Neurogenic bladder in HAM (HTLV-I associated myelopathy)]

Bladder dysfunction is one of the major symptomatologies characteristic to HAM (HTLV-I associated myelopathy). Four patients, 3 females and 1 male, were diagnosed by neurologists to have HAM with spastic gait disturbance and increased titer of antibody to HTLV-I. They complained of urge incontinence, bed wetting, difficulty in micturition and/or pollakisuria. Urodynamically, in 3 of them severe uninhibited detrusor contractions were observed. On the other hand, in one case detrusor contractility was lost completely at voiding. In all patients, bladder sensation was well preserved. Corticosteroids and interferon could not improve their urological symptoms. Clean intermittent catheterization (CIC) put on 3 patients who had a significant amount of residue relieved them of urinary incontinence. We believe that HAM in patients suffering from severe difficulty in micturition is a good indication for CIC.     

Human T-lymphotropic virus type I (HTLV-I): risk of transmission with transfusion

PATHOGENIC ROLE: The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus discovered, is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and of HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) and has a widespread but uneven worldwide distribution. HTLV-I has a high seroprevalence in Southern Japan, the Caribbean basin and Sub-Sahara Africa. Blood transfusion, intravenous drug use, breast feeding and sexual contacts are major routes of contamination. IMPLICATIONS FOR BLOOD TRANSFUSION: The screening of blood donors for antibody to HTLV-I became systematic in 1989 in French West Indies and in 1991 in Continental France. This review deals with the transfusional implications of the HTLV-I, which belongs to the group of the blood-borne viruses: the prevalence of transfusion-linked HTLV-I infection before the implementation of the specific preventive measures, the parameters influencing the risk of transfusional contamination (the type of blood products, the age of the blood product with regards to its collection date, the proviral load of the blood donor), the prognosis of HTLV-I infection in patients contaminated by transfusion, the prophylactic strategies of transfusion contamination and the residual risk of infection through HTLV-I-infected risk blood products.     

HTLV-I viral-associated myelopathy after blood transfusion in a multiple trauma patient

This may be the first documented case in the United States and in the orthopedic literature of transfusion-transmitted human T-cell leukemia virus Type I (HTLV-I)-associated myelopathy (HAM). Progressive myelopathy occurred in a 58-year-old white man with serologic and molecular evidence of HTLV-I infection after multiple trauma and subsequent transfusion with multiple units of banked blood products. Symptoms of myelopathy occurred 15 months after the transfusions. Myelopathy from HTLV-I infection simulates a disorder of orthopedic interest. Physicians should be aware of the symptoms of HAM and unexplained myelopathy.     

Bladder involvement in HTLV-I associated myelopathy

The HTLV-I infection was endemic in south western Kyushu. This human T-lymphotropic virus type I may cause HTLV-I associated myelopathy (HAM), a neurological disease characterized by a spastic paraparesis. And one of the minor diagnostic features of HAM is the presence of cystorectal disturbance. We experienced 35 HAM patients with a neurogenic bladder. A gradually progressive contracted bladder was observed in 3 of them. The main pathological finding in these patients was submucosal infiltration of lymphocytes. These findings suggest that immunologic mechanisms account for the development of bladder lesions.     

Erectile dysfunction and HTLV-I infection: a silent problem

The human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with a chronic myelopathy known as HTLV-I-Associated Myelopathy or Tropical Spastic Paraparesis (HAM/TSP). The main objective was to assess the frequency of erectile dysfunction (ED) in HTLV-I-infected individuals from Salvador and other cities from Bahia, Brazil, as well as to verify if sexual dysfunction correlates with urinary symptoms and overall neurological impairment. From January 2001 to April 2004, 218 HTLV-I carriers (111 male and 107 female subjects) had complete clinical, neurological, and urological evaluation. They were assessed using standardized questionnaires to determine urinary complaints (Urinary Distress Inventory) and ED (Brief Male Sexual Function Inventory). Neurological impairment was established by Expanded Disability Status Scale (EDSS) from 0 to 10. HAM/TSP was considered as EDSS> or =2. A total of 17 males had clinically defined HAM/TSP (group 1). From the 94 HTLV-I-infected males, 62 were selected (group 2) and paired by age with patients in group 1. A total of 79 individuals were selected for this study. The age ranged from 35 to 81 y (mean=47.9+/-9.65). The percentage of ED in the studied population was 40.5%. In the HAM/TSP group, ED frequency was 88.2%. The associations among sexual dissatisfaction, erectile dysfunction, urinary symptoms (frequency, nocturia, and urgency) and EDSS> or =2 were statistically significant. In HAM/TSP, there is a slow and progressive degeneration of the lateral funiculus of the spinal cord. HTLV-I-infected individuals present a high frequency of ED and it is closely associated to urinary symptoms and the overall neurological picture. The HTLV-I carriers already had prominent compromise of the sexual activity.     

