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Biomedical subjects

M W Saif

Publications and source records attributed to M W Saif.

At least 19 recordsLinked to original sources
PubMed2006

DPYD*2A mutation: the most common mutation associated with DPD deficiency.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the elimination of approximately 80% of administered dose of 5-FU. DPD deficiency has been associated with severe 5-FU toxicity. Syndrome of DPD deficiency manifests as diarrhea, stomatitis, mucositis, and neurotoxicity and in some cases death. This is a true pharmacogenetic syndrome, with symptoms being unrecognizable until exposure to the drug. PATIENTS AND METHODS: A 75-year-old patient with metastatic pancreatic adenocarcinoma developed grade 4 thrombocytopenia, grade 3 coagulopathy, and grade 3 neurologic toxicity with a fatal outcome following administration of 5-FU. Due to pancytopenia, DPD activity could not be determined in peripheral blood mononuclear cells (PBMC) using a previously described radioassay. Therefore, screening and genotypic analysis of homozygous and heterozygous, known and unknown sequence variants, in the DPYD gene were performed using DHPLC as previously described. All DPYD sequence variants identified by DHPLC were confirmed by DNA sequencing using a dideoxynucleotide chain termination method and capillary electrophoresis on an ABI 310 Automated DNA Sequencer. RESULTS: Genotyping analysis of the DPYD gene revealed the presence of the heterozygous mutation, IVS14 + 1 G > A, DPYD*2A. CONCLUSION: Genotypic analysis using DHPLC can be employed to screen DPD deficiency in a patient with severe neutropenia. The mutation IVS14 + 1 G > A, DPYD*2A, is the most common mutation associated with DPD deficiency. A G > A base change at the splice recognition sequence of intron 14, leads to exon skipping and results in a 165-bp deletion in the DPD mRNA. We have previously demonstrated that a homozygote DPYD*2A genotype results in complete deficiency while the heterozygous DPYD*2A genotype results in partial deficiency of DPD.

Adenocarcinoma↗
PubMed2005

DIC secondary to acute pancreatitis.

Various hematological abnormalities including fall in serial values of hemoglobin or hematocrit, coagulation factor abnormalities, leukocytosis, acute hemolytic anemia, thrombocytopenia, and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome have been reported in patients with acute pancreatitis. Similarly, abnormalities of blood coagulation factors consistent with disseminated intravascular coagulopathy (DIC) have also been noticed in patients with pancreatitis. We report a case of a 33-year-old female with acute pancreatitis who presented with one episode of epistaxis and abnormal prothrombin time and partial prothrombin time. Coagulation work-up revealed thrombin time 24.3 s fibrinogen 110 mg/dl, D-dimers >1 and < 2, and fibrin degradation products >22. Pancultures did not show any evidence of infection. The patient maintained a normal renal and mental status during her illness. Her D-dimers continued to decrease with resolution of acute pancreatitis as evidenced by decreased abdominal pain, relief of nausea, control of vomiting, and decrease in serum amylase and lipase levels. This case report suggests that coagulation abnormalities are encountered in patients with acute pancreatitis. It is hypothesized that such hemostatic abnormalities may be related to early intravascular consumption of coagulation factors secondary to circulating pancreatic enzymes, particularly trypsin, or secondary to vascular injury. Recognition of these hematological complications including DIC is paramount. Physicians caring for these patients should be aware of such a complication of acute pancreatitis.

Acute Disease↗
PubMed2004

Thromboembolism following removal of femoral venous apheresis catheters in patients with breast cancer.

