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1.
Breast Cancer Res Treat ; 206(1): 155-162, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38689173

ABSTRACT

PURPOSE: There has been a UK national directive to ensure that patients are offered reconstructive surgical options. We aimed to assess any change in oncoplastic practice over a 10-year period. METHODS: The surgical management of 7019 breast cancers was retrospectively assessed at Nightingale Breast Centre, Manchester University UK, from 2010 to 2019. The procedures were categorised into breast conservative surgery (BCS) and mastectomy ± immediate reconstruction. The data were analysed using inclusion and exclusion criteria. RESULTS: The overall rates of BCS and mastectomy were 60.1% and 39.9% respectively. No statistically significant change in the overall rates of BCS or mastectomy was observed over the last decade (p = 0.08). The rate of simple wide local excision (WLE) decreased from 98.7% to 89.3% (p < 0.001), whilst the rate of therapeutic mammoplasty (TM) increased from 1.3% to 8% (p < 0.01). The rate of chest wall perforator flaps (CWPF) changed from zero to account for 2.7% of all BCS by 2019. The overall rate of immediate breast reconstruction (IBR) did not significantly change over the study period, but it consistently remained above the national average of 27%. The rate of implant-based IBR increased from 61.3% to 76.5% (p = 0.012), whilst the rate of Latissimus Dorsi (LD) reconstruction decreased from 26.7% to 5.1% (p < 0.05). Additionally, the rate of nipple-sparing mastectomy significantly increased from 5.2% to 24%. CONCLUSION: No significant changes in the overall rates of BCS was observed, the rates of advanced breast conservation techniques, nipple-sparing mastectomy, and implant-based IBR all have increased, whilst the use of LD reconstruction decreased.


Subject(s)
Breast Neoplasms , Mammaplasty , Mastectomy , Humans , Female , Mammaplasty/trends , Mammaplasty/methods , Mammaplasty/statistics & numerical data , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Neoplasms/epidemiology , Retrospective Studies , Middle Aged , Mastectomy/methods , Mastectomy/statistics & numerical data , Mastectomy/trends , Adult , Aged , Mastectomy, Segmental/methods , Mastectomy, Segmental/statistics & numerical data , United Kingdom/epidemiology
2.
IJID Reg ; 2: 51-54, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35721439

ABSTRACT

Background: The SARS-CoV-2 pandemic has led to a strain on medical resources. The development of countermeasures to prevent its spread is evolving. Healthcare workers (HCWs) are at high risk for contracting and transmitting the disease. Methods: Serology testing of volunteer HCWs was performed at King Faisal Specialist Hospital and Research Center in Riyadh (the Center) in order to determine the prevalence of SARS-CoV-2 antibodies, as well as the associated risk factors, in the hope of implementing adequate prevention and control measures. Results: 1076 subjects participated in this study, of whom 24.3% were seropositive. The majority were nurses (379, 35%) or physicians (245, 22.2%). 392 (36.4%) of the 1076 subjects were caregivers for COVID-19 patients, and 463 (43.0%) reported contact with infected employees. There was a statistically significant association between taking care of COVID-19 patients and being diagnosed with COVID-19 (chi-square test, p = 0.046). There was a significant association between being in contact with infected employees and having a positive IgG result (chi-square test, p < 0.001). Conclusions: A baseline analysis of SARS-CoV-2 seropositivity in HCWs at a large tertiary care hospital in Riyadh was performed as the first part of a prospective study of HCWs. The reported seropositivity was 24.3% - higher than that of other hospitals in Riyadh. IgG testing was very useful in the detection of previous SARS-CoV-2 infection, as it has high negative predictive value.

