Fabrication and mechanical characterization of 3D electrospun scaffolds for tissue engineering.

Electrospinning is a polymer processing technique that produces fibrous structures comparable to the extracellular matrix of many tissues. Electrospinning, however, has been severely limited in its tissue engineering capabilities because this technique has produced few three-dimensional structures. Sintering of electrospun materials provides a method to fabricate unique architectures and allow much larger structures to be made. Electrospun mats were sintered into strips and cylinders, and their tensile and compressive mechanical properties were measured. In addition, electrospun materials with salt pores (salt embedded within the material and then leached out) were fabricated to improve porosity of the electrospun materials for tissue engineering scaffolds. Sintered electrospun poly(D,L-lactide) and poly(L-lactide) (PDLA/PLLA) materials have higher tensile mechanical properties (modulus: 72.3 MPa, yield: 960 kPa) compared to unsintered PLLA (modulus: 40.36 MPa, yield: 675.5 kPa). Electrospun PDLA/PLLA cylinders with and without salt-leached pores had compressive moduli of 6.69 and 26.86 MPa, respectively, and compressive yields of 1.36 and 0.56 MPa, respectively. Sintering of electrospun materials is a novel technique that improves electrospinning application in tissue engineering by increasing the size and types of electrospun structures that can be fabricated.

The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community.

OBJECTIVES: To develop a simple method for identifying community-dwelling vulnerable older people, defined as persons age 65 and older at increased risk of death or functional decline. To assess whether self-reported diagnoses and conditions add predictive ability to a function-based survey. DESIGN: Analysis of longitudinal survey data. SETTING: A nationally representative community-based survey. PARTICIPANTS: Six thousand two hundred five Medicare beneficiaries age 65 and older. MEASUREMENTS: Bivariate and multivariate analyses of the Medicare Current Beneficiary Survey; development and comparison of scoring systems that use age, function, and self-reported diagnoses to predict future death and functional decline. RESULTS: A multivariate model using function, self-rated health, and age to predict death or functional decline was only slightly improved when self-reported diagnoses and conditions were included as predictors and was significantly better than a model using age plus self-reported diagnoses alone. These analyses provide the basis for a 13-item function-based scoring system that considers age, self-rated health, limitation in physical function, and functional disabilities. A score of >or=3 targeted 32% of this nationally representative sample as vulnerable. This targeted group had 4.2 times the risk of death or functional decline over a 2-year period compared with those with scores <3. The receiver operating characteristics curve had an area of.78. An alternative scoring system that included self-reported diagnoses did not substantially improve predictive ability when compared with a function-based scoring system. CONCLUSIONS: A function-based targeting system effectively and efficiently identifies older people at risk of functional decline and death. Self-reported diagnoses and conditions, when added to the system, do not enhance predictive ability. The function-based targeting system relies on self-report and is easily transported across care settings.

Selecting target conditions for quality of care improvement in vulnerable older adults.

OBJECTIVE: To identify a set of geriatric conditions as optimal targets for quality improvement to be used in a quality measurement system for vulnerable older adults. DESIGN: Discussion and two rounds of ranking of conditions by a panel of geriatric clinical experts informed by literature reviews. METHODS: A list of 78 conditions common among vulnerable older people was reduced to 35 on the basis of their (1) prevalence, (2) impact on health and quality of life, (3) effectiveness of interventions in improving mortality and quality of life, (4) disparity in the quality of care across providers and geographic areas, and (5) feasibility of obtaining the data needed to test compliance with quality indicators. A panel of 12 experts in geriatric care discussed and then ranked the 35 conditions on the basis of the same five criteria. We then selected 21 conditions, based on panelists' iterative rankings. Using available national data, we compiled information about prevalence of the selected conditions for community-dwelling older people and older nursing home residents and estimated the proportion of inpatient and outpatient care attributable to the selected conditions. RESULTS: The 21 conditions selected as targets for quality improvement among vulnerable older adults include (in rank order): pharmacologic management; depression; dementia; heart failure; stroke (and atrial fibrillation); hospitalization and surgery; falls and mobility disorders; diabetes mellitus; end-of-life care; ischemic heart disease; hypertension; pressure ulcers; osteoporosis; urinary incontinence; pain management; preventive services; hearing impairment; pneumonia and influenza; vision impairment; malnutrition; and osteoarthritis. The selected conditions had mean rank scores from 1.2 to 3.8, and those excluded from 4.6 to 6.9, on a scale from 1 (highest ranking) to 7 (lowest ranking). Prevalence of the selected conditions ranges from 10 to 50% among community-dwelling older adults and from 25 to 80% in nursing home residents for the six most common selected conditions. The 21 target conditions account for at least 43% of all acute hospital discharges and 33% of physician office visits among persons 65 years of age and older. Actual figures must be higher because several of the selected conditions (e.g., end-of-life care) are not recorded as diagnoses. CONCLUSIONS: Twenty-one conditions were selected as targets for quality improvement in vulnerable older people for use in a quality measurement system. The 21 geriatric conditions selected are highly prevalent in this group and likely account for more than half of the care provided to this group in hospital and ambulatory settings.

