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Biomedical subjects

P Griffith

Publications and source records attributed to P Griffith.

At least 19 recordsLinked to original sources

A prospective population-based study of pediatric trauma patients with mild alterations in consciousness (Glasgow Coma Scale score of 13-14).

OBJECTIVE: Considerable controversy surrounds the appropriate evaluation of children with mild alterations in consciousness after closed head trauma (Glasgow Coma Scale [GCS] score of 13-14). The objective of the current study was to determine the incidence of intracranial lesions in pediatric patients with a field GCS score of 13 or 14 after closed head injuries. METHODS: The current study is a population-based, multicenter prospective study of all patients to whom emergency medical services responded during a 12-month period. The setting was urban Los Angeles County, encompassing a patient population of 2.3 million children, 13 designated trauma centers, and 94 receiving hospitals. RESULTS: In the pediatric age group (<15 yr old), 8488 patients were transported by emergency medical services for injuries. Of these, 209 had a documented field GCS score of 13 or 14. One hundred fifty-seven patients were taken to trauma centers, and 135 (86%) underwent computed tomography. Forty-three patients (27.4%) had abnormal results on computed tomographic scans, 30 (19.1%) had an intracranial hemorrhage, and 5 required an operative neurosurgical procedure for hematoma evacuation. Positive and negative predictive values of deteriorating mental status (0.500 and 0.844, respectively), loss of consciousness (0.173 and 0.809), cranial fracture (0.483 and 0.875, and extracranial injuries (0.205 and 0.814) were poor predictors of intracranial hemorrhage. CONCLUSION: Pediatric patients who have mild alterations in consciousness in the field have a significant incidence of intracranial injury. The great majority of these patients will not require operative intervention, but the implications of missing these hemorrhages can be severe for this subgroup of head-injured patients. Because clinical criteria and cranial x-rays are poor predictors of intracranial hemorrhage, it is recommended that all children with a GCS score of 13 or 14 routinely undergo screening via non-contrast-enhanced computed tomography.

Adolescent↗

Multielectrode nerve cuff stimulation of the median nerve produces selective movements in a raccoon animal model.

In this study, an electrode system consisting of twelve small platinum dot electrodes imbedded in a spiral silicone rubber insulating cuff was used to investigate the feasibility of selective (regional) stimulation of the median nerves of the raccoon. Acute experiments in four raccoons consisted of functional responses observations, isometric force recordings from tendon attachments and postmortem fascicular mapping. Functional responses (elbow, wrist and/or digit flexion, pronation and/or thumb abduction) to selective stimulation were noted as dependent upon cuff electrode configuration (longitudinal tripole with and without field steering, as well as a transverse bipolar arrangement) and current level (threshold, 1/2 maximal, maximal). Muscle force recruitment curves (force as a function of stimulus amplitude) were plotted for flexor digitorum superficialis, flexor digitorum profundus, flexor carpi radialis, palmaris longus and pronator teres of three raccoons. Fascicular maps at the level of the nerve cuff were created indicating the approximate position of innervation to each of the aforementioned muscles, as well as other innervation such as paw fascicles, sensory fascicles, and elbow innervation (such as coracobrachialis). The greatest selectivity was observed at or near threshold current levels. In all four raccoons studied, a threshold electrode choice and stimulation strategy could be identified enabling selective production of either digit flexion, wrist flexion and/or digit and wrist flexion. It was possible to elicit a selective pronation response at threshold in three of the four animals. Selective elbow flexion at threshold could be produced in all four experiments. With stronger currents, additional movements were usually induced. The raccoon therefore appears to be a suitable, if challenging, animal model for further development of not only nerve cuff electrode approaches but perhaps other stimulation electrode technologies prior to human neuroprosthetic studies.

Animals↗

The raccoon as an animal model for upper limb neural prosthetics.

The raccoon was evaluated as an animal model for upper limb neural prosthetics. This animal was selected primarily because the functional use of its forelimb mimics in many ways the usage in humans and because of its optimal size and commercial availability. Eight cadaver and fresh specimen forearms were dissected. Important characteristics of the raccoon forearm were: 1) large muscles in the volar forearm, 2) large digits in the paw that appear more similar to humans than to other species such as cat or dog, 3) persistence of two median nerve cords into the forearm, 4) no separation of individual tendons of flexor digitorum superficialis and flexor digitorum profundus in the carpal tunnel, 5) a small thumb digit with little function and 6) a primary origin of flexor policis longus on the proximal ulna with a secondary origin on the radius. Four animals were anesthetized and responses of the forearm and paw to stimulation of the volar forearm muscles with percutaneous electrodes were evaluated. A pair of stimulating electrodes was placed in each of four muscles or muscle groups. Recording electrodes were placed in two muscles which showed the greatest separation of muscle movements to stimulation. Stimulation currents just above threshold produced discrete motion as well as recordable EMG M-waves. Incremental increases in stimulation current produced an increase in M-wave amplitude up to a maximal stimulating current. Torque recordings for pronation, wrist flexion and finger flexion showed graded and selective responses. These results including anatomical descriptions indicate both the limitations of this animal model and its potential use in the development of upper limb neural prosthetics. We conclude that the raccoon model may be superior to other nonprimate animal models such as the cat because of its extensive forearm and paw movements.

