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Biomedical subjects

P Stern

Publications and source records attributed to P Stern.

At least 37 records · Page 2Linked to original sources
PubMed1993

A phase I study of intravenous bryostatin 1 in patients with advanced cancer.

Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginning of each 2 week treatment cycle. A maximum of three treatment cycles were given. Doses were escalated in steps from 5 to 65 micrograms m-2 in successive patient groups. The maximum tolerated dose was 50 micrograms m-2. Myalgia was the dose limiting toxicity and was of WHO grade 3 in all three patients treated at 65 micrograms m-2. Flu-like symptoms were common but were of maximum WHO grade 2. Hypotension, of maximum WHO grade 1, occurred in six patients treated at doses up to and including 20 micrograms m-2 and may not have been attributable to treatment with bryostatin 1. Cellulitis and thrombophlebitis occurred at the bryostatin 1 infusion site of patients treated at all dose levels up to 50 micrograms m-2, attributable to the 60% ethanol diluent in the bryostatin 1 infusion. Subsequent patients treated at 50 and 65 micrograms m-2 received treatment with an intravenous normal saline flush and they did not develop these complications. Significant decreases of the platelet count and total leucocyte, neutrophil and lymphocyte counts were seen in the first 24 h after treatment at the dose of 65 micrograms m-2. Immediate decreases in haemoglobin of up to 1.9g dl-1 were also noted in patients treated with 65 micrograms m-2, in the absence of clinical evidence of bleeding or haemodynamic compromise. No effect was observed on the incidence of haemopoietic progenitor cells in the marrow. Some patients' neutrophils demonstrated enhanced superoxide radical formation in response to in vitro stimulation with opsonised zymosan (a bacterial polysaccharide) but in the absence of this additional stimulus, no bryostatin 1 effect was observed. Lymphocyte natural killing activity was decreased 2 h after treatment with bryostatin 1, but the effect was not consistently seen 24 h or 7 days later. With the dose schedule examined no antitumour effects were observed. We recommend that bryostatin 1 is used at a dose of 35 to 50 micrograms m-2 two weekly in phase II studies in patients with malignancies including lymphoma, leukaemia, melanoma or hypernephroma, for which pre-clinical investigations suggest antitumour activity.

Adult↗
PubMed1992

Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors.

To cast light on the subunit composition of native NMDA-type glutamate receptors, four cloned subunits of the NMDA receptor have been expressed, in pairs, in Xenopus oocytes, and their single-channel properties have been measured. The conductances of the channels, and their characteristic patterns of sublevel transitions, turn out to be useful diagnostic criteria for subunit composition. The NR1-NR2A and NR1-NR2B combinations (which have identical TM2 sequences) are very similar to each other. Both have 50 pS openings and brief 40 pS sublevels (in 1 mM external Ca2+), with similar mean lifetimes and frequencies. They also show close quantitative resemblance to the channels of hippocampal CA1 and dentate gyrus cells and of cerebellar granule cells, except that the NR1-NR2A combination has a lower glycine sensitivity than the native channels. In contrast, the NR1-NR2C combination produces a channel with 36 pS and 19 pS conductances of similar (brief) duration; these closely resemble the 38-18 pS channels that have previously been observed in large cerebellar neurons in culture (together with 50 pS channels).

Animals↗
PubMed1992

Recombinant human interleukin 4 (IL-4) given as daily subcutaneous injections--a phase I dose toxicity trial.

Recombinant Interleukin 4 was administered by subcutaneous injection at daily doses of 0.5, 1.0 or 5.0 micrograms kg-1 to nine patients as part of a Phase I Dose Toxicity Study. Dose limiting toxicity was reached at 5 micrograms kg-1 day-1. Symptoms of toxicity included fatigue, 'flu like symptoms and elevated liver enzymes. Modest but significant elevations of neutrophil and platelet counts occurred. No clear evidence of antitumour effects emerged although pain in metastatic lymph nodes and a small fall in myeloma paraprotein levels during dosing were observed. In vitro and murine in vivo studies indicate that patients with lymphoproliferative disease should be selected for Phase II trials.

