Effective oral ganciclovir prophylaxis against cytomegalovirus disease in heart transplant recipients

The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.     

Efficacy of oral ganciclovir in prevention of cytomegalovirus infection in post-kidney transplant patients

We devised a diagnosis and management algorithm for acute onset of central diabetes insipidus (CDI), and conducted a retrospective evaluation of its efficacy. Fourteen patients admitted to our pediatric intensive care unit (PICU) over a three year period were diagnosed with acute CDI secondary to various brain injuries. All patients were treated as per the algorithm guidelines. The initial dose of aqueous vasopressin ranged from 0.25 to 1.0 mU/kg/h. Low sodium content solution (0-0.5 normal saline) was used to replace urine output in excess of 3 ml/kg/h and for maintenance fluid therapy. The therapeutic goals included: urine output 2-3 ml/kg/h, urine specific gravity 1.010-1.020 and serum sodium 140-145 mEq/l. The pitressin dose was adjusted as deemed necessary to achieve the aforementioned goals. Our results indicate that urine specific gravity is the most sensitive parameter to respond to treatment. It was the best determinant of the adequacy of pitressin dose as it had the best linear correlation with it (r = 0.96; p = 0.009). Urine output was second best (r = 0.93; p = 0.02), whereas no linear correlation was established between pitressin dose and serum sodium concentration, nor with serum osmolality. We conclude that the algorithm developed and used by us for the management of CDI is generally efficacious. Changes in urine specific gravity follow changes in pitressin dose very closely and thus should be used as the primary parameter for determination of intravenous pitressin dose adjustment.     

Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients

BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.     

A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients

BACKGROUND: Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy. METHODS: A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation. RESULTS: The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection. CONCLUSIONS: Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.     

Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy

BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.     

Significance of human cytomegalovirus DNA detection in immunocompromised heart transplant patients

Fifteen lactose malabsorbers were studied to evaluate the effects of consumption of milk containing different strains of Bifidobacterium longum on lactose digestion. Influences of different growth substrates, bile sensitivity, and lactose transport on lactose digestion by bifidobacteria were also investigated. Lactose malabsorption was determined by measuring breath hydrogen excretion of subjects fed four different test milks (three of which contained 5 x 10(8) cfu/ml of B. longum) on 4 different d using a randomized, double-blinded trial. Test milks included 1) 400 ml of lowfat milk (control), 2) 400 ml of milk containing B. longum B6 that had been grown with lactose, 3) 400 ml of milk containing B. longum B6 grown with lactose plus glucose, or 4) 400 ml of milk containing B. longum ATCC 15708 grown with lactose. beta-Galactosidase activity was highest in milk containing B6 grown with lactose but was extremely low in milk containing B6 grown with lactose and glucose. Consumption of milk containing B6 grown with lactose resulted in significantly less hydrogen production and flatulence than occurring after consumption of control milk or the milk containing B6 grown with both lactose and glucose. Hydrogen production after ingestion of 15708 was also significantly lower than hydrogen production after ingestion of the control milk. We concluded that milks containing B. longum might reduce breath hydrogen response and symptoms from lactose malabsorption when the culture is grown in a medium containing only lactose to induce a higher beta-galactosidase level and increase rate of lactose uptake.     

Ganciclovir treatment of active hepatitis B virus infection in a heart transplant patient

We report a 51-year-old woman with alopecia caused by sarcoidosis. The lesion enlarged within 4 years and only repeated biopsies enabled the diagnosis. The medical work-up revealed that the patient had asymptomatic pulmonary involvement. Scarring alopecia is a rare complication of sarcoidosis and biopsy from the active margin may lead to the diagnosis.     

The Cys607-->Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients

Two ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strains recovered from an AIDS patient (strain VR4990) and a heart transplant recipient (strain VR5474) showed a Cys607-->Tyr change in the UL97-encoded phosphotransferase. No amino acid substitutions were observed in the viral DNA polymerase. Marker transfer experiments showed marked reduction in GCV phosphorylation and drug susceptibility of the recombinant HCMV strain VR4990rec2-1-1. These results further extend the region of the carboxy-terminal domain of the UL97 phosphotransferase involved in GCV substrate recognition.     

