Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

T cell suppression in the bone marrow of visceral leishmaniasis patients: impact of parasite load.

Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo-endothelial system caused by protozoan parasites Leishmania donovani and L. infantum, which are known to induce host T cell suppression. To understand the impact of parasite load on T cell function, the present was focused on parasite load with T cell function in bone marrow of 26 VL patients. We observed significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0·0003) and interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg ) (P = 0·004) in the bone marrow (BM) of patients with high parasite load (HPL) compared with low parasite load (LPL). Concordantly, T effector cells producing interferon (IFN)-γ (P = 0·005) and IL-17A (P = 0·002) were reduced in the BM of HPL. Blocking of Treg -cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)-ß] rescued the effector T cells and their functions. However, it was observed that TGF-ß levels were dominant, favouring Treg cell differentiation. Furthermore, the low ratio of IL-6/TGF-ß favours the suppressive milieu in HPL patients. Here we show the change in levels of various cytokines with the parasitic load during active VL, which could be helpful in devising newer immunotherapeutic strategies against this disease.

Programmed death-1+ T cells inhibit effector T cells at the pathological site of miliary tuberculosis.

Optimal T cell activation is vital for the successful resolution of microbial infections. Programmed death-1 (PD-1) is a key immune check-point receptor expressed by activated T cells. Aberrant/excessive inhibition mediated by PD-1 may impair host immunity to Mycobacterium tuberculosis infection, leading to disseminated disease such as miliary tuberculosis (MTB). PD-1 mediated inhibition of T cells in pulmonary tuberculosis and TB pleurisy is reported. However, their role in MTB, particularly at the pathological site, remains to be addressed. The objective of this study was to investigate the role of PD-1-PD-ligand 1 (PD-L1) in T cell responses at the pathological site from patients of TB pleurisy and MTB as clinical models of contained and disseminated forms of tuberculosis, respectively. We examined the expression and function of PD-1 and its ligands (PD-L1-PD-L2) on host immune cells among tuberculosis patients. Bronchoalveolar lavage-derived CD3 T cells in MTB expressed PD-1 (54·2 ± 27·4%, P ≥ 0·0009) with significantly higher PD-1 ligand-positive T cells (PD-L1: 19·8 ± 11·8%; P ≥ 0·019, PD-L2: 12·6 ± 6·2%; P ≥ 0·023), CD19+ B cells (PD-L1: 14·4 ± 10·4%; P ≥ 0·042, PD-L2: 2·6 ± 1·43%; not significant) and CD14+ monocytes (PD-L1: 40·2 ± 20·1%; P ≥ 0·047, PD-L2: 22·4 ± 15·6%; P ≥ 0·032) compared with peripheral blood (PB) of MTB and healthy controls. The expression of PD-1 was associated with a diminished number of cells producing effector cytokines interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2 and elevated apoptosis. Locally accumulated T cells were predominantly PD-1+ -PD-L1+ , and blocking this pathway restores the protective T cell response. We conclude that M. tuberculosis exploits the PD-1 pathway to evade the host immune response by altering the T helper type 1 (Th1) and Th2 balance at the pathological site of MTB, thereby favouring disease dissemination.

Exonal switch down-regulates the expression of CD5 on blasts of acute T cell leukaemia.

To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T-ALL) have not been studied closely. We observed a significant reduction in surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non-leukaemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukaemic T cells. A total of 250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flow cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T origin. Amplification of early region of E1A and E1B transcripts of CD5 was correlated with the levels of surface and intracellular expression of CD5 protein. Functional studies were performed to show the effect of CD5 blocking on interleukin IL-2 production and survival of leukaemic and non-leukaemic cells. Lack of expression of sCD5 on T-ALL blasts was correlated closely with predominant transcription of exon E1B and significant loss of exon E1A of the CD5 gene, which is associated with surface expression of CD5 on lymphocytes. High expression of E1B also correlates with increased expression of cytoplasmic CD5 (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading possibly to their increased survival at 48 h. Our study provides understanding of the regulation of CD5 expression on leukaemic T cells, and may help in understanding the molecular mechanism of CD5 down-regulation.