3.
Arch Gynecol Obstet ; 299(2): 551-558, 2019 02.
Article in English | MEDLINE | ID: mdl-30564930

ABSTRACT

OBJECTIVE: The ultimate goal of this study is to reassess the five-dimensional implantation markers and pregnancy predictors on the day of human chorionic gonadotropin injection in the intracytoplasmic sperm injection and embryo transfer programs. DESIGN: A pilot prospective clinical trial. SETTING: The Assisted Reproductive Technology Unit of Ain Shams Maternity Teaching Hospital during the period from April 2014 to December 2017. PATIENTS AND METHODS: The study was conducted on 400 women undergoing intracytoplasmic sperm injection (ICSI). Those women were not older than 40 years, with normal uterine cavity and with no previous uterine scars. INTERVENTION: The ovarian stimulation protocol, used in this study for all patients, was the long protocol, before ovarian stimulation therapy, patients were instructed to use oral contraceptive pills from day 2 starting in the preceding cycle, then the standard regimen. On the day of hCG administration, 5D transvaginal ultrasound measurements were performed by the same observer after the patients had emptied their bladders. Measurements included endometrial volume and 3D power Doppler parameters, endometrial vascularization index, flow index, and vascularization flow index. RESULTS: The present study shows that endometrial volume ≥ 5 in the prediction of endometrial receptivity in ICSI patients had good sensitivity and low specificity in a group application; in an individual application it had good predictive negative value and bad predictive positive value. So it could be used as a good test to exclude success. Overall pregnancy rate was 40.5%; endometrial volume, flow index, vascularization index, and vascularization flow index were significantly lower in the nonpregnant group than those of the pregnant group. The area under curve in the receiver operating characteristic for three-dimensional ultrasound and power Doppler angiography parameters was statistically significant, but their values were suggestive but not conclusive in the prediction of endometrial receptivity in ICSI patients, no cutoff points with good diagnostic characteristics could be obtained. CONCLUSION: Five-dimensional ultrasound and power Doppler angiography is a useful exam to assess the endometrial receptivity in IVF/ICSI and embryo transfer cycles.


Subject(s)
Endometrium/diagnostic imaging , Sperm Injections, Intracytoplasmic/methods , Ultrasonography, Doppler/methods , Adult , Female , Humans , Male , Pregnancy , Prospective Studies , Reproducibility of Results
4.
J Clin Pharm Ther ; 37(6): 630-6, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23121257

ABSTRACT

BACKGROUND: A substantial proportion of patients have recurrence of vascular events despite daily intake of low-dose aspirin therapy. Therefore, different patients may require different aspirin dosages to achieve complete inhibition of platelet function. OBJECTIVE: The aim of this work was to measure the response to low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non-ST-segment elevation myocardial infarction and to find out whether titrating aspirin dosage to 300 mg/day, would provide a better therapeutic response in the resistant cases. Moreover, we also aimed to study any association between aspirin non-responsiveness and atherothrombotic risk factors. METHODS: The antiplatelet effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients with unstable angina or non-ST-segment elevation myocardial infarction. Platelet aggregation was measured using optical platelet aggregometry and serum thromboxane B(2) level. Aspirin resistance was defined as collagen (1 µg/mL) and adenosine diphosphate (ADP) (5 µmol/L)-induced platelet aggregation of ≥ 40% when compared with control values. Twenty healthy age- and sex-matched individuals were taken as a control group. All patients were subjected to complete medical history (risk factors, medications), thorough clinical examination, ECG, coronary angiography and laboratory investigations including: complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood glucose and glycated haemoglobin (HbA(1C) ). RESULTS: Eleven of 50 patients (22%) were found to be aspirin resistant. A highly significant difference was found between the mean values of ADP, collagen-induced platelet aggregation percentage and thromboxane B(2) level after aspirin 150 mg/day when compared with the corresponding mean values after aspirin 300 mg/day among the resistant patients (66 ± 7.01%, 62 ± 4.34% and 620 ± 64.58 pg/mL, respectively, vs. 26.87 ± 2.85%, 16.5 ± 3.8% and 77 ± 11.3 pg/mL) indicating enhanced response to aspirin after escalating the dose. The presence of atherothrombotic risk factors (hypertension, smoking, family history of ischaemic heart disease and previous MI) were not statistically different between aspirin-resistant and aspirin-sensitive patients. However, there was a highly significant difference between the aspirin sensitive and the resistant patients regarding the other risk factors (diabetes mellitus and dyslipidaemia) (P < 0.01). CONCLUSION: There is inter-individual variability in response to the antiplatelet effect of standard doses of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in resistant patients when compared to 150 mg/day. There was a significant association between aspirin resistance and atherothrombotic risk factors (diabetes, hyperlipidaemia and obesity).


