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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 199 records · Page 11Linked to original sources
PubMed1999

Renal cell carcinoma. Guidelines for diagnosis and treatment.

Diagnosis of renal cell carcinoma (RCC) is established using sonography and confirmation by computed tomography (CT). Due to the widespread use of these imaging techniques for numerous indications, small renal tumors are increasingly detected by chance. As the sensitivity of CT is very high, treatment of RCC is routinely initiated without histological confirmation. Standard therapy of locally confined tumors without evidence of lymph node or hematogenic metastases is nephrectomy. However, the results of tumor excision equal those of nephrectomy if tumor size does not exceed 4 cm in diameter. Whereas the prognosis of organ-confined tumors is excellent, no curative treatment for primary metastasized RCC is available to date. Immunotherapy - the only systemic treatment modality with clinically relevant response rates - has so far failed to effect a survival advantage for the patient. Surgery is only potentially curative for asychronous metastases occurring more than 2 years after surgery.

Carcinoma, Renal Cell↗
PubMed1999

Memory self-appraisal in middle-aged and older adults with the apolipoprotein E-4 allele.

OBJECTIVE: Because subjective memory complaints may indicate subtle functional brain abnormalities, the authors studied the influence of the major genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele, on self-reports of memory performance in middle-aged and older adults. METHOD: Subjective and objective assessments of memory performance were compared in relation to the presence or absence of the APOE-4 allele in 39 cognitively intact persons with mild memory complaints. RESULTS: Subjects with the APOE-4 allele had lower scores on objective verbal memory and on the subjective memory measure for retrospective functioning. Among the subjects in the age range where APOE-4 has its greatest influence on the risk of Alzheimer's disease (55-74 years), the APOE-4 group had lower scores on the subjective memory measure for frequency of forgetting. Moreover, the standardized difference in retrospective functioning scores between the two genetic risk groups increased when the mid-age-range group was examined rather than the whole study group. CONCLUSIONS: The APOE-4 allele is associated with increased subjective memory impairment in middle-aged and older adults. Longitudinal studies of age-related memory loss should include genetic risk and subjective memory measures as potential predictors of decline.

Adult↗
PubMed1999

Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women.

A novel lipodystrophy syndrome (characterized by insulin resistance, hypertriglyceridemia, and fat redistribution) has recently been described in human immunodeficiency virus (HIV)-infected patients. However, investigation of the lipodystrophy syndrome has generally been limited to men; and a comprehensive evaluation of insulin, lipids, and regional body composition has not been performed in the expanding population of HIV-infected women. In this study, we assessed fasting insulin, lipid levels, virologic parameters, and regional body composition, using dual-energy x-ray absorptiometry, in a cohort of 75 HIV-infected women (age, 25-46 yr), in comparison with 30 healthy weight-matched premenopausal control subjects. HIV-infected women demonstrated significant truncal adiposity (38.5 +/- 0.9 vs. 34.9 +/- 1.3%, P < 0.05) hyperinsulinemia (15.9 +/- 1.5 vs. 7.5 +/- 0.6 microU/mL, P < 0.001) and an increased insulin-to-glucose ratio (0.2 +/- 0.02 vs. 0.1 +/- 0.03, P < 0.001), compared with control subjects. Insulin and the insulin-to-glucose ratio were increased, even among HIV-infected patients with low body weight (<90% of ideal body weight) (insulin, 13.3 +/- 2.8 microU/mL, P < 0.01 vs. control; insulin/glucose, 0.2 +/- 0.04, P < 0.01 vs. control). Insulin and the insulin-to-glucose ratio were most significantly elevated among patients with increased truncal adiposity (insulin, 28.2 +/- 3.2 microU/mL, P < 0.001 vs. control; insulin/ glucose, 0.32 +/- 0.04, P < 0.001 vs. control). In contrast, no differences in insulin were seen in relation to protease inhibitor (PI) use. Similarly, HIV-infected women also demonstrated significant hypertriglyceridemia (144 +/- 15 vs. 66 +/- 23 mg/dL, P < 0.01 vs. controls), which was present even among low-weight patients (148 +/- 32 mg/dL, P < 0.001 vs. control) but was not related to truncal adiposity or PI usage. These data demonstrate significant hyperinsulinemia and truncal adiposity in HIV-infected women. Our data suggest that these metabolic abnormalities occur at baseline in HIV-infected women, independent of PI use. However, these data do not rule out a direct effect of PI therapy on fat metabolism or indirect effects of PI therapy to further worsen glucose and lipid homeostasis in association with weight gain and disease recovery.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea.