BACKGROUND: Apheresis catheters have simplified collection of peripheral blood stem cells (PBSC), but may be associated with thrombosis of the instrumented vessels. We performed a retrospective analysis to study the prevalence of thromboembolism associated with the use of femoral apheresis catheters in patients with breast cancer. PATIENTS AND METHODS: Patients were participants in clinical trials of high-dose chemotherapy with autologous PBSC rescue. They underwent mobilization with either high-dose cyclophosphamide (n = 21) or cyclophosphamide/paclitaxel (n = 64), followed by filgrastim. Double lumen catheters (12 or 13 Fr) were placed in the femoral vein and removed within 12 h of the last apheresis procedure. Apheresis was performed using a continuous flow cell separator and ACD-A anticoagulant. Thromboembolism was diagnosed by either venous ultrasonography or ventilation-perfusion scan. RESULTS: Nine of 85 patients (10.6%) undergoing large volume apheresis with use of a femoral catheter developed thromboembolic complications. Pulmonary embolus (PE) was diagnosed in five and femoral vein thrombosis in four patients. Four of the five patients who developed PE were symptomatic; one asymptomatic patient had a pleural-based, wedge-shaped lesion detected on a staging computed tomography scan. The mean number of apheresis procedures was 2.4 (range one to four) and the mean interval between removal of the apheresis catheter and diagnosis of thrombosis was 17.6 days. In contrast, none of 18 patients undergoing apheresis using jugular venous access and none of 54 healthy allogeneic donors undergoing concurrent filgrastim-mobilized PBSC donation (mean 1.7 procedures/donor) using femoral access experienced thromboembolic complications. CONCLUSIONS: Thromboembolism following femoral venous catheter placement for PBSC collection in patients with breast cancer may be more common than previously recognized. Healthy PBSC donors are not at the same risk. Onset of symptoms related to thrombosis tended to occur several weeks after catheter removal. This suggests that the physicians not only need to be vigilant during the period of apheresis, but also need to observe patients for thromboembolic complications after the catheter is removed. The long interval between the removal of apheresis catheter and the development of thromboembolism may have a potential impact on prophylactic strategies developed in future, such as the duration of prophylactic anticoagulation. Avoidance of the femoral site in breast cancer patients, and close prospective monitoring after catheter removal, are indicated.

Adolescent↗
PubMed2001

Reactivation of chronic hepatitis B infection following intensive chemotherapy and successful treatment with lamivudine: a case report and review of the literature.

BACKGROUND: Hepatitis B virus reactivation has been reported in cancer patients following administration of chemotherapy or immunosuppressive therapy and may result in liver damage of varying degrees of severity. Although treatment is supportive in nature, lamivudine, a nucleoside analogue has been found to suppress HBV replication as evidenced by reports of 13 cases in the medical literature. PATIENTS AND METHODS: We report a patient who achieved a successful outcome with lamivudine following reactivation of HBV during combination chemotherapy for non-Hodgkin's lymphoma, and provide a brief overview of the literature including the 13 published case reports. RESULTS: Lamivudine therapy resulted in clinical improvement as well as in normalization of liver function tests and coagulation profile. CONCLUSIONS: Lamivudine has been found to suppress HBV replication manifested both by histology and serum HBV-DNA levels in chronic carriers of HBV who developed reactivation of hepatic disease following chemotherapy. Physicians caring for such patients should be able to recognize this clinical challenge, and lamivudine should be considered.

Adult↗
PubMed2001

HIV and thrombosis: a review.

The array of clinicopathologic factors associated with acquired immune deficiency syndrome (AIDS) patients continues to increase and surprise many physicians. The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection. Various abnormalities predisposing to a hypercoagulable state have also been reported in AIDS patients including the presence of antiphospholipid antibodies and the lupus anticoagulant; deficiencies of protein C, protein S, heparin cofactor II, and antithrombin and increased levels of von Willebrand factor, and d-dimers. These abnormalities correlate with the severity of HIV-associated immunosuppression as measured by the CD4 cell counts and with the presence of concurrent infectious or neoplastic diseases. The authors reviewed the medical literature and describe various abnormalities predisposing to a hypercoagulable state in AIDS patients along with the management of such complications. This issue is important because deep venous thrombosis (DVT), pulmonary embolus (PE), or thrombosis at other sites can develop in patients with AIDS who are ambulatory and have no known risk factors for pathologic thrombus formation, providing another challenge in an already difficult clinical situation. This also provides a strong rationale for careful prospective studies focusing on the prevalence and risk factors involved in the development of thromboembolic complications in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2001

HIV-associated autoimmune hemolytic anemia: an update.

In addition to developing immunosuppression, opportunistic infections, and malignancies, patients infected with human immunodeficiency virus (HIV) also develop many hematologic disorders. Although cytopenias including thrombocytopenia, anemia, and leukopenia, and bone marrow dysplasia are the most common hematologic complications encountered in such patients, hemostatic abnormalities that predispose patients to thromboembolism have also been recognized. Anemia in HIV patients can be multifactorial but an increased incidence of autoimmune hemolytic anemia has been manifested by the increased incidence of positive Coombs' test reported in patients with acquired immune deficiency syndrome (AIDS). Overt hemolysis is a rare complication. This review article discusses the etiology, pathophysiology, clinical features, diagnosis, treatment, and complications of autoimmune hemolytic anemia (AIHA) associated with HIV infection.

Anemia, Hemolytic, Autoimmune↗
PubMed2001

AIDS and thrombosis: retrospective study of 131 HIV-infected patients.

