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A case of an 11-year-old boy with rapidly progressing quadriparesis with bowel and bladder incontinence is reported. MRI of the spine revealed an intramedullary tuberculoma at the level of C5-7. Investigations further revealed evidence of tuberculosis in the brain and lungs as well. The child made a rapid recovery with medical management alone.
Quantitative characters are often said to evolve rather slowly, taking many generations to exhibit appreciable differences among populations. We tested this notion experimentally by performing bi-directional selection on corolla diameter of plants from a wild population of Phlox drummondii for three generations. By monitoring flower size, tube length and stigma-anther proximity of flowers, we obtained the direct and indirect responses to selection, and calculated genetic correlations, realized and narrow sense heritabilities using offspring-mother regression. Realized heritability of flower size was high (0.83), whereas genetic correlations among traits were weak or not significant. The per-generation average of the response in corolla diameter was about 5%. We found that P. drummondii has a great capacity to respond rapidly to selection, and this capacity may be in part responsible for the observed high degree of differentiation within the species. We also concluded that rapid evolution of morphological floral traits is possible.
A case of rapid cycling bipolar disorder in a person with Down's syndrome, responsive to divalproex sodium, a valproic acid derivative, is presented. This case and three other reported cases of mania in association with Down's syndrome suggest that this chromosomal disorder does not preclude the development of mania.
Bisphosphonate treatment for severe Paget's disease leads to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. A case is presented of a 60-year-old woman with polyostotic Paget's disease and postsurgical hypoparathyroidism. In 1993 her Paget's disease--alkaline phosphatase (ALP), 1260 U/liter (35-135 U/liter), and fasting urinary hydroxyproline excretion, 13.7 micromol/liter GF (0.4-1.9 micromol/liter)--was treated with intravenous pamidronate. Symptomatic hypocalcemia followed the first 60-mg dose, requiring large doses of calcium supplementation and calcitriol. Pamidronate therapy to a total dose of 360 mg was followed by rapid and prolonged remission with indices of bone turnover in the normal range within 2 months and persisting for at least 19 months after treatment. In 1999 relapse of Paget's disease--ALP, 511 U/liter (35-135 U/liter), and fasting urinary deoxypyridinoline/creatinine 53.1 micromol/mol (5-27 micromol/mol)--was treated with alendronate, 10 mg daily. Symptomatic hypocalcemia occurred again, requiring increased calcium and calcitriol therapy. Indices of bone turnover were within the normal range 9 weeks after the start of therapy. These responses were significantly more rapid and sustained than those observed in euparathyroid subjects. This case suggests that the lack of parathyroid response may modify the response to bisphosphonates by: (a) increasing intrinsic uptake of bisphosphonate into the pagetic skeleton, allowing response to a smaller dose; (b) increasing duration and severity of hypocalcemia after bisphosphonate therapy; and (c) removing the hyperparathyroid drive to reactivation of pagetic osteoclasts, leading to a prolonged remission. These observations have implications for optimizing bisphosphonate therapy both in Paget's disease and in osteoporosis.
A patient presented with widespread small cell carcinoma, abnormalities on liver function tests, and rapidly progressive lactic acidosis. The acidosis was totally corrected following chemotherapy. Prompt treatment in tumor-associated lactic acidosis may significantly prolong survival.
PURPOSE: We present a case of peripheral corneal ulceration in a patient with hepatitis C, which rapidly and dramatically responded to intravenous steroid treatment. METHODS: Clinical examination and photographs were obtained to document initial presentation and therapeutic response of Mooren's-type ulcers to steroids. RESULTS: Bilateral peripheral corneal ulceration with documented progression responded to intravenous administration of steroids within 5 days. CONCLUSION: Previous reports of Mooren's-type ulcers in patients with chronic hepatitis C have shown a response to interferon alfa-2b, but not to oral corticosteroid therapy. Given the medical contraindications to interferon use in selected patients and the cost, we suggest a trial of high-dose systemic steroids as a possible therapy.
