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Biomedical subjects

I A Malik

Publications and source records attributed to I A Malik.

At least 19 recordsLinked to original sources
PubMed2004

Zero tolerance to shunt infections: can it be achieved?

OBJECTIVE: To evaluate the rigid application of a technique of shunt placement aimed at the eradication of postoperative shunt infection in neurosurgical practice. METHOD: All shunt procedures were performed or closely supervised by the senior author (MSC). The essentials were the use of intravenous peri- and postoperative antimicrobials, rigid adherence to classical aseptic technique, liberal use of topical antiseptic (Betadine), and avoidance of haematomas. RESULTS: Of 176 operations, 93 were primary procedures; 33 patients underwent revisions, some multiple. Only one infection occurred, seven months postoperatively, secondary to appendicitis with peritonitis. The infecting Streptococcus faecalis appeared to ascend from the abdominal cavity. CONCLUSION: A rigidly applied protocol and strict adherence to sterile technique can reduce shunt infections to a very low level.

Adolescent↗
PubMed2003

Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjects.

OBJECTIVE: There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. PATIENTS AND METHODS: A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). RESULTS: Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36.0 +/- 26.4 (range 13-159) months. Mean age was 43.9 +/- 15.8 years (37 males) in treated GHD patients compared to a mean age 41.7 +/- 10.5 years (32 males) in the controls. Mean IGF-1 levels were 22.5 +/- 13.6 nmol/l in the GHD patients and the mean dose of GH replacement was 1.2 +/- 0.4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P </= 0.0001, except life fulfilment-material, P = 0.33) compared to the control population. CONCLUSIONS: This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes).

Adult↗
PubMed2003

An autopsy study of hypertrophic cardiomyopathy.

OBJECTIVE: To see the pathological features of this disease in our set up and to emphasise the importance of morphological examination in making the diagnosis of hypertrophic cardiomyopathy (HCM) especially in cases of sudden cardiac death. METHODS: A retrospective, descriptive study of 15 autopsies of this particular disease was carried out at the Armed Forces Institute of Pathology (AFI) Rawalpindi during the period from 1990 to 1995. The hearts along with blood vessels were fixed in 10% formalin and were dissected according to the modified Virchow's method for eliciting the gross appearance of cardiac chambers and valves. Representative sections were taken for histological examination. RESULTS: All the cases were young adult males. The age range was from 17-34 years (mean, 26-6 years). Ten cases died suddenly and five cases had an evidence of moderate to severe exertion preceding their death. Symmetrical as well as asymmetrical hypertrophy was noted in this study. The thickness of inter ventricular septum (mean 20 mm) and left ventricular wall (mean 22.5 mm) was increased. All the specimens revealed disarray of hypertrophic myocardial fibres and patchy interstitial fibroses. CONCLUSION: Sudden death is usually the first manifestation of disease. The hearts showed asymmetric as well as concentric hypertrophy. Myofibre hypertrophy and disarray was an important pathological findings in our cases. While carrying out post-mortem examination of a case of sudden cardiac death one should also keep in mind the possibility of this disease.

Adolescent↗
PubMed2002

Food fails to suppress ghrelin levels in obese humans.

UNLABELLED: Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. METHODS: We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. RESULTS: Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). CONCLUSIONS: Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

Adult↗
PubMed2002

Clinico-pathological features of breast cancer in Pakistan.

OBJECTIVE: To obtain information about presenting features of women with breast cancer in Pakistan, to compare these data with information on patients with breast cancer in the United States and to highlight the differences. METHODS: Patients referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1994 and February 28, 1999 who had been recently diagnosed with breast cancer were prospectively evaluated. A printed questionnaire was used as an interview guide. Information was obtained about demographic features/clinical characteristics, stage of the disease and previous therapy. RESULTS: Five-hundred sixty-six patients were evaluated. Mean age was 47.7 +/- 11.8 years. Risk factors for breast cancer were observed in a minority. Mean number of pregnancies was 4.4. Eighteen percent had positive family history mostly in first-degree (64%) relatives. The vast majority (93%) discovered the lump accidentally. Average size was 5.7 +/- 2.3 cm. Over half had used unconventional therapies before receiving standard medical care. Most patients had undergone modified radical mastectomy and only 5% had conservative surgery done. Almost one third had locally-advanced disease. Seventeen percent had metastases at the time of diagnosis. CONCLUSION: Despite significant advances made in cancer care in the United States, patients in Pakistan still present at an advanced stage. Antecedent use of unconventional therapies before seeking any medical advice is widespread. There is a great need for public education to enhance awareness about cancer and other health habits.

