Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients.

Late-onset cytomegalovirus (CMV) disease commonly occurs after discontinuation of antiviral prophylaxis. We determined the utility of testing CD8+ T-cell response against CMV as a predictor of late-onset CMV disease after a standard course of antiviral prophylaxis. Transplant patients at high-risk for CMV disease were enrolled. CD8+ T-cell-mediated immunity (CMI) was tested using the QuantiFERON-CMV assay at baseline, 1, 2 and 3 months posttransplant by measurement of interferon-gamma response to whole blood stimulation with a 21-peptide pool. The primary outcome was the ability of CMI testing to predict CMV disease in the first 6 months posttransplant. There were 108 evaluable patients (D+/R+ n = 39; D-/R+ n = 34; D+/R- n = 35) of whom 18 (16.7%) developed symptomatic CMV disease. At the end of prophylaxis, CMI was detectable in 38/108 (35.2%) patients (cutoff 0.1 IU/mL interferon-gamma). CMV disease occurred in 2/38 (5.3%) patients with a detectable interferon-gamma response versus 16/70 (22.9%) patients with a negative response; p = 0.038. In the subgroup of D+/R- patients, CMV disease occurred in 1/10 (10.0%) patients with a detectable interferon-gamma response (cutoff 0.1 IU/mL) versus 10/25 (40.0%) patients with a negative CMI, p = 0.12. Monitoring of CMI may be useful for predicting late-onset CMV disease.

An assessment of herpesvirus co-infections in patients with CMV disease: correlation with clinical and virologic outcomes.

The effect of herpesvirus co-infections (HHV-6, HHV-7) on cytomegalovirus (CMV) disease and its response to therapy is unknown. We prospectively analyzed herpesvirus co-infections in transplant recipients with CMV disease. All patients received 3 weeks of antiviral therapy. Samples were collected at baseline (day 0) and then day 3, 7, 14 and 21 poststart of therapy. Viral load testing for CMV, HHV-6 and HHV-7 was done using quantitative PCR assays in 302 patients of whom 256 had documented symptomatic CMV viremia. In this subset, day 0 HHV-6 co-infection was present in 23/253 (9.1%) and HHV-7 in 17/253 (6.7%). Including those positive at any time point raised the prevalence to 79/256 (30.9%) for HHV-6 and 75/256 (29.3%) for HHV-7. Viral co-infection did not influence the response of CMV disease to antiviral therapy. Baseline CMV viral loads, time to eradication and risk of recurrence were similar in patients with and without HHV-6 or HHV-7 co-infection. Ganciclovir and valganciclovir had no clear effect on HHV-6 and HHV-7 viremia. In conclusion, herpesvirus co-infections are common in patients with CMV disease but with standard antiviral therapy, no clear clinical effects are discernable. Routine monitoring for viral co-infection in patients with CMV disease is not indicated.

Validation of optical coherence tomography in vivo using cryostat histology.

We aimed to validate for the first time optical coherence tomography (OCT) measurements of epidermal thickness (ET) using cryopreparation for histology. OCT assessments of ET were performed on healthy skin using the algorithms as follows: first, peak-to-valley analysis of the A-scan (ET-OCT-V), second, line-traced image analysis of the B-scan (ET-OCT-IA). Histology was performed using cryostat sections which were also evaluated using the image analysis (ET-Histo). We selected 114 samples, including B-scans and corresponding histology, for method comparison between ET-OCT-IA and ET-Histo. Forty-two A-scans were available for method comparison between ET-OCT-V and ET-Histo. Bland and Altman plots revealed a marked bias with wide 95% limits of agreement for ET-OCT-V versus ET-Histo. Comparison of ET-OCT-IA versus ET-Histo revealed only a slight bias and narrow 95% limits of agreement. A-scan analysis for ET determination is linked to significant limitations and lacks agreement with histology. By contrast, we observed satisfactory agreement between ET-OCT-IA and ET-Histo indicating that both methods can be utilized interchangeably. OCT using the line-traced image analysis of the B-scan appears to be a valid and relatively practicable method for the determination of ET in vivo. Furthermore, the comparisons with the in vivo OCT profiles demonstrate that cryostat sectioning provides a better preservation of relative and absolute dimensions of skin layers than paraffin embedding.

Reference limits for erythema-effective UV doses.

