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Biomedical subjects

J Berman

Publications and source records attributed to J Berman.

At least 19 recordsLinked to original sources
PubMed2007

Cerebellar and brainstem infarction as a complication of CT-guided transforaminal cervical nerve root block.

A 60-year-old man with a 4-year history of intractable neck pain and radicular pain in the C5 nerve root distribution presented to our department for a CT-guided transforaminal left C5 nerve root block. He had had a similar procedure on the right 2 months previously, and had significant improvement of his symptoms with considerable pain relief. On this occasion he was again accepted for the procedure after the risks and potential complications had been explained. Under CT guidance, a 25G spinal needle was introduced and after confirmation of the position of the needle, steroid was injected. Immediately the patient became unresponsive, and later developed a MR-proven infarct affecting the left vertebral artery (VA) territory. This is the first report of a major complication of a cervical root injection under CT guidance reported in the literature. We present this case report and the literature review of the potential complications of this procedure.

Brain Stem Infarctions↗
PubMed2006

Treatment of Bolivian mucosal leishmaniasis with miltefosine.

BACKGROUND: Although mucosal leishmaniasis is a prominent disease, it has been studied only to a limited extent. It is classically treated with parenteral antimony or, as a last resort, amphotericin B. METHODS: We treated Bolivian mucosal leishmaniasis due to Leishmania braziliensis with the oral agent miltefosine, 2.5 mg/kg/day for 28 days, and followed-up for 12 months. RESULTS: Seventy-two patients were evaluable. The cure rate for the 36 patients who had "mild" disease (i.e., affecting nasal skin and nasal mucosa) was 83%. The cure rate for the 36 patients who had more extensive disease (involving the palate, pharynx, and larynx) was 58%. Patients refused to be randomized to parenteral agents, but the cure rate for an almost contemporary group who was receiving amphotericin B (45 mg/kg over 90 days) was 7 (50%) of 14. CONCLUSIONS: In this unrandomized trial, oral miltefosine was at least as effective as heroic doses of parenteral amphotericin B. The cure rate for miltefosine was approximately equivalent to historical cure rates using parenteral pentavalent antimony for mild and extensive disease in neighboring Peru. Although gastrointestinal side reactions do occur with miltefosine, its toxicity profile is superior to that of antimony and far superior to that of amphotericin B--in part because of the inherent attractiveness of oral versus parenteral agents. Our results suggest that miltefosine should be the treatment of choice for mucosal disease in North and South America.

Adolescent↗
PubMed2006

Treatment of New World cutaneous leishmaniasis with miltefosine.

Miltefosine (2.5 mg/kg/day for 28 days) was investigated for treatment of New World cutaneous leishmaniasis in Colombia and Guatemala. The data from a controlled study was remarkably similar to the data of a prior uncontrolled pilot study. In the controlled study, the per-protocol 6-month cure rate for Leishmania panamensis disease was 91% compared with a concomitant placebo cure rate of 38%. In Guatemala, the cure rate for L. braziliensis and L. mexicana disease was approximately 50% compared with approximately 20% for placebo. In both countries, nausea but not 'motion sickness' and vomiting but not diarrhoea were experienced by approximately 30% more miltefosine patients than placebo patients. Mild elevation of creatinine, but not of aspartate aminotransferase or alanine aminotransferase, was also more frequently seen in the miltefosine group than in the placebo group. Miltefosine was well tolerated, and as effective as historic values of antimony for treatment of L. panamensis disease.

Administration, Oral↗
PubMed2006

Miltefosine: issues to be addressed in the future.

Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.

Abnormalities, Drug-Induced↗
PubMed2005

Short report: efficacy of pentavalent antimony for treatment of colombian cutaneous leishmaniasis.

Two hundred twenty-six consecutive adult patients with cutaneous leishmaniasis in Colombia were treated with Glucantime and 81% were cured. The 19% who failed treatment had received a statistically significant lower total amount of antimony (354 mg/kg) than those who were cured (405 mg/kg) (P = 0.002). Thirty-nine of the failures were re-treated with Glucantime and 59% were cured. This large experience on initial and re-treatment cure rates probably represents the values found in clinical practice. In this series, parasite resistance may have been induced by the relatively low initial dose of antimony administered to some patients.

Adult↗
PubMed2004

Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.

Adult↗
PubMed2004

Comparison of generic to branded pentavalent antimony for treatment of new world cutaneous leishmaniasis.

The cost of generic pentavalent antimony (generic stibogluconate) is approximately one-sixth that of branded pentavalent antimony (stibogluconate in the form of Pentostam or meglumine antimoniate in the form of Glucantime. We compared generic stibogluconate to Pentostam and Glucantime for the treatment of cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients, the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were 75-83%. The highest values were in the generic stibogluconate group. The incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic stibogluconate group. The efficacy and tolerance of inexpensive generic stibogluconate appears comparable to branded formulations for the treatment of cutaneous leishmaniasis in these endemic regions.