Bone Marrow↗
PubMed1992

Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex.

1. Voltage and current recordings were made from visually identified non-pyramidal neurones in slices of layer IV of rat primary visual cortex using the whole-cell configuration of the patch clamp technique. These neurones are characterized by a high input resistance (0.5-2 G omega) and a non-adaptive behaviour of action potential frequency following depolarizing current injection, which suggests that they are stellate cells. 2. Excitatory postsynaptic currents (EPSCs) were recorded from these neurones during focal stimulation of neighbouring cells by a second patch pipette, the tip of which was placed on the soma of the stimulated cell. The response amplitude as a function of stimulus strength showed a sharp increase at a critical stimulus strength suggesting that stimulus-evoked currents represent unitary EPSCs. 3. In most cases the latencies of stimulus-evoked EPSCs were unimodally distributed with means in the range of 2.1-3.6 ms. In some experiments two peaks were seen in the distribution of latencies. The EPSC rise times, measured as the time from 20 to 80% peak amplitude, fell into a distribution ranging from 0.1 to 0.8 ms with a peak at 0.2 ms. The EPSC decay time course at -70 mV membrane potential was fitted by a single exponential with a time constant of 2.39 +/- 0.99 ms (mean +/- S.D.). The rise and decay times were independent of EPSC peak amplitudes. 4. The peak amplitude of successive unitary EPSCs, elicited by a constant stimulus, fluctuated at random. At a holding potential of -70 mV the peak amplitudes varied between 5 and 90 pA. In two out of ten cells the histogram of peak amplitudes could be well fitted by the sum of several equidistant Gaussians with a peak distance of around 10 pA. This suggests that the quantal conductance change underlying the peak current fluctuations is of the order of 100 pS. 5. At membrane potentials more positive than -70 mV the decay of stimulus-evoked EPSCs showed two components with very different time courses. In standard extracellular solution the current-voltage (I-V) relation for the fast component was almost linear whereas the slow component showed a J-shaped I-V relation with a region of negative slope conductance between -30 and -70 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Controlled localized heat therapy in cutaneous warts.

BACKGROUND: Controlled localized heating as a method of superficial tissue destruction has been used in veterinary medicine for the treatment of benign and malignant tumors. The rationale for its use is that the diseased tissue being treated is more sensitive to the effects of heating than is normal tissue. This technology was applied to the treatment of common hand warts in a placebo-controlled study. OBSERVATIONS: Twenty-nine warts were treated one to four times (median, two times) at 50 degrees C for 30 to 60 seconds. Twenty-five (86%) of 29 treated verrucae regressed completely while seven (41%) of 17 control warts resolved during the course of the study. No wart that regressed regrew during the follow-up period (mean, 15.6 weeks). CONCLUSIONS: Controlled localized heating can cause the regression of hand warts. The 86% regression rate compares favorably with other wart treatment modalities. The mechanism of action and the effect of heat on these virally induced tumors is not known but may involve direct antiviral effects, physical destruction of the tumor, or the promotion of an inflammatory response that ultimately eradicates the lesion.

Adult↗
PubMed1991

Complications associated with brachytherapy alone or with laser in lung cancer.

Relatively little has been reported about destruction through brachytherapy of mucosa-perforating and extraluminary tumors with probable large vessel involvement causing major hemorrhagic or fistular complications. We report 12 patients subjected to laser and brachytherapy for centrally occluding lung cancer, whom we have periodically followed up from June 1986 until they died. Although all laser procedures were free from complications, necrotic cavitation in five cases, two of which were accompanied by large bronchoesophageal fistulas, and massive fatal hemoptysis occurred in six. Minor complications included radiation mucositis (two), noncritical mucosal scarring (two), and cough (four). Characteristics that will identify patients at risk of developing fatal hemoptysis and fistulas should be better defined by imaging and endoscopic techniques. In such cases, modifying the protocol or using alternative procedures should be considered. Minor complications, such as cough, can be avoided by using topical steroid therapy (eg, beclomethasone dipropionate).

