PubMed Health⌕ Search

Biomedical subjects

C Harman

Publications and source records attributed to C Harman.

At least 19 recordsLinked to original sources
PubMed2004

A retrospective survey on the safety of Replenine, a high-purity factor IX concentrate.

PURPOSE: To assess the safety of a plasma-derived highly purified factor IX concentrate (Replenine) in routine clinical use. METHODS: Following guidelines entitled Safety Assessment of Marketed Medicines (SAMM), safety data were collected in the UK by retrospective review of the hospital notes of 114 patients who received an estimated 14.8 million IU of Replenine. Included were 40 patients undergoing 44 surgical procedures or dental extractions [corrected]. RESULTS: The study detected a total of nine adverse events (AEs), four of which were possibly product-related, four that were unrelated to the product and one whose causality was unknown. None of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. One patient was switched from Replenine because of infusion site irritation, but no unexpected adverse reactions were noted. There were no reports of virus transmission or new factor IX inhibitor development. The mean factor IX recovery value was 1.44 IU/dl per IU/kg (95%CI: 1.31-1.57 IU/dl per IU/kg). CONCLUSIONS: The study was a practical application of the SAMM guidelines to the collection of pharmacovigilance data on patients with Haemophilia B. Replenine is well tolerated in routine clinical practice.

Adult↗
PubMed2004

A retrospective survey on the safety of Replenate, a high-purity factor VIII concentrate.

PURPOSE: To assess the safety of a highly purified, plasma-derived factor VIII concentrate (Replenate) in routine clinical use. METHODS: Following guidelines entitled safety assessment of marketed medicines (SAMM), safety data were collected in the UK on 194 patients who received an estimated 47.6 million IU of Replenate. This population included 47 patients undergoing 53 surgical operations or dental extractions. RESULTS: The study detected four cases of new factor VIII inhibitor development and twelve other adverse events, five that were unrelated to the product, five whose causality was unknown, one that was possibly product-related and one case due to possible lack of efficacy. Only one of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. Three patients were switched from Replenate as a result of an adverse event (one case of infusion site irritation and two cases of a rise in titre of an existing inhibitor), but no unexpected adverse reactions were noted and there were no reports of virus transmission. The median factor VIII recovery value was 2.17 IU/dl per IU/kg, but recovery was shown to be dependent on several variables, namely inhibitor status, treatment centre and the patient's body weight. The median factor VIII recovery in inhibitor-free patients was 2.28 IU/dl per IU/kg (range: 1.20-6.62). CONCLUSIONS: The study confirms that Replenate is well tolerated by the majority of patients in routine clinical practice.

Adolescent↗
PubMed2002

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20-21-week fetuses.

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified.

Adult↗
PubMed1999

Technical factors in early amniocentesis predict adverse outcome. Results of the Canadian Early (EA) versus Mid-trimester (MA) Amniocentesis Trial.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentered (12) prospective, randomized trial comparing continuous ultrasound-guided early amniocentesis (EA) and mid-trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures 'judged to be difficult' by the operator, and post-procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11. 1 per cent, compared with non-hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first-trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype.

Abortion, Spontaneous↗
PubMed1995

Perinatal outcome in relation to second-stage duration.

OBJECTIVE: The second stage of labor has been thought of as a time of particular asphyxial risk for the fetus. This perceived risk has been invoked to justify arbitrary time limits and high rates of operative vaginal delivery. The purpose of this study was to determine whether perinatal outcome worsened as the second stage lengthened. STUDY DESIGN: Over a 5-year period at one university teaching hospital, 6041 nulliparous women reached the second stage of labor with a live singleton cephalic fetus with birth weight > or = 2500 gm. A retrospective review of perinatal morbidity and mortality was performed and the results related to the duration of the second stage. RESULTS: The second stage lasted > 3 hours in 11% of nulliparous women and > 5 hours in 2.7%. There were no perinatals death unrelated to anomaly. There was no significant relationship between second-stage duration and low 5-minute Apgar score, neonatal seizures, or admission to the neonatal intensive care unit. CONCLUSION: Operative intervention in the second stage is not warranted merely because some set number of hours has elapsed.

Apgar Score↗
PubMed1994

Development of orienting to locations and objects in human infants.

Two experiments investigated preference for orienting to novel locations and novel objects in young infants. Adults and infants of six months and older show a propensity to orient to locations that have not recently been inspected (inhibition of return). Preference for novel locations undergoes development. We show that, similar to adults, its development is related to the ability to program eye movements to attended locations. This preference appears to emerge as infants gain the ability to program eye movements to target locations. Experiment 1 demonstrates that three-month-olds show inhibition of return for 10 degrees target eccentricities, but not for 30 degrees target eccentricities. In a second experiment, three- and six-month-old infants oriented to 10 degrees targets that varied in location and object identity. Infants of both ages strongly preferred orienting to novel objects at novel locations. At three months, the preference for novel objects was equal to the preference for novel locations, while at six months a tendency to prefer novel objects over novel locations emerged. Overall, the findings support separate development of these two forms of novelty preference, and suggest that novel location preferences (inhibition of return) relates closely to the eye movement system. The findings are discussed in relation to issues concerning development, physiology, and cognition.

