Progressive Familial Intrahepatic Cholestasis-2 Mimicking Non-accidental Injury.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of disorders characterized by defective secretion of bile acids or transport defects resulting in progressive cholestasis. These disorders usually present during infancy or childhood and are associated with progressive liver disease. PFIC is estimated to affect 1 in 50,000-100,000 births, with PFIC-2 representing half of PFIC cases. PFIC-2 presents with hepatosplenomegaly, jaundice, pruritus, fat-soluble vitamin deficiencies, and growth failure. Laboratory findings include low/normal gamma glutamyl transpeptidase levels and elevated bilirubin, transaminases, and alpha-fetoprotein levels. In this report, we present a case of PFIC-2 presenting with severe coagulopathy, bruising, subcutaneous hematomas, and acute-onset anemia.

Measurement of visual functioning following first and second eye cataract surgery using Vision-Related Activity Limitation Item Bank.

PURPOSE: This study aims to compare visual functioning (VF) after first or second eye cataract surgery using the vision-related activity limitation (VRAL) item bank. METHODS: This prospective, interventional study included 787 patients (mean age, 58.2 years) with cataract undergoing cataract surgery (first eye surgery with/out ocular comorbidity, second eye surgery with/out ocular comorbidity) at a tertiary eye care center, South India, who were administered the item bank pre- and at 6 weeks postoperatively to assess change in VF. Rasch analysis was used to estimate VF at both time points, and responsiveness to cataract surgery was calculated as effect size (ES) which was interpreted as small (≤ 0.2), moderate (0.3-0.7), and large (≥ 0.8). RESULTS: Mean best-corrected logMAR VA in surgical eye improved significantly postoperatively compared to preoperative VA (0.20 ± 0.40 vs. 1.19 ± 0.96; P < 0.0001) across all groups. Patients reported significant and large improvements in VF postoperatively across all groups: largest ES for first eye surgery without comorbidity (1.87 [95% CI, 1.61, 2.13]) and smallest for second eye without ocular comorbidity (1.55 [95% CI, 1.22, 1.88]). Compared to patients undergoing second eye surgery, first eye surgery patients reported significantly lower VF preoperatively (-0.72 ± 2.39 vs. 0.17 ± 2.34 logits; P < 0.0001), and a larger change in VF postoperatively (3.71 ± 2.33 logits vs. 4.27 ± 2.83 vs.; P = 0.004). CONCLUSIONS: Cataract surgery resulted in large and significant improvements in VF, regardless of ocular comorbidity and first or second eye surgery. The VRAL item bank is a useful tool to measure responsiveness to cataract surgery.

Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5).

Maturity-onset diabetes of the young type 5 (MODY 5) is characterized by a single gene mutation in the HNF1B gene. This frequently leads to insulin resistance and presents as young-onset diabetes. Other manifestations can occur in organs expressing hepatocyte nuclear factor-1 beta. This case report highlights family members with MODY 5 presenting with increased liver enzymes with no etiology. The siblings and their mother had a point mutation p.Arg235Trp in HNF1B gene located at 17q12. This variant is associated with autosomal dominant MODY 5 with renal cysts also known as renal cysts and diabetes syndrome.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Organ-Specific Comorbidities Are Associated With Distinct Complications After Liver Transplantation for Biliary Atresia.

Although transplant outcomes for biliary atresia (BA) have improved, there are few data to predict the risk of specific posttransplant complications. We therefore defined the impact of comorbidities in BA on posttransplant outcomes. Patients enrolled in the Society of Pediatric Liver Transplantation registry from 2011 to 2019 (n = 1034) were grouped by comorbidities of >1.0% incidence: any supplemental feeding, dialysis, other abdominal surgery (not Kasai portoenterostomy [KPE]), hepatopulmonary syndrome, and cardiac disease requiring intervention. Demographic and outcome data were compared using the Kruskal-Wallis, chi-square, and log-rank tests. Cox proportional hazards models and binary logistic regression were performed for modeling. Patients with BA with comorbidities comprised 77% (n = 799) of our cohort and had evidence of greater medical acuity, including higher calculated Pediatric End-Stage Liver Disease scores and hospitalizations in the intensive care unit before transplant (P < 0.001 for both) versus those without comorbidities. After transplant, patients with BA with comorbidities had more graft loss (P = 0.02), longer initial hospitalization and intubation (P < 0.001 for both), and increased rates of reoperation (P = 0.001) and culture-proven infection (P < 0.001) within 30 days after transplant. Only patients with BA with comorbidities on supplemental feed had increased rates of patient death (P = 0.02). Multivariate analysis identified lower z weight and higher creatinine as risk factors for graft and patient loss in patients with BA with comorbidities. Prior KPE was protective against culture-proven infection and vascular complications within 30 and 90 days, respectively. Patients with BA with comorbidities have evidence of higher medical acuity at transplant and reduced graft survival; however, they overall did not experience greater incidence of patient death. Our data provide organ-system-specific data to risk-stratify patients with BA and posttransplant outcomes.

