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Biomedical subjects

S Halpern

Publications and source records attributed to S Halpern.

At least 37 records · Page 2Linked to original sources
PubMed1994

Preliminary report: cerebral blood flow abnormalities in older schizophrenic patients.

We compared global and regional cerebral blood flow in 11 schizophrenic patients and 11 normal comparison subjects, all over the age of 45 years. The schizophrenic patients had lower global cortical uptake than the control subjects. Among the individual regions of interest, the schizophrenic patients had significant decrements in the left posterior frontal region and in the bilateral inferior temporal regions. The uptake did not correlate with age of onset or duration of schizophrenia, current daily neuroleptic dose, severity of psychopathology, or global cognitive impairment.

Age of Onset↗
PubMed1994

Recent developments in medical applications of SIMS microscopy.

The purpose of this review is to present the recent developments in the medical applications of SIMS microscopy. This technique is one of the microanalytical mass spectrometry methods which allow in theory the detection of all the elements of the Mendeleiev table as well as the separation of stable and radioactive isotopes. It is based on a phenomenon whereby a biological sample surface is sputtered by bombardment with an energetic 'primary ion' beam. Part of the sputtered matter is ionized and the resulting 'secondary ions' are characteristic of the atomic composition of the analyzed area. These secondary positive or negative ions are collected and separated in a mass spectrometer at low or high mass resolution, which is dependent on both the element studied and its concentration. An analytic image which conserves the tissue distribution of the selected element is displayed on a fluorescent screen linked to an image processing system. Local elemental concentration can also be measured. Results are highly dependent on the techniques used for sample preparation which should preserve both the chemical and the structural integrity of the tissue. Further, the ionic images must be correlated with corresponding images of the same areas of the serial sections observed in a photonic microscope. With our SIMS microscope (lateral resolution approximately 0.5 microns, and mass resolution 300 to 12,000) we have demonstrated that this microscopic imaging technique is suitable for physiopathological studies. We revisited thyroid iodine metabolism by mapping chemical elements such as 32S and 127I, characteristic of hormonal physiology. Newly organified iodine (radioiodine) can be evaluated in relation to previously stored iodine (127I) in a given follicle, thus allowing an appraisal of glandular adaptation to aging and iodine overload. Another area in which SIMS can be used in medicine, is for the localization of drug markers in tumor tissue (e.g. fluorine-5-fluouracil, iodine in iododeoxyrubicin). This could facilitate the evaluation of the intratumor drug concentration at the onset of the treatment. Likewise, SIMS can be used to localize radiopharmaceuticals used in diagnosis (e.g. technetium) and therapy (131I of metaiodobenzylguanidine). This would permit a better evaluation of the radiation dose delivered to tissue. Further prospects are within reach with the imminent advent of higher lateral resolution (0.05 microns) SIMS microscopes.

3-Iodobenzylguanidine↗
PubMed1994

Postdural puncture headache and spinal needle design. Metaanalyses.

BACKGROUND: Attempts have been made to reduce the incidence of postdural puncture headache (PDPH) after spinal anesthesia by changing the size and design of the needle. We wished to determine whether these strategies are effective in reducing PDPH and whether they affect the incidence of back pain and the failure rate of spinal anesthesia. METHODS: The literature was searched for trials comparing noncutting spinal needles with cutting needles and larger spinal needles with smaller needles. Trials were included if they were randomized or blinded and if outcomes included PDPH, backache, or failure of the method. The pooled odds ratio for each side effect was computed, and the results were considered statistically significant if the 95% confidence interval excluded 1. RESULTS: Four hundred fifty articles were identified by title using computerized search strategies. Thirty-one abstracts, 25 correspondences, 44 original articles, and 12 reviews were assessed. There was a reduction in the incidence of PDPH when noncutting spinal needles rather than cutting needles were used (P < 0.05), unless the discrepancy in needle size was very large. There also was a reduction in PDPH when a small spinal needle was used compared with a large needle of the same type (P < 0.05). There was no difference in the incidence of failure of spinal anesthesia or the incidence of back pain. CONCLUSIONS: We conclude that a noncutting needle should be used for patients at high risk for PDPH, and the smallest gauge needle available should be used for all patients.

