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Biomedical subjects

H Sussman

Publications and source records attributed to H Sussman.

At least 19 recordsLinked to original sources

[Vascular exploration of erectile dysfunction].

INTRODUCTION: Since its development echo-Doppler investigation has become the mainstay in the diagnosis of vascular impotence. This paper reviews its present use. METHOD: Personal experience and a review of the literature form the basis of a critical analysis of this investigation. RESULTS: The standardised technique proposed by the AA for the echo-Doppler investigation of impotence includes: Doppler examination of the dorsal and deep arteries of the penis; a pharmacological test with volume measurements and direct examination of the penile arteries by pulsed echo-Doppler. Future developments will allow venous exploration (of the deep vein of the penis); power Doppler examination of the 2nd and 3rd degree arteries of the penis. CONCLUSIONS: There is no present consensus. The arterial inflow, caverno-venous retention and overall size of the erection, can be quantified.

Alprostadil↗

[Exploration of the deep dorsal vein of the penis using pulsed Doppler ultrasonography. Preliminary study].

OBJECTIVES AND METHODS: This was an open preliminary study of 36 unselected men suffering from erectile dysfunction (DE) for the evaluation of the deep dorsal vein of the penis (VDP) by duplex scan (EDP). All men had an intravenous injection (IIC) with a vaso active agent: alprostadil (Edex) (n = 24), a mixture of papaverine ifenprodyl tartrate (Vadilex) (n = 4) or papaverine, ifenprodyl tartrate and alprostadil (n = 7). The deep dorsal vein was evaluated, with a 13 mHz mechanical probe 5 and 10 minutes after the injection, during visual sexual stimulation (SSV) carried on for 10 mn, and 3 mn after having stopped SSV. The influence of deep breathing and contraction of the ischio and bulbo-cavernous muscles was recorded at each of the periods. RESULTS: The deep dorsal vein was identified in all cases. After pharmacological stimulation flow was present in 61% of the cases, with a statistically significant difference between alprostadil (80%) and both mixtures (20%). The addition of sexual stimulation caused flow to disappear in 64% of the cases (91% for the mixture and 44% for alprostadil). There was a range of variation under breathing and muscular contraction which deserves further evaluation. CONCLUSIONS: 1) The deep dorsal vein is easily studied under duplex scan and should be part of the routine examination of the vascular component of erection during erectile dysfunction. 2) The vein is subjected to modification of flow after intracavernous injection and sexual stimulation which varies with the agent injected and the clinical condition of the patients. 3) Absent flow early after injection seems to be predictive of the possibility of a prolonged erection.

Adult↗

[Vascular and functional evaluation of erectile dysfunctions using erection provocation tests].

The provoked erection test (TEP) consists in exploring successively, the sexual arteries, the penile volume and rigidity charges after pharmacological and sexual visual stimulation. Quantified arteria were proposed to evaluate the arterial flow and the caverno venous component obtained though a global appraisal of the erectile function. From these, TEP allows a quick approach to the diagnosis of erectile dysfunction for an early therapeutic decision.

Alprostadil↗

Cross-linking hybridization assay for direct detection of factor V Leiden mutation.

A nucleic acid photocross-linking technology was used in the development of a direct assay for factor V Leiden, a point mutation in the factor V gene (G1691A) that is the most common inherited risk factor for thrombosis. This cross-linking hybridization assay included two allele-specific capture probes and six signal-generating reporter probes; all were modified with a photoactivated cross-linking compound. By using two different capture probes complementary to a 16-base sequence at the factor V Leiden mutation site, but differing in the nucleotide opposite the mutation site (C vs T), wild-type and factor V Leiden alleles were differentiated in purified DNA specimens. The assay was also successfully applied to genomic DNA in leukocytes isolated from whole blood; the factor V status of 122 patients as determined by this method was in complete concordance with a standard PCR-based assay and clearly discriminated between healthy individuals and factor V Leiden heterozygotes.

Alleles↗

Massive cisplatin overdose by accidental substitution for carboplatin. Toxicity and management.

