Gilian Wharfe

Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection

The pathogenesis of human T-cell lymphotropic virus type I (HTLV-I) in adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is poorly understood. We prospectively followed up and evaluated the virologic correlates of infection in transfusion recipients after seroconversion, in asymptomatic carriers, and in ATL and HAM/TSP patients. Proviral DNA levels (copies/105 lymphocytes) were determined by real-time automated polymerase chain reaction and antibody titers by end-point dilution by use of an HTLV-I enzyme-linked immunoassay. In early infection, proviral load was initially elevated (median, 212 copies/105 lymphocytes at time 1) and later decreased (median, 99 copies at time 2, and 27 copies at time 3). Corresponding antibody titers were low at time 1 (1:2154), had significantly increased by time 2 (1:12312), and were stable by time 3 (1:4694). These viral markers were significantly lower in asymptomatic carriers than in HAM/TSP or ATL patients. Therefore, proviral load and antibody titers may be useful as predictive markers of disease among carriers.

The Combination of Zidovudine and Interferon AIpha-2B in the Treatment of Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretro-viral drug zidovudine (AZT) and interferon alpha (IFNα) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNα-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic, crisis, acute or lymphoma type) were treated with the combination of AZT (50–200 mg orally 5 times a day) and IFNα-2b (2.5–10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received.

Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma ☆

Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8 mg/kg. Up to 8 mg/kg of daclizumab administered every 3 weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma

Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs. cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.

A woman with diabetes presenting with pyomyoma and treated with subtotal hysterectomy: a case report

IntroductionPyomyoma (suppurative leiomyoma of the uterus) is a rare condition resulting from infarction and infection of a leiomyoma. It is more usual in pregnant women or postmenopausal women who have vascular disease. The condition is usually fatal unless treated with appropriate antibiotics and surgical intervention.Case presentationWe report a case of a 44-year-old Afro-Caribbean woman with diabetes who presented with recurrent episodes of abdominal pain and fever over a period of five months. Her problem proved to be a diagnostic dilemma mimicking cholecystitis, pyelonephritis and ovarian cancer. Her blood cultures were positive on one occasion for methicillin-resistant Staphylococcus epidermidis. An ultrasound scan suggested uterine fibroids but a computed tomography scan suggested an ovarian malignancy because the mass appeared heterogeneous with fluid filled areas. She was treated with several courses of antibiotics and eventually at laparotomy, she was found to have a large pyomyoma which was successfully removed by subtotal hysterectomy with immediate and complete resolution of her symptoms.ConclusionThe diagnosis of pyomyoma should be considered in perimenopausal women with large fibroids and pyrexia of unknown origin.

Venous thromboembolism as a complication of uterine fibroids: A retrospective descriptive study

Summary This study describes cases of fibroids with venous thromboembolism (VTE) managed at UHWI between the years 1999–2004. We examined records to find patients with fibroids and VTE diagnosed before or after surgery. We found 438 women with VTE and 72 of these (16.4%) with fibroids. A total of 1,979 patients had fibroids during the period; cases were therefore 3.63% of fibroids. Cases were younger, median age 44 years than the total cohort: the median age was 57 and the mean age was 55.43 (SD 19.87) p = 0.000 about 9.5 years older than cases. Age over 50 years was less common in cases 27% vs 52%p = 0.0001 as were other risk factors for VTE such as cancer 4.9 vs 14%p = 0.03; diabetes 8.6 vs 25.2%p = 0.004 and cardiac disease 8.6% vs 26.6%p = 0.002. However, thrombocytosis was more frequent, 23% vs 9%p = 0.008. Other risk factors were not significantly different. A total of 21 cases (29.1%) had surgery for fibroids; 15 (71.4%) hysterectomy, and six (28.5%) myomectomy. Most cases 67/72 (93%) had VTE without surgery. Of the five cases with VTE after surgery for fibroids, none had prophylactic heparin. Of the cases, 15 died – 23% of women with VTE at PM and 0.8% of those with fibroids.

Placental separation from a seat belt injury due to severe turbulence during aeroplane travel.

Introduction We present a case of a patient 14 weeks pregnant who while travelling by air sustained abdominal trauma from a lap seat belt during severe air turbulence. Clinical examination revealed lower abdominal tenderness and no vaginal bleeding. Ultrasonography revealed placental separation with a live fetus compatible with dates. We believe that, as in the case with car seat belts, shoulder restraints need to be provided for pregnant women who travel by air to avoid this and other obstetric complications.

