Chronic effects of therapeutic irradiation for localized prostatic carcinoma on anorectal function

PURPOSE: To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. METHODS AND MATERIALS: The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (+/- SD) of 1.4 (+/- 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). RESULTS: All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric parameters at 1 year, cf. baseline. The predictor variables used included individual patient tumor and treatment characteristics as well as individual patient symptom scores and parameters of anorectal motor and sensory function at baseline and 4-6 weeks after RTH. The results of the univariate logistical regression analysis showed that (1) frequency of defecation at 4-6 weeks and (2) rectal volumes at baseline both for (a) perception (p < 0.001) and (b) desire to defecate (p < 0.001), predicted significantly for the patients who had symptoms and signs of anorectal dysfunction at 1 year. Individual patient tumor and treatment-related variables tested, in contrast, had no predictive significance. CONCLUSIONS: Anorectal symptoms following RTH for prostatic carcinoma are common and persist at least until 1 year after its completion and are associated with objective evidence of heightened rectal sensitivity.     

Effect of a sea snake (Enhydrina schistosa) venom on the ganglionic nicotinic actions of acetylcholine

The effects of venom from a common sea snake, Enhydrina schistosa, on the actions of acetylcholine in the superior cervical ganglion, the adrenal medulla and in the atropinized cat were investigated. The crude venom reduced nictitating membrane responses to preganglionic nerve stimulation and intra-arterial injection of acetylcholine, without lowering the responses to postganglionic nerve stimulation or intra-arterial adrenaline. In the eviscerated cat, the venom also antagonized rises in heart rate and blood pressure induced by in-injections into the coeliac artery of acetylcholine but not those of histamine. Pressor effects due to splanchnic nerve stimulation and carotid artery occlusion were blocked. In the atropinized cat, the venom depressed heart rate and pressor responses to intravenous acetylcholine, but not the responses to adrenaline. It was concluded that the venom antagonized the actions of acetylcholine at autonomic ganglia and the adrenal medulla.     

Multidisciplinary assessment at triage: a new way forward

Objective: To evaluate a dual doctor and nurse triage system at a tertiary referral hospital. Methods: Data were compared between periods of multidisciplinary triage and periods of standard triage. Data comparison was also made between rostered multidisciplinary triage shifts and non‐multidisciplinary triage shifts. Staff satisfaction with the process was assessed. Results: The percentage of patients seen within Australasian Triage Scale performance indicator thresholds increased from 75% to 81% in Category 2 patients (P = 0.12) and 56% to 78% in Category 3 patients (P < 0.0001). There was a reduction of 50% in the number of patients who left prior to being seen by a doctor (P = 0.024). Surveys showed high staff satisfaction with the process. Conclusions: We feel that multidisciplinary triage performs a useful function in our department enabling us to reduce waiting times. The process is widely accepted amongst the staff and it ensures a senior doctor assesses most patients. It reduces the number of patients leaving prior to being seen by a doctor and it provides one way of getting around access block and a physically small department.     

The upper and lower airway responses to nasal challenge with house-dust mite Blomia tropicalis

BACKGROUND: The house dust mite Blomia tropicalis (B. tropicalis) was found to be the most prevalent domestic mite in Singapore. However, its pathogenicity in allergic airway diseases remains to be investigated. METHODS: Twenty adults with persistent allergic rhinitis (PAR) were studied. Five had a history of asthma, and all were asymptomatic except one who was under treatment with low-dose inhaled corticosteroid. Nasal challenge was carried out by nasal spray with phosphate-buffered saline (PBS) and with increasing concentrations of crude B. tropicalis extracts (0.6, 6.0 and 60 micro g/ml) at 15 min intervals. Subjective symptom scores and absolute number of sneezes were recorded together with objective measurements of spirometry (forced expiratory volume in 1 s, FEV1) and acoustic rhinomanometry (volume of the nasal cavity). These were performed at baseline, 5 min after each incremental challenge, and 30 min, 1 h, 3 h, 5 h and 7 h after the last challenge. Meanwhile, concentrations of mediators in nasal secretions (tryptase, leukotriene C4 (LTC4) and eosinophil cationic protein (ECP)) were measured in nasal aspirate samples at similar time intervals. An identical (control) challenge procedure with PBS alone was repeated in seven patients after a washout period of at least 2 weeks. RESULTS: Significant increases in the subjective and objective nasal symptoms, together with a significant increase of tryptase and LTC4 concentrations in nasal secretion, were found 5 min after each challenge with B. tropicalis, but not with PBS. There was no definitive pattern of the late-phase nasal response in either subjective symptoms or objective measurements. Three patients (3/5) with a history of asthma showed a fall in FEV1 readings (33%, 22% and 11% from baseline, respectively) at 7 h post challenge with concomitant mild wheezing in the night. CONCLUSIONS: Our study demonstrates direct evidence of allergic nasal response to B. tropicalis in sensitized adults. It shows that nasal provocation may also provoke concomitant asthmatic symptoms during the late-phase reaction, especially in people with a history of asthma.     