Subject(s)
Acute Coronary Syndrome/drug therapy , Aspirin/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Acute Coronary Syndrome/physiopathology , Adenosine Diphosphate/metabolism , Aspirin/administration & dosage , Aspirin/therapeutic use , Collagen/administration & dosage , Dose-Response Relationship, Drug , Drug Resistance , Female , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests , Prospective Studies , Risk Factors , Thromboxane B2/blood
5.
Int J Tuberc Lung Dis ; 12(9): 1085-91, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18713509

ABSTRACT

OBJECTIVES: To investigate tobacco use, beliefs and attitudes among medical students in Syria. METHODS: A cross-sectional study of a random sample of 570 medical students (first and fifth year) registered at the Damascus University Faculty of Medicine in 2006-2007. We used a self-administered questionnaire for demo-graphic information, smoking behaviour (cigarette, waterpipe), family and peer smoking, attitudes and beliefs about smoking and future role in advising patients to quit smoking. RESULTS: The overall prevalence of tobacco use was 10.9% for cigarettes (15.8% men, 3.3% women), 23.5% for waterpipe (30.3% men, 13.4% women) and 7.3% for both (10.1% men, 3.1% women). Both smoking methods were more popular among the fifth year students (15.4% and 27%) compared to their younger counterparts (6.6% and 19.7%). Regular smoking patterns predominated for cigarettes (62%), while occasional use patterns predominated for waterpipes (83%). More than two thirds of students (69%) thought they might not address or would have difficulty addressing smoking in their future patients. CONCLUSION: The level of tobacco use among Syrian medical students is alarming and highlights the rapidly changing patterns of waterpipe use, especially among female students. Medical schools should work harder to tackle this phenomenon and address it more efficiently in their curricula.


Subject(s)
Health Knowledge, Attitudes, Practice , Smoking/epidemiology , Students, Medical/statistics & numerical data , Adult , Confidence Intervals , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Odds Ratio , Prevalence , Sex Factors , Smoking/psychology , Surveys and Questionnaires , Syria/epidemiology , Universities
6.
Plast Reconstr Surg ; 118(4): 919-926, 2006 Sep 15.
Article in English | MEDLINE | ID: mdl-16980851

ABSTRACT

BACKGROUND: The use of ventricular assist devices for patients with end-stage cardiac failure awaiting heart transplantation has become increasingly common. Ventricular assist devices improve the longevity and the quality of life for these patients. In addition, they serve as a bridge to cardiac allograft transplantation until a donor heart is found. However, ventricular assist device-related infections remain a major problem complicating their long-term use. Clinical infection and sepsis can critically threaten these patients with ventricular assist devices. Infection can delay immediate transplantation and potentially require the removal of the device for definitive treatment of the problem. METHODS: Patients who underwent insertion of a ventricular assist device at the University of Pittsburgh Medical Center were identified through accessing the medical records archives of the hospital. Review of patients' medical records was conducted to obtain patient demographics, preoperative diagnosis and disease state, type of ventricular assist device inserted, postoperative day of ventricular assist device infection onset, infectious organism identified, timing of omental flap procedure after the initial insertion, duration of ventricular assist device support before cardiac transplantation, and patient follow-up. RESULTS: There were 76 patients who underwent a ventricular assist device insertion procedure during the 4-year period between January of 2000 and January of 2004. Of the 76 patients who received a device, 11 (14 percent) had evidence of clinical infection secondary to insertion. Two of these 11 patients died before surgical intervention, four had their devices explanted, and the remaining five underwent omental flap transposition with bilateral pectoralis major advancement flaps in surgically addressing their infections. Of the five patients with infections who received omental transposition flaps, two went on to undergo successful transplantation, two continue to await cardiac allograft transplantation, and one died as a result of an unknown cause. CONCLUSIONS: The authors present their experience with five patients who received omental transposition flaps to cover infected ventricular assist device pumps and the associated tubing in large, open sternoabdominal wounds. Treatment included the direct application of an omental transposition flap over the infected device with use of a bilateral pectoralis advancement flap to aid in complete sternal and skin closure of the sternal wound defect. In each of these cases, the use of the omental flap was followed by resolution of the mediastinal infection. In addition, the treatment with an omental flap prevented the removal of infected devices in patients who were otherwise pump dependent during their waiting periods for transplantation. The use of omental transposition flaps can be an effective technique in salvaging infected ventricular assist devices and preserving this valuable device for patients awaiting a cardiac transplant.