Predictors of Unplanned Hospitalizations Among Older Adults Receiving Cancer Chemotherapy.

PURPOSE: Hospitalizations during cancer treatment are costly, can impair quality of life, and negatively affect therapy completion. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy. METHODS: This is a secondary analysis of a multisite cohort study (N = 750) of patients ≥ 65 years of age evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity. The primary outcome of this analysis was unplanned hospitalizations during treatment; the secondary outcome was length of stay (LOS) of the first hospitalization. Independent variables included pretreatment GA measures, laboratory values, cancer type and stage, and treatment intensity characteristics. We used logistic regression to estimate the odds of hospitalization and generalized linear models for LOS in multivariable analyses. RESULTS: The sample median age was 72 years (range, 65-94 years); 59% had stage IV disease. At least one unplanned hospitalization occurred in 193 patients (25.7%) during receipt of chemotherapy. In multivariable analyses controlling for cancer type, the following baseline characteristics were significantly associated with increased odds of hospitalization: needing help bathing or dressing (odds ratio [OR], 1.8; 95% CI, 1.0 to 3.1), polypharmacy (≥ 5 meds) (OR, 1.6; 95% CI, 1.1 to 2.4), more comorbid conditions (OR, 1.1; 95% CI, 1.0 to 1.3), availability of someone to take them to the doctor (OR, 2.0; 95% CI, 1.0 to 4.1), CrCl < 60 mL/min (OR, 1.7; 95% CI, 1.1 to 2.4), and albumin < 3.5 g/dL (OR, 1.8; 95% CI, 1.2 to 2.8). In multivariable analyses, older age, self-reported presence of liver or kidney disease, living alone and depressive symptoms were associated with longer LOS. CONCLUSION: Readily available GA variables and laboratory data, but not age, were associated with unplanned hospitalizations among older adults receiving chemotherapy. If validated, these data can inform prediction models and the design of interventions to decrease unplanned hospitalizations.

Improved Outcomes for Liver Transplantation in Patients with Biliary Atresia Since Pediatric End-Stage Liver Disease Implementation: Analysis of the Society of Pediatric Liver Transplantation Registry.

OBJECTIVE: To identify changes in demographics, outcomes, and risk factors for patient and graft loss in patients with biliary atresia undergoing liver transplantation since Pediatric End-Stage Liver Disease implementation (2002). STUDY DESIGN: Demographics and outcomes were compared between patients enrolled in the Society of Pediatric Liver Transplantation registry before (n = 547) and after (n = 1477) 2002. Kruskal-and χ2 Wallis tests identified significant differences between eras. Risk factors for patient and graft loss after 2002 were determined by Cox regression model analysis of time to event data. RESULTS: Significant patient differences after 2002 support increasing disease severity including more status 1 patients and those with a derived Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score of greater than 30 awaiting transplant. Both patient and graft survival improved after 2002 from 90% to 97% and 81% to 90%, respectively (primary transplant; P < .0001). Significant differences in complications within 30 days included reduced relisting for transplant, rejection, culture-positive infection, repeat operation, hepatic artery thrombosis, portal vein thrombosis, and death/transplant before discharge. Multivariable analysis identified deceased technical variant vs whole graft and retransplantation predictive for patient death, hazard ratios of 4.041 and 8.308, respectively. Deceased technical variant vs whole graft (hazard ratio, 1.963) and donor age 0-5 months vs 1-17 years (hazard ratio, 5.525) were risk factors for graft loss. CONCLUSIONS: The overall outcomes of patients receiving liver transplantation for patients with biliary atresia have improved since 2002 despite evidence of increased disease severity at the time of transplant. Risk factors impacting post-transplant morbidity and mortality in patients with biliary atresia are now mainly surgical including donor variables.

