Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine

Antidrug IgG antibodies have been detected in some patients receiving amodiaquine (AQ). Antidrug antibodies were detected in 6/7 patients who experienced serious well-defined adverse drug reactions during malaria prophylaxis and in 7/22 patients who received comparable doses of the drug (at least 400 mg weekly x 6) but did not present with clinical adverse drug reactions. In contrast antidrug antibodies were not detected in 7 patients who received the drug for treatment (1.0-1.2 g total over 3 days). The specificity of the IgG response was defined by hapten inhibition experiments (IC50 value for AQ ranged between 0.050 and 0.282 microM) which suggest that the antibody recognised the drug linked to cysteine residues in protein via the 4-hydroxyanilino side chain. The data show that AQ is immunogenic in man and are consistent with the hypothesis that idiosyncratic adverse reactions to the drug have an immunological aetiology.     

Questionnaire analysis of the swallowing‐related outcomes following total laryngectomy

Objective: To determine the effects of a total laryngectomy on the swallow and subsequent quality of life in head and neck cancer patients. Design: Cross‐sectional single centre cohort study. Setting: Head and Neck Oncology Unit, Tertiary Referral Unit. Patients: Sixty‐two patients who underwent total laryngectomy at our centre participated in the study. Methods: Subjects were stratified by age, sex, tumour stage, other procedures such as myotomy and nerve re‐implantation. Pharyngectomy, glossectomy, flap reconstruction, neck dissection and previous radio‐ and chemotherapy were also assessed to see if they affected swallow and subsequent quality of life. Main outcome was measured using the MD Anderson Dysphagia Inventory questionnaire. Results: Responses were received from 46 males and 16 females (response rate of 80.5%) with a mean age of 64.7 years (SD 9.4). Median follow‐up in patients was 90 months (range 1–276). The mean MD Anderson Dysphagia Inventory total score in our series of patients was 77.7 (SD 16.6). MD Anderson Dysphagia Inventory global score was 79.4 (SD 22.6), Emotional score was 77.7 (SD 17.8), Functional score 81.3 (SD 15.9) and Physical score was 74.1(SD 18). Statistically significant differences were seen between the emotional scores of glossectomised and non‐glossectomised patients (Mann Whitney, P = 0.04). No significant correlation was seen between the subscale scores and the remaining treatment variables such as age, gender, site, tumour stage, myotomy, nerve implantation, radiotherapy, reconstruction and major complications. Conclusion: This questionnaire study is the largest of its type to assess the swallow of patients who have undergone laryngectomy at a single centre. The overall result confirmed that most patients had a subjectively good swallow. Only glossectomy and the method of PE segment closure were shown to significantly affect swallowing outcomes following surgery. We recommend further work especially prospective studies pre and post surgery using this or similarly validated instruments to fully assess swallow in the laryngectomy population.     

Regional lipiodolized chemotherapy for cholangiocarcinoma associated with oral contraceptives

We describe a case of cholangiocarcinoma in a young woman, who presented with cholestatic jaundice following oral contraceptive ingestion. Following diagnostic laparotomy she received intra-arterial 'lipiodolized' chemotherapy. Intravenous mitozantrone was given for 2 years and she is asymptomatic, with computed tomographic evidence of tumour response, 27 months after diagnosis. We suggest that this form of treatment is of value for cholangiocarcinoma.     

Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

The effects of inverse ratio ventilation on intracranial pressure: a preliminary report

Objective: To determine the effects of pressure control inverse ratio ventilation [PC-IRV], as compared with volume controlled normal ratio ventilation [VC], on the intracranial pressure [ICP] of patients with severe head injury. Design: A prospective study with unblinded intervention. Setting: The Intensive Therapy Unit of a base hospital. Patients and participants: Nine cases of head injury requiring mechanical ventilation and intracranial pressure monitoring were studied. Interventions: Patients were twice transferred from VC (I:E ratio 1:2) to PC-IRV (I:E ratio 2:1). Firstly, tidal volume was maintained at an equal value. Secondly, end tidal CO₂ was maintained at an equal value. No other changes were made to ventilation, vasopressor therapy or ICP control. Measurements and results: Measurements were taken of ICP, mean arterial pressure (MAP) end tidal CO₂ and respiratory parameters. In the first observation, there were significant changes in peak inspiratory pressure (PIP), mean airway pressure (Paw) and intrinsic positive end expiratory pressure (PEEP) but not for ICP, end tidal CO₂, MAP and cerebral perfusion pressure (CPP). The correlation between change in ICP and change in end tidal CO₂ was r=–0.74. In the second observation there were significant changes in tidal volume, PIP, Paw and intrinsic PEEP but not for ICP, MAP and CPP. The correlation between the change in ICP and the change in Paw was insignificant. Conclusions: PC-IRV has a minimal net effect on ICP. Changes in ICP correlate more strongly with changes in CO₂ than changes in Paw. Received: 16 January 1996 Accepted: 2 September 1996     

Deoxyribonucleic acid amplification and hybridisation in Crohn''s disease using a chlamydial plasmid probe.

The possibility that Crohn's disease is caused by infection with Chlamydia trachomatis was examined by probing for chlamydial plasmid deoxyribonucleic acid (DNA) in DNA extracts from Crohn's disease tissue and by means of a serological study. Gut DNA extracts were obtained from 10 patients with Crohn's disease and four control subjects and were probed with a chlamydial plasmid probe after Southern blotting. The polymerase chain reaction was also used to amplify any chlamydial plasmid DNA present in tissue DNA extracts, before Southern blotting and probing. Chlamydial proctitis control specimens were not available: gut DNA extracts mixed with traces of chlamydia plasmid served as positive controls. Using these techniques, no chlamydial plasmid DNA sequences were found in Crohn's disease tissue. An enzyme linked immunosorbent assay for C trachomatis LI was performed on 48 patients with Crohn's disease and 48 control subjects. Seropositivity was present in 14.6% of patients and 29% of control subjects and was not statistically significant (p greater than 0.05). The failure to show chlamydial DNA and the lack of serological response to chlamydia make C trachomatis infection a very unlikely factor in the pathogenesis of Crohn's disease.     

Chromosome mapping of Rett syndrome: a likely candidate region on the telomere of Xq.

Rett syndrome (RS) is a disease of neurological development. First reported 30 years ago in 1966, its biological and genetic basis remains obscure. RS is commonly thought of as an X linked dominant disorder lethal to hemizygous males. The few familial cases would arise through mosaicism or because of occasional females failing to manifest the disorder through skewed X inactivation in relevant cell types. We have one family where the mother and daughter are affected with RS, and which can be explained according to this hypothesis. If the alternative proposal of Thomas (1996) is correct, that the lack of males affected by such disorders is the result of a high male to female ratio of germline mutations rather than of gestational lethality, then the RS gene should be located on the grandpaternal chromosome. Genomic screening with markers covering the whole X chromosome has been performed. Studies using multiple informative markers indicate that the RS locus is likely to be located close to one of the X chromosome telomeres. Further investigations in eight additional families suggest the most likely region for the RS gene to be is the distal part of Xq (Xq28).