Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Validation and clinical application of molecular methods for the identification of molds in tissue.

BACKGROUND: Invasive fungal infections due to less-common molds are an increasing problem, and accurate diagnosis is difficult. METHODS: We used our previously established molecular method, which allows species identification of molds in histological tissue sections, to test sequential specimens from 56 patients with invasive fungal infections who were treated at our institution from 1982 to 2000. RESULTS: The validity of the method was demonstrated with the establishment of a molecular diagnosis in 52 cases (93%). Confirmation of the causative organism was made in all cases in which a mold had been cultured from the tissue specimen. Less-common molds were identified in 7% of cases and appear to be an increasing problem. CONCLUSIONS: Our previously established method has proven to be of value in determining the incidence of invasive infection caused by less-common molds. Institutions should continue to pursue diagnosis of invasive fungal infections by means of tissue culture and microbiologic analysis.

Development of molecular methods for the identification of aspergillus and emerging moulds in paraffin wax embedded tissue sections.

BACKGROUND/AIMS: Invasive infection with emerging moulds is increasing in incidence and reliable methods for speciating these organisms in tissue sections need to be developed. METHODS: Two methods for extracting fungal DNA from paraffin wax embedded tissue sections, based on the TaKaRa DEXPAT kit and QIAamp DNA mini kit, were optimised and compared. DNA was amplified by PCR using pan-fungal probes, and detected by Southern blot hybridisation using a high stringency method with a probe specific for Aspergillus fumigatus and A flavus. RESULTS: The method based on the TaKaRa DEXPAT kit, with additional steps using lyticase and ethanol precipitation, was superior. Less than 10 conidia were detectable using spiked samples and a positive result was obtained with 100% of clinical samples known to be culture positive for A fumigatus. Other moulds could be identified by using species specific probes or by sequencing PCR products. CONCLUSIONS: The method based on the TaKaRa DEXPAT kit could detect less than 10 conidia/sample. The method allowed accurate identification of A fumigatus and A flavus and other species could be identified using species specific probes or by DNA sequencing. These methods will provide a valuable diagnostic tool for both patient management and future antifungal and epidemiological studies.

Treatment failure in invasive aspergillosis: susceptibility of deep tissue isolates following treatment with amphotericin B.

OBJECTIVES: To determine whether treatment failure in invasive aspergillosis (IA) is the result of resistance of Aspergillus spp. isolates to amphotericin B. METHODS: Six Aspergillus fumigatus and six Aspergillus flavus isolates cultured from deep tissue biopsies in 11 patients with haematological malignancies during 1991-1998 were tested. A method based on the NCCLS M38-A broth microdilution method, with colorimetric determination of MICs, was used to determine the MICs of amphotericin B and itraconazole. RESULTS: All A. fumigatus isolates were susceptible to amphotericin B (MIC 0.25-0.5 mg/L), as were three A. flavus isolates (MIC 1 mg/L), but three were less susceptible (MIC 2 mg/L). All isolates were susceptible to itraconazole (MIC 0.125-0.25 mg/L). All patients had been treated with amphotericin B, having received a median of 12 days of treatment when the tissue was obtained. CONCLUSION: The difficulty in treating IA may not be because of the susceptibility of the isolates, but because of poor penetration of antifungal agents into infected tissue. Aspergillus spp. invade blood vessels causing thrombosis and tissue infarction, and therefore it may be difficult for antifungal drugs to exceed MICs in infected tissues. This highlights the need for different treatment strategies, such as surgery and the administration of cytokines.

The CAG trinucleotide repeat length in the androgen receptor does not predict the early onset of prostate cancer.