Reduced bone density is observed in over half of women with anorexia nervosa (AN), in whom the risk of fracture is significantly increased even at a young age. It is unknown to what extent low bone density in AN differs from other conditions of premenopausal osteoporosis and is related to estrogen deficiency and/or other factors, such as nutritional status. We therefore investigated bone loss in nutritionally replete and nutritionally deplete amenorrheic women by comparing patients with AN (n = 30) to age-matched subjects with hypothalamic amenorrhea (HA; n = 19) in whom duration of amenorrhea, prior estrogen use, and age of menarche were comparable. Healthy, age-matched, eumenorrheic women were studied as a control group (NL; n = 30). Weight and nutritionally dependent factors including (body mass index, 20.7 +/- 0.3 vs. 16.7 +/- 0.3 kg/m2; P < 0.0001), insulin-like growth factor I (270 +/- 18 vs. 203 +/- 17 ng/mL; P < 0.01), percent body fat (26% vs. 19%; P < 0.0001), and lean body mass (38.7 +/- 1.1 vs. 34.3 +/- 0.8, P < 0.01) were significantly different between the HA and AN groups, respectively. The bone densities of the anterior-posterior (AP) spine, total hip, and total body measured by dual energy x-ray absortiometry were reduced in both amenorrheic groups compared to those in control subjects, but were significantly lower in women with AN than in those with HA. The t scores for AP spine and hip were -1.80 +/- 0.15 (AN), -0.80 +/- 0.22 (HA), and 0.28 +/- 0.19 SD (NL) for the AP spine and -1.62 +/- 0.17 (AN), -0.51 +/- 0.21 (HA), and 0.25 +/- 0.16 (NL) for the total hip, respectively (P < 0.01 for all comparisons). Among the amenorrheic subjects, duration of amenorrhea, age of menarche, and N-telopeptide were inversely correlated with bone density at all sites, whereas body mass index, insulin-like growth factor I, lean body mass, and fat intake were positively correlated with bone density at all sites measured. In multivariate regression analyses, bone density was most significantly related to lean body mass (P = 0.05 and P = 0.03 for the spine and hip, respectively), but not to the duration of amenorrhea or other indexes of estrogen status among patients with AN. In contrast, bone density of the lumbar spine was significantly related to weight and duration of amenorrhea among patients with HA. These data demonstrate that the severity of osteopenia in AN is greater than that in patients with HA and is critically dependent upon nutritional factors in addition to the degree or duration of estrogen deficiency itself. Lean body mass, independent of the duration or severity of estrogen deficiency, is an important predictor of bone loss among women with AN.

Absorptiometry, Photon↗
PubMed1999

Laparoscopic adjustable gastric banding: a prospective 4-year follow-up study.

BACKGROUND: A body mass index of > or =40 kg/m2 represents clinically severe obesity and warrants operative treatment if requested. The adjustable silicone gastric band and the Swedish adjustable gastric band are recently produced laparoscopic gastric restrictive devices. The aim of this study was to assess all complications linked to both the available gastric bands in a long-term follow-up. METHODS: In a prospective study, the effects, complications, and outcomes of this procedure were analyzed. The complications found were divided into early and general complications, and complications correlated to the bands. The technique of laparoscopic adjustable gastric banding is described. Follow-up was performed by the operating team. RESULTS: Between July 1994 and August 1998, the authors operated on 158 patients and performed 102 adjustable silicone gastric bandings and 54 Swedish adjustable gastric bandings. The mean age at surgery was 36 years (range 17-72). The mean preoperative weight was 136 kg (89-230). Of 158 patients who underwent laparoscopic procedures, 156 (98%) could be followed up (mean 28 months; duration of follow-up, 6 weeks to 46 months). In early postoperative complications that required operation, one trocar wound hematoma (0.6%) and one wound infection of the port site (0.6%) were observed. The late complications that required reoperation were two pouch dilatations (1.3%), three band leakages (2%), one band migration (0.6%), and one late infection of the port (0.6%). A debanding operation was necessary in one patient because of esophageal dysmotility disorder. No early or late postoperative mortality was registered. The overall reoperation rate is currently about 7%. CONCLUSION: The operation is safe and effective. Moreover, adjustable gastric banding is fully reversible and is adjustable to the patient's needs. This study verifies the importance of correct operating technique. The authors' study and experience clearly indicate that laparoscopic adjustable gastric banding is an attractive alternative in the surgical treatment of morbid obesity.