Animals↗

Lack of efficacy of tranexamic acid in thrombocytopenic bleeding.

A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.

Anemia, Aplastic↗

Antenatal aminophylline and steroid exposure: effects on glomerular filtration rate and renal sodium excretion in preterm newborns.

Creatinine clearance and renal sodium excretion were measured consecutively in three groups of 12 premature infants (gestational age less than or equal to 35 weeks) whose mothers had received either steroids or aminophylline, or steroids and aminophylline before delivery. We found no significant differences for plasma and urine creatinine and its clearance in the groups considered. The steroid group presented urine osmolality and urine/plasma osmolality ratio significantly higher than among the other groups. Furthermore, urine potassium excretion increased, and urine sodium and sodium fractional excretion were reduced. Aminophylline exposure did not interfere with the hydrosaline equilibrium nor with renal function of the preterms at birth. Our results reconfirm that corticosteroid hormones play an important part in the fetal renal maturation process, inducing a precocious maturation of the tubular Na(+)-K+ ATPase enzymatic system, that is substantially unmodified by aminophylline exposure. However, due to the prolonged half-life of aminophylline in prematures, it seems reasonable to verify the coupling of tubular and glomerular functions also in the following days of life.

Aminophylline↗

Premorbid personality assessments of first onset of major depression.

This is a report on personality traits associated with the first onset of major depression in a sample of high-risk subjects. The subjects are the first-degree relatives, spouses, and their controls of patients with affective disorders. None of these subjects had any history of mental disorder as of their initial evaluation. In the subsequent six years, 29 subjects had a first onset of major depression. These first onset subjects were compared with 370 subjects who continued to be free of illness during the six-year follow-up. Personality traits were assessed at the initial evaluation (ie, before the onset of depression in subjects with first onset) by means of scales from five self-report inventories. Lower emotional strength and resiliency significantly differentiated the first onset from the never ill group; overall differences were not found on measures of interpersonal dependency or extraversion. Age was a significant predictor of first onset, both alone (younger age predicted first onsets) and in interaction with personality measures. Among younger subjects (17 to 30 years of age), personality variables did not significantly discriminate between the two comparison groups. Among older subjects (31 to 41 years of age), however, decreased emotional strength, increased interpersonal dependency, and increased thoughtfulness were associated with first onset of depression.

Adult↗

Cyclosporine therapy of aplastic anaemia, congenital and acquired red cell aplasia.

We treated 22 patients with severe aplastic anaemia refractory to antithymocyte globulin (ATG) with cyclosporine, alone or in combination with prednisone. Eight patients showed significant clinical improvement, all but one to transfusion-independence. Although cyclosporine alone was effective, the addition of prednisone resulted in prompter and fuller haematologic improvement. No patient with an absolute granulocyte count less than 0.2 x 10(9)/l responded to treatment. Haematologic remissions were sustained beyond the treatment period. Of nine patients with Diamond-Blackfan syndrome, one showed a complete response to two separate courses of cyclosporine and relapse with withdrawal of therapy, and a second achieved significant reduction in corticosteroid dose without relapse; however, seven cases failed to respond. Two of three adults with acquired pure red cell aplasia recovered. A combination of cyclosporine and corticosteroids may be effective therapy in patients with aplastic anaemia who have failed ATG treatment. Occasional cases of congenital and acquired pure red cell aplasia may also respond to cyclosporine.

Adolescent↗

Dexamethasone in the treatment of bronchopulmonary dysplasia.

Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible during the therapy period. Ventilatory parameters were lowered in 3 other newborns. FIO2, respiratory rate, PIP, and PEEP, assessed before and after dexamethasone administration, decreased in a statistically significant way. Our data confirm the utility of dexamethasone in the extubation in chronically ventilated infants with BPD.

Bronchopulmonary Dysplasia↗

The mechanism of mucus clearance in cough.

An instability resembling an avalanche is proposed as the mechanism by which mucus is expelled from the respiratory tract during cough. The cough event was simulated in a model airway. In these experiments, air was forced through a channel whose walls were lined with a non-Newtonian material rheologically similar to tracheal mucus. Frames from high-speed cine photographs showed an unstable event which began as an undulation of the free surface and progressed to a catastrophic clearance of the channel. Measurements of the longitudinal pressure gradient support the hypothesis that the clearance event is initiated when the total stress applied to the mucus analog exceeds its finite yield stress. A continuum model predicts that yielding occurs within the bottom layers of the mucus analog. Calculations based upon estimates of tracheal geometry and air flow show that the clearance event studied here would be expected to occur during a cough but not during normal breathing. Experiments also show that a lubricant introduced between the channel walls and the mucus blanket can reduce the air flow rate required to precipitate the clearance.