The development and evaluation of a community-based clinical diagnosis tool and treatment regimen for postpartum sepsis in Bangladesh and Pakistan.

BACKGROUND: Postpartum sepsis accounts for most maternal deaths between three and seven days postpartum, when most mothers, even those who deliver in facilities, are at home. Case fatality rates for untreated women are very high. Newborns of ill women have substantially higher infection risk. METHODS/DESIGN: The objectives of this study are to: (1) create, field-test and validate a tool for community health workers to improve diagnostic accuracy of suspected puerperal sepsis; (2) measure incidence and identify associated risk factors and; (3) describe etiologic agents responsible and antibacterial susceptibility patterns. This prospective cohort study builds on the Aetiology of Neonatal Infection in South Asia study in three sites: Sylhet, Bangladesh and Karachi and Matiari, Pakistan. Formative research determined local knowledge of symptoms and signs of postpartum sepsis, and a systematic literature review was conducted to design a diagnostic tool for community health workers to use during ten postpartum home visits. Suspected postpartum sepsis cases were referred to study physicians for independent assessment, which permitted validation of the tool. Clinical specimens, including urine, blood, and endometrial material, were collected for etiologic assessment and antibiotic sensitivity. All women with puerperal sepsis were given appropriate antibiotics. DISCUSSION: This is the first large population-based study to expand community-based surveillance for diagnoses, referral and treatment of newborn sepsis to include maternal postpartum sepsis. Study activities will lead to development and validation of a diagnostic tool for use by community health workers in resource-poor countries. Understanding the epidemiology and microbiology of postpartum sepsis will inform prevention and treatment strategies and improve understanding of linkages between maternal and neonatal infections.

Diagnosis of extra pulmonary tuberculosis: An update on novel diagnostic approaches.

Tuberculosis (TB) remains a major global public health problem worldwide. Though Pulmonary TB (PTB) is mostly discussed, one in five cases of TB present are extrapulmonary TB (EPTB) that manifests conspicuous diagnostic and management challenges with respect to the site of infection. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, pauci-bacillary nature of the disease, and lack of laboratory facilities in the resource limited settings. Culture, the classical gold standard for the diagnosis of tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. Other than culture, several other tests are available but their feasibility and effciacy for the detection of EPTB is still the matter of interest. We need more specific and precise test/s for the various forms of EPTB diagnosis which can easily be applied in the routine TB control program is required. A test that can contribute remarkably towards improving EPTB case detection reducing the morbidity and mortality is the utmost requirement. In this review we described the scenario of molecular and other noval methods available for laboratory diagnosis of EPTB, and also discussed the challenges linked with each diagnostic method. This review will make the readers aware of new emerging diagnostic techniques in the field of EPTB diagnosis. They can make an informed decision to choose the appropriate one according to the test availability, their clinical settings and financial considerations.

Stress resilience in patients with drug-resistant TB.

BACKGROUND: The worldwide increase in drug-resistant pulmonary TB (DR-PTB) has a significant impact on patient´s physical and mental health. The objective of this study is to assess the stress resilience of DR-PTB patients along with the factors associated with it.METHODS: A total of 385 adult DR-PTB patients with multidrug-resistant (MDR) and pre-extensive drug-resistant (pre-XDR) TB admitted to the National Institute of Diseases of the Chest Hospital (Dhaka, Bangladesh) between January 2020 and March 2021 were conveniently recruited. Resilience data were collected using a validated Stress Resilience Scale (RS 25) questionnaire.RESULTS: The mean resilience scores were significantly higher for patients with MDR-PTB than those with pre-XDR-PTB (P = 0.02). A majority of the MDR-PTB (77.0%) and pre-XDR-PTB (65.1%) patients belonged to the ≤45 years age group. Multiple linear regression revealed that sex (P < 0.001), level of education (P < 0.001), employment status (P = 0.003) and presence of asthma (P = 0.010) were significantly associated with stress resilience.CONCLUSION: We observed that stress resilience significantly differed between patients with MDR-PTB and those with pre-XDR-PTB based on sociodemographic characteristics.

Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation.

BACKGROUND: Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients. OBJECTIVE: This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. METHODS: Thirty-three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders. RESULTS: The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant (P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders (P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders. CONCLUSION: Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation.

Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception.

PURPOSE: Standard semen parameters are poor predictors of fertility potential. To date, apart from, paternal karyotyping sperm factors are not evaluated in recurrent pregnancy loss (RPL), only recent studies have emphasized the role of sperm factors in early embryonic development as sperm transcribes genes critical for early embryonic development. Sperm DNA integrity is useful diagnostic and prognostic marker and has clinical implications in idiopathic recurrent pregnancy loss (iRPL) following spontaneous conception. The aim of this study was to assess DNA integrity in cases experiencing iRPL following spontaneous conception. METHODS: Semen samples from 45 patients and 20 controls were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was used to measure DNA fragmentation index (DFI). RESULTS: By applying receiver operating curve (ROC) analysis, sperm DFI of approximately 26 % was found in male partner of couples experiencing iRPL. CONCLUSIONS: Our data indicate that sperm from men with a history of iRPL have a higher percentage of DNA damage as compared to control group, and this can explain pregnancy loss in these patients. Men with higher DFI are infertile whereas men with lower DFI (26 %) are able to conceive but experience recurrent pregnancy loss. Thus it is important to evaluate sperm DFI in couples experiencing iRPL to understand exact aetiology of RPL and determine prognosis and management.

Intracellular cytokine expression in invasive fungal sinusitis and its impact on patient outcome.

BACKGROUND: Cell-mediated immunity plays an important role in host defence against fungal pathogens, regulated by differentiation of lymphocytes towards T-helper 1 or 2 cells. This study reports intracellular cytokine variation in terms of invasive fungal sinusitis type and outcome. METHODS: The mononuclear leukocytes of 15 patients with invasive fungal sinusitis (mucormycosis in 8, aspergillus in 7) were stained with antibodies against intracellular cytokines, after fungal antigen stimulation and culture, and immunophenotyped. Patients were followed up for six months, with clinical course categorised as improvement, worsening or death. RESULTS: The mean percentages of mononuclear cells producing interleukins 4, 5, 10 and 12, and interferon-γ, in the mucormycosis group were 0.575, 0.284, 8.661, 4.460 and 1.134, respectively, while percentages in the aspergillosis group were 0.233, 0.492, 4.196, 4.466 and 1.533. Cells producing interleukin 4 and 10 were higher in the mucormycosis group, while those producing interleukin-12 and interferon-γ were lower. Cells producing interleukins 4 and 12 were higher in patients with a poor outcome (p-values of 0.0662 and 0.0373, respectively), while those producing interferon-γ were lower (p = 0.0864). CONCLUSION: Adaptive cell-mediated immunity is expressed differently in two categories of invasive fungal sinusitis, and the cytokine expression pattern is related to prognosis.

Enrichment of invariant natural killer T cells in the bone marrow of visceral leishmaniasis patients.

Lipid antigens of Leishmania donovani like lipophosphoglycans are shown as a potent ligand for the activation of invariant natural killer T (iNKT) cells. It is reported that activation of iNKT cells augments the disease pathology in experimental visceral leishmaniasis (VL). In this study, we demonstrate the enrichment of iNKT cells in the bone marrow, one of the disease sites among patients with VL.

High concentration of adenosine in human visceral leishmaniasis despite increased ADA and decreased CD73.

Absence of an effective Th-1 response has been demonstrated as a major cause for the disease pathology among patients with visceral leishmaniasis (VL). Defining strategies to prevent the development of Th-2 response and/or initiate/activate effective Th-1 response may be of help to reduce the growing incidence of drug unresponsiveness. Adenosine, which is considered as an endogenous anti-inflammatory agent is generated in injured/inflamed tissues by the enzymatic catabolism of adenosine triphosphate (ATP), and it suppresses inflammatory responses of essentially all immune cells. The extracellular adenosine-producing pathway comprises two major enzymes CD39 (ATP → ADP → AMP) and CD73 (AMP → Adenosine). In contrast, the adenosine-degrading pathway contains only one major enzyme adenosine deaminase (ADA). Our study shows high concentration of adenosine in diseased condition, varying expression of enzyme involved in adenosine-producing (CD73↓) and adenosine-degrading (ADA↑) pathways. These are less studied in infections like VL but are very important in terms of endogenous regulation of immune response among patients.