Diagnostic phototesting, including the determination of the minimal erythema dose (MED), is a useful procedure to detect abnormal sensitivity to UV radiation. We aimed to estimate the reference limits (RLs) of the MED in a reasonably large reference sample of white individuals. Skin phototypes and MED values for broadband UVB and for UVA were determined in 461 white subjects. When appropriate, the 95% reference intervals, including the 0.025 fractile and 0.975 fractile, were computed for the MED-UVB reference values (by means of parametric methods) and the MED-UVA reference values (by means of nonparametric methods). MED data were also converted to standard erythema doses (SEDs). As described elsewhere we observed a considerable overlap of MED values for all skin phototypes and confirmed that age and sex do not substantially influence the MED. The lower RLs observed for MED-UVB were 33 mJ cm(-2) (0.5 SEDs) and for MED-UVA 12.6 mJ cm(-2) (1.2 SEDs). The MED and SED findings from this investigation may serve as reference data for white individuals and give support to the clinician in differentiating between normal and pathologically abnormal photosensitivity. Although the MED data given here are limited to the phototest device used in the present study, the SED results establish comparability between our data and phototest results obtained from laboratories using different UV sources.

Lymphomatoid granulomatosis presenting as ulcerodestructive gastrointestinal tract lesions in patients with human immunodeficiency virus infection. A new association.

We describe cases of severe odynophagia, extensive oral ulcerations, and bowel perforation in patients with human immunodeficiency virus infection that were caused by lymphomatoid granulomatosis. Such presentations in human immunodeficiency virus-infected individuals are usually ascribed to other causes and may be incorrectly treated on an empiric basis. In addition, deep tissue specimens obtained at the margin of ulcerative lesions are often necessary for definitive diagnosis. We review our limited treatment experience with zidovudine, interferon alfa, and H2 blockers in our patients. Based on the markedly increased frequency in which lymphomatoid granulomatosis is being diagnosed at our institution in the post-human immunodeficiency virus era, we postulated an association between these two entities.

A randomised trial comparing cytomegalovirus antigenemia assay vs screening bronchoscopy for the early detection and prevention of disease in allogeneic bone marrow and peripheral blood stem cell transplant recipients.

Preemptive antiviral therapy is often employed for CMV prevention following allogeneic BMT. Two common strategies are a screening bronchoscopy for CMV post-BMT or regular CMV antigenemia testing with ganciclovir administration for a positive result. In a randomised trial, we prospectively compared the efficacy of these two preemptive strategies. Consecutive patients were randomised to either a bronchoscopy for CMV on day 35 post BMT or weekly CMV antigenemia testing. If the bronchoscopy was positive for CMV, patients received preemptive ganciclovir for 8-10 weeks. If the antigenemia was positive for CMV, patients received a minimum of 2 weeks of preemptive ganciclovir. The primary endpoint was the development of active CMV disease. One hundred and eighteen allogeneic BMT patients were enrolled (60 in the antigenemia arm and 58 in the bronchoscopy arm). The two groups were comparable with respect to baseline demographic data, underlying disease, conditioning regimen, and immunosuppression. Active CMV disease developed in 7/58 (12.1%) patients in the bronchoscopy arm vs 1/60 patients (1.7%) in the CMV antigenemia arm (P = 0.022). Based on the screening test, 13.8% of patients received preemptive ganciclovir in the bronchoscopy arm vs 48.3% of patients in the antigenemia arm (P < 0.001). There was no significant difference in the rate of graft-versus-host disease, bacteremia, invasive fungal infections or mortality between the two groups. Preemptive therapy based on regular CMV antigenemia monitoring is superior to screening bronchoscopy for the prevention of CMV disease after allogeneic BMT.

The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.

At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy.

The Osborn wave of hypothermia in normothermic patients.

The Osborn wave (also referred to as "the J wave," "the J deflection," or "the camel's hump") is a distinctive deflection occurring at the QRS-ST junction of approximately 80% of hypothermic patients (core body temperature < or = 95 degrees F). Generally, the amplitude and duration of Osborn waves are inversely related to core temperature. We report on eight normothermic patients whose 12-lead electrocardiograms demonstrated QRS-ST junction notches similar to those seen in hypothermia. These data support the concept that the Osborn wave is not pathognomonic of hypothermia.

[Anterior lenticonus, suggesting Alport syndrome. Apropos of a first case in Zaire]. / Le lenticône antérieur, évoquant un syndrome d'Alport. A propos de la première observation zaïroise.

Anterior lenticonus is a rare condition, in which there is a conical or spherical protrusion of the anterior surface into the anterior chamber. This is demonstrated by this case report, which has not been previously described in the Black African or Zairian ophthalmological literature. The patient was 28 years old and complained of gradual deterioration of vision over several years. The visual acuity was 20/200. The slit lamp biomicroscope showed an anterior lenticonus with microopacities of the lens. On fundus examination, a fundus albipunctatus-like appearance with midperipheral retinal flecks and macular hole were found. The presence of associated ocular abnormalities, deafness and hematuria, is suggestive of Alport's syndrome.

