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Disseminated infection with Prototheca zopfii is a rare disease in immunosuppressed patients. We here report the first case of lethal infection with P. zopfii following unrelated stem cell transplantation for leukemia. Breakthrough protothecosis occurred during long-term administration of voriconazole in the case of pulmonary aspergillosis.
The recent resurgence of mumps epidemics in many countries with ongoing vaccination programs along with evidence of antigenic diversity among mumps virus strains have recently challenged the assumption that mumps virus is serologically monotypic. To address this controversy, we sought to identify two mumps virus strains that would best represent different serotypes, should multiple serotypes exist, and assess the ability of human sera to neutralize both strains. The virus strains, Enders and Lo1, were selected based upon a phylogenetic analysis of the major target of neutralizing antibody, the viral hemagglutinin-neuraminidase (HN) protein, along with data reported by others indicating that (1) these viruses are antigenically distinct and (2) genotypically similar strains have been implicated in cases of reinfection. Our results show that of sera capable of neutralizing one of the virus strains, 90% could neutralize the other, although significant differences in neutralization titers were noted. Though the latter confirms the existence of inter-strain antigenic variability, the fact that few sera were unable to neutralize both virus strains argues against the presence of multiple serotypes. Of those sera incapable of co-neutralization, all but one had low neutralization titers (1:8), suggesting that individuals possessing low levels of neutralizing antibody may be at risk for breakthrough infections, thereby providing an explanation for cases of infection in previously infected or vaccinated individuals.
Mild and moderate vesicoureteral reflux is expected to resolve spontaneously in most children treated medically; however, maximum benefit or minimum risk of such therapy has not been defined. A prospective 5-year followup study of infants and children younger than 5 years at entry with primary vesicoureteral reflux (grades I to III/V) and radiographically normal kidneys after the first recognized urinary tract infection was initiated in 1984. A total of 113 patients was entered from 5 centers and 61% of the patients were less than 2 years old. Vesicoureteral reflux was unilateral in 65 cases (58%) and bilateral in 48 (42%). Of the 226 renal units reflux was grade IV in 4 (2%), III in 51 (22%), II in 81 (36%) and I in 25 (11%), and 65 (29%) had no vesicoureteral reflux. Data on 59 patients who have completed the protocol were analyzed for this report. Breakthrough urinary tract infection occurred in 20 patients. Of the 84 ureters with vesicoureteral reflux at diagnosis reflux resolved in 67%, and it was of lower grade in 22%, same grade in 8% and higher grade in 2%. Grade I vesicoureteral reflux resolved in 82%, grade II in 80% and grade III in 46% of the ureters. Resolution was better when vesicoureteral reflux was unilateral left (74%) than unilateral right (46%) or bilateral (60%). Renal scarring occurred, on average, in 10% of the kidneys without known vesicoureteral reflux or exposed only to nondilating (grades I and II) reflux and in 28% of those with dilating (grade III) reflux. Thirteen cases had breakthrough urinary tract infection but only after the scar was noted in 5. We conclude that under good medical management during 5 years of followup, even mild and moderate vesicoureteral reflux can be associated with renal injury.
PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.
Treatment approaches with recombinant IFN-alpha2b and natural IFN-beta in a patient with chronic hepatitis C (genotype 1b) and cirrhosis had, in both cases, to be terminated prematurely due to breakthrough phenomena and thrombo-leukocytopenia up to WHO grade 3. After the patient was switched to highly purified natural IFN-alpha (Multiferon) the thrombocyte and leukocyte counts increased significantly, and sustained complete biochemical and virological response could be achieved.
Three cases of endovascular infection of atherosclerotic aneurysm of the abdominal aorta due to Salmonella spp. are described. 'Breakthrough' or relapsing bacteraemia were major clues for diagnosis in each case. They were treated with a prolonged course of bactericidal antibiotics before surgery. Resection with an interposed graft was performed in all cases and antibiotic treatment continued. Two of our patients have survived for more than two years and the other for 18 months without evidence of relapse. Thus, it would appear possible at times to treat successfully mycotic aneurysm of the abdominal aorta with antimicrobial agents plus resection of the aneurysm followed by in situ bypass grafting. Extra-anatomical grafts should be kept for infections due to antimicrobial-resistant organisms or when periaortic infection is widespread.
