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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 577 records · Page 32Linked to original sources

Trauma: the leading cause of maternal death.

The records of the Cook County Medical Examiner were reviewed for the period January, 1986, to December, 1989. Ninety-five maternal deaths were identified. The causes of maternal death were categorized as direct maternal, indirect maternal, or nonmaternal. Direct maternal causes of death (18.9%) were the result of complications of pregnancy, labor, delivery, or its management. Indirect maternal causes of death (12.6%) occurred when pre-existing health problems were exacerbated by pregnancy. All other maternal deaths were the result of nonmaternal causes. Nonmaternal causes of maternal death were further classified as traumatic or nontraumatic. Traumatic maternal deaths (46.3%) were attributed to homicide in 57% and suicide in 9%. The mechanism of injury in traumatic maternal deaths included gunshot wounds (22.7%), motor vehicle crashes (20.5%), stab wounds (13.6%), strangulation (13.6%), blunt head injuries (9.1%), burns (6.8%), falls (4.5%), toxic exposure (4.5%), drowning (2.3%), and iatrogenic injury (2.3%). Trauma was therefore the leading cause of maternal death, accounting for 46.3% of deaths in this series.

Adolescent↗

Presence of phospholipase C in coated vesicles from bovine brain. Dual regulatory effects of GTP-analogs.

Bovine brain coated vesicles display free calcium-dependent phospholipase C activity. Gpp(NH)p and GTP gamma S inhibited phospholipase C at nanomolar concentrations. Increasing concentrations of Gpp(NH)p and GTP gamma S reversed the inhibitory effects and stimulated phospholipase C activity. Preincubation of coated vesicles with pertussis toxin blocked the poorly-hydrolyzable GTP-analogs' inhibitory effects on phospholipase C. These data indicate that guanine nucleotides exert a dual regulatory control of phospholipase C in coated vesicles and that the inhibitory pathway is mediated by a pertussis toxin-sensitive G-protein.

Animals↗

Separation of living red blood cells by gravitational field-flow fractionation.

The field-flow fractionation technique, using the earth's gravitational field, has been applied to peripheral blood cell populations. A more or less symmetrical, gaussian-like, elution peak is generally observed for the red cell population. The bimodal cell population obtained after a massive transfusion is shown to result in a shoulder on the red blood cell elution profile. In one case where a similar shouldering peak was obtained from a non-transfused donor, the existence of an immunological double population has been demonstrated. This suggests that field-flow fractionation has some potential for complementary biomedical diagnosis.

Cell Separation↗

Identification of a unique membrane receptor for adenosine 5',5"'-P1,P4-tetraphosphate.

Adenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) has been implicated as a modulator of cell stress. We have performed binding studies which indicate that membranes from all tissues tested bind tritium-labeled Ap4A. The characteristics of Ap4A binding were determined on brain membrane homogenates after development of an optimized in vitro filter-binding assay. Ap4A binding is specific for adenylated dinucleotides and for the length of the phosphate bridge. A Kd of 0.71 microM for Ap4A was determined.

Animals↗

Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients.

We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem.

Antineoplastic Combined Chemotherapy Protocols↗

Enhanced in vivo targeting of an asymmetric bivalent hapten to double-antigen-positive mouse B cells with monoclonal antibody conjugate cocktails.

In order to target specifically double-Ag-positive cells in vivo, we synthesized chemically two mAb conjugates with specificities for both an allelic murine B cell-surface Ag and for a synthetic hapten. One conjugate was designed for its specificities for I-Ek and for N-epsilon-(2,4-DNP)-amino-caproate, and the other one for its reactivity to Lyb-8.2 and to indium-diethylenetriamine pentaacetate. A radiolabeled tracer, containing both the N-epsilon-(2,4-DNP)-amino-caproate and the indium-diethylenetriamine pentaacetate haptens, was obtained by reacting diethylenetriamine pentaacetic acid dianhydride with mono-[N-epsilon-(2,4-DNP)-amino-caproyl]-tyrosyl-lysine and labeling with indium-111. Mice from various strains (CBA/N: I-Ek+, Lyb-8.2+; AKR/N: I-Ek+, Lyb-8.2-; BALB/c: I-Ek-, Lyb-8.2+; and DBA/2: I-Ek-, Lyb-8.2-) were given simultaneous i.v. injections of microgram amounts of less than anti-[N-epsilon-(2,4-DNP)-amino-caproate], anti-I-Ek greater than and of [anti-(indium-diethylene-triaminepentaacetate), anti-Lyb-8.2] antibody conjugates and picomole amounts of the tracer. As expected, specific uptake of the tracer by the spleen was observed in strains where spleen cells expressed at least one Ag (CBA/N, AKR/N, and BALB/c). Furthermore, spleen cells from the double-Ag-positive mouse strain (CBA/N), when compared with spleen cells from single-positive mouse strains, exhibited a significantly higher uptake of the bivalent hapten. This specificity for double-Ag-positive cells, it is suggested, occurs through the formation of stable complexes between both cell-surface Ag, both conjugates, and the asymmetric bivalent hapten. The use of such asymmetric bivalent haptens, together with matched (anti-hapten, anti-cell) antibody conjugates, is proposed as a general method for increasing the in vivo specificity of immunoimaging and radioimmunotherapy.