Adult↗
PubMed1990

Investigation of expression of 5T4 antigen in cervical cancer.

A monoclonal antibody detecting amniotrophoblastic antigen 5T4 has shown reactivity against various neoplastic cell lines and tumour specimens but with a relatively restricted normal tissue expression. This antibody has been investigated as a potential indicator of premalignant changes identified as cervical intra-epithelial neoplasia and malignant cervical lesions using immunohistochemistry on frozen tissue biopsies. The basal cells of normal cervical stratified epithelium exhibited faint staining, but a general increase in intensity and extent of specific labeling of this tissue was seen from the first premalignant stage through to carcinoma. In most cases, this was in accordance with the distribution of dysplastic cells, and was accompanied by increased specific staining of the stromal tissue. All invasive squamous carcinomas of the cervix were 5T4 antigen positive. Common inflammatory non-malignant diseases did show a certain degree of epithelial and stromal reactivity. These results, showing 5T4 reactivity with neoplastic and pre-neoplastic lesions, may provide a quantitative basis for its potential use as a tumour marker in the immunochemical detection on immunoassay of cervical cancer.

Antigens, Neoplasm↗
PubMed1990

Gay men's perceptions and responses to AIDS.

Gay men continue to be the largest group in Canada developing AIDS. They have responded to this threat on a personal and community level. The purpose of this study was to explore the perceptions of gay men about AIDS, and how they responded to these perceptions. Data were gathered through unstructured interviews with 34 healthy gay men, from participant observations chosen from logs that described nursing interactions with gay men who had AIDS, and fieldnotes collected during AIDS education programmes with health care workers and gay men. Using constant comparative analysis, a substantive conceptual framework was developed. Trusting was identified as the basic social psychological process that determined how gay men responded to AIDS. AIDS was perceived by all gay men in this study to threaten their own health and their acceptance by society. Variables identified behaviour, ranging from denial of personal risk to taking leadership roles in organizations to fight AIDS related to the trusting theory. This theoretical explanation of gay men's responses provides direction for programmes to educate gay men about HIV-related diseases, as well as to support those who acquire the HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Coaches' goals for young children in a recreational sports program.

Almost all children participate in sports at some time, and programs are being established for even younger children. Adults who coach the children largely determine what the children's sports experience will be. Coaches' perceptions of what is important for the young children they instruct have not yet been carefully investigated. This study was designed, therefore, to determine coaches' goals for young children. Data were gathered by use of an attitude questionnaire administered to 29 coaches of a recreational basketball program of children ranging in age from 6 to 10 years old. Of the 12 goals, feeling part of a team, learning to do my best, and having fun and excitement were most highly rated as extremely important, while becoming popular was lowest rated as not important. Results revealed that coaches in general are able to clearly define their goals and priorities, and these goals seem developmentally appropriate for the children. However, coaches make little differentiation in goals based on age.

Attitude↗
PubMed1988

Human trophoblast glycoproteins defined by monoclonal antibody 1D2.

A cell surface antigen has been defined by a monoclonal antibody 1D2, raised following immunisation with lectin-purified syncytiotrophoblast glycoproteins. 1D2 was nonreactive with any one of 8 common trophoblast proteins in immunodot. Analysis of nonreduced western blots of syncytiotrophoblast microvillous plasma membrane (StMPM) protein indicated that mAb 1D2 was reactive with a series of sialylated proteins with molecular weights of 16-22 kilodaltons. Immunoprecipitates of radiolabelled StMPM protein contained molecules that co-migrated with placental alkaline phosphatase in addition to those identified by western blotting. This set of human trophoblast molecules has not been previously identified by monoclonal antibodies; the antigenicity is widely distributed in human tissues.

Alkaline Phosphatase↗
PubMed1986

Indomethacin inhibits thrombin-, but not thyroxin-stimulated resorption of fetal rat limb bones.

