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Splenomegaly, macrothombocytopenia and stomatocytosis in healthy Mediterranean subjects (splenomegaly in Mediterranean macrothrombocytopenia).

Spleen size, stomatocytosis, macrothrombocytopenia, haemoglobin level, white cell count, and abdominal pain episodes were assessed in a coded study of healthy Mediterranean immigrants to Australia. Spleen size was estimated from a length measurement, L, on a standardized plain abdominal radiograph and expressed both as spleen weight and as a spleen length index, L/square root BSA; the platelet count and size parameters were determined electronically and the presence of stomatocytes was evaluated in stained blood films. In relation to 16 Northern European control women 12 of 25 Mediterranean women had radiographic splenomegaly, 10 had macrothrombocytopenia, 9 had stomatocytosis, but none had episodes of abdominal pain. The median spleen weights of the two groups were estimated as 157 and 247 g with ranges from percentile 2.3 to 97.7 of 75 to 328 and 112 to 669 g. Within the Mediterranean group splenomegaly correlated with macrothrombocytopenia (P less than 0.001) but not with stomatocytosis, haemoglobin values or white cell counts. Thus, mild splenomegaly may be expected in Mediterranean macrothrombocytopenia, Mediterranean stomatocytosis appears unrelated, and all of these apparently benign anomalies may be incidental findings in patients from the Italian and Balkan peninsulas.

Adult

[Ultrasonographic analysis of splenomegaly in patients with sarcoidosis].

Thirty seven patients with sarcoidosis were examined using ultrasound (US) to determine the size of the spleen. A Spleen Index (SI) was employed to evaluate splenomegaly and the SI was calculated using long (a) and short (b) dimensions on the sectional splenotomogram (SI = a x b). In 21 (57%) of these patients the spleen was judged ultrasonographically to be enlarged (SI 30), but in only 3 was it palpable. The clinical records of patients with and without splenomegaly detected by US were compared. There were no differences between patients with or without splenomegaly in hematologic findings (peripheral blood and bone marrow) or blood chemistry; furthermore no patients with hypersplenism were seen. In immunological parameters, the serum immunosuppressive acid protein level was significantly (p less than 0.05) higher in patients with splenomegaly than in those without splenomegaly; however, there were no differences in serum angiotenins converting enzyme activity, serum lysozyme level, PPD skin test or bronchoalveolar lavage fluid analysis. The patients with splenomegaly had significantly higher evidence of increased uptake of 67-Gallium in lung fields and positive lung infiltrates in chest X-ray than those without splenomegaly (p less than 0.01, p less than 0.05). These data suggest that ultrasound is a promising diagnostic tool for the assessment of the size of the spleen and is useful to detect disease activity and extent of disease in sarcoidosis. Patients with sarcoidosis who had splenomegaly had more disseminated disease, especially pulmonary parenchymal disease, than did those without splenomegaly.

Adult

[Pathological classification of splenomegaly in portal hypertension].

The morphometric analysis was carried out for 150 cases splenomegaly pathological sections (1010 sections) after being stained with histochemical, immunohistochemical, hematoxylin and eosin methods, summarizing that the proliferation of three types of fibers, the number and distribution of T, B lymphocytes and macrophages, the changes of sections stained with HE, the ultrastructure of splenomegaly under electron microscope would be the criteria for partially preserving splenomegaly. The data of morphometry was treated by IBM/PC computer. The research was aimed to establish a pathological indication for preserving partial splenomegaly clinically. The study demonstrated that the pathological classification, based on the fibrosis degree of splenomegaly, may objectively reflect the changes of immunological function of splenomegaly, by which it was also revealed that the immunological function in pathological class II and III was markedly lowered. Because the proportion of class I splenomegaly remained only in 31% of good function, there are less splenomegaly worth preserving.

B-Lymphocytes

Duplex sonography in splenomegaly.

