INTENSIVE PLASMA THERAPY IN THE HEMOPHILIAS.
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Anticoagulants↗
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A "NEW" ANTIGEN IN LEUKEMIA SERA.
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Antigen-Antibody Reactions↗
Successful treatment of naturally occurring influenza A/USSR/77 H1N1.
Forty-five university students with proved influenza A/USSR/77 H1N1 infection were randomly treated with either amantadine hydrochloride (14 students), rimantadine hydrochloride (19 students), or placebo (12 students). By 48 hours after initiation of therapy, amantadine and rimantadine recipients had significantly less fever and greater improvement compared with subjects given the placebo. Minor reversible CNS side effects at the end of the five-day course of therapy were observed in one third of the amantadine-treated subjects. However, both amantadine and rimantadine recipients returned to classes earlier and shed smaller amounts of virus than placebo recipients. Thus, both drugs exerted a notable therapeutic effect. Hence, during an influenza outbreak, five days of empirical therapy with amantadine or rimantadine for persons with an influenza-like syndrome should ameliorate clinical symptoms and might decrease spread of virus.
Adult↗
Tube feeding in patients with advanced dementia: a review of the evidence.
Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We searched MEDLINE, 1966 through March 1999, to identify data about whether tube feeding in patients with advanced dementia can prevent aspiration pneumonia, prolong survival, reduce the risk of pressure sores or infections, improve function, or provide palliation. We found no published randomized trials that compare tube feeding with oral feeding. We found no data to suggest that tube feeding improves any of these clinically important outcomes and some data to suggest that it does not. Further, risks are substantial. The widespread practice of tube feeding should be carefully reconsidered, and we believe that for severely demented patients the practice should be discouraged on clinical grounds.
Activities of Daily Living↗
Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.
CONTEXT: Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. OBJECTIVE: To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. DESIGN, SETTING, AND PARTICIPANTS: A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998. INTERVENTIONS: Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design. MAIN OUTCOME MEASURES: Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects. RESULTS: In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006). CONCLUSIONS: In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.
Aged↗
Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth.
The characteristic sclerotic appearance of bone metastases from prostate cancer is unexplained but could involve excess peritumoural activity of osteoblast mitogens such as the insulin-like growth factors (IGFs). Since prostatic metastases are distinguished by androgen-dependent secretion of prostate-specific antigen (PSA), a serine protease which cleaves extracellular IGF-binding proteins and thereby enhances the bioavailability of IGFs, the relationship was examined between tumour PSA expression and the osteoblastic phenotype. To this end, a cohort of 27 prostate cancer patients was evaluated to determine the relationship between serum PSA and radiographic bone lesion density at first presentation with metastatic disease. No linear correlation between absolute PSA levels and metastatic osteosclerosis was apparent. However, non-parametric statistical analysis revealed a highly significant link between low-PSA (<20 ng/ml) metastatic prostate cancer and osteolytic bone lesions (p<0.0001, chi(2)=21.5). This finding raises the possibility that the osteoblastic phenotype of prostate cancer derives in part from PSA-dependent proteolysis of IGF-binding proteins within bone matrix.
Bone Neoplasms↗
Inflammatory mediators in acute pancreatitis.
Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.
Acute Disease↗
Hyperparathyroidism after neck irradiation.
A retrospective review of 1550 cases of hyperparathyroidism (HPT) treated surgically over a 30-year period reveals a past history of exposure to neck irradiation in 10 cases (0.7 per cent). The indication for radiotherapy was benign disease in nine and papillary thyroid carcinoma in one case. The mean interval between radiation exposure and the detection of HPT was 32 years (range 3-63 years). Patients treated with radioactive iodine alone developed HPT after a mean of 5 years while the interval for those treated with external beam therapy alone was a mean of 44 years. The parathyroid histology was adenoma in six cases, carcinoma in three cases and nodular hyperplasia in one case. All patients had coincident benign thyroid disease apart from one that had previously had papillary carcinoma and another with follicular carcinoma. Neck irradiation has been shown to confer an increased risk of HPT due to parathyroid adenoma and carcinoma. Radiotherapy for benign disease has generally been abandoned and these cases demonstrate a further contra-indication for the use of neck irradiation.
