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Biomedical subjects

H Freeman

Publications and source records attributed to H Freeman.

At least 19 recordsLinked to original sources
PubMed2006

Type-2 diabetes: a cocktail of genetic discovery.

Diabetes is one of the most challenging health problems of the 21st century with an alarming increase in the prevalence of type-2 diabetes mellitus (T2DM) and associated conditions such as hypertension, dyslipidemias and obesity. T2DM is a complex genetic disease comprised of many metabolic disorders with a common phenotype of glucose intolerance. Patients with T2DM would have inherited a variety of different genetic factors that together with environmental factors combine as the primary cause. This complicates the genetic study of the disease and means that different methodological approaches are needed if we hope to identify susceptibility genes and genetic variants. The biochemical and physiological processes that underpin T2DM are still unclear although most certainly involve impairment in insulin secretion and insulin action. In this review, we will discuss the most exciting advances in understanding the genetics of T2DM by looking at recent discoveries employing human association studies and candidate genes arising from animal models.

Animals↗
PubMed2006

Nicotinamide nucleotide transhydrogenase: a link between insulin secretion, glucose metabolism and oxidative stress.

This paper reviews recent studies on the role of Nnt (nicotinamide nucleotide transhydrogenase) in insulin secretion and detoxification of ROS (reactive oxygen species). Glucose-stimulated insulin release from pancreatic beta-cells is mediated by increased metabolism. This elevates intracellular [ATP], thereby closing KATP channels (ATP-sensitive potassium channels) and producing membrane depolarization, activation of voltage-gated Ca2+ channels, Ca2+ influx and, consequently, insulin secretion. The C57BL/6J mouse displays glucose intolerance and reduced insulin secretion, which results from a naturally occurring deletion in the Nnt gene. Transgenic expression of the wild-type Nnt gene in C57BL/6J mice rescues the phenotype. Knockdown of Nnt in the insulin-secreting cell line MIN6 with small interfering RNA dramatically reduced Ca2+ influx and insulin secretion. Similarly, mice carrying ENU (N-ethyl-N-nitrosourea)-induced loss-of-function mutations in Nnt were glucose intolerant and secreted less insulin during a glucose tolerance test. Islets isolated from these mice showed impaired insulin secretion in response to glucose, but not to the KATP channel blocker tolbutamide. This is explained by the fact that glucose failed to elevate ATP in Nnt mutant islets. Nnt is a nuclear-encoded mitochondrial protein involved in detoxification of ROS. beta-Cells isolated from Nnt mutant mice showed increased ROS production on glucose stimulation. We hypothesize that Nnt mutations enhance glucose-dependent ROS production and thereby impair beta-cell mitochondrial metabolism, possibly via activation of uncoupling proteins. This reduces ATP production and lowers KATP channel activity. Consequently, glucose-dependent electrical activity and insulin secretion are impaired.

Animals↗
PubMed2001

Dysplasia-associated polypoid mucosal lesion in a pelvic pouch after restorative proctocolectomy for ulcerative colitis.

A 32-year-old man with ulcerative colitis had a colectomy for toxic colitis. Later, a rectal mucosectomy was performed along with the creation of a pelvic pouch. In 1998, approximately 10 years after this staged restorative proctocolectomy was completed, endoscopic examination of the pelvic pouch detected a small mucosal polypoid mass lesion. Although the lesion had the macroscopic appearance of an inflammatory polyp, microscopic sections of the resected lesion revealed dysplastic changes. Endoscopic polypectomy was performed to remove the lesion, and further histological surveillance examinations of the pelvic pouch have not detected additional dysplastic mucosal changes.

Adult↗
PubMed2000

External beam irradiation as an adjunctive treatment in failing dialysis shunts.

