The nociceptive withdrawal reflex: Normative values of thresholds and reflex receptive fields

Assessments of spinal nociceptive withdrawal reflexes can be used in human research both to evaluate the effect of analgesics and explore pain mechanisms related to sensitization. Before the reflex can be used as a clinical tool, normative values need to be determined in large scale studies. The aim of this study was to determine the reference values of spinal nociceptive reflexes and subjective pain thresholds (to single and repeated stimulation), and of the area of the reflex receptive fields (RRF) in 300 pain‐free volunteers. The influences of gender, age, height, weight, body‐mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short‐Form 36 (SF‐36) were analyzed by multiple regressions. The 95% confidence intervals were determined for all the tests as normative values. Age had a statistically and quantitatively significant impact on the subjective pain threshold to single stimuli. The reflex threshold to single stimulus was lower on the dominant compared to the non‐dominant side. Depression had a negative impact on the subjective pain threshold to single stimuli. All the other analyses either did not reveal statistical significance or displayed quantitatively insignificant correlations. In conclusion, normative values of parameters related to the spinal nociceptive reflex were determined. This allows their clinical application for assessing central hyperexcitability in individual patients. The parameters investigated explore different aspects of sensitization processes that are largely independent of demographic characteristics, cognitive and affective factors.     

Effect of sertraline hydrochloride on dialysis hypotension

Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease (ESRD) and plays a key role in HH in some patients. Sertraline hydrochloride, a central nervous system serotonin reuptake inhibitor, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction in disorders such as neurocardiogenic syncope and idiopathic orthostatic hypotension. This study sought to determine whether sertraline was effective in ameliorating HH. A retrospective chart analysis was performed that included nine consecutive patients (aged > or = 54 years, time on hemodialysis > or = 2.2 years) placed on sertraline (50 to 100 mg/d) for depression who also had HH (defined as prehemodialysis systolic blood pressure [SBP] < or = 100 mm Hg, > or = 40 mm Hg decrease in SBP during hemodialysis, SBP <90 mm Hg, any diastolic blood pressure <40 mm Hg, or a decrease in blood pressure-causing symptoms) before treatment with sertraline. The data from a 6-week pre-sertraline period were compared with the data from a 6-week sertraline period (defined as 6 weeks after drug begun). Blood pressure medications were unchanged during the trial period of sertraline. However, nadir mean arterial pressure recorded during a given dialysis session in the pre-sertraline period (55+/-4 mm Hg) was significantly lower than that recorded in the sertraline period (68+/-5 mm Hg; P < 0.05). In addition, the number of hypotensive episodes (same definition as HH) per dialysis session during the sertraline period was significantly lower than that during the pre-sertraline period (mean, 0.6+/-0.2 episodes per session v 1.4+/-0.3 episodes per session; P < 0.005). The number of therapeutic interventions required for hypotension during the sertraline period was also significantly less than that during the pre-sertraline period (mean, 1.7+/-0.8 interventions v 11.0+/-3.0 interventions; P < 0.005). The urea reduction ratio (62.7%+/-4.7% v 63.1%+/-9.3%; P = NS) and hematocrit (28.9%+/-0.8% v 29.5%+/-1.0%; P = NS) did not change significantly. It is concluded that the short-term (6 weeks) use of sertraline hydrochloride reduces HH in some patients with ESRD. A possible mechanism for this effect is sertraline-induced attenuation of the paradoxical sympathetic withdrawal that may underlie HH in some patients with ESRD.     

Developmental Background and Outcome in Patients with Nonepileptic Versus Epileptic Seizures: A Controlled Study

Summary: Purpose: This study was designed to evaluate the relevance of developmental emotional stress factors, which are considered to influence emotional functioning, as contributing factors in the development of psychogenic symptoms.
Methods: Ten patients with nonepileptic seizures (non-ESs)(frequently referred to as psychogenic seizures), in whom diagnosis had been confirmed by a placebo-infusion test (PT), and 10 control patients with complex partial seizures (ESs) were evaluated with regard to developmental background by using structured in-depth interviews performed by a single interviewer blinded to the diagnosis. In addition, outcome assessment in the non-ES group after PT was done.
Results: There were no significant differences between groups in developmental psychosocial stress or in any single developmental stress factor. Six months after PT, the outcome was favorable in patients with non-ES: six were seizure free, and two had a considerable reduction in frequency of seizures.
Conclusions: Our research indicates the following: (a) a high incidence of developmental stress factors and functional disturbances may be found in patients with non-ESs and ESs; (b) assessment of developmental emotional stress and functional disturbances as a basis for validating the diagonsis of non-ES should be treated with caution; (c) use of PT followed by supportive information about the nonepileptic origin of the attacks may have a positive therapeutic effect or help to introduce psychotherapeutic treatment.     

Increased HbF in sickle cell anemia is determined by a factor linked to the beta S gene from one parent

Members of 7 large families, containing 20 patients with sickle cell anemia (SS) characterized by high levels of fetal hemoglobin (HbF), were studied using immunofluorescence to count F cells and a radioimmunoassay to measure small amounts of HbF. In five of these families, one of the sickle cell trait (AS) parents had a much higher HbF and F-cell count than the other; in one family, both parents had a marked increase in HbF and F cells; in the remaining family, HbF and F cells were at borderline values in both parents. Seven of 14 AS siblings, but only 1 of 8 normal hemoglobin (AA) siblings, also had HbF and F-cell counts above the "normal" range. It seems that a factor for increased F cells, linked to the beta S gene of one parent, is segregating in these families and is responsible for the greatly increased HbF and F cells in the SS subjects. HbF per F cell in AS parents and siblings was the same as that of normal AA subjects, whereas in the SS offspring it was greatly increased, suggesting that it was the result of marrow hyperplasia associated with their hemolytic anemia. The similarity of this "increased F-cell gene" to heterocellular hereditary persistence of fetal hemoglobin (HPFH). Swiss type, is discussed, and it is suggested that it may control the persistent synthesis of HbF in sickle cell anemia by its presence in early infancy.     