Thiopurine methyltransferase polymorphisms in a multiracial asian population and children with acute lymphoblastic leukemia

The purpose of this study was to determine the frequency of thiopurine methyltransferase (TPMT) polymorphisms in a multiracial Asian population and to assess its relevance in the management of childhood acute lymphoblastic leukemia (ALL). Six hundred unrelated cord blood samples from 200 Chinese, Malay, and Indian healthy newborns were collected at the National University Hospital, Singapore; an additional 100 children with ALL were analyzed for five of the commonly reported TPMT variant alleles using polymerase chain reaction/restriction fragment length polymorphism and allele-specific polymerase chain reaction-based assays. In the cord blood study, the TPMT*3C variant was detected in all three ethnic groups; Chinese, Malays, and Indians had allele frequencies of 3%, 2.3%, and 0.8%, respectively. The TPMT*3A variant was found only among the Indians at a low allele frequency of 0.5%. The TPMT*6 variant was found in one Malay sample. Among the children with ALL, two white and one Chinese were heterozygous for the TPMT*3A variant and showed intermediate sensitivity to 6-mercaptopurine during maintenance therapy. Three Chinese patients and one Malay patient were heterozygous for the TPMT*3C variant. Mercaptopurine sensitivity could be validated in only one out of four TPMT*3C heterozygous patients. The overall allele frequency of the TPMT variants in this multiracial population was 2.5%. The TPMT*3C was the most common variant allele; TPMT*3A and TPMT*6 were rare. These results support the feasibility of performing TPMT genotyping in all children diagnosed with acute leukemia to minimize toxicity from thiopurine chemotherapy.     

Surgical intervention in traumatic facial nerve paralysis

A four years review from June 1998 to June 2002 of traumatic facial nerve paralysis from temporal bone fractures that required surgical intervention is presented. The aim of this clinical presentation was to determine the current pattern of cases with traumatic facial paralysis which required surgical intervention at our center. There were six cases, of which four (66%) were longitudinal fractures, one each (17%) had transverse fracture and fracture over the lateral wall of mastoid. Hearing loss (83%) was the commonest associated clinical symptom. All cases underwent decompression via the transmastoid surgical approach. Intraoperative findings revealed oedema of facial nerve involving vertical segment and horizontal segment in three cases each respectively. Two cases had concomitant bony impingement. The facial nerve functions in four cases (66%) and one case recovered to House Brackmann grade 2 and 4, 12 months and 3 months respectively postsurgery. The case with transverse fracture remained as House Brackmann grade 5 after two years.     

Methotrexate misadventure: a case for counselling

SIR, Methotrexate (MTX), a broad-spectrum anti-cancer agent,is used to treat a number of autoimmune diseases, includingrheumatoid arthritis and psoriasis. Oral MTX carries particularrisks of serious illness through inappropriate prescribing anddispensing errors. The majority of reported medication errorshave been due either to the dispensing of the wrong strength,or the patient taking the wrong strength [1–4]. The riskof misadventure is increased when a patient has supplies ofboth strengths, as may be needed to provide a particular dose.Counselling patients receiving low-dose oral MTX is essentialat each consultation and dispensing. We report