Two cases of neurogenic bladder due to HTLV-1 associated myelopathy (HAM)

Case-1 (24-year-old female) had complained of slowly progressive urinary incontinence (since 14 years old) and gait disturbance (since 18 years old). A marked pyramidal disorder was observed, and anti-HTLV-1 antibody (1:640) was present in her peripheral blood. She was diagnosed as having HTLV-1 associated myelopathy (HAM). Repeated urodynamic studies (UDS) revealed exacerbation of overactive bladder and detrusor-sphincter dyssynergia (DSD) with the progress of the disease. Case-2 (48-year-old male) had complained of gait disturbance (since 32 years old) and progressive urinary hesitancy (since 46 years old). Physical examination revealed a marked pyramidal disorder. Anti-HTLV-1 antibody (1:200) and ATL-like cells were present in his peripheral blood. He was diagnosed as having HAM. The voiding cystourethrography demonstrated an abnormal change of the bladder wall. UDS revealed overactive bladder and marked DSD. Medications based on adrenocortical steroids and urological cares have improved urinary disturbance, in both cases.     

Human immunodeficiency virus and human T-cell leukemia virus type I in patients undergoing maintenance hemodialysis in Miami

The high prevalence of human immunodeficiency virus (HIV-1) infection in populations at risk in Miami prompted a seroepidemiologic study of both HIV-1 and the human T-cell leukemia virus type I (HTLV-I), a closely related virus, in our patients receiving chronic hemodialysis. One hundred twenty-nine patients undergoing hemodialysis in 1986 and 1987 were tested for antibody against both viral antigens by EIA (Abbott Laboratories, Abbott Park, IL). Seroreactive samples for HIV-1 and/or HTLV-I were confirmed by Western blot and, for HTLV-I, by viral cultures. Thirty patients (23.2%) were positive for retroviral infection (22 for HIV-1 alone, four for HTLV-I alone, and four for both HIV-1 and HTLV-I). The most important risk factor was intravenous drug use, followed by blood transfusion. Patients with HIV-1 had lower T4-T8 ratios and higher mortality than those with HTLV-I infection alone. It was concluded that HTLV-I, as well as HIV-1, infection is endemic in chronic dialysis centers in Miami. The clinical consequences of HTLV-I infection in relatively immunocompromised patients with chronic uremia who are undergoing chronic hemodialysis remains to be established.     

Bronchoalveolar lymphocytosis correlates with human T lymphotropic virus type I (HTLV-I) proviral DNA load in HTLV-I carriers

Background: A study was undertaken to investigate the pathogenesis of pulmonary involvement in human T lymphotropic virus type I (HTLV-I) carriers.

Methods: The bronchoalveolar lavage (BAL) cell profile of 30 HTLV-I carriers (15 asymptomatic HTLV-I carriers (AHCs) and 15 symptomatic HTLV-I carriers (SHCs)) with chronic inflammatory diseases of respiratory tract and eight patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) was investigated. The HTLV-I proviral deoxyribonucleic acid (DNA) load in peripheral blood mononuclear cells (PBMCs) and BAL fluid from HTLV-I carriers was estimated using the quantitative polymerase chain reaction method and the correlation between the lymphocyte number in BAL fluid and the HTLV-I proviral DNA load in PBMCs and BAL fluid was examined.

Results: The percentage of lymphocytes in BAL fluid was increased (>18%) in 11 of 30 HTLV-I carriers although there was no significant difference compared with control subjects. In HTLV-I carriers the lymphocyte number in BAL fluid correlated well with the copy number of HTLV-I proviral DNA in PBMCs. In addition, the copy number of HTLV-I proviral DNA in BAL fluid correlated well with the number of lymphocytes (both CD4+ and CD8+ cells) in BAL fluid.

Conclusions: These findings suggest that pulmonary lymphocytosis can occur in a subset of HTLV-I carriers without HAM/TSP and that the increased HTLV-I proviral DNA load may be implicated in the pathogenesis of pulmonary involvement in HTLV-I carriers.

