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Biomedical subjects

R Malik

Publications and source records attributed to R Malik.

At least 145 records · Page 8Linked to original sources

What do adolescent girls experience when they visit family practitioners?

OBJECTIVE: To describe the experiences of 12- to 17-year-old girls when they visit general or family practitioners and to gain some understanding of how they relate to these caregivers. DESIGN: Qualitative analysis of the oral narratives of eight adolescent girls. SETTING: After-school community drop-in centre for youth in downtown Toronto. PARTICIPANTS: Eight adolescent girls between the ages of 12 and 17 years attending the drop-in centre. MAIN OUTCOME FINDINGS: Five themes emerged: adolescent girls feel more comfortable with female physicians, they feel uncomfortable during physical examinations, they would like doctors to explain medical issues, they would like doctors to be more like friends, and they want to be treated as teenagers by their doctors. CONCLUSIONS: This study was unique in its use of personal interviews with adolescent girls to understand the experiences they have had with family physicians. The themes indicated how family physicians could improve therapeutic relationships between themselves and their female adolescent patients.

Adolescent↗

Peripheral blood stem cell mobilization for hematopoietic support of radioimmunotherapy in patients with breast carcinoma.

BACKGROUND: In clinical trials of radiolabeled monoclonal antibodies targeting metastatic breast carcinoma, myelosuppression has been the initial dose-limiting toxicity. We previously have shown that mobilized peripheral blood stem cell transfusions ameliorate this toxicity of radioimmunotherapy (RIT). Because of the difficulty we experienced harvesting adequate numbers of precursor cells from some of these heavily pretreated patients, we have compared the mobilization results and clinical histories of the metastatic breast carcinoma patients referred for RIT with those of metastatic breast carcinoma patients referred for high dose chemotherapy (HDCT) with transplantation. METHODS: Mobilization of stem cells into the peripheral blood was accomplished using granulocyte-colony stimulating factor with or without chemotherapy. Granulocyte macrophage colony-forming assays (CFU-GM) and flow cytometric analysis for CD34 positive cells were used to evaluate the number of hematopoietic precursors mobilized and collected with each apheresis procedure. Clinical characteristics, including prior chemotherapy and external beam radiotherapy, tumor bulk, and performance status, were determined by chart review. RESULTS: Significantly fewer hematopoietic precursors (both CD34 positive cells and CFU-GM) were harvested per procedure from the six RIT patients compared with a group of six patients with metastatic breast carcinoma who had stem cells harvested prior to HDCT (P = 0.002). There was no significant difference between the groups with regard to age or prior radiotherapy. All the RIT patients had received more chemotherapy, had a less favorable performance status (1 vs. 0), and had measurable tumor, whereas all the HDCT patients had minimal residual disease. CONCLUSIONS: Patients enrolled in RIT studies had lower stem cell yields than metastatic breast carcinoma patients scheduled to receive HDCT with stem cell transplantation. Poor mobilization is unlikely to be due to the mobilizing regimen alone and may be related to the intensity of prior therapy and/or tumor bulk. Mobilizing adequate stem cells for multiple treatment cycles from patients on Phase I/II RIT trials may require new, more effective mobilizing regimens, but referral of patients earlier in their disease course, prior to chronic bone marrow damage and disease progression, is recommended strongly.

Adult↗

Simultaneous cardiac and renal sympathetic neural responses to activation of left ventricular sympathetic afferents.

In separate sets of experiments, we observed that activation of left ventricular sympathetic afferents by transmural myocardial ischemia (TMI) appeared to elicit greater reflex increases in efferent sympathetic nerve activity (SNA) to the heart than to the kidney. To assess this observation more rigorously, we simultaneously measured changes in cardiac and renal SNA elicited by TMI and by epicardial and intracoronary bradykinin (BK). Experiments were performed in 19 chloralose-anesthetized dogs with sinoaortic denervation and vagotomy. TMI was created by a 2 min complete occlusion of the anterior descending coronary artery while a collateral flow limiting stenosis was present on the circumflex coronary artery. Epicardial BK was applied to small sponges (1 cm2) which were placed on the anterior wall of the left ventricle. Intracoronary BK was injected into a branch of the anterior descending artery. We observed that mean maximal reflex increases in SNA during TMI and intracoronary BK were significantly greater in cardiac than in renal nerves (TMI; 58 +/- 11% versus 36 +/- 9%, p = 0.01; intracoronary BK; 144 +/- 48% versus 77 +/- 26%, p = 0.05). Epicardial BK elicited reflex increases in cardiac and renal SNA which were not significantly different (167 +/- 44% versus 127 +/- 36%; p = 0.72). Our results indicate that activation of left ventricular sympathetic afferents by TMI and intracoronary BK elicits greater reflex increases in sympathetic outflow to the heart than to other end-organs such as the kidney. We speculate that these augmented excitatory responses are most likely related to engagement of cardio-cardiac spinal sympathetic reflexes during intense stimulation of sympathetic afferent endings.

