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Biomedical subjects

J D Walker

Publications and source records attributed to J D Walker.

At least 73 records · Page 4Linked to original sources
PubMed1995

Medical patients' assessments of their care during hospitalization: insights for internists.

OBJECTIVE: To assess, from the patient's perspective, selected aspects of the quality of inpatient hospital care in the United States. DESIGN: A cross-sectional survey, using telephone interviews of patients discharged from the medical services of a probability sample of 62 public and private, nonprofit, nonfederal acute care hospitals in the United States. The participating patients reported; discrete, clinically important elements of hospital care; preferences for involvement in care; health status; sociodemographic characteristics; and overall satisfaction with their hospitalization. PATIENTS/PARTICIPANTS: 2,839 patients drawn as a probability sample. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 32 of the 50 questions about potential problems encountered during hospitalization, at least 10% of the patients gave a response indicating a problem. One-third of the patients having a physician (31.8%) reported that that physician did not care for them during hospitalization. Other frequently reported problems included not receiving information about the hospital routine (45.1%), not being told whom to ask for help (33.9%), having pain that could have been relieved by more prompt attention (19.9%), and not being given adequate information and guidance about activities and care after discharge from the hospital (21.4-36.1%). Most patients preferred to be informed about important aspects of their care (94.7%), but their preferences for involvement in care varied widely. CONCLUSIONS: Information from hospitalized medical patients identified several areas of concern that should be the focus of attention and could lead to systematic restructuring of hospital-based care.

Adult↗
PubMed1995

3,5,3' Triiodo-L-thyronine pretreatment with cardioplegic arrest and chronic left ventricular dysfunction.

BACKGROUND: The active form of thyroid hormone, T3, may be an important determinant of left ventricular (LV) function after hypothermic cardioplegic arrest and rewarming, particularly in patients with preexisting LV dysfunction. Thus, the present project tested the hypothesis that T3 pretreatment will improve myocyte contractile performance after hypothermic cardioplegic arrest and rewarming in the setting of chronic LV dysfunction. METHODS: Control LV porcine myocytes (n = 160) and cardiomyopathic LV (rapid pacing for 3 weeks at 240 beats/min) myocytes (n = 100) were treated with or without 80 pmol/L T3. Myocytes then were maintained in normothermic conditions (2 hours at 37 degrees C in media) or exposed to hypothermic cardioplegic arrest ([K+], 24 mmol/L; 2 hours at 4 degrees C) with subsequent rewarming. RESULTS: After cardioplegic arrest and rewarming, T3 pretreatment increased myocyte velocity of shortening by 41% in control myocytes and by 35% in cardiomyopathic myocytes when compared to untreated myocytes. Furthermore, T3 pretreatment followed by beta-adrenergic receptor stimulation with isoproterenol (25 nmol/L) improved myocyte velocity of shortening by 24% in control myocytes and 90% in cardiomyopathic myocytes after hypothermic cardioplegic arrest and rewarming, as compared with untreated myocytes. CONCLUSIONS: In summary, this study provides evidence to suggest that preemptive treatment with T3 may improve LV pump function and beta-adrenergic responsiveness after hypothermic cardioplegic arrest and rewarming in patients with underlying LV dysfunction.

Animals↗
PubMed1995

The direct effects of 3,5,3'-triiodo-L-thyronine (T3) on myocyte contractile processes. Insights into mechanisms of action.