Acute pulmonary edema caused by ingestion of hydrochlorothiazide.

Hydrochlorothiazide is one of most commonly prescribed antihypertensive diuretics. In this case, an allergic reaction to hydrochlorothiazide resulted in severe pulmonary edema. Hydrochlorothiazide, one of the most commonly prescribed drugs, is a diuretic which is usually well tolerated. Common side effects include dizziness, weakness, fatigue, and cramps. These side effects are usually caused by fluid and electrolyte imbalances. Acute pulmonary edema, first reported by Steinberg in 1968, is a rare but potentially life-threatening allergic reaction to hydrochlorothiazide. This case illustrates many of the typical presenting features of the reaction.

Improving patient quality of life with feedback to physicians about functional status.

OBJECTIVE: To improve functional status among primary care patients. INTERVENTION: 1) Computer-generated feedback to physicians about the patient's functional status, the patient's self-reported "chief complaint," and problem-specific resource and management suggestions; and 2) two brief interactive educational sessions for physicians. DESIGN: Randomized controlled trial. SETTING: University primary care clinic. PARTICIPANTS: All 73 internal medicine house officers and 557 of their new primary care patients. MEASURES: 1) Change in patient functional status from enrollment until six months later, using the Functional Status Questionnaire (FSQ); 2) management plans and additional information about functional status abstracted from the medical record; and 3) physician attitude about whether internists should address functional status problems. RESULTS: Emotional well-being scores improved significantly for the patients of the experimental group physicians compared with those of the control group physicians (p < 0.03). Limitations in social activities indicated as "due to health" decreased among the elderly (> or = 70 years of age) individuals in the experimental group compared with the control group (p < 0.03). The experimental group physicians diagnosed more symptoms of stress or anxiety than did the control group physicians (p < 0.001) and took more actions recommended by the feedback form (p < 0.02). CONCLUSIONS: Computer-generated feedback of functional status screening results accompanied by resource and management suggestions can increase physician diagnoses of impaired emotional well-being, can influence physician management of functional status problems, and can assist physicians in improving emotional well-being and social functioning among their patients.

Functional disability screening of ambulatory patients: a randomized controlled trial in a hospital-based group practice.

The authors conducted a randomized controlled trial of functional disability screening in a hospital-based internal medicine group practice. They assigned 60 physicians and 497 of their patients to either an experimental or a control group. Every four months the patients in both groups completed a self-administered questionnaire measuring physical, psychological, and social function. The experimental group physicians received reports summarizing their patients' responses; the control group physicians received no report. At the end of one year the authors found no significant difference between the patients of the experimental and control group physicians on any measure of functional status. Functional disability screening alone does not improve patient function.

Failure of physicians to recognize functional disability in ambulatory patients.

OBJECTIVE: To assess the ability of internists to identify functional disabilities reported by their patients. DESIGN: Comparison of responses by physicians and a random sample of their patients to a 12-item questionnaire about physical and social function. SETTING: A hospital-based internal medicine group practice in Boston, Massachusetts, and selected office-based internal medicine practices in Los Angeles, California. SUBJECTS: Five staff physicians, three general internal medicine fellows, and 34 internal medicine residents in the hospital-based practice and 178 of their patients. Seventy-six physicians in the office-based practices and 230 of their patients. MEASUREMENTS AND MAIN RESULTS: Physicians underestimated or failed to recognize 66% of disabilities reported by patients. Patient-reported disabilities were underestimated or unrecognized more often in the hospital-based practice than in the office-based practices (75% compared with 60%, P less than 0.05). Physicians overstated functional impairment in 21% of paired responses in which patients reported no disability. CONCLUSIONS: Physicians often underestimate or fail to recognize functional disabilities that are reported by their patients. They overstate functional impairment to a lesser degree. Because these discrepancies may adversely affect patient care and well-being, medical educators and clinicians should pay more attention to the assessment of patient function.

Hyperthyroidism during pregnancy due to coexistence of struma ovarii and Graves' disease.

A patient with hyperthyroid Graves' disease and struma ovarii is described. She had pre-existing Graves' disease and positive thyrotrophin receptor antibody. She was treated with radioactive iodine 5 months before she became pregnant. Paripartum she had torsion of an ovarian cyst with histological evidence of a functional struma ovarii. Immediate exacerbation of her thyrotoxic state was observed after operation as a result of release of thyroid hormone from the tumour. It is postulated that the tumour was stimulated by circulating thyrotrophin receptor antibody.

