Biomedical subjects
Publications and source records attributed to R Griffith.
Many complaints can be dealt with by the staff immediately concerned. Complaints procedures have been criticised as being too complicated. New procedures will extend the terms of reference of the Health Service Commissioner and should simplify the complaints procedure.
OBJECTIVE: To describe HIV-related media events in the context of first-time HIV-1-antibody testing trends at a London genitourinary medicine clinic. DESIGN: Demographic and behavioural data were collected prospectively for individuals tested for HIV-1 antibodies between September 1985 and September 1993, at the genitourinary medicine clinic of St Mary's Hospital, London. RESULTS: A total of 19,242 individuals were tested of whom 37% were women. Of the men tested 60% were heterosexual. The women at first time of testing were significantly younger [29.3 years; 95% confidence interval (CI), 28.8-29.7] than the men (32.5 years; 95% CI, 29.2-35.8); mean ages for both sexes did not change significantly over time. Overall, 199 women and 1539 men tested HIV-antibody-positive. The proportions of women testing positive increased significantly over time (chi 2 = 21.7, degrees of freedom = 1; P < 0.001), whereas the proportion of HIV-positive men remained constant for all sexual orientation groups. The proportion of heterosexual women testing positive (2.8%) was similar to the proportion of HIV-positive heterosexual men (2.9%). HIV-positive individuals were significantly older for both sexes. Throughout the study period numerous education campaigns were run using a variety of media complemented by a number of other HIV-related media events. CONCLUSIONS: Peak periods of attendance for HIV testing generally corresponded with increased HIV-related media activity and the greatest testing rates were observed when various HIV media events occurred concurrently. The increase in the number of heterosexuals tested suggests that the risk of heterosexual transmission of HIV has been recognized, at least among older individuals. The exact role of HIV-related media events, including celebrities disclosing their HIV-positive status, remains to be elucidated. Whether the relative under-representation of younger people is due to a lack of awareness, increased use of safer sex practices or reluctance to use the service also remains to be addressed. Given the increasing number of HIV-positive women and the relatively constant rate of HIV-positive tests in the male attendees an urgent need exists to assess the impact and effectiveness of specific HIV media campaigns.
Several laboratories have shown that isoproterenol induces or accelerates cell process formation in primary astrocyte cultures. These observations, together with the demonstration of beta-adrenergic receptors in astrocytes isolated from adult rat brain, led us to test the hypothesis that beta-antagonists prevent astrocyte hypertrophy in the injured spinal cord. Since blood-borne macrophages express beta-adrenergic receptors and release cytokines acting on glial cells, we avoided physical trauma and induced glial scar formation indirectly by injecting the cytotoxic ligand Ricinus communis into the sciatic nerve. Seven days later sections of the lumbar spinal cord in regions of motor neuron degeneration were processed for glial fibrillary acidic protein (GFAP) immunocytochemistry. Astrocyte hypertrophy was evaluated by optical density measurements of immunolabeled GFAP. Seven days after ricin treatment there is a mean increase of GFAP in the ventral horn of 11.8 +/- 4.4% (P < 0.0001) compared to the intact side. When L-propranolol is continuously infused from a subcutaneously implanted osmotic pump at a concentration calculated to produce a free plasma level of 4.4 nM, the GFAP increase is only 3.2 +/- 3%, reflecting a 73% reduction in astrocyte hypertrophy (P < 0.001). Receptor autoradiography with the ligand [125I]iodocyanopindolol showed a 26% increase in beta-adrenergic receptor density on the gliotic side. After propranolol treatment, there was only a 3.5% increase in ventral horn beta-adrenergic receptor density in the region of the glial scar.(ABSTRACT TRUNCATED AT 250 WORDS)
STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.
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We have enhanced the polymerase chain reaction (PCR) such that specific DNA sequences can be detected without opening the reaction tube. This enhancement requires the addition of ethidium bromide (EtBr) to a PCR. Since the fluorescence of EtBr increases in the presence of double-stranded (ds) DNA an increase in fluorescence in such a PCR indicates a positive amplification, which can be easily monitored externally. In fact, amplification can be continuously monitored in order to follow its progress. The ability to simultaneously amplify specific DNA sequences and detect the product of the amplification both simplifies and improves PCR and may facilitate its automation and more widespread use in the clinic or in other situations requiring high sample throughput.
