Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5.

We report the case of a male patient presenting with eosinophilia, pulmonary oedema and eosinophilic fasciitis (EF). He had the classic clinical appearance and magnetic resonance imaging of EF. Cytogenetic analysis of the bone marrow revealed a previously undescribed pericentric inversion of chromosome 5. Overall, the presentation was consistent with a diagnosis of chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS). Dermatologists should consult a haematologist in cases of EF, in order to rule out possible haematological malignancies.

The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.

PURPOSE: To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies. PATIENTS AND METHODS: One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response. RESULTS: The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sézary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sézary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T-cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sézary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results. CONCLUSION: We conclude that DCF is effective as a single agent in T-PLL, Sézary syndrome, and LGL leukemia, but has low activity in other T-cell disorders.

Sezary cell leukaemia: a distinct T cell disorder or a variant form of T prolymphocytic leukaemia?

We report the clinical, ultrastructural, immunophenotypic and virological features of nine cases of a rare type of mature T cell disorder formerly designated Sezary cell leukaemia. All patients presented with lymphocytosis ranging from 12.7 to 133 x 10(9)/l, bone marrow infiltration, splenomegaly and lymphadenopathy. Skin involvement was absent at presentation but developed as a terminal event in two patients, one of whom showed a pattern of dermal infiltration different from that characteristic of Sezary syndrome. Cells from eight cases bore a mature T cell phenotype and electronmicroscopy revealed lymphocytes with cerebriform nuclei resembling Sezary cells. All cases except one were HTLV-I negative. Patients were treated with various chemotherapy regimens but with poor outcome, the median survival being 13 months. Laboratory and clinical data suggest great similarity between Sezary cell leukaemia and T prolymphocytic leukaemia (T-PLL), namely coexpression of CD4 and CD8 (3/9 cases), identical chromosomal abnormalities in the three cases studied (isochromosome 8q plus inversion 14 or t(X;14)(q28;q11)) and a remarkable sensitivity to CAMPATH-1H (complete remission of 21 months' duration in one patient), suggesting that this entity could be considered a variant form of T-PLL. The alternative diagnosis of adult T cell leukaemia/lymphoma could not be excluded in one patient in whom positive HTLV-I serology was documented.

Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia.

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.

Incidence and significance of abdominal lymphadenopathy in hairy cell leukaemia.

We have investigated the incidence and significance of abdominal lymphadenopathy in hairy cell leukemia (HCL) by routinely CT scanning 88 patients. These included 70 men and 18 women with a median age of 51 years (range 25-83). Abdominal CT scans were performed at diagnosis in 29 patients and in 59 during the course of the disease. Abdominal lymphadenopathy was documented in 25 patients (28%) overall; the incidence of abdominal lymphadenopathy was higher in relapse (56%) than at diagnosis (17%). All patients with lymphadenopathy had bone marrow disease. There is no association with age or sex but lymphadenopathy tends to be more common in patients with long-standing disease (median duration of disease 6 years v one year in those without nodes) and in patients with bulky disease, particularly in the relapse group (splenomegaly/splenectomy in 95% vs 40%). The presence of abdominal nodes is also associated with relative resistance to treatment, with more treatment failures and fewer complete responses seen in this group. Most patients with lymphadenopathy had large, immature-looking hairy cells present in both the bone marrow and lymph nodes, when these were examined. Abdominal lymphadenopathy in HCL is more common than previously recognised, particularly in relapsed patients, and is always associated with active disease. The presence of large hairy cells and the relative resistance to treatment suggest that this phenomenon represents a form of transformation of the disease. Longer follow up is required to confirm this.

Aggressive NK cell lymphoma preceded by a ten year history of neutropenia associated with large granular lymphocyte lymphocytosis.

We report a case of aggressive natural killer (NK) cell lymphoma in an 82 year old man who first presented 10 years earlier with neutropenia in association with a large granular lymphocyte (LGL) lymphocytosis. The diagnosis of NK cell lymphoma was made on the basis of morphological and immunological characteristics (CD3-CD56+) found on skin biopsy of one of multiple skin nodules which subsequently developed in association with splenomegaly, thrombocytopenia and continuing neutropenia. In addition there was BM infiltration and a cytogenetic abnormality [add(6)(p25)] was detected. Combination chemotherapy led to an initial clinical response but a relapse occurred shortly afterwards and the patient died 8 months later from infection whilst neutropenic following re-introduction of chemotherapy. Previously reported cases of aggressive NK cell lymphoma have shown a young male predominance with a rapidly progressive clinical course and without evidence of a preceding chronic phase of LGL lymphocytosis and neutropenia.

Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience.