BACKGROUND: Unlike the related drug carboplatin, cisplatin is highly nephrotoxic and must be given with vigorous intravenous hydration at a much lower dose. As the result of an accidental substitution of cisplatin for carboplatin, a 68-year-old woman received a massive overdose of cisplatin without intravenous hydration. METHODS: Laboratory documentation included measurements of platinum concentrations by atomic absorption spectroscopy and of xeroderma pigmentosum group E (XPE) binding factor, a protein that is involved in the recognition step of DNA repair. RESULTS: Toxicities included severe emesis, myelosuppression, renal failure, and deafness, which are well known. Other toxicities were seizures, hallucinations, loss of vision, and hepatic toxicity, which were unusual and may have been caused by the magnitude of the overdose. As late as day 19, there was a continued cellular response from cisplatin, as evidenced by decreased levels of XPE binding factor in extracts from the patient's peripheral blood lymphocytes. Plasmapheresis was effective in lowering the platinum concentration from greater than 2900 ng/ml to 200 ng/ml and appeared to be of clinical benefit. Even after the onset of renal failure, hydration to increase urine volume resulted in increased urinary excretion of platinum. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to ameliorate myelosuppression. The patient received a transplanted kidney from her monozygotic twin sister and survived with no clinically significant deficit except for deafness. CONCLUSION: No previous reports exist of survival after such a high dose of cisplatin without intravenous hydration. In the future, patients may benefit from similar management and heightened awareness of the possibility of accidental substitution.

Aged↗

Pathologic parameters and flow cytometric ploidy analysis in predicting recurrence in carcinoma of the prostate.

Recurrence of prostate cancer following radical prostatectomy is determined by the extent of local disease. Tumor volume and grade have improved our ability to predict extraprostatic extension, but tumors of intermediate volume and grade vary in their biologic behavior. To assess the prognostic significance of DNA ploidy, we performed flow cytometry in 85 patients with prostate cancer volumes > 4 cm3. Post-radical prostatectomy serum prostate-specific antigen was used to prove recurrence of cancer. Mean follow-up was 35 months (median 31 months). 26 patients (30%) had diploid histograms, 55 (65%) non-diploid histograms. In 4 cases (5%) the histograms were uninterpretable. Tumor volume and percent of Gleason grades 4 or 5 separated the recurrent from nonrecurrent groups in a highly significant manner (p < 0.001). When tested alone, ploidy had no ability to predict recurrence (p = 0.26). However, in a subset of patients with 4-8 cm3 of cancer with < 30% Gleason grade 4 or 5 tumor, ploidy conferred significant additional prognostic information (p < 0.005).

DNA, Neoplasm↗

Intracellular glutathione levels in T cell subsets decrease in HIV-infected individuals.

The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4+ and CD8+ T cells from HIV+ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4+ T cells, CD8+ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p less than 0.0001) and are 62% of normal in CD8+ T cells (p less than 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4+ T cells (p less than 0.003) and are 69% of normal in CD8+ T cells (p less than 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.

AIDS-Related Complex↗

A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.

Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.

Angiotensin-Converting Enzyme Inhibitors↗

A clinical and biochemical assessment of prinomide in patients with rheumatoid arthritis.

Prinomide (CGS-10787B), a potential disease modifying drug, was evaluated clinically and biochemically in 15 patients with active rheumatoid arthritis. The single group study design included monthly assessments of 7 clinical measures and 22 laboratory measures. Twelve patients completed 24 weeks' therapy with prinomide 1.2 g/day. All clinical variables showed improvement which consistently reached statistical significance for articular index from Week 8 (p less than 0.01), for summated change score from Week 12 (p less than 0.01) and for pain score from Week 16 (p less than 0.05). Sustained significant improvement in laboratory variables was seen by Week 2 for erythrocyte sedimentation rate and platelet count (both p less than 0.05), and by Week 4 for plasma viscosity (p less than 0.01), IgG, IgA, IgM (all p less than 0.05).

Aged↗

[Impotence of vascular origin].