We hypothesized that substitution of the hydroxyl group (OH) on the beta carbon of norepinephrine (NE) with an amino group would yield a compound, 1-(3,4-dihydroxyphenyl)-1,2-diaminoethane (DHPDAE), that would maintain the hemodynamic properties of NE during CPR, but would decrease the rate of post-defibrillation dysrhythmias. Six mixed breed swine weighing greater than 28 kg were studied. The animals were instrumented for cerebral (CBF) and myocardial blood flow (MBF) measurements. Ventricular fibrillation (VF) was induced. After 10 min of VF, CPR was begun. After 3 min of CPR, 2.5 mg/kg of DHPDAE was administered and CPR continued. Defibrillation was attempted 3.5 min after drug administration. CBF, MBF and defibrillation rates were compared to an historical control group receiving 0.16 mg/kg of NE. Outcome variables were compared using a Wilcoxon Rank Sum test and Fisher-exact test. NE significantly improved CBF and MBF compared to DHPDAE. All the animals in the NE group were successfully defibrillated into a perfusing rhythm. Sixty percent of the NE treated animals experienced post-defibrillation ventricular dysrhythmias. None of the animals in the DHPDAE were successfully defibrillated into a perfusing rhythm. Substitution of the hydroxyl group on the beta-carbon of NE with an amino group significantly decreases the hemodynamic properties of the parent molecule.
Fibroblasts from 5 1/2-day-old chick embryos go through a sequential series of changes when exposed to a constant electromagnetic field (EMF) of 10 V/cm. These changes include rounding up, becoming bipolar in shape, assuming a cylindrical profile, elongating perpendicular to the EMF, and migrating to the cathode. These morphological changes are associated with changes of the cell surface, which include the formation of filopodia and extensive sheet-like contacts on the cathodic cell surface, the retraction of processes and the formation of focal contacts on the anodic cell surface.
Elutriator-purified human monocytes were cultured in a serum-free (SF) medium, and various serum proteins and functional activating agents were assessed for their effects on the in vitro maturation of human monocytes to macrophages. Following 3 days of suspension culture in Teflon labware, 60% of the monocytes were easily recovered. When varying concentrations of human AB serum (HuAB) were employed, human monocyte maturation progressed rapidly; the kinetics of this maturation process during cell suspension culture were very similar to the pattern observed following adherence culture. In contrast, when SF medium was employed, a marked retardation of the monocyte maturation process was observed; this could not be attributed to any changes in cell recovery and/or viability. Thus, cells could be maintained in their monocytoid form for 3 days when cultured in SF medium. When HuAB was added after 3 days of culture, human monocyte maturation into macrophages proceeded at a normal rate. We attempted to characterize certain of the serum protein(s) found in HuAB which promoted the monocyte maturation process. Human immunoglobulin G (IgG) was found to be the most potent serum protein in increasing 5'-N activity and decreasing peroxidase activity of suspension cultured monocytes. Immunoglobulin M (IgM) and albumin (Alb) were shown not to have significant monocyte maturation activity. Heat-treated human gamma globulin and IgG purified by high-performance liquid chromatography (HPLC) were shown to have patterns identical with that of untreated HGG and IgG with regard to promoting monocyte maturation; F(ab')2 was not an active maturation promoter, indicating the need for an intact Fc portion of the IgG molecule. Fibrinogen and fibronectin also had maturation promoting activity. Finally, addition of the potent monocyte functional activators, muramyl dipeptide (MDP), polyriboinosinic:polyribocytidilic acid (Poly I:C), and lipopolysaccharide (LPS) had no effect on the monocyte maturation process. Thus, neither cell adherence or activation appear to be critical for the monocyte to macrophage maturation process. Instead, we hypothesize that in addition to proper nutritional support, a group of serum proteins (unified mainly by their ability to interact with monocyte membrane receptors) appear to be the principal promoters of this process.