Administration of 3,5,3'-triiodo-L-thyronine (T3) has recently been suggested to acutely improve left ventricular performance. However, the cellular and molecular mechanisms responsible for this improvement in left ventricular function with T3 remained unknown. Accordingly, the present study examined the direct effects of T3 administration on myocyte contractile function and the sarcolemmal systems that might potentially contribute to these effects. In isolated porcine left ventricular myocytes (n = 81), velocity of shortening increased in the presence of 80 pmol/L T3 compared with that in untreated myocytes (117.0 +/- 5.0 versus 77.3 +/- 3.3 microns/sec, p < 0.05). In a separate series of experiments (n = 29), myocyte velocity of shortening increased in the presence of both T3 and beta-adrenergic receptor stimulation (25 nmol/L isoproterenol) to greater than that with beta-adrenergic receptor stimulation alone (274.3 +/- 16.9 versus 203.7 +/- 16.2 microns/sec, p < 0.05). Cyclic adenosine monophosphate generation was next examined in isolated myocyte preparations (n = 9). In the presence of T3, no significant increase in cyclic-adenosine monophosphate generation was observed compared with that in untreated myocytes (39.1 +/- 8.3 versus 24.7 +/- 5.8 fmols/myocyte, p = 0.17). However, in the presence of both T3 and beta-adrenergic receptor stimulation, cyclic-adenosine monophosphate generation increased significantly to greater than that with beta-adrenergic receptor stimulation alone (224.4 +/- 61.1 versus 120.1 +/- 35.5 fmoles/myocyte, p < 0.05). Because cyclic-adenosine monophosphate modulates intracellular Ca2+ processes, L-type Ca+2 channel current (patch clamp methods; -picoamp/picofarad, n = 15) and peak intracellular Ca+2 levels (fura 2 ionic measurement, n = 47) were next measured. In the presence of T3, a shift in the activation voltage at peak L-type Ca+2 channel current was observed from baseline (5.5 +/- 1.4 versus 9.0 +/- 1.0 mV, p < 0.05). Furthermore, in the presence of both T3 and beta-adrenergic receptor stimulation, peak L-type Ca+2 channel current (8.9 +/- 0.7 versus 6.3 +/- 1.0 mV, p < 0.05) and peak intracellular Ca+2 levels (189.9 +/- 8.4 versus 171.7 +/- 8.3 nmol/L, p < 0.05) increased compared with values obtained with beta-adrenergic receptor stimulation alone. Important findings from the present study were twofold: (1) T3 improved myocyte contractile processes through a cyclic-adenosine monophosphate-independent mechanism and (2) T3 potentiated the effects of beta-adrenergic receptor stimulation transduction by increasing cyclic-adenosine monophosphate production, L-type Ca+2 channel current, and Ca+2 availability to the myocyte contractile apparatus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Pretreatment with 3,5,3'triiodo-L-thyronine (T3). Effects on myocyte contractile function after hypothermic cardioplegic arrest and rewarming.

Circulating levels of 3,5,3'triiodo-L-thyronine are depressed after cardiopulmonary bypass and have been implicated to play a contributory role in the alterations in left ventricular function after hypothermic cardioplegic arrest and rewarming. The central hypothesis of the present study was that pretreatment of isolated myocytes with triiodothyronine will have a direct and beneficial effect on contractile performance after hypothermic cardioplegic arrest and rewarming. Contractile function in isolated pig left ventricular myocytes was examined by video microscopy after the following treatment protocols: (1) 37 degrees C incubation in medium (normothermia) for 2 hours with triiodothyronine followed by a 2-hour normothermic incubation with no triiodothyronine, (2) 4 hours of normothermic incubation with no triiodothyronine, (3) normothermic incubation for 2 hours with triiodothyronine followed by 2 hours of hyperkalemic, hypothermic cardioplegic arrest ([K+]:24 mmol/L; 4 degrees C) and subsequent rewarming, and (4) normothermic incubation for 2 hours with no triiodothyronine followed by 2 hours of hyperkalemic, hypothermic cardioplegic arrest and rewarming. Two hours of normothermia with triiodothyronine increased myocyte contractile function by 30% compared with values in untreated control myocytes, and this increase persisted after a subsequent 2-hour incubation under normothermic conditions with no triiodothyronine. For example, myocyte velocity of shortening in triiodothyronine-pretreated myocytes was 84 +/- 4.9 microns/sec compared with 62 +/- 2.8 microns/sec in control myocytes (p < 0.05). Cardioplegic arrest and subsequent rewarming caused a significant reduction in myocyte velocity of shortening from normothermic values (37 +/- 3.4 microns/sec, p < 0.05). However, in myocytes pretreated with triiodothyronine, myocyte contractile function was significantly higher after hypothermic cardioplegic arrest and rewarming (54 +/- 2.5 microns/sec, p < 0.05). In a second series of experiments, beta-adrenergic responsiveness was examined after pretreatment with triiodothyronine. In the presence of the beta-adrenergic agonist isoproterenol (25 nmol/L), myocyte contractile function was increased by 26% in the triiodothyronine-treated myocytes compared with that in untreated control myocytes. This enhanced beta-adrenergic responsiveness with triiodothyronine pretreatment persisted with subsequent exposure to hypothermic cardioplegic arrest and rewarming. In summary, triiodothyronine pretreatment caused an increase in myocyte contractile function and beta-adrenergic responsiveness under normothermic conditions and after hypothermic cardioplegic arrest and rewarming. Thus the present study provides direct evidence to suggest that preemptive treatment with triiodothyronine may improve left ventricular contractile performance after hypothermic cardioplegic arrest and rewarming.