Adolescent↗
PubMed1999

Investigating fatigue of less than 6 months' duration. Guidelines for family physicians.

OBJECTIVE: To develop an evidence-based systematic approach to assessment of adult patients who present to family physicians complaining of fatigue of less than 6 months' duration. The guidelines present investigative options, making explicit what should be considered in all cases and what should be considered only in specific situations. They aim to provide physicians with an approach that, to the extent possible, is based on evidence so that time and cost are minimized and detection and management of the cause of the fatigue are optimized. QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the key words "family practice" and "fatigue." Articles about chronic fatigue syndrome were excluded. Articles with level 3 evidence were found, but no randomized trials, cohort studies, or case-control studies were found. Articles looking specifically at the epidemiology, demographics, investigations, and diagnoses of patients with fatigue were chosen. Articles based on studies at referral and specialty centres were given less weight than those based on studies in family physicians' offices. MAIN MESSAGE: Adherence to these guidelines will decrease the cost of investigating the symptom of fatigue and optimize diagnosis and management. This needs to be proved in practice, however, and with research that produces level 1 and 2 evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6 months' duration should be assessed for psychosocial causes and should have a focused history and physical examination to determine whether further investigations should be done. The guidelines outline investigations to be considered. The elderly require special consideration. These guidelines have group validation, but they need to be tested by more physicians in various locations and types of practices.

Adult↗
PubMed1999

Extremity pain in a child: a case report of leukemia.

Early clinical diagnosis of leukemia in a child is difficult. Leukemia must be considered in the differential diagnosis of extremity pain in children, especially if the "bone" pain is out of proportion to a suspected etiology. Initial laboratory studies, radiographs, and scintigraphy may be normal. Indistinct radiographic findings of periosteal reaction, osteolytic lesions, sclerotic lesions, osteopenia, or leukemic lines in a child older than two years should alert a physician to the possibility of leukemia. Clinical suspicion of leukemia should be piqued if bone scan results seem to be inconsistent with a suspected diagnosis or unanticipated sites of increased metabolic activity are found in the lower extremities. If leukemia is probable, a bone marrow aspiration may be needed to confirm the diagnosis.

Child↗
PubMed1999

Time for physicians to reconfigure.

The days when medical professionals made unilateral patient-care decisions are gone. Accelerating trends are converging to create a climate for what we call "consumer-centric healthcare," and that raises new and unsettling questions for physicians.

Community Participation↗
PubMed1999

Coronary artery bypass surgery in women and men: preoperative profile and postoperative outcomes.

The incidence and presentation of symptoms of coronary heart disease differ in women and men. Gender variations also have been documented in their postoperative recovery after coronary artery bypass surgery. Women undergoing this procedure are older and have more preoperative co-morbidities. The presence of these health problems translates into unequal rates of morbidity and mortality for women and men during their postoperative recovery in the hospital and has implications for adult-health nurses.

Coronary Artery Bypass↗
PubMed1999

[Prophylactic treatment in children with migraine presenting changes in electrophysiological and cerebral blood flow examinations: preliminary report].

Idiopathic headache is common in children, but lack of specific tests makes diagnosis and treatment of migraine difficult. It has been proved, that in some migrainous children paroxysmal changes in eeg records can be found. The aim of the study was to examine the influence of prophylactic treatment on clinical course and bioelectric brain activity in children. The group examined consisted of 50 migrainous children (29 girls and 21 boys aged 6-18 years, mean 11.5 y.). In every patient routine eeg and ecg were recorded, and in 30 of them cerebral blood flow was examined. Some ecg abnormalities were observed in 6 children (12%) and cerebral blood flow disturbances--in 23 (77%). In 15 patients, in whom paroxysmal changes in routine eeg were found, an average 6-month prophylactic antimigrainous treatment (with Hydacorn in 14 and with Sermion in 1 patient) was performed and then control routine eeg and 24-hours eeg were recorded. In all children clinical improvement was observed after prophylactic medication. Paroxysmal changes in eeg records persisted in 6 children. The coexistence of electroencephalographic changes with disturbed cerebral blood flow migrainous children can indicate some connection between migraine and epilepsy, and/or reflect an influence of angiospasm resulting in hypoxia on the incidence of epileptiform changes in eeg records. The obtained results show clinical efficiency of combined treatment in child migraine and they reflect its good influence on bioelectrical brain activity.

Adolescent↗
PubMed1999

Breast cancer: challenges and opportunities.

