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Biomedical subjects

J Rosenfeld

Publications and source records attributed to J Rosenfeld.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fasciculations without fibrillations: the dilemma of early diagnosis.

The challenge of identifying patients at the earliest stage of disease has highlighted the role of subtle markers of clinical pathology. Electrophysiological changes usually precede evidence of clinical weakness and have, therefore, been implicated. Specifically, the onset of fasciculations, particularly those widespread in distribution, in the absence of fibrillation potentials, have been suggested as an early indicator of motor neuron disease. Several cases will be presented here to highlight instances where diffuse fasciculations were not enough to accurately implicate the current diagnostic criteria for amyotrophic lateral sclerosis (ALS). In two instances, alternative diagnoses were eventually supported. If the purpose of early diagnosis is to lead to early treatment with experimental therapy, we must be certain that we study as homogenous a population of patients as possible. Fasciculations by themselves are not enough to implicate early diagnosis; disease progression is probably the single most important historical characteristic for diagnosis. Signs of active denervation (i.e. fibrillation potentials) are critical. Chronic weakness should be proportional to either atrophy or upper motor neuron signs in the affected muscle. This should be true for both early and late recognition of the disease.

Adolescent↗
PubMed2000

Recovery of intellectual ability following traumatic brain injury in childhood: impact of injury severity and age at injury.

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine the relationship between recovery, injury severity, age at injury and pre-injury ability. 124 children were divided according to (1) age at injury: 'young' (3-7 years) 'old' (8-12) and (2) injury severity (mild, moderate, severe). Children were evaluated acutely (T1) and at 12 months post-injury (T2), using standardized intellectual measures (IQ). Results showed a relationship between greater injury severity and poorer IQ. Age at injury was not predictive of outcome for children with mild/moderate TBI. For severe TBI, younger age at injury led to minimal recovery in IQ, while recovery from later injury was similar to that for adults. Findings suggest that children sustaining severe TBI in early childhood may be particularly at risk for residual problems post-injury.

Adaptation, Psychological↗
PubMed2000

A new approach to blood pressure measurement in the primary care setting.

In this study, a method of taking one blood pressure reading using a sphygmomanometer was compared with a method of taking multiple successive readings using an automatic device. With multiple readings the blood pressure tended to be lower and fewer patients were classified as hypertensive. Using an automatic blood pressure recording device seems to be a practical way of achieving multiple readings in a busy clinic setting.

Adult↗
PubMed1999

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Aged↗
PubMed1999

Acute and chronic effects of spirapril, alone or in combination with isradipine on kidney function and blood pressure in patients with reduced kidney function and hypertension.

In the present study we investigated the effect of a single dose, and 3 months of treatment with spirapril on kidney function, renin-angiotensin system, renal handling of sodium and blood pressure, in patients with reduced kidney function (serum creatinine 1.5-3 mg%) and hypertension. A single dose of 6 mg spirapril given at the beginning of the study did not affect glomerular filtration rate (GFR), renal plasma flow (RPF), angiotensin converting enzyme (ACE) activity, plasma renin activity (PRA) or renal handling of sodium. When the single dose of spirapril was given after 3 months of treatment with this agent, renal hemodynamics and PRA did not change. ACE activity, which was depressed by the previous spirapril treatment, decreased further (from 9.5 +/- 3.1 to 1.4 +/- 1.0 nmol/ml/min), (p < 0.05). Administration of 6 mg spirapril o.d. for 3 months did not have any effect on GFR or RPF. Serum ACE activity decreased from 92.1 +/- 8.0 to 5.1 +/- 2.6 nmol/ml/min (p < 0.05) and PRA increased from 1.4 +/- 1.2 to 4.1 +/- 3.6 ng/ml/min (p < 0.05). Plasma aldosterone did not change. Similar results were obtained when spirapril was combined with 5 mg isradipine in the initial and final single dose, or in the 3 months' treatment (5 mg o.d.). Blood pressure was normalized in 38% of the patients who received spirapril and in 71% of the patients who received spirapril and isradipine. Thus, (a) treatment with spirapril in patients with mild to moderate chronic renal insufficiency was not associated with deleterious effects on kidney function; (b) spirapril in a dose of 6 mg alone or in combination with 5 mg isradipine is effective in reducing blood pressure in hypertensive patients with reduced kidney function.