Volvulus of the liver with intrathoracic herniation.

INTRODUCTION: We present a rare case of a liver volvulus, stomach and transverse colon herniating through the diaphragm. This scenario has not been reported previously. We discuss the presentation and management of this interesting case. CASE HISTORY: A 65-year-old woman with a history of sarcoidosis and recurrent pericardial effusions, treated previously with a subxiphoid pericardial oval window fenestration, presented with acute upper abdominal pain radiating to the chest. High contrast computed tomography showed a volvulus of the liver with consequent venous congestion, and herniation of the liver, stomach and transverse colon through an anterior diaphragmatic defect. With liver perfusion threatened, an urgent laparoscopic repair was performed. The stomach and transverse colon were reduced, and the twisted left lobe of the liver was unrotated and reduced into the abdominal cavity. A double-sided synthetic mesh was used to repair the defect. The patient made an uneventful recovery. CONCLUSIONS: This is a novel complication of a patient presenting with abdominal pain with a previous history of pericardial window fenestration. A laparoscopic reduction and repair can be performed safely with excellent postoperative results.

Prophylactic prosthetic reinforcement of midline abdominal incisions in high-risk patients.

BACKGROUND/AIM: Incisional hernia is one of the major elements of morbidity after abdominal surgery, with high incidence in vertical midline abdominal incisions. However, the risk of developing an incisional hernia can be increased due to the patient's related factors; therefore, more consideration has to be given to the choice of incision, wound closure and wound healing to protect against incisional hernia, especially in high-risk patients. In this study, we used prophylactic subfascial non-absorbable mesh reinforcement of midline closure in high-risk patients to detect whether fixing the wound with mesh is risky on a short-term basis and whether it is protective on a long-term basis. PATIENTS AND METHODS: From October 2000 to December 2002, 40 high-risk patients liable to develop postoperative incisional hernia underwent elective abdominal operations through midline abdominal incisions at the Department of Surgery, Gastroenterology and Laparoscopic Unit, Tanta University Hospital, Egypt. They were randomly divided into two groups; group A: patients for whom the midline abdominal incisions were closed by conventional method and reinforced by subfascial polypropylene mesh (20 patients); and group B: patients for whom the midline abdominal incisions were closed by conventional method only (20 patients) with a follow up period of more than 20 months. RESULTS: There was no significant difference (P = 0.075) in both groups regarding the age, sex and the average risk factor. Twenty-three patients (57.5%) presented with more than one risk factor (11 in group A and 12 in group B). The upper midline abdominal incisions were reported in 33 patients (19 upper and 14 extended upper). There was no significant difference between the overall local and systemic complications in both groups (P = 0.4082). However, the subcutaneous seroma and chronic wound pain were greater in patients with prophylactic mesh than those without mesh. One group A patients (5%) and three group B patients (15%) developed postoperative incisional hernia during the follow up period. CONCLUSION: Prophylactic subfascial non-absorbable mesh reinforcement of midline closure in high-risk patients can be used safely and effectively to provide extrinsic strength of the wound without relying too much on the defective development of its own intrinsic strength and to prevent subsequent incisional hernia. There was no risk in the use of the mesh regarding local and systemic complication. However, the final statement should await the outcomes of the long-term follow up of the studied cases.

Optical coherence tomography of cutaneous lupus erythematosus correlates with histopathology.

Diagnosis of cutaneous forms of lupus erythematosus (LE), including chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE), is usually based on characteristic clinical and histopathological findings. We aimed to visualize morphological changes in lesions of cutaneous LE using optical coherence tomography (OCT), and to correlate the OCT findings with histopathology. Six patients with CDLE and five patients with SCLE were investigated. Prior to skin biopsy, OCT assessment was performed on previously marked lesions. The images of OCT and corresponding histology were evaluated side-by-side on the PC screen. The thickening and disruption of the entrance signal in OCT images correlated with the hyperkeratosis which was observed in the histological sections. Atrophy of the epidermis, which was demonstrated by histology, could also be detected in the OCT pictures showing a thinned layer below the entrance signals. On OCT, a patchy reduction of reflectivity was observed in the upper dermis corresponding to dense patchy, partly lichenoid, lymphocytic infiltrates and oedema of the upper dermis. Furthermore, OCT images displayed increased signal-free cavities which histopathologically corresponded to dilated vessels in the upper dermis. All OCT parameters studied significantly (P < 0.05) correlated with histopathological features as indicated by coefficients of correlation ranging from 0.55 to 0.94. OCT enables to demonstrate micromorphological changes in cutaneous LE which correlate with histopathological findings. Nevertheless, the current technique does not allow one to visualize definite diagnostic features of cutaneous LE. However, OCT may be a promising method for objective monitoring of LE activity and treatment effects over time in vivo.