The pace of research in breast cancer has picked up significantly in recent years, due to both increased public awareness and improved technology. The availability of many new agents in an already crowded field has resulted in several challenges (both practical and conceptual) for the research community. This report suggests that the "business-as-usual" approach to drug development has important limitations rendering it inadequate to the current research climate. Future drug development, in the form of biologically targeted therapies, offers the best hope for defeating this disease.

Angiogenesis Inhibitors↗
PubMed1998

Microsatellite analysis of plasma DNA from patients with clear cell renal carcinoma.

Deletions of DNA sequences on chromosome 3p [loss of heterozygosity (LOH)] are characteristic of clear cell renal carcinoma, which accounts for about 80% of all renal malignancies. Comparing tumor DNA to DNA from normal cells, LOH analysis of microsatellite sequences has aided in molecular diagnosis of renal carcinoma. Because clinically useful tumor markers do not exist for this cancer entity, the aim of the present study was to detect chromosome 3p microsatellite alterations (LOH and microsatellite instability) in plasma DNA from patients with clear cell renal carcinoma. Four chromosome 3p microsatellites (D3S1307, D3S1560, D3S1289, and D3S1300) were amplified by fluorescent PCR using DNA isolated from normal blood cells and plasma of 40 patients. Corresponding tumor DNA was available from 21 patients. Analyzing PCR products on an automated DNA sequencer, we found LOH in at least one locus in 25 plasma samples (63%), and 14 plasma samples (35%) exhibited LOH at more than one locus. Microsatellite instability of plasma DNA was detectable in one patient (3%). No significant association of advanced (>T2N0M0) tumor stages with LOH in plasma DNA could be demonstrated. If present, modifications of plasma DNA and tumor DNA were identical. No alterations of plasma DNA were found in healthy controls. Analysis of plasma DNA from patients with clear cell renal carcinoma reveals tumor-specific microsatellite alterations and may therefore have diagnostic potential as a molecular tumor marker.

Adenocarcinoma, Clear Cell↗
PubMed1998

The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement.

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.

Administration, Oral↗
PubMed1998

Two distantly positioned PDZ domains mediate multivalent INAD-phospholipase C interactions essential for G protein-coupled signaling.

Drosophila INAD, which contains five tandem protein interaction PDZ domains, plays an important role in the G protein-coupled visual signal transduction. Mutations in InaD alleles display mislocalization of signaling molecules of phototransduction which include the essential effector, phospholipase C-beta (PLC-beta), which is also known as NORPA. The molecular and biochemical details of this functional link are unknown. We report that INAD directly binds to NORPA via two terminally positioned PDZ1 and PDZ5 domains. PDZ1 binds to the C-terminus of NORPA, while PDZ5 binds to an internal region overlapping with the G box-homology region (a putative G protein-interacting site). The NORPA proteins lacking binding sites, which display normal basal PLC activity, can no longer associate with INAD in vivo. These truncations cause significant reduction of NORPA protein expression in rhabdomeres and severe defects in phototransduction. Thus, the two terminal PDZ domains of INAD, through intermolecular and/or intramolecular interactions, are brought into proximity in vivo. Such domain organization allows for the multivalent INAD-NORPA interactions which are essential for G protein-coupled phototransduction.

Amino Acid Sequence↗
PubMed1998

Non-radioactive measurement of telomerase activity in human bladder cancer, bladder washings, and in urine.

Early diagnosis is still the most important prerequisite for successful cancer treatment and this holds true for bladder cancer. Urine cytology is commonly used as a non-invasive screening procedure for the detection of bladder carcinoma, but this method is labour-intensive and often generates false-negative results. The ribonucleoprotein telomerase appears to be promising new cancer marker, since its activity has been reported to correlate with indefinite growth. The aim of this study was to investigate whether telomerase activity can be detected in bladder cancer and in corresponding bladder washings. For this purpose, a sensitive non-radioactive TRAP (telomeric repeat amplification protocol) detection system was developed. With this technique, telomerase activity was found in 95 per cent of the carcinomas (n = 20), in 70 per cent of the corresponding bladder washings, but in none of the urine samples obtained from patients with bladder carcinoma. No telomerase activity was detectable in normal urothelium or in samples from dysplastic urothelium. The data obtained from bladder washings show that superficial carcinoma cells released into the bladder still harbour telomerase activity. The absence of telomerase activity in voided urine is thus most likely due to degradation or inactivation under these conditions. The high rate of telomerase activity in bladder carcinoma indicates that the activation of telomerase in a common step in the tumourigenesis of bladder cancer.

Aged↗