). The granulomatous component is negligible, particularly in immunocompromised individuals. Pathologically these amebas produce a patchy, chronic or subacute granulomatous encephalitis with the presence of trophozoites and cysts. The portal of entry is probably through the respiratory tract or an ulceration of the skin reaching the CNS by hematogenous spread. As of October 1, 1996, 166 cases (103 due to Acanthamoeba and 63 due to Balamuthia) of GAE have been reported from around the world. Of these 103 cases due to Acanthamoeba (72 have been reported in the USA alone, > 50 in AIDS). It is well known that several species of Acanthamoeba can also produce, chronic sight threatening ulceration of the cornea called Acanthamoeba keratitis (AK), mostly in contact lens wearers or in individuals with minor corneal abrasions. Hundreds of cases of AK have been documented world wide.

Acanthamoeba Keratitis↗

Granulomatous amebic encephalitis due to Balamuthia mandrillaris (Leptomyxiidae): report of four cases from Mexico.

In this report, we describe four cases of granulomatous amebic encephalitis caused by Balamuthia (Leptomyxid ameba) in four previously healthy Mexican patients. All four cases were characterized by focal neurologic signs, increased intracranial pressure, and cerebral hyperdense lesions in computed tomography scans of the head. These patients underwent craniotomies for evaluation of mass lesions for possible brain tumors. Granulomatous chronic inflammatory reaction and amebic trophozoites were found in brain biopsies. At autopsy, areas of hemorrhagic encephalomalacia were located in both basal frontal lobes, right parieto-occipital lobes, and, less often, in the brainstem and cerebellum. Angiitis, necrotizing granulomatous encephalitis, and large numbers of amebic trophozoites in perivascular spaces were present. Amebic trophozoites were seen in the left adrenal gland in one of the cases. The amebas in all four cases were identified as Balamuthia mandrillaris (Leptomyxiidae) based on their reactivity with the anti-Balamuthia (Leptomyxiidae) serum in an immunofluorescence test.

Adolescent↗