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Biomedical subjects

A M Hussein

Publications and source records attributed to A M Hussein.

At least 19 recordsLinked to original sources

Diagnosis of tuberculous lymphadenitis by FNAC, microbiological methods and PCR: a comparative study.

Despite its usefulness in the diagnosis of tuberculous lymphadenitis, fine needle aspiration cytology (FNAC) faces several limitations, and its sensitivity and specificity are not well established. The diagnostic accuracy and limitations of FNAC were studied in comparison with conventional microbiological methods and polymerase chain reaction (PCR). Sixty patients with lymphadenopathy and a clinical diagnosis of tuberculous lymphadenitis were subjected to FNA. The aspirate was used for cytological examination, Ziehl-Neelsen staining, mycobacterial culture and PCR. PCR was performed using two sets of oligonucleotide primers for Mycobacterium tuberculosis and a single primer for M. bovis species. The results of FNAC, microbiological methods and PCR correlated with the clinical outcome after follow-up for an average period of 24 months. Twenty-five cases (41.6%) were treated and responded well to anti-tuberculosis therapy, among them 17 were correctly diagnosed by FNAC (68%), eight by microbiological methods (32%) and 24 by PCR (96%). When PCR is considered the gold standard, FNAC predicted the correct diagnosis in 62% of cases with a high false negative rate (38%) due to the absence of granuloma/necrosis in smears from cases of early tuberculosis. In the latter group PCR proved to be the most valuable and a diagnostic success of 100% was achieved when FNAC and PCR were combined. In addition, PCR allowed immediate characterization of M. tuberculosis in the vast majority (96.2%) of cases in the study population.

Adult↗

Granulomatous mammary disease: ten years' experience with fine needle aspiration cytology.

OBJECTIVE: To determine the aetiological types of granulomatous disease of the breast in women presenting with mammary complaints in the Sudan. METHODS: Clinical history and physical examination, complete blood counts, Mantoux test, histopathology and fine needle aspiration cytology (FNAC). RESULTS: Granulomatous mastitis was seen in 11/2500 (0.44%) patients with mammary disease over a 10-year period. All were of childbearing age (mean 26.0 +/- 5.9 years). Common presentations were diffuse swelling, well-circumscribed masses, nipple retraction, multiple sinuses and superficial skin ulcers. Lymphadenopathy was seen in more than 60% of the patients. Diagnosis was based on cytomorphological features in 10/11 cases and histopathology in one. Nine were diagnosed with tuberculous mastitis and two with idiopathic granulomatous mastitis. Acid-fast bacilli (AFB) could not be demonstrated in any of the cytology smears. Tuberculous mastitis responded to empirical anti-tuberculosis treatment, with a minimum follow-up of 2 years in seven women. CONCLUSION: Tuberculous mastitis is a rare entity in women with mammary disease in the Sudan. Alternative diagnoses such as idiopathic granulomatous mastitis should be made only after failure of an adequate trial of anti-tuberculosis treatment. FNAC is a useful diagnostic tool even if AFB cannot be demonstrated.

Adult↗

Ligation-anopexy for treatment of advanced hemorrhoidal disease.

PURPOSE: Destruction of the anchoring tissue system is considered to be the essential prerequisite to the pathogenesis of advanced hemorrhoidal disease. Ligation-anopexy was designed to 1) restore fixation of the hemorrhoidal cushions to the underlying internal sphincter, 2) reduce hemorrhoidal prolapse, and 3) minimize the hemorrhoidal blood flow. The purpose of this study was to evaluate the ligation-anopexy as a new technique for the treatment of advanced stages of hemorrhoidal disease. METHODS: This study included 40 patients with hemorrhoidal disease (mean age 29.63 +/- 9.79 years, male/female ratio 34:6). Twenty-two patients had third-degree and 18 patients had fourth-degree hemorrhoids; of those with fourth-degree hemorrhoids, two patients had associated anal fissure and three patients had partial mucosal prolapse. Informed consent was obtained from all patients. After reduction of hemorrhoidal prolapse and under general or spinal anesthesia, a needle with 2-0 polyglactin (Vicryl) was inserted 1.5 cm above the dentate line using a Sims' speculum. The needle was inserted deep enough to fix the mucosa and the submucosa to the underlying internal sphincter. After the suture was tied, the redundant mucosa was pulled distally to be incorporated in the ligature, and the thread was relegated around it to form a mucosal tag. RESULTS: Inclusion of a part of the internal sphincter with ligation of the redundant mucosa ensures adequate retraction of prolapsed hemorrhoids (hemorrhoid lift). Postoperative pain was accepted by 90 percent of the patients and disappeared after treatment with oral diclofenac. The immediate complications included anal spasm in 10 percent, postoperative bleeding in 2.5 percent, and thrombosis of the external hemorrhoids in 2.5 percent of patients. Neither recurrence nor anal stenosis was observed after 12 months of follow-up. CONCLUSION: Despite the limited number of patients and the short follow-up, the preliminary results of ligation-anopexy in the treatment of advanced hemorrhoidal disease are encouraging.