Adult↗
PubMed1999

Rates of sugar uptake by guard cell protoplasts of pisum sativum L. Related To the solute requirement for stomatal opening

We wished to determine whether the capacity of the sugar uptake mechanisms of guard cells of the Argenteum mutant of pea (Pisum sativum L.) sufficed to support a concurrent stomatal opening movement. Sugar uptake by guard cell protoplasts was determined by silicone-oil-filtering centrifugation. The protoplasts took up [(14)C]glucose, [(14)C]fructose, and [(14)C]sucrose (Suc), apparently in symport with protons. Mannose, galactose, and fructose competed with Glc for transport by a presumed hexose carrier. The uptake of Glc saturated with a K(m) of 0.12 mM and a V(max) of 19 fmol cell(-1) h(-1). At external concentrations <1 mM, the uptake of Suc was slower than that of Glc. It exhibited a saturating component with a K(m) varying between 0.25 and 0.8 mM and a V(max) between 1 and 10 fmol cell(-1) h(-1), and at external concentrations >1 mM, a non-saturating component. At apoplastic sugar concentrations below 4 mM, sugar import was estimated to be mainly in the form of hexoses and too slow to support a simultaneous stomatal opening movement. If, however, during times of high photosynthesis and transpiration, the apoplastic Suc concentration rose and entered the range of non-saturating import, absorbed Suc could replace potassium malate as the osmoticum for the maintenance of stomatal opening.

Journal Article↗
PubMed1999

The international database of self-recorded blood pressures in normotensive and untreated hypertensive subjects.

OBJECTIVES: To pool data from individual subjects in an attempt to determine an operational threshold for making clinical decisions based on the self-recorded blood pressure (SRBP) and to examine how many hypertensive subjects, diagnosed by conventional blood pressure (CBP) measurement, would have a self-recorded blood pressure within the normotensive range if the proposed thresholds were applied. DATA SOURCES: Thirteen research groups studied 4668 untreated subjects. RESULTS: In total 2401 subjects were normotensive, 494 were borderline hypertensive and 1773 were definitely hypertensive. Hypertension had been diagnosed from the mean of 1-6 (median 3) CBP measurements obtained during 1-3 (median 1) visits. The reference values for SRBP measurements determined from the 95th percentiles of the distributions for normotensive subjects were 137 mmHg systolic and 85 mmHg diastolic. Of the subjects with systolic hypertension, 16% had systolic SRBP </= 137 mmHg. Similarly, 25% of those with diastolic hypertension had diastolic SRBP </= 85 mmHg. The probability that hypertensive subjects had SRBP below these thresholds was 34% (diastolic) to 62% (systolic) greater for women than it was for men, was 2-3 times greater if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension, and increased by 50% (diastolic) to 126% (systolic) when SRBP had been measured on more than 3 days. In contrast, for each 10 mmHg increment in systolic CBP, this probability decreased by 35% for systolic SRBP and by 11% for diastolic SRBP; for each 5 mmHg increment in diastolic CBP it decreased by 36% for diastolic SRBP. In addition, for systolic blood pressure, the probability decreased by 31% for each 10-year increment in age. CONCLUSIONS: Until the relationship between SRBP and the incidence of cardiovascular morbidity and mortality has been clarified further by prospective studies, a mean self-recorded blood pressure above 137 mmHg systolic or 85 mmHg diastolic may be considered hypertensive. Among the hypertensive patients 16-31% had SRBP below these thresholds, but this proportion decreased if the hypertensive subjects had higher CBP.

Adolescent↗
PubMed1998

Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase.

SR31747 is a novel agent that elicits immunosuppressive and anti-inflammatory effects. This drug was shown to inhibit Delta8-Delta7 sterol isomerase in yeast. To test whether this enzyme could also be an SR31747 target in mammals, the binding, antiproliferative and sterol biosynthesis inhibitory properties of various drugs were studied in recombinant sterol isomerase-producing yeast cells. Our results clearly show that SR31747 is a high affinity ligand of recombinant mammalian sterol isomerase (Kd = 1 nM). Tridemorph, a sterol biosynthesis inhibitor that is widely used in agriculture as an antifungal agent, is also a powerful inhibitor of murine and human sterol isomerases (IC50 value in the nanomolar range). Some drugs, like cis-flupentixol, trifluoperazine, 7-ketocholestanol and tamoxifen, inhibit SR31747 binding only with the mammalian enzymes, whereas other drugs, like haloperidol and fenpropimorph, are much more effective with the yeast enzyme than with the mammalian ones. Emopamil, a high affinity ligand of human sterol isomerase, is inefficient in inhibiting SR31747 binding to its mammalian target, suggesting that the SR31747 and emopamil binding sites on mammalian sterol isomerase do not overlap. In contrast, SR31747 binding inhibition by tamoxifen is very efficient and competitive (IC50 value in the nanomolar range), indicating that mammalian sterol isomerase contains a so-called antiestrogen binding site. Tamoxifen is found to selectively inhibit sterol biosynthesis at the sterol isomerase step in the cells that are producing the mammalian enzyme in place of their own sterol isomerase. Finally, we also show that tridemorph, a sterol biosynthesis inhibitor widely used in agriculture as an antifungal agent, is not selective of yeast Delta8-Delta7 sterol isomerase but is also highly efficient against murine Delta8-Delta7 sterol isomerase or human Delta8-Delta7 sterol isomerase. This observation contrasts with our already published results showing that fenpropimorph, another sterol isomerase inhibitor used in agriculture, is only poorly efficient against the mammalian enzymes.