Diffraction by ruled gratings with variable spacing: fundamental method of intensity calculation.

A regular diffraction grating produces intensity patterns that combine waves coming through equispaced slits, so that the waves emerging from any two neighboring slits have identical phase differences. In this paper, we calculate the degradation in the intensity pattern when the grating has irregular spacing. The model of randomness considers the grating spacing and openings as being created by a "random walk." The resolving power of the grating is evaluated in relation to the D lines of sodium. It is shown that as the number of rulings increases, the uniformity of their spacing becomes more important in precision spectroscopic measurements, such as in astrophysical spectroscopy.

Psychometric Properties of an Indian Translation of the Vision-related Activity Limitation Item Bank in Cataract.

SIGNIFICANCE: The Indian translated and culturally adapted version of the vision-related activity limitation (VRAL) item bank is a validated instrument to assess the difficulty in performing daily activities by cataract patients and can also be used to capture self-reported changes in ability to perform daily activities after cataract surgery. PURPOSE: The purpose of this study was to document (a) translation, cross-cultural adaptation of VRAL item bank into an Indian language, and (b) its validation using Rasch analysis in a South Indian cataract population. METHODS: At the first stage, a translated Indian version of VRAL item bank was produced using recommended procedures. At the second stage, Rasch analysis was performed to investigate its psychometric properties in 787 cataract patients (mean age, 58.2 years; mean ± SD visual acuity [logMAR], 1.19 ± 0.96 at baseline in eye for surgery) including comparison with the original version. RESULTS: Post-translation equivalence of meaning was achieved, but some English phrases required cross-cultural adaptation. Subsequently, all items were appropriate for the Indian culture, and VRAL item bank demonstrated excellent measurement precision (7.39). Dimensionality assessment suggested that VRAL construct may contain other dimensions such as self-care and visual search, and mobility. Self-care and visual search formed a unidimensional measure but was highly correlated with main VRAL dimension, and the removal of its items weakened precision of the main VRAL dimension measurement. Taken together, evidence favored retaining self-care and visual search items in a larger VRAL item bank. Mobility subscale lacked adequate measurement precision, so it was not examined further; again, items were retained in VRAL scale because they strengthened its measurement properties. Majority of items (99%) did not demonstrate notable differential item functioning (>1.0 logit) by presenting visual acuity (median, 0.20 logMAR) in the better-seeing eye. CONCLUSIONS: Items in the translated Indian VRAL item bank measure the same construct as the English version and fulfilled the psychometric requirements for use in cataract patients.

DECT evaluation of noncalcified coronary artery plaque.

PURPOSE: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (ρ(e)) and the effective atomic number (Z(eff)) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. METHODS: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (ρ(e), Z(eff)) lie in the range of (2.65 × 10(23) ≤ ρ(e) ≤ 3.64 × 10(23)/cm(3)) and (6.80 ≤ Z(eff) ≤ 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V1) and HU(V2), with V1,V2 = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (ρ(e), Z(eff)) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (ρ(e), Z(eff)) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. RESULTS: The authors find that the calibration gives ρ(e) with an accuracy of ±3.5% while Z(eff) is found within ±1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques are practically nonexistent, and microcalcification, as observed in histopathology, has to be taken into account to explain the nature of the observed (ρ(e), Z(eff)) data. This also enables us to judge the composition of the plaque in terms of basic model which considers the plaque to be composed of fibres, lipids, and microcalcification. CONCLUSIONS: This simple and reliable method has the potential as an effective modality to investigate the composition of noncalcified coronary artery plaques and thus help in their characterization. In this inversion method, (ρ(e), Z(eff)) of the scanned sample can be found by eliminating the effects of the CT machine and also by ensuring that the determination of the two unknowns (ρ(e), Ze(ff)) does not interfere with each other and the nature of the plaque can be identified in terms of a three component model.

Intensity profile of light scattered from a rough surface.