PURPOSE: To evaluate the utility of low-dose irradiation as adjunctive treatment for failing dialysis shunts related to stenoses. MATERIALS AND METHODS: Thirty-one patients with 41 lesions in their dialysis shunts were successfully enrolled for this study. After imaging of the shunt and calculation of venous stenoses, each patient was randomized into one of two segments of the protocol: (i) angioplasty and/or stent placement alone, and (ii) angioplasty and/or stent placement followed by external beam irradiation. All patients with significant venous stenoses (> or =50%) were treated with appropriately sized PTA (percutaneous transluminal angioplasty) and Wallstents. Patients randomized to the external irradiation segment underwent localized irradiation via a Theratron cobalt unit of 7 Gy 0-24 hours and 24-48 hours after intervention. Those patients randomized to the control group received no additional treatment. Clinical follow-up included resumption of successful dialysis with appropriate hemodynamic parameters. Two follow-up shunt images were obtained, follow-up 1 (fu-1) from 90 to 179 days and follow-up 2 (fu-2) from 180 to 365 days. Percentages of significant recurrent stenoses, defined as greater than 50%, were recorded and re-treated as needed. RESULTS: Sixteen of the 31 patients underwent external beam irradiation. There were 21 lesions in the test group that underwent irradiation after intervention, and 20 lesions were treated with intervention alone. There were seven native arteriovenous fistulas and 24 Gore-tex grafts. All stenoses were either venous outflow stenoses (68%) or central stenoses (32%). The authors utilized chi2 analysis to compare restenoses rates between the control and irradiated groups at fu-1 (P<.99) and fu-2 (P<.10). CONCLUSIONS: Although the results show that external beam irradiation has minimal effects on the restenoses of dialysis grafts when used in conjunction with PTA and stent placement, further studies with a larger, more homogenous population are needed to assess the trend of improving patency rates after external beam irradiation.

Adult↗
PubMed2000

Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom.

OBJECTIVE: To estimate the cost effectiveness of different classes of antidepressants in the UK National Health Service. DESIGN, PATIENTS AND INTERVENTIONS: The use of the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with that of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with major depressive disorder (MDD). A meta-analysis determined the clinical success rate, and a decision tree was constructed by interviewing general practitioners and psychiatrists. Adding pharmacological and nonpharmacological treatment costs, meta-analytic rates were applied to the decision tree to calculate the expected cost and outcome for each drug. Cost effectiveness was determined using a composite measure of outcome [symptom-free days (SFD)]. MAIN OUTCOME MEASURES AND RESULTS: The meta-analysis included data from 44 studies on 4033 patients. The highest overall efficacy rate for outpatients with MDD was with venlafaxine use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with venlafaxine yielded the lowest outpatient cost for a SFD (10.53 Pounds), compared with 13.23 Pounds for SSRIs and 15.52 Pounds for TCAs (1998 values). CONCLUSIONS: Using this economic model, venlafaxine appears to be a cost-effective treatment for outpatients with MDD in the UK.

Antidepressive Agents↗
PubMed1999

Psychiatry in the National Health Service 1948-1998.

BACKGROUND: The 50th anniversary of the inauguration of the NHS provided the occasion to review the evolution of mental health services and of psychiatry itself in Britain during that period. AIMS: The principal themes to be followed were the decline of a mental hospital system that had existed for over a century, the development of an alternative policy of 'community care', the emergence of a numerous and well-trained psychiatric profession, and the interaction between political and legal processes and mental health care. METHOD: An examination of Ministry of Health and Department of Health and Social Security files in the Public Record Office, interviews with influential figures, examination of the secondary literature, and personal experience of events described. RESULTS: The material has been analysed, in the light of the expressed aims, and important trends have been described. The current situation is assessed. CONCLUSIONS: The replacement of one system of care and treatment in Britain by another has been a process fraught with overwhelming difficulties. While adhering to the aim of 'community care', governments have been reluctant to provide the means for achieving this. The psychiatric profession is now faced with very large but ill-defined responsibilities.

Government↗
PubMed1998

Management of extremely low birth weight infants: perceptions of viability and parental counseling practices.

OBJECTIVE: To determine physician opinions, parental counseling, and medical practices for extremely low birth weight (LBW) infants. METHODS: A retrospective survey was sent in August 1996 to 450 California physicians practicing obstetrics. RESULTS: There was a 41% response rate. The mean thresholds for antenatal steroid administration, cesarean delivery for fetal distress and delivery room resuscitation were gestational age between 23 and 24 weeks and weight close to 500 g. Most obstetricians counsel parents regarding survival, resuscitation, and possible death in the delivery room before delivery of an extremely LBW infant. Just over 60% of obstetricians believe that parents have a role in deciding not to resuscitate an infant born at 22 weeks' gestation, this decreases to less than 50% at 24 weeks, and decreases further to less than 30% by 26 weeks' gestation. Just over 40% of obstetricians report their counseling is affected by pediatric opinion, 33% by previous maternal perinatal losses, and less than 20% by maternal drug use or lack of prenatal care, and young maternal age. Language barriers, parental education level, and family insurance affect treatment options in less than 10% of obstetricians. CONCLUSION: Obstetric opinions about delivery room resuscitation of extremely LBW infants are influenced by birth weight and gestational age thresholds, infant, and parental factors. There is a limited willingness by physicians to allow a parental role in decision making in the delivery room for extremely LBW infants.

Adult↗
PubMed1998

A revised measure of symptom-specific health care use.