Animals↗
PubMed1997

Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint. METHODS: All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. FINDINGS: At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22). INTERPRETATION: Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.

Aged↗
PubMed1997

A novel muscle sodium channel mutation causes painful congenital myotonia.

Mutations in the skeletal muscle voltage-gated sodium channel alpha-subunit gene (SCN4A) have been associated with a spectrum of inherited nondystrophic myotonias and periodic paralyses. Most disease-associated SCN4A alleles occur in portions of the gene that encode the third and fourth repeat domains with the conspicuous absence of mutations in domain 1. Here we describe a family segregating an unusual autosomal dominant congenital myotonia associated with debilitating pain especially severe in the intercostal muscles. A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome. Myotonia was resistant to treatment; however, the most severely affected family member responded dramatically to the sodium channel blocking agent flecainide.

Alleles↗
PubMed1997

Expression of superoxide dismutase following axotomy.

Oxidative injury has been implicated in the pathophysiology of neuronal injury and neurodegenerative disease. Antioxidant proteins provide an endogenous defense against such oxidative injury and may yield important clues to mechanisms of cytoprotection and neuronal recovery. Axotomy is the simplest model of neuronal injury and lesioning the sciatic nerve allows concurrent study of both motor (spinal cord) and sensory (dorsal root ganglia, DRG) neurons affected by the same injury. This study was designed to examine the expression of superoxide dismutase (SOD), an essential antioxidant protein, in motor and sensory neurons following complete axotomy of peripheral nerve. Immunocytochemical, quantitative immunoblot, and enzymatic activity assay techniques are used. By 12 days after axotomy, immunocytochemical expression of Mn-SOD is markedly increased in affected DRG and spinal cord. A similar increase in Cu/Zn-SOD is not seen in DRG or spinal cord. This immunocytochemical staining is associated with a significant increase in specific activity and Mn-SOD protein content as measured on quantitative immunoblots. This report suggests, for the first time, that Mn-SOD and not Cu/Zn-SOD increases in sensory neurons of the DRG and motor neurons of the spinal cord following distal axotomy of the sciatic nerve. Quantitative measurements of Mn-SOD following axotomy reveals that the increase in immunocytochemical reactivity is associated with an approximately 30% increase in specific activity when comparing lesioned and contralateral spinal cord samples. These data suggest that Mn-SOD may have a more significant role in the pathophysiology of neuronal injury than Cu/Zn-SOD.

Animals↗
PubMed1997

Determining the trough-to-peak ratio in parallel-group trials. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

We explored how in parallel-group trials interindividual variability, correction for placebo effects, and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension (> or = 60 years) enrolled in the placebo-controlled Systolic Hypertension in europe Trial. Net treatment effects were computed by subtracting the mean changes from baseline during placebo (n = 133) from those during active treatment (n = 111). At entry, systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring. With corrections applied for baseline and placebo, nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d), reduced (P < .001) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg, respectively. The net trough-to-peak ratios were first determined from blood pressure profiles (12 hours) with 1-hour precision, synchronized by the morning and evening doses of the double-blind medication. According to the usual approach, disregarding interindividual variability, the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening. In individual subjects, the baseline-adjusted trough-to-peak ratios were nonnormally distributed. We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects. In the morning, these ratios averaged 0.25 systolic (95% confidence interval, 0.09 to 0.41) and 0.15 diastolic (95% confidence interval, 0.00 to 0.31) and in the evening, 0.19 and 0.36 (95% confidence intervals, 0.00 to 0.38 and 0.14 to 0.56), respectively. When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling, the trough-to-peak ratios remained unchanged after the morning dose (0.20/0.13, 0.20/0.14, and 0.16/0.21, respectively) but tended to increase in the evening (0.32/0.38, 0.28/0.40, and 0.48/0.49). In conclusion, the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo, to account for interindividual variability, and to calculate a confidence interval for the net trough-to-peak ratio. Accounting for interindividual variability reduces the trough-to-peak ratio. Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided.