The aetiology of splenomegaly is seldom clear from either clinical or imaging assessment of the spleen. In the majority of cases sonographic assessment of the spleen produces a homogeneous enlargement of variable echodensity, but with very poor correlation with pathology. A study has been undertaken to assess the Doppler characteristics of the splenic artery in splenomegaly, excluding cases of portal hypertension in an attempt to provide further diagnostic information. Duplex assessment of 18 normal subjects and 10 patients with splenomegaly due to five different causes was undertaken. Analysis of waveform, peak frequency and pulsatility index were compared and failed to demonstrate any significant change. In the normal subject there is a broad systolic spectrum related to the tortuosity of the splenic artery, with persistence of forward flow throughout diastole, a reflection of the low peripheral resistance of the spleen. In splenomegaly the broad systolic spectrum is unchanged, since vessel tortuosity persists. Pathological and physiological assessment of the spleen in splenomegaly shows that a low resistance circulation persists, explaining maintenance of the diastolic flow pattern in splenomegaly. Increased blood flow to the spleen in splenomegaly occurs either as a result of an increase in vessel diameter or an increase in flow velocity, or a variable combination of the two which does not seem to be governed by specific pathology. An increase in peak frequency in some cases reflected some increase in flow velocity but provided no useful correlation. Analysis of the pulsatility index supported the above findings without adding further information.

Adolescent

Splenomegaly in murine trypanosomiasis: T cell-dependent phenomenon.

Splenomegaly resulting from Trypanosoma musculi infection was found to be dependent upon a functioning T-lymphocyte system. When both humoral and cell-mediated immune systems were suppressed by treatment with cyclophosphamide 2 days after infection, splenomegaly was inhibited for about 6 days. However, when only humoral immunity was suppressed by treatment with cyclophosphamide 3 days before infection, splenomegaly still occurred. In addition, splenomegaly was absent in congenitally athymic nude mice. Nude mice and immunologically intact heterozygote mice were also sacrificed at varying times after infection, and spleens were examined histologically. A lymphocytic hyperplasia was observed in immunologically intact mice but not in nude mice. These data indicate that splenomegaly of T. musculi infections is T cell dependent and that splenomegaly is the result of a proliferation of B and/or T lymphocytes.

Animals

[Difficulties in the differential diagnosis of splenomegaly].

The authors discuss diagnostic difficulties that may occur in the interpretation of splenomegaly. In some cases, other tumorous formations, palpable in the left hypochondrium (renal tumor and retroperitoneal fibroma in cases demonstrated) may be taken for splenomegaly. In other cases, diagnostic difficulties may be related to establishing the cause of genuine splenomegaly. Out of 10 patients with genuine splenomegaly, the cause of which could not be ascertained at the prehospital stage, the enlargement of the spleen in 2 was due to liver cirrhosis, in 3, to subleukemic myelosis, in 1, to splenic tuberculosis, in 2, to multiple capillary angiomas of the spleen, in 1, to chronic monocytic leukemia, and in 1 patient, to splenic echinococcosis. In 3 patients out of the 10, the diagnosis was verified by surgery followed by histological examination of the spleen. The conclusion is made about the necessity of the use of clinical and laboratory examinations, of patients with obscure "splenomegaly" together with the use of x-ray and ultrasonography of the spleen, kidneys, gastrointestinal tract, puncture of the bone marrow and spleen. In some cases, splenectomy may be performed along with histological examination of the spleen as the final stage of differential diagnosis of splenomegalies.

Adult

Malignant histiocytosis with massive splenomegaly in asymptomatic patients. A possible chronic form of the disease.

Four patients with malignant histiocytosis (MH) are described whose initial manifestation of the disease was massive splenomegaly without associated systemic symptoms. The diagnosis of MH was made after histologic evaluation of splenectomy specimens. Splenomegaly in an otherwise asymptomatic patient is unusual for malignant histiocytosis, but when such a clinical picture is seen, it may be confused with other diseases that often present with massive splenomegaly and that have a similar diffuse infiltrative pattern in the spleen. Although three of these patients did eventually develop systemic symptoms characteristic of MH 3, 6, and 10 months after the detection of splenomegaly, the 15-month asymptomatic survival of one patient who received no chemotherapy suggests that MH presenting with massive splenomegaly, rather than with constitutional symptoms, may have a protracted course.

Abdomen

Diethylcarbamazine in the control of splenomegaly associated with Bancroftian filariasis in the Ok Tedi area of Papua New Guinea.

Bancroftian filariasis is highly endemic in the Ok Tedi region of Papua New Guinea, with a reported mean rate of 39% before the implementation of a single-dose diethylcarbamazine (DEC) treatment programme in 1986. This was followed by a 72% decline in the rate of detectable microfilaraemia and a 40% reduction in pre- and post-treatment splenomegaly. No significant difference was observed when spleen enlargement was compared to the presence of patent malaria. A significant difference in splenomegaly was observed between DEC-treated villagers and their untreated counterparts. Significant differences were reported in the rate of detectable microfilariae of Wuchereria bancrofti, but not of malaria, between the two groups. The number of DEC administrations and the period of time since the first treatment played a significant role immunologically. Significant differences were observed in immunoglobulin (Ig) M and IgG levels and in the extent of splenomegaly between DEC-treated and untreated areas. Filarial infection associated with malaria resulted in higher spleen rates and size. W. bancrofti is a major contributor to splenomegaly in the Ok Tedi region, and splenomegaly associated with bancroftian filariasis can be reduced or controlled by low, well-spaced doses of DEC.