Renal impairment as a complication of uterine fibroids: A retrospective hospital-based study

Leiomyomas can cause obstructive renal impairment and renal failure. This was a retrospective study of women with renal impairment seen at the University of the West Indies Hospital, Jamaica, between 2000 and 2004, looking at aetiology and severity (group 1). We also evaluated patients, in the same hospital, with fibroids who had ultrasonography during a later period (2006–2011), comparing those who had hydronephrosis and those without (group 2). In group 1, 274 women were coded as renal impairment. Case notes for 160 patients (59%) were analysed. Uterine fibroids accounted for 13/160 (8.1%) of cases. Comparing cases with and without fibroids, none of those with fibroids were over 50 years old compared with 59.3% of the others, OR 0.02 (CI 0.00–0.35) p = 0.0001. Hospital data for renal failure showed that most mean values were significantly better for those with fibroids. Urea, 8.59 mmol/l (SD 9.89) vs 17.00 mmol/l (SD 13.41) p = 0.003; Creatinine 300.15 μmol/l (SD490.92) vs 424.05 μmol/l (SD553.29) p = 0.022 and Creatinine clearance 73.21 ml/min (SD 38.92) vs 44.25 ml/min (SD 49.71) p = 0.017. However, mean potassium values were similar, 4.52 mmol/l (SD 0.61) vs 4.85 mmol/l (SD1.03) p = 0.2. In group 2, there were 216 patients and we found 31 (14.35%) patients at ultrasonography with hydronephrosis from fibroids. These patients had significantly larger uteri than those without hydronephrosis but renal function was similar, with only urea values significantly worse. Leiomyomas can cause renal impairment, however the prognosis appears good.

Antiphospholipid and other autoantibodies in a cohort of habitual aborters and healthy multiparous women in Jamaica.

Blood samples from 50 women who had had recurrent spontaneous abortions and 135 healthy multiparous women were investigated for anticardiolipin (aCL) antibodies and anti-β 2 Glycoprotein 1 (anti-β 2 GP1 ) dependent aCL antibodies by enzyme-linked immunosorbent assays (ELISA), lupus anticoagulant activity was measured by activated partial thromboplastin time, antinuclear antibodies, rheumatoid factors and thyroid antibodies using standard techniques. Serological tests for syphilis were performed on all sera and thyroid function was evaluated. There was no significant difference in the prevalence of autoantibodies in habitual aborters and control subjects (60% and 44%, respectively). Habitual aborters differed from controls only in the prevalence of positive aCL antibody tests (15/50, 30% vs. 15/135, 1 1%; χ 2 = 8.5, P = 0.01); medium/high concentrations of aCL antibodies (9/50, 18% vs. 9/135, 7%; χ 2 4.3, P = 0.05); aCL antibodies of the IgM isotype (8/50, 16% vs. 7/135, 5%; χ 2 = 4.5, P = 0.05) and anti-β 2― GPI antibodies (7/50, 14% vs. 3/135, 2%; χ 2 = 6.1, P = 0.05). We recommend aCL antibody screening in habitual aborters and the performance of the anti-β 2 GP1 antibody tests to identify those most at risk.

Intestinal obstruction and thromboembolism in a postmenopausal woman with large calcified fibroids

A 75-year-old nulliparous woman, presented with a 6-day history of abdominal pain and vomiting. When she was examined, she was ill looking with a tender distended abdomen with hypertonic bowel sounds. She had a large uterine fibroid, diagnosed many years previously, noted on examination as 28-week size. The patient’s blood test results revealed a haemoglobin of 15.6 g/dl, white cell count of 8.86 10/l and platelets of 328610/l. Her urea and electrolytes revealed an elevated urea 11.6 mmol/l, a normal creatinine 73 mmol/l, low sodium 133 mmol/l, low chloride 94 mmol/l and normal potassium of 4.1 mmol/l in keeping with excessive vomiting. Abdominal radiography revealed dilated loops of small bowel and a calcified left-sided abdominal mass (Figure 1). A laparotomy was performed for the bowel obstruction. The patient did not receive any form of thromboprophylaxis such as low-molecular weight heparin, compression stockings or intermittent pneumatic compression. A large uterine fibroid was noted with adhesions to omentum and small bowel. Adhesiolysis with decompression of the small bowel was done. Because she was very ill, it was decided not to do hysterectomy at that time. Postoperatively, she developed a deep vein thrombosis, confirmed on venous colour and pulsed Doppler ultrasonography, affecting the left common and superficial femoral veins, as well as the left external iliac vein. She was started on unfractionated heparin then warfarin and remained on this with INR studies in the therapeutic range. After 7 months, an elective total abdominal hysterectomy was done under the cover of low-molecular weight heparin with warfarin discontinued and normal INR. Postoperatively, warfarin was started after 6 h and she has had no further problems 2 years later.