Tuberculosis presenting as acute hepatitis in a renal transplant recipient

We have studied the effect of food on the interaction of ofloxacin with sucralfate. Six healthy men took a single oral dose of ofloxacin (200 mg) on 4 occasions: alone after overnight fasting or after breakfast (non-fasting), and with sucralfate fasting or non-fasting. There were no significant differences in the plasma concentration-time profiles of ofloxacin after ofloxacin alone between fasting and non-fasting conditions. On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61% compared with ofloxacin alone; the changes non-fasting were 39 and 31% respectively. The interaction of ofloxacin with sucralfate was markedly reduced by food, but still could not be disregarded.     

Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient

PURPOSE: To compare U.S. medical student Match results in 1996 for 19 categorical residency positions by specialty with those of the overall Match reported by the National Resident Matching Program (NRMP). METHOD: Data for the numbers of "active" senior U.S. student applicants (those who submitted rank lists), the numbers of U.S. seniors matched, and the numbers of unfilled positions for 19 specialties were obtained from a variety of sources. Chi-square analysis was performed to compare Match results for each independent specialty with the overall Match results. The level for statistical significant was set at p < .005. RESULTS: Eight specialties were identified as significantly more competitive than the overall Match process for both the percentage of U.S. seniors who successfully matched in that specialty and the ratio of unmatched U.S. senior applicants to unfilled categorical positions. Five specialties were identified as significantly less competitive for these two measures. Six specialties showed no significant difference in the percentages of U.S. students matching, but for three of these specialties there were more unmatched students than unfilled categorical positions. CONCLUSION: U.S. medical student Match results for categorical residency positions for different specialties vary significantly from the overall Match process. This information can be used in counseling senior medical students on their specialty selection and the residency application process.     

Echocardiographic analysis of rejection in the infant heart transplant recipient

Eleven children who received transplants at less than 2 years of age underwent 59 echocardiograms at the time of endomyocardial biopsy for the assessment of the ability of echocardiography to predict acute rejection in the infant heart transplant recipient. Two patients died of acute rejection and autopsy findings were compared with premortum echocardiograms. Biopsy specimens were graded as no rejection (n = 46), mild rejection (cellular infiltrate, n = 5), or moderate-severe rejection (myocyte necrosis/edema, n = 8). Echocardiographic indexes measured included the following: left ventricular mass, left ventricular volume, ejection fraction, heart rate, and peak rate of posterior wall thinning. Compared with controls, patients during mild rejection had slower posterior wall diastolic thinning (p < 0.01). No significant change was noted in left ventricular mass until endomyocardial biopsy specimens showed severe rejection. No significant changes were noted in heart rate or ejection fraction in any of the groups. In conclusion, decrease in the peak rate of posterior wall diastolic thinning may be a sensitive indicator of acute rejection in the infant heart transplant recipient.     

Successful outcome after massive bleeding in a heart transplant recipient with mycotic aortitis. Case report

Sudden mediastinal haemorrhage one month after heart transplantation in an 18-year-old youth was found to originate from a rupture of the ascending aorta associated with mycotic aortitis. Aortic continuity was restored with a Dacron graft. Cultures from the resected vessel wall showed Candida albicans. The patient recovered, and 11 months later is well.     

Transcatheter embolisation of an enlarging acquired coronary arteriovenous fistula in a heart transplant recipient

We reported two rare cases of diffuse pulmonary arteriovenous fistulas in infants and children. Both pulmonary angiography and chest computed tomography were obtained and revealed fine network formations clearly, from which the final diagnosis was made.     

Infective endocarditis of the tricuspid valve in an orthotopic heart transplant recipient

A 43-year-old orthotopic heart transplant recipient had coagulase-negative staphylococcus endocarditis 26 weeks after the operation. A diagnosis of endocarditis was confirmed and followed up by serial transoesophageal echocardiography. Treatment with intravenous gentamycin and vancomycin cured her endocarditis, and a 2.5 cm vegetation regressed significantly. She has been well since and, at 14 months after transplantation, was back to her normal activities. Although repeated blood culture yielded only intermittent light growths of coagulase-negative staphylococci, there were several positive samples. In a setting of infective features, light growths of coagulase-negative staphylococcus should be taken seriously if repeatedly positive in heart transplant recipients or other immunocompromised patients. Transesophageal echocardiography offers significant advantages over the transthoracic modality in suspected endocarditis.