OBJECTIVE: To relate the repeat length of the androgen-receptor CAG trinucleotide to the age of onset of prostate cancer, stage and grade of disease. PATIENTS AND METHODS: After obtaining ethical approval, 265 patients with locally confined or locally advanced/metastatic prostate cancer were identified and evaluated for age at diagnosis (< 65 years and > 75 years). DNA was extracted from peripheral blood lymphocytes and 1 micro g aliquots subjected to polymerase chain reaction using fluorescently labelled primers. Samples were then run on an ABI 377 gene scan analysis gel with an internal molecular weight marker. The length of the CAG repeat was determined by comparing the gene scan product size to samples where the CAG repeat length had been quantified using direct sequencing. The Kruskal-Wallis, Mann-Whitney and Wilcoxon two sample tests were used to analyse the data. RESULTS: The mean (range) length of the CAG repeat in the androgen receptor was 22.2 (10-31) in the younger and 22.5 (16-32) in the older group, and was not statistically different. There was no significant association between the CAG repeat length and the age of onset of prostate cancer (P = 0.568) or with stage (P = 0.577) and grade (P = 0.891) of prostate cancer. CONCLUSION: These results suggest that there is no correlation between the androgen receptor CAG repeat length and the age of onset, stage and grade of prostate cancer, confirming recent doubts from other similar studies of a suggested correlation between shorter androgen receptor CAG repeat and early onset and aggressiveness of prostate cancer.

Toxoplasmosis in bone marrow transplantation: a report of two cases and systematic review of the literature.

Toxoplasma infection represents a rare but often fatal complication in bone marrow transplant (BMT) recipients. We report two cases of toxoplasmosis: one of successfully treated cerebral toxoplasmosis after peripheral blood stem cell transplantation, and a fatal case of pulmonary toxoplasmosis in a BMT recipient. We have systematically reviewed the 110 published cases of toxoplasmosis following BMT. We analyzed the pre-transplant and clinical features of BMT recipients developing toxoplasmosis, together with the diagnostic procedures used and treatment given. By univariate and multivariate statistical analysis we analyzed the risk factors for diagnosis (during life vs post-mortem) and Toxoplasma-related mortality. Ante-mortem diagnosis was made in 47% of cases. Site of infection (P = 0.02; odds ratio 10.8), presence of symptoms at onset (P = 0.01) and conditioning regimen (P = 0.04) were factors influencing whether the diagnosis was made before or after death. Overall mortality rate was 80% and that attributed to toxoplasmosis was 66%. Variables influencing outcome were: site of infection (P = 0.02; odds ratio 5.28), day of onset (P = 0.04) and conditioning regimen (P = 0.04). Underlying disease (P = 0.02; odds ratio 9.45), among patients diagnosed before death, was the most significant factor influencing outcome.

The combination of oral amphotericin B with azoles prevents the emergence of resistant Candida species in neutropenic patients.

The role of antifungal prophylaxis remains controversial and concerns exist that the use of azoles may potentiate the emergence of resistant Candida species. We used a strategy of combining the latest azole/triazole with oral amphotericin B to reduce this risk. We analysed data on Candida colonization and candidaemia in neutropenic patients from four prophylaxis periods (1985/6: ketoconazole and amphotericin B suspension; 1991/2 & 1997: fluconazole and amphotericin B suspension; 1998/9: itraconazole) to look for evidence of the emergence of potentially resistant species. Overall, the percentage of patients colonized with Candida fell significantly (69.3%, 57.5%, 43.2% and 46%, respectively, P < 0.001) due to a decrease in colonization with C. albicans (49%, 23.1%, 22.2% and 25.2%, respectively, P < 0.001). However, in 1998/9, increased colonization, particularly with C. glabrata in the lower gastrointestinal tract, was noted to coincide with the omission of oral amphotericin B. Despite an increasing population of 'high risk' patients, the incidence of candidaemia has not changed significantly (2%, 1.4%, 1.2% and 2% respectively). However, species causing candidaemia have changed, with resistant organisms now predominating. Our findings support the use of azole prophylaxis although, in view of the trends noted when itraconazole was used alone, we would recommend the additional use of oral amphotericin B.

Fatal invasive cerebral Absidia corymbifera infection following bone marrow transplantation.

A 56-year-old dairy farmer received a fully HLA matched unrelated donor marrow transplant for high risk CML in chronic phase. His early post-transplant course was complicated by a series of massive intracerebral bleeds and by sepsis related to a malignant otitis externa. The microbial pathogen isolated from ear swabs was found to be Absidia corymbifera, but CT scan at the time showed no intracerebral extension. Despite neutrophil engraftment and aggressive antifungal management he succumbed. Autopsy revealed invasion of Absidia into the brain from the ear. We speculate that colonisation by Absidia resulted from occupational exposure.

