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Biomedical subjects

M Lahav

Publications and source records attributed to M Lahav.

At least 19 recordsLinked to original sources

Formation of Chiral Interdigitated Multilayers at the Air-Liquid Interface Through Acid-Base Interactions

Thin interdigitated films composed of a long-chain, water-insoluble chiral acid (p-pentadecylmandelic acid of absolute configuration R) and a water-soluble chiral base (phenylethylamine, R') were constructed at the air-solution interface. The (R, R') structure was characterized to near-atomic resolution by grazing-incidence x-ray diffraction (GIXD). The two diastereomeric systems, (R, R') and (R, S'), demonstrate similar surface pressure-molecular area isotherms, but their structures are completely different on the molecular level, as monitored by GIXD. Complementary data on these two architectures were provided by atomic force microscopy.

Journal Article

Severe myelotoxicity of oral etoposide in heavily pretreated patients with non-Hodgkin's lymphoma or chronic lymphatic leukemia.

BACKGROUND: Promising results have been reported for patients with non-Hodgkin's lymphoma (NHL) receiving chronic oral etoposide. Due to the small number of patients reported, information regarding side effects is limited, and therefore warrants further evaluation. METHODS: Twenty eligible patients with NHL and chronic lymphatic leukemia (CLL), resistant to or relapsed after previous protocols of polychemotherapy were treated with oral etoposide at a dosage of 50 mg/m2/day for 21 days in a 28-day cycle. Response and toxicity were evaluated according to standard criteria. RESULTS: Total response was noted in 13 patients, complete response in 2 patients, and partial response in 11 patients. Two patients had stable disease and five patients had progression of disease during treatment. Seventy-five percent of patients experienced neutropenia below 1500/microL. Half acquired infection and required hospitalization. Fifty-five percent required blood transfusions. All patients needed course shortening and dosage reduction. CONCLUSIONS: Chronic daily administration of oral etoposide is effective in patients with NHL and CLL. In heavily pretreated patients, myelotoxicity is severe. Therefore, modification of the schedule plan is mandatory in this group of patients.

Adult

Paradoxical effect of 3-isobutyl-1-methylxanthine on cytochrome P450 cholesterol side-chain cleavage mRNA accumulation in porcine granulosa cells.

Earlier studies in immature porcine granulosa cells cultured in serum-free medium showed dual actions of the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In cells incubated for 24 h, TPA inhibited follicle-stimulating hormone (FSH)-stimulated cytochrome P450 cholesterol side-chain cleavage (P450scc) mRNA accumulation. In contrast, at 4 h, TPA increased P450scc mRNA concentration in the absence and presence of FSH or 8-bromo-cAMP; in addition, TPA augmented FSH-stimulated cAMP accumulation. The actions of TPA were then examined in the presence of the phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). With IBMX present, TPA caused a smaller relative augmentation of cAMP accumulation during a 4-h incubation period, suggesting that TPA may both increase cAMP synthesis and inhibit its degradation. The stimulatory effect of FSH or 8-bromo-cAMP on P450scc mRNA concentration was not modified by IBMX. However, TPA no longer augmented the FSH- or 8-bromo-cAMP-stimulated P450scc mRNA accumulation when IBMX was present. In cells treated with FSH for 24 h, IBMX augmented progesterone production, but paradoxically accentuated the inhibitory effect of TPA on steroidogenesis. These results indicate that IBMX converts TPA from a stimulatory into an inhibitory agent by an action unrelated to cAMP, and points to the need for caution in interpreting experiments with this drug.

1-Methyl-3-isobutylxanthine

Ocular toxicity following topical application of anesthetic cream to the eyelid skin.

BACKGROUND AND OBJECTIVE: The use of topical anesthetic cream in the periorbital region may be of clinical value. The potential for toxic effects from such use has not been studied in a controlled manner. This study was performed to evaluate the potential ocular toxicity of anesthetic cream topically applied to the eyelid in an animal model. MATERIALS AND METHODS: Ten rabbits underwent periorbital eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5 percent prilocaine) application and were observed for evidence of gross or microscopic ocular toxicity. Baseline external and anterior segment examinations were performed, including biomicroscopy and fluorescein staining, after which a standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and covered with an occlusive dressing. After 1 hour of treatment, the eyelid and anterior segment were examined for evidence of adverse reaction. The eyelids were excised and examined histopathologically. RESULTS: No significant adverse effects were noted on external lid and anterior segment examination. The histopathologic findings were within normal limits. CONCLUSIONS: This study suggests that external application of EMLA cream to the eyelid does not induce local toxicity in the rabbit model. The external application of EMLA cream may be safe in the periorbital region.

Administration, Topical

Combined dacryops with underlying benign mixed cell tumor of the lacrimal gland.

PURPOSE/METHODS: Computed tomographic scan disclosed a well-defined mass in the right lacrimal fossa of a 57-year-old woman. We excised and examined the mass. RESULTS/CONCLUSIONS: The mass was a combination of a small benign mixed cell tumor and a large ductal cyst of the lacrimal gland. It is possible that a cyst in the lacrimal duct may mask an underlying neoplasm of the lacrimal gland.

Adenoma, Pleomorphic

Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile.

Animals

Dual actions of phorbol ester on cytochrome P450 cholesterol side-chain cleavage messenger ribonucleic acid accumulation in porcine granulosa cells.

