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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 325 records · Page 18Linked to original sources
PubMed1997

TNF-alpha-induced corticosterone elevation but not serum protein or corticosteroid binding globulin reduction is vagally mediated.

Immune activation leads to production of mediators such as cytokines, which act to induce both brain-mediated and peripheral defense processes. We used intraperitoneal administration of the cytokine tumor necrosis factor-alpha (TNF-alpha) to investigate whether defense processes induced by this cytokine are mediated by vagal afferents and/or interleukin-1 (IL-1) receptors. Because some effects of TNF-alpha are mediated, at least in part, by the brain [plasma corticosterone (CORT) elevation] and some are mediated by peripheral organs [reduction of serum protein and corticosteroid binding globulin (CBG)], we also investigated whether the effects of vagotomy are specific to those defense processes mediated by the brain. Both vagotomy and IL-1 receptor antagonist attenuated serum CORT elevation, but had no effects on serum protein or CBG reduction. These results support the idea that vagal afferents provide a true immune-to-brain pathway that may include IL-1 receptors.

Animals↗
PubMed1997

[Effects of CO2 and adrenaline on 1% lidocaine in axillary block].

OBJECTIVES: To compare lidocaine hydrocarbonate and lidocaine hydrochloride, with and without adrenaline, in the axillary block obtained with a neurostimulator. STUDY DESIGN: Prospective, randomized, double blind study. PATIENTS: Sixty-six patients undergoing surgery of the upper limb under axillary block, allocated into four groups. METHODS: The criteria for evaluation were: onset time, duration and quality of sensory and motor blockades, and blood concentrations of lidocaine in 39 patients. In all patients musculocutaneous, radial, median and ulnar nerves were stimulated and the volume of local anaesthetic administered was 25 mL per square meter of body surface. Group 1 received lidocaine hydrocarbonate 1% (n = 17), group 2, lidocaine hydrocarbonate 1% with adrenaline 1/200,000 (n = 17), group 3, lidocaine hydrochloride 1% (n = 16) and group 4, lidocaine hydrochloride 1% with adrenaline 1/200,000 (n = 16). RESULTS: No significant inter-group differences were found concerning sensory and motor blockades and onset time. The duration of analgesia was longer in groups CO2 + A and HCL + A. The lidocaine blood concentrations were globally lower in group HCL + A. CONCLUSIONS: Considering the cost/benefit ratio and the absence of clinical benefits of lidocaine hydrocarbonate, lidocaine hydrochloride should be preferred.

Adult↗
PubMed1997

The evaluation of velopharyngeal function using flexible nasendoscopy.

Nasendoscopy is an essential tool in assessing the dynamic function and structure of the velopharyngeal sphincter during speech and swallowing. Flexible fibre-optic nasendoscopy has been used by the cleft palate team at Withington Hospital, Manchester since 1989. Seventy-six patients were referred between 1989 and 1994 for evaluation of velopharyngeal function during speech. Flexible nasendoscopic evaluation was attempted in 50 patients, and successfully carried out in 43 patients. The age range was four years to 77 years (mean 21 years). The patients were divided into two groups: Group 1 consisting of patients with cleft palate and Group 2 comprised of patients with non-overt cleft palate-related velopharyngeal dysfunction of various aetiologies; such as, submucous cleft, post-tonsillectomy, post-adenoidectomy, neurological and post-traumatic. Based on the findings on nasendoscopy, videofluoroscopy and clinical speech/voice analysis the following treatment options were recommended: 17 (40 per cent) for pharyngoplasty, five (11 per cent) for revision pharyngoplasty, 15 (35 per cent) for speech therapy, four for an obturator and one for tonsillectomy. Two previously undetected submucous clefts were diagnosed.

Adolescent↗
PubMed1997

Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes.