Adult↗
PubMed2002

A prospective study of clinico-pathological features of epithelial ovarian cancer in Pakistan.

BACKGROUND: Although geographic and racial differences in the incidence of cancer are well recognized, information regarding any dissimilarity in clinico-pathological behavior of cancers is scarce. In particular, information from the developing countries regarding clinico-pathologic features of even some of the common cancers such as ovarian cancer is lacking. METHODS: Information was prospectively collected on all patients with epithelial ovarian cancer referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1993 and June 30, 1998. Information was obtained directly from the patients and a close relative. Medical records were reviewed and radiologic and pathologic re-evaluation was done when necessary. RESULTS: Two hundred and eighty six patients were accrued. Mean age was 49.5 (+/- 13) years. Most of the well defined risk factors such as early menarche, late menopause, nulliparity, lack of lactation were uncommonly observed. Twenty percent of the patients had a positive family history of cancer. Most of these relatives were young (46.1 years), first degree (68%) and had breast or ovarian cancer. Clinical presentation, histologic features and stage of disease were similar to the North American or European women with epithelial ovarian cancer. CONCLUSION: Younger age at presentation and higher frequency of positive family history are two unusual features of Pakistani patients with epithelial ovarian cancer. This suggests a more significant role played by the genetic factors in these patients. Further work is needed.

Adult↗
PubMed2001

Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer.

BACKGROUND: Management of patients with recurrent epithelial ovarian cancer is difficult. Although several agents are active, responses are short-lived and observed in only a small number of patients. Side effects of these drugs are substantial. There is a need for more effective and less toxic therapies. Altretamine is a well tolerated oral agent with minimal toxicity. There are only a few trials evaluating its efficacy as a single agent in recurrent epithelial ovarian cancer. METHODS: We prospectively studied patients with recurrent epithelial ovarian cancer who were able to take oral medication and had adequate bone marrow, liver and renal functions. All had been previously treated with at least one platinum-based chemotherapy regimen and had either relapsed or failed to achieve an adequate response. RESULTS: Seventeen patients were studied. The commonest histological subtype was serous adenocarcinoma. Seven patients had platinum refractory disease. The mean duration of therapy was 6.1 months. Six patients (35%) achieved complete or partial remission, time to progression was 6.0 months and mean overall survival was 15.1 months. Toxicity was primarily nausea, vomiting and asthenia and was easily manageable. CONCLUSION: Altretamine is an acceptable and apparently less toxic alternative to other cytotoxic drugs used for palliation of patients with recurrent epithelial ovarian cancer.

Administration, Oral↗
PubMed2001

Morphological spectrum of ophthalmic tumors in northern Pakistan.

OBJECTIVE: The objective of the study was to assess the frequency and pattern of ophthalmic tumours in Northern Pakistan. METHODS: This study included all ophthalmic tumours diagnosed during a one year period (January to December 1992). RESULTS: One hundred and fourteen ophthalmic tumours were diagnosed at the Armed Forces Institute of Pathology (AFIP) and Pathology Department of the Army Medical College (AMC), Rawalpindi. Of these tumours, 70 were malignant (61.5%) and 44 were benign (38.5%). The age distribution of malignant ophthalmic tumours had two peaks. The first was seen in the paediatric age group and was mainly due to retinoblastoma. The second peak was seen above 50 years of age and was mainly due to conjunctival squamous cell carcinoma and malignant eyelid tumours which constituted 85% of the malignant ophthalmic tumours in paediatric age group. The average age at presentation of retinoblastoma was 3.8 years. The average age at presentation for squamous cell carcinoma was 56 years. Basal cell carcinoma was the most common malignant eyelid tumour (55%). The most common extraocular malignant orbital tumour was non-Hodgkin's lymphoma. Malignant melanoma of the uvea formed 22% of all melanomas diagnosed during this period. The most common benign tumours were naevi (33%), epidermal inclusion cysts (18%), choristomata (16%) and haemangioma (8%). The malignant ophthalmic tumours constituted 3% of all the malignant tumours diagnosed in Northern Pakistan during 1992 at AFIP and AMC, Rawalpindi. CONCLUSION: The ophthalmic tumours, both benign and malignant are not infrequent in clinical practice in Northern Pakistan.