Subject(s)
Heart-Assist Devices/adverse effects , Omentum/transplantation , Prosthesis-Related Infections/surgery , Surgical Flaps , Surgical Wound Infection/surgery , Heart Failure/surgery , Heart Transplantation , Humans , Male , Middle Aged , Pectoralis Muscles/transplantation
7.
J Pediatr Hematol Oncol ; 23(5): 318-20, 2001.
Article in English | MEDLINE | ID: mdl-11464992

ABSTRACT

Autoimmune hemolytic anemia (AIHA) is a hematologic disorder that is rarely seen in infants and young children. Most cases are associated with viral or bacterial infection, but the immunologic events leading to hemolysis are poorly understood. We describe two infants with severe cytomegalovirus (CMV)-associated warm antibody AIHA. One case was immunohematologically analyzed and showed suggestive evidence that endogenous anti-CMV IgG antibodies were the pathogenic antibodies leading to hemolysis, implicating a possible causal relationship between AIHA and CMV infection. Both patients were ultimately treated with intravenous CMV immune globulin, with subsequent improvement. These cases suggest that investigation for the presence of CMV in infantile AIHA is warranted and that CMV immune globulin should be considered as a therapeutic option.


Subject(s)
Anemia, Hemolytic, Autoimmune/etiology , Autoimmune Diseases/etiology , Cytomegalovirus Infections/complications , Anemia, Hemolytic, Autoimmune/blood , Anemia, Hemolytic, Autoimmune/therapy , Antibodies, Viral/blood , Antibodies, Viral/therapeutic use , Autoimmune Diseases/blood , Autoimmune Diseases/therapy , Combined Modality Therapy , Coombs Test , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/therapy , Female , Humans , Immune Sera , Immunization, Passive , Immunoglobulin G/immunology , Infant , Methylprednisolone/therapeutic use , Nasopharynx/virology , Urine/virology
8.
J Pediatr Hematol Oncol ; 21(1): 58-62, 1999.
Article in English | MEDLINE | ID: mdl-10029815

ABSTRACT

PURPOSE: Report the unusual presentation, clinical course, and cytogenetic abnormalities in a child with multifocal osteosarcoma. PATIENTS AND METHODS: A 10-year-old boy had multifocal osteosarcoma involving the entire skeleton, pleura, bone marrow, and lungs. He had marked anemia, thrombocytopenia, and severe hypocalcemia at diagnosis. RESULTS: Despite aggressive chemotherapy, he died from progressive disease 1 month after diagnosis. Cytogenetic analysis of tumor cells within the pleural fluid showed multiple chromosomal abnormalities with amplification of the c-myc oncogene. CONCLUSION: Multifocal osteosarcoma should be considered in the differential diagnosis of a child with pancytopenia and multiple bone lesions. Amplification of the c-myc oncogene may have had a significant role in the pathogenesis, etiology, and rapid progression of this patient's multifocal disease. Additional studies will be needed to determine the biologic significance of c-myc amplification in multifocal osteosarcoma.