Despite increasing survival rates for patients with colorectal cancer, additional treatment options are required, including active or passive immunotherapy for patients with metastatic disease. Freshly harvested colorectal cancer specimens and in vitro cultured colorectal cancer cell lines were examined for IL-7 protein secretion in order to examine the potential role of this cytokine in the interaction between tumour cells and the host immune system. Freshly harvested colorectal cancer specimens (21/21), or normal adjacent mucosa (3/3), as well as long-term established colorectal cancer cell lines (3/4) exhibited IL-7 mRNA expression as detected by RT-PCR and confirmed by Southern Blot analysis. Freshly harvested colorectal cancer tissue (16/18), or long-term established colorectal cancer cell lines (2/4) secreted in vitro IL-7 as detected by ELISA. In contrast, breast, pancreatic, or lung cancer cell lines, as well as several haematopoietic cancer cells lines, tested negative for IL-7 mRNA and protein. The authors tested different cytokines (IL-1 beta, IL-2, IL-7, or a combination of IL-1 beta/IL-7) in vitro for the ability to expand tumour-infiltrating T lymphocytes (TIL) from individual patients (n = 9) with colorectal cancer. TIL populations were tested at day 14 after in vitro propagation for phenotypic analysis by FACS and for reactivity directed against NK and LAK sensitive target cells and autologous cancer cells as measured by cytotoxicity and cytokine release. TIL obtained from colorectal cancer lesions can be efficiently expanded in the presence of IL-7, some(3/9) of which appear to exhibit autologous tumour recognition as measured by cytolytic effector functions and by detection of IFN gamma and TNF alpha release. Detection of IL-7 mRNA expression in colorectal cancer, in normal mucosa adjacent to tumour, as well as the ability of colorectal cancer tissue to secrete IL-7, raises new questions about the biology of the host/tumour interactions in colorectal cancer.

Blotting, Southern↗
PubMed1997

Simultaneous pancreas-/kidney transplantation--the Bochum experience.

Since the introduction of the bladder drainage technique, the number of pancreas transplants performed has now reached 1,000 per year worldwide. Most of these transplants have been performed in the United States. In contrast, the number of pancreas transplants performed in the Eurotransplant community has remained at a low level for several years. The results of a consecutive series of 40 simultaneous pancreas/kidney transplantations (SPK) performed between June 1994 and July 1996 demonstrate that high 1-year graft function rates of 87.1% for pancreas and 94.8% for kidney grafts can be achieved. Therefore, SPK can be recommended as a standard procedure for patients with insulin-dependent diabetes mellitus and end-stage renal disease in Germany, too.

Adult↗
PubMed1997

Funding a primary care led NHS: achieving a model for more equitable allocation of healthcare resources at a sub-district level.

BACKGROUND: Current resource allocation for health services have developed in a haphazard and inequitable way. This project aimed to determine a fairer and more rational way to distribute health authority's (HA's) money to general practitioners (GPs). METHODS: A dataset was developed to examine the way resources were spent on patients at the level of general practice. Important managerial aspects of the project were addressed. This involved the establishment of the 'Equity Group' of GPs to work with the HA. The group sought a measure of health need that was rigorous and scientifically based but was also practical and politically acceptable to GPs and the HA. The York Relative Needs Index (RNI) was chosen, and applied to populations at practice level. An implementation plan was then developed by the Equity Group. RESULTS: Results demonstrated considerable inequalities between practices in age-adjusted use of healthcare resources. There was low correlation between the level of need in practices and the per capita expenditure. Applying the York RNI to practice populations indicated current practice allocations were within the range 82-126 per cent of their needs-based target. The managerial implications of the proposed changes are described. CONCLUSIONS: The new methods for resource allocation appear to be an advance on the unplanned methods which have evolved. Full evaluation of the long-term results of redistributing health resources will be needed. Important aspects of this project were the participation of GPs and general development of the concept of equity in North Derbyshire.

Age Factors↗
PubMed1997

On-site HIV testing in resource-poor settings: is one rapid test enough?