Animals↗
PubMed1994

Strategies employed to determine the acute aquatic toxicity of ethyl benzene, a highly volatile, poorly water-soluble chemical.

Studies are described in which ethyl benzene (EB) was tested to determine its acute toxicity to three marine organisms, Atlantic silversides (Menidia menidia), mysid shrimp (Mysidopsis bahia), and diatoms (Skeletonema costatum), and to one freshwater algae (Selenastrum capricornutum). The respective 96-hr median lethal concentration (LC50) values and 95% confidence intervals for EB in the flow-through studies with fish and mysid shrimp were 5.1 (4.4-5.7) mg/liter and 2.6 (2.0-3.3) mg/liter. While the 96-hr median effective concentrations (EC50's) for growth inhibition and 95% confidence intervals for the static studies with diatoms and algae were 7.7 (5.9-10.0) mg/liter and 3.6 (1.7-7.6) mg/liter, respectively. Problems were encountered in all four studies as a result of the high volatility and poor water solubility of EB in water and an apparent "salting out" effect noted in seawater. This effect was found particularly true in the diatom and algae studies where the salinity was increased with the addition of culture medium. Measures are described which were used to overcome this stability problem with EB. These included sealing the test systems tight without any air spaces to prevent the collection of EB vapors. Also, increased mixing of EB in the test solutions was found to be essential in the flow-through studies to maintain stable levels. In the case of the diatom and algal studies, since current EPA test guidelines were judged to be inadequate to overcome EB volatility from the test medium, a new closed test system had to be developed and employed, after validation with a nonvolatile reference toxicant in the new and conventional static test systems. The results of these studies indicate that previous reports underestimated the potential acute aquatic toxicity of EB by at least one order of magnitude. The implications of these findings are discussed in relation to the potential environmental impact of EB and the resultant regulatory actions.

Animals↗
PubMed1994

Direct effects of acute administration of 3, 5, 3' triiodo-L-thyronine on myocyte function.

Recent studies have suggested that acute administration of 3, 5, 3' triiodo-L-thyronine (T3) may increase ventricular performance; however, the direct cellular effects of acute T3 administration are not understood. The objectives of this study were to determine (1) whether T3 acts directly on the cardiac muscle cell (myocyte) itself, and (2) whether T3 acts independently of the myocyte beta-adrenergic receptor. Accordingly, isolated myocyte function was examined using video-microscopy in normal porcine myocytes (n = 60) in the control state and in the presence of increasing T3 concentrations (10 to 500 pmol/L). T3 caused myocyte shortening extent, shortening velocity, and lengthening velocity to increase in a dose-dependent manner. For example, shortening velocity increased from 49.2 +/- 4.3 microns/s at baseline to 66.5 +/- 6.1 microns/s with 100 pmol/L T3 (p < 0.05). beta-Adrenergic stimulation with 25 nmol/L isoproterenol increased shortening velocity to 97.6 +/- 5.7 microns/s; isoproterenol with T3 increased shortening velocity further to 168.5 +/- 10.9 microns/s. Analysis of variance revealed that this increase with T3 was independent of and additive to the beta-adrenergic receptor system. In summary, T3 caused a dose-dependent increase in myocyte contractile performance, and these effects were independent of and additive to beta-adrenergic receptor stimulation. Thus, acute T3 administration may provide a novel modality to improve left ventricular contractile function independent of the beta-adrenergic receptor system.

Animals↗
PubMed1994

Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151.

AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis who had just completed a 14-day course of ganciclovir induction therapy were randomly assigned to an alternating or concurrent combination regimen of chronic ganciclovir-foscarnet therapy for CMV retinitis. Each regimen used lower weekly cumulative doses of each drug than standard monotherapy maintenance treatment regimens. Dose-limiting toxicity attributable to foscarnet occurred in only 2 (7%) of 29 evaluatable patients, and no patients experienced dose-limiting nephrotoxicity. Although absolute neutrophil counts < 500 cells/microL occurred in 11 (38%) of 29 patients, all who subsequently used adjunctive granulocyte colony-stimulating factor had severe neutropenia prevented. Severe toxicity of any type and neutropenia, in particular, occurred significantly more frequently in patients assigned to the concurrent treatment regimen. CMV was isolated from none of 21 patients who had urine cultured and from only 1 of 24 who had blood cultured while being treated during the study (median evaluation, 12 weeks). This suggests that combination therapy provides better in vivo antiviral activity in suppressing CMV replication than previously reported with monotherapy regimens.