We report 2 cases of Budd-Chiari syndrome that are due to complete membranous obstruction between the junction of the inferior vena cava and the right atrium. Both cases were treated successfully by King's bioptome breakthrough followed by balloon dilatation of the membrane. The patients showed remarkable symptomatic improvement and promising hemodynamic and angiographic results immediately after the procedure and 6 years later. We conclude that balloon angioplasty is a safe and effective method for treating this rare disease in selected cases.
Two cases of unruptured pial arteriovenous malformations (AVMs) presenting with intracranial hypertension and papilledema are reported. In the absence of previous hemorrhage or associated hydrocephalus, such a manifestation of pial AVMs is quite unusual. Both patients experienced prompt and sustained resolution of papilledema after surgical removal of the malformation. One case was complicated by the normal perfusion pressure breakthrough phenomenon postoperatively. The pathophysiology of intracranial hypertension associated with unruptured pial AVMs and the relationship to pseudotumor cerebri are discussed.
OBJECTIVES AND STUDY DESIGN: The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and varicella breakthrough rates when VARIVAX (varicella vaccine) is given at the same time as M-M-R II (measles, mumps, rubella vaccine) and TETRAMUNE (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs. VARIVAX given 6 weeks after M-M-R II and TETRAMUNE (Group B). Six hundred nine healthy children, 12 to 23 months of age, were randomized to one of two treatment (immunization) groups (Group A and Group B). Blood for antibody titers was drawn on the day of immunization, 6 weeks after each injection and 1 year later. Local and systemic adverse reactions were recorded. Exposure and cases of varicella were documented through a 1-year follow-up period. RESULTS: Measles, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversion rates were also similar between groups. However, varicella GMTs and percent with a varicella-protective level [> or =5.0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] did not meet the prespecified criteria for similarity were lower for Group A (GMT 10.5; 82.8% > or =5.0 gp ELISA units) than for Group B (GMT 14.5; 91.2% > or =5.0 gp ELISA units). The GMTs between groups for other antibodies were similar. At the 1-year follow-up antibody titers were comparable in both groups and breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX injection sites (9.8% and 2.9%, Group A and B, respectively) than at the TETRAMUNE sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R II was administered alone (8.6%) or concomitantly with VARIVAX (8.9%). When VARIVAX was given alone AEs were 1.8%. The rate of fever > or =102 degrees F after M-M-R II and TETRAMUNE administered together was 10.7% on Days 0 to 3 and 23.7% on Days 7 to 21. When VARIVAX was administered alone, the rate of fever was 5.4% on Days 0 to 3 (P = 0.018) and 10.8% on Days 7 to 21 (P<0.001). CONCLUSION: Because the varicella titers were comparable and varicella breakthrough rates generally similar at 1 year in both groups, we expect that the concomitant administration of VARIVAX with M-M-R II and TETRAMUNE has clinical effectiveness similar to that with VARIVAX 6 weeks after the administration of these other two vaccines. VARIVAX appears to be less reactogenic than M-M-R II and TETRAMUNE.
Recently the awareness of the issues surrounding male rape has received increased attention by both mental health workers and the general public following the introduction of the Sexual Offences Act 1994, and the recent case at the Old Bailey where a historical breakthrough was made in June 1995 following the first conviction for male rape under the new law. However, most of this attention has not resulted in many clinical breakthroughs in helping male rape survivors overcome the post-assault impact. Little is known about the prevalence, types of assault, consequences facing survivors and therapeutic options. Some evidence is being reported that male rape survivors develop Post Traumatic Stress Disorder following the assault. It has long been recognized that this is the case with female rape survivors, but to date there have been no significant UK prevalence studies which have examined this relationship. This paper discusses some of the issues surrounding male rape by focusing on the possible effects of the recent legal change on the clinical area.