Animals↗

Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

BACKGROUND AND OBJECTIVE: Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. STUDY DESIGN/MATERIALS AND METHODS: An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. RESULTS: Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. CONCLUSION: The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

Action Potentials↗

The effect of N-methyl-N'-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cells.

Normal dog gallbladder epithelial cells in long-term culture were used as a model to study the morphologic, genetic, and secretory processes associated with the progression to cancer formation. Dog gallbladder epithelial cells cultured on collagen-coated plates grew into polarized monolayers, could be passaged repeatedly, and showed the typical morphological profile of well-differentiated columnar epithelial cells. After cells were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 10(-5) mol/L for 48 hours, the treated cells grew on plastic and could be cloned. Flow cytometry revealed emergence of an aneuploid cell subpopulation. In organotypic culture, treated cells showed a pseudostratified appearance, with cellular and nuclear pleomorphism. Large and hyperchromatic nuclei were present as well as increased mitotic rate. The proteins of MNNG-treated dog gallbladder epithelial cells showed increased phosphorylation of tyrosine residues. Treated cells showed a decrease in mucin secretion in response to prostaglandin E2, manifesting an altered pattern of mucin secretion. Transforming growth factor-beta failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibition in normal cells. Together, the data reflected changes representing preliminary steps on the pathway to develop cancer cells. Our results indicate that carcinogenic chemicals can cause measurable chromosomal and cellular modifications to normal biliary epithelial cells in vitro. This model may be useful in understanding the sequential steps in carcinogenesis and affords an opportunity to study chromosomal damage, cytokinetics, changes in molecular genetic markers, and expression, as well as cell biological function during cellular transformation.

Animals↗

Stage IV ovarian cancer: impact of surgical debulking.

OBJECTIVE: To evaluate the influence of surgical debulking performed on patients with Stage IV ovarian cancer and to determine prognostic factors which identify pts who may benefit from aggressive initial surgical debulking. METHODS: A retrospective chart review was conducted (1/1/87-12/31/93). Eligible patients included all women with FIGO Stage IV ovarian cancer. Clinical information abstracted included age at diagnosis, histology type, tumor grade, criteria for Stage IV classification, surgical procedure performed, and tumor residuum. Optimal surgical status was defined as < or = 2 cm residual disease. Chemotherapy treatment was recorded, as was follow-up. Survival estimates were computed by Kaplan-Meier method with differences in survival calculated by the log-rank test. The Cox proportional hazards regression model was used to identify independent variables which were associated with an improved survival rate. RESULTS: One hundred five women were found in our database with Stage IV ovarian cancer and 97 had complete information available. Median age of the patients was 57 years (range 24-81 years). Papillary-serous histology was found in 55/97 patients (57%) and 50 patients (52%) had grade 3 tumors. Forty-one of 97 patients (42%) had malignant pleural effusion and 20/97 (21%) had liver metastases. Ninety-two patients underwent a primary attempt at surgical debulking and 40/92 were optimally debulked. Twenty-one of 41 patients (51%) with pleural effusion were optimally debulked compared to 20/51 (39%) with other criteria for Stage IV disease (P = NS). Overall median survival was 21 months; optimally debulked patients' median survival was 40 months compared to 18 months for patients with bulky residual disease (P = 0.01). The survival advantage for optimally debulked patients was statistically significant for the two subgroups of patients with and without malignant pleural effusion. In the multivariate analysis only age less than 65 years and optimal debulking were independent predictors of outcome. CONCLUSIONS: Surgical debulking appears to be an important determinant of prognosis in women with Stage IV ovarian cancer, including patients with malignant pleural effusion.

Adult↗

The gallbladder also secretes.

The gallbladder is traditionally regarded as an absorptive organ. There is increasing evidence that the gallbladder mucosa can have a secretory function. We studied a patient with primary sclerosing cholangitis whose gallbladder was excluded from his extrahepatic bile ducts by stricture formation. He was admitted into hospital because of cholecystitis and cholangitis and required separate drainage tubes into his gallbladder and common hepatic duct. This unique combination of drains afforded the opportunity to examine hepatic bile and gallbladder secretion. We analyzed samples for fluid volume, protein, electrolyte concentrations and biliary lipids. The simultaneous, yet separate, drainage from the gallbladder and the liver had a striking difference. The former was colorless to opalescent; the latter always golden brown. Hepatic bile flow was continuous but gallbladder drainage was variable in volume, intermittent, and occurred only after a meal. The gallbladder fluid had no bilirubin, bile salts, cholesterol, or phospholipids and had the ionic profile of an extracellular fluid. It was alkaline and contained abundant bicarbonate. We have shown that the gallbladder can secrete. In addition, these observations may also have important implications in the pathogenesis and prevention of gallbladder sludge and stones.