Animals

Massive splenomegaly in sarcoidosis.

We have presented a case of massive splenomegaly. Our patient was initially thought to have lymphoma, but at operation she was found to have sarcoidosis with splenic involvement. At 2250 g, the spleen was one of the largest recorded in the literature on sarcoidosis. Although the spleen is frequently involved in sarcoidosis, a review of 6074 cases showed that the incidence of actual splenomegaly is only 10%. In 628 of these cases the authors described various degrees of splenomegaly, but the incidence of massive splenomegaly was only 3%. We conclude that sarcoidosis must be considered in the differential diagnosis of splenomegaly.

Adult

Experimental models for prevention of graft-versus-host reaction in bone marrow transfusion. I. Selective suppression and augmentation of splenomegaly and cytotoxicity.

Induction and suppression of splenomegaly and cytotoxicity against C57BL/L cells were studied in (AKR X C57BL/6) F1 hybrid adult mice after the transfer of AKR lymphoid and bone marrow cells. 1) Splenomegaly and cytotoxicity were dissociated in the developmental stages of the graft-versus-host reaction. When lymphoid and bone marrow cells of normal AKR mice were injected into F1 recipients, splenomegaly was prominent on days 5 and 7, but cytotoxicity of spleen cells was not detected. Splenomegaly became less prominent but the cytotoxicity became detectable on day 14 after the injection. 2) Cytotoxic activity of spleen cells of F1 recipients was suppressed by the treatment of AKR donors with C57BL/6 lymphoid cells in Freund's complete adjuvant. Splenomegaly, however, was substantially enhanced by such a treatment of the donors. On the other hand, induction of the cytotoxic activity was facilitated by the treatment of donors with C57BL/6 skin grafts. 3) F1 hybrid mice could be protected from the graft-versus-host reaction by the injection of AKR anti-C57BL/6 serum or pretreatment of AKR donors with sonicated cellular antigens of C57BL/6.

Animals

Inverse relationship between splenomegaly and stem cell compartment size in mice treated with nitrogen mustard.

Following the administration of similar doses of nitrogen mustard (4 mg/kg) to different strains of mice, wide variations in the subsequent degree of splenomegaly were observed, implying strain differences in the role of the spleen in the compensatory erythropoietic response to haematopoietic stress. This investigation was undertaken to determine whether or not these differences were related to the size of the haematopoietic stem cell compartment size in the various strains of mice. Groups of 4 different strains of mice (Swiss Webster, A/J, C57BL/6J and CS1/ASH) were injected i.v. with nitrogen mustard (4 mg/kg body weight) and autopsied at regular intervals up to 20 d post-injection. At autopsy, the wet weight of the spleen was determined. Subsequently, groups of the same 4 strains of mice were exposed to single doses of wholebody gamma-irradiation in the range of 500-900 rads. 9 d after gamma-irradiation the mice were autopsied, their spleens removed, and the number of endogenous spleen colonies determined. The greatest degree of splenomegaly was observed in the C57BL/6J mice. The Swiss Webster mice showed no splenomegaly during the time period studied. There existed a linear inverse relationship between the maximum degree of splenomegaly observed and the dose of wholebody gamma-irradiation required to completely eliminate endogenous spleen colonies. This data is in accord with the hypothesis that there exists an inverse relationship between the extent of splenomegaly observed following haematopoietic stress and the haematopoietic stem cell compartment size.

Animals

Viral etiology of obscure splenomegaly in Egyptian children.