Patients with coarctation of the aorta (CoA) who previously underwent successful surgery are often diagnosed on standard electrocardiograms as having partial right bundle branch block. After surgery 24 patients with CoA had body surface potential mapping (BSPM) with the Case Western Reserve University 180 electrode system; of these 7 had additional aortic stenosis and none had ever had intracardiac communication. The average age at the initial surgery for CoA was 4.0 +/- 3.3 years and at the time of the BSPM it was 12.7 +/- 5.9 years. For the 17 patients with CoA without aortic stenosis the average age at the initial surgery was 5.0 +/- 3.4 years and at the time of the BSPM it was 14.2 +/- 6.0 years. In 11 of the 24 patients, a cardiac catheterization was performed, and each patient demonstrated normal pulmonary artery and right ventricular systolic pressure except for one child with 40 mmHg systolic. In the others all indications were that right ventricular pressure was normal. In 11 of the 24 patients, congestive heart failure had been present in infancy. All 24 cases had evidence for epicardial right ventricular breakthrough on the BSPM, a finding believed to indicate right ventricular activation from endocardium to epicardium via the normal Purkinje system. There were no findings on the BSPM suggesting that right bundle branch block was present. Right ventricular hypertrophy with or without terminal right conduction delay was present on the BSPM in 19 of the 24 patients (9 with additional left ventricular hypertrophy--left ventricular hypertrophy alone in 5). Right ventricular hypertrophy could be considered in 6 of 19 patients in the electrocardiogram, and in 11 of 19 in the vectorcardiogram. The mechanism for the persistent electrocardiographic right ventricular hypertrophy is postulated to involve right ventricular hyperplasia in utero or in early neonatal life, which never disappears.
Phosphodiesterase 5 terminates the cellular actions of the second messenger molecule cyclic GMP; inhibitors of phosphodiesterase 5 will therefore increase and prolong the actions of endogenous substances that signal via the cyclic GMP pathway, including nitric oxide released as a neurotransmitter from nitrergic nerves. To date, the most widely used phosphodiesterase 5 inhibitors, zaprinast and sildenafil, have proved vital in the elucidation of the widespread role of cyclic GMP in nitrergic transmission and, specifically in the case of sildenafil, have provided a major breakthrough in the treatment of erectile dysfunction in men. Although still a matter of debate, early evidence indicates that sildenafil may also be of benefit in some forms of sexual dysfunction in women. The remarkable clinical success of sildenafil has prompted the search for further novel phosphodiesterase 5 inhibitors which might be used to enhance nitrergic function in other disease states.
STUDY DESIGN: A prospective study was performed to evaluate the effectiveness of evoked and spontaneous electromyography in predicting pedicle wall breakthrough and subsequent lumbar radiculopathy occurring after placement of pedicle screw instrumentation of the lumbar spine. OBJECTIVES: To correlate cortical breakthrough of the pedicle wall with an electrically evoked electromyography threshold of stimulation, to assess the sensitivity of mechanically evoked electromyography for nerve root irritation, and to correlate postoperative nerve root irritation with intraoperative findings. SUMMARY OF BACKGROUND DATA: Pedicle wall breakthrough has been evaluated by radiographic means and found to be difficult to evaluate. Methods to perform both electrically evoked and mechanically evoked electromyography have been developed more sensitive tests for breakthrough. METHODS: Twenty-five patients receiving 112 pedicle screws were evaluated. RESULTS: Cortical breakthrough was associated with electrically evoked electromyography threshold of less than 11 milliAmps. Not all screws that had broken through the pedicle wall caused a postoperative radiculopathy. Electromyographic activity was sensitive to nerve root stimulation. CONCLUSIONS: Measuring the electrically evoked electromyography threshold of stimulation helps to assess pedicle screw placement. Mechanically evoked electromyography indicates intraoperative nerve root displacement. Postoperative radiculopathy correlated with pedicle wall breakthrough, but did not occur in every case.
AIM: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. METHODS: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. RESULTS: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. CONCLUSION: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.