Evaluation of the epidermal refractive index measured by optical coherence tomography.

BACKGROUND/AIMS: It has recently been proposed that the refractive index (RI) measured by means of optical coherence tomography (OCT) may be a valid measure for hydration of skin. In this pilot study, using OCT in vivo, we aimed to investigate the interday variability of RI measurements and acute changes of RI following the application of a moisturizer. METHODS: Twenty healthy Caucasian volunteers were investigated on their forearms using a commercially available OCT system (SkinDex 300, ISIS optronics GmbH, Mannheim, Germany) fitted with an integrated algorithm for the evaluation of the RI. The interday repeatability of the OCT method was determined performing symmetrical measurements on both forearms on day 1, 5, 9, and 13. In order to investigate the acute effect of a moisturizer on RI, OCT assessments were performed before and 10 min after the application of an aqueous lotion with a lipophilic phase. As a control, the contralateral site was investigated in the same way, except for the use of distilled water instead of the lotion. RESULTS: Assessments of interday variability revealed insignificant (P>0.05) variances between the four measurement times as expressed in very small repeatability coefficients (right arm: 0.039; left arm 0.053) and small coefficients of variance (right arm: 1.02%; left arm: 1.38%). With regard to the RIs measured over time, we could not observe significant (P>0.05) differences between the two symmetrical anatomic sites (mean+/-SD of RI: 1.3893+/-0.0142 (right arm); 1.3875+/-0.0192 (left arm)). The acute effect of the moisturizer was indicated by a significant decrease of the RI 5 min after the application of the lotion (1.399+/-0.01 vs. 1.387+/-0.02; difference between means: 0.012; P=0.033; 95% confidence interval: 0.001-0.0023). However the control site treated with distilled water did not show significant differences between the two measurement times (1.387+/-0.013 vs. 1.391+/-0.023; difference between means: -0.004; P=0.57; 95% confidence interval: -0.019-0.011). CONCLUSIONS: In this pilot study, we have demonstrated that RI evaluation via OCT is a promising technique that may be used for the assessment of skin hydration in vivo. However, the direct comparison of OCT with standard methods, ideally such as nuclear magnetic resonance spectroscopy, is necessary.

Epidermal thickness assessed by optical coherence tomography and routine histology: preliminary results of method comparison.

BACKGROUND: Optical coherence tomography (OCT) is a promising non-invasive imaging technique for studying the epidermis and upper dermis in vivo. As proposed previously by Welzel et al. (J Am Acad Dermatol 1997; 37: 958-963), distance measurements between the entrance peak and the second peak of the A-scan seem to correspond to epidermal thickness (ET). However, there is a lack of systematic studies comparing OCT with histology. METHODS: Sixteen healthy subjects were included in this pilot study. OCT assessments were conducted on the upper back. To determine ET by OCT, the distance between the entrance peak and the second peak of the A-scan was calculated (ET-OCT). After OCT measurement a 4 mm punch biopsy was taken on each subject from the same site previously assessed. The maximum thickness of the epidermis (ET-Histo) was determined microscopically using routine histological slices (formalin-paraffin technique, haematoxylin-eosin staining). Correlation and agreement between the two methods were assessed by means of the Pearson correlation procedure and Bland-Altman plots, respectively. RESULTS: ET-Histo was 79.4 +/- 21.9 microm, including a stratum corneum thickness of 20 +/- 12.1 microm. OCT measurements resulted in an ET of 106 +/- 15.4 microm. No correlation between ET-Histo and ET-OCT was observed (r = 0.29, P = 0.27). There was a considerable lack of agreement between histology and OCT measurements as expressed in a high bias of 26.63 microm [95% confidence interval (CI) 14.49-38.77]. Furthermore, the lower 95% limits of agreement were -18.03 microm (95% CI -37.11 to 1.05) and the upper 95% limits of agreement were 71.28 microm (95% CI 52.2-90.36) indicating that ET-OCT may be 71.28 microm above or 18.03 microm below ET-Histo. CONCLUSIONS: Our preliminary data suggest that the above-described OCT algorithm is probably not a valid measure for the evaluation of ET. The second peak of the A-scan seems not to correspond to the dermo-epidermal junction zone, but rather to fibrous structures in the upper dermis. Nevertheless, further systematic comparison studies between OCT and histology are warranted, using different OCT algorithms for ET determination and cryopreparation, which has a higher reliability than the formalin-paraffin technique.