Fifty seven Egyptian children aged 1.5 to 9.5 years with mild splenomegaly (less than 3 cm below the costal margin) were screened for antibodies against the three common viruses of the Herpes group: Cytomegalovirus (CMV), Epstein-Barr (EB) and Herpes type 1 virus. A group of 57 healthy children were studied similarly. All patients were subjected to a comprehensive laboratory and clinical work up to exclude any hematological, metabolic or malignant etiology for the splenomegaly. Splenic aspirates from five cases were examined histologically and by immunohistochemistry for the antigens of CMV. Only primary or reactivation of CMV might be considered a cause of splenomegaly, as there was a statistically significant increase in the prevalence of IgM antibodies to CMV in the patients compared to normal controls (63% of patients and 19.4% of controls had IgM antibodies, P less than 0.001; 68.3% of patients and 54% of controls had IgG antibodies, P is insignificant). An almost equal proportion of children with and without splenomegaly had antibodies to EB-Viral Capsid Antigen (EBVCA) both IgG and IgM. (28% of cases and 33% of controls had IgM antibodies; 26% of patients and 21% of controls had IgG antibodies). A role of Epstein-Barr viral infection could not be ruled out in these patients. There was a higher prevalence of antibodies to Herpes type 1 virus in asymptomatic controls than in children with splenomegaly. (10% of patients and 43% of controls had IgM antibodies, 10.6% of patients and 38% of controls had IgG antibodies).

Antigens, Viral

Serum immunoglobulin concentrations, malarial and schistosomal antibodies in patients with massive splenomegaly in Malawi.

Serum immunoglobulin concentrations, malarial antibodies and schistosomal antibodies were measured in 33 patients with a provisional diagnosis of schistosomal splenomegaly, 16 with TSS of presumed malarial aetiology and in 52 controls. IgG and IgM were higher in both splenomegaly groups than in the controls and IgG was significantly higher in patients with schistosomal splenomegaly than in TSS. Although a very high IgM was found more often in the TSS group, there was no significant difference between the mean IgM levels in the two splenomegaly groups. The mean antischistosomal antibody titres were significantly higher in the schistosomal group than in those with TSS but there was no difference in the antimalarial antibody titres. These results emphasise the problems of diagnosis of gross splenomegaly in areas where schistosomiasis and malaria coexist.

Adolescent

Platelet storage in the spleen in idiopathic thrombocytopenic purpura and congestive splenomegaly.

The kinetics of 51Cr-tagged platelets was studied in 10 patients with idiopathic thrombocytopenic purpura and in 8 patients with congestive splenomegaly. The surgically removed spleens were examined for their platelet content and for their microscopic structure. In idiopathic thrombocytopenic purpura the life-span of platelets was reduced, the number of platelets washed out from the spleen averaged 4.36 X 10(10)/100 g splenic tissue (intrasplenic platelet reserve). The index platelets per g splenic tissue/platelets per ml whole blood reflecting the tendency of platelets to concentrate in the spleen was 8.06. Microscopically, extensive phagocytosis of platelets by macrophages and a preserved lienal architecture were seen. In the group of congestive splenomegaly the life-span of platelets was not significantly shortened and the intrasplenic platelet reserve agreed with the figure found in idiopathic thrombocytopenic purpura. The spleen was characterized by fibroid degeneration and endothelial hypertrophy causing partial obstruction of the sinusoids. It is concluded that while the intrasplenic platelet reserve is nearly the same in idiopathic thrombocytopenic purpura and congestive splenomegaly, in idiopathic thrombocytopenic purpura hypersequestration while in congestive splenomegaly platelet storage predominates.

Adolescent

Splenectomy for undiagnosed splenomegaly.

During the 9-year period 1968-76 116 splenectomies were performed at the General Hospital, Nottingham. Of these, 13 (11 per cent) were undertaken for unexplained splenomegaly. In 6 patients a diagnosis was established by the operative procedure (2 with sarcoidosis, 2 splenic cysts, 1 Gaucher's disease and 1 haemangiosarcoma). Histological examination of the excised spleens in the remaining 7 patients showed no specific features. Two of these patients benefited considerably from removal of very large spleens. Another patient died from lymphosarcoma which was diagnosed 21 months after splenectomy. In the remaining 4 patients with mild to moderate splenomegaly, there were no real diagnostic or therapeutic advantages. It is concluded that splenectomy should always be considered in patients with unexplained moderate or gross splenomegaly but it may not be helpful in the patient whose spleen is only midly enlarged.

Adolescent

Splenomegaly and splenectomy in sarcoidosis.

The natural history of 30 patients with sarcoidosis who showed histological evidence of granulomatous involvement of the spleen has been studied; 24 patients had splenomegaly, 16 of whom had splenectomy. The main indication for splenectomy was splenomegaly and resultant discomfort. Corticosteroids reduced spleen size but reduction or withdrawal of the relatively high dosage required resulted in rebound splenomegaly within a period of three months to three years. Haematological abnormalities were controlled by splenectomy in all patients so affected, but the natural history of their sarcoidosis remained unaltered.

Adolescent