High concentrations (up to 600 pg/ml) of corticotropin-releasing hormone (CRH) were detected in plasma of the teleost fish Oreochromis mossambicus (tilapia) when screening peripheral tissues of tilapia exposed to stress. Notably, the plasma CRH response to stressors in tilapia is much more pronounced than that in higher vertebrates, such as rats. After characterisation by RIA, by spiking plasma with synthetic tilapia CRH and by methanol-acid extraction, it is concluded that the immunoreactive (ir) material in plasma represents tilapia CRH(1-41). Results indicate that a CRH-binding protein is absent in tilapia plasma. Unstressed fish had plasma CRH levels under the limit of detection (<2 pg/ml), but following capture stress plasma CRH levels (170-300 pg/ml) as well as plasma cortisol levels (120 ng/ml) increased rapidly to plateau levels, which were reached after approximately 5 min. Tilapia CRH(1-41) tested at concentrations between 10(-11) and 10(-7) M in vitro did not stimulate the cortisol release from interrenal tissue. Also pretreatment of interrenal tissue with 10(-9) M CRH did not sensitise the cortisol-producing cells to a subsequent ACTH challenge. Forty-eight hours of net confinement or 48 h of cortisol treatment abolished the plasma CRH response and cortisol response to capture stress. The rapidity of the plasma CRH response and its inhibition after 48 h of stress or cortisol treatment point to release by central nervous tissue. Therefore the distribution of glucocorticoid receptors (GRs) in the brain and pituitary of tilapia was investigated. Main GR-ir cell clusters were found in the medial part (Dm) and posterior part of the dorsal telencephalon, in the preoptic region, in the inferior lobe of the hypothalamus and in the cerebellum. We conclude from comparison of CRH brain contents of unstressed and stressed fish that plasma CRH was released by CRH-ir cells located in the lateral part of the ventral telencephalon (Vl), and suggest that the cortisol feedback on CRH release by Vl is mainly exerted via the forebrain Dm region. We propose that CRH is mobilised during stress to fulfil peripheral functions, such as the regulation of circulating leukocytes or of cardiac output, as CRH receptors have been reported in these organs for fish species.
Specific absorption rates (SARs) of microwave energy that altered firing rates were determined for individual pacemaker neurons in the abdominal ganglion of Aplysia californica. A stripline apparatus provided both for artifact-free recording of transmembrane potentials and for precise determination of the rate of absorption of microwave energy. Exposure for two to three minutes at an SAR of only a few mW/g was capable of changing the firing rate of some pacemakers. Two types of responses were observed. The response that was seen in all neurons developed slowly, reaching a steady state in one to three minutes. The other response was seen in a few neurons and occurred within five seconds from the onset of irradiation. Similar responses were obtained for two microwave frequencies, 1.5 and 2.45 GHz. Pulsed radiation induced rapid changes of firing rate more readily than did CW radiation at the same SAR. A convective heating scheme was used to study the effects of temperature changes on the pacemakers' firing rates. Since all of the responses are not readily explained by general heating of the preparation, alternate mechanisms are suggested for the observed effects.
There is a generalized age-related decline in immune responses which leads to increased susceptibility of elderly to infection and, possibly, to autoimmune disease and cancer. This is associated with phenotypic changes of CD8+ T lymphocytes that include the loss of costimulatory molecules CD28 and CD27, which are important for proliferation and cell survival of CD8+ T cells. Loss of these molecules is associated with less ability to respond to recurrent infection. Functional changes within T cells during ageing include a reduction in the number of naive T cells and a progressively limited T cell repertoire. Furthermore, persistent life-long antigenic stress upon the memory pool leads to telomere erosion and concomittant loss of proliferative capacity, a phenomenon known as replicative senesence. In this review, we discuss that replicative senescence, or clonal exhaustion, may also occur in relatively young individuals, as evidenced from HIV-infected individuals and healthy Ethiopians. We discuss data suggesting that T cell defects may arise in individuals because of chronic antigen activation leading to rapid ageing of the memory CD8+ T cell pool.
Recent observation of objects speeds up their subsequent identification and classification. This common form of learning, known as repetition priming, can operate in the absence of explicit memory for earlier experiences, and functional neuroimaging has shown that object classification improved in this way is accompanied by 'neural priming' (reduced neural activity) in prefrontal, fusiform and other cortical regions. These observations have led to suggestions that cortical representations of items undergo 'tuning', whereby neurons encoding irrelevant information respond less as a given object is observed repeatedly, thereby facilitating future availability of pertinent object knowledge. Here we provide experimental support for an alternative hypothesis, in which reduced cortical activity occurs because subjects rapidly learn their previous responses. After a primed object classification (such as 'bigger than a shoebox'), cue reversal ('smaller than a shoebox') greatly slowed performance and completely eliminated neural priming in fusiform cortex, which suggests that these cortical item representations were no more available for primed objects than they were for new objects. In contrast, prefrontal cortex activity tracked behavioural priming and predicted the degree to which cue reversal would slow down object classification--highlighting the role of the prefrontal cortex in executive control.