OBJECTIVE: To determine the feasibility, accuracy and cost-effectiveness of a rapid, on-site, HIV testing strategy in a rural hospital, and to assess its impact on test turnaround time and the proportion of patients post-test counselled. DESIGN: Prospective comparison of two testing strategies [double rapid test on-site versus central enzyme-linked immunosorbent assay (ELISA)-based testing], and an economic evaluation. SETTING: Hlabisa Hospital, a rural South African district hospital. PATIENTS: A total of 454 consecutive adult inpatients requiring and consenting to HIV testing as part of their clinical management. MAIN OUTCOME MEASURES: Concordance between rapid tests, and between the rapid and ELISA strategies, test turnaround time, proportion of patients post-test counselled, and cost-effectiveness. RESULTS: HIV seroprevalence was 49.6%. Both rapid tests were concordant in all patients [one-sided 95% confidence interval (CI) of probability, 99.3-100]. The rapid strategy was 100% sensitive (95% CI, 97.9-100) and 99.6% specific (95% CI, 97.2-100) compared with the ELISA strategy. The mean interval between ordering a test and post-test counselling fell from 21 days prior to the introduction of the rapid test strategy to 4.6 days after its introduction (P < 0.00001). The proportion of patients post-test counselled increased to 96% from 17% after the introduction of the rapid test strategy (P < 0.00001). By using a double rapid test strategy the cost per patient post-test counselled was almost halved to US$ 11. Accuracy of the rapid strategy was not substantially increased by performing two tests. CONCLUSION: In high prevalence, resource-poor settings, rapid, on-site HIV testing is feasible, accurate and highly cost-effective, substantially increasing the number of patients post-test counselled. A single rapid test may be sufficient.

AIDS Serodiagnosis↗
PubMed1997

Comorbidity in ADHD: implications for research, practice, and DSM-V.

OBJECTIVE: Since the introduction of DSM-III/III-R, clinicians and investigators have shown increasing interest in the study of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity patterns is needed to guide treatment, research and future classification approaches. METHOD: The ADHD literature from the past 15 years was reviewed to (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the correlates and longitudinal predictors of comorbidity; and (3) determine the extent to which comorbid patterns convey unique information concerning ADHD etiology, treatment and outcomes. To identify potential new syndromes, the authors examined comorbid patterns based on eight validational criteria. RESULTS: The largest available body of literature concerned the comorbidity with ADHD and conduct disorder/aggression, with a substantially smaller amount of data concerning other comorbid conditions. In many areas the literature was sparse, and pertinent questions concerning comorbidity patterns remain unexplored. Nonetheless available data warrant the delineation of two new subclassifications of ADHD: (1) ADHD aggressive subtype, and (2) ADHD, anxious subtype. CONCLUSIONS: Additional studies of the frequency of comorbidity and associated factors are greatly needed to include studies of differential effects of treatment of children with various comorbid ADHD disorders, as well as of ADHD children who differ on etiological factors.

Aggression↗
PubMed1997

Inhibition of tumor necrosis factor and amelioration of brain infarction in mice.

Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated.

Animals↗
PubMed1997

A prospective multicenter trial of octreotide in 24 patients with visual defects caused by nonfunctioning and gonadotropin-secreting pituitary adenomas. French Multicenter Octreotide Study Group.

OBJECTIVE: The somatostatin analog octreotide has been demonstrated to improve optic tract compression caused by pituitary macroadenomas within hours of its administration and/or reduce tumor size in some patients. We report the results of a prospective multicenter study of the effects of octreotide on visual function and tumor size in patients with nonfunctioning pituitary adenomas or gonadotropin-secreting adenomas. METHODS: Twenty-four patients with visual defects caused by histologically confirmed macroadenomas were administered octreotide via continuous subcutaneous infusion, as follows: 100 micrograms the 1st day and, if necessary, 200 micrograms the 2nd and then 100 or 200 micrograms three times daily if visual function improved. Vision was assessed after 4 days, 1 month, and 2 months, including tumor size evaluation. Visual improvement was defined by a net gain of at least 2/10 in acuity and/or of more than 20% of the surface of one isopter (a reduction in tumor volume of > or = 20% of the initial measurement); opposite changes were defined as deterioration. RESULTS: Visual improvement was noted in 13 of 24 patients, 10 of 23 patients and 9 of 22 patients, and was not noted in 11 of 24 patients, 14 of 23 patients, and 13 of 22 patients after 4 days, 1 month, and 2 months, respectively. After 2 months, three adenomas had shrunk, three had not changed in size, and one had increased; visual function improved in the seven patients with these adenomas. Octreotide was discontinued in 13 patients for lack of efficacy. CONCLUSION: The incidence of visual improvement and tumor shrinkage noted in this study was higher than previously reported. Our data suggest that early onset of visual improvement might help in deciding which patients profit from octreotide. However, concomitant gain in visual acuity with deterioration in visual fields or visual improvement with an increase (moderate) in tumor size can occur.