Adolescent↗
PubMed2001

2-(Anilinomethyl)imidazolines as alpha(1)-adrenoceptor agonists: the identification of alpha(1A) subtype selective 2'-carboxylic acid esters and amides.

2-(Anilinomethyl)imidazolines with 2'-esters or 2'-amides are potent agonists of the cloned human alpha(1)-adrenoceptors in vitro. The size and shape of the ortho substituent can have significant effects on the potency, efficacy, and subtype selectivity of these 2-(anilinomethyl)imidazolines. alpha(1A)-subtype selective agonists have been identified.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2001

Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent.

There is no recognized oral treatment for American cutaneous leishmaniasis. A rising-dose, open-label phase I/II trial of the oral agent miltefosine against Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32 patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32 patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure rate for standard injections of antimony is 93%. "Motion sickness" that did not interfere with normal duties was experienced by 40% of patients and was dose related. Vomiting and diarrhea were reported on approximately 2% of treatment days. In this uncontrolled study of oral miltefosine for treatment of patients with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day for 3-4 weeks was effective and tolerated.

Administration, Oral↗
PubMed2001

Cassettes for PCR-mediated construction of green, yellow, and cyan fluorescent protein fusions in Candida albicans.

We have developed a set of plasmids containing fluorescent protein cassettes for use in PCR-mediated gene tagging in Candida albicans. We engineered YFP and CFP variants of the GFP sequence optimized for C. albicans codon usage. The fluorescent protein sequences, linked to C. albicans auxotrophic marker sequences, were amplified by PCR and transformed directly into yeast. Gene-specific sequence was incorporated into the PCR primers, such that the tag-cassette integrates by homologous recombination at the 3'-end of the gene of interest. This technique was used to tag Cdc3 and Tub1 with GFP, YFP and CFP, which were readily visualized by fluorescence microscopy and localized as expected. In addition, Tub1-YFP and Cdc3-CFP were visualized in the same cells. Thus, this technique directs one-step construction of multiple fluorescent protein fusions, facilitating the study of protein co-expression and co-localization in C. albicans cells in vivo.

Bacterial Proteins↗
PubMed2001

Serum cholesterol, suicidal behavior and impulsivity in cocaine-dependent patients.

Relationships between serum cholesterol and suicidal behavior have been reported. As suicidal behavior is common in cocaine dependence, we looked for a relationship with serum cholesterol. To do this, we compared 57 cocaine-dependent patients who had attempted suicide with 111 cocaine-dependent patients who had never attempted suicide for their admission total serum cholesterol levels. We found that there were no significant differences between cocaine-dependent patients who had or had not attempted suicide in their total serum cholesterol levels. Also, there were no significant correlations between total serum cholesterol levels and scores on the Barratt Impulsivity Scale. Thus, admission total serum cholesterol does not appear to be clinically useful in the assessment of suicidal behavior in cocaine-dependent patients.

Adult↗
PubMed2001

Cholesterol and serotonin indices in depressed and suicidal patients.

BACKGROUND: Prolactin and cortisol responses to d-fenfluramine challenge of central serotonin are reduced in depressed and suicidal patients. Low serum cholesterol levels are also reported in suicidal behavior. Thus, we examined for a relationship between serum cholesterol and fenfluramine challenge responses in patients with depression and/or attempted suicide. METHODS: We studied 12 patients and six controls. Blood was drawn for baseline serum cholesterol and the d-fenfluramine challenge test performed. RESULTS: Serum cholesterol levels were significantly lower in suicidal patients than in either non-suicidal patients or controls. However, neither the prolactin nor cortisol responses to d-fenfluramine correlated significantly with serum cholesterol levels. CONCLUSION: No relationship was found between serum cholesterol and these peripheral indices of serotonergic function.

Adult↗
PubMed2001

Hypoglycaemia caused by secretion of insulin-like growth factor 2 in a primary renal cell carcinoma.

Non-islet cell tumour hypoplycaemia (NICTH) due to the production of an aberrant form of insulin-like growth factor 2 (IGF 2) is a well-recognised phenomenon. This is the first formally reported case occurring in an adult with a primary renal cell carcinoma. This case report describes in detail the various treatment modalities that were used in an attempt to palliate this patient's severe hypoglycaemia.

Carcinoma, Renal Cell↗
PubMed2001

Gastrointestinal stromal tumor workshop.