Attention↗
PubMed1994

A cross-over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate.

A prospective cross-over study was carried out on 19 patients with haemophilia B. comparing the pharmacokinetics of a purified factor IX concentrate prepared by metal chelate affinity chromatography (9MC) with a conventional three-factor prothrombin complex concentrate (9A). The highly purified factor IX concentrate was shown to have a half-life comparable to the PCC; the in vivo recovery of the purified concentrate was significantly greater than that of the complex (P < 0.01). The 20% change in the value of the International Standard for Factor IX Concentrate, introduced in 1988, might have been expected to lower the recovery values. However, the in vivo recovery for both concentrates was somewhat higher than reported previously, particularly in the older literature. In nine patients, serial assays for fibrinopeptide A, prothrombin fragment F1+2 and thrombin-antithrombin complexes (TAT) were performed to assess the potential thrombogenicity of the two concentrates. Evidence was obtained that there was significantly less activation of coagulation following administration of purified factor IX (9MC), as compared to the activation that occurred after the PCC.

Blood Coagulation↗
PubMed1992

Foscarnet and Ganciclovir in the treatment of CMV retinitis in AIDS patients: a randomised comparison.

Ganciclovir and Foscarnet were compared in an open randomised trial as treatment and secondary prophylaxis of cytomegalovirus (CMV) retinitis in patients with AIDS. Patients responded more rapidly to Ganciclovir than to Foscarnet although eventual response rates were similar with both drugs. During maintenance therapy there were trends towards more delayed reactivation of CMV and fewer adverse events requiring changes in therapy, in the Ganciclovir group. However, these patients had more line infections and a higher blood transfusion requirement.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Immunoglobulin and cytokine production by neonatal lymphocytes.

Growth and differentiation of cord blood B cells were studied using T cell-depleted populations. In the absence of in vitro activation, cord blood B cells proliferated in response to cytokines including interleukin-2 (IL-2) and interleukin-4 (IL-4); anti-mu-stimulated cord B cells had a lesser response to IL-2 than adult cells. IgM synthesis by cord blood B cells was enhanced by interleukin-6 (IL-6) and decreased by IL-2. In cultures activated by Staphylococcus aureus Cowan I (SAC), cord blood B cells produced lesser increases in IgM than adult B cells regardless of the cytokine added. Cord blood B cells produced no IgG or IgA with any cytokine preparation with or without SAC activation. Supernatants of cord blood T cells pulse-stimulated with phytohaemagglutinin and phorbol myristate acetate contained less IL-2 and IL-6 and had less growth and differentiation activity than adult T cell supernatants. The results confirm a limited cord blood B cell response and also suggest a limitation in production of B cell stimulatory lymphokines by cord blood T cells.

Adult↗
PubMed1991

Intravenous drug abuse causes Rh immunization.

Intravenous drug abuse causes many health problems. From March 1989 to January 1990 of 27 Rh-negative women (28 pregnancies) referred to our centre, 4 women (5 pregnancies) were Rh immunized due to the sharing of needles and blood with their Rh-positive partners. Severe hydrops was present in 4 of their 5 fetuses when they were first seen at 17-35 weeks of gestation. Only the fetus first seen at 35 weeks survived. That infant was moribund at birth and now has evidence of leukomalacia and porencephaly. The fifth fetus, not hydropic, required two intravascular fetal transfusions in order to survive. A fifth woman, immunized in a similar manner, had a spontaneous abortion. These fetuses represent some of the earliest and severest examples of hydrops fetalis ever seen at our centre. The severity of their fetal hemolytic disease is probably due to the fact that their mothers' exposure to Rh(D) antigen by blood sharing was continuous and ongoing. Because of their aberrant behaviour, these women have suffered irreversible reproductive damage.

Abortion, Spontaneous↗
PubMed1991

Nebulized pentamidine for the prevention of Pneumocystis carinii pneumonia in AIDS patients: experience of 173 patients and a review of the literature.

Nebulized pentamidine is increasingly used for the prevention of Pneumocystis carinii pneumonia in HIV antibody-positive patients. We report our experience of the efficacy and tolerance of a high dose regimen (300 mg every second week) in 173 HIV-positive patients over a 2 1/2-year period. Only seven episodes of P. carinii pneumonia occurred but 48 patients (28 per cent) died of other AIDS-related illnesses. Patients who had never had an episode of P. carinii infection were less likely to accept long-term prophylaxis (17 of 81), compared to those who had previously been treated for the condition (five of 92). Nebulized pentamidine is an effective form of prophylaxis against P. carinii pneumonia, but long-term mortality is still high in AIDS patients. Side-effects with this regimen were almost always local and confined to the period of nebulization.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The role of the chest roentgenogram in febrile neutropenic patients.