Adenoma↗
PubMed1997

To treat or not to treat: issues in decisions not to treat older persons with cognitive impairment, depression, and incontinence.

OBJECTIVES: To examine decisions not to treat problems identified during outpatient geriatric assessment, particularly problems of cognitive impairment, depression, or urinary incontinence. DESIGN: A descriptive study using patients' medical charts and survey data and interviews with clinical staff. SETTING: Four hospital-based, ambulatory, geriatric assessment clinics in Allegheny Country, PA. PARTICIPANTS: The sample comprised 128 older adults, recruited to a randomized, controlled clinical trial, who had problems associated with cognitive impairment, depression, or urinary incontinence. RESULTS: Although treatment was recommended for most of the problems relating to cognitive impairment, depression, and/or incontinence experienced by this group, slightly more than one-third of cognitive impairment and depression problems and nearly one-half of incontinence did not receive treatment recommendations. Treatment rates varied considerably by condition and combination of comorbidity. Decisions not to treat are classified into six categories: patient or family refused treatment, the assessment was not completed, an intervention was already in place, concurrent problems or comorbities might have interfered with treatment, there was no documented diagnosis or there was a documented consideration and rule out of the problem, or no documented reason. CONCLUSION: Outpatient geriatric assessment units are designed to deal with the multiple problems experienced by their geriatric patients, and they identify successfully most problems presented by their frail constituents. However, identification of the patient's problems is only the first step in the assessment process and does not necessarily lead to either a documented diagnosis or to a treatment recommendation. Multiple social, cultural, environmental, and medical factors complicate the assessment process and, hence, the decision clinicians face when they decide whether to make recommendations to treat. These clinicians must weigh all medical and non-medical factors, including the patient's receptivity to treatment, when prioritizing the problems they deem to be treatable and making recommendations to treat.

Aged↗
PubMed1997

A multicenter, randomized trial comparing an active can implantable defibrillator with a passive can system. Jewel Active Can Investigators.

Replacing one defibrillation electrode lead by the defibrillator can may simplify implantation of the ICD. In this multicenter study, 304 patients were randomized to receive either the biphasic active can (AC) (model 7219C system, Medtronic, Inc.) or the passive can (PC) (model 7219D system). The AC and PC systems were compared with respect to their ability to meet the implant defibrillation criterion and to defibrillate VF, and to DFTs, implant time, patient adverse events, and survival rates. A higher percentage fulfilled the implant defibrillation criterion on the first configuration with the AC (86.3% vs 75.9% for PC; P = 0.023), and the first shock success for terminating induced VF was 94% for AC compared to 89% for PC (P = 0.026). DFTs were significantly lower (10.9 vs 12.7 J; P = 0.031), and implant time was significantly shorter for the AC patients (99.2 vs 112.0 min; P = 0.002). The two groups showed no significant differences in 3-month adverse event rates, 3-month survival, and hospital stay.

Adolescent↗
PubMed1997

Comparison of single-dose oral grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in men. The STD Study Group.

In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males.

Administration, Oral↗
PubMed1997

Clinical and biological heterogeneity in pseudohypoparathyroidism syndrome. Results of a multicenter study.

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome frequently associated with Albright's hereditary osteodystrophy (AHO). We conducted a multicenter study including 71 PHP children and 77 relatives. Erythrocyte Gsalpha biological activity was measured in each patient (normal range 85-110%). 61 patients were classified into four subtypes based on clinical and endocrine data and Gsalpha activity: 45 PHP Ia, 8 PHP Ib, 2 PHP II, and 6 PHP Ic. PHP Ia had decreased Gsalpha (58 +/- 9%), PHP Ib patients had PTH resistance, no AHO and normal Gsalpha (96 +/- 9%), PHP Ic patients had PTH resistance, AHO and no decreased Gsalpha (97 +/- 13%). The 10 remaining patients were considered to have pseudo-pseudohypoparathyroid (Pseudo-PHP) and were divided into two subtypes. One subtype had decreased Gsalpha and the second subtype had normal Gsalpha activity. The heterogeneous expression of Pseudo-PHP and thyrotropin resistance, which preceded parathyroid hormone resistance in 24% of the children, suggested that PHP might be a gradually evolving disease. GRF resistance was found in 4 out of 9 children investigated. The pedigree analysis showed PHP Ia had a dominant mode of inheritance with increased severity through generations. Pedigree analysis did not support a genomic imprinting hypothesis. Two children out of 9 had a chromosome 2 abnormality. This study confirms that Gsalpha activity is a significant marker in the diagnosis and classification of PHP.