The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection and various abnormalities predisposing to a hypercoagulable state have also been reported in such patients. To study the incidence of thrombosis in patients infected with HIV, and to assess the correlation of thrombosis with the degree of immunosuppression as well as the association with active illnesses and neoplasms, we reviewed the charts of 131 patients, which include all the patients with the diagnosis of HIV admitted or seen in the clinic between January 1, 1993, and January 1, 1998. The diagnosis of thrombosis was based on documented reports of venous plethysmography or venography for deep venous thrombosis and ventilation-perfusion scan or pulmonary angiography for pulmonary embolus. Risk factors for thrombotic disease were evaluated including general risk factors such as family history, ambulatory status, medications, and data were also collected regarding CD4 cell counts and the presence of concurrent or remote opportunistic infections, acquired immune deficiency syndrome (AIDS)-related malignancy or other AIDS-related diseases at the time of diagnosis of the thrombotic event. We also reviewed the medical literature via MEDLINE and found 45 cases of patients with HIV who developed thromboembolic complications. We found thrombotic complications in 9 of 37 patients with a CD4 count less than 200 cells/mm3 and in 1 of the remaining 94 patients with a CD4 count more than 200 cells/mm3. The difference was significant, with p = 0.00004, and the estimated odds of an event given CD4 cell counts less than 200/mm3 is 29.89 (95% confidence interval). Three patients had abnormalities of anticoagulation proteins. There was a history of opportunistic infections in 5 patients and malignancy in 3 patients. Two patients with autoimmune hemolytic anemia (AIHA) secondary to HIV-infection developed PE upon transfusion of packed red blood cells. The results of this study suggests that AIDS appears to predispose to thrombosis. It also revealed a significant correlation between thrombotic disease and CD4 counts (<200/mm3) as well as the presence of opportunistic infections, AIDS-related neoplasms, or autoimmune disorders associated with HIV such as AIHA. Therefore, clinicians caring for these patients should be aware of thromboembolic disease as a possible complication of AIDS. Further studies to elucidate the mechanisms underlying this abnormal hemostatic profile, the epidemiology, and to answer several questions such as should patients with risk factors for HIV infection who develop thromboembolic complications be further evaluated including tests for HIV are warranted.

AIDS-Related Opportunistic Infections↗
PubMed2001

Bleeding diathesis in multiple myeloma.

Patients with multiple myeloma having a higher titer of serum paraproteins can manifest hemostatic abnormalities. Most of these abnormalities predispose the patient to hemorrhage. Less commonly, thrombotic complications may occur in association with paraprotein disorders. We investigated a 56-year-old female diagnosed with multiple myeloma (type IgG kappa, 59 g/L) whose coagulation profile showed an increase in thrombin time and prothrombin time. To investigate the etiology of the abnormal coagulopathy, further diagnostic studies including coagulation factor assays, platelet aggregation studies, replitase time, mixing studies using pooled normal plasma, and protamine were performed. Mixing studies demonstrated correction of the prothrombin time. Thrombin time was near-corrected but the replitase-time was not corrected by these mixing studies. After chemotherapy, the paraprotein concentration decreased (12g/L) and the coagulation results returned to normal. Patients with multiple myeloma may develop bleeding diathesis secondary to a variety of mechanisms. One such mechanism is direct inhibition of fibrin monomer aggregation due to the paraprotein, resulting in prolongation of the thrombin time and the replitase time. The failure to correct the former by the addition of protamine further augments the direct role of FAB portion of the paraprotein molecule on inhibition of fibrin monomers.

Blood Coagulation Factors↗
PubMed2001

Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil.

5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur abruptly or more gradually during the course of chemotherapy. Peripheral neuropathy with 5-FU therapy has only rarely been reported. Two patients treated in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans of the brain and neurologic examination did not support a CNS basis for the condition. Electromyograms and nerve conduction studies revealed sensorimotor polyneuropathy. Other common etiologies of peripheral neuropathy were excluded. The neurological condition of these patients stabilized after 5-FU dose reduction and partial resolution gradually occurred when protocol therapy was stopped. Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy is unexpected. Patients with DPD deficiency treated with conventional doses of 5-FU typically develop acute CNS toxicity shortly after therapy, accompanied by extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may also experience CNS toxicity, particularly with high-dose schedules, and both parent drug and its catabolites may be contributory. Since DPD was profoundly inhibited during eniluracil therapy in these two patients, it is likely that 5-FU or its active metabolites were contributing factors to the peripheral neuropathy.

Adult↗
PubMed2001

Castleman disease in an HIV-infected patient with Kaposi sarcoma.

Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder, characterized by systemic symptoms, generalized lymphadenopathy, hepatosplenomegaly, proteinuria, and rash. The clinical course is variable and may range from indolent to aggressive, fulminating in a rapidly fatal illness. Mortality is usually from infective complications and less commonly from malignancies, such as lymphoma or Kaposi sarcoma. The association of concurrent or preceding Castleman disease with Kaposi sarcoma is well documented. Castleman disease developed in a 51-year-old patient with AIDS about 10 months after diagnosis of Kaposi sarcoma. MCD was found to be associated with human herpesvirus 8/Kaposi sarcoma-associated herpesvirus.

Blotting, Southern↗
PubMed2000

Varicella zoster meningitis preceeded by thrombophlebitis in a patient with Hodgkin's disease.

Varicella zoster (V-Z) infections are common among patients with hematological malignancies, particularly Hodgkin's disease (HD). The common denominator in both HD and V-Z infections is immunosuppression. Most of V-Z infections occur in patients with HD during the remission period, who have mixed cellularity sub-type, with stage III disease and who have received combined chemo-radiation therapy. Involvement of the central nervous system usually manifests as post-herpetic neuralgia or encephalitis. Angiitis has also been found in association with V-Z infections. The authors describe a case of HD who developed V-Z meningitis preceeded by superficial thrombophlebitis of upper extremities during the period of active chemotherapy.

Adult↗
PubMed2000

Thromboembolism associated with HIV infection: a case report and review of the literature.

The array of the clinicopathologic spectrum related to HIV infection continues to increase and present new challenges to physicians caring for HIV-infected patients. Recent literature is encumbered with reports of various abnormalities consistent with a hypercoagulable state leading to thromboembolic complications. The coexistence of HIV/AIDS-related illnesses, such as malignancies, opportunistic infections, or autoimmune diseases, as well as drug therapy, may also predispose HIV-infected patients to thromboembolic disease. A case report of a 39-year-old man with Kaposi sarcoma who developed pulmonary embolism is presented, along with a review of the literature.

Adult↗
PubMed1999

Malignant ascites as only manifestation of metastatic prostate cancer.

Prostate cancer is the most common malignancy in men in the US. Both at diagnosis and throughout the disease progression it can metastasize to multiple organs (bone and lymph being the most common). Effusions (either pleural or abdominal) are relatively uncommon, but usually occur as a result of soft tissue lesions. Herein we report on a patient with androgen independent prostate cancer and an elevated PSA with disease confined to ascites of the abdomen.

Journal Article↗
PubMed1998

Abdominal presentation of Burkitt's lymphoma in an HIV-positive patient.

The incidence of non-Hodgkin's lymphoma (NHL) has greatly increased in the AIDS population. It has been estimated that 8% to 27% of newly diagnosed cases of NHL are related to AIDS. The vast majority are clinically aggressive B cell-derived lymphomas. AIDS-associated NHLs are classified according to their anatomic site of location into three classes: (1) systemic (both nodal as well as extranodal), (2) primary central nervous system, and (3) body cavity-based lymphomas. We present a case report of a patient with HIV infection who presented with abdominal pain and distension and was found to have an intraabdominal type of Burkitt's lymphoma. This case underlines the following points: 1. In the evaluation of acute abdominal disease in a patient with AIDS, both AIDS-related infections as well as malignancies should be sought in the differential diagnosis. 2. Computed tomographic scanning of the abdomen is the modality of choice for characterization of disease as well as direction of appropriate therapy. 3. AIDS-related NHL remains an important biologic model for investigating the development and progression of lymphomas in the immune-deficient host. 4. With the improved survival of patients with AIDS secondary to better prevention and treatment of infections, there may be an increase in AIDS-associated malignancies; therefore, further research pertaining to the development and characterization of therapy modalities of such malignant tumors is mandatory.

Abdominal Neoplasms↗
PubMed1998

HIV-associated autoimmune hemolytic anemia complicated by pulmonary embolism following a red blood cell transfusion: case report and review of the literature.

BACKGROUND: Though positive direct antiglobulin tests are common in AIDS patients, overt hemolysis is rare. A hypercoagulable state has recently been recognized in these patients and may contribute to the thromboembotic complications previously reported in three patients with HIV-associated autoimmune hemolytic anemia. CASE REPORT: An AIDS patient with severe warm autoimmune hemolytic anemia developed a pulmonary embolus after a single red blood cell transfusion. CONCLUSION: There may be an increased risk of thromboembolism in AIDS patients with autoimmune hemolytic anemia who receive red blood cell transfusions, a concern we have previously raised. Prophylactic anticoagulation should be considered in this setting.

Adult↗