Subject(s)
Osteosarcoma/diagnosis , Osteosarcoma/genetics , Child , Diagnosis, Differential , Disease Progression , Fatal Outcome , Genes, myc/genetics , Humans , Male , Osteosarcoma/pathology
9.
J Chromatogr B Biomed Sci Appl ; 710(1-2): 121-8, 1998 Jun 12.
Article in English | MEDLINE | ID: mdl-9686878

ABSTRACT

A sensitive, selective and efficient reversed-phase high-performance liquid chromatographic (HPLC) method is reported for the determination of furosemide in human plasma and urine. The method has a sensitivity limit of 5 ng/ml in plasma, with acceptable within- and between-day reproducibilities and good linearity (r2>0.99) over a concentration range from 0.05 to 2.00 microg/ml. The one-step extract of furosemide and the internal standard (warfarin) from acidified plasma or urine was eluted through a muBondapak C18 column with a mobile phase composed of 0.01 M potassium dihydrogenphosphate and acetonitrile (62:38, v/v) adjusted to pH 3.0. Within-day coefficients of variation (C.V.s) ranged from 1.08 to 8.63% for plasma and from 2.52 to 3.10% for urine, whereas between-day C.V.s ranged from 4.25 to 10.77% for plasma and from 5.15 to 6.81% for urine at three different concentrations. The minimum quantifiable concentration of furosemide was determined to be 5 ng/ml. The HPLC method described has the capability of rapid and reproducible measurement of low levels of furosemide in small amounts of plasma and urine. This method was utilized in bioavailability/pharmacokinetic studies for the routine monitoring of furosemide levels in adults, children and neonate patients.


Subject(s)
Chromatography, High Pressure Liquid/methods , Furosemide/blood , Furosemide/urine , Biological Availability , Furosemide/pharmacokinetics , Humans , Male , Reproducibility of Results , Sensitivity and Specificity
12.
Toxicon ; 34(9): 1011-26, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8896193

ABSTRACT

The pharmacokinetic profiles of labelled Naja melanoleuca, Naja nivea, Naja nigricollis and Naja haje venoms and their alpha neurotoxins were determined following rapid i.v. injection into rabbits. The data obtained fitted a triexponential equation characteristic of a three-compartment open pharmacokinetic model comprising a central compartment 'blood', a rapidly equilibrating 'shallow' tissue compartment and a slowly equilibrating 'deep' tissue compartment. The distribution half-lives for the shallow compartment ranged from 3.2 to 5 min, reflecting the rapid uptake of venoms and toxins compared with 22-47 min for the deep tissue compartment denoting much slower uptake. The overall elimination half-lives, t1/2 beta, ranged from 15 to 29 hr, indicating a slow body elimination. Peak tissue concentration was reached within 15-20 min in the shallow tissue compartment. The corresponding values for the deep tissue compartment were 120 min for N. melanoleuca and N. nigricollis venoms and their toxins and 240 min for N. nivea and N. haje venoms and their toxins. Steady-state distribution between the shallow tissue compartment and the blood gave values of 0.50 and 0.92 (N. melanoleuca), 1.64 and 1.05 (N. nivea), 0.78 and 0.92 (N. nigricollis) and 1.70 and 1.03 (N. haje) for the venoms and their toxins, respectively. The corresponding values for the deep tissue compartment gave ratios of 3.31 and 3.44 (N. melanoleuca), 2.99 and 1.68 (N. nivea), 3.74 and 3.79 (N. nigricollis) and 1.39 and 2.46 (N. haje) for the venoms and their toxins, respectively. Ratios lower than unity indicate lower venom and toxin concentrations in the tissues than in the blood, while larger ratios denote higher tissue concentrations. The values thus reflect a higher affinity of the venoms and their toxins for the central than the shallow tissue compartment and for the deep tissue than the central compartment. The sites of action of the venoms seem to be located in the deep tissue compartment since most of the pharmacological, biochemical and electrocardiographic effects of the venoms started 30-60 min after i.v. injection. The mean residence time in the body, MRTb, ranged from 20.8 to 51.8 hr, which correlated well with the long duration of the pharmacological and biochemical effects induced by the venoms. The tissue distribution of the venoms and toxins was similar, with the highest uptake being in the kidneys, followed by the stomach, lungs, liver, spleen, intestine, heart and diaphragm. Very high radioactivity was found in the stomach contents, which reached values higher than the kidneys. Some of the biochemical markers were significantly changed by one or more venoms but the grouped parameters did not reflect significant changes in cardiac, renal, hepatic or electrolyte profiles as a function of time. It is concluded that antivenom, even if injected several hours after a cobra bite, is still capable of neutralizing the slowly eliminating venom. To speed up neutralization of the venom effects, doses of antivenom higher than the calculated in vitro neutralizing dose ought to be injected to compensate for the slow rate of transfer of antivenom to the tissues.