Vitamin D status among patients with fractured neck of femur in Hong Kong.

Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control.

Improving patient function: a randomized trial of functional disability screening.

STUDY OBJECTIVES: To test whether a 34-item functional status questionnaire measuring physical, psychological, and social function can be used by physicians in practice to help improve their patients' outcomes. DESIGN: Prospective randomized trial. SETTING: Community internal medicine practices. PATIENTS: Five hundred and ten continuing patients with functional disabilities who saw their physicians at least four times a year. PHYSICIANS: Seventy-six UCLA clinical volunteer faculty who are internists in community office practices. INTERVENTIONS: Physicians and their patients were randomly assigned to the experimental or the control group. Experimental group physicians attended a 2-hour multimedia educational session and received four functional status reports on each of their study patients over a 1-year period. Control group physicians received no education and no functional status feedback. Control group and experimental group patients were tested for functional status with the functional status questionnaire every 4 months for 1 year. Both groups also completed monthly diaries that measured use of health services. Experimental group physicians answered an anonymous evaluation questionnaire at 6 months after study entry. MEASUREMENTS AND MAIN RESULTS: Forty-three percent of experimental group physicians reported that they had used the functional status questionnaire to change therapy. Ninety-five percent reported that it was useful and accurate. Patient diaries did not show any difference between experimental group patients and control group patients in number of medications used, visits to physicians or other health professionals, equipment purchased, diet, or exercise programs. There were no significant differences between experimental and control group patients at exit from the study on any functional status or health outcome measure. CONCLUSION: A more powerful intervention than a 2-hour educational session and the regular provision of functional status information is needed to help office-based internists improve patient outcomes.

Hyperinsulinism in infancy.

Five infants with persistent hypoglycaemia due to hyperinsulinism were reported. Provocative tests for insulin release were unhelpful. Diazoxide was useful in the treatment of three patients but many side-effects were observed. These included petechial rash, hypertrichosis, acute renal failure, fluid retention and cardiac failure. Two patients underwent spontaneous remission. Three patients had nesidioblastosis, two of whom were subjected to 95% pancreatectomy. Postoperatively, recurrence of hypoglycaemia was due to hyperinsulinism in one patient and to presumed glucagon deficiency in the other. Phenytoin effectively corrected the hypoglycaemia in the patient who had postoperative hyperinsulinism. It is recommended that medical therapy with diazoxide (10-15 mg/kg per day) together with a diuretic be commenced once hyperinsulinism is diagnosed. Subtotal pancreatectomy should be performed early in these patients if hypoglycaemia cannot be controlled with medical therapy or if side-effects of treatment are documented.

The use of glucagon challenge tests in the diagnostic evaluation of hypoglycemia due to hepatoma and insulinoma.

We previously found that patients with hypoglycemia due to chronic renal and liver disease had anomalous metabolic responses to glucose and glucagon stimulation. In this study we evaluated the use of glucagon (2 mg, iv) tests in the diagnosis of spontaneous hypoglycemia secondary to hepatocellular carcinoma (HCC) and insulinoma. Twenty-one normal subjects, 45 patients with HCC (11 with hypoglycemia), and 14 patients with insulinoma (all with hypoglycemia) were studied. The fasting blood glucose level was low in all patients with hypoglycemia. The fasting plasma insulin and C-peptide concentrations were high in patients with insulinoma and low in patients with HCC and hypoglycemia. The blood glucose responses to glucagon administration were less than normal in patients with HCC and hypoglycemia and within normal limits in patients with insulinoma. The insulinoma patients had increased plasma insulin and C-peptide responses to glucagon despite having low blood glucose levels. Compared with the HCC patients without hypoglycemia, HCC patients with hypoglycemia had impaired plasma insulin and C-peptide responses. The fasting hypoglycemia, hypoinsulinemia, and impaired insulin/C-peptide responses to glucagon in patients with hepatoma and hypoglycemia presumably reflect the production of insulin-like substances by the hepatoma. We conclude that glucagon administration results in characteristic responses in these groups of patients and can be of use in the diagnosis of spontaneous hypoglycemia secondary to hepatoma or insulinoma.

Long term pulsatile growth hormone (GH)-releasing hormone therapy in children with GH deficiency.