In earlier studies in cultures of porcine granulosa cells prepared from small antral follicles, steroidogenesis-related loci were inhibited by treatment for 48 h with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC). In the present investigation, cells were incubated in serum-free medium for 48 h, with various agents present during the last 2-24 h. With TPA at 30 ng/ml, the FSH-stimulated cAMP accumulation was markedly enhanced at all time points. FSH increased the concentration of cytochrome P450 cholesterol side-chain cleavage (P450scc) mRNA throughout the 24-h incubation. At 4 and 8 h, TPA increased the accumulation of P450scc mRNA, having an additive effect with FSH. However, at 24 h, TPA markedly suppressed the FSH-induced increased in P450scc mRNA. Pretreatment of cells with FSH did not shorten the time required for TPA to become inhibitory. The stimulatory effect of 8-bromo-cAMP on P450scc mRNA also was augmented by TPA at 4 h, but significant inhibition was not observed at 24 h. The concentration of glyceraldehyde-3-phosphate dehydrogenase mRNA, intended to be used for correction of gel loading, was stably increased by both cAMP and TPA. These effects of TPA suggest multiple actions of PKC(s) on the regulation of P450scc expression and other endpoints in ovarian granulosa cells.

8-Bromo Cyclic Adenosine Monophosphate

Interferon alpha-2b modulates beta-galactoside alpha-2,6-sialyltransferase gene expression in rat testes.

Sperm surface glycoproteins are modified during passage through the epididymis, a process believed to be important in the production of functionally mature spermatozoa. The effect of various cytokines on reproductive events has recently been investigated, with conflicting results. In the present investigation, the effect of interferon-alpha-2b (IFN alpha 2b) on sialyltransferase (ST) activity and beta-galactoside alpha-2,6-sialyltransferase (Gal 2,6-ST) mRNA expression was studied in rat testicular tissue. The results revealed the presence of Gal 2,6-ST mRNA in rat testicular tissue, similar in molecular size to that found previously in rat spleen, lung, ovary, kidney, heart, and brain. In addition, we observed that IFN alpha 2b reduced Gal 2,6-ST mRNA and ST activity in rat testes by a comparable magnitude. These findings provide insight into an additional mechanism by which cytokines may affect the reproductive system.

Animals

The role of crystal polarity in alpha-amino acid crystals for induced nucleation of ice.

The hydrophobic faces of single crystals of a series of pairs of racemic and chiral-resolved hydrophobic alpha-amino acids were used as a substrate, onto which water vapor has been cooled to freezing. The morphologies and molecular packing arrangements within each crystal pair are similar but only one of each pair exhibits a polar axis, parallel to the hydrophobic face exposed to water. Those crystals that have a polar axis induce a freezing point higher by 4 degrees to 5 degrees C than the corresponding crystals that do not have a polar axis. The results are interpreted in terms of an electric field mechanism that helps align the water molecules into ice-like clusters en route to crystallization.

Amino Acids

Life threatening hypophosphataemia in a patient with Philadelphia chromosome-positive chronic myelogenous leukaemia in acute blastic crisis.

Life-threatening hypophosphataemia developed in a 47 year old woman with blastic crisis of chronic myelogenous leukaemia. The patient's hospitalization was characterized by reciprocal relationship between her white cell count and the serum phosphorus levels. The patient did not demonstrate any of the usual causes of profound hypophosphataemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing leukaemic cells. To the best of our knowledge this is the first case in the English literature of hypophosphataemia associated with blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia.

Blast Crisis

Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure.

Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure.

Aged

Immunologic abnormalities associated with primary anetoderma.

BACKGROUND AND DESIGN: Primary anetoderma is a rare cutaneous elastolytic disorder, the etiopathogenesis of which has not yet been established. Six patients with primary anetoderma were studied in an attempt to assess the role of the immunologic system in the elastolytic process. The investigation included the medical history, physical examination, routine blood tests, specific tests for collagen diseases, prothrombin time, activated partial thromboplastin time, thyroxine, indirect immunofluorescence test, and skin biopsies for histopathologic study and direct immunofluorescence. RESULTS: Two of the patients presented with autoimmune disorders: the first had Graves' disease, lupus anticoagulant, and autoimmune hemolysis, and the second had systemic scleroderma. There were positive direct immunofluorescence findings in most of the patients. Furthermore, all of them were found to have serologic immunologic abnormalities, of which the most common was a positive antinuclear factor. CONCLUSIONS: These findings indicate that there is an immunologic involvement in primary anetoderma.

Adult

Primary anetoderma associated with a wide spectrum of autoimmune abnormalities.

Although the underlying pathologic mechanisms of primary anetoderma have not yet been identified, data suggest the participation of an immunologic mechanism in some cases. In a woman with clinical and histopathologic features of primary anetoderma (Jadassohn-Pellizzari type) of 30 years' duration, laboratory investigation disclosed positive antinuclear factor, hypocomplementemia, hypergammaglobulinemia, granular deposits of immunoreactants along the dermoepidermal junction, and fibrillar deposits in the papillary dermis. In addition, she was found to have autoimmune hemolysis and circulating lupus anticoagulant associated with recurrent deep-vein thrombosis and a history of Graves' disease (starting 5 years after onset of primary anetoderma). To our knowledge, none of the latter three autoimmune conditions has been previously associated with primary anetoderma.

Antibodies, Antinuclear

Image analysis of changes in drusen area.

Computerized image processing was used to analyze color fundus photographs of 11 patients (22 eyes) with macular drusen who were followed for more than 2 years (mean follow-up, 4.7 years). Significant changes over time (more than +/- 20% of baseline area) were measured in the surface area of macular drusen in 18 of 22 (82%) eyes. An increase in the drusen area was associated significantly with eyes with mostly hard drusen and an initially smaller drusen area; but a decrease was associated with eyes with mostly soft drusen and an initially larger drusen area (P less than 0.01). The mean absolute rate of change in the drusen area was more than twice as great in eyes with mostly soft drusen compared with those with mostly hard drusen (P less than 0.05). All eye pairs studied showed a concomitant increase or decrease in the drusen area.

Aged