Adolescent↗
PubMed2000

The Src/Csk regulatory circuit arose early in metazoan evolution.

We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.

Animals↗
PubMed2000

Use of unconventional methods of therapy by cancer patients in Pakistan.

Most of the studies related to the use of unconventional methods of therapy by cancer patients have been carried out in the developed countries. This study was conducted to ascertain the frequency, type, and duration of use of unconventional methods of therapy by cancer patients in Pakistan. We also wanted to identify individuals who are most likely to use these methods and to compare the findings with those reported from the developed countries. Between 1 April and 30 May 1994, all patients with histologically proven cancer who visited the oncology unit were interviewed. A printed questionnaire with questions and options was used as an interview guide. Informed consent was obtained. One hundred and ninety-one patients were interviewed, on average, for 25 minutes each. Use of unconventional methods of therapy by cancer patients was widespread (54.5% of all patients). The majority (83.7%) were influenced by family members to use these methods. Traditional herbal medicines (70.2%) and homeopathy (64.4%) were the most commonly employed methods. Thirty-six percent of the users employed these methods before receiving any conventional therapy. Only 15% used these methods after conventional therapeutic options had been exhausted. Patients generally perceived these methods as useful, non-toxic and inexpensive. Age, marital status, socio-economic background, education level and status of underlying neoplasm did not influence the frequency of use of unconventional methods. The use, however, was influenced by gender, family size, and type of underlying malignancy. Patients aware of their diagnosis were less likely to use these methods. This study suggests that use of unconventional methods by cancer patients in Pakistan is widespread. Unlike western countries, these methods are often employed before receiving any conventional therapy. This probably results in a significant delay which can be expected to adversely influence the subsequent disease management and survival. Public education, reduction of cost and easy availability of conventional therapy may be helpful in reducing the use of methods which otherwise may have no proven value.

Adolescent↗
PubMed1998

A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.

PURPOSE: Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated. PATIENTS AND METHODS: We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection. RESULTS: Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia. CONCLUSIONS: These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.

Adolescent↗
PubMed1998

Effect of subcutaneous injection of granulocyte-macrophage colony stimulating factor (GM-CSF) on healing of chronic refractory wounds.

OBJECTIVE: To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on healing of chronic wounds. DESIGN: Prospective open study. SETTING: 1 cancer hospital and 2 University hospitals, Pakistan. SUBJECTS: 35 patients with chronic wounds (duration 3 months or longer) that had not responded to standard treatment. Patients with malignant ulcers were excluded. INTERVENTION: GM-CSF 10 microg/cm2 was injected subcutaneously along the edges and base of the wound. The treatment was given only once and patients were followed weekly for a minimum of six weeks. MAIN OUTCOME MEASURES: Changes in size, shape, depth, edges and base of the wound, amount and quality of the granulation tissue, and type of discharge. RESULTS: Six patients were excluded from the analysis, 4 who died early of underlying disease and were not evaluable, and 2 who were excluded when histological examination of the wound showed that it was malignant. Although various types of wounds were studied, most (n = 10, 34%) were postoperative. 23 of the wounds were over 2 cm in diameter (mean 4.8 x 4.6 cm) with thin granulation tissue, and almost half were infected. Nine of the 29 wounds healed completely within six weeks while another 11 decreased in size by more than 50%; 7 patients responded slightly. Only two wounds showed no evidence of healing during the observation period. More than half of the 20 wounds that responded had healed by three weeks. Response did not correlate with any clinical variable including the presence of infection. Toxicity was negligible. CONCLUSIONS: We conclude that subcutaneous injection of a single dose of GM-CSF may induce healing in refractory chronic wounds. Trials are necessary to validate these initial observations and to decide the optimal dose and route, and whether any additional benefit may be derived from repeated injections.