Animals↗

Failure to detect hepatitis C virus genome in human secretions with the polymerase chain reaction.

Although hepatitis C infection has been clearly demonstrated to be transmitted through blood products or blood contamination, most cases of sporadic hepatitis C infection are unassociated with parenteral risk factors, and it is unclear how infection might be acquired by nonparenteral means. One potential mode of nonparenteral transmission is through body secretions. We used a highly sensitive and specific polymerase chain reaction assay to determine whether hepatitis C viral genomic RNA could be detected in secretions obtained from nineteen individuals with chronic hepatitis C virus infection. Although hepatitis C genomic RNA was found in all 19 sera, hepatitis C virus RNA was not detected in any samples of saliva, semen, urine, stool or vaginal secretions from these patients. Viral titers in serum ranged from 10(2) to 10(7) polymerase chain reaction units/ml. The sensitivity of our polymerase chain reaction assay indicates that, if hepatitis C virus were in secretions, it would be present in amounts less than 1 to 4 polymerase chain reaction units/ml. This contrasts with hepatitis B virus infection, in which serum titers frequently are in excess of 10(9) copies of hepatitis B genomes/ml. Body secretions have been found to contain up to 10(6) copies of hepatitis B genomes/ml. Our findings support seroepidemiological studies indicating that nonparenteral transmission of hepatitis C through secretions is uncommon and probably much less efficient than hepatitis B virus infection.

Body Fluids↗

Characterization of recombinant human renin: kinetics, pH-stability, and peptidomimetic inhibitor binding.

The kinetic behavior and pH-stability of recombinant human renin was analyzed using a new fluorogenic substrate based on the normal P6-P3' renin cleavage sequence in human angiotensinogen. The design of this fluorogenic substrate makes possible, for the first time, direct monitoring of the kinetics of proteolytic conversion of prorenin to renin. The pH-stability profile for renin, measured with the substrate at 25 degrees C, indicated a broad plateau of stability between pH 6.0 and 10.0. Analysis of the pH-activity profile of renin for the substrate indicated a minimum Km (approximately 1.8 microM) at pH approximately 7.4 and a maximum Vm between pH 7.4 and 8.0. The thermodynamics of the binding of a novel, soluble, peptidomimetic inhibitor to renin indicated it is possible to retain the tight-binding characteristics and enthalpy contributions to binding of larger peptide-derived inhibitors, while reducing inhibitor size and entropic contributions to binding. A novel derivative of the fluorogenic substrate, containing a 3-methyl histidine substitution at the P2 site, was used to test the recent hypothesis that renin functions by virtue of substrate-directed catalysis.

Amino Acid Sequence↗

Does anxiety lead to selective processing of threat-related information?

Four experiments investigating the detailed nature of the attentional bias in anxiety are reported. Previous research using the Stroop task has shown that, when compared with non-patient controls, anxious patients are relatively slower at colour naming threat-related words than non-threat words. Experiments One and Two investigated whether this apparent attentional bias is a function of anxiety per se and/or is related to patient/non-patient status. Experiment One compared colour-naming times for threat and non-threat words in low, medium and high trait anxiety normal subjects. High anxiety was not associated with slower colour-naming times for threat words. Experiment Two compared generalized anxiety disorder patients with equally anxious non-patients and found that the patients were significantly slower at colour-naming threat words. Read aloud and dwell tasks were also included in these experiments in order to identify the mechanism of Stroop interference. Experiments Three and Four investigated whether anxious patients' attentional bias is specific to threat-related material or also extends to certain positive, emotional material. In Experiment Three words used in previous Stroop studies were rated for emotionality. Threat words were more emotional, as well as more threatening, than control words, indicating that previous studies have confounded threat and emotionality. Experiment Four compared colour-naming times for threat words, equally emotional positive words, and neutral words. Consistent with the emotionality hypothesis, generalized anxiety disorder patients were slower than non-anxious controls at colour naming both threat words and positive words. The theoretical, methodological and clinical implications of these results are discussed.

Adult↗

Serum postdexamethasone prolactin measures in depressive patients and control subjects.

