Biomedical subjects

D Mistry

Publications and source records attributed to D Mistry.

At least 19 recordsLinked to original sources

PubMed2006

Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response. The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined. Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml, 37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169). These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.

Adult↗

PubMed2006

The role of adenosine in chondrocyte death in murine osteoarthritis and in a murine chondrocyte cell line.

OBJECTIVE: To investigate the role of adenosine in chondrocyte death in murine osteoarthritis (OA). METHODS: 5'-Nucleotidase (5'NT) generates adenosine. Enzyme activity was measured histochemically in normal murine and osteoarthritic STR/ort strain tibial cartilage. Adenosine-mediated cell death was investigated in MC615 chondrocyte cultures. Adenosine receptors (ARs) were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Cellular uptake of [(3)H] adenosine was measured with or without the inhibitor, nitrobenzylthioinosine (NBTI). Cell death was assessed by cell counting and DNA laddering following selective receptor stimulation, or after modulating adenosine metabolism with adenosine deaminase (ADA) or adenosine kinase (AK) inhibitors [erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and Iodotubericidin (Itub)], or with homocysteine (HC). Markers of apoptosis were assessed by Western blotting. Cell studies were validated by incubating normal murine knee joints in a medium containing adenosine and metabolic inhibitors. Apoptotic chondrocytes were identified with the TUNEL reaction. RESULTS: 5'NT activity in STR/ort tibial cartilage increased with development of OA, especially close to OA lesions. Adenosine induced MC615 cell death in the presence of ADA inhibition (100 microM EHNA), or 1mM HC, or both. Adenosine uptake, mediated by NBTI-sensitive adenosine transporters, was required for cell death. ARs were expressed (A2b>A2a>A1) but were not involved in mediating cell death. Cell death involved the activation of caspase-3 and DNA fragmentation and was prevented by inhibiting caspase activity. However, neither caspase-8 nor caspase-9 was detected. Adenosine+EHNA induced chondrocyte apoptosis in normal murine knee joints. CONCLUSION: Increased adenosine production may induce chondrocyte apoptosis and play a role in OA in STR/ort mice.

5'-Nucleotidase↗

PubMed2006

Rhinological, laryngological, oropharyngeal and other head and neck side effects of drugs.

Following a previous paper in which we documented the otological side effects of drug therapy, we here review other drug side effects that ENT surgeons may encounter when dealing with patients. Although otological drug side effects such as hearing loss and tinnitus are well recognized there are many rhinological, laryngeal, oropharyngeal and other head and neck drug side effects. Our data were sourced from the British National Formulary and Electronic Medical Compendium websites.

Databases, Factual↗

PubMed2005

Otologic side effects of drugs.

Otolaryngologic symptoms are common and patients presenting to the otolaryngologist will often be taking drugs for the treatment of unrelated diseases. As a doctor, one must not forget the potential of these drugs to cause otologic side effects and, in some cases, to be the cause of the presenting symptom. We performed a comprehensive search of the British National Formulary and Electronic Medical Compendium websites to classify the otologic side effects caused by drugs. Not all the data were found at both websites. We have compiled all the data together, subclassified them and produced a review of the otologic side effects of drugs, in table form.

Dizziness↗

PubMed2005

Large B-cell non-Hodgkin's lymphoma presenting as a laryngeal cyst.

Cystic lesions of the larynx are most commonly benign. However, we report a case of non-Hodgkin's lymphoma (NHL) of the larynx which presented as a supraglottic cyst. This form of presentation has not been previously described in the medical literature.

Antibodies, Monoclonal↗

PubMed2004

Chondrocyte death during murine osteoarthritis.

OBJECTIVE: To determine whether chondrocyte apoptosis occurs during the progression of osteoarthritis (OA) in the STR/ort mouse model of OA. METHODS: Serial cryostat sections were cut (10 microns) through the knee joint of young and old male STR/ort mice and graded for the severity of OA lesions. Age- and sex-matched CBA mice were used as controls. Apoptotic chondrocytes were detected using the TUNEL assay. Ultrastructural changes were examined using electron microscopy (EM). Expression of biochemical markers associated with apoptosis (bax, bcl-2 and caspases-3, -8 & -9) was investigated using immunohistochemistry. RESULTS: TUNEL assays on histological sections of STR/ort knee joints showed that the number of TUNEL-positive chondrocytes in the tibial medial articular cartilage correlated with the severity of the OA damage. These cells were located close to the lesional area. Only very occasional TUNEL positive chondrocytes were detected in either morphologically normal STR/ort cartilage or in control CBA cartilage. Ultrastructural analysis of chondrocytes neighboring focal osteoarthritic lesions in STR/