AIDS-Related Opportunistic Infections↗
PubMed1994

The novel effects of 3,5,3'-triiodo-L-thyronine on myocyte contractile function and beta-adrenergic responsiveness in dilated cardiomyopathy.

Medical management of patients with chronic left ventricular dysfunction continues to be a difficult problem. Recent clinical and experimental studies have suggested that 3,5,3'-triiodo-L-thyronine improves left ventricular pump function. However, whether 3,5,3'-triiodo-L-thyronine directly improves myocyte contractile function in cardiomyopathic states is unknown. Accordingly, this study examined the direct effects of 3,5,3'-triiodo-L-thyronine on isolated myocyte contractile function in cardiocytes obtained from control (n = 6) pigs and pigs with tachycardia-induced dilated cardiomyopathy (atrial pacing at 240 beats/min for 3 weeks; n = 6). Myocyte percent shortening and velocity of shortening were obtained at baseline and in the presence of 3,5,3'-triiodo-L-thyronine doses of 80 and 100 pmol/L. For both control and dilated cardiomyopathy groups, 3,5,3'-triiodo-L-thyronine caused a significant increase in myocyte contractile function. For example, a 100 pmol/L dose of 3,5,3'-triiodo-L-thyronine increased myocyte velocity of shortening by 51% in control myocytes and by 54% in dilated cardiomyopathy myocytes compared with baseline. A second series of experiments was performed to determine whether 3,5,3'-triiodo-L-thyronine altered the responsiveness of the beta-adrenergic receptor system in control and dilated cardiomyopathy myocytes. Myocyte contractile function was examined during beta-adrenergic stimulation with isoproterenol alone and in myocytes preincubated with 3,5,3'-triiodo-L-thyronine doses of 80 and 100 pmol/L to which isoproterenol was added. Isoproterenol alone increased velocity of shortening by 139% in control and by 233% in dilated cardiomyopathy myocytes compared with baseline. This was significantly greater than the increase with 3,5,3'-triiodo-L-thyronine alone. 3,5,3'-triiodo-L-thyronine followed by isoproterenol increased velocity of shortening by 245% in control and 313% in dilated cardiomyopathy myocytes compared with baseline. This was significantly greater than the response with 3,5,3'-triiodo-L-thyronine or isoproterenol alone and appeared to be greater than an additive response. The results from this study clearly demonstrated that 3,5,3'-triiodo-L-thyronine directly augmented myocyte contractile function in both control and dilated cardiomyopathy myocytes. In addition, 3,5,3'-triiodo-L-thyronine enhanced the contractile response to beta-adrenergic stimulation in dilated cardiomyopathy. This study provides unique evidence to suggest that 3,5,3'-triiodo-L-thyronine may be a useful adjunct to conventional inotropic support in the setting of advanced left ventricular dysfunction.

Animals↗
PubMed1993

Malignant prolactinoma with extracranial metastases: a report of three cases.

OBJECTIVE: Prolactin-secreting tumours of the pituitary almost never metastasize extracranially. However, we have recently seen three such patients, whose presentation, clinical course and response to treatment are reviewed in order to determine whether they possess unique clinical features, and to assess optimum therapy. DESIGN AND PATIENTS: Three patients with extracranial metastases from prolactinomas have been retrospectively reviewed. MEASUREMENTS: Clinical courses, biochemical parameters and imaging modalities (CT, MR and radiolabelled somatostatin analogue scanning) and histopathology were assessed before and during different therapeutic regimens. RESULTS: All three patients' presentations were initially unremarkable, but later each had persistent and relentlessly increasing serum prolactin concentrations and evidence of distant spread of their tumours. The first patient presented aged 32 and was treated with repeated transsphenoidal resections of the tumour, pituitary radiotherapy, high dose bromocriptine therapy, the somatostatin analogue octreotide and chemotherapy. Nine years after the original diagnosis a liver biopsy revealed carcinoma cells positively immunostaining for prolactin. At autopsy further microscopically similar metastases were seen in both lungs and the left hilar lymph nodes. The second patient presented aged 48 and was treated with external beam pituitary radiotherapy, bromocriptine, transsphenoidal hypophysectomy and chemotherapy. Fifteen years after the original diagnosis bone biopsy revealed carcinoma cells positively immunostaining for prolactin; the patient developed interstitial nephritis and died in renal failure. The third patient presented aged 48 with hypogonadism and bitemporal hemianopia due to a macroadenoma. This was removed transfrontally and followed by external beam radiotherapy. After recurrence, further surgery and radiotherapy were undertaken, but the tumour continued to grow and the patient died suddenly of a pulmonary embolus. At autopsy, tumour was found in thoracic lymph nodes and lung capillaries. CONCLUSIONS: These three patients may be added to the previous two reported cases of malignant prolactinoma with extracranial spread. Several different therapies were tried but were of limited value in controlling the progression of the disease, although chemotherapy is an important modality to be considered. No particular factor or combination of factors at presentation differentiated these patients from more typical patients whose disease is much less aggressive.