Fludarabine 25 mg/m2 was given on five consecutive days every four weeks to 85 patients with B- and T-cell malignancies. The median number of courses given was five. All patients except one had received previous chemotherapy. The overall response rate in non-Hodgkin's lymphoma (NHL) was 50% (five complete responses (CR) and 19 partial responses (PR)). The response rate in chronic lymphocytic leukemia (CLL) was 43% (four CR and 12 PR). Responses were seen in all groups of B-cell malignancies, but no T-cell malignancies (n = 4) responded. The median duration of CR has not been reached and the median duration of PR was 14 months for NHL and 16 months for CLL. The median survival from starting fludarabine for patients who achieved a CR or PR in NHL has not been reached and the median duration of PR in CLL was 23 months. The median duration of survival in non-responders was five months. Fludarabine was well tolerated and the main toxicity was myelosuppression. Our results suggest that even in patients who have never responded to any chemotherapy, regardless of the number of treatment regimens previously given, there is a 36% chance of response. In addition, this is the first report of fludarabine activity in Franklin's disease.

Use of an automated external defibrillator: a prospective observational study of first-year medical students.

UNLABELLED: This study evaluated the ability of young adults to respond to a simulated cardiac arrest using an automated external defibrillator (AED). METHOD: The study population was first-year medical students. None had received their mandatory training in emergency medicine. They role-played in pairs and entered a room in which a third person was lying on the floor and simulating unconsciousness and respiratory arrest. An AED and the corresponding poster-format instructions were clearly visible in the room, next to a telephone. The actions of pairs of responders were recorded. RESULTS: Interpretable results were obtained for 90 pairs of subjects. Most (96%) assessed vital signs and 20% performed this assessment correctly. Chest compressions were performed by 57%, 71% called emergency services, 4.5% removed the AED from the wall (but only one pair used it) and 8.9% did nothing. For 41% of the pairs, at least one member already had a cardiopulmonary resuscitation (CPR) certificate. The only statistically significant difference between students with and without a CPR certificate concerned use of the telephone to call emergency services. DISCUSSION: Despite the presence of an AED next to the telephone, the defibrillator was almost never used by the participants. Four out of ten pairs did not start chest compressions. The absence of any significant differences in performance between students with and without a CPR certificate casts doubt on the efficacy of the CPR training they had received. CONCLUSION: Results indicate the need for greater awareness of how to deal with cardiac arrest and the use of an AED when one is available.

Acute renal failure due to rhabdomyolysis associated with use of a straitjacket in lysergide intoxication.

Acute renal failure is a known sequel to rhabdomyolysis, both traumatic and non-traumatic. Two patients who had been placed in straitjackets after taking lysergide (LSD) developed acute renal failure and rhabdomyolysis. One subsequently died. The rhabdomyolysis probably resulted from a combination of severe restraint and the violent movements induced by the drug. The use of straitjackets cannot be considered to be completely safe in such cases.

2-Chlorodeoxyadenosine in the treatment of hairy cell leukaemia: differences in response in patients with and without abdominal lymphadenopathy.

We treated 26 patients with hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine, including nine with abdominal lymphadenopathy and of whom two had HCL-variant; 18 were previously treated. The overall response in 23 evaluable HCL patients was 100% with 87% complete remission (CR). The CR rate was 57% in patients with abdominal lymphadenopathy. Neither of the patients with HCL-variant achieved CR. Of four patients who had become refractory to 2'-deoxycoformycin, two achieved CR and one partial remission (PR). The lower response in HCL with abdominal lymphadenopathy supports the view that this represents a more resistant form of the disease.

Comparison of immunofiltration assay of plasma D-dimer with diagnostic imaging in deep vein thrombosis.

This prospective study was designed to assess the diagnostic sensitivity, specificity and negative predictive value of the NycoCard D-dimer plasma immunofiltration assay in patients with suspected deep vein thrombosis (DVT) confirmed by ultrasonography/venography. 84 medical patients were recruited: 43 patients (51%) had proven venous thrombosis, 33 by venography and 10 by ultrasonography. The sensitivity of NycoCard D-dimer in patients with DVT was 95.3%, the specificity was 22.0% and the negative predictive value was 81.8%. An algorithm including the NycoCard D-dimer test for the acute management of DVT is proposed. This would enable low-risk patients to be discharged early from hospital, without imaging or anticoagulant therapy.

Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.

Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.

DNA vaccines for bacterial infections.

DNA vaccines are an exciting development in vaccine technology which may have a special role in preventing viral infections and as 'theracines' for cancer. Their use in preventing bacterial infections has, by comparison, been less well documented. While it is unlikely that traditional, highly successful and cheap vaccines for diseases such as diphtheria will be replaced by DNA vaccines, naked DNA may be particularly appropriate for preventing bacterial infections where cytotoxic T cells confer protection, or where a Th1 type T cell response mediates resistance. For example, DNA vaccines containing different mycobacterial antigens have been shown to inhibit overt infections by Mycobacterium tuberculosis in rodent models. The use of DNA vaccines in bacterial infections may be complicated by fundamental differences between prokaryotic and eukaryotic genes and gene products, including mRNA stability, codon bias, secondary structures surrounding native start sequences and glycosylation. These problems can be solved by re-synthesis of bacterial genes to produce 'new' sequences which are more highly expressed by eukaryotic cells.