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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 127 records · Page 7Linked to original sources

Chemoradiotherapy for the treatment of regionally advanced head and neck cancers.

Despite the use of aggressive surgery and radiotherapy, patients with locoregionally advanced squamous cell carcinoma of the head and neck continue to suffer poor local control and poor survival. Chemotherapy produces excellent regressions of locoregional disease when given as part of initial induction therapy. The use of chemoradiotherapy for regionally advanced disease offers the possibility of organ preservation and retention of organ function for many of these patients. Randomized studies have suggested that chemoradiotherapy also offers better local control and survival than radiotherapy alone. Many chemotherapy regimens used in modern chemoradiotherapy include cisplatin. Because of its ease of outpatient administration, lesser degree of nausea and vomiting, reduced nephrotoxicity, improved nutritional status during therapy, and predictable myelotoxicity, carboplatin has important advantages over cisplatin. Carboplatin possesses well-defined single-agent activity against head and neck cancers, and produces excellent responses in combination with 5-fluorouracil in previously untreated patients. Sequential studies at the University of Maryland Cancer Center showed that weekly carboplatin could be safely and easily combined with standard doses and fractions of radiotherapy. With this regimen, 57% of the patients achieved a complete response and 21% achieved a partial response. Although the addition of bleomycin to this regimen proved somewhat toxic, concurrent carboplatin and radiotherapy allows for the further testing of new agents in developing a combination chemotherapy/concurrent radiotherapy program. Such regimens may improve local control and survival, and may be developed further for organ preservation studies.

Antineoplastic Combined Chemotherapy Protocols↗

Maintenance therapy for obstructive lung disease. How to achieve the best response with the fewest agents.

Asthma is now thought to be primarily an inflammatory condition with secondary bronchospasm; hence, the mainstay of maintenance therapy is an inhaled anti-inflammatory drug, either a corticosteroid (especially in adults) or a mast-cell stabilizer (especially in children). Inhaled beta agonists are reserved for acute exacerbations and systemic corticosteroids for severe refractory disease. Oral theophylline is sometimes helpful, especially for nocturnal exacerbations. Chronic bronchitis and emphysema almost always stem from cigarette smoking. Bronchospasm is the predominant cause of symptoms, and maintenance therapy with an inhaled anticholinergic (eg, ipratropium bromide [Atrovent]) is the best approach. If symptoms are not controlled, an inhaled bronchodilator should be added. An oral or inhaled corticosteroid benefits a minority of patients. Theophylline is especially helpful for chronic bronchitis and nocturnal exacerbations.

Administration, Inhalation↗

Probucol and other antioxidants prevent the inhibition of endothelium-dependent relaxation by low density lipoproteins.

Hypercholesterolaemia and atherosclerosis impair responses to endothelium-derived nitric oxide (EDRF) in human and animal coronary arteries, a dysfunction that correlates with elevated low density lipoproteins (LDL). Previous studies show that native LDL immediately and reversibly inhibit acetylcholine-evoked EDRF responses in rabbit aortic ring precontracted with noradrenaline or serotonin whereas Cu(2+)-oxidised LDL (oxLDL) inhibit relaxations after 30 min with a potency that varies with the donor. We now show that antioxidants, probucol (10 microM) and ascorbic acid (100 microM) in vitro, prevent the inhibition by native LDL, indicating that this effect involves free radicals. As expected, the antioxidants had no influence on the inhibition by oxLDL. Superoxide dismutase appeared to have no effect on the inhibition by native or oxLDL. The oral administration of probucol to selected volunteers also prevented the inhibition of relaxation by their native LDL. These preparations showed a diminished susceptibility to oxidation and their oxLDL caused a markedly reduced and always reversible inhibition of relaxation compared to the potent and sometimes irreversible inhibition prior to administration of the drug. We conclude that antioxidants such as probucol reduce the formation of free radicals and the oxidative modification of LDL that lead to the impairment of EDRF responses and may prevent this same dysfunction in hypercholesterolaemia and atherosclerosis.

Acetylcholine↗

College students' perception of vulnerability/susceptibility and desire for health information.

The specific aims of this study were to develop a questionnaire and conduct a survey of college students 18-22 years of age, in order to determine (1) their perception of being vulnerable and susceptible to health problems and (2) their interest in receiving help and information about health maintenance. Material from four 2-h focus groups provided the content for the initial questionnaire. Pilot testing of the early drafts consisted of several phases in which students completed the tool in both group situations and in face-to-face interviews. The final questionnaire was completed by 364 students on two campuses in the Midwest. Two scales were identified using factor analysis and analysis for internal consistency. The Vulnerability/Susceptibility Scale demonstrated a good reliability (Kuder-Richardson-20 = 0.8136) and five factors were identified through factor analysis. The Information Scale demonstrated a high reliability (Kuder-Richardson-20 = 0.8958) and two factors were identified through factor analysis. Based on analysis of variance (ANOVA) data, a model was developed using the variables of the Vulnerability/Susceptibility Scale, the Information Scale, gender and health rating. The model was then tested using multiple regression analysis. This study identified health related areas about which the students feel vulnerable/susceptible and are interested in receiving health help/information. This study suggests which population of college students might be most receptive to health information and future behavioral strategies.

