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Biomedical subjects

M Silverman

Publications and source records attributed to M Silverman.

At least 91 records · Page 5Linked to original sources

Follicular and Hürthle cell carcinoma: predicting outcome and directing therapy.

BACKGROUND: Follicular thyroid cancer is a heterogeneous disease including follicular and Hürthle cell and tumors with and without vascular and major capsular invasion. Analyses of prognosis and risk groups have been criticized for not taking these differences into account. METHODS: Retrospective analysis was done of 240 patients treated from 1940 to 1997. RESULTS: Ninety-two patients without vascular or major capsular invasion followed up for a median of 14 years had no recurrences or deaths. In the remaining 148 patients, 32 had Hürthle cell and 116 had follicular cell carcinoma. Patients with Hürthle cell carcinoma were significantly older (55 vs 47 years; P = .0014). Lymphatic metastases did not influence outcome. Patients who were at high risk by age and sex, metastases, extent, and size had a 20-year survival rate of 36% for follicular and 35% for Hürthle cell carcinoma; patients at low risk had 20-year survival rates of 94% and 89%, respectively, with no significant difference between follicular and Hürthle cell carcinoma. Recurrences were treated successfully in 33% of patients with follicular carcinoma but never cured in patients with Hürthle cell carcinoma. Bilateral versus unilateral operation or radioiodine for ablation did not alter outcome. CONCLUSIONS: Follicular and Hürthle cell carcinoma with minimal capsular invasion behaved benignly. Age and sex, metastases, extent, and size risk criteria differentiate strongly between patients with high-risk and low-risk follicular and Hürthle cell carcinoma. Controlling for risk factors, Hürthle cell and follicular cell carcinomas have similar prognoses.

Adenocarcinoma, Follicular↗

Glutathione and neonatal lung disease.

Glutathione (GSH) was measured using HPLC-electrochemical detection in bronchoalveolar lavage fluid from 28 neonates for up to 21 days after birth. GSH levels varied from 0.1-11.2 mumol l-1 (with a geometric mean concentration of 1.3 mumol l-1). GSH in epithelial lining fluid was estimated using the urea dilution method at 15.0 mumol l-1 (range 0.5-196 mumol l-1), which is significantly lower than observed in adult subjects. There was an L shaped relationship between GSH and the two markers of oxygen therapy, oxygen index and FiO2. The lowest GSH levels were associated with the group of infants with the most severe airways problems who required high oxygen.

Bronchoalveolar Lavage Fluid↗

Recruiting older adults for clinical trials.

More than 400 community-dwelling older adults were recruited into a clinical trial which compared the effectiveness of diagnosis and treatment through geriatric assessment with that provided through usual community physician care. Six recruitment methods were utilized: referrals, solicitations, presentations, media, mailings, and fliers. Each method is described and its results reported in terms of numbers recruited, yield, and cost per participant. The most efficient method was referrals; the method producing the largest number was presentations; the least effective method was fliers. Problems and solutions are discussed, and guidelines for recruiting older adults are suggested. These guidelines include: monitoring with accompanying adaptation, targeting the groups most likely to benefit, providing incentives, and reducing uncertainty among potential participants.

Advertising↗

Acute renal failure due to indinavir crystalluria and nephrolithiasis: report of two cases.

Two patients with oliguric acute renal failure (ARF) attributed to crystalluria and nephrolithiasis with obstructive uropathy caused by the human immunodeficiency virus protease inhibitor indinavir are described. In both patients, ARF resolved with administration of intravenous fluids. One patient required urologic intervention to relieve bilateral ureteral obstruction.

Acute Kidney Injury↗

Studies of the renal action of melatonin: evidence that the effects are mediated by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral membrane of the proximal tubule.

