Effective treatment of cobalamin deficiency with oral cobalamin

Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 micromol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37. 2 micromol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 micromol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 micromol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 micromol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.     

T3, T4 and TSH serum levels in patients on long-term treatment for epilepsy

The serum T3, T4 and TSH concentrations were assessed by RIA method in 25 (14 females, 11 males) long-term treated (mean treatment duration 12.8 years) epileptic patients. The mean serum T3, T4 and TSH levels were lower than in control group according to clinical picture of epilepsy and treatment applied. The lowest mean serum TSH concentration was in patients with known aetiology of epilepsy. Patients with tonic-clonic seizures had lower serum levels of all hormones measured in comparison with the patients with partial seizures. Mean serum T3, T4 and TSH levels were low in patient group receiving valproic acid. The lowest mean TSH serum concentration as compared to control group was in the patients treated with phenytoin. None of the epileptic patients developed clinical symptoms of hypothyreoidism.     

Manual circumlaryngeal therapy for functional dysphonia: an evaluation of short- and long-term treatment outcomes

In a liquid environment, at high dilutions, fertility of bull sperm is maintained for 3-5 days when stored at ambient temperatures (10-21 degrees C), after which time it steadily declines at a rate of 3-6% per day. This decline in fertility occurs irrespective of whether the sperm are stored at 5 degrees C or at 15 degrees C, but the rate is greater once storage temperatures exceed 25 degrees C. Sperm motility can be maintained for extended periods in an environment where the extracellular oxidative stress is minimized by reducing the oxygen tension, by addition of antioxidants and chelating agents; however, this will not prevent a significant drop in fertility after five days of storage at ambient temperature. The requirement of energy by the sperm-motility apparatus demands a high level of respiratory activity. This system is very active and the free radicals produced in vivo during this process could lead to chromatin damage. As no internal repair mechanism exists in sperm, an extraneous supply of protectants, or an environment where damage is minimized, is essential to maintain its fertilizing potential. The lack of extended storage potential of sperm, even in the presence of antioxidants, seems to suggest that although oocyte-penetrating ability of the sperm could still be intact, the high rate of intracellular metabolic activity could lead to mitochondrial DNA damage and chromosomal abnormalities that would compromise the viability of the resulting conceptus.     

Differing mechanisms of expression for short- and long-term potentiation

Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity that is of great interest as a cellular mechanism that may contribute to memory storage. It is the sustained phase of population excitatory postsynaptic potential induced by high-frequency stimulation (HFS). HFS can also induce short-term potentiation (STP), a decremental potentiation lasting approximately 15 min. It has been unclear whether STP is simply a reversible form of LTP elicited by subthreshold stimuli or whether it is an independently expressed form of synaptic plasticity. We have attempted to clarify the relationship between LTP and STP in the extracellular recording technique in area CA1 of the adult rat hippocampal slice preparation to test four predictions of the hypothesis that LTP and STP are expressed via the same mechanism. First, occluding LTP expression should block STP expression. Saturating LTP under six different conditions, however, did not occlude STP expression. Second, occluding STP expression should occlude LTP expression. The partial or full occlusion of STP by two maneuvers (increasing the stimulus intensity used for HFS or applying 3-isobutyl-1-methylxanthine), however, did not occlude LTP expression. Third, LTP increases and decreases paired-pulse facilitation (PPF), and STP should have the same effect. STP did not change PFF, however. The first three results, then, suggest that STP and LTP are expressed via different mechanisms. Fourth, STP should be maximal near the LTP induction threshold, and then decrease above it. Surprisingly, STP was maximal at or very close to the LTP induction threshold, but it did not decrease above this threshold. This relationship suggests the possibility that STP and LTP share an induction step(s). What is the function of the independently expressed STP? We find that LTP can be induced by two HFSs, each of which is subthreshold for LTP, if the second is given during STP from the first. This suggests that STP can temporarily lower the LTP induction threshold. Three lines of evidence, then, suggest that STP and LTP may be expressed via different mechanisms; however, the proximity of STP saturation to LTP induction suggests that they may share an induction step(s). STP may also have the very important function of temporarily lowering the LTP induction threshold. Finally, these data suggestion caution in interpreting LTP data obtained <20-30 min after HFS, because they may be contaminated by STP, which appears to have different underlying mechanisms.     

