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Biomedical subjects

K Ali

Publications and source records attributed to K Ali.

At least 19 recordsLinked to original sources

Patients' perceived health status following primary surgery for oral and oropharyngeal cancer.

How oral and oropharyngeal cancer patients view their 'quality of life' is of fundamental importance. Any differences seen in their health state compared with normative data and with other disease conditions allows a wider perspective on their outcome after surgery. A cross-sectional postal survey was undertaken of patients treated for oral/oropharyngeal squamous cell carcinoma by primary surgery using the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL v4) and the EuroQol EQ-5D. Of 348 patients surveyed, 224 returned analysable forms, (response rate 64%). In the EQ-5D items, 40% of the group reported a problem in walking, 23% with self-care, 44% in performing usual activities, 50% with pain or discomfort and 33% with anxiety or depression. The mean overall health visual analogue scale (VAS) score was 74 (SE 1) minimum 30 and maximum 100. The mean utility (health index) score was 0.75 (SE 0.02) minimum -0.18 and maximum 1.0. Compared to national reference data, patients in our cohort of under 60 years of age fared significantly worse than expected for their age but this was not so for older patients. There were strong correlations between appropriate domains of the EQ-5D and UW-QOLv4 and between UW-QOL global measures and EQ-5D VAS.

Age Factors↗

Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report.

BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.

Adolescent↗

Quality of life evaluations in patients with ovarian cancer during chemotherapy treatment.

OBJECTIVES: To examine the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. PATIENTS AND METHODS: Over 18 months period, all patients with ovarian cancer receiving chemotherapy at the Saskatoon Cancer Center were recruited. The Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire was used to assess patients' quality of life before each chemotherapy cycle. Platinum-based chemotherapy was used initially or in patients with a platinum-free interval of more than 6 months in a recurrence setting. After progression on the platinum-based regimens, liposomal doxorubicin, topotecan, and cisplatinum/etoposide were used as salvage chemotherapy pending on drug availability and convenience of administration to patients. Regression analysis was used to identify significant disease and treatment-related factors that can significantly affect patients' quality of life measures. RESULTS: Seventy-two patients participated in the study providing 270 separate observations. The mean age was 57.81 years with a standard deviation of 13.40. The median duration of chemotherapy-free interval for patients with recurrent disease was 7 months. All patients had stage 3 or 4 disease. About half (52.2%) of the patients had optimal surgical resection with small (<1 cm) residual cancer masses before primary adjuvant chemotherapy. Seventy percent of the patients had either a first diagnosis or a first recurrence of cancer with the other 30% previously treated with two or more chemotherapy regimens. Sixty-two percent had an initial complete response to platinum-based chemotherapy. Multivariate regression analysis showed the use of topotecan or cisplatinum/etoposide, patients' poor responses to chemotherapy, experience with two or more previous line of chemotherapy treatment, and younger ages were significant predictors of poor quality of life during chemotherapy. CONCLUSION: There were significant differences in side effects of commonly used chemotherapy regimens on patients' quality of life. Quality of life assessments should be routinely incorporated in selecting specific chemotherapy to be used. Future research should be carried out to identify the best strategies to further integrate the results of quality of life assessments in cancer treatment protocols and to examine the long-term effects of cancer and its treatment on patients and their families.

Adult↗

Quality of life evaluations of caregivers of ovarian cancer patients during chemotherapy treatment.