A pilot study on the prevalence of sexually transmitted infections among clients of brothel-based female sex workers in Jessore, Bangladesh.

The prevalence of bacterial sexually transmitted infections among clients of female sex workers (FSWs) was studied. A total of 156 condoms were collected from clients of 13 sex workers during three consecutive days. Condoms used by clients of FSWs were collected and DNA was extracted from the seminal fluid and used for the diagnosis of Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis by polymerase chain reaction. The prevalence of N. gonorrhoeae, C. trachomatis and T. vaginalis among clients of FSWs was 4.5% (7/156), 2.5% (4/156) and 7% (11/156), respectively.

CD4+ CD25+ FOXP3+ T cell frequency in the peripheral blood is a biomarker that distinguishes intestinal tuberculosis from Crohn's disease.

BACKGROUND: Distinguishing between Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) has been a challenging task for clinicians due to their similar presentation. CD4+FOXP3+ T regulatory cells (Tregs) have been reported to be increased in patients with pulmonary tuberculosis. However, there is no such data available in ITB. The aim of this study was to investigate the differential expression of FOXP3+ T cells in patients with ITB and CD and its utility as a biomarker. METHODS: The study prospectively recruited 124 patients with CD, ITB and controls: ulcerative colitis (UC) and patients with only haemorrhoidal bleed. Frequency of CD4+CD25+FOXP3+ Tregs in peripheral blood (flow cytometry), FOXP3 mRNA expression in blood and colonic mucosa (qPCR) and FOXP3+ T cells in colonic mucosa (immunohistochemistry) were compared between controls, CD and ITB patients. RESULTS: Frequency of CD4+CD25+FOXP3+ Treg cells in peripheral blood was significantly increased in ITB as compared to CD. Similarly, significant increase in FOXP3+ T cells and FOXP3 mRNA expression was observed in colonic mucosa of ITB as compared to CD. ROC curve showed that a value of >32.5% for FOXP3+ cells in peripheral blood could differentiate between CD and ITB with a sensitivity of 75% and a specificity of 90.6%. CONCLUSION: Phenotypic enumeration of peripheral CD4+CD25+FOXP3+ Treg cells can be used as a non-invasive biomarker in clinics with a high diagnostic accuracy to differentiate between ITB and CD in regions where TB is endemic.

HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.

In this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1. The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults.

Urethral duplication in association with anorectal malformation.

Urethral duplication is an uncommon congenital anomaly, not often reported, which may be partial or complete. Anorectal malformations are not as uncommon and they may be associated with a host of associated anomalies. However, the association of urethral duplication with anorectal malformation is rare; this report describes two such cases. In one case the intervening septum could be incised endoscopically and in the other case the duplicated urethra was excised.

Vdelta1 and Vdelta2 gammadelta T cells express distinct surface markers and might be developmentally distinct lineages.

We report here that the two major types of gammadelta T cells found in human blood, Vdelta1 and Vdelta2, were found to have markedly different phenotypes. Vdelta2 cells had a phenotype typical of most alphabeta T cells in blood; i.e., they were CD5(+), CD28(+), and CD57(-). In contrast, Vdelta1 cells tended to be CD5(-/dull), CD28(-), and CD57(+). Furthermore, although Vdelta1 T cells appeared to be "naive" in that they were CD45RA(+), they were CD62L(-) and on stimulation uniformly produced interferon-gamma, indicating that they are in fact memory/effector cells. This phenotype for Vdelta1 cells was similar to that of intestinal intraepithelial lymphocytes, a subset that can develop in the absence of the thymus. We suggest that the Vdelta1 and Vdelta2 T cell subsets represent distinct lineages with different developmental pathways. The disruption of the supply of normal, thymus-derived T cells in HIV-infected individuals might be responsible for the shift in the Vdelta2/Vdelta1 ratio that occurs in the blood of individuals with HIV disease.