Adult↗
Management of colovesical fistulae associated with pelvic malignancy.
Thirteen patients with malignant colovesical fistulae are presented. The underlying pathology was cancer of the colon (seven cases), bladder (four cases) and cervix (two cases). The series demonstrates that wide surgical excision may be needed to achieve tumour clearance and that this may necessitate pelvic exenteration. Three patients who underwent inadequate tumour excision developed recurrence in the bladder, two with a fatal outcome. Wide excision of the bladder may be performed without urinary diversion by subtotal cystectomy and a reconstructive procedure. Substitution cystoplasty was performed on two patients at the time of tumour excision. Urinary tract involvement by such tumours is often extensive and optimal results may be achieved with a multidisciplinary approach.
Aged↗
Primary retroperitoneal germ cell tumours: excision via a thoracoabdominal extraperitoneal approach.
BACKGROUND: Primary retroperitoneal germ cell tumours usually present as a large abdominal mass in young men. The testes are normal on examination and ultrasonography but there are usually raised serum levels of human chorionic gonadotrophin and/or alpha-fetoprotein. METHODS: Fourteen men (median age 33 years) with primary retroperitoneal germ cell tumours were treated by chemotherapy followed by surgical resection of the primary tumour and metastases via a thoracoabdominal extraperitoneal approach. RESULTS: There was minimal morbidity. The survival rate was 13 of 14 and the disease-free survival rate was 11 of 14 after a median follow-up of 15 months. CONCLUSION: The thoracoabdominal extraperitoneal approach for the removal of retroperitoneal germ cell tumours and their metastases after chemotherapy improves tumour clearance, morbidity and recovery time compared with the transperitoneal anterior approach.
Adult↗
Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis.
BACKGROUND: Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. RESULTS: Treatment with Met-RANTES had little effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63) lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27) versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). CONCLUSION: Treatment with Met-RANTES reduces lung damage associated with caerulein-induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis.
Acute Disease↗
The voice of detainees in a high security setting on services for people with personality disorder.
BACKGROUND: British government Home and Health Departments have been consulting widely about service development for people with ' dangerous severe personality disorder' (DSPD). There has, however, been no consultation with service users, nor is there any user view literature in this area. METHODS: All people detained in one high security hospital under the legal classification of psychopathic disorder were eligible but those on the admission or intensive care wards were not approached. Views of service were elicited using a purpose designed semi-structured interview. The principal researcher was independent of all clinical teams. Confidentiality about patients' views was assured. AIMS: To establish views on services from one subgroup of people nominated by the government department as having 'DSPD'. RESULTS: Sixty-one of 89 agreed to interview. With security a given, about half expressed a preference for a high security hospital setting, 20% prison and 25% elsewhere, generally medium secure hospitals. Participants most valued caring, understanding and 'experience' among staff. An ideal service was considered to be one within small, domestic living units, providing group and individual therapies. Some found living with people with mental illness difficult, but some specified not wanting segregated units. Views were affected by gender and comorbidity. CONCLUSIONS: As the sample were all in hospital, the emphasis on treatment may reflect a placement bias. All but five participants, however, had had experience of both health and criminal justice services, so were well placed to talk with authority about preferences.
Antisocial Personality Disorder↗
Most human CD3+WT31- clones with T cell receptor C gamma 1 rearrangements show strong non-MHC-restricted cytotoxic activity in contrast to those with C gamma 2 rearrangements.