Adult↗

Schistosomal pelvic floor myopathy contributes to the pathogenesis of rectal prolapse in young males.

PURPOSE: Rectal prolapse is common in young males in Egypt. The role of schistosomiasis in the pathogenesis of rectal prolapse is not clearly defined. The purpose of this work is to study changes in the pelvic floor muscles in patients of rectal prolapse associated with schistosomiasis. METHODS: This study included 33 male patients with rectal prolapse of whom 27 patients with schistosomiasis and 6 patients free from schistosomiasis. Biopsies were taken from the pelvic floor muscle during surgery. The prepared sections were examined for histopathologic structural changes, for ultrastructural changes (by using electron microscopy) and after immunohistochemical staining by using anti-IgG and anti-IgM antibodies. RESULTS: The muscles from the patients without schistosomiasis had no histologic or EM changes and showed negative staining for IgG and IgM. Myopathic changes were found in the group of patients with schistosomiasis, including increased variation in the fiber diameter in 66.6 percent of patients, degenerative changes in 59.26 percent of patients, fiber splitting and fragmentation in 44.4 percent of patients, and endomysial fatty changes in 55.5 percent of patients. Ultrastructural study revealed starting loss of striation and margination of the nucleus in 70.37 percent of patients, distorted myofibrillar pattern in 51.85 percent of patients, disturbed endoplasmic reticulum and increased glycogen granules in all patients, the mitochondria are irregularly arranged with electron dense matrix in 40.74 percent of patients, and prominent nuclear sap in 13.72 percent of patients. The muscles of all the schistosomal patients showed a positive cytoplasmic staining for immunoglobulin G, of them only 12 patients showed positive staining for IgM. CONCLUSION: Patients with schistosomiasis suffer from pelvic floor myopathic changes that may contribute to the pathogenesis of rectal prolapse in young males. The immunohistochemical findings suggest immunologic mechanism for this myopathy.

Adolescent↗

A phase I/II study of high-dose cyclophosphamide, cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies.

The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colony-stimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m2 per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m2 per day as a 24-h continuous i.v infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300-900 mg/m2) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 microliter was 10 days (range, 9-12 days) for those who received PBPCs and 15 days (range, 15-34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2-17 months). The maximally tolerated dose of thioTEPA was 600 mg/m2 given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration, The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies.

Adult↗

Evaluation of GM-CSF mouthwash for prevention of chemotherapy-induced mucositis: a randomized, double-blind, dose-ranging study.

Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis. The mechanism of this effect could be related to acceleration of haematopoiesis and/or increase in functional activation of WBC. We conducted a double-blind, placebo-controlled, dose ranging study of GM-CSF (mol-gramostim) mouthwash in patients with breast cancer during the first treatment cycle of a combination chemotherapy regimen which has historically produced dose-limiting (grade > or = 3) mucositis in approximately 39% of patients. Subjects were randomized to receive either placebo mouthwash (0.1 percent albumin) or one of four concentrations of GM-CSF mouthwash (0.01, 0.1, 1.0 or 10 mcg/ml). The primary endpoint was to evaluate the relationship between dose of GM-CSF mouthwash received and probability of grade > or = 3 mucositis using a logistic model. Solutions were administered four times daily starting within 24 hours of chemotherapy initiation and continuing until the end of the cycle (day 21). Mucositis was assessed on days 1-6, 10, 15 and 21. Day 6 plasma samples were assayed for GM-CSF. Forty-five patients were evaluable for response (nine per dosing group). A 42% risk (15/36) of mucositis grade > or = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 patients on the placebo arm. No evidence of dose response was found by logistic regression. Five patients had a detectable plasma concentration of GM-CSF (56-209 pg/ml). A positive correlation between GM-CSF dose and leukocyte recovery was noted (P = 0.04).