Does endoscopic laser ablation of the prostate stand the test of time? Five-year results from a multicentre randomized controlled trial of endoscopic laser ablation against transurethral resection of the prostate.

OBJECTIVE: To determine the long-term objective and subjective outcome of patients with benign prostatic enlargement (BPE) treated by endoscopic laser ablation of the prostate (ELAP), as part of a multicentre randomized controlled trial of ELAP against TURP. PATIENTS AND METHODS: Initially, 151 patients with BPE were randomized to undergo either ELAP or TURP, starting in March 1992. ELAP was performed using the Urolasetrade mark fibre (Bard, Covington, GA, USA) in conjunction with a Nd:YAG laser source. All patients who had originally participated in the study were approached 5 years later to obtain a urological history, American Urological Association (AUA) symptom score and two measurements of urinary flow rate, with an ultrasonographic assessment of the postvoid residual urine volume (PVR). RESULTS: The mean duration of follow-up was 61 months; 109 patients were traced, comprising 69 who were alive and well, and had undergone no further bladder outlet surgery, 26 who had required revision surgery, 12 who were dead or terminally ill and three who had dementia. Both ELAP and TURP produced sustained improvements in mean AUA score, maximum flow rate and PVR, with respective values at 5 years of 6.3, 17.8 mL/s and 76 mL, and 6.5, 20.0 mL/s and 55 mL. Eighteen of 47 ELAP patients (38%) and eight of 51 (16%) TURP patients underwent revision surgery within the follow-up. CONCLUSION: ELAP and TURP produced similar subjective and objective outcomes at 5 years. The re-operation rate after ELAP was more than double that after TURP and suggests that ELAP should not be used routinely in the management of men with BPE.

Extra-anatomic urinary diversion.

In five patients with chronic intractable ureteral obstruction, a fine-bore nephrostomy tube was placed in a subcutaneous tunnel to drain the kidney without an external appliance. Good quality of life was achieved for 6 months to 2 years. When conventional intraluminal stents cannot be used, consideration should be given to subcutaneous diversion rather than long-term nephrostomy tubes.

Quality of life after a Marshall-Marchetti-Krantz procedure for stress urinary incontinence.

PURPOSE: We assessed the long-term results of the Marshall-Marchetti-Krantz procedure. MATERIALS AND METHODS: A total of 151 case records was reviewed and a questionnaire was mailed to patients to estimate the success rate and patient satisfaction. RESULTS: The response rate was 67.3% (101 replies). The overall success rate was 72.8% (mean followup 51.5 months). The success rates in patients with irritative symptoms and pure stress incontinence were 65% and 82.6%, respectively. The procedure was equally effective for recurrent stress incontinence. CONCLUSIONS: The procedure is characterized by a high success rate 5 years postoperatively. The method of review, based on a mailed questionnaire, appears to be more objective than conventional reviews but further improvements may increase the accuracy.

Clear cell sarcoma of the kidney in an adult.

An adult case of clear cell sarcoma of the kidney is described. The clinical, histological, immunohistochemical and electron microscopical features of the tumour are described.

Severe urethral obstruction diagnosed at 14 weeks' gestation: variability of outcome with and without drainage.

We present 3 case reports to illustrate the variability of outcome of severe fetal posterior urethral obstruction. Two of the described cases support the view that early in-utero decompression of an obstructed fetal urinary system into the amniotic cavity, in the selected patient, will allow adequate lung development and will prevent the development of severe renal dysplasia. It will not prevent the abdominal wall deformity of the prune belly syndrome. The evidence suggests that to allow maximum time for lung development and to prevent increasing renal dysplasia, drainage should be performed before 18 weeks of gestation. To obtain maximum effect, this drainage should continue until at least 32-33 weeks' gestation, so that the possible respiratory problems of prematurity would not be severe enough to compound the degree of lung hypoplasia which might be present. Case 3 supports our view that an endoscopic approach to in-utero drainage of the urinary tract has the advantage of achieving drainage with minimal risk to both mother and fetus.

Subcutaneous urinary diversion: an alternative to percutaneous nephrostomy.