OBJECTIVES: (1) To examine the quality of life (QOL) of caregivers of women undergoing chemotherapy for advanced ovarian cancers, and (2) to correlate the QOL measures of caregivers to those of the women undergoing chemotherapy. METHODS: Over a 9-month period, all women undergoing chemotherapy for ovarian cancer at the Saskatoon Cancer Centre, and their caregivers, were offered participation. Two well-validated instruments were used to measure the "quality of life" concept. Women with ovarian cancer completed the Functional Assessment of Cancer Therapy--Ovarian (FACT-O) questionnaire in the clinic prior to each course of chemotherapy. Each caregiver completed a Caregiver Quality of Life Index--Cancer (CQOL-C) questionnaire at home at the start and conclusion of each chemotherapy regimen (cycle 1 and after the last chemotherapy treatment). The demographics of the caregivers were described. A paired t test was used to detect changes to caregivers' QOL scores before and after chemotherapy treatment. Correlation analysis was carried out to examine the relationship between the caregivers' total QOL scores and the various subscale and total scores of the FACT-O questionnaires completed by the women with ovarian cancer. Multivariate regression models were constructed to examine the relative importance of each of the QOL domain measures of the woman with cancer in predicting the effect on her caregiver's QOL. RESULTS: Thirty different patient-caregiver pairs participated in the study, providing 50 separate assessments since not all pairs had completed the post-chemotherapy assessments. There was improvement (P <.05) in the caregiver's QOL scores at the conclusion of the chemotherapy treatment compared to the baseline assessments. The improvement was unrelated to the performance status or response to chemotherapy of the woman undergoing treatment. There was also a correlation (P <.05) between an increase in a caregiver's distress and worsening scores in the "emotional," "functional," and "concerns" QOL domain assessments of the woman undergoing treatment. Stepwise regression analysis showed the "concerns" score, measuring specific ovarian cancer-related symptoms, to be the only predictor of a caregiver's distress (P <.05). CONCLUSIONS: Standard chemotherapy for ovarian cancer does not worsen a caregiver's QOL. There is a direct relationship between the QOL of women with cancer and that of their caregivers. Future research is required to identify how best to integrate the results of QOL assessments in cancer treatment protocols and to examine the long-term effects of ovarian cancer and its treatment on both caregivers and the women for whom they care.

Adult↗

A survey of factor prophylaxis in the Canadian haemophilia A population.

High-dose factor prophylaxis, defined as the infusion of 25-40 factor (F) VIII International Units (IU) kg bodyweight (bw)(-1)> or = x 3 per week, started at age 1-2 years of life in boys with severe haemophilia A prevents the development of significant bleed-related arthropathy. However, programmes of prophylaxis are very expensive and venous access is a challenge. To ascertain patterns of prophylaxis in Canada during the period of a global shortage of recombinant FVIII concentrate a survey was conducted in 2001. The response rate was 83% and the survey identified 247 inhibitor-negative haemophilia A cases receiving prophylaxis, defined as the regular administration of FVIII at least once weekly, from 14 Canadian haemophilia treatment centres. The median age of the group identified was 13 years (range: 1-65) and 95% of cases had severe haemophilia A defined by a circulating factor level of <1%. The median FVIII infusion dose was 26 (range: 16-33) IU kg(-1); infusions were administered > or = x 3 per week in 67% of cases. High-dose factor prophylaxis was used most frequently in boys <5 years of age (23 of 28 cases, 82%) as compared with 56% (56 of 100), 66% (40 of 61) and 62% (36 of 58) of males ages 5-12, 13-18 and >18 years. Prophylaxis accounted for 50% of the annual Canadian FVIII consumption and was a major driving force in the 10% increase (=19.3 million FVIII IU) in the FVIII consumption in Canada in the 4-year period 1999-2003. Given the economic implications of increased use of prophylaxis prospective studies are warranted to better define optimal prophylaxis regimens in the haemophilia A population.

Adolescent↗

Neonatal estrogen exposure of male rats alters reproductive functions at adulthood.