The pineal hormone melatonin controls circadian behavior of a variety of organs in different species, including humans. However, the precise mechanism (or mechanisms) by which this occurs remains largely unknown. At the cellular level its effects are believed to be mediated via interaction with specific melatonin receptors (MR), which have previously been cloned from human brain (Mel1a) and retina (Mel1b). At the tissue level, MR have been investigated primarily through empirical definition of specific binding sites, but so far there has been little success in biochemical or molecular characterization of native MR. In the kidney, there is strong circumstantial evidence that melatonin affects diurnal variations in renal function, but relatively little is known about the overall glomerular vs. tubular contributions to these effects. The strategy behind the present study was to use a panel of peptide-specific antibodies to identify MR proteins in various tissues, and from a determination of the intrarenal distribution of MR, gain insight into the mechanism by which melatonin might regulate kidney function. We used two peptide-specific antibodies directed against different regions of Mel1a to identify MR. Our results show that the native Mel1a receptor is a 37 kilodalton (kDa) protein in human and rat brain. Further, immunofluorescent studies carried out in guinea pig kidney have revealed that anti-Mel1a antibody is also localized to the basolateral membrane (BLM) of the renal cortical epithelium, especially the early proximal tubule. Immunoblotting of purified BLM fractions from guinea pig renal cortex and small intestine using the two different peptide-specific antibodies reveals the presence of a single peptide-blockable band at 37 kDa. These same BLM fractions also demonstrate the presence of high-affinity 2-[125I]iodomelatonin (125I-MEL) binding sites, with the pharmacological specificity of binding expected of the Mel1a receptor subtype, inhibited by guanosine 5'-O-(3'-thiotriphosphate) (GTPgammaS) and pertussis toxin. We conclude that functional MR in guinea pig kidney and small intestine are of the Mel1a subtype, and are expressed as 37 kDa proteins localized to the BLM and coupled to a pertussis toxin-sensitive G-protein (Gi). This localization strongly suggests that the proximal tubule plays a significant role in mediating the renal action of melatonin.

Animals↗

Treatment of renal failure and blood pressure.

Some of the more important advances in slowing progression of renal disease in the past few years include the following: the identification of specific racial groups, such as African-Americans and Mexican-Americans, who are at higher risk for renal disease progression than the general population; the observation that African-Americans may require lower levels of blood pressure reductions (i.e. < 125/75 mmHg) than the general population in order to achieve a similar degree of protection against renal disease progression; the understanding that angiotensin-converting enzyme inhibitors in the early stages of diabetic renal disease and nondihydropyridine calcium-channel blockers in those with established renal insufficiency from diabetes slow renal disease progression and reduce proteinuria; and lastly, aggressive blood pressure reduction in dialysis patients is associated with a reduction in cardiovascular events.

Adrenergic beta-Antagonists↗

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↗

Risk assessments for acute violence to third parties: a review of the literature.

OBJECTIVES: To provide an overview of risk assessments for acute violence to third parties by combining a clinical and research focus and to offer guidelines to physicians conducting clinical assessments. METHOD: A computerized literature search of the MEDLINE and PSYCHINFO data bases from 1967 to 1996 was completed using the key words violence, aggression, dangerous behaviour, risk, risk assessment, risk factors, and practice guidelines. The search yielded 116 relevant references, 26 of which were original research articles on risk factor identification. A secondary search, based on the citations from the primary search, yielded an additional 8 general discussion articles. RESULTS: Risk assessments may be conducted using different methods, although all methods should be systematic and comprehensive. Research shows that risk assessments do have validity for use in short-term prediction and that it is possible to develop clinical guidelines in this area. A combined clinical and research approach holds the most promise for improving the accuracy of probability estimates, and most published guides and tools rely on such a combination. CONCLUSIONS: Risk assessments are an important and necessary part of the clinical examination. Because this field has sufficiently evolved, there is abundant literature to refer to when determining what constitutes an acceptable assessment for risk of violence to third parties and when it is appropriate to conduct such an examination.

Duty to Warn↗

Factors relating to the severity of symptoms at 5 yrs in children with severe wheeze in the first 2 yrs of life.

