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Biomedical subjects

B Porter

Publications and source records attributed to B Porter.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cardiovascular collapse after femoral prosthesis surgery for acute hip fracture.

PURPOSE: Prosthetic revision of hip fractures may result in embolization of tissue products leading to death. In this report, from cases reported to the Anaesthesia Advisory Committee to the Chief Coroner of Ontario, emphasis is placed on the immediate resuscitative procedures which may offset a fatal outcome. CLINICAL FEATURES: Two elderly patients are reported in whom hip fractures necessitated primary prosthetic hip repair. The first patient, with a history of limited cardiac reserve and syncope, suffered a subcapital hip fracture. Under general anaesthesia, a Moore's prosthesis was inserted. The anaesthetic period remained relatively stable until surgical reaming of the femoral canal. Bradycardia, hypotension and cyanosis developed and quickly proceeded to a fatal cardiac arrest. Autopsy demonstrated diffuse pulmonary embolism of fat and thrombus. The second patient suffered a fracture around the stem of a previously inserted femoral prosthesis. Under general anaesthesia, a new cemented hip prosthesis was inserted, following which hypotension occurred. This was supported with small doses of ephedrine, ventilation was controlled with oxygen and the procedure was quickly terminated. Despite addition of a dopamine infusion, cardiac arrest and death followed. Autopsy disclosed massive fat and bone marrow embolization. CONCLUSION: The combination of hip fracture, activated clotting factors and borderline cardiopulmonary function presents a risk of death from embolization of tissue products released during the placement of a cemented hip prosthesis. While the outcome of this catastrophe is generally poor, all practitioners should be prepared to immediately institute resuscitative procedures to manage the accompanying cardiovascular collapse.

Acute Disease↗
PubMed1997

Gestational diabetes: should it be added to the syndrome of insulin resistance?

OBJECTIVE: The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance). RESEARCH DESIGN AND METHODS: On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test > or = 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied. RESULTS: GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), beta-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting beta-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM. CONCLUSIONS: Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.

Adolescent↗
PubMed1996

New low-density lipoprotein receptor upregulators acting via a novel mechanism.

The synthesis and biological activity of a new series of benzamides and related compounds that upregulate the expression of the low-density lipoprotein (LDL) receptor in human hepatocytes (HepG2 cells) by a novel mechanism are described. The lead compound, N-[5-[(3-cyclohexylpropionyl)amino]-2-methylphenyl]-4-hydroxybe nzamide (1, RPR102359), increased the expression of the LDL receptors in HepG2 cells by 80% when tested at a concentration of 3 microM. Mevinolin (lovastatin) was found to increase the LDL receptor expression by 70% at the same concentration. In contrast to mevinolin, 1 was found to have no effect on cholesterol biosynthesis in liver homogenates or in HepG2 cells at doses where substantial upregulation of the LDL receptor was observed and thus stimulated LDL receptor expression by a novel mechanism.

Benzamides↗
PubMed1996

Acyl-CoA:Cholesterol O-acyltransferase (ACAT) inhibitors. 2. 2-(1,3-Dioxan-2-yl)-4,5-diphenyl-1H-imidazoles as potent inhibitors of ACAT.

The second in this series of papers concerns our further investigations into the search for a potent bioavailable acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor suitable for the treatment of atherosclerosis. The design, synthesis, and structure-activity relationship for a series of ACAT inhibitors based on the 2-(1,3-dioxan-2-yl)-4,5-diphenyl-1H-imidazole pharmacophore are described. Compounds such as 13a bearing simple alkyl or hydroxymethyl substituents at the 5-position of the 1,3-dioxane ring are potent bioavailable inhibitors of the rat hepatic microsomal enzyme in vitro (IC50 < 100 nM) but are only weak inhibitors of the human hepatic enzyme. We have found however that 1,3-dioxanes substituted at the 5-cis position with pyrazolylalkyl or aminoalkyl groups are potent inhibitors in vitro of human macrophage ACAT, the potency depending on the nature of the terminal heterocycle and the length of the alkyl chain. An ex vivo bioassay herein demonstrates that potent inhibitors such as 13t (IC50 = 10 nM) which contain lipophilic terminal heterocycles do not appear to be systematically available. Less potent but more water soluble compounds such as 13h (IC50 = 60 nM) and 13n (IC50 = 70 nM) are absorbed following oral dosing and achieve plasma levels significantly in excess of their IC50 for ACAT inhibition. These compounds are therefore possible candidates for further investigation as oral antiatherosclerotic agents.

Animals↗
PubMed1995

Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas.

25 patients with relapsed B-cell lymphomas were evaluated with trace labelled doses (2.5 mg/kg, 185-370 MBq [5-10 mCi]) of 131I-labelled anti-CD20 (B1) antibody in a phase II trial. 22 patients achieved 131I-B1 biodistributions delivering higher doses of radiation to tumour sites than to normal organs and 21 of these were treated with therapeutic infusions of 131I-B1 (12.765-29.045 GBq) followed by autologous haemopoietic stem cell reinfusion. 18 of the 21 treated patients had objective responses, including 16 complete remissions. One patient died of progressive lymphoma and one died of sepsis. Analysis of our phase I and II trials with 131I-labelled B1 reveal a progression-free survival of 62% and an overall survival of 93% with a median follow-up of 2 years. 131I-anti-CD20 (B1) antibody therapy produces complete responses of long duration in most patients with relapsed B-cell lymphomas when given at maximally tolerated doses with autologous stem cell rescue.