Adolescent↗

Effect of hypothermic storage in liver allograft preservation solutions on vasoactivity and prostacyclin synthesis by the rabbit aorta, in vitro.

Primary graft dysfunction following orthoptic liver transplantation has been ascribed to thrombotic and ischemic complications in a high proportion of cases. It has been suggested that hypothermic storage of livers in preservation solutions elicits damage to the vascular endothelium. Since the endothelium controls vasoactivity and hemostasis via release of endothelium derived relaxing factor (EDRF) and prostacyclin (PGI2), storage injury to the endothelium may predispose the allograft to thrombosis, ischemia and impaired perfusion. In order to test this, the effect of long-term hypothermic storage in modified University of Wisconsin solution (UW), kidney perfusion solution (KPS) and minimum essential medium (MEM) on phenylephrine (PE)-stimulated contraction and acetylcholine (ACh)-stimulated relaxation, as well as PGI2 release by rabbit aortic rings was investigated. Following cold storage for 24, 48 and 72 h, PE and ACh dose response curves were unaffected by storage in MEM, UW or KPS. Following hypothermic storage for 24 h and 48 h, PGI2 release (stimulated with PE, ACh, arachidonate, fluoride, calcium ionophore and phorbol ester) was not significantly altered from zero time responses. These results demonstrate that hypothermic storage of rabbit aortic rings in both UW and KPS do not influence two key endothelial functions (the release of EDRF or PGI2) which in turn indicates that endothelial damage associated with reperfusion following hypothermic storage is not causally related to alterations in EDRF and PGI2 release.

Animals↗

Bacillus subtilis PrsA is required in vivo as an extracytoplasmic chaperone for secretion of active enzymes synthesized either with or without pro-sequences.

In prsA (protein secretion) mutants of Bacillus subtilis, decreased levels of exoproteins, including alpha-amylase and subtilisins, are found extracellularly. The effect of prsA on subtilisin secretion is elaborated here. Extracytoplasmic folding and secretion of active subtilisin is assisted by the N-terminal pro-sequence of its precursor. In this paper we present evidence that the product of the prsA gene is additionally required for these processes in vivo. We examined inducible expression of different subtilisin-alkaline phosphatase fusion genes in the prsA3 mutant. We found massive degradation of the fusion proteins, and a lack of enzymatic activity in the protein secreted. We suggest that PrsA is a novel chaperone with a predicted extracytoplasmic location, and is important in vivo for the proper conformation of various exoproteins, including those with pro-sequence (like subtilisin) and those without (like alpha-amylase).

Alkaline Phosphatase↗

Eye movement and electrophysiological findings in an infant with hemispheric pathology.

A visually unresponsive infant had a normal ophthalmological examination. Eye-movement studies using electro-oculography revealed asymmetrical binocular smooth pursuit, binocular optokinetic nystagmus and vestibulo-ocular reflex. Electrophysiological testing showed markedly asymmetrical occipital flash and pattern visual evoked potentials. Both investigations suggested a posterior right-hemispheric problem, which was confirmed with cranial ultrasound. This case study illustrates the usefulness of non-invasive techniques in neuro-ophthalmological investigations of young children.

Brain Diseases↗

ICI 169,369, A 5-HT2/5-HT1C antagonist, that can evoke endothelium-dependent relaxation in rabbit aorta.

1. The direct effects of ICI 169,369 on vascular reactivity were investigated in rabbit aortic rings with and without endothelium. 2. ICI 169,369 evoked an endothelium-dependent relaxation in aortic rings precontracted with PGF2 alpha. No direct effects on vascular reactivity were found in endothelial denuded rings. 3. The relaxations induced by ICI 169,369 were inhibited by haemoglobin, an agent known to interfere with the responses to endothelium-derived nitric oxide (EDRF) but not by the cyclo-oxygenase inhibitor, indomethacin. Inhibition of the ICI 169,369-induced relaxation by the L-arginine analogue, NG-monomethyl L-arginine (L-NMMA) confirmed that the relaxations evoked by ICI 169,369 were mediated by the endothelial L-arginine: nitric oxide pathway. 4. Studies with competitive receptor antagonists showed that in the rabbit aorta, ICI 169,369 evoked relaxations which were not elicited by the activation of any known 5-HT1, 5-HT2, 5-HT3, muscarinic, histamine, adenosine receptor or adrenoceptors. 5. The diacylglycerol kinase inhibitor, R 59022 also failed to affect these relaxations. It is concluded that ICI 169,369 has a post-receptor action, possibly by directly affecting intracellular calcium levels in the endothelial cells.