When adherent mononuclear cells are removed from whole blood, the separated lymphocytes respond rapidly by proliferation to foreign cocultured lymphocytes. The reaction of responding cells against a pool of foreign stimulating cells can be detected in this rapid mixed lymphocyte culture (r-MLC) within 28 h and antigenic disparity between family members, differing for only one HLA haplotype, can be measured within 36 h. These early responses show genetic specificity corresponding to those observed in a standard MLC at 96 h. The involvement of similar cell populations in the regulation of early responses to allogeneic cells and increased responses to autologous cells in r-MLC, as well as accelerated responses in secondary MLC, is discussed.
Functional brain imaging studies of priming assume that the behavioral facilitation and activity reductions resulting from multiple repetitions reflect the continued tuning of processes engaged during the initial processing of items. Utilizing an object priming paradigm in which participants were asked to make relative size judgments about visually presented common objects, we tested an alternate hypothesis that states that with multiple repetitions participants come to rely on a more efficient response learning mechanism. In experiment 1, the decision cue was inverted such that previous judgments made either once or three times were rendered invalid. Decision inversion resulted in a reduction of all priming, but most critically, led to a reduction of multiple-repetition priming to the level of single-repetition priming. In experiment 2, patients with amnesia failed to show a priming advantage for multiple repetitions, indicating that response learning is dependent on the medial temporal lobes. Taken together, these results suggest that a different process increasingly mediates priming behavior as repetitions increase. With repeated exposure, behavioral facilitation rapidly comes to reflect a more efficient response learning mechanism rather than facilitated access to object knowledge.
Vitamin D(3) produces biologic responses as a consequence of its metabolism into 1alpha,25(OH)(2)-vitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25(OH)(2)-vitamin D(3). The metabolic production of these two seco steroids and their generation of the plethora of biologic actions that are attributable to the parent vitamin D(3) are orchestrated via the integrated operation of the vitamin D endocrine system. This system is very similar in its organization to that of classic endocrine systems and is characterized by an endocrine gland (the kidney, the source of the two steroid hormones), target cells which possess receptors for the steroid hormones, and a feed-back loop involving changes in serum Ca(2+) that alter the secretion of parathyroid hormone (a stimulator of the renal 1-hydroxylase) which modulates the output by the kidney of the steroid hormones. There are, however, at least two unique aspects to the vitamin D endocrine system. (a) The chemical structures of vitamin D and its steroid hormones dictate that these be highly conformationally flexible molecules present a wide variety of shapes to their biologic environments. (b) It is now believed that 1alpha,25(OH)(2)D(3) produces biologic responses through two distinct receptors which recognize totally different shapes of the conformationally flexible 1alpha,25(OH)(2)D(3). Thus, the classic actions of 1alpha,25(OH)(2)D(3) to regulate gene transcription occur as a consequence of the stereospecific interaction of a modified 6-s-trans bowl-shape of 1alpha,25(OH)(2)D(3) with its nuclear receptor (VDR(nuc)). The ability of 1alpha,25(OH)(2)D(3) to generate a variety of rapid (seconds to minutes) biologic responses (opening of chloride channels, activation of PKC and MAP kinases) requires a planar 6-s-cis ligand shape which is recognized by a putative plasma membrane receptor (VDR(mem)) to initiate appropriate signal transduction pathways. This report summarizes the evidence for the specificity of different ligand shapes and the operation of the two receptor families for 1alpha,25(OH)(2)D(3).