We present in this paper, approximate analytical expressions for the intensity of light scattered by a rough surface, whose elevation ξ(x,y) in the z-direction is a zero mean stationary Gaussian random variable. With (x,y) and (x',y') being two points on the surface, we have 〈ξ(x,y)〉=0 with a correlation, 〈ξ(x,y)ξ(x',y')〉=σ2g(r), where r=[(x-x')2+(y-y')2]1/2 is the distance between these two points. We consider g(r)=exp[-(r/l)ß] with 1≤ß≤2, showing that g(0)=1 and g(r)→0 for r≫l. The intensity expression is sought to be expressed as f(vxy)={1+(c/2y)[vx2+vy2]}-y, where vx and vy are the wave vectors of scattering, as defined by the Beckmann notation. In the paper, we present expressions for c and y, in terms of σ, l, and ß. The closed form expressions are verified to be true, for the cases ß=1 and ß=2, for which exact expressions are known. For other cases, i.e., ß≠1, 2 we present approximate expressions for the scattered intensity, in the range, vxy=(vx2+vy2)1/2≤6.0 and show that the relation for f(vxy), given above, expresses the scattered intensity quite accurately, thus providing a simple computational methods in situations of practical importance.

Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons.

Transplantation is common in clinical practice where there is availability of the tissue and organ. In the case of neurodegenerative disease such as Parkinson's disease (PD), transplantation is not possible as a result of the non-availability of tissue or organ and therefore, cell therapy is an innovation in clinical practice. However, the availability of neuronal cells for transplantation is very limited. Alternatively, immortalized neuronal progenitors could be used in treating PD. The neuronal progenitor cells can be differentiated into dopaminergic phenotype. Here in this article, the current understanding of the molecular mechanisms involved in the differentiation of dopaminergic phenotype from the neuronal progenitors immortalized with SV40 LT antigen is discussed. In addition, the methods of generating dopaminergic neurons from progenitor cells and the factors that govern their differentiation are elaborated. Recent advances in cell-therapy based transplantation in PD patients and future prospects are discussed.

A tropical oviparous lizard, Calotes versicolor, exhibiting a potentially novel FMFM pattern of temperature-dependent sex determination.

Among squamate reptiles, lizards exhibit an impressive array of sex-determining modes viz. genotypic sex determination, temperature-dependent sex determination, co-occurrence of both these and those that reproduce parthenogenetically. The oviparous lizard, Calotes versicolor, lacks heteromorphic sex chromosomes and there are no reports on homomorphic chromosomes. Earlier studies on this species presented little evidence to the sex-determining mechanism. Here we provide evidences for the potential role played by incubation temperature that has a significant effect (P < 0.01) on gonadal sex and sex ratio. The eggs were incubated at 14 different incubation temperatures. Interestingly, 100% males were produced at low (25.5 ± 0.5 ° C) as well as high (34 ± 0.5 ° C) incubation temperatures and 100% females were produced at low (23.5 ± 0.5 ° C) and high (31.5 ± 0.5 ° C) temperatures, clearly indicating the occurrence of TSD in this species. Sex ratios of individual clutches did not vary at any of the critical male-producing or female-producing temperatures within as well as across the seasons. However, clutch sex ratios were female- or male-biased at intermediate temperatures. Thermosensitive period occurred during the embryonic stages 30-33. Three pivotal temperatures operate producing 1:1 sex ratio. Histology of gonad and accessory reproductive structures provide additional evidence for TSD. The sex-determining pattern, observed for the first time in this species, that neither compares to Pattern I [Ia (MF) and Ib (FM)] nor to Pattern II (FMF), is being referred to as FMFM pattern of TSD. This novel FMFM pattern of sex ratio exhibited by C. versicolor may have an adaptive significance in maintaining sex ratio.

Influence of surgical technique on axillary seroma formation: a randomized study.

The aim of this study was to evaluate the influence of surgical technique in the form of electrocautery and suction drains on seroma formation following surgery for breast cancer. A prospective randomized study was carried out. One hundred and sixty patients with breast cancer who underwent surgery were allocated to four arms using a 2 x 2 factorial design. This method enabled us to evaluate the independent effect of two different causative factors on the incidence of postoperative seroma formation using a single dataset with limited numbers. The main outcome measure was postoperative seroma formation defined as a postoperative axillary collection requiring more than one aspiration after removal of the drain. The incidence of seroma in our institution is 90%. Incidence of postoperative seroma was 88.3% if electrocautery was used, which reduced to 82.2% if surgery was carried out using scissors for dissection and ligatures for haemostasis (P = 0.358). There was no influence on the incidence of seroma formation whether suction drain (84.6%) or corrugated drains (86.1%) were used (P = 0.822). The use of electrocautery in axillary dissection does not adversely affect postoperative seroma formation after surgery for breast cancer. The use of different drainage techniques has no bearing on the postoperative seroma formation. The surgical technique has no influence on the rate of seroma formation after surgery for breast cancer.