In a retrospective review of patients with neutropenia and fever, we sought to determine how often roentgenograms detected pulmonary disease, especially pneumonia, not suggested by signs and symptoms. Further, we sought to determine how often therapy was changed as a result of roentgenographic findings. Overall, 41 (22%) of 187 chest roentgenograms obtained during initial febrile episodes, recurrent fevers, or persistent fevers were abnormal. While most patients had signs and symptoms suggesting the presence of pulmonary disease, 17% had roentgenographic abnormalities detected in the absence of such findings. During initial febrile episodes, therapy was not changed in response to findings on the chest roentgenogram. However, during episodes of persistent or recurrent fever, findings on chest roentgenograms led to changes in therapy in eight (61%) of 13 episodes of which six (40%) resulted in clinical improvement. Chest roentgenograms were therefore found to be an important diagnostic tool in evaluating recurrent or persistent fever in the neutropenic patient but of little use during initial febrile episodes.

Bone Marrow Transplantation↗
PubMed1989

Amniotic fluid particles: are they related to a mature amniotic fluid phospholipid profile?

In a prospective, blinded clinical study, the relationship between amniotic fluid free-floating particles measured by a dynamic ultrasound imaging method and phospholipid profile was studied in 82 women undergoing amniocentesis between 26-42 weeks' gestation. None of 11 patients with sonographically clear amniotic fluid had a mature phospholipid profile (lecithin-sphingomyelin ratio greater than 2 and detectable phosphatidylglycerol). Thirty-eight of 71 women (53%) with turbid or markedly turbid amniotic fluid had a mature phospholipid profile. The sensitivity of this method was 100%, specificity 25%, positive predictive value 53%, and negative predictive value 100%. Although the finding of sonographically clear amniotic fluid may eliminate unnecessary amniocentesis, markedly turbid amniotic fluid is not a reliable indicator of a mature amniotic fluid phospholipid profile.

Amniotic Fluid↗
PubMed1986

Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios.

Severe oligohydramnios, defined as a condition in which the largest pocket of amniotic fluid measures less than 1 cm in its vertical axis as determined by an ultrasound method, was observed in 113 patients in a population of 15,431 referred high-risk patients (0.7%). In all cases, intervention took place unless there was a recognized structural anomaly or extreme prematurity. Overall gross perinatal mortality was 132.7/1000, and the incidence of major anomaly was 13.3%. With intervention the corrected perinatal mortality rate was 17.7/1000, a rate not significantly different from that observed in the entire population. All end points of perinatal mortality were significantly increased in patients with severe oligohydramnios, in comparison with randomly selected control subjects with normal amniotic fluid. These findings are interpreted to indicate that severe oligohydramnios in a structurally normal fetus is an indication for delivery.

Adolescent↗
PubMed1985

A controlled study of ticarcillin plus clavulanic acid versus piperacillin as empiric therapy for fever in the immunocompromised host.

Clavulanic acid, a potent beta-lactamase inhibitor, was studied in fixed combination with ticarcillin and used with tobramycin as empiric therapy for fever in the immunocompromised host. Fifty febrile episodes were evaluated in patients with hematologic malignancy and/or neutropenia. Eighty-one percent of evaluable infections treated with the study regimen of ticarcillin, clavulanic acid, and tobramycin responded. Seventy-four percent of evaluable infections treated with the control regimen of piperacillin, tobramycin, and vancomycin responded (p = 0.4). Resistance to piperacillin and ticarcillin were noted in 23.8 percent of 21 isolated organisms. Resistance to ticarcillin and clavulanic acid was noted in only one (4.7 percent) of the isolated organisms (p = 0.092). Untoward reactions, including rash, nephrotoxicity, and superinfection, were unusual and occurred with equal frequency in the study and control groups. Clavulanic acid in combination with ticarcillin was effective and safe in treating fever in the immunocompromised host.

Bacterial Infections↗
PubMed1984

Treatment of the fetus in utero: evolving concepts.

The rapidly evolving ability to detect the presence of major anomalies in the developing fetus and the emerging prospect of intrauterine treatment of some of these disorders are coupled to create an exciting new frontier in care of the high-risk pregnancy. Preliminary reports suggest that in some highly selected instances perinatal death and morbidity may be prevented by intrauterine surgical procedures. The technical ability to treat the disorder as described is at hand and is unlikely to be the limiting factor in the advance of this area of fetal treatment. However, the very fact that treatment is possible cannot be considered as proof of efficacy. The physician faced with the knowledge that a potentially treatable condition is present in a given fetus may feel the necessity of instituting treatment, but the validity of such an approach is far from established. It is our opinion that efforts should be made to set at the earliest point proper controlled scientific studies from which the benefit, if any, of this surgical approach to fetal disease may be established. Such clinical studies should be conducted in concert with studies in appropriate animal models. It should be noted that fetal surgical treatment is not without potentially lethal fetal and maternal complications. Before such risks, however small, are taken, it seems reasonable to determine the long-term benefits of the surgical procedure. To this end, participation in the International Fetal Surgery Registry is encouraged.

Arnold-Chiari Malformation↗