     

Osteoporosis in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been associated with changes in extracellular matrix of neural tissue. HTLV-I infection has multiple other systemic effects. Extracellular matrix is important for bone mineral deposition. We examined bone mineral density (BMD) in patients with HAM/TSP. BMD was assessed by ultrasonographic calcaneous densitometry in 24 patients (7 males, 17 females) with HAM/TPS, and 23 healthy HTLV-I-seronegative controls matched by age and sex. Patients with HAM/TPS had a mean BMD T-score of -3.07 +/- 0.64 in males and -2.93 +/- 0.69 in females. Control patients revealed a T-score of -0.77 +/- 1.31 in males and -1.17 +/- 1.08 females. The difference in T-score between HAM/TSP patients and control groups is significant (P < 0.001). Of HAM/TPS patients, 7 of 24 (29.2%) had osteopenia (T-score between -1 and -2.5) and 17 of 24 (70.8%) were diagnosed with osteoporosis (T < -2.5). Respective figures for control patients were 10 of 23 (43.5%) with a normal T-score, 11 of 23 (47.8%) with osteopenia, and 2 of 23 (8.7%) with osteoporosis. After adjustment for age and sex, odds ratio of osteoporosis for HAM/TSP patients was 31.52 (95% confidence interval, 5.07 to 195.88). No correlation was found in HAM/TSP patients between T-score and age, menstrual status, gait functionality, or years of evolution of HAM/TSP. HAM/TSP patients have a significantly diminished BMD of the calcaneous that appears not to be explained by paresis, age, years of disease, menstrual status; may be the result of systemic alterations due to HTLV-1 infection.     

Report of two operated cases with erythrocyte antibody

Two operated cases with erythrocyte antibodies were reported. In the first case who required the second open heart operation for mitral stenosis, delayed hemolytic transfusion reaction by erythrocyte antibodies was recognized. The direct and indirect Coombs' tests were negative and the erythrocyte antibodies were not detected preoperatively. Massive blood transfusion during perioperative period precipitated secondary immunoreaction and reproduction of antibodies. An anti-c antibody and anti-E antibody were detected by the serologic studies on the 11th and 16th postoperative day. In the second case, stenotic mitral valve was replaced without homologous blood transfusion, because anti-C antibody was detected preoperatively. We believe that open heart operations without blood transfusion should be done, whenever possible, it should be kept in mind that delayed hemolytic transfusion reaction by erythrocyte antibody may occur after blood transfusion.     

Rapid development of subacute myelopathy in three organ transplant recipients after transmission of human T-cell lymphotropic virus type I from a single donor

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) causes a subacute myelopathy in less than 5% of chronic carriers. However, the risk of neurologic disease appears to increase in persons infected through blood transfusion. METHODS: We report three recipients of solid organ transplants who developed a subacute myelopathy within 2 years after becoming infected with HTLV-I from a single asymptomatic HTLV-I donor. Genetic studies were performed in and sequences in proviral DNA, and HTLV-I proviral load was measured by real-time quantitative polymerase chain reaction. RESULTS: HTLV-I sequences were obtained in two of these individuals, and they were almost identical and clustered within the Cosmopolitan A HTLV-I subtype, which indicates a common source. All typical changes in Tax amino acid sequence of the HTLV-I Cosmopolitan A were identified, plus two additional changes were noted. Although A has been associated with a greater risk of neurologic disease, both patients were positive for human leukocyte antigen-A*02, which is considered a protective factor. CONCLUSION: Rapid development of subacute myelopathy may occur in recipients of organ transplants from asymptomatic HTLV-I donors. A particular virulence of the virus strain, the large size of the virus inoculum, and the immunosuppressed condition after transplantation may have contributed to produce this unusual rapid development of HTLV-I associated myelopathy.     

A patient with HTLV I-associated myelopathy (HAM) complaining of burning pain on the bilateral feet: a case report

A 67-year-old man complained of a burning pain and weakness of bilateral feet after contusion of the left lumbar region. Skin as well as bone dystrophy and disturbance of bladder function were not seen, but low skin temperature was observed in the left lower leg. Glove anesthesia was seen on bilateral feet. Patellar tendon reflex was accentuated but Achilles tendon reflex was diminished, and bilateral Babinski sign was positive. Compression of the spinal cord or spinal root nerve was not noticed by MRI, myelography and myelo-CT (from cervical to lumbar level). We suspected the complex regional pain syndrome type I, and performed sympathetic blockade, but burning pain was not relieved. We looked for spinal tumor, myelitis, collagen disease, vitamin deficiency and malignancy but could not find out any disorder. However, the patient had neuropathic sign in electromyogram, and high anti-HTLV-I antibody titers in blood serum (8192x) and cerebrospinal fluid (256x). We diagnosed this case as HTLV I-associated myelopathy (HAM). He developed, so called, HTLV I-associated pneumonia at 74 years of age. We suggest that HAM may rarely accompany a burning pain and neuropathy (not myelopathy) as main symptoms. The present case suggests that a patient with HAM may develop HTLV I-associated pneumonia during its process; indicating a new concept of this very rare disease.     