Adult↗

Protection against cytosine arabinoside-induced alopecia by minoxidil in a rat animal model.

BACKGROUND: Alopecia is one of the most physically and psychologically distressing side effect of cancer chemotherapeutic agents. In the past 2 years, we reported that: (a) treatment of 8-day-old rats with 1-B-D-arabinofuranosylcytosine (Ara-C), doxorubicin, and cyclophosphamide (CYC) consistently produced alopecia; (b) Imuvert, a biological response modifier, produced complete protection against alopecia induced by Ara-C and doxorubicin, but not that produced by CYC, most probably through the release of interleukin-1; and (c) n-acetylcysteine protected against CYC-induced alopecia in the newborn rat. METHODS: As an extension to these observations, we chose to test the efficacy of minoxidil, a drug known to be a hypertrichotic agent, in preventing chemotherapy-induced alopecia in the newborn rat animal model. RESULTS: Minoxidil, when injected locally, offered good local prevention against Ara-C but not CYC-induced alopecia. Minoxidil 2% dissolved in a vehicle of ethanol, propylene glycol, and water was not effective when applied topically. CONCLUSIONS: The mechanism of action of minoxidil in its prevention against Ara-C-induced alopecia is currently unknown. This observation may shed some light on the in vivo mechanism of action of minoxidil and may prove to be important in our efforts to search for agents to prevent alopecia among patients receiving chemotherapy.

Alopecia↗

Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.

Peripheral blood progenitor cells (PBPCs) were collected without prior association with chemotherapy but after the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) produced in Chinese hamster ovary cells (CHO-GM, regramostim), Escherichia coli (E. coli-GM, molgramostim), or yeast (Yeast-GM, sargramostim) and used in conjunction with autologous bone marrow after high-dose chemotherapy in 69 patients with breast cancer or melanoma. The mean peripheral white blood cell (WBC) counts increased by 2.2 to 2.7-fold after regramostim, 4.5 to 7.3-fold after molgramostim and 4.3-fold after sargramostim. All patients underwent three leukaphereses. The mean (+/- standard error) total nucleated pheresed cells per kg x 10(8) were 4.15 +/- 0.56, 15.10 +/- 1.77 and 7.24 +/- 1.00 for patients receiving regramostim, molgramostim or sargramostim respectively. The mean (+/- standard error) granulocyte-macrophage colony-forming units per kg x 10(4) mobilized into the PB were 8.75 +/- 3.63, 71.03 +/- 17.85, and 65.11 +/- 18.74 for patients receiving regramostim, molgramostim, or sargramostim respectively. The total mean (+/- standard error) CD34+ cells per kg x 10(7) collected by three leukaphereses were 3.28 +/- 1.62, 1.34 +/- 0.51 and 2.57 +/- 1.93, for patients receiving regramostim, molgramostim or sargramostim respectively. The use of either molgramostim- or sargramostim-primed PBPCs led to complete elimination of absolute leukopenia with a WBC count under 100/mm3 in 64% and 77% of patients treated, respectively. Patients receiving molgramostim-primed PBPCs required fewer red blood cells transfusions than patients receiving regramostim-primed PBPCs (p = 0.0062). Our data indicate that PBPCs collected without prior association with chemotherapy but after either molgramostim or sargramostim with autologous bone marrow support and GM-CSF shorten the hematopoietic recovery after myeloablative chemotherapy in patients with breast cancer or melanoma.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of granulocyte-macrophage colony stimulating factor produced in Chinese hamster ovary cells (regramostim), Escherichia coli (molgramostim) and yeast (sargramostim) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.