Adult↗
PubMed1995

Simultaneous exposure to nicotine and hyperoxia causes tumors in hamsters.

BACKGROUND: We have shown that the nicotine-derived nitrosamine 4-(methyl-nitrosamino)-3-(pyridyl)-1-butanone (NNK) causes a high incidence of neuroendocrine lung tumors in male Syrian golden hamsters when administered to animals maintained in an atmosphere of 60% hyperoxia. In vitro studies with fetal hamster pulmonary neuroendocrine cells (PNE cells) and human neuroendocrine lung cancer cell lines revealed that nicotine and NNK are both potent mitogens for normal and neoplastic PNE cells when the cells were maintained in an atmosphere of high CO2. These effects were completely inhibited by antagonists of nicotinic acetylcholine receptors (nAChR). NNK displaced 3H-(-)L-nicotine from the nAchR in radioreceptor assays with cell membrane fractions from hamster lungs enriched in PNE cells. We therefore hypothesized that NNK acts as an agonist of the nAchR in PNE cells and that stimulation of this receptor in an environment of impaired pulmonary oxygenation is an important molecular event leading to the development of lung tumors with a neuroendocrine phenotype. EXPERIMENTAL DESIGN: To test this hypothesis, we exposed male Syrian golden hamsters maintained in 60% hyperoxia to s.c. injections of nicotine for the duration of their life. To allow for a survival time long enough to assess a potential carcinogenic effect of this treatment, animals demonstrating symptoms of respiratory distress were returned to ambient air for 24 hours throughout the experiment. RESULTS: A low but significant number of the animals exposed to hyperoxia and nicotine developed tumors of the nasal cavity, lungs, and adrenal glands. All of the tumor-bearing animals had survived 40 weeks or longer. The lung tumors demonstrated focal areas of positive immunoreactivity to neuron-specific enolase (NSE) and 5-hydroxy-tryptamine (5-HT, serotonin), both of which are markers of neuroendocrine differentiation. Hamsters maintained in ambient air and receiving identical injections with nicotine as well as animals maintained in hyperoxia and injected with saline did not develop tumors in any organs. All hamsters exposed to hyperoxia and surviving more than 12 weeks had thickened alveolar walls and emphysema. CONCLUSIONS: Our data support the hypothesis that chronic stimulation of the nAChR in an environment of impaired pulmonary oxygenation contributes to the carcinogenic burden associated with exposure to cigarette smoke and provides selective growth advantage for lung tumors with a neuroendocrine phenotype.

Adrenal Gland Neoplasms↗
PubMed1994

Characteristics of community-based individuals with mental retardation and aggressive behavioral disorders.

A cohort of 199 individuals with mental retardation referred for behavioral and psychiatric crisis intervention services was studied to determine attributes differentiating physically aggressive behavior from other behavioral problems. Individuals with aggressive and nonaggressive behavior had similar neurological histories and current medical status and similar levels of seizure disorders and CNS abnormalities. Aggressive individuals more often had psychiatric diagnoses of organic brain syndrome, but frequencies of this diagnosis in each group were small. Current aggression was predicted by gender, level of mental retardation, and history of previous institutional placement; the strongest predictor was history of aggression. These data suggest a complex equation to describe social inadequacy involving interactions between CNS functioning and developmental cognitive and social variables that are only partially defined at this time. Further work to characterize this interaction almost certainly must include a prospective longitudinal analysis of social and developmental functions early in life.

Activities of Daily Living↗
PubMed1993

Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support.

BACKGROUND: Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse. METHODS: Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol. RESULTS: Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs. CONCLUSIONS: High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.

Antibodies, Monoclonal↗
PubMed1993

[Rett syndrome].

Rett syndrome was described relatively recently. It affects only females and is characterized by progressive deterioration of neurological status and impairment of psychomotor development. Psychomotor development is normal in the first year of life, but then there is deterioration of fine motor and language skills and later still, of gross motor skills. This results in severe motor function handicap and dementia. The arrested head growth, severe psychomotor retardation and typical "washing hands" movements are typical of Rett syndrome. We describe a 3-year-old Bedouin girl with the clinical picture of the syndrome and review the world literature, stressing the difficulty in detection and diagnosis.

Child, Preschool↗
PubMed1992

[Infantile neuroaxonal dystrophy].

Infantile neuroaxonal dystrophy is a degenerative disease, mostly of nerve endings in the central and peripheral nervous system, with typical pathological findings. We describe a 3-year-old boy who had suffered from nystagmus, progressive muscle weakness and dementia since the age of 10 months. Biochemical work-up, MRI of the brain, and electrophysiological studies were within normal limits. Only skin biopsy, and sural nerve biopsy at a later stage, were diagnostic. We stress the importance of performing tissue biopsy even when intensive investigation is negative.

Biopsy↗
PubMed1992

Conformationally constrained tachykinin analogues: potent and highly selective neurokinin NK-2 receptor agonists.

The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structure-activity relationships for related analogues. Compound 12 (EC50 = 3.7 nM at NK-2 receptors in the rat colon; selectivity > 1000- and > 300-fold with respect to NK-1 and NK-3 receptors, respectively) was derived by incorporation of a Gly-Leu gamma-lactam conformational constraint into the C-terminal region of the neurokinin A octapeptide analogue [Lys3]-NKA(3-10). Compound 31 (EC50 = 15 nM in rat colon) contains a novel fused-bicyclic constraint at the corresponding site in the substance P hexapeptide analogue [Ava6]-SP(6-11).

Amino Acid Sequence↗