Wheezing in early childhood covers a wide spectrum of morbidity. Since little is known about the factors determining either the pattern or the severity of this range of symptoms, 51 children, admitted to hospital with acute wheeze in the first 2 yrs of life, were monitored prospectively between the ages of 4.5-5.5 yrs. Our hypothesis was that the predictors of severe episodes and of interval symptoms in 5 year olds would differ. Symptom diaries were kept, from which the symptom pattern and severity was assessed. The frequency and severity of acute episodes were analysed separately from day-to-day (interval) symptoms. A physiological assessment was made at 5 yrs. During the 12 month study period, 11 children were symptom-free, 15 were reported to wheeze only in response to viral infections, and 25 wheezed from multiple triggers. Bronchial responsiveness was significantly increased in those with a family history of asthma but was unrelated to any index of atopy. In a multiple logistic regression analysis, a family history of asthma and a personal history of allergy (but not results of skin-prick testing or serum immunoglobulin E (IgE) significantly predicted both attack severity and interval symptoms. An additive effect of two factors (atopy plus a family history of asthma or bronchial responsiveness) on symptom severity was suggested, without any evidence of an interaction. It is concluded that in this population of 5 year olds, with an early history of severe wheezing, familial bronchial responsiveness and atopy of operated independently to determine both interval symptoms and attack severity.

Acute Disease↗

Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line.

The expression of melatonin receptors (MR) of the Mel1a subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro culture model. Epithelial cell lines originating from kidneys of dog (MDCK), pig (LLC-PK1), opossum (OK), and human embryo (HEK-293) were each tested for the presence of MR using 2-[125I]iodomelatonin (125I-MEL) as a radioligand. The HEK-293 cell line exhibited the highest specific 125I-MEL binding. By intermediate filament characterization, the HEK-293 cells were determined to be of epithelial origin. Binding of 125I-MEL in HEK-293 cells demonstrated saturability, reversibility, and high specificity with an equilibrium dissociation constant (Kd) value of 23.8 +/- 0.5 pM and a maximum number of binding sites (Bmax) value of 1.17 +/- 0.11 fmol/mg protein (n = 5), which are comparable with the reported Kd and Bmax values in human kidney cortex. Coincubation with GTPgammaS (10 microM) and pertussis toxin (100 ng/ml) provoked a marked decrease in binding affinity (Kd was increased by a factor of 1.5-2.0), with no significant difference in Bmax. Melatonin (1 microM) decreased the forskolin (10 microM) stimulated cAMP level by 50%. HEK-293 cells do not express dopamine D1A receptor. Following transient transfection of HEK-293 cells with human dopamine D1A receptor (hD1A-R), exposure of the cells to dopamine stimulated an increase in the level of cAMP. Similarly, transient transfection of HEK-293 cells with rat glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and PTH type 1 receptors, each resulted in an hormone inducible increase in cAMP levels. Surprisingly, only the stimulatory effect of dopamine could be inhibited by exposure to melatonin. The inhibitory effect of melatonin on dopamine D1-induced increase in cAMP was completely inhibited by pertussis toxin (100 ng/ml, 18 h). Immunoblot and immunocytochemical studies were carried out using two polyclonal antibodies raised against the extra and cytoplasmic domains of Mel1a receptor. Immunoblot studies using antibody against the cytoplasmic domain of Mel1a receptor confirmed the presence of a peptide blockable 37 kDa band in HEK-293 cells. Indirect immunofluorescent studies with both antibodies revealed staining predominantly at the cell surface, but staining with the antibody directed against the cytoplasmic domain required prior cell permeabilization. By RT-PCR, HEK-293 cells express both Mel1a and Mel1b messenger RNAs, but the messenger RNA level for Mel1b is several orders of magnitude lower than for Mel1a. We conclude that HEK-293 cells express MR predominantly of the Mel1a subtype. Our evidence suggests that one of the ways that melatonin exerts its biological function is through modulation of cellular dopaminergic responses.

Animals↗

Development of a pilot quality assessment tool for long-term care facilities.

Recently the demand to provide exceptional health care services has become of paramount importance. Facilities are competing with each other to provide to the public data which illustrates why one facility is superior to another. One area that has become important is demonstrating the performance of quality of care. The problem with proving the quality of services provided arises from the fact that defining quality as a single entity is difficult. Realizing this factor has created the need to define and measure quality of care in concrete ways. The intent of this research was to facilitate a technique to measure quality of care in long-term care facilities (LTCFs). This research resulted in the development of a pilot quality assessment tool to measure areas of care in LTCFs.

Aged↗

The DCC protein and prognosis in colorectal cancer.

BACKGROUND: Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS: The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS: The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS: DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.

Aged↗