The effects of neonatal exposure to different doses of diethylstilbestrol (DES) on the reproductive functions of male rats at adulthood were evaluated. Sprague-Dawley rats (5-8/group) received sc injections of 25 microl olive oil containing DES (Sigma Chemical Co., St. Louis, MO) at a dose of 10 microg, 1 microg, 100 ng, 10 ng, or 1 ng per rat on alternate days from Postnatal Days 2-12. Control animals received olive oil only. All animals were allowed to develop until 83-91 days of age; however, when they were 70 to 80 days old, four male rats each from the 10 microg, 1 microg, 100 ng, and control groups were cohabited with untreated 60- to 70-day-old females (1:1) for 12 days. At the end of cohabitation, both mated and unmated male rats were weighed, and blood and tissue samples were collected and processed. Results revealed that although sperm motility patterns and sperm morphology were adversely affected in the 10- microg group, other reproductive parameters, including 1). daily sperm production (DSP)/testis; 2). absolute and relative weights of the testis, epididymis, and seminal vesicle; and 3). sperm numbers in both regions of the epididymis declined significantly in a dose-dependent manner in the 10- and 1- microg groups. Conversely, in the <1- microg groups, none of these parameters (except DSP/testis and weight of the epididymis in the 100-ng group, and sperm numbers in the epididymis of the 100- and 10-ng groups) was different from controls. Generally, plasma testosterone levels decreased in the 10- and 1- microg groups, FSH level increased in the 10-microg group, and prolactin and LH levels were unaltered. In the fertility study, although each male in the 1-microg, 100-ng, and control groups produced a copulatory plug and impregnated a female, none could do so in the 10-microg group. The mean number of pups per litter was reduced to eight in the 1-microg group, in contrast to 15 each in the 100-ng and control groups. In conclusion, exposure of neonatal male rats to DES altered sperm motility patterns, sperm fertility (as evident from the reduced number of pups in the 1-microg group), and sexual behavior (as evident from the absence of copulatory plugs in the 10-microg group) and reduced weights of reproductive organs, DSP/testis, and sperm numbers in the epididymis. Whether these alterations/reductions persist in older rats (6-8 mo of age) is under investigation.

Animals↗

Quality-of-life issues in patients with ovarian cancer and their caregivers: a review.

UNLABELLED: Significant progress has been made towards the treatment of ovarian cancer resulting in longer median survival despite a persistent low cure rate. Relatively few studies have examined the impact of the cancer and its treatment on the patients and their caregivers due to the difficulty in the definition and measurement of the Quality of Life (QOL) concept. A review of the literature revealed significant alterations in the quality of life of ovarian cancer patients during treatment and long term follow ups. For the caregivers, it is important for health care providers to realize that: 1) caregivers are being asked to assume an increasing number of complex care giving tasks at home, 2) there exists a high proportion of unmet caregiver needs, 3) the care giving experience includes both positive and negative elements and, 4) perception of caregivers' burden is positively linked to negative reactions to care giving. Supportive programs for patients and caregivers should be designed with these needs in mind. Future research should study the best way to incorporate results of quality of life assessments into routine treatment decision-making. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to outline the current data on QOL issues in patients with ovarian cancer, and to describe potential working definitions of QOL.

Caregivers↗

Antioxidant vitamins improves hemoglobin level in children with group a beta hemolytic streptococcal infection.

A study was done on school children infected with group A beta hemolytic streptococci to examine whether antioxidant vitamins play a role in improving the hemoglobin level. A total of 606 primary school children aged 5 to 15 years were randomly divided into two intervention groups. Group 1 (n=299) was treated with pehnoxymethyl penicillin V and group 2 (n=307) was treated with phenoxymethyl penicillin V plus antioxidant vitamins for eight weeks. From each group two blood samples were drawn in acute and convalescent (after eight weeks) states. Before treatment, mean hemoglobin values were 11.0 and 10.8 mg/dL in groups 1 and 2 respectively. After treatment hemoglobin values were 10.5 and 11.6 mg/dL respectively. Values were significantly decreased in group 1 (P=0.0001), whereas increased in group 2 (P=0.001). Adjustment for age and sex by ANCOVA confirmed the difference in hemoglobin levels between group (LS means-0.5 vs 0.8 in groups 1 and 2 respectively (P=0.0001). Hemoglobin level increases after antioxidant vitamin supplementation in children suffering from group A beta hemolytic streptococcal infection.

Adolescent↗

Ancient adaptation of the active site of tryptophanyl-tRNA synthetase for tryptophan binding.