Water filtration of the forearm in short- and long-term diabetes mellitus

Blood flow and capillary filtration coefficient (CFC) were measured by strain-gauge plethysmography on the upper and lower third of the forearm in 9 normal subjects and 29 well regulated patients with diabetes mellitus of varying duration (less than 10 years, 10 to 20 years, and more than 20 years). There was no difference in blood flow in the four groups, but CFC was significantly increased in long-term diabetes (duration above 20 years) when measured at the distal part of the forearm near the wrist. Calculations showed that this was probably due to the relatively high contribution of connective tissue in this part of the forearm. Increased water filtration in connective tissue in long-term diabetics is in accordance with earlier findings of a lowered subcutaneous interstitial fluid albumin concentration in long-term diabetics, this being explained by an increase in net water outflux from the microcirculation.     

Effects of practice and learner control on short- and long-term gain and efficiency

This study investigated the effects of practice opportunities and learner control on short- and long-term learning from a computer-based introductory statistics curriculum. In all, 380 participants were assigned to one of five conditions. The first four conditions differed in terms of the number of problems to solve per problem set. The fifth condition allowed learners to choose the amount of practice. A subset (n = 120) of the original participants returned for testing following a six-month interval. Overall, the fixed-practice conditions showed learning gains that varied in relation to the amount of practice (i.e., more was better). The data from the learner-control condition was unexpected, showing learning gains comparable with the most extended practice condition yet the fastest tutor-completion times. We discuss implications of these findings in relation to the design of efficacious instruction. Actual or potential applications of this research include the modification of computer-based instruction that can enhance individuals' learning efficiency and outcome scores.     

Effect of short-course high-dose methylprednisolone treatment on serum IL-2 levels in children with myelodysplastic syndromes: a pilot study

Promising results in children with myelodysplastic syndromes (MDS) have been reported with high-dose methylprednisolone (HDMP) as a differentiation inducer, combined with cytotoxic chemotherapy. HDMP treatment has been shown to stimulate some cytokines in patients with acute leukemia. In the present study the effect of HDMP treatment on serum levels of interleukin 2 (IL-2) was evaluated in five children with MDS. Remarkable increases in serum IL-2 levels were observed 3 and 7 days after HDMP (30 mg/kg per day) treatment in three patients with chronic myelomonocytic leukemia (CMML). There was no correlation between the peripheral blood absolute lymphocyte counts and serum IL-2 levels. The results of this preliminary study indicate that the use of short-course HDMP treatment might be beneficial to increase the serum IL-2 level in patients with CMML.     

Laryngeal manifestations of gastroesophageal reflux before and after treatment with omeprazole

BACKGROUND: Laryngeal manifestations of gastroesophageal reflux disease are thought to be prevalent in our society. In general, diagnosis has been primarily based on symptoms. Historically, additional testing has included laryngoscopy, barium swallow, manometry, and single and double probe pH monitoring. METHODS: We assessed 96 patients who had symptoms suggestive of reflux laryngitis. We administered surveys grading their symptoms. All patients had standardized videolaryngostroboscopic evaluation and computerized acoustic analysis. Patients then received a uniform regimen of dietary restrictions and omeprazole (a proton pump inhibitor) for 12 weeks, after which they were retested. RESULTS: Using the new laryngoscopic grading system, we found that this regimen produced statistically significant improvement in all symptoms except granulomas. In patients with the pretherapy complaint of hoarseness, acoustic measurements of jitter, shimmer, habitual frequency, and frequency range all showed significant improvement. CONCLUSIONS: We conclude that in patients with symptomatic reflux laryngitis, standardized videolaryngoscopy and, if the patient is hoarse, acoustic analysis are useful techniques to aid diagnosis and monitor therapy. Antireflux therapy with omeprazole is effective, and improvement can be objectively shown with the techniques described.     

A longitudinal study of short- and long-term activity levels in male and female spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats.

The pattern of locomotor activity across development was assessed in male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. Open field activity did not indicate hyperactivity in the SHR. Instead, the SD strain was generally more active. Strains and sexes did not differ in open-field locomotor response to drug challenges. When short-term (10-12 min) activity in different apparatuses was compared, the SD were most active in the open field, the SHR in the residential figure-eight maze, and the WKY in the running wheel. Long-term tests indicated hyperactivity in the SHR in the residential figure-eight maze and hypoactivity in the SD in the running wheels. Until such strain differences in activity are thoroughly defined, the use of the SHR as a model of attention-deficit/hyperactivity disorder is limited. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

OBJECTIVE: To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. MATERIAL AND METHODS: We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). RESULTS: Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. CONCLUSION: Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.     

Positive and negative reinforcement with short- and long-term hospitalized schizophrenics in a probability learning situation.