Clones expressing CD3 in the absence of WT31 expression were obtained by growing highly purified WT31- cells in the presence of interleukin 2 and phytohemagglutinin. Most clones showed rearrangements of T cell receptor (TcR) gamma genes on both chromosomes involving all five currently identified J gamma segments. About a third of these clones had a rearranged 12 kb Kpn I band with the J gamma probe, consistent with a V9JPC gamma 1 rearrangement. All clones with both chromosomes rearranged to C gamma 2 had low or intermediate cytotoxic activity while most of those with at least one chromosome rearranged to C gamma 1 had high cytotoxic activity against both natural killer-sensitive and natural killer-resistant targets. This applied both to clones with and without the V9JPC gamma 1 rearrangement. Of three clones with both C gamma 1 and C gamma 2 rearrangements two had high activity and the other was only weakly cytotoxic. In addition, most clones showed rearrangement of TcR beta genes. Some clones were capable of secreting levels of interferon-gamma and tumor necrosis factor-alpha which were as high as those produced by CD3+4+WT31+ T cell clones. The results suggest that most human CD3+WT31- clones expressing a disulfide-linked C gamma 1/delta heterodimer are capable of mediating strong non-major histocompatibility complex-restricted cytotoxicity whereas those expressing non-disulfide-linked C gamma 2/delta heterodimers are not.
Blotting, Southern↗
Changes in immunologic cell surface markers during cocaine withdrawal in pregnant women.
To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcgammaRII (CD32), FcgammaRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3-5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.
Adult↗
Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro.
Cell lines derived from human colon carcinomas secrete interleukin 8 (IL-8) in vitro and this chemokine has also been detected immunohistochemically in human colon carcinoma specimens, in which it is tumour cell associated. In these experiments, IL-8 was shown to comprise an important component of the angiogenic activity of colon carcinoma cell line supernatants. The effect of modulating IL-8 activity upon the growth of the colon carcinoma cell lines HCT116A, HT29 and CaCo2 was investigated. Supplementing endogenously produced IL-8 by recombinant chemokine led to stimulation of cell growth. Neutralization of the effect of endogenously produced IL-8, either with the specific antagonist peptide AcRRWWCR or with blocking anti-IL-8 antibody, resulted in around 50% inhibition of cell growth (P<0.05). All of the colon carcinoma cell lines tested expressed mRNA for both IL-8RA and RB when grown at confluence. At the protein level, all cell lines expressed IL-8RA. Expression of IL-8RB was weak, although increased expression was seen in HCT116A cells as they approached confluence. Antibodies to IL-8RA and RB did not affect proliferation at low cell density but were strongly inhibitory when cells were cultured at a higher density. These data suggest that IL-8 acts as an autocrine growth factor for colon carcinoma cell lines and would support the concept that a similar autocrine loop operates in vivo.
Carcinoma↗
Aggregation and dispersion characteristics of calcium oxalate monohydrate: effect of urinary species.
In this research, screening and central composite experimental designs are used to determine the effect of various factors on the aggregation and dispersion characteristics of previously grown calcium oxalate monohydrate (COM) crystals in artificial urinary environments of controlled variables. The variables examined are pH and calcium, oxalate, pyrophosphate, citrate, and protein concentrations in ultrapure water and artificial urine. Optical density measurements, particle size analysis, optical microscopy, AFM force measurements, and protein adsorption have been used to assess the state of aggregation and dispersion of the COM crystals and to elucidate the mechanisms involved in such a complex system. The data indicate that our model protein, mucin, acts as a dispersant. This is attributed to steric hindrance resulting from the adsorbed mucoprotein. Oxalate, however, promotes aggregation. Interesting interactions between protein and oxalate along with protein and citrate are observed. Such interactions (synergistic or antagonistic) are found to depend on the concentrations of these species. Surface responses for these interactions are presented and discussed in this paper. In summary, solution, surface, and interface chemistries interact in a complex manner in the physiological environment to either inhibit or promote aggregation, and an understanding of such interactions may help determine and control the factors affecting kidney stone formation.
Adsorption↗