The objective was to determine physicians' ratings of the clinical importance of common adult symptoms and to use these ratings to develop a new measure of symptom-specific use of health care services. We developed a list of common symptoms using the National Ambulatory Medical Care survey. We surveyed a random sample of internists, family physicians, general practitioners and emergency medicine physicians from the American Medical Association's Physician Masterfile and asked them to rate symptoms' seriousness, impact on quality of life and urgency of need for medical attention. The symptoms' prevalences were determined in a general population survey (National Access to Care Survey). Eleven items were classified as "serious" (median seriousness ratings of 7 or higher on scale from 1 to 10); most of these also were judged to have high impact on quality of life. Another 12 items that were not judged "serious" had median quality of life impact scores of 7 or higher and were classified as "morbid". Sixteen items did not meet criteria for either "serious" or "morbid" symptoms and were classified as "intermediate". Six other items had median seriousness and quality of life impact scores of 3 or less and were classified as "benign". A total of 24 of these items (7 "serious", 8 "morbid", 8 "intermediate" and 1 "benign") were selected to form the symptom-response measure. In the national survey, 26.3% reported one or more serious symptom, 30.6% reported one or more morbid symptom and 29.6% reported one or more intermediate symptom. This new instrument expands on earlier "symptom-response" measures by including a larger number and a broader spectrum of symptoms. This measure should be useful to assess differences in patterns of health care use for particularly serious or morbid conditions; such variations may indicate problems with access to medical care.

Adult↗
PubMed1997

Early onset of action of amineptine.

A priority in the treatment of depression is to obtain rapid improvement at an early stage. Since depressed patients, who are often convinced that nothing can be done for them, may well have difficulty in adhering to the therapeutic management plan, they can be both uncooperative and neglectful of treatment measures. The rapid correction of this often resigned apathy is an essential aspect of treatment. According to a variety of clinical criteria, amineptine often achieves rapid improvement, particularly on measures of psychomotor retardation. Initially, antidepressant medication is an essential measure in the relief of depressive symptoms, although subsequently, it may also become a complement to psychotherapeutic support. Amineptine has been shown to act directly on the dopaminergic pathway, unlike other antidepressants, which act on this system only via their effects on the serotonergic or noradrenergic systems.

Antidepressive Agents, Tricyclic↗
PubMed1997

Cortical and hippocampal volume deficits in temporal lobe epilepsy.

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.

Adolescent↗
PubMed1997

Prospective evaluation of neutrophil autoantibodies in 500 consecutive patients with inflammatory bowel disease.

Previous studies have shown antineutrophil cytoplasmic autoantibodies (ANCA) in patients with inflammatory bowel disease (IBD). A particular subclass, the so-called 'atypical' (perinuclear) p-ANCA type, occurs in the majority of patients with ulcerative colitis. The purpose of this prospective study was to assess, in a blinded fashion, this 'subclinical' serological marker in a consecutive series of IBD patients. Five hundred patients were evaluated, including 247 patients with ulcerative colitis and 253 with Crohn's disease involving the small and/or large intestine. Overall, 194 (38.8%) of all patients with IBD were positive, including 164 (66.3%) with ulcerative colitis and 30 (11.9%) with Crohn's disease. Except for coexistent sclerosing cholangitis, no other clinical or laboratory variable had an effect on the rate of ANCA detection. This is the largest single study of ANCA in patients with IBD and the only study to provide data solely from a single Canadian centre. Results emphasize the immunopathological differences between ulcerative colitis and Crohn's disease, and indicate that both disorders are heterogeneous inflammatory disease processes.

Adult↗
PubMed1997

The costs and effects of cervical and breast cancer screening in a public hospital emergency room. The Cancer Control Center of Harlem.

OBJECTIVES: This study assessed the cost-effectiveness of cervix and breast cancer screening in a public hospital emergency room. METHODS: Age-eligible women with nonurgent conditions and without recent screening were offered screening by a nurse. A decision analysis compared the costs and outcomes of emergency room screening and standard hospital screening efforts. RESULTS: The undiscounted cost-effectiveness results for establishing new programs were $4050 (cervical cancer), $403,203 (breast cancer), and $4375 (joint cervix and breast cancer) per year of life saved. If screening is added to an existing program, results are more favorable ($429, $21,324, and $479 per year of life saved for cervix, breast, and joint screening, respectively). Results were most sensitive to volume and probability of receiving treatment after an abnormal screen. CONCLUSIONS: Emergency room screening was cost-effective for cervical cancer; breast cancer screening was relatively expensive given the low number of women reached. More intensive recruitment and follow-up strategies are needed to maximize the cost-effectiveness of such programs.

Breast Neoplasms↗