Nephrostomy has been the standard method of urinary diversion when placement of ureteral stents has failed in cancer patients. We describe our early experience with an alternative method of urinary diversion, the subcutaneous urinary diversion. This extra-anatomical urinary diversion was done in 5 patients during a 15-month interval. The diversion is created using a specially designed 7F double pigtail stent. The proximal end of the stent is inserted into the renal pelvis via a percutaneous nephrostomy puncture. A subcutaneous tunnel is created from the flank to the bladder down which the distal end of the stent is passed and via a suprapubic bladder puncture the stent is passed into the bladder. The stent is changed at 4-month intervals over a guide wire. Our early experience with this extra-anatomical method of urinary diversion suggests it to be a safe, effective and acceptable alternative to nephrostomy that improves quality of life.

Endometrial ablation: an option for the management of menstrual problems in the intellectually disabled.

OBJECTIVE: To evaluate endometrial ablation as an alternative to hysterectomy for intellectually disabled women with inadequate menstrual hygiene. DESIGN AND SETTING: A retrospective review of all intellectually impaired women referred to a menstrual management clinic at a university teaching hospital for management of inadequate menstrual hygiene between October 1989 and September 1992. RESULTS: Endometrial resection was considered an appropriate alternative to hysterectomy for eight intellectually disabled women. To date, seven women have undergone the procedure and one is receiving medical treatment. Endometrial ablation was performed with roller-ball electrocautery. Three patients underwent sterilisation at the time of surgery. The mean operating theatre time was 75 minutes. Postoperative hospital stay was less than 48 hours for all but one patient, who underwent minilaparotomy for sterilisation--postoperative analgesia was required only by this patient. There were no complications during or after surgery. Six weeks after surgery, all patients were amenorrhoeic and they and/or their carers expressed satisfaction with the procedure. Four women, followed up for between 16 and 38 months, remain amenorrhoeic and two, followed up for six months, have each experienced one episode of spotting but are otherwise amenorrhoeic. The seventh patient has had irregular bleeding but this is deemed due to erroneous continuation of progesterone therapy and is being monitored. CONCLUSION: Endometrial ablation provides a valuable alternative to hysterectomy. It should be the surgical treatment of choice for intellectually disabled women with inadequate menstrual hygiene unresponsive to medical therapy.

Relationship between intra-abdominal and intrarectal pressure in the proctometrogram.

During normal defaecation the intrarectal pressure increases but, in the absence of a reference catheter in the pelvis, the contribution of abdominal straining and rectal contraction to this rise is unclear. Anorectal manometry was performed in ten consecutive women with no gastrointestinal symptoms in an attempt to measure intrapelvic pressure using a catheter in the bladder. During filling the mean (s.e.m.) rectal pressure increased from 2(1) to 18(4) cmH2O. The mean(s.e.m.) intravesical pressure remained unchanged at 2(1) cmH2O. Evacuation of the rectal balloon produced an increase in mean (s.e.m.) intrarectal pressure from 18(4) (end-filling pressure) to 68(15) cmH2O. The mean (s.e.m.) intravesical pressure increased from 2(1) to 51(18) cmH2O. The true intrarectal pressure (intrarectal minus intravesical) did not rise during defaecation. The rise in intrarectal pressure during rectal evacuation occurs by increased intrapelvic pressure alone.

Expression of xenobiotic metabolizing enzymes in breast cancer.

We have studied the expression of different xenobiotic metabolizing enzymes in primary operable breast cancer of no special type. The expression of two forms of cytochrome P450, microsomal epoxide hydrolase, and three classes of glutathione S-transferase was investigated using immunohistochemistry. The tumours were characterized by consistent expression of microsomal epoxide hydrolase and by variable expression of the two forms of cytochrome P450 and the three types of glutathione S-transferase. Cytochrome P450 1A and cytochrome P450 3A were identified in 39 and 22 per cent of tumours, respectively. In each case, immunostaining was present only in areas of invasive carcinoma. Epoxide hydrolase was identified in 89 per cent of tumours and glutathione S-transferases pi, mu, and alpha were identified in 56, 65, and 44 per cent of tumours, respectively. Immunoreactivity for epoxide hydrolase and glutathione S-transferases was identified in both tumours and non-neoplastic breast tissue. The presence of different xenobiotic metabolizing enzymes may have a role in determining the intrinsic drug resistance of breast cancer to a variety of anti-cancer drugs, and the expression of these enzymes can readily be assessed using immunohistochemistry.