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We evaluated the performance of commercially available infant and pediatric cervical collars, both alone and in combination with commonly used supplemental devices (eg, Kendrick Extrication Device, half-spine board). One infant and 11 pediatric-sized collars were tested on mannequins representing an infant and a 5-year old child. Maximum forces generated by cooperative children were measured, then applied to the mannequins to reproduce head and neck flexion, extension, rotation, and lateral motion. Limitation of motion was measured in each direction for each collar and combination method. In general, collars of rigid plastic construction performed better than did foam types. However, when used alone none of the collars provided acceptable immobilization, with even the best allowing 17 degrees flexion, 19 degrees extension, 4 degrees rotation, and 6 degrees lateral motion. When combined with supplemental devices, immobilization to 3 degrees or less in any direction could be achieved. Findings were verified using cooperative children and selected collars. Overall, combination methods were more effective than cervical collars alone (P less than .001) or supplemental devices alone (P less than .05). The modified half-spine board used with a rigid collar and tape was the most effective combination method. We conclude that prehospital cervical spine stabilization in pediatric patients is best accomplished using a rigid-type cervical collar in combination with supplemental devices as described.
Seventeen patients with malignant lymphoma, including 13 with progressive disease and four in remission following primary chemotherapy, received high-dose chemotherapy, fractionated total-body irradiation (TBI), and allogeneic marrow transplants. Eleven of the 13 (85%) patients in relapse who received transplants achieved remission, and three remain disease free 41, 21, and 17 months later; one patient in second remission who received a transplant is disease free at 11 months. Thirteen patients are dead: four because of progressive lymphoma, seven because of interstitial pneumonitis, and two because of complications of severe acute graft-v-host disease. These results are similar to those noted in marrow transplantation series for advanced acute leukemia; since transplantation during remission has decreased relapse and improved survival in leukemia, earlier transplantation may produce improved results in lymphoma patients as well. However, the effectiveness of conventional therapy regimens for most lymphomas and the high incidence of severe transplant-related complications usually limit allogeneic transplantation to lymphoma patients in situations other than consolidation of first remission. Initial partial remission, early relapse from an initial remission, and perhaps second remission are situations in which conventional therapy is often ineffective, but the adverse features of very advanced lymphoma are not present; marrow transplantation may be considered in eligible patients. Transplant recipients with more advanced disease are anticipated to have poorer survivals.
Human cytotoxic T lymphocytes specific for A/JAP/57 (H2N2) influenza virus were cloned from in vitro stimulations of peripheral blood lymphocytes. Analysis of the viral specificity in cytotoxic function revealed one clone that killed all type A influenza-infected targets, another clone that was specific for the hemagglutinin subtype of the immunizing influenza virus, and the third clone that demonstrated cytotoxicity restricted to the hemagglutinin of A/JAP/57 and A/JAP/62 (H2N2) and not other type A influenza strains with the H2N2 subtypes. The phenotype of these three clones was Leu 2-, Leu 3+, Leu 4+; MHC restriction of their cytotoxic function was mapped to HLA-DR by a panel of target cells as well as by inhibition of cytotoxicity with monoclonal antibodies. Proliferation of these clones, examined in a tritiated thymidine incorporation assay, was found to be driven by antigen in the absence of exogenous lymphokines. For all three clones antigen-dependent production and secretion of lymphokines with IL-2 activity was demonstrated. The antigen specificity of proliferation and factor production was shown to be identical to the pattern that each clone revealed in its cytotoxic function.
Human monocytes have been shown to be critical immunoregulatory cells for a variety of frequently measured in vitro human immune functions and are secretors of potent biologic response modifiers ( BRMs ). These BRMs , such as interferon (IFN), colony stimulating factor (CSF) and prostaglandin E (PGE), may play important roles in the host immune response to cancer. A new approach for culturing circulating peripheral blood monocytes has been developed to retain the native characteristics of these cells, avoiding possible alteration or activation by adherence. The ability of elutriator-purified human monocytes to secrete IFN and PGE was examined under conditions of suspension culture as well as after adherence, and no difference in secretion of these BRMs was noted. In contrast, Teflon-cultured monocytes demonstrated a significantly enhanced CSF release over culturing in polystyrene plates. A new serum-free medium has also been developed, and monocytes cultured in vitro in this medium showed a 5-fold increase in IFN release, and up to a 72% increase in CSF release when compared to optimal standard culture medium (containing 10% AB serum) and an increased stimulation index for PGE release. By these procedures, hundreds of millions of highly purified human monocytes can be sterilely isolated in suspension and cultured in suspension in serum-free medium with retention of BRM-releasing capabilities. This system should permit more detailed molecular studies of monocytes (in which serum can be an impediment) and may also facilitate clinical therapy studies involving the in vivo transfer of monocytes activated in suspension in vitro.