Between 1977 and 1986, 3,500 patients were examined for the symptom of impotence; 1,250 of them received multidisciplinary investigation permitting the diagnosis of a pure organic or mixed disorder in 85% of cases, including 62% of vascular disease subdivided into arterial (40%) and venous (22%). For 1,062 patients, 1 or several of the following therapies were used: intracavernous infusion of vasoactive drugs (N = 725), auto-injections (N = 235), vascular surgery (N = 357) and prostheses (N = 23). The diagnostic approach, formerly analytical and making use of multiple non-invasive methods, such as nocturnal erection plethysmography (NPT) and invasive methods (artificial erection, arteriography) have been transformed by the use of pharmacological tests associated with visual sexual stimulation (VSS) which enable, together with Doppler velocimetric examination, simple screening of vascular impotence based on the study of 4 parameters: penile pressure index (PPI) when less than 0.91 is always a sign of an arterial problem, the severity of which is directly proportional to the lowering of this index and the association with maintenance insufficiency; the initial intracavernous flow rate (IICF) depends overall on the maintenance flow and the state of erectile tissue, resulting from pharmacological stimulation by a low dose of papaverine (8 mg); penile rigidity attained by the combined action of pharmacological and visual sexual stimulation, reflecting the functional erectile capacity; the duration of the rigidity thus obtained on stoppage of VSS indicating the capacity for maintenance of erection. In the event of suspicion of an isolated venous leak or in association with arterial problems, it is the artificial erection with cavernosography, carried out after pharmacological stimulation, which enables the severity of the leak to be assessed. The following specific investigations are carried out to investigate a specific associated etiology: electromyogram for neurological disorders, hormone assay for endocrine disorders and psychological study using the MMPI questionnaire (Multiphasic Minnesota Personality Inventory). One can thus distinguish several groups of patients suffering from vascular impotence depending on the degree of arterial involvement: minor (PPI between 0.75 and 0.9), moderate (PPI between 0.65 and 0.75) and severe (PPI less than 0.65); depending on the degree of venous leaking: absent (MI less than 0.3 and/or MF less than 25 ml/min), minor (MI between 0.3 and 0.5 and MF between 30 and 50 ml/min), moderate (MI between 0.5 and 75 ml/min) and severe (MI greater than 0.75 and/or MF greater than 75 ml/mn).(ABSTRACT TRUNCATED AT 400 WORDS)

Erectile Dysfunction↗

Modulation of the transferrin receptor during DMSO-induced differentiation in HL-60 cells.

When HL-60 cells are induced to differentiate by dimethyl sulfoxide along a granulocytic pathway there is a fivefold decrease in the total number of transferrin receptors within 3 days, as compared to untreated cells. This decrease is due primarily to a rapid decline in the synthesis of the receptor rather than an increase in the degradation of the receptor. The decrease in transferrin receptor synthesis is a specific and early event that precedes the cessation of cell proliferation, differentiation, and the decrease in total protein synthesis.

Cell Differentiation↗

Characterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity.

We characterized the alkaline phosphatase activity of the human osteogenic sarcoma cell line, SAOS-2, and studied the regulation of this enzyme and 3',5'-cyclic adenosine monophosphate levels by 1,25-dihydroxyvitamin D3 and triamcinolone acetonide. We report that the basal alkaline phosphatase activity of SAOS-2 cells was 100-1000 times greater than that of other established human osteogenic sarcoma cell lines. The enzymatic activity was thermolabile, could be inhibited by levamisole and L-homoarginine, but not by L-phenylalanine, and was immunoprecipitable with anti-bone/liver/kidney, but not with anti-placental antibody, confirming that it is the tissue-unspecific or bone/liver/kidney isoenzyme. However, in contrast to other established human osteosarcoma cell lines (TE-85, SAOS-1), in which alkaline phosphatase activity is stimulated several-fold by the steroid hormones 1,25-dihydroxyvitamin D3 and hydrocortisone, the alkaline phosphatase activity of SAOS-2 cells was not affected by 1,25-dihydroxyvitamin D3 treatment despite the presence of classical receptors for this hormone. Furthermore, administration of the potent glucocorticoid analogue, triamcinolone acetonide, induced only a modest increase in activity. The SAOS-2 cell line expressed low basal cAMP levels (28 pmol/10(6) cells) which could be increased 25-40 times by pretreatment with parathyroid hormone. However, unlike other osteoblastic models, in which PTH-induced cAMP stimulation is modulated by 1,25-dihydroxyvitamin D3 and glucocorticoids, neither of these hormones had an effect on the PTH-stimulated cAMP levels in SAOS-2 cells. We conclude that the SAOS-2 cell line is an osteoblastic cell model which expresses high levels of tissue-unspecific alkaline phosphatase activity and exhibits limited responsiveness to two steroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Compensatory articulation in Broca's aphasia.