The amino acid binding domains of the tryptophanyl (TrpRS)- and tyrosyl-tRNA synthetases (TyrRS) of Bacillus stearothermophilus are highly homologous. These similarities suggest that conserved residues in TrpRS may be responsible for both determining tryptophan recognition and discrimination against tyrosine. This was investigated by the systematic mutation of TrpRS residues based upon the identity of homologous positions in TyrRS. Of the four residues which interact directly with the aromatic side chain of tryptophan (Phe5, Met129, Asp132, and Val141) replacements of Asp132 led to significant changes in the catalytic efficiency of Trp aminoacylation (200-1250-fold reduction in k(cat)/K(M)) and substitution of Val141 by the larger Glu side chain reduced k(cat)/K(M) by 300-fold. Mutation of Pro127, which determines the position of active-site residues, did not significantly effect Trp binding. Of the mutants tested, D132N TrpRS also showed a significant reduction in discrimination against Tyr, with Tyr acting as a competitive inhibitor but not a substrate. The analogous residue in B. stearothermophilusTyrRS (Asp176) has also been implicated as a determinant of amino acid specificity in earlier studies [de Prat Gay, G., Duckworth, H. W., and Fersht, A. R. (1993) FEBS Lett. 318, 167-171]. This striking similarity in the function of a highly conserved residue found in both TrpRS and TyrRS provides mechanistic support for a common origin of the two enzymes.

Acylation↗

Study of water quality of Hudiara drain, India-Pakistan.

This paper examines the extent of pollution in Hudiara drain water due to untreated industrial and sewage waste of India and Pakistan. Ninety-nine surface water samples from the Pakistani side of the Hudiara drain were collected during September 1997, and April and June 1998. The analytical results of the Hudiara drain samples point out the industrial and sewage inputs from India and Pakistan. Higher values of biochemical oxygen demand (BOD), chemical oxygen demand(COD), total organic carbon(TOC), and trace metals in drain samples from the Indo-Pak border clearly indicate the Indian industrial and sewage pollution. Large variations in the levels of various measured parameters (COD, BOD, TOC, pH, total soluble substances, and trace metals) were observed along the Hudiara drain in the Pakistani vicinity. These variations were due to different types of industrial effluents and small village drains. The study showed that suspended solids(SS), COD, and fecal coliform (FC) were the major pollutants. Accordingly, the most feasible alternative is to convert the drainage network to a sedimentation and temporary storage reservoir. If disinfected, the runoff water can be used for restricted irrigation. Groundwater samples taken from the drain's surrounding area have also been analyzed. Thirty percent of the samples are not fit for drinking purposes due to NO3-N, Se and FC counts as prescribed by World Health Organization (WHO) guidelines. A trilinear diagram clearly indicates the influence of surface water of the Hudiara drain on ground water; moreover, higher values of nitrate and FC clearly indicate the seepage from the Hudiara drain.

Environmental Monitoring↗

Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry.

The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.

Adolescent↗

Retroperitoneal actinomycosis masquerading as inflammatory pseudotumor.

Inflammatory pseudotumors present clinically as mass lesions and microscopically show a spectrum of nonspecific inflammatory and regenerative changes. When the mesentery or retroperitoneum are involved, differentiation from inflammatory fibrosarcoma poses a diagnostic problem. The authors report on a 7-year-old boy who presented with fever, anemia, weight loss, and a retroperitoneal mass. Needle biopsy results of the mass showed features consistent with inflammatory pseudotumor. Examination of the resected mass showed actinomycosis.

Actinomycosis↗

Correcting for ethnicity when defining large for gestational age infants in diabetic pregnancies.