Acetylcholine↗

Posttraumatic seizures: consensus and controversies.

Seizures after traumatic brain injury may cause acute deterioration in level of consciousness, signal the presence of significant intracranial pathology, herald potentially lethal status epilepticus and carry some risk for the development of a chronic disorder. Specific implications of immediate, early and late seizures are different and vary across age groups. While there is a consensus to manage status epilepticus aggressively, and some agreement to treat a seizure once it has begun, no such unanimity exists about management of patients who have one or more seizures after injury. This article identifies controversies about seizures that occur after traumatic brain injury in paediatric and adult populations. It concludes with a summary of research imperatives for the future.

Brain Injuries↗

Surveillance for colorectal neoplasia: is patient adherence following treatment a problem?

This study was conducted in order to assess prospective adherence to surveillance colonoscopy and fecal occult blood testing (FOBT) at 1 year following treatment for an index lesion among colorectal cancer and polyp patients. The investigation was carried out in cooperation with two gastroenterology and two surgical practices in Philadelphia and surrounding communities. Subjects in this study were patients who were treated for colorectal cancer (N = 9) or polyps (N = 169) and were recommended to undergo surveillance colonoscopy at 12 months following treatment. Overall, 96 (54%) subjects underwent surveillance colonoscopy. Of the 178 subjects included in the study, 52 (29%) were willing to participate in an assessment of FOBT sensitivity in surveillance. Of the 52 subjects who were mailed an FOBT packet, 24 (46%) actually returned specimen. Of the 24 patients who returned FOBTs, 17 (71%) also underwent colonoscopy, whereas only 10 (36%) of 26 patients who did not do FOBTs underwent colonoscopy. These findings indicate that adherence to surveillance is low, and that adherence to FOBT may be a marker for adherence to colonoscopy.

Adenomatous Polyps↗

Phase II trial of 5 day continuous intravenous infusion of 6-thioguanine in patients with recurrent and metastatic squamous cell carcinoma of the head and neck.

Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vomiting was moderate and well controlled with antiemetics. No complete or partial responses were observed, with a median time to progression of 58 days and a median survival of 227+ days for the entire group. Based on these results we do not recommend I.V. 6-thioguanine for the treatment of this disease.

Adult↗

Role of 5-hydroxytryptamine receptors on luteinizing-hormone-releasing hormone release in the ovariectomized, estradiol-treated rat.

The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5-HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) treated rats using in vitro superfusion techniques. Regularly cycling female Holtzman rats (250-300 g) were maintained on a photoperiod of 0500-1900 h light at 22 +/- 2 degrees C. Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150 micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2 receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist Lilly 53857 (1 x 10(-6) M or 1 x 10(-5) M) did not increase LHRH release above control levels. Neither 5-HT nor quipazine had a significant effect on LHRH release at 1 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(-5) M) significantly (p less than 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT1 receptor plays a role in LHRH release and this effect may be related to the opposing effects of postsynaptic and autoreceptors. However, the failure of Lilly 53857 to reproduce the stimulatory effect of ketanserin on LHRH release suggests that 5-HT2 receptors in the MBH-POA-SCN may not modify LH release during the estrous cycle.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Ophthalmologic assessment of young patients with Alport syndrome.

BACKGROUND: Alport syndrome is an X-linked disease affecting basement membrane collagen. It is characterized by nephritis associated with high-tone sensorineural hearing impairment and ophthalmic signs. Although ocular changes have been described in adults, few data exist regarding the incidence of abnormal ocular features in adolescence and childhood. METHODS: Fifteen male and five female patients with Alport syndrome underwent ophthalmologic, audiologic, and nephrologic assessments. All patients studied had hematuria and a positive family history of Alport syndrome. Thirteen patients had a renal biopsy that showed characteristic electron microscopic changes of the disease. Eleven patients had high-tone sensorineural impairment. Electrophysiologic investigations performed included electroretinography, visual-evoked potentials, and electro-oculography. RESULTS: Two patients had early signs of anterior lenticonus, three had flecks in the retina, and two patients also had posterior subcapsular cataracts. None of the patients had significant electrophysiologic abnormalities. CONCLUSION: These findings indicate that ocular changes are uncommon and subtle in young patients with Alport syndrome, and suggest that the signs increase in frequency and severity with age.

Adolescent↗

Management of the subluxed crystalline lens.

There has been a traditional reluctance to remove a subluxed (ectopic) lens because of the high surgical risk. The use of closed intraocular microsurgical techniques, however, now allows greater intraoperative control with few complications. The authors present the results of subluxed lens extraction, by limbal or pars plana lensectomy, in 44 eyes of 24 patients, in which the indication for surgery was lens subluxation causing a reduction in visual acuity or uncorrectable refractive error. Visual acuity was improved in all cases after surgery, with no significant complications. Patients with reduced visual acuity secondary to ectopic lenses have a good visual prognosis after lensectomy using a closed intraocular microsurgical technique.

Adult↗