Adult↗
PubMed1993

Using patient reports to improve medical care: a preliminary report from 10 hospitals.

This article describes the early activities of the Picker/Commonwealth Program for Patient-Centered Care and reports results from a study of 10 hospitals trying to develop better ways of providing patient-centered care. Reported problems were relatively infrequent, but several problems occurred as often as in an earlier national study of acute care hospitals. Academic medical centers and other teaching hospitals tended to have more problems than nonteaching hospitals, but there was great variability within hospital types. The article discusses ways patient reports can be used to improve the quality of hospital care.

Data Collection↗
PubMed1993

Effect of beta-blocker therapy on serum lipoprotein profiles in patients on renal dialysis and in diabetic nephropathy.

We determined whether the serum lipoprotein levels in insulin-dependent diabetic patients (IDDM) with nephropathy and in patients on haemodialysis or continuous ambulatory peritoneal dialysis were affected by beta-blocker therapy. A case control study was performed in 18 IDDM patients with diabetic nephropathy, in 18 patients receiving chronic haemodialysis (HD) and 16 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In IDDM patients with diabetic nephropathy very low density lipoprotein-cholesterol (VLDL-CHOL) (0.680 +/- 0.17 vs 0.197 +/- 0.04 mmol/l, p = 0.004), total triglycerides (1.71 +/- 0.23 vs 0.808 +/- 0.14 mmol/l, p = 0.004) and very low density lipoprotein triglyceride (VLD-TG) were higher in the beta-blocker therapy group. In haemodialysis patients, beta-blocker therapy caused no significant changes in the serum lipoprotein profiles compared to the control group. In patients receiving continuous ambulatory peritoneal dialysis VLDL-CHOL was significantly higher (1.47 +/- 0.24 vs 1.08 +/- 0.21 mmol/l, p = 0.042) and cholesterol-high density lipoprotein (HDL-CHOL) was lower in the beta-blocker therapy group. The elevated VLDL-CHOL level (0.96 +/- 0.12 vs 1.24 +/- 0.14 mmol/l, p = 0.021) was correlated with the duration of CAPD in patients receiving beta-blocker therapy. Antihypertensive therapy with beta-blockers in IDDM patients with persistent proteinuria and in patients on continuous ambulatory peritoneal dialysis appears to adversely effect serum lipoproteins which may add to their cardiovascular risk.

Adrenergic beta-Antagonists↗
PubMed1992

Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.

Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy.

Albuminuria↗
PubMed1992

Nissen fundoplication in children with profound neurologic disability. High risks and unmet goals.

Anti-reflux procedures have been advocated in children with profound neurologic disability referred for feeding gastrostomy when gastroesophageal reflux is present. Facilitation of care, reduction in pneumonia and vomiting, and improvement in the general health and survival of these children have been major goals of fundoplication and gastrostomy. In large pediatric series, these procedures have been reported to have low risk and negligible mortality rates. Recent reports, however, document an increased incidence of sequelae of fundoplication in children with profound neurologic disability. This paper retrospectively reviews a series of 35 nonverbal, nonambulatory pediatric patients undergoing a total of 39 fundoplications (37 Nissen, 1 Thal, and 1 Belsey) over an 11-year period. Neurologic impairment of 17 (49%) patients was acquired, 13 (37%) congenital, and 5 (14%) due to a syndrome. Perioperative complications occurred in six (17%). Three additional complications led to early postoperative death. A fourth early death was unexplained. Fourteen (40%) had recurrent pneumonia, 11 (31%) recurrent vomiting, 8 (23%) choking-gagging-retching complex, and 3 (9%) bowel obstruction requiring laparotomy. Recurrent gastroesophageal reflux was documented in seven (20%) patients. A second ARP was performed in six (17%). There were 14 (40%) late deaths. Although the major goals of anti-reflux procedure are clearly achieved in many severely impaired children with gastroesophageal reflux, the use of Nissen fundoplication to resolve the complications of swallowing disorders and improve outcome with an acceptably low risk in this complex set of patients does not appear to be established.

Adolescent↗