The large-for-gestational-age (LGA) infant, defined as > 90th birthweight percentile, is associated with mild disturbances of maternal glucose tolerance. In the UK the same birthweight percentile charts are used for all ethnic groups when assessing LGA infants. The influence of maternal hyperglycaemia on LGA infants of Asian (Indian Subcontinent) mothers in the UK is likely to be under-reported, as Asian birthweights tend to be lower than White/Europid birthweights. We assessed the number of LGA infants born consecutively to 21 Asian and 26 White/Europid mothers with gestational diabetes mellitus (GDM), delivered between 37 and 42 weeks gestation, and also in 34 Asian and 121 White/Europid mothers with a positive screening test for GDM but a normal 75 g oral glucose tolerance test (OGTT). Large-for-gestational-age infants were identified using both the standard UK percentile charts of the Medical Research Council and percentile charts constructed from 30,418 Asian and 162,477 White/Europid singleton births, delivered between 37 and 42 weeks gestation to non-diabetic mothers delivered in the North West Thames Region of England. The standard Medical Research Council percentile charts, compared with the ethnically derived charts, identified fewer LGA Asian (7/56 vs 15/56) but more White/Europid infants (33/147 vs 21/147). When correcting for ethnicity more Asian than White/Europid GDM mothers delivered LGA infants (9/21 vs 3/26, chi 2 = 4.76, p < 0.05). The maternal 2 h OGTT plasma glucose was a significant independent contributor to birthweight in the Asian (r2 = 0.319, p < 0.0005) but not the White/Europid infants, in whom gestational age and maternal height were significant independent contributors to birthweight (r2 = 0.158, p < 0.0001). We conclude that ethnic influences are important when defining LGA infants and that mild disturbances of maternal glycaemia have a greater influence on the birthweight of Asian than White/Europid infants.

Adult↗

Overnight metabolic fuel deficiency in patients treated conventionally for hypopituitarism.

BACKGROUND: Hormone replacement in hypopituitary adults attempts to reproduce normal physiology. Conventional regimens fail to mimic normal hormone profiles over 24 hours. OBJECTIVE: To investigate the metabolic consequences of conventional hormone replacement in hypopituitary adults by measuring circulating levels of the major fuels, glucose, non-esterified fatty acids (NEFA), glycerol and 3-hydroxybutyrate (3-OHB) over 24 hours in hypopituitary subjects and controls. SUBJECTS: Ten GH and adrenocorticotrophin deficient hypopituitary adults on conventional replacement and 13 controls matched for age, sex and body mass index were studied. The patients received replacement with hydrocortisone twice daily (at 0730 and 1730 h; mean (range) daily dose 22 (10-30) mg/24 h) but not with GH. Other hormones were replaced as clinically necessary. MEASUREMENTS: Circulating glucose, NEFA, glycerol and 3-OHB levels were measured over 24 hours together with concentrations of cortisol (total and free), GH and insulin, and urinary free cortisol. RESULTS: Levels of glucose, NEFA and 3-OHB were lower in patients than controls (mean +/- SEM) (4.3 +/- 0.1 vs 5.3 +/- 0.1 mmol/l, P = 0.0001; 291 +/- 46 vs 448 +/- 48 mumol/l, P = 0.015; 78 +/- 8 vs 136 +/- 24 mumol/l, P = 0.035, respectively) before breakfast. This decrease in glucose, NEFA and 3-OHB was observed in the patient group throughout the night, from midnight to breakfast. For NEFA, the decrease persisted throughout the 24 hours. Glycerol did not differ significantly in patients and controls. Integrated levels of total and free plasma cortisol, and 24-hour urine cortisol excretion, were normal in patients but total and free plasma cortisol concentrations overnight were markedly decreased (overnight area under the curve (AUC) of total cortisol: 440 +/- 154 vs 1593 +/- 267 nmol/l h, P = 0.0024; overnight AUC of free cortisol: 24 +/- 8 vs 161 +/- 26 nmol/l h, P = 0.0001). GH levels were low throughout the whole 24 hours in the patient group (24-hour AUC: 10.6 +/- 5.1 vs 74.6 +/- 19.6 mU/l h, P = 0.008). CONCLUSIONS: Hypopituitary adults on conventional hormone replacement regimens have low concentrations of metabolic fuels, glucose, non-esterified fatty acids and 3-hydroxybutyrate throughout the night, possibly related to GH deficiency or to decreased overnight circulating cortisol levels. This overnight fuel deficiency may underlie the mechanism for the non-specific symptoms, such as fatigue and headache in the early morning, which are frequent in this group of patients.

3-Hydroxybutyric Acid↗