Urodynamics-based evidence for the beneficial effect of imipramine on valve bladders in children.

AIMS: In an era, in which valve bladder is recognised as perhaps the single most important determinant of long-term outcome in patients with posterior urethral valves (PUV), an insight into the etiopathogenesis and management of valve bladders is warranted. The present study was designed to evaluate bladder dysfunction in PUV and to assess the response to imipramine in these patients, both subjectively and objectively, by serial urodynamic studies (UDS). METHODS: From 1998-2001, 30 patients with PUV who had documented bladder dysfunction on UDS were studied. Patients with non-compliant or unstable bladders were treated with imipramine (1.5 - 2 mg/kg). All the patients in the present study were 5 years or older and hence old enough to be toilet trained. Assessment of continence and side effects of the drug was done after 3 months and repeat UDS were done at 3-6 months, 1 and 2 years. RESULTS: On the basis of initial treatment, the patients were divided into 2 groups; a fulguration group (n = 10, 33.3 %) and a vesicostomy group (n = 20, 66.6 %). Symptomatic voiding dysfunction was present in 27 of the 30 patients (90 %). Two patterns of urodynamic abnormalities were noted in the present study; 1) unstable bladders with single or multiple uninhibited contractions (18/30 patients, 60 %), and 2) small capacity, hypocompliant, hypertonic bladder (12/30 patients, 40 %). Post imipramine therapy significant symptomatic improvement was noted in 16/30 patients. On serial UDS, there was a 18-20 % increase in maximum cystometric capacity (MCC) and 30-35 % increase in pressure specific bladder volume (PSBV) following one year of imipramine therapy in 16/30 patients and 11/30 patients, respectively. 4 patients failed to show any improvement in MCC and PSBV with imipramine, they had been initially diverted with vesicostomy and later required augmentation cystoplasty. CONCLUSION: Unstable bladders and those with marginal bladder capacity and compliance showed the best response to imipramine therapy. Fibrotic, small capacity, hypertonic bladders are less responsive to imipramine. However, a trial of imipramine therapy is still warranted in these patients, as only 4/12 (33.3 %) patients with fibrotic hypertonic bladders failed to show any response and ultimately required augmentation cystoplasty. Imipramine qualifies as an effective and cheap drug for valve bladders.

Reconstitution of naïve T cells and type 1 function after autologous peripheral stem cell transplantation: impact on the relapse of original cancer.

BACKGROUND: Phenotypic and functional reconstitution of T cells after peripheral blood stem cell transplantation (PBSCT) and its influence on posttransplant immune status is important in terms of immune surveillance and relapse of original cancer. We investigated the relationship between the dominant immune reconstitution pathway and the immune surveillance. We also tested the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy. METHODS: Immunophenotyping of naïve and memory T cells was performed by flow cytometry on patients who underwent PBSCT for various cancers. Cytokine production by peripheral memory helper (CD4) and cytotoxic (CD8) T cells was investigated at various pretransplant and posttransplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). Data on T-cell subsets and polarized cytokines gamma-interferon (Ifn) and interleukin 4 produced by memory T cells were compared with that of healthy controls. RESULTS: The reconstitution of naïve T cells and gamma-Ifn-producing memory cells was significantly lower in patients who experienced relapse of original cancer within 1 year of PBSCT compared to those who showed no signs of relapse even after 2 years and compared to normal subjects. The results indicate that efficient reconstitution of naïve T cells and type 1 function of memory T cells are important in maintaining T-cell repertoire diversity after PBSCT. It also confers appropriate levels of immune surveillance against diverse neoantigens that evolve from residual tumor burden. The data reveal that chemotherapy-induced thymic injuries may impair regeneration of naïve cells that result in a naivopenic state in a susceptible host. CONCLUSIONS: The study highlights the importance of naïve T-cell reconstitution and points towards cell replacement strategies for improving immune surveillance after PBSCT.

Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis.

UNLABELLED: Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development.