Anesthesia, Spinal↗
PubMed1994

Non-covalent antibody-mediated drug delivery.

High background activity produces imaging problems when scanning with antibodies. The following work is directed towards reducing this background. The murine monoclonal antibody (MAb) CHA-255 selectively binds 111In-nitrobenzyl EDTA, a molecule referred to as a 'hapten'. Balb/c mice studies indicate that if the antibody is administered prior to the hapten, it predictably modifies the biodistribution and pharmacokinetics of the hapten. The pharmacokinetics for the hapten were proportional to antibody dose and inversely proportional to the time interval between injection of the antibody and the hapten. A hybrid MAb was produced by the enzymatic digestion of CHA-255 and ZCE-025, an anticarcinoembryonic antigen (CEA) MAb, followed by joining of the two via a thioether linkage. The result was a F(ab')2 with affinity for both CEA and the hapten. The pharmacokinetics of the hapten were again dependent upon the kinetics and distribution of the hybrid antibody. Data in tumour models are also presented for 111In-nitrobenzyl EDTA and 111In-thioureabenzyl EDTA (TUBE), a newer hapten. The data indicate that the antibody-hapten system is capable of targeting tumour quickly while normal tissue rapidly becomes depleted of radioactivity. We conclude that the hapten-antibody technique shows some advantages over directly labelled MAb as a targeting system.

Animals↗
PubMed1994

Lichen sclerosus and the Köbner phenomenon.

Two patients with lichen sclerosus (et atrophicus) are described in whom there was conspicuous localization of lesions to sites subjected to friction from tight clothing. This was highly suggestive of the Köbner phenomenon. Both patients experienced symptomatic improvement following avoidance of pressure on the skin from tight clothing.

Clothing↗
PubMed1994

HIV infection in the parturient.

As the incidence of AIDS continues to increase in the female population, there will be more cases of HIV-positive women in the obstetric suite requiring anesthesia services. Many may be asymptomatic, but there will be patients with active opportunistic infections and malignancies who may or may not have been treated. The impact of both the disease AIDS and the drugs used to treat it on anesthetic technique can be significant. Hematological, neurological, respiratory, and immune dysfunction can be expected in a significant proportion of these women. Universal precautions should be utilized for all deliveries regardless of known HIV status. The ubiquitous presence of blood and amniotic fluid during labor and delivery mandate the use of gloves, gowns, and eye protection in the obstetric suite to avoid transmission of HIV to health care workers. Transmission to the newborn during delivery can be minimized by avoidance of skin and mucous membrane trauma and careful removal of secretions and blood. Infected parturients should be carefully assessed for neurological and hematological dysfunction prior to the use of regional anesthesia, and anesthesiologists must be aware of the potential toxicities of therapeutic drug treatment and their impact on anesthesia.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A comparison of two doses of epidural fentanyl during caesarean section.

A prospective, randomized, double-blind study was performed to compare the analgesic efficacy and side effects of epidural fentanyl, 25 micrograms vs 50 micrograms, when used to supplement epidural anaesthesia for elective Caesarean section. Fifty ASA I and II patients were randomized into two groups: Group I (n = 24) received 25 micrograms and Group II (n = 26) received 50 micrograms of epidural fentanyl after the epidural test dose. No differences between the two groups were found on any measures of intraoperative pain, nausea, drowsiness, respiratory depression, hypotension, pruritus and neonatal outcome. The low levels of pain experienced by patients indicates that doses higher than 50 micrograms of epidural fentanyl are usually unnecessary for optimal analgesia.

Adult↗
PubMed1993

Detection on liver tissue sections of S-phase markers in synchronized cycling rat hepatocytes by SIMS microscopy.