Recently, some researchers noted significant positive relationships between postdexamethasone serum cortisol and prolactin levels, whilst endogenous depressives exhibited a significantly lower suppression of prolactin by dexamethasone than non-endogenous patients or normal controls. To ascertain the extent of prolactin responses to dexamethasone in severely depressed patients, we measured 8 a.m. pre- and postdexamethasone prolactin levels in 104 depressed and 42 normal subjects. Serum cortisol levels were also determined in depressed patients before and after dexamethasone administration. We found a significant suppressive effect of dexamethasone on prolactin levels. There were no significant differences either in pre- or postdexamethasone prolactin, or in actual dexamethasone-induced decrements in prolactin between normal controls, melancholics, simple major or minor depressed subjects. We have not found any significant relationships between cortisol and prolactin, either under baseline or postdexamethasone conditions.

Adjustment Disorders↗

Effect of physical training on ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats.

This study was designed to assess the effect of physical training on the ventricular beta-adrenergic receptor adenylate cyclase system of diabetic rats. Mild diabetes mellitus was induced by an intravenous (IV) injection of streptozotocin (45 mg/kg). Rats were randomized into a group submitted to a progressive 10-week running program on a treadmill, while another group was kept sedentary. A group of sedentary nondiabetic rats was used as normal controls. Results showed a similar reduction in the density of beta-adrenergic receptors in sedentary diabetic (P less than .05) and trained diabetic rats (P less than .01) compared with controls, without any significant alteration in the dissociation constant. The basal and the sodium fluoride-stimulated maximal adenylate cyclase activities were similar in the three groups. However, the maximal response of adenylate cyclase to isoproterenol was significantly reduced in the two diabetic groups compared with controls (P less than .01). The decrease in adenylate cyclase response to isoproterenol observed in the diabetic groups appeared to be associated with a reduction in the total number of beta-adrenergic receptors and more specifically in those existing in the high-affinity state. On the other hand, the hyperglycemia and hyperglucagonemia present in sedentary diabetic rats was improved by training. These data suggest that the beneficial effects observed in response to training in experimental diabetes are not associated with changes in beta-adrenergic receptor adenylate cyclase system on membranes from ventricular tissue.

Adenylyl Cyclases↗

Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192: is elective neck dissection indicated?

This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive branchytherapy. Minimum follow-up is 3 years. Treatment of neck was chosen by a multidisciplinary team, according to age, medical status and availability for regular follow-up. One hundred and ten patients (47%) underwent elective neck dissection (END); 28 (25%) had positive nodes and received neck irradiation post-operatively. One hundred and twenty three patients (53%) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17%): 12/60 (20%) in patients with mobile tongue carcinoma and 7/50 (14%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 9/19 (47%) cases. In the TND group, there were 21 neck relapses (17%): 16/82 (20%) in patients with mobile tongue carcinoma and 5/41 (10%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13/21 (62%) cases. Ten-year survival is 37% for the END group and 31% for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p less than 0.04).

Adult↗

Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences.

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Influence of pretreatment clinical characteristics on the response rate to mitomycin/vindesine/cisplatin (MVP) in unresectable non-small cell lung cancer. ATTIT (Association pour le Traitement des Tumeurs Intra-Thoraciques).

The authors report their experience with the MVP (mitomycin/vindesine/cisplatin) regimen of the Memorial Sloan-Kettering Cancer Center (MSKCC) which showed the highest response rate in non-small cell lung cancer (NSCLC). The aim was to respect the original reported schedule to appreciate its activity, because the same drug combination with dose and schedule variations used by other investigators has failed to reproduce the original report results. 82 consecutive previously untreated patients with unresectable and/or metastatic NSCLC received mitomycin (8 mg/m2 days 1, 29, 71), vindesine (3 mg/m2, days 1, 8, 15, 22, 29, 43, 57, 71) and cisplatin (120 mg/m2, days 1, 29, 71), with evaluation on day 71. 24 objective responses were noted (29%) (2 complete response/22 partial response) (95% CI 19%-39%), without differences according to histology. Differences in median survival were noted according to the performance status and type of response. Overall survival rates in responding patients were similar to those noted with the original schedules. Analysis of selection criteria showed that there were more patients with bone (P less than 0.01) or liver metastases (P less than 0.05), less women (P less than 0.001) and less adenocarcinoma (P less than 0.001) than the MSKCC trial. A dose intensity analysis showed only a minimal difference in the average weekly doses of vindesine (10% lower than MSKCC trial: 1.8 mg/m2 vs. 2.25 mg/m2). Disease improvement, a subjective response criterion used in the MSKCC trial, was probably underestimated in the current study. We conclude that the potential benefit of chemotherapy with a three-drug combination in NSCLC is greatest in patients with stage IIIa and IIIb disease or stage IV disease with a good performance status and a low metastatic volume.

Adult↗