We treated seven GH-deficient children with 3-hourly 1 microgram/kg sc pulses of GHRH-(1-44) for 6 months and 2 micrograms/kg.pulse for another 6 months. Four patients had a serum GH response to iv GHRH before treatment, and an additional patient responded to iv GHRH after 1 month of pulsatile sc GHRH administration. The mean cumulative growth velocity increased from a pretreatment mean of 2.7 +/- 0.2 (+/- SE) to 8.4 +/- 2.5 and 5.4 +/- 0.7 cm/yr after 2 months and 1 yr of treatment, respectively. Low dose pulsatile GHRH therapy was effective in promoting growth in five of seven children, with height gain ranging from 4.4-7.5 cm at the end of 1 yr's therapy. Only one of the two patients who did not respond to GHRH had an improvement in linear growth when they were subsequently treated with synthetic GH. The other patient, a 16.5-yr-old pubertal girl who had both satisfactory GH and somatomedin-C responses during GHRH therapy, did not respond to either GHRH or, later, synthetic GH. The pretreatment serum GH response to iv GHRH, the serum somatomedin-C concentrations, and the peak serum GH response during sc GHRH therapy were not reliable predictors of clinical response.

Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes.

The glucose and lipid metabolism in a group of women with previous history of gestational diabetes were evaluated before and after 6 months treatment with a low-dose triphasic oral contraceptives pill (TP). This group was compared with a control group of women, also with history of gestational diabetes, using intrauterine devices (IUD). In the TP group, 26.7% of the women developed impaired glucose tolerance which reverted to normal in all but one after cessation of the TP. The IUD group showed no change in glucose tolerance. The integrated insulin response to a 75g OGTT in the TP group increased by 48.3% at 6 months compared with an increase of 23.4% for the same period in the IUD group. In the TP group there was a significant decrease in serum total cholesterol without changes in HDL-cholesterol and triglycerides level. We conclude that even low-dose triphasic oral contraceptive pills can cause glucose intolerance in women with previous gestational diabetes mellitus.

PIP: The glucose and lipid metabolism in a group of 20 women with a previous history of gestational diabetes were evaluated before and after 6 months of treatment with a low-dose triphasic oral contraceptive (OC). Another group of 5 women, also with a history of gestational diabetes but who were given an IUD, served as controls. 26.7% of the women in the triphasic OC group developed impaired glucose tolerance; however, values reverted to normal in all but 1 woman after OC discontinuation. The IUD group showed no change in glucose tolerance. The integrated insulin response to a 75 gm oral glucose tolerance test increased by 48.3% at 6 months in the OC group compared with an increase of 23.4% for the same period in the control group. Also recorded in the OC group but not among controls was a significant increase in serum total cholesterol without changes in high density lipoprotein-cholesterol and triglyceride levels. It was concluded that even low-dose triphasic OCs can cause glucose intolerance in women with previous gestational diabetes mellitus. Thus, the theoretical risk of precipitating permanent diabetes should be weighed against the risk of pregnancy. In cases where OCs are the only reliable method possible, careful and frequent monitoring of carbohydrate metabolism should be performed. Older, heavier women with a family history of diabetes are in particular need of close surveillance and constant monitoring of their glucose and lipid metabolism.

The Functional Status Questionnaire: reliability and validity when used in primary care.

A comprehensive functional assessment requires thorough and careful inquiry, which is difficult to accomplish in most busy clinical practices. This paper examines the reliability and validity of the Functional Status Questionnaire (FSQ), a brief, standardized, self-administered questionnaire designed to provide a comprehensive and feasible assessment of physical, psychological, social and role function in ambulatory patients. The FSQ can be completed and computer-scored in minutes to produce a one-page report which includes six summated-rating scale scores and six single-item scores. The clinician can use this report both to screen for and to monitor patients' functional status. In this study, the FSQ was administered to 497 regular users of Boston's Beth Israel Hospital's Healthcare Associates and 656 regular users of 76 internal medicine practices in Los Angeles. The data demonstrate that the FSQ produces reliable sub-scales with construct validity. The authors believe the FSQ addresses many of the problems behind the slow diffusion into primary care of systematic functional assessment.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Reverse consultations: the profiles of patients referred from subspecialists to generalists.

To determine the characteristics of patients referred by subspecialists to generalists, we compared 67 patients referred by three medical subspecialty clinics to the general internal medicine clinic to 162 randomly chosen patients who were retained by those clinics, with respect to the patients' need for a broad array of services. A trained abstractor reviewed the records for the prior year for patient characteristics indicating a need for broad-based care. The mean referred patient age was 53.7 yr compared to 46.2 yr in the retained group (p = 0.001); 33% of referred patients, as compared to 20% of those retained, had references to psychosocial problems in the physician notes (p = 0.03). Referred patients had 2.34 diagnoses outside of the subspecialty, compared to 1.27 for retained patients (p = 0.001). Referred patients had more recorded complaints outside of the subspecialty, 1.18 vs 0.71, (p = 0.02). Referred patients also had significantly more total clinic visits and visited twice as many different types of clinics in the past year (p = 0.001). There were no differences in payment method or insurance status. These findings suggest that university based subspecialists prefer to refer medically and psychosocially complex patients. If it is desirable that subspecialists value such patients more highly, changes in subspecialty training programs might be needed. If not, more generalists may be needed to care for such patients.