Aged↗
PubMed1997

De novo 14484 mitochondrial DNA mutation in monozygotic twins discordant for Leber's hereditary optic neuropathy.

Monozygotic twin brothers, clinically discordant for Leber's hereditary optic neuropathy (LHON), had a heteroplasmic point mutation at position 14484 in the mitochondrial DNA that was not detected in their mother. Moreover, the mutation occurred on the rare European haplogroup X, rather than the haplogroup J commonly associated with the 14484 mutation. These data indicate that the 14484 mutation in this family was a new mutation, indicating that it was the de novo occurrence of a common, primary LHON mutation.

Adolescent↗
PubMed1997

Predicting recovery from head injury in young children: a prospective analysis.

It has been argued that young children's brains are "plastic," and may sustain substantial brain insult with little loss of function. Recent research suggests that this notion may not apply for generalized cerebral pathology. The present study aimed to evaluate this proposition using a sample of 73 young children, divided into 3 groups: severe head injury (HI; N = 17); mild-moderate HI (N = 32); and noninjured controls (N = 24). Preinjury screening established equivalence across groups for age, sex, preinjury ability, behavioral adjustment, socioeconomic status, and family functioning. Children were evaluated as soon as possible postinjury, and again 12 months postinjury, in three domains: intellectual ability, language, and memory. Results indicated that severe HI was associated with substantial, persisting difficulties in all areas. In contrast, children with mild-moderate HI experienced fewer difficulties, and often performed similarly to controls, both acutely and 12 months postinjury. There was no evidence of differential recovery of function associated with injury severity, with performance increments consistent across groups and probably due to either age-appropriate developmental gains, or test-related practice effects. Poorer outcome at 12 months postinjury was predicted by injury severity primarily, with earlier age at injury, and premorbid ability associated with outcome in specific domains.

Age Factors↗
PubMed1995

Spontaneous intracranial hypotension: headache with a reversible Arnold-Chiari malformation.

Spontaneous intracranial hypotension is characterized by severe postural headache in the setting of low CSF pressure, usually attributed to a cryptic CSF leak. We report a patient whose prolonged refractory headache was characterized by the clinical symptoms of occipital neuralgia, but was also associated with the radiographic appearance of an Arnold-Chiari malformation, type I and low CSF pressure. After extensive diagnostic evaluation, CT cisternomyelography ultimately demonstrated a CSF leak at the C2 vertebral level. Symptomatic relief was sustained only with long-term theophylline administration. The apparent Arnold-Chiari malformation resolved with treatment of the low CSF pressure.

Adult↗
PubMed1994

Modulation of plasma arginine vasopressin during rehydration in the Bedouin goat.

When severely dehydrated Bedouin goats were allowed to drink to satiation their plasma arginine vasopressin concentration immediately dropped from a value of 19.9 +/- 9.4 pmol.l-1 to 9.4 +/- 3.9 pmol.l-1 (P < 0.05). It continued to drop further until a concentration of 1.8 +/- 2.9 pmol.l-1 was recorded, similar to that reported for goats allowed to drink freely. When the goats were shown the water but drinking was denied, plasma arginine vasopressin immediately dropped to 11.7 +/- 4.0 pmol.l-1 (P < 0.05) and further decreased to 10.0 +/- 4.8 pmol.l-1 5 min following their sighting the water. This level, however, was not sustained and 2 h after the initial drop the high pre-trial concentration of plasma arginine vasopressin was regained. Presumably, sighting of water by dehydrated goats induces an abrupt drop in their plasma arginine vasopressin level even before drinking commences. When rehydrated, by introducing water directly to the rumen, circumventing both the sensing of the water and the drinking proper, no immediate drop in the plasma arginine vasopressin concentration of the newly rehydrated goats was observed. A delayed drop in the plasma arginine vasopressin levels took place slowly, concurrently with the drop in osmolality and concentration of Na+ in the plasma. It is suggested that sighting of water by dehydrated goats is involved in the modulation of plasma arginine vasopressin.

Animals↗
PubMed1993

Myelitis following chickenpox: a case report.

An 18-year-old woman presented with myelopathic symptoms and a T-8 sensory deficit during a primary varicella infection. There were significant MRI changes in both the cervical and thoracic regions. Following treatment with steroids and intravenous acyclovir, the patient improved clinically and the abnormalities on MRI improved.

Adolescent↗