Peripheral blood progenitor cells (PBPCs) were collected without prior association with chemotherapy but after the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) produced in Chinese hamster ovary cells (CHO-GM, regramostim), Escherichia coli (E. coli-GM, molgramostim), or yeast (Yeast-GM, sargramostim) and used in conjunction with autologous bone marrow after high-dose chemotherapy in 69 patients with breast cancer or melanoma. The mean peripheral white blood cell (WBC) counts increased by 2.2 to 2.7-fold after regramostim, 4.5 to 7.3-fold after molgramostim and 4.3-fold after sargramostim. All patients underwent three leukaphereses. The mean (+/- standard error) total nucleated pheresed cells per kg x 10(8) were 4.15 +/- 0.56, 15.10 +/- 1.77 and 7.24 +/- 1.00 for patients receiving regramostim, molgramostim or sargramostim respectively. The mean (+/- standard error) granulocyte-macrophage colony-forming units per kg x 10(4) mobilized into the PB were 8.75 +/- 3.63, 71.03 +/- 17.85, and 65.11 +/- 18.74 for patients receiving regramostim, molgramostim, or sargramostim respectively. The total mean (+/- standard error) CD34+ cells per kg x 10(7) collected by three leukaphereses were 3.28 +/- 1.62, 1.34 +/- 0.51 and 2.57 +/- 1.93, for patients receiving regramostim, molgramostim or sargramostim respectively. The use of either molgramostim- or sargramostim-primed PBPCs led to complete elimination of absolute leukopenia with a WBC count under 100/mm3 in 64% and 77% of patients treated, respectively. Patients receiving molgramostim-primed PBPCs required fewer red blood cells transfusions than patients receiving regramostim-primed PBPCs (p = 0.0062). Our data indicate that PBPCs collected without prior association with chemotherapy but after either molgramostim or sargramostim with autologous bone marrow support and GM-CSF shorten the hematopoietic recovery after myeloablative chemotherapy in patients with breast cancer or melanoma.

Animals↗

Protection against chemotherapy-induced alopecia by cyclosporin A in the newborn rat animal model.

BACKGROUND: We have previously shown that several agents will protect against chemotherapy-induced alopecia in the newborn rat animal model. Such protective agents render the hair follicle keratinocytes resistant to chemotherapy possibly by the expression of P-glycoprotein (Pgp). Cyclosporin A (CSA) is a potent inhibitor of Pgp. METHODS AND RESULTS: Efficacy of CSA was tested in its effects on chemotherapy-induced alopecia in the newborn rat animal model. CSA, when applied topically, protected rats from local alopecia induced by various agents. CONCLUSION: The mechanism of protection by CSA and its relationship to Pgp remain uncertain. The potential clinical applicability of this observation remains to be determined.

Administration, Cutaneous↗

Chemotherapy-induced alopecia: new developments.

Alopecia (hair loss) is one of the most physically and psychologically distressing side effects of cancer chemotherapeutic drugs. Since its first recognition as a common outcome to most chemotherapeutic agents, only a few trials have been reported, using either a method to temporarily reduce the scalp blood flow (scalp tourniquet or hypothermia) or vitamin E, with undocumented and variable efficacy. The lack of progress in the treatment and prevention of chemotherapy-induced alopecia is in part due to the lack of a reproducible animal model. In the past 2 years, we reported on the following observations: (1) treatment of 8-day-old rats with vidarabine (ara-C), doxorubicin, and cyclophosphamide consistently produced either total body alopecia (ara-C and cyclophosphamide) or alopecia confined to the head and proximal part of the back (doxorubicin); (2) Imuvert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against alopecia induced by ara-C and doxorubicin but not that produced by cyclophosphamide; (3) the protective effect of Imuvert against chemotherapy-induced alopecia is mediated by a monocyte-mediated cytokine; and (4) this monocyte-derived cytokine is, possibly, interleukin-1. These observations constitute important progress in the understanding and prevention of chemotherapy-induced alopecia.

Alopecia↗

Phase II trial of 4'-0-tetrahydropyranyladriamycin (pirarubicin) in head and neck carcinoma.