Aged↗

Clinical and neurophysiological features of tick paralysis.

The clinical and neurophysiological findings in six Australian children with generalized tick paralysis are described. Paralysis is usually caused by the mature female of the species Ixodes holocyclus. It most frequently occurs in the spring and summer months but can be seen at any time of year. Children aged 1-5 years are most commonly affected. The tick is usually found in the scalp, often behind the ear. The typical presentation is a prodrome followed by the development of an unsteady gait, and then ascending, symmetrical, flaccid paralysis. Early cranial nerve involvement is a feature, particularly the presence of both internal and external ophthalmoplegia. In contrast to the experience with North American ticks, worsening of paralysis in the 24-48 h following tick removal is common and the child must be carefully observed over this period. Death from respiratory failure was relatively common in the first half of the century and tick paralysis remains a potentially fatal condition. Respiratory support may be required for > 1 week but full recovery occurs. This is slow with several weeks passing before the child can walk unaided. Anti-toxin has a role in the treatment of seriously ill children but there is a high incidence of acute allergy and serum sickness. Neurophysiological studies reveal low-amplitude compound muscle action potentials with normal motor conduction velocities, normal sensory studies and normal response to repetitive stimulation. The biochemical structure of the toxin of I. holocyclus has not been fully characterized but there are many clinical, neurophysiological and experimental similarities to botulinum toxin.

Acetylcholine↗

Anatomy of the ductus venosus in neonatal dogs (Canis familiaris).

Anatomical features of the ductus venosus in 84 neonatal dogs are described. The ductus venosus was a straight conduit 1-3 mm wide and 4-12 mm long in pups with a crown-rump length of 80-200 mm. It arose from the left main portal vein branch opposite the umbilical vein, passed between the left lateral liver lobe and the papillary process of the caudate lobe, and terminated in the dorsal aspect of the proximal part of the left hepatic vein. The left hepatic vein was dilated at this point. There was no variation in the location of the ductus venosus in the animals studied.

Animals↗

Rickets in a litter of racing greyhounds.

Rickets was diagnosed in six 14-week-old racing greyhound littermates presented with musculoskeletal disease. Physical findings included listlessness, profound muscle weakness, lameness, lateral bowing of the antebrachii and focal hard swellings proximal to the tarsi and carpi. Radiological findings included generalised osteopenia, axial and radial thickening of growth plates, and "cupping' of the adjacent metaphyses; the distal ulnar growth plates were most severely and consistently affected. The diagnosis was confirmed by demonstrating subnormal concentrations of 25-hydroxycholecalciferol in serum samples collected at admission. The pups' diet consisted of an inexpensive generic kibble formulated for adult dogs, porridge, milk, pasta, minced beef, vegetables and a small quantity of calcium carbonate powder. The pups were successfully treated by feeding a nutritionally complete, vitamin D-containing ration formulated for growing pups. Bilateral growth retardation of distal ulnar physes occurred as a sequel in one pup.

Animals↗

Benign cranial mediastinal lesions in three cats.

Cranial mediastinal lesions were detected in three cats, associated with respiratory impairment (case one), spontaneous pneumothorax (case two) and myasthenia gravis (case three), respectively. On gross and histological examination, the first case was considered either a lymphangioma or a branchial cystic mass of the thymic region of the mediastinum; a cystic lesion was suggested by sonographic detection of multiple anechoic cavitations within a circumscribed mass, while fine needle aspiration cytology excluded lymphosarcoma. The second case was diagnosed histologically as a cystic thymoma, but the third case was not examined microscopically. The masses were amenable to surgical excision in the first two cats, while this proved unnecessary in the third case because of resolution following treatment with dexamethasone. Corticosteroid responsiveness was unhelpful in distinguishing between these benign lesions and lymphosarcoma, as in two cases there was a partial or complete response to dosing with prednisolone or dexamethasone. These cases are presented to emphasise that conditions other than lymphosarcoma can produce cranial mediastinal lesions in cats, and that the prognosis for surgical treatment of lymphangiomas, multilocular thymic cysts and cystic thymomas can be excellent.

Animals↗

Nasopharyngeal cryptococcosis.