Scattering of light by a periodic structure in the presence of randomness. V. Detection of successive peaks in a periodic structure.

We address the problem of detecting periodic structures hidden behind roughness. We have shown that if r(0) is the coherence length of the scattered radiation, due to the random part of the surface, and Lambda is the wavelength of the periodic part of the surface, then with a matched filtering method that we introduce, and by using simple computations with the intensity data, it is possible to detect the hidden first-order peak even when (r(0)/Lambda) approximately 0.11. Here we advance the method to bring out very weak second-order peaks, which we demonstrate for what we believe is the first time. The unmistakable presence of both the first- and second-order peaks, which have identical shapes as the zeroth-order peak, is strong evidence of the hidden periodicity and serves as a novel method for the detection of weak periodicities hidden behind strong randomness.

Breast conservation surgery without pre-operative mammography--a definite feasibility.

Mammography is mandatory before breast conservation. Its limited availability in developing countries has discouraged surgeons in rural areas from practicing breast conservation. We analyzed the database of breast surgeries at our institute to investigate whether breast conservation could be safely performed if clinically feasible without the use of mammography. If mammography had not been performed in the 735 patients undergoing surgery, breast conservation could have been erroneously performed in 38 (5.17%) patients; 13 had impalpable mammographic multicentricity and 25 had extensive microcalcifications. A detailed analysis showed that this error in decision would have been detected and rectified in each of the above patients before commencement of radiotherapy. We conclude that although mammography cannot be totally excluded from the treatment algorithm for palpable breast cancer, conservative surgery can be offered in clinically suitable cases even if pre-operative mammography is not available due to limited resources in the developing world.

Efficacy of HCG and ovarian steroids in the maintenance/interruption of pregnancy in-albino rats.

We investigated the efficacy of human chorionic gonadotrophin (HCG) and ovarian steroids in the maintenance/interruption of pregnancy in normal pregnant rats. Holtzman's strain rats were laparotomized to observe the number of implantations. In this study, continuous administration of HCG (5 IU) to normal pregnant rats, from day 8 through days 14 or 19, interrupted gestation, resulting in fetal resorption with many placentomas and placental scars. By contrast, a single injection of HCG (5 IU or 1 IU) on day 8 had no deleterious effect on pregnancy, except that the percent fetal survival was slightly reduced, attributable to a slight hyperstimulation of the ovaries of the pregnant rats. One possibility is that prolonged treatment with HCG might have caused progesterone/luteal hormone deficiency with a concomitant increase in estrogen secretion, resulting in the interruption of pregnancy. Hence, here we tested whether progesterone (5 mg) or estradiol-17beta (1 microg) administered to HCG treated rats could compensate this deficiency and maintain pregnancy. The results indicate that these steroids cannot prevent the interruption of pregnancy induced by the continuous administration of HCG, possibly due to an overstimulation of the ovaries by gonadotrophin.

Maintenance or interruption of pregnancy by human chorionic gonadotrophin in adrenalectomized albino rats.

In the present study, we investigated the efficacy of human chorionic gonadotrophin (HCG) in the maintenance of pregnancy in adrenalectomized rats. Holtzman's strain albino rats were adrenalectomized on day 8 of pregnancy and at the same time were laparotomized to observe the number of implantations. Adrenalectomy on day 8 caused abortions or fetal resorption in almost all rats. Administration of 5 or 50 IU HCG in adrenalectomized rats, from day 8 through 14 or 19, was not able to maintain gestation, resulting in fetal resorption with many placentomas and placental scars. However, a single injection of 5 IU or 1 IU HCG administered on day 8 only maintained the pregnancy to full term in adrenalectomized rats. Hence, the present experiment indicates that replacement therapy of a single dose of 5 IU or 1 IU HCG might be sufficient for maintaining pregnancy in adrenalectomized rats.

Multicentric reticulohistiocytosis.

A 41 -year-old man presented with multiple, painful and tender nodules on the palms, soles, scalp; and on the limbs predominantly around the joints with associated arthropathies. Smaller nodules were seen on the ear helices. There was no other clinically evident or investigative abnormality. Histopathological study confirmed a diagnosis of multicentric reticulo histiocytosis.