Groups of 40 long-term (LT) and 40 short-term (ST) schizophrenics were randomly assigned to positive (PR) and negative (NR) extrinsic reinforcement conditions during a probability learning task. Prior to experimental conditions, paper-and-pencil test measures of neuroticism, extroversion, paranoia, and process-reactive were administered. The results supported the major hypotheses that (a) ST schizophrenics are more responsive to PR than NR, (b) LT schizophrenics are more responsive to NR than PR, and (c) ST schizophrenics are more responsive to both PR and NR than LT schizophrenics. None of the correlations between personality variables and responsiveness to PR or NR were significant. The significant interaction between length of hospitalization and type of reinforcement was interpreted as reflecting schizophrenics' adjustment to the hospital environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of blood letting on serum aminotransferase levels of patients with chronic hepatitis C and iron overload

We found in the Ca2+ channel alpha1C subunit gene a new repetitive element of three paired exon 45/46-related sequences. We also identified a new exon 45/46-related sequence in the human genome and mapped it by fluorescence in situ hybridization to the 12p11.2 and 12p13.2-p13.1 bands. These positions are not recognized by DNA probes generated from the 5'- and 3'-terminal regions of the alpha1C gene. A possible existence of a new genomic homologue of the alpha1C subunit gene is discussed.     

Human rectal absorption of short- and medium-chain C2-C10 fatty acids

PURPOSE: To study the effects of running suture adjustment for reduction of astigmatism after penetrating keratoplasty. Suture adjustments performed during surgery and during the early postoperative and late postoperative periods were retrospectively compared. METHODS: We studied 53 patients who received running suture adjustment after penetrating keratoplasty, either intraoperatively (ISA group, n = 18), early (< 2 weeks) postoperatively (EPSA group, n = 19), or late (> 1 month) postoperatively (LPSA group, n = 16). Refractive and topographic astigmatism and corneal topography were examined at 1, 3, and 6 months after surgery. RESULTS: Overall mean refractive astigmatism and topographic astigmatism at 6 months were 2.55 +/- 1.61 D and 3.12 +/- 1.89 D, respectively (mean +/- SD). The mean refractive astigmatism and topographic astigmatism were 1.88 +/- 1.04 D and 2.35 +/- 1.35 D in the ISA group, 2.32 +/- 1.17 D and 2.70 +/- 1.21 D in the EPSA group, and 3.01 +/- 1.62 D and 4.62 +/- 2.51 D in the LPSA group, respectively (mean +/- SD). The LPSA group demonstrated significantly increased topographic astigmatism compared to the ISA group (p = 0.0048) and the EPSA group (p = 0.015). Although 31.6 and 25.0% of the EPSA and LPSA groups, respectively, did not require postoperative suture adjustments, more eyes (10/18 eyes, 55.6%) in the ISA group did not require the procedure. CONCLUSIONS: Early postoperative suture adjustment was more effective than late postoperative adjustment. Intraoperative suture adjustment may further reduce final astigmatism and the necessity for postoperative suture manipulation.     

Testosterone treatment in men with erectile disorder and low levels of total testosterone in serum

Since decreased serum levels of testosterone (T) do not necessarily predict good outcome of testosterone treatment for erectile disorder, the purpose, of this study was to determine which men with erectile disorder and decreased serum levels might benefit from treatment. From a sample of 31 men (mean age = 39 years), 15 (48%) with erectile disorder and decreased serum levels of T responded well after 8 weeks of testosterone treatment (100 mg of testosterone propionate in the sustained-release form given im once a week). Good treatment outcome was associated with several variables, but only high levels of luteinizing hormone (LH) and low values of the T/LH (testosterone/LH) ratio consistently emerged as significant correlates and/or predictors of effective treatment. Levels of LH above 7.5 IU/L or the values of the T/LH ratio equal to or below 0.87 nmol/IU in patients with erectile disorder and decreased serum levels of T suggest that testosterone treatment may be effective.     

Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear.

Examines the effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on contextual fear conditioning in 48 female rats. Freezing behavior served as the measure of conditioning. Unlesioned control Ss showed reliable conditional freezing in the testing chamber when observed both immediately and 24 hrs after footshocks. In contrast, Ss with amygdala or ventral PAG lesions exhibited a significant attenuation in freezing both immediately and 24 hrs after the shocks. Dorsal PAG lesions had no effect on freezing at either time. Ss with hippocampal lesions displayed robust freezing behavior immediately following the shock, even though they showed a marked deficit in freezing 24 hrs after the shock. These results indicate that there are anatomically dissociable short- and long-term conditional fear states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)