A murine model for the switch from fetal to adult hemoglobin during ontogeny

In murine erythroleukemia cells, the minor/major hemoglobin (Hb) ratio depends on the cell line and the inducing agent. To determine whether mouse minor hemoglobin is a "fetal" hemoglobin in vivo, globin chain composition and synthesis rates were determined in DBA/2 mice of various ages ranging from 14-day embryos to > 6-mo adults. Globin chains were separated by electrophoresis on polyacrylamide gels containing urea and Triton X-100. This method separates the embryonic (x,y,z) and the adult (alpha, beta ma, beta mi) globin chains. Fourteen day embryos had only 5%-10% adult globins but approximately 30% of the adult beta chains were beta mi. The % beta mi decreased with age and reached 20% in adult mice. Biosynthetic studies led to more pronounced differences: beta mi synthesis was 45% of total beta chain production in 14-day embryos and declined to 22% in adults. Thus beta minor/total beta globin synthesis declines during mouse ontogeny. This resembles qualitatively the human switch from fetal to adult hemoglobin and provides a murine model for studies of hemoglobin regulation.     

Fetal erythropoiesis following bone marrow transplantation

"Fetal" erythrocytes are present in older children and certain adults with hematologic disorders. To determine if regenerating bone marrow produces such cells, we examined the blood of seven allogeneic bone marrow transplant recipients. Six patients were engrafted with donor cells, while on e patients recovered autologous bone marrow after rejection of a marrow transplant. All seven patients had fetal hemoglobin levels of up to 10% by 100 days after transplant. In three patients, the Ggamma to Agamma ratio in the fetal hemoglobin was "newborn", while in one it was "adult". Gamma chain synthesis in blood and bone marrow never exceeded 20% of total non-alpha globin synthesis. The fetal hemoglobin was heterogeneously distributed in the cells. High titer i antigen also appeared. All fetal characteristics declined by 200 days. Erythropoiesis during bone marrow recovery appears to be associated with an accelerated, albeit partial, recapitulation of ontogeny.     

Ulcer healing properties of different extracts of Origanum majorana in streptozotocin-nicotinamide induced diabetic rats

ObjectiveThe aim of the present investigation was to evaluate the ulcer healing properties of different extracts of Origannum majorana, viz., hydrodistilled volatile oil (OMO), methanolic (OMM) and aqueous extract (OMW) in streptozotocin-nicotinamide induced diabetic rats.MethodsAll the extracts were administered in different doses (100, 200 and 400 mg/kg, p.o.) to investigate the ulcer healing potential. Streptozotocin (STZ; 65 mg/kg, i.p.) along with nicotinamide (120 mg/kg, i.p.) was used to induce non-insulin dependent diabetes mellitus in rats. Aspirin (200 mg/kg, i.p.) was administered for initial 7 d to induce gastric ulcerations in the diabetic rats. Various biochemical markers of blood and tissue origin were estimated to compare the ulcer healing potential of these extracts.ResultsThe OMO and OMM exhibited dose dependent significant (P<0.01) ulcer healing property than the OMW. Additionally, the antidiabetic property of OMO and OMM was better than OMW.ConclusionThe OMO and OMM of Origanum majorana leaves can prove to be beneficial in the concomitant treatment of gastric ulcers and diabetes.     

Fetal hemoglobin synthesis in erythroid cultures in hereditary persistence of fetal hemoglobin and beta o-thalassemia

To determine whether hemoglobin regulation is normal in diseases affecting beta-globin gene expression, globin synthesis was examined in members of a family of a patient with hereditary persistence of fetal hemoglobin/beta o-thalassemia (HPFH/beta o-thal). The HPFH defect is the Ghanian type II, with a deletion from psi beta 1 to at least 20 kb 3' to beta. The beta o-thal gene has the haplotype II restriction enzyme pattern and has the beta 39 nonsense mutation. Erythroid colonies from blood BFU-E were radiolabeled, and globin chains were separated by gel electrophoresis. Colonies from the beta o-thal heterozygote had non-alpha/alpha ratios more balanced than in the reticulocytes. Gamma synthesis was 11% of non-alpha, which is higher than in reticulocytes, but within the range seen in normal adult colonies. Both HPFH heterozygotes produced 20%-30% gamma in erythroid colonies as well as reticulocytes, although non-alpha/alpha was more balanced in the colonies. The HPFH/beta o-thal patient produced 100% gamma in reticulocytes and in colonies. G gamma and gamma-synthetic proportions were not correlated at the individual colony level in the heterozygotes, suggesting that they had "adult" and not "fetal" progenitor cells. The Hb expression of these adult progenitors is presumably modulated normally in vivo in beta o-thal, but the normal decrease in HbF production does not occur in gene deletion HPFH.     

De novo minimal change disease

Beyond the acute posttransplantation period, glomerular causes of proteinuria in the renal allograft include recurrent glomerulopathy, transplant-associated entities, and de novo disease. We present a case of de novo minimal change disease with reversible acute renal failure occurring 2.5 years posttransplantation in a 56-year-old man. The cause of end-stage renal disease in the native kidney was membranous glomerulopathy. De novo minimal change disease in the renal allograft is an extremely rare entity requiring stringent clinical-pathological criteria for diagnosis. Many of the cases previously reported as de novo minimal change disease fail to meet these criteria. We review the eight reported cases that appear to fulfill a strict definition of minimal change disease in the context of the current report.