Urinary disturbance due to HTLV-1 associated myelopathy]

Patients with human T-cell lymphotropic virus type 1 associated myelopathy (HAM) have complaints of urinary disturbance frequently. Symptoms and urodynamic examinations were evaluated in untreated twenty-one patients with HAM. Although two cases (11%) had no urinary symptom, nineteen cases (89%) suffered from dysuria, pollakisuria, incontinence or urgency. The combination of irritative and obstructive urinary disturbance was a characteristic symptom in the HAM patients. In three cases the urinary symptoms preceded the gait disturbance which is a main symptom of HAM. In urodynamic study overactive bladder was found in fourteen cases (66%), although three cases (15%) showed underactive or acontractile bladder with disturbance of urinary sensation. There was no abnormal finding by urethral pressure profile (UPP), but detrusor sphincter dyssynergia (DSD) was revealed frequently by EMG. This typical dysfunction of the HAM patients was thought to be caused by destruction of the lateral column of the spinal cord.     

Prognosis of HTLV-I-positive renal transplant recipients

HTLV-I is the pathogen that causes adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). The rate of disease development is low and the latency time is a few decades. However, the possible influence of immunosuppression on this disease development is unclear. The purpose of this study was to investigate the risk of development of ATL and HAM among the large number of HTLV-I-positive renal transplant recipients in western Japan. In principle immunosuppressive drugs have the possibilities to accelerate ATL development but are thought to suppress HAM development. Of 120 renal transplant recipients, 10 HTLV-I-positive recipients were reviewed, none of whom developed ATL or HAM. There are 11,896 dialysis patients in Japan and 300 dialysis patients in Okinawa who are registered with the JOTN for cadaveric renal transplant. The numbers of HTLV-I-positive patients in these groups were 97 (0.82%) and 26 (8.67%), respectively. These numbers are thought to be sufficient for an HTLV-I-positive recipient pool for HTLV-I-positive donors. Ten cases of ATL development and two of HAM development have been previously reported. Because of low number of ATL development, renal transplantation does not appear to be a contraindication for HTLV-I-positive chronic renal failure patients. In other words, kidneys from HTLV-I carriers, which include cadaveric donors, could be used for HTLV-I-positive recipients.     

Effect of blood transfusion on long-term survival after cardiac operation

BACKGROUND: Blood transfusions have been linked to increased morbidity and mortality. Bleeding during and after cardiac operations and the hemodilution effects of cardiopulmonary bypass commonly result in blood transfusions. Because we could not find any studies evaluating the effects of transfusion on long-term survival after cardiac operation, we sought to determine these effects. METHODS: We studied 1,915 patients who underwent first-time isolated coronary artery bypass operations between July 6, 1994 and December 31, 1997 at our institution. Patients with transfusions were compared with those who had not been transfused. Long-term survival data were obtained from the United States Social Security Death Index. Groups were compared by Cox proportional hazard models, Kaplan-Meier survival plots, and hazard functions. RESULTS: Six hundred forty-nine of 1,915 study patients (34%) received a transfusion during their hospitalization. Transfused patients were older, smaller, and more likely to be female, and had more comorbidity. Transfused patients also had twice the 5-year mortality (15% vs 7%) of nontransfused patients. After correction for comorbidities and other factors, transfusion was still associated with a 70% increase in mortality (risk ratio = 1.7; 95% confidence interval = 1.4 to 2.0; p = 0.001). By multivariate analysis, transfusion, peripheral vascular disease, chronic obstructive pulmonary disease, New York Heart Association functional class IV, and age were significant predictors of long-term mortality. CONCLUSIONS: We found that blood transfusions during or after coronary artery bypass operations were associated with increased long-term mortality.     