The aim of this study was to localise two ionic S-phase markers in tissue sections using SIMS microscopy: aluminium as a potential endogenous marker and bromine as an exogenous marker after in vivo injection of bromodeoxyuridine (BrdU). This study was performed in an experimental model of hyperplastic proliferation after partial hepatectomy in rat. Aluminium was never detected in nuclei which were positive or negative for tritiated thymidine uptake, as determined by autoradiography in tissue prepared by cryotechniques. In contrast, bromine of BrdU was found in hepatocyte nuclei. However, there was a discrepancy between SIMS bromine images and BrdU immunohistochemistry detection which appears more sensitive. This is probably due to problems of stereology intrinsic to the correlation method which requires serial sections for this multi-instrumental approach.

Aluminum↗
PubMed1993

SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier-free.

3-Iodobenzylguanidine↗
PubMed1992

Quantitative mapping of 4'-iododeoxyrubicin in metastatic squamous cellcarcinoma by secondary ion mass spectrometry (SIMS) microscopy.

Secondary ion mass spectrometry microscopy enables quantitative mapping of chemical elements in tissue sections. It was used for the detection of 127I contained in 4'-iododeoxyrubicin (IDX). Metastatic cutaneous squamous cell carcinoma from 7 patients participating in a phase I study (IDX dose, 80 mg/m2, 10-min i.v. infusion) were biopsied 10 min after drug administration and compared to 3 controls who did not receive any treatment (one squamous cell carcinoma and 2 gastric carcinomas). Biopsy specimens were fixed and embedded in methacrylate resin. Then, serial semithin sections (3 microns) were analyzed simultaneously with ionic and optimal microscopes in order to identify the histological structures given by the 31P distribution in which 127I in IDX was mapped. The iodine signal was undetected in controls and found mainly in the nuclei of tumor cells of the treated patients. Its concentration, measured in at least 30 nuclei of each specimen, was undetectable in 8% of the nuclei and 91% of them were within 1 and 16 ng/mg. The mean concentration of each specimen ranged from 5 to 23 ng/mg. This study demonstrates the capacity of ion microscopy to localize a cytotoxic drug (IDX) in a human biopsy specimen without the need for radioactive labeling and enables the evaluation of drug penetration in cancer cells which is critical for its activity.

Carcinoma, Squamous Cell↗
PubMed1992

Epidural anaesthesia for caesarean section in an achondroplastic dwarf.

This report describes the anaesthetic management of an 18-yr-old achondroplastic dwarf who presented for elective Caesarean section. Epidural anaesthesia was performed without technical difficulty using 8 ml carbonated lidocaine 2% with epinephrine 1:200,000. Although the skeletal abnormalities of achondroplasia have been cited as contraindications to the use of epidural anaesthesia, clinical experience does not support this contention. Previous reports have described technical difficulties in these patients, such as dural puncture and inability to advance the catheter into the epidural space, but no serious complications resulted and epidural anaesthesia was successful on subsequent attempts. The existing literature on the anaesthetic management of achondroplasia for Caesarean section is reviewed and considerations are presented concerning the choice of local anaesthetic, the epidural test dose, and dose titration.

Achondroplasia↗
PubMed1992

SIMS microscopy in the biomedical field.

We attempted to indicate the requirements for biomedical applications of SIMS microscopy. Sample preparation methodology should preserve both the structural and the chemical integrity of the tissue. Furthermore, it is often necessary to correlate ionic and light microscope images. This implies a common methodological approach to sample preparation for both microscopes. The use of low or high mass resolution depends on the elements studied and their concentrations. To improve the acquisition and processing of images, digital imaging systems have to be designed and require both ionic and optical image superimposition. However, the images do not accurately reflect element concentration; a relative quantitative approach is possible by measuring secondary ion beam intensity. Using an internal reference element (carbon) and standard curves the results are expressed in micrograms/mg of tissue. Despite their limited lateral resolution (0.5 microns) the actual SIMS microscopes are very suitable for the resolution of biomedical problems posed by action modes and drug localization in human pathology. SIMS microscopy should provide a new tool for metabolic radiotherapy by facilitating dose evaluation. The advent of high lateral resolution SIMS imaging (less than 0.1 microns) should open up new fields in biomedical investigation.

Animals↗
PubMed1992

Significance of SIMS microscopy for the radioiodine detection in animal and human thyroid tissue.