Large and rapid increases in the activities of two enzymes of general phenylpropanoid metabolism, phenylalanine ammonia-lyase and 4-coumarate:CoA ligase, occurred in suspension-cultured parsley cells (Petroselinum hortense) treated with an elicitor preparation from Phytophthora megasperma var. sojae. Highest enzyme activities were obtained with an elicitor concentration similar to that required for maximal phenylalanine ammonialyase induction in cell suspension cultures of soybean, a natural host of the fungal pathogen.The changes in phenylalanine ammonia-lyase activity in parsley cells were caused by corresponding changes in the mRNA activity for this enzyme. Phenylalanine ammonia-lyase mRNA activity increased much faster and transiently reached a much higher level in elicitor-treated than in irradiated cell cultures. In contrast to irradiation, treatment of the cells with the elicitor did not induce the enzymes of the flavonoid glycoside pathway, as demonstrated for acetyl-CoA carboxylase and chalcone synthase. Induction of these enzymes by light was abolished by simultaneous application of the elicitor.
Based on the assumption that there is a biological basis behind the individual differences in the speed with which an antidepressant produces its therapeutic effects, we compared initial serotonin (5HT) uptake characteristics in platelets of rapid (2 weeks), slow (4 weeks) and non-responders in a group of 47 depressed patients who were treated with amitriptyline for at least 4 weeks. A response was defined as a reduction in the Hamilton Depression Rating Scale score of > or =50% from baseline. In 16 rapid responders, a significantly higher mean 5HT uptake efficiency (Vmax/Km) corresponded with a significantly higher 5HT uptake activity at a low, physiological substrate concentration in comparison with the 15 non-responders or the 16 slow responders (33.1+/-7.8 versus 25.5+/-7.7 versus 24.1+/-5.8 pMol [3H]-5HT/10(9) plat. x 5 min, respectively). The findings indicate that pre-treatment 5HT uptake activity contributes to the individual variability in response time to amitriptyline treatment.
Ten Type I insulin-dependent diabetics who were receiving single daily injections of intermediate acting insulin were studied to assess time-response characteristics of this therapy on 24-hour profiles of both glucose and free insulin. Nine of ten patients had undetectable postprandial levels of C-peptide. All patients had insulin antibodies typical of chronically treated Type I diabetes. Mean peak free insulin levels occurred four hours post injection with free insulin rising from 12.3 +/- 1.6 microU/ml to 26.5 +/- 1.4 microU/ml; p less than 0.01. The glucose nadir for the 24-hour profile also occurred at four hours after injection with glucose declining from 199 +/- 29 mg/dl fasting to 155 +/- 5 mg/dl; p less than 0.05. There was significant negative correlation between mean glucose and free insulin throughout the first six hours after insulin injection (r = -0.74; p less than 0.02); no correlation occurred 8 to 12 hours post injection. Two of the ten patients had hypoglycemic symptoms within four hours after their morning insulin. Although free insulin levels remained above basal for 20 hours, single dose intermediate insulin therapy never really controlled postprandial glucose levels after breakfast or lunch. These data suggest there may be limitations in managing Type I diabetics with single dose intermediate insulin. Furthermore, some patients on intermediate acting insulin may have a more rapid than anticipated maximal hypoglycemic response, often within four hours.
Transcatheter arterial embolization was used to treat a patient with glucagonoma metastatic to the liver after chemotherapy failed. Rapid amelioration of the syndrome's manifestations followed.
This study has described the organization of EMG activities among the muscles of a standing subject's legs during rapid postural adjustments (95--120 ms latencies). Adjustments were elicited by the horizontal translation of both feet (causing antero-posterior sway), by the synchronous vertical displacement of both feet (causing changes in height) and by the reciprocal vertical displacement of the feet (causing changes in height) and by the reciprocal vertical displacement of the feet (causing a locomotor-like motion of the legs and lateral sway of the body). The resulting patterns of EMG activity were highly specific for each kind of displacement, and all subjects completely reorganized the pattern of activity from one form to another within the first trials, even immediately following unexpected stimulus changes. The organization of EMG activities during reciprocal vertical displacements was qualitatively quite similar to those observed during the comparable swing and stance phases of the locomotor step cycle; flexor muscles of the ankle and knee (those being shortened by the displacement) contracted in the upwardly displaced leg while extensor muscles were active in the downwardly displaced leg. This pattern was in marked contrast to the activation of lengthening muscles during synchronous vertical and antero-posterior sway displacements. Finally, electrical cutaneous stimulation of the dorsum of one foot during reciprocal vertical displacements always enhanced the EMG activity of the agonist leg muscles, in-phase with the vertical movement.