BACKGROUND: 4'-0-tetrahydropyranyladriamycin (Pirarubicin, Meiji Seika (USA) Inc., New York, NY) may be less toxic than doxorubicin. METHODS: A Phase II trial of Pirarubicin was done in 26 patients who had not previously had chemotherapy and who had measurable and incurable head and neck carcinoma. All patients received an intravenous bolus dose of 60 mg/m2 Pirarubicin in the first cycle without any prophylactic antiemetic. The cycles were repeated every 3 weeks. Based on tumor response, nadir counts, or complications of myelosuppression, the doses were escalated or de-escalated by 10 mg/m2, if necessary, in the second cycle to achieve mild leukopenia (3000-4000 leukocytes/microliters). RESULTS: Leukopenia was mild, moderate (2000-2999 leukocytes/microliters), severe (1000-1999 leukocytes/microliters), and life threatening (less than 1000 leukocytes/microliters) in 13%, 31%, 27%, and 9% of the first two courses, respectively. The median interval to nadir leukopenia was 13 days (range, 7-21 days), with a median of 8 days (range, 5-13 days) to recover to normal. One patient with a leukocyte count of 800/microliters and an absolute granulocyte count (AGC) of 488/microliters died of sepsis 15 days after the first course. All patients had at least one course that resulted in leukopenia. One episode each of mild (100,000-150,000 platelets/microliters) and severe (25,000-49,999 platelets/microliters) thrombocytopenia occurred in the first two courses. Leukocyte, granulocyte, and platelet counts were not done routinely after the second cycle. Six patients who received four or more courses with cumulative doses of 310, 610, 340, 260, 660, and 550 mg/m2 had decrements of 0%, 1%, 7%, 10%, 12%, and 13%, respectively, in radionuclide left ventricular ejection fraction (LVEF). All other toxic effects were mild. CONCLUSIONS: In the 24 patients with disease evaluable for response to Pirarubicin therapy, 1 had a complete response that lasted 5 months and 4 had a partial response of 2, 3, 6, and 8 months. The median survival time in patients with disease that responded to Pirarubicin therapy was 27 months; in patients with disease that did not respond to Pirarubicin therapy, the median survival time was 4 months, and in the total cohort, it was 5 months. Pirarubicin was well tolerated and was an active agent in head and neck squamous cell carcinoma.

Adult↗

Five-drug antiemetic combination for cisplatin chemotherapy.

A combination of metoclopramide, dexamethasone, droperidol, lorazepam, and diphenhydramine was used in prophylaxis of high-dose (greater than or equal to 100 mg/m2) or moderate dose (greater than or equal to 50 mg/m2) cisplatin. Sixty minutes prior to starting cisplatin, 16 mg dexamethasone, 50 mg diphenhydramine, and 0.5 mg lorazepam were given orally (PO). Droperidol 1 mg was given intramuscularly (IM) 15 minutes prior to beginning cisplatin. Repetitive doses of intravenous (IV) metoclopramide, 2 mg/kg in 75 ml 5% dextrose in water over 15 minutes was given 30 minutes prior to, and at 1 1/2, 4 1/2, and 7 1/2 hours after beginning cisplatin chemotherapy. Only patients with nausea and/or vomiting received subsequent doses of 2 mg/kg metoclopramide IV every 3 hours as needed. Patients refractory to metoclopramide were given 1 mg droperidol IM and 50 mg of diphenhydramine PO every 6 hours. There were 19 men and 9 women with a median age of 58 (range 31-75) years. Complete protection from nausea and vomiting in all courses of treatment occurred in 17 (61%) patients. In 63% and 70% of the 57 evaluable courses, there was neither nausea nor vomiting, during the first 24 hours after cisplatin. When present, nausea was mild and the median number of vomiting episodes was 2 (range 1-3). This antiemetic regimen was well tolerated. Toxicities were mild and occurred in 3 patients (angioneurotic edema, transient episode of facial twitching, and heaviness of tongue, respectively). The 5-drug antiemetic combination can prevent cisplatin-induced nausea and vomiting in a majority of patients.

Adult↗