Clinical manifestation of human T-cell lymphotropic virus type-I-associated myelopathy and vesicopathy

Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) sometimes have accompanying voiding disturbances. We performed clinical surveys and urodynamic examinations on 25 untreated patients with HAM. Although 4 cases (16%) were entirely aware of urinary symptoms, the onset of urinary symptoms preceded other pyramidal symptoms in 6 cases (24%). All cases suffered from dysuria. The cause of dysuria was thought mainly to be detrusor external sphincter dyssynergia, but in some cases an underactive detrusor and poor opening of the bladder neck at voiding were also the causes of dysuria. There was a tendency for urinary dysfunction to become worse as the primary disease progresses. Patients with HAM must be carefully followed up by urologists in order to prevent deterioration of the urinary tract.     

Are Blood Transfusions Associated with Greater Mortality Rates?: Results of the Sepsis Occurrence in Acutely Ill Patients Study

Background: Studies have suggested worse outcomes in transfused patients and improved outcomes in patients managed with restricted blood transfusion strategies. The authors investigated the relation of blood transfusion to mortality in European intensive care units (ICUs).

Methods: The Sepsis Occurrence in Acutely Ill Patients study was a multicenter, observational study that included all adult patients admitted to 198 European ICUs between May 1 and May 15, 2002 and followed them until death, until hospital discharge, or for 60 days. Patients were classified depending on whether they had received a blood transfusion at any time during their ICU stay.

Results: Of 3,147 patients, 1,040 (33.0%) received a blood transfusion. These patients were older (mean age, 62 vs. 60 yr; P = 0.035) and were more likely to have liver cirrhosis or hematologic cancer, to be a surgical admission, and to have sepsis. They had a longer duration of ICU stay (5.9 vs. 2.5 days; P < 0.001) and a higher ICU mortality rate (23.0 vs. 16.3%; P < 0.001) but were also more severely ill on admission (Simplified Acute Physiology Score II, 40.2 vs. 34.7; P < 0.001; Sequential Organ Failure Assessment score, 6.5 vs. 4.5; P < 0.001). There was a direct relation between the number of blood transfusions and the mortality rate, but in multivariate analysis, blood transfusion was not significantly associated with a worse mortality rate. Moreover, in 821 pairs matched according to a propensity score, there was a higher 30-day survival rate in the transfusion group than in the other patients (P = 0.004).     

A one-centre prospective audit of peri- and postoperative blood loss and transfusion practice in patients undergoing hip or knee replacement surgery

We prospectively audited peri-operative blood loss and blood transfusion practice in 42 elderly patients (mean age, 71.8 years, 68% female) undergoing hip or knee surgery in an orthopaedic unit. Only in 57% of all operations was blood loss recorded. Compliance with the Maximum Surgical Blood Ordering Schedule (MSBOS) was variable, and Cross-matching to Transfusion (C/T) ratios were low. In 86% of operations, blood had been issued pre-operatively (average three units, range = 1-61 units). Of these patients, 75% subsequently received a transfusion. In 26% of all the operations, the transfusion, although confirmed by the blood transfusion laboratory records, had not been recorded in the medical or nursing notes. The average pre-operative Hb in the transfusion group was 123 g/l (range, 80-144 g/l) and 112 g/l postoperatively and after a transfusion (range, 75-133 g/l). This compared to the non-transfusion group's value of 124 g/l (range, 86-186 g/l) and 113 g/l (range, 77-147 g/l) postoperatively. The high blood issuing and transfusion rates raise the concern that transfusions are being given in response to habit or blood availability, and not medical indications. This would imply that some patients are exposed to unnecessary risks. Furthermore, inadequate documentation of the transfusion process opens the medical profession to criticism and medical, legal and ethical complications regarding patient care. Positive improvements suggested by regular medical audit may help address these problems.     

Clinical use of autologous frozen blood in the surgery of three esophageal cancer patients

Autologous frozen blood transfusion (AFBT) has advantages both of autologous and frozen blood transfusion. In AFBT there are no remarkable adverse effects which often emerge after usual heterologous blood transfusion. As a rule, four hundred milliliters of blood were drawn twice from patients and reserved as autologous frozen blood (AFB) preoperatively. It is supposed that radical operation of esophageal cancer using only AFB is difficult to perform because of various kinds of preoperative risks. In this paper three cases of radical esophageal cancer operations, in which only AFBT were used are reported. Pre- and postoperative liver functions were uneventful. RBC counts, Hb and Hct dropped after drawing blood and did not recover until the day of operation. Postoperatively, they deteriorated further but recovered to initial values without any specific treatment within 5 months after operation. Pre- and postoperative PaO2 values of AFBT were not different from those of the usual blood transfusion. Thus using only AFBT, esophageal cancer operations were performed without any disadvantageous effects.