Thirteen patients clinically diagnosed as Broca's aphasics, were administered a vowel bite block task to ascertain their on-line compensatory articulation ability. Formant frequencies for F1 and F2 were obtained from a pitch-synchronous spectral analysis of digitized vowel waveforms. Bite block/i/productions were consistently characterized by higher F1 and lower F2 frequencies compared to normal vowel productions. Undershooting of tongue elevation and fronting explains this result. No consistent pattern of "off-target" productions were found for/a/tokens. A multiple correlation analysis among clinically derived quantitative measures (BDAE score, oral and verbal apraxia), experimentally derived measures (bite block performance, articulatory reaction time), and neurological measures (brain lesion volume) was highly successful despite a relatively small sample size. Compensatory articulation was significantly related to both oral apraxia scores (r = -.70) and the BDAE total score (r = -.51). A multiple regression analysis nearly reached statistical significance (p = .11) in predicting bite block performance, with oral apraxia the most powerful predictor variable. Descriptive accounts of loci of brain lesion vis-à-vis compensatory articulation ability are given to delimit brain areas thought to possibly mediate this articulatory adaptive skill. Preliminary speculation supports the notion that an intact Area 44 is a prerequisite for successful compensatory ability.

Adaptation, Physiological↗

Circulating human mammary epithelial antigens in breast cancer.

Heterologous specific antisera against human mammary epithelial antigens (HME-Ags), which are present in the human milk fat globule membrane and breast epithelial cells, were used in a solid-phase radioimmunoassay to determine the presence of these antigens in the sera of patients with disseminated cancer of the breast and other organs. Breast cancer patients carry high levels of HME-Ags in their circulation, while patients with disseminated nonbreast cancer, as well as normal female controls, do not. A similar release of HME-Ags in the circulation was shown by us in a model system. To further corroborate these findings, a three-step procedure for the extraction and identification of HME-Ags from the sera was devised. In this analytical procedure, circulating HME-Ags are recovered on a solid phase carrying their corresponding antibody (anti-HME) and radioiodinated in situ. Later, the labeled HME-Ags are released from the solid phase and characterized by NaDodSO4 gel electrophoresis. With this procedure, HME-Ags were isolated from sera of breast cancer patients but not from sera of nonbreast cancer patients or of normal female controls. The extracted HME-Ags had molecular masses of 150,000, 70,000, and 46,000 daltons. To further support these findings, a monoclonal antibody, BLMRL-HMFG-Mc3, directed to the 46,000-dalton HME-Ag was also used to extract its corresponding antigen from sera. Breast cancer patient sera contained such antigen while the sera of the other patients and controls did not. This highly sensitive methodology offers a specific approach to breast cancer diagnosis as well as further insight into the nature of circulating antigens with a view to increasing our understanding of breast cancer biology.

Antigens, Neoplasm↗

Zinc deficiency: improvement in growth and growth hormone levels with oral zinc therapy.

A 14-year-old girl and a 13-year-old boy were found to be growth hormone deficient by insulin-arginine stimulation tests, and were also found to be zinc deficient. When oral zinc replacement was given, they both had a significant increase in growth rate which continued for at least 2 years, and subsequent growth hormone tests were normal.

Administration, Oral↗