Gastrointestinal stromal tumor (GIST) has emerged in the past year as a prototypical neoplasm that responds to therapy directed against a single target molecule-the KIT receptor tyrosine kinase protein. Although GIST seldom responds to conventional chemotherapeutic agents, early experience with the tyrosine kinase inhibitor, STI-571 (Gleevec; Novartis, Basel, Switzerland), has been extremely encouraging. Early results have appeared in a recent case report in the New England Journal of Medicine (April 5, 2001),(1) and in early clinical trials from the United States and Europe that were reported at the plenary session of the American Society of Clinical Oncology in San Francisco on May 14, 2001. STI-571 is one of the earliest examples of a nontoxic chemotherapeutic agent (an agent whose anti-cancer activity is not predicated on a cytotoxic mechanism). STI-571 has already shown clinical value in BCR-ABL-positive leukemias. Early clinical results in GIST are so encouraging that oncologists may soon be wrestling with the opportunity of referring every patient with malignant GIST into clinical trials with STI-571. To ensure appropriate treatment, pathologists need to understand the biology and treatment of this tumor and to have standard methods and criteria for providing diagnosis (GIST or not GIST) and consistent prognostic classification (high risk of metastasis or low risk of metastasis).

Benzamides↗
PubMed2001

Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells.

The ability to switch between yeast and hyphal morphologies is an important virulence factor for the opportunistic pathogen Candida albicans. Although the kinetics of appearance of the filamentous ring that forms at the incipient septum differ in yeast and cells forming hyphae (germ tubes) (), the molecular mechanisms that regulate this difference are not known. Int1p, a C. albicans gene product with similarity in its C terminus to Saccharomyces cerevisiae Bud4p, has a role in hyphal morphogenesis. Here we report that in S. cerevisiae, Int1p expression results in the growth of highly polarized cells with delocalized chitin and defects in cytokinesis and bud-site selection patterns, phenotypes that are also seen in S. cerevisiae septin mutant strains. Expression of high levels of Int1p in S. cerevisiae generated elaborate spiral-like structures at the periphery of the polarized cells that contained septins and Int1p. In addition, Int1p coimmunoprecipitated with the Cdc11p and Cdc12p septins, and Cdc12p is required for the establishment and maintenance of these Int1p/septin spirals. Although Swe1p kinase contributes to INT1-induced filamentous growth in S. cerevisiae, it is not required for the formation of ectopic Int1p/septin structures. In C. albicans, Int1p was important for the axial budding pattern and colocalized with Cdc3p septin in a ring at the mother-bud neck of yeast and pseudohyphal cells. Under conditions that induce hyphae, both Cdc3p and Int1p localized to a ring distal to the junction of the mother cell and germ tube. Thus, placement of the Int1p/septin ring with respect to the mother-daughter cell junction distinguishes yeast/pseudohyphal growth from hyphal growth in C. albicans.

Candida albicans↗
PubMed2001

Candida albicans INT1-induced filamentation in Saccharomyces cerevisiae depends on Sla2p.

The Candida albicans INT1 gene is important for hyphal morphogenesis, adherence, and virulence (C. Gale, C. Bendel, M. McClellan, M. Hauser, J. M. Becker, J. Berman, and M. Hostetter, Science 279:1355-1358, 1998). The ability to switch between yeast and hyphal morphologies is an important virulence factor in this fungal pathogen. When INT1 is expressed in Saccharomyces cerevisiae, cells grow with a filamentous morphology that we exploited to gain insights into how C. albicans regulates hyphal growth. In S. cerevisiae, INT1-induced filamentous growth was affected by a small subset of actin mutations and a limited set of actin-interacting proteins including Sla2p, an S. cerevisiae protein with similarity in its C terminus to mouse talin. Interestingly, while SLA2 was required for INT1-induced filamentous growth, it was not required for polarized growth in response to several other conditions, suggesting that Sla2p is not required for polarized growth per se. The morphogenesis checkpoint, mediated by Swe1p, contributes to INT1-induced filamentous growth; however, epistasis analysis suggests that Sla2p and Swe1p contribute to INT1-induced filamentous growth through independent pathways. The C. albicans SLA2 homolog (CaSLA2) complements S. cerevisiae sla2Delta mutants for growth at 37 degrees C and INT1-induced filamentous growth. Furthermore, in a C. albicans Casla2/Casla2 strain, hyphal growth did not occur in response to either nutrient deprivation or to potent stimuli, such as mammalian serum. Thus, through analysis of INT1-induced filamentous growth in S. cerevisiae, we have identified a C. albicans gene, SLA2, that is required for hyphal growth in C. albicans.

Actins↗
PubMed2001

CAC3(MSI1) suppression of RAS2(G19V) is independent of chromatin assembly factor I and mediated by NPR1.

Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF-I), a complex that assembles histones H3 and H4 onto replicated DNA. CAC3 overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction pathway by an unknown mechanism. We investigated this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function. CAC3 suppression was also independent of other chromatin-modifying activities, indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient transporters by antagonizing a ubiquitin-mediated protein degradation pathway. Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway. Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway by sequestering Npr1p. Deletion of NPR1 did not affect the quantity, phosphorylation state, or localization of Ras2p. Consistent with the idea that Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin-mediated process, excess ubiquitin suppressed both the heat shock sensitivity and the sporulation defects caused by constitutive activation of the RAS/cAMP pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin-independent mechanism that involves the sequestration of Npr1p and may be due to the increased ubiquitination of an Npr1p substrate.

Alleles↗