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Biomedical subjects

J D Walker

Publications and source records attributed to J D Walker.

At least 19 recordsLinked to original sources
PubMed1995

Angiotensin-converting enzyme inhibition and the progression of congestive cardiomyopathy. Effects on left ventricular and myocyte structure and function.

BACKGROUND: Clinical trials have demonstrated that angiotensin-converting enzyme inhibition (ACEI) improves survival in patients with long-term left ventricular (LV) dysfunction. However, it remained unclear from these clinical reports whether the beneficial effects of ACEI were due to direct improvements in LV myocardial structure and function. Accordingly, the overall objective of the present study was to examine the direct effects of ACEI on both LV and myocyte structure and function in the setting of cardiomyopathic disease. METHODS AND RESULTS: LV and isolated myocyte function and structure were examined in control dogs (n = 6), in dogs after the development of dilated cardiomyopathy caused by rapid ventricular pacing (RVP, 216 beats per minute, 4 weeks, n = 6), and in dogs with RVP and concomitant ACEI (RVP/ACEI, fosinopril 30 mg/kg BID, n = 6). LV ejection fraction fell with RVP compared with control values (35 +/- 3 versus 73 +/- 2%, P < .05) and was higher with RVP/ACEI compared with RVP values (41 +/- 4%, P = .048). LV end-diastolic volume increased with RVP compared with control values (78 +/- 7 versus 101 +/- 7 cm3, P < .05) and was lower with RVP/ACEI (82 +/- 3 cm3, P < .05). Isolated myocyte length increased with RVP (182 +- 1 versus 149 +/- 1 micron), and the velocity of shortening decreased (36 +/- 1 versus 57 +/- 1 micron/s) compared with control values (P < .05). With RVP/ACEI, myocyte length was reduced (169 +/- 1 micron) and velocity of shortening was increased (45 +/- 1 micron/s) compared with RVP values (P < .05). Myocyte velocity of shortening after beta-adrenergic receptor stimulation with 25 nmol/L isoproterenol was reduced with RVP compared with control values (142 +/- 5 versus 193 +/- 8 micron/s, P < .05) and significantly improved with RVP/ACEI (166 +/- 6 micron/s, P < .05). In the RVP group, beta-adrenergic receptor density fell 26%, and cAMP production with beta-adrenergic receptor stimulation was reduced 48% from control values. RVP/ACEI resulted in a normalization of beta-adrenergic receptor density and cAMP production. LV myosin heavy-chain content when normalized to dry weight of myocardium was unchanged with RVP (149 +/- 11 mg per gram dry weight of myocardium [gdwt]) and RVP/ACEI (150 +/- 4 mg/gdwt) compared with control values (165 +/- 4 mg/gdwt). LV collagen content decreased with RVP compared with control values (7.6 +/- 0.4 versus 9.6 +/- 0.8 mg per gram wet weight of myocardium [gwwt], P < .05) but was increased with RVP/ACEI (14.4 +/- 1.3 mg/gwwt, P < .05). CONCLUSIONS: Concomitant ACEI with chronic tachycardia reduced LV chamber dilation and improved myocyte contractile function and beta-adrenergic responsiveness. Contributory cellular and extracellular mechanisms for the beneficial effects of ACEI in this model of dilated cardiomyopathy included a normalization of beta-adrenergic receptor function and enhanced myocardial collagen support. The results from this study provide evidence that ACEI during the development of cardiomyopathic disease provided beneficial effects on LV myocyte contractile processes and myocardial structure.

Angiotensin-Converting Enzyme Inhibitors↗
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

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↗
PubMed1992

Evaluation of the integrity of the blood-brain barrier after meningeal trauma.

RATIONALE AND OBJECTIVES: The authors used magnetic resonance imaging (MRI) techniques to examine the effect of meningeal trauma produced by cisterna magna puncture on the integrity of the blood-cerebrospinal fluid barrier (BCB) in a rat model. METHODS: Intravenous gadolinium-DTPA (Gd-DTPA), a relaxation rate modifier which normally does not cross the BCB, was used as a probe to follow leakage of fluid across the BCB. After Gd-DTPA injection, cerebrospinal fluid (CSF) serial samples were obtained through the needle used to create the experimental trauma. These samples were subsequently examined in vitro by MRI to obtain their T1 relaxation rates and assayed by mass spectrometry for gadolinium and elemental iron concentrations. RESULTS: The iron levels reflected the severity of puncture-related subarachnoid hemorrhage. Rats with ongoing meningeal damage showed significantly higher CSF levels of gadolinium and significantly higher CSF T1 relaxation rates than controls at all samples times over 1 hour after the puncture. Blood in the CSF could not explain these changes because the CSF iron levels did not significantly differ from control levels. CONCLUSIONS: Intravenously administered Gd-DTPA can gain access to the subarachnoid space through minor defects in the BCB and cause significant increases in CSF T1 relaxation rates.

Animals↗
PubMed1992

Na+/H+ antiport activity and cell growth in cultured skin fibroblasts of IDDM patients with nephropathy.

IDDM patients with incipient and overt nephropathy have been found to exhibit an overactivity of RBC sodium-lithium countertransport. To explore the physiological relevance of this finding, we measured the activity of Na+/H+ antiport in serially passaged cultured skin fibroblasts from IDDM patients with and without nephropathy and from normal, nondiabetic control subjects. Na+/H+ antiport activity (measured as the rate of amiloride-sensitive Na+ influx at pHi = 6.4, extracellular pH = 8.0, and [Na+] = 1 mM) was elevated significantly in IDDM patients with nephropathy compared with IDDM patients without nephropathy and nondiabetic control subjects (13.35 +/- 3.8 vs. 8.54 +/- 2.0 vs. 7.33 +/- 2.3 nmol Na+.mg protein-1.min-1; P less than 0.006 and P less than 0.001, respectively). A kinetic analysis of Na+/H+ antiport activity showed that the raised activity in IDDM patients with nephropathy was caused by an increased Vmax for extracellular Na+. Km values were similar in the three groups. pH-stimulated amiloride-sensitive Na+ influx also was higher under baseline conditions and after serum stimulation in cells from IDDM patients with nephropathy. pHi values were significantly higher, both during active proliferation and after 10-min exposure to serum, in cells from IDDM patients with nephropathy, compared with IDDM patients without nephropathy and nondiabetic control subjects. Serum-stimulated incorporation of [3H]thymidine into DNA was greater in IDDM patients with nephropathy than in the other two groups (35.7 +/- 18.9- vs. 17.4 +/- 7.5- vs. 11.9 +/- 8.7-fold stimulation above baseline; P less than 0.01 for both.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