Naturally occurring cryptococcosis in five cats, a dog and a koala is described. Involvement of the nasopharynx was documented in all patients, and nasopharyngeal mass lesions accounted for the major presenting complaints in four. Signs referable to nasopharyngeal disease included snoring, stertor, inspiratory dyspnoea and aerophagia. Diagnoses were made by caudal rhinoscopy using a retroverted flexible endoscope, vigorous orthograde flushing with saline, or at necropsy. Concurrent cryptococcal rhinitis was present in all cases, although involvement appeared limited to the caudal nasal cavity in most cases. Typical signs of nasal cavity disease, such as sneezing and nasal discharge, were often absent. Treatment of nasopharyngeal cryptococcosis should include physical dislodgement or debulking of lesion(s) to provide immediate alleviation of upper airway obstruction, followed by systemic antifungal therapy to eliminate residual infection from the nasal cavity. Infections caused by Cryptococcus neoformans var gattii accounted for a disproportionately large number of these cases.

Animals↗

Prevalences of feline leukaemia virus and feline immunodeficiency virus infections in cats in Sydney.

OBJECTIVE: To determine prevalences of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) infections in 'healthy' cats that, through acute misadventure or other circumstance, were presented to veterinary practitioners. Prevalences of FeLV and FIV in this population were compared to those in a population of predominantly sick cats. DESIGN AND PROCEDURES: Serum specimens were obtained over a 2-year period from 200 cats older than 1 year of age presented to veterinary clinics for routine procedures, including cat fight injuries or abscesses, vehicular trauma, neutering, dental scaling, vaccination, grooming or boarding. An additional 894 sera were obtained over approximately the same period from specimens submitted by veterinarians to a private clinical pathology laboratory, mainly from sick cars suspected of having immune dysfunction, but including some sera from healthy cats being screened prior to FeLV vaccination. FIV antibody and FeLV antigen were detected in samples using commercial enzyme immunoassays. RESULTS: Amongst 200 'healthy' cats, the prevalence of FeLV infection was 0 to 2%, and the prevalence of FIV was 6.5 to 7.5%, depending on the stringency of the criteria used to define positivity. FIV infection was significantly more prevalent in cats which resided in an inner city environment (P = 0.013). Of the 894 serum specimens submitted to the laboratory by practitioners, 11/761 (1.4%) were FeLV positive, while 148/711 (20.8%) were FIV positive. The prevalence of FIV was significantly higher in these predominantly 'sick' cats than in cats seen for routine veterinary procedures (P < 0.00001), while there was no difference in the prevalence of FeLV (P = 0.75) CONCLUSIONS: The prevalence of FeLV and FIV in healthy cats may have been substantially overestimated in some previous Australian surveys. FeLV infection would appear to be a rare cause of disease in Australian cats. The higher prevalence of FIV positivity in sick as opposed to healthy cats infers that FIV infection contributes to the development of disease.

Animals↗

Lung capillary changes in hepatic cirrhosis in rats.

The hypoxemia of the hepatopulmonary syndrome may result from dilated intrapulmonary vascular segments. Knowledge of the size, density, and branching frequency of the lung capillaries might confirm this hypothesis and suggest that the pathogenesis may involve vascular dilatation or angiogenesis. To investigate these changes, the common bile duct of rats was tied off to cause biliary cirrhosis. Later (4 wk), the pulmonary vasculature of these animals was cast, and the casts were studied with scanning electron microscopy. In the ligated animals, evidence for enhancement of the bronchial to pulmonary circulation was found: cast vasa vasorum of the pulmonary arteries and cast bronchial veins emptying into pulmonary veins. Ligated animals had more adherent intracapillary cells per alveolus than the sham-operated animals. The diameters of all capillary beds were larger in the ligated animals. The alveolar capillary density was increased, but the branching frequency was not. A few areas suggesting angiogenesis were found. Induction of biliary cirrhosis enhances the pulmonary-systemic circulation, increases intracapillary adherent cells, capillary diameter, and density, and may be associated with angiogenesis.

Animals↗

Failure to uncover the effects of unconscious symbiotic fantasies on heart rate and fine motor performance.

18 men and 18 women were tachistoscopically shown the stimuli MOMMY AND I ARE ONE, DADDY AND I ARE ONE, and MYMMO NAD I REA ENO, at subjective thresholds (subliminal condition) and at 500 msec. (supraliminal condition). Following exposure to each stimulus, subjects performed a fine motor line-tracing task. Heart rate was monitored continuously during stimulus presentation and the fine motor task. Analysis showed subjects did not respond more positively with decreased heart rate or fewer errors on the fine motor task following the MOMMY message than the anagram phrase, thereby providing no support for the hypotheses. No correlation was found between responsiveness to the MOMMY message and scores on measures of self-perception and kinship. In the light of mounting negative evidence, the validity of the method of subliminal psychodynamic activation is questioned.

Adult↗

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis).

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.

Acute Disease↗