UVA1 and UVB irradiated skin investigated by optical coherence tomography in vivo: a preliminary study.

In histological studies, it has frequently been demonstrated that ultraviolet (UV) exposure, in particular UVB, can induce significant thickening of the viable epidermis and/or stratum corneum. Since skin biopsy alters the original skin morphology and always requires an iatrogenic trauma, we aimed to introduce optical coherence tomography (OCT) in vivo for the investigation of changes of epidermal thickness (ET) following UVA1 and UVB irradiation. Twelve healthy subjects received daily 60 J/cm2 of UVA1 and 1.5 minimal erythema doses UVB on their upper back over 3 consecutive days. Twenty-four hours after the last irradiation, OCT assessments were performed on UV exposed and adjacent nonirradiated control sites. Data of ET as expressed by comparison of the averaged A-scans differed significantly between nonirradiated (94.2 +/- 15.7 microm), UVA1 (105.4 +/- 12.8 microm) and UVB (125.7 +/- 22.1 microm) exposed sites. In comparison to the nonirradiated sites, UVA1 exposed skin showed significant (P = 0.022) increase of ET of 11% and UVB exposed sites a significant (P < 0.001) increase of 25%. ET of UVA1 and UVB exposed skin sites differed significantly (P =0.005). Our results obtained from OCT in vivo measurements confirm data of previous histological studies indicating that not only erythemogenic doses of UVB, but also suberythemogenic doses of UVA1 may have a significant impact on ET. OCT appears to be a promising bioengineering technique for photobiological studies. However, further studies are needed to establish its measurement precision and validity, and to investigate in vivo spectral dependence on UV induced skin changes such as skin thickening.

Human herpesvirus-6 is associated with cytomegalovirus reactivation in liver transplant recipients.

Human herpesvirus-6 (HHV-6) may be a risk factor for cytomegalovirus (CMV) disease in posttransplant patients, possibly through a direct interaction or through a general immunomodulatory effect. To examine this possibility, 88 liver transplant recipients were monitored with serial HHV-6 polymerase chain reaction (PCR), CMV antigenemia, and CMV plasma viral load. HHV-6 infection was defined by a positive PCR of peripheral blood lymphocytes. Forty-eight (54.4%) of 88 patients had at least 1 positive HHV-6 PCR. CMV recurrence was significantly more common in patients with HHV-6 infection (38/48 patients [79. 2%]), compared with recurrence in those without HHV-6 infection (18/40 patients [45%]; P=.001). Peak CMV viral load was 24, 147+/-6799 copies/mL in patients with HHV-6 infection versus 8391+/-4598 copies/mL in patients without HHV-6 infection (P=.001). Symptomatic CMV disease was more common in patients with HHV-6 infection than it was in those without infection (15/48 patients [31. 3%] vs. 4/10 patients [10.0%]; P=.013). In a multivariate analysis including other risk factors for CMV, HHV-6 infection remained an independent risk factor for CMV disease (P=.013; odds ratio, 7.26; 95% confidence interval, 1.52-34.72). HHV-6 is associated with CMV infection and disease, thus supporting an interaction between these viruses.

Refractory anaphylactoid shock potentiated by beta-blockers.

Allergic reactions, including anaphylactoid shock due to contrast material, are not uncommon. However, persistent anaphylactoid shock refractory to conventional therapy is rare. We present a case of refractory anaphylactoid shock during coronary angiography unresponsive to aggressive standard therapy in a patient on beta-blockers. Significant clinical improvement was noted upon administration of glucagon. Since beta-blockers are commonly used in patients with coronary artery disease, this potentially life-threatening complication has to be kept in mind with any procedure involving contrast media in patients on beta-blockers. Immediate access to glucagon by keeping it in the procedure room may be lifesaving in these situations.

Conjunctival rhinosporidiosis. Report of three cases from Zaire.

The authors report three cases of conjunctival rhinosporidiosis from Zaire, two of which are believed to be the first documented in the northeastern part of the country. All patients were males. Two patients were very young children, respectively 5 and 6 years old. The third patient was a 35-year-old man. The diagnosis was based on histopathology which revealed the characteristic features of Rhinosporidium seeberi. Total excision was the elective treatment. The disease recurred eleven months later in one case, probably from local dissemination of the parasite during surgery.