Analysis of Variance↗
PubMed1998

Pattern of malignant tumors observed in a university hospital: a retrospective analysis.

A retrospective analysis of all malignant tumors observed in adults over a four-years period is presented. From January 1, 1989 to December 31, 1992, 2623 patients were coded by the Indexing and Coding Unit of Medical Records, The Aga Khan University Hospital to have cancer. Data presented reflect the relative frequency of different cancers seen at a single institution. Lung cancer was the commonest tumor observed in males. It was closely followed by head and neck cancer and lymphoma. In females, breast was the commonest cancer followed by ovarian and gallbladder. In comparison to the Western figures, an increased frequency of lymphomas and head and neck cancers was observed in males. Prostatic and colorectal cancers were less frequently observed. In females, gallbladder cancer is strikingly more frequent. Cervical cancer was less commonly observed as compared to the other developing countries and uterine cancer was infrequent in comparison to the Western countries. These data carry important implications for future health planning.

Adolescent↗
PubMed1998

Immuno-histochemical analysis of estrogen receptors on the malignant gallbladder tissue.

Sex steroids play an important part in the functioning of normal gallbladder, formation of gallstones and possibly in the pathogenesis of gallbladder cancer. Steroids receptors have been previously demonstrated on normal and malignant gall bladder tissues. To study this phenomenon further, we correlated clinicopathological features and survival with estrogen receptor (ER) status of the tumour in 30 patients with histologically-proven adenocarcinoma of the gallbladder. Estrogen receptor assay was performed immuno-histochemically utilizing Universal Immunoperoxidase Staining Kit. Tumor tissue was obtained either surgically or with fine needle aspiration of the gallbladder mass. There were 27 females and 3 males. Eighteen patients had estrogen receptors expressed on the malignant tissue, 12 were negative. Comparison of clinicopathological characteristics and survival between the two groups demonstrated no significant difference in gender, mean age, marital status and parity. Similarly, presence of gallstones, histologic grade or survival did not correlate with the estrogen receptor status. There is, however, a trend in favour of poorly differentiated tumors being more often receptor negative. Further studies are necessary to elucidate the biologic significance of these receptors.

Adenocarcinoma↗
PubMed1998

The effect of subcutaneous recombinant human erythropoietin (r-HuEPO) on anemia in cancer patients receiving platinum-based chemotherapy.

Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy.

Activities of Daily Living↗
PubMed1997

Effect of ifosfamide on intracellular glutathione levels in peripheral blood lymphocytes and its correlation with therapeutic response in patients with advanced ovarian cancer.

The successful outcome of ovarian cancer therapy with alkylating agents and cisplatin is seriously hampered by the development of acquired drug resistance. An increase in intracellular glutathione (GSH) levels in cancer cells is one of the major mechanisms involved. Depletion of GSH overcomes drug resistance and restores the chemosensitivity of malignant cells. Ifosfamide (IFEX), an alkylating agent, has been demonstrated to decrease intracellular GSH levels in vitro in malignant cell lines and in vivo in peripheral blood lymphocytes (PBL) obtained from patients with cancer. We studied the effect of IFEX on intracellular GSH levels in PBL isolated from patients with advanced ovarian cancer who were receiving chemotherapy. A total of 14 patients received IFEX plus mesna as a continuous infusion (1 g/m2 per day) for 6 consecutive days and cisplatin (100 mg/m2) as a 24-h continuous infusion on the 6th day. PBL were isolated prior to the initiation of chemotherapy and on the 3rd and 6th days of IFEX infusion. Intracellular GSH levels were determined by a modification of Tietze's method. IFEX caused a 20% or greater suppression of intracellular GSH levels in nine patients, eight of whom achieved complete remission of their disease. Six patients responded poorly to this chemotherapeutic regimen, five of whom showed no significant suppression of GSH levels. These data suggest that IFEX suppresses intracellular GSH levels in PBL from patients with ovarian cancer and that this suppression correlates closely with the subsequent clinical outcome.

Adult↗
PubMed1997

A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis.

We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial.

Adult↗