We defined the SIMS conditions for radioiodine detection in animal and man thyroid follicles, in tissue sections (3 microns) chemically fixed and resin embedded. Two radioisotopes were tested: 125I and 129I, of high (14 mCi 125I micrograms-1) and low specific activity (1.07 10(-6) mCi 129I micrograms-1). In animal study, Wistar rats fed a normal iodine diet (10 micrograms 127I day-1) were injected ip 24 h before sacrifice either with 125I (7 10(-3) micrograms) or with 129I at a dose identical to iodine diet (10 micrograms) or 3 times higher (30 micrograms). No SIMS signal of 125I was obtained in vivo due to its too low concentration, while radioiodine distribution was evidenced with both doses of 129I. Local concentration of previously stored 127I in follicular lumen was not modified, when compared to control (4.14 +/- 0.03 micrograms/mg, m +/- SE), by 125I or 129I at a dose of 10 micrograms, but was nearly doubled with 129I at a dose of 30 micrograms, proof of a pharmacological effect on thyroid iodine regulation. In human study 129I was excluded due to its long half-life (1.6 10(7) years), and 125I was tested only in vitro on two surgical specimens of normal perinodular thyroid tissue maintained in mini-organ culture for 48 h in presence of 100 microCi/ml of 125I. The 125I was detectable, its concentration was 1,000-fold higher than that of 127I (1.5 +/- 0.004 micrograms/mg). For both in vivo and in vitro studies, a positive correlation exists between newly organified radioiodine (125I or 129I) and previously stored iodine (127I).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Direct evaluation of thyroid I-127 in an iodine overload situation: in vivo study by X-ray fluorescence and in vitro by analytical ion microscopy].

This review describes the two methods which allow direct estimation of stable iodine (127I) within thyroid gland either in vivo by X-ray fluorescence or in vitro by secondary ion mass spectrometry (SIMS) microscopy on tissue section. Although the measurement of thyroid iodine content (TIC) by X-ray fluorescence has little relevance for routine explorations of thyroid function, this is a valuable method for understanding complex pathophysiological conditions such as the thyroid adaptation to iodine overload. On the other hand, SIMS microscopy which is able to characterize the functional activity of thyroid tissue by measuring 127I concentration within the thyroid follicles, can be used to determine the extent to which exogenous iodine affects the regulation of iodine within the thyroid follicles. Both methods were used to evaluate the quantitative changes in thyroid 127I induced by amiodarone iodine overload. TIC measurements shows that hyperthyroidism occurred only in patients who increased their iodine stores, while the patients who developed hypothyroidism had low iodine stores. The SIMS microscopy data obtained in mice demonstrated that the thyroid response to amiodarone is related to dietary iodine intake leading to an increase in local iodine concentration in iodine deficient mice and to a decrease in iodine supplemented mice. This response is specific and different from that induced by an iodide overload. These results could explain that hyperthyroidism with high thyroid iodine content occurred in areas with low thyroid iodine intake and hypothyroidism with low thyroid iodine content in areas with a supplemented iodine diet.

Amiodarone↗
PubMed1992

Significance of secondary ion mass spectrometry microscopy for technetium-99m mapping in leukocytes.

Secondary ion mass spectrometry (SIMS) microscopy is the only method potentially capable of mapping all the elements in the periodic table including stable and radioactive isotopes. We used this method to study 99mTc distribution by detecting and localizing of 99Tc, a daughter product which has the same mass and the same chemical properties. It was combined with albumin macroaggregates or with Hexamethylpropylene-amine oxime (HMPAO) in leukocytes. The efficiency of 99Tc ionization under Cs+ bombardment was higher than with an O2+ beam. By using high mass resolution we succeeded in detecting and localizing 99Tc in cell sections by eliminating polyatomic ions that arise from this biological matrix. The 99Tc specific signal was obtained with a mass resolution of 2000 for labeled albumin macroaggregates, and 5000 for HMPAO-labeled leukocytes. In the latter, the labeling varied from one cell to another and 99Tc was present in both the nucleus and the cytoplasm. The results indicate that SIMS microscopy can provide new insights into 99mTc dosimetry.

Humans↗