Subject(s)
Elapid Venoms/pharmacokinetics , Animals , Biomarkers/blood , Elapid Venoms/administration & dosage , Elapid Venoms/blood , Elapid Venoms/isolation & purification , Elapid Venoms/metabolism , Elapid Venoms/toxicity , Feasibility Studies , Gastric Mucosa/metabolism , Half-Life , Heart/drug effects , Injections, Intravenous , Isotope Labeling , Kidney/drug effects , Kidney/metabolism , Lethal Dose 50 , Liver/drug effects , Liver/metabolism , Models, Theoretical , Myocardium/metabolism , Rabbits , Species Specificity , Stomach/drug effects , Tissue Distribution
13.
J Pediatr Hematol Oncol ; 18(3): 289-92, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8689344

ABSTRACT

PURPOSE: An atypical case of childhood intraabdominal desmoplastic small round cell tumor (DSRCT) is presented. PATIENT AND METHODS: An 11-year-old boy presented with progressive nausea and vomiting, abdominal pain, hepatomegaly, and an epigastric mass. Computed tomographic scanning as well as findings at gastroscopy and laparotomy revealed a large gastric mural tumor accompanied by multiple large intrahepatic masses. Histopathologic examination of biopsy samples revealed evidence of a polyphenotypic neoplasm diagnostic of DSRCT. RESULTS: Unlike most reported cases of DSRCT, no evidence of peritoneal involvement or ascites was detected. Despite an excellent initial response to multiagent chemotherapy, the patient eventually died of progressive tumor. CONCLUSIONS: Though the radiographic and surgical findings in DSRCT usually suggest a mesenteric, peritoneal, or retroperitoneal site of tumor origin, this case demonstrates that intraabdominal DSRCT can present with a primary visceral lesion without evidence of peritoneal or mesenteric involvement or ascites. Combination chemotherapy using vincristine, doxorubicin, cyclophosphamide, cisplatin, and 5-fluorouracil may be of some benefit to patients with this rare tumor.


Subject(s)
Abdominal Neoplasms/diagnosis , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Stomach Neoplasms/diagnosis , Abdominal Neoplasms/drug therapy , Abdominal Neoplasms/secondary , Abdominal Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tomography, X-Ray Computed , Vincristine/administration & dosage
16.
Am J Pediatr Hematol Oncol ; 15(4): 383-5, 1993 Nov.
Article in English | MEDLINE | ID: mdl-7605400

ABSTRACT

Giant hemangiomas occurring in the neonatal period often present a therapeutic challenge, especially when confounded by consumptive coagulopathy (Kasabach-Merritt syndrome). We treated three infants with tranexamic acid after therapy with corticosteroids was ineffective. One patient had a partial response. The remaining two developed progressive disease.


Subject(s)
Hemangioma, Cavernous/drug therapy , Hemangioma/drug therapy , Tranexamic Acid/therapeutic use , Female , Humans , Infant , Infant, Newborn , Male , Prednisone/therapeutic use
17.
J Pediatr ; 123(4): 546-52, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8410505

ABSTRACT

We evaluated final adult height in 109 patients treated for childhood acute lymphoblastic leukemia on two multiarm Pediatric Oncology Group protocols between 1974 and 1981. Fifty-one patients received 2400 cGy cranial irradiation (XRT), and 58 patients received no XRT. All patients had no central nervous system involvement at diagnosis, achieved and maintained a complete response, entered puberty spontaneously, and had achieved final height. Height data were converted to standardized deviation scores. Mean age at diagnosis was 7.8 +/- 4.2 years. Distribution of heights at diagnosis was similar to that of the U.S. population. Relative to gender-specific heights for the population, female subjects in this study had lower attained heights than male subjects (p = 0.03). There was a monotonic trend of patients treated at an earlier age to have a reduction in final height (p = 0.057). Cranial irradiation was strongly associated with final height (mean standardized deviation score with XRT = -1.04 and without XRT = -0.14; p < 0.001). Final height was not associated with age at diagnosis, prognostic risk group, or Pediatric Oncology Group protocol. By multivariate analysis, only XRT and XRT x age were significantly associated with final height (p < 0.001 and p = 0.002, respectively). There was no significant gender effect. We conclude that XRT is significantly associated with reduced final adult height after treatment for childhood acute lymphoblastic leukemia. For survivors, therapy devoid of XRT does not appear to affect final height.