The bone-resorbing effects of thrombin and thyroxin, two agents that stimulate resorption in neonatal mouse calvaria by prostaglandin-dependent mechanisms, were examined in cultures of fetal rat limb bones. Thrombin produced maximal resorption in the limb bone cultures at a concentration of 100 U/ml when bones were cultured in BGJ supplemented with 1 mg/ml bovine serum albumin. The effects of thrombin were partially inhibited by 0.5 and 10 uM indomethacin. Thrombin failed to elicit resorption when the limb bones were cultured in DMEM with 15% horse serum. Thyroxin stimulated the resorption of limb bones in both BGJ-albumin and DMEM-serum media. Resorption was elicited by thyroxin concentrations of 10 nM-10 uM. 30 uM thyroxin failed to stimulate resorption. The dose-response curve to thyroxin was shallow, and the agent did not produce maximal resorption. The bone-resorbing effects of thyroxin were not affected by 0.5 or 10 uM indomethacin.

Animals↗
PubMed1986

Plasma and cerebrospinal fluid progesterone concentrations in pregnant and nonpregnant women.

Pregnancy is associated with a wider dermatomal spread of local anesthetics after epidural and spinal anesthesia. This phenomenon also exists in the immediate postpartum period. The mechanism of this observation is unresolved. However, an increase in progesterone concentration in pregnancy has been implicated as one of the factors. Although plasma progesterone concentrations in humans have been well-documented, the cerebrospinal fluid (CSF) progesterone levels, which may also be important in this regard, have not been determined. Therefore, this study was undertaken to measure plasma and CSF progesterone in the nonpregnant, term parturient and in the immediate postpartum patient and also to determine the relationship between the CSF progesterone concentration and the intrathecal spread of lidocaine used for spinal anesthesia. The plasma progesterone concentrations in 12 nonpregnant, 21 term and eight postpartum patients were 2.3 +/- 61 (SEM) ng/ml, 122 +/- 8 ng/ml and 16 +/- 2.2 ng/ml, respectively. The CSF progesterone concentrations in term parturients (3 +/- 0.28 (SEM) ng/ml) and postpartum patients (1.03 +/- 0.16 ng/ml) were eight and three times greater than that of nonpregnant women (0.39 +/- 0.01 ng/ml). Significantly less lidocaine was needed (P less than 0.05) for comparable segmental levels of spinal anesthesia in term and postpartum patients than in nonpregnant individuals. These data suggest that high CSF, plasma progesterone concentrations, or both may augment the anesthetic spread of lidocaine.

Adolescent↗
PubMed1984

Effect of vitamin D and its metabolites on developing myogenic cultures.

Growth, protein synthesis and expression of creatine kinase (CK) by embryonic chick myogenic cells are inhibited by vitamin D and certain of its metabolites. 25-OH cholecalciferol was most active in concentrations of 10(-5) - 10(-6) M, with cholecalciferol and ergocalciferol less active in that order. Ergosterol had no activity of this sort. Inhibition of CK was most marked on the 4th and 5th day of culture and was due to suppression of the appearance of CK-NM and MB. CK-BB was not affected and CK-MB was more affected than CK-BB. Skin fibroblasts by comparison were slightly stimulated in growth at 10(-6) M and much less affected at 10(-5) M than the myogenic cells. It is suggested that vitamin D has a direct effect upon the muscle cell, to cause a selective diminution in the production of certain polypeptides.

Animals↗
PubMed1984

A monoclonal antibody which detects a 125 kd glycoprotein on embryonal carcinoma cells and is mitogenic for murine spleen cells.

The isolation and characterisation of a monoclonal antibody (2H9), selected for reactivity against murine teratocarcinoma stem cells, is described. This antibody recognizes one major glycoprotein on the surface of embryonal carcinoma (EC) cells but detects multiple glycoprotein species on various murine or human derived cell types. The binding of the antibody to cells is abolished by treatment with periodate or neuraminidase. These results suggest that 2H9 antibody detects a carbohydrate determinant; this is apparently distinct from other anti-EC reactive monoclonal antibodies and a variety of lectins. These antibodies are mitogenic for a population of lymphocytes in murine spleen. The antibodies recognize numerous cell surface glycoproteins on the surface of the spleen cells.

Animals↗