Adolescent↗
PubMed1997

Acoustic measures of dysphonic severity across and within voice types.

The purpose of the study was to explore an interaction between pathologic voice type and the acoustic prediction of dysphonic severity. One hundred and two phonatory samples, representing a wide range of laryngeal conditions, were categorized by listeners into three voice types: breathy, rough, and hoarse. A second group of trained listeners rated the severity of the samples on a 7-point scale. Twenty-five frequency- and time-domain measures were used to predict perceptual severity. Multiple regression analyses showed that the most useful measure for the prediction of severity across voice types was noise-to-harmonic ratio (NHR). The severity of individual voice types was predicted with differential results on the basis of both short- and long-term measures of perturbation.

Adolescent↗
PubMed1997

Behavioral and neuroendocrine responses to sodium lactate infusion in subjects with posttraumatic stress disorder.

OBJECTIVE: Sodium lactate infusion has induced flashbacks accompanied by panic attacks in male combat veterans with posttraumatic stress disorder (PTSD) and concurrent panic disorder. This study addressed whether sodium lactate induces flashbacks or other intrusive PTSD symptoms in PTSD patients free of concurrent panic disorder. METHOD: Behavioral, cardiovascular, catecholamine, and cortisol responses to infusion of 0.5 M sodium lactate were compared among seven subjects with PTSD without panic disorder, seven subjects with panic disorder only, and seven healthy subjects. RESULTS: Six of the seven PTSD subjects but no panic disorder or healthy subjects reported flashbacks or other intrusive PTSD symptoms during lactate infusion. Flashbacks were accompanied by substantial anxiety symptoms. Cortisol levels were low in the PTSD subjects. CONCLUSIONS: Sodium lactate induces flashbacks in persons with PTSD without comorbid panic disorder. The relationship between anxiety responses accompanying a PTSD flashback and those in a panic attack remains unclear.

Adult↗
PubMed1997

Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer.

PURPOSE: We performed a phase I study to determine the appropriate dose of PN401, a uridine (URD) prodrug, to use as a rescue agent for fluorouracil (FU) and than to determine the maximum-tolerated dose (MTD) of FU when given with PN401. PATIENTS AND METHODS: Patients with advanced cancer received oral PN401 as either a suspension or a tablet in escalating doses. A pharmacokinetic analysis was performed to determine which dose best achieved a target value of sustained levels of URD > or = 50 mumol/L. In the first phase of the study, all patients received a fixed dose of FU 600 mg/m2 as a rapid intravenous bolus followed by 10 doses of PN401 given at 6-hour intervals. PN401 therapy commenced 24 hours after FU. After determination of the appropriate dose of PN401, a second group of patients received escalating doses of FU with a fixed dose of PN401. RESULTS: Thirty-eight patients with advanced cancer received PN401 and FU. Pharmacokinetic analysis indicated that either 6.6 g of PN401 as an oral suspension or 6 g given in tablet form resulted in high bioavailability of URD, with sustained plasma concentrations greater than 50 mumol/L. In the second phase of the study, FU doses were escalated from 600 to 1,000 mg/m2. FU was given as a rapid intravenous bolus weekly for 6 weeks with a 2-week rest. The MTD of FU given in this fashion with PN401 rescue was 1,000 mg/m2, at which level two of six patients had neutropenic fever. FU at doses of 800 mg/m2 for 6 weeks was well tolerated without significant toxicity when given with PN401 rescue. CONCLUSION: Oral PN401 is well tolerated and total doses of 6 g every 6 hours yield sustained levels of URD in the target range of 50 mumol/L. The MTD of FU with PN401 rescue is 1,000 mg/m2 and the recommended dose for phase II trials is 800 mg/m2 given weekly for 6 weeks with dose escalation. Further studies to define better the appropriate interval for PN401 rescue and the appropriate dose of FU when given with biochemical modulation, such as with leucovorin, are indicated.

Acetates↗