AIM: To compare additive efficacy of combination therapy including interferon (IFN)-alpha2a+lamivudine (3TC) to IFN-alpha2b+3TC in children with chronic hepatitis B virus (HBV) infection. MATERIAL AND METHODS: Chronic hepatitis B infection was determined by presence of HBsAg, HBeAg and HBV DNA in serum screened at 3 months intervals for at least 1 year, serum alanine transaminase (ALT) levels more than 1.5-times the upper normal limit and chronic hepatitis with histological activity index (HAI) more than 6 by liver biopsy. Sixty-three children with chronic hepatitis B infection were treated randomly with thrice-weekly subcutaneous injections of 5 MU/m2 recombinant IFN-alpha2a (n=29) or recombinant IFN-alpha2b (n=34) with the same dose, intervals for 6 months. Patients also received 3TC (4 mg/kg/day, max 100 mg/day) orally daily combined with IFN and continued for 12 months. End of therapy response was defined as ALT normalization, HBV DNA clearance and HBe/anti-HBe seroconversion. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. Response rate, incidence of side effects and breakthrough infection were compared between IFN-alpha2a+3TC- and IFN-alpha2b+3TC-treated patients. RESULTS: Response rate was 44.8% (n=13) with IFN-alpha2a+3TC and 47.1% (n=16) with IFN-alpha2b+3TC (P=1.0). No significant difference was found in respect to the DNA clearance (P=0.32), anti-HBe (P=1.0), anti-HBs (P=0.09) seroconversion and response rates (P=1.0) between the groups. Breakthrough infection was detected in 1 (3.4%) case on IFN-alpha2a and none of the cases on IFN-alpha2b (P=0.46). All of the patients experienced flu-like symptoms, malaise and fatigue; however, side effect interfering with therapy was not encountered. CONCLUSION: No significant difference was found in response rates achieved by combination therapies based on IFN-alpha2a and IFN-alpha2b. Clinical efficacy of 3TC and two different IFN subtypes was found similar.
Chemoprophylaxis of malaria on the Thai-Cambodian border is difficult due to the high level of drug resistance. Thirteen separate companies of Royal Thai Marine Militia were placed on 250 mg weekly mefloquine chemoprophylaxis from August 1989 to January 1990. A mean number of 722 soldiers received two or more doses of mefloquine per month for the five month study. The medication was well tolerated and compliance averaged 91%. Substantial numbers of prophylaxis breakthroughs were seen which resulted in 3.2 cases of malaria/100 man-months. Sixty-eight falciparum malaria cases were documented in men who had taken at least two mefloquine doses in the previous four weeks. No serious neuropsychiatric reactions occurred. Mefloquine chemoprophylaxis failures exist on the Thai-Cambodian border and are one sign of the spread of mefloquine resistance.
OBJECTIVE: To describe the results and follow-up of 34 vesico-ureteral reimplantations in infants. METHODS: From 1985 to 1994, 34 vesico-ureteral reimplantations (Cohen transtrigonal technique) were performed in 20 infants aged 1-13 months. The indications for surgery were high grade congenital vesico-ureteral reflux and breakthrough pyelonephritis that had presented in some cases despite prophylactic measures. RESULTS: At 4 years mean follow-up, all reimplanted ureters showed no reflux. One case with bilateral reimplantation was lost to follow-up. CONCLUSIONS: Many of the infants with vesico-ureteral reflux can be managed medically and the reflux will cease in some cases. But a few of them with difficult to control infections, can benefit from early surgery.
Hemodynamic changes are of importance while removing large and high-flow arteriovenous malformations (AVM), because a phenomenon called "normal perfusion pressure breakthrough" may occur. In this report, we evaluated hemodynamic changes in 14 cases of high-flow AVM with cerebral angiogram and intraoperative monitoring of cortical-surface blood flow. The criteria we used for high-flow AVM are; nidus larger than 4 cm, a few large feeders, high-flow shunt in the nidus, and reduced circulation or dilated arteries in the adjacent brain tissue. For last 2 years, we experienced 14 cases of high-flow AVM which fulfilled the criteria, and 9 of these were operated on for total removal of AVM. Of those, 2 cases evolved postoperative local edema and hemorrhage and was thought to be due to "normal perfusion pressure breakthrough." Intraoperative monitoring of cortical-surface blood flow was useful to predict occurrence of "perfusion breakthrough", because blood flow in the adjacent brain tissue increased markedly with feeder clipping. Intraoperative barbiturate protection and postoperative controlled hypotension were thought to be useful for prevention of "normal perfusion pressure breakthrough", though the details of mechanisms are unknown.