Cough↗

A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases.

One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

Anemia, Aplastic↗

Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia.

Twenty-two patients with adult onset aplastic anaemia were analysed before and after therapy with anti-thymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy; clinical response was determined 1 year post-therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL-2 receptor) and in the proportion of HLA-DR+ lymphocytes. For T cells bearing HLA-DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre-ATG to post-ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non-responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. Gamma-interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post-ATG, gamma-interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post-treatment, but pre-treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T-cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.

Adolescent↗

Analysis of lymphocyte subsets in patients with aplastic anaemia.

Lymphocyte subsets have been measured in the blood of 28 patients with aplastic anaemia. The mean helper/inducer:suppressor/cytotoxic T lymphocyte ratio (1.24 +/- 0.74) was significantly decreased in the total population in comparison to mean ratios in a normal population (1.78 +/- 0.57) and in patients with other haematological diseases (1.82 +/- 0.92). A reversed ratio (less than or equal to 1) was present in a large proportion (53%) of aplastic patients, due both to an absolute deficiency of helper/inducer lymphocytes and an increase in suppressor/cytotoxic lymphocytes. Increased HLA-DR expression, evidence of lymphocyte activation, was present in seven of 12 patients evaluated and was confined to the suppressor/cytotoxic lymphocyte population. In the bone marrow, the percentage of lymphocytes was increased two-fold compared to normal bone marrow but the ratio of T cell subsets was not abnormal. Two of four patients evaluated after haematopoietic recovery following ATG treatment showed a return to normal of the T4/T8 ratio; in two others a low T4/T8 ratio persisted despite recovery. These results indicate that lymphocyte subset imbalance and lymphocyte activation are present in many patients with aplastic anaemia, either as a contributing factor or as a result of bone marrow failure.

Adolescent↗

A trial of immunotherapy in aplastic anemia and pure red cell aplasia.

Immunotherapy, consisting of lymphocyte depletion or plasmapheresis in combination with cyclophosphamide and prednisone, was employed in three patients with refractory pure red cell aplasia and six patients with aplastic anemia of various etiologies. All three patients with pure red cell aplasia responded to plasmapheresis. One patient with atypical aplastic anemia showed partial recovery following lymphocyte depletion; the other five patients showed no evidence of a clinical response. The effect of patients' sera or bone marrow on formation of myeloid or erythroid colonies by bone marrow from normal individuals was determined in vitro. A decline in serum inhibition of erythroid colony formation was observed in the patients with pure red cell aplasia following treatment. Any changes in serum inhibition were less marked or unrelated to treatment outcome in the patients with aplastic anemia, although the single patient who responded to lymphocyte depletion exhibited reversal of coculture bone marrow inhibition. Our experience suggests that in vitro assay methods may not adequately predict the response of patients with aplastic anemia to this form of immunotherapy, and furthermore clinical improvement was too sporadic for this treatment to be recommended. Plasmapheresis may be a useful adjunct in patients with pure red cell aplasia, but remissions may not be dramatic or sustained.

Adult↗

Regulation by complementary idiotypes. Ig protects the clone producing it.

A/He mice actively producing complementary or anti-idiotypic antibody directed against a combining site structure for phosphorylcholine (PC) have profound and long-lasting suppression of their response to PC. B cells from unresponsive mice are unresponsive in vitro, and attempts to demonstrate suppressor cells in unresponsive mice were unsuccessful. Although the process ultimately responsible for suppression has not been defined, suppression can be initiated by anti-idiotypic antibody alone and prevented by complementary Ig; i.e., by anti-PC antibody. Furthermore, a suppressed anti-PC response can be rescued by sublethal irradiation and anti-PC antibody given passively. The recovery of the suppressed response is slow and presumably results from maturation from "stem" cells, which are protected from tolerization by the passively given antibody. Thus, by extrapolation, one of the functions of secreted Ig may be to protect the clone that produces it.

Animals↗

Selective isolation of young erythrocytes for transfusion support of thalassemia major patients.

Transfusion-induced hemochromatosis remains a major therapeutic complication in the management of thalassemia major patients. Using available blood cell component separators, a system has been devised to selectively harvest young red cells from transfusion support of these subjects. Red cell units isolated by this method have an average estimated mean cell age of 30 days, compared to 60 days for unfractionated blood, and contain 80% of the hemoglobin content of standard red cell units. Radiochromium half-life for young cells measured in 7 asplenic thalassemia major patients averaged 47.4 days compared to 29.5 days for routine frozen red cells. The enhanced survival is not due to reticulocyte enrichment alone, but represents a true cohort of younger red cells. Although costly, this modality could theoretically halve the transfusion requirement in transfusion-dependent patients. When combined with modern iron chelator regimens, it may be possible to achieve consistently negative iron balance prior to the onset of hemochromatosis.

Cell Separation↗