With the advent of computed tomography, lymphomatous involvement of sites other than lymph nodes is being seen with increasing frequency. Review of computed tomographic scans in 400 patients with newly diagnosed or recurrent non-Hodgkin lymphoma revealed 37 patients to have involvement of 56 unusual sites below the diaphragm: psoas/iliacus muscle (16 patients), kidney (13 patients), pancreas (5 patients), adrenal (4 patients), skin/subcutaneous tissue (4 patients), abdominal wall musculature (4 patients), peritoneum (4 patients), omentum (3 patients), and female reproductive tract (3 patients). These were mostly seen in patients with lymphomas of diffuse architecture, especially diffuse histiocytic lymphoma. Concomitant retroperitoneal and/or mesenteric adenopathy was very common; extranodal involvement was rarely the only site of initial or recurrent lymphoma.
We describe here a series of 88 consecutive patients with bone marrow fibrosis. Primary causes for the fibrosis were discovered in 26% of the cases shortly after the initial diagnosis. Pathology review of the remaining cases revealed an 8% incidence of "hairy cell leukemia" that had escaped detection originally. The remaining cases, characterized as having "unexplained bone marrow fibrosis" or "idiopathic myelofibrosis," are the subject of this study. The clinical and laboratory findings are compared to those reported in previous series of selected cases with similar features in which patients were diagnosed as having "agnogenic myeloid metaplasia," "myelosclerosis," or "myelofibrosis." A brief summary of the treatment modalities used, and the clinical course and outcome of these patients are also presented. There was a marked variability in the clinical severity of the disease and in the survival of these patients. A detailed statistical analysis of 40 variables at the time of initial diagnosis showed that the factors that best predicted a poor survival were unexplained fever, weight loss, night sweats, anemia and thrombocytopenia. On the other hand, the size of the spleen or of the liver, the degree of immaturity of the peripheral blood white cells, and the degree of fibrosis or cellularity in the bone marrow biopsy were of no detectable prognostic significance. These findings suggest that in patients with unexplained fibrosis of the bone marrow (the syndrome of idiopathic myelofibrosis) a poor prognosis is not a direct consequence of the marrow fibrosis or the associated extramedullary hematopoiesis, but rather is related to the presence and/or the severity of some unexplained primary marrow defect, which is also often associated with the nonspecific symptoms of a systemic illness.
Lateral nasal glands of 12-15 weeks old pups are immature. Gland acini of pups and mature dogs contain numerous electron-lucent vacuoles with basophilic, electron-dense cores. The vacuoles contain both acid and neutral glycoproteins, sialated glycoproteins being the dominant acidic moiety. Lateral and basal cytoplasmic extensions of the acinar cytoplasm greatly increase the cell surface are. Electron-dense granules, smaller and less numerous than the lucent vacuoles of acini, occur in intercalated duct cells. Secretions collected form the excretory duct of the lateral nasal gland from conscious dogs contain 235 mg protein/100 ml secretory fluid. Immunoglobulin A accounts for 14% of the secretory protein. Total sialic acid content is 0.024% of the secretion by weight.
A retrospective review is reported of 128 patients presenting with multiple myeloma and 16 patients presenting with solitary plasmacytoma. Ninety-one percent of 116 evaluable patients treated for palliation of painful bone disease received some degree of subjective pain relief. The radiation dose most frequently prescribed was between 1500 and 2000 rad. Of the 278 ports treated, only 17 (6.1%) were re-treated to the same area at a later date. There was no increase in incidence of re-treatment with lower radiation doses. Ten of the 13 patients treated for a solitary plasmacytoma with a minumum follow-up period of three years have local tumor control. The median survival in the solitary plasmacytomas is five and one-half years. Data from the literature on 27 additional solitary plasmacytomas combined with our data suggest an improved local control and a decrease in dissemination with doses greater than 5000 rad. It is concluded that low doses of radiation are usually adequate to treat painful bone lesions of multiple myeloma and doses of 5000-6500 rad in six to seven weeks are recommended for solitary plasmacytomas.