Subject(s)
Body Height , Cranial Irradiation , Growth Disorders/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Child , Clinical Protocols , Combined Modality Therapy , Female , Growth Disorders/epidemiology , Humans , Male , Multivariate Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Reference Values , Sex Characteristics
19.
Biopharm Drug Dispos ; 13(5): 321-6, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1498265

ABSTRACT

The interaction between indomethacin (IND) and methotrexate (MTX) was investigated in rabbits. The study was designed so as to evaluate the effect of IND (1 mg h-1) during a continuous MTX infusion (1 x 2 mg kg-1) over 240 min. IND was injected i.v. at hourly intervals after a steady state MTX concentration had been established. Plasma MTX concentration before and after IND did not differ significantly (p greater than 0.05). The elimination half-life (t1/2 beta) calculated during the washout interval (mean +/- SD) was 47 x 4 +/- 21 x 5 min which is close to that calculated in a reference group of rabbits. This excludes the possibility of delayed elimination as responsible for this toxicity. The toxicity of this combination was confirmed despite the absence of significant pharmacokinetic changes. It is possible that the toxic interaction was caused by enhanced cytotoxic effect of MTX.


Subject(s)
Indomethacin/pharmacology , Methotrexate/pharmacokinetics , Animals , Drug Interactions , Male , Metabolic Clearance Rate/drug effects , Methotrexate/blood , Rabbits
20.
Toxicon ; 28(11): 1265-84, 1990.
Article in English | MEDLINE | ID: mdl-2087694

ABSTRACT

Four fatal cases following scorpion sting in children are presented. Two victims had rectal temperature above 41 degrees C, the third exhibited a temperature of 40.9 degrees C from the combined effects of scorpion sting and heat stroke, while the fourth was hypothermic. All victims developed hypothermia 48 hr following the sting. The hyperthermia was effectively treated by acetaminophen suppositories, ice packs and water sponges. All victims showed late hypotension that was refractory to dopamine infusion. This was explained by bradykinin released by the venom blocking the dopaminergic receptors. Deterioration of the cortical activity of the victims maintained on mechanical ventilation before the incidence of asystole suggests a central component in the cardiovascular manifestations of envenomation. A. amoreuxi venom was selected as a model for the pharmacokinetic and quantitative toxicological studies since it has no effect on body temperature. In hyperthermic rabbits injected with labelled lethal fraction of A. amoreuxi venom, there was a significant decrease in the elimination half-life, t1/2 beta, the apparent volume of the tissue compartment, Vt, the apparent volume of distribution, Vdss, and the intercompartmental rate constant, kCT. Hypothermic rabbits showed a significant decrease in the apparent first-order elimination rate constant, kd, and a significant increase in the elimination half-life. In both states a higher concentration of the lethal fraction in the blood was calculated. This would explain the rapidity of onset of the electrocardiographic effects and the decreased survival time in both the hyperthermic and hypothermic rabbits injected with venom when compared to normothermic animals. The s.c. LD50 in mice and the i.v. MLD in rats were significantly reduced in the hypothermic mice and hypothermic and hyperthermic rats.


Subject(s)
Body Temperature , Scorpion Stings/metabolism , Scorpion Venoms/poisoning , Animals , Blood Glucose/analysis , Child , Child, Preschool , Electrocardiography , Female , Half-Life , Heat Exhaustion/complications , Humans , Infant , Male , Mice , Rabbits , Rats , Retrospective Studies , Scorpion Stings/complications , Scorpion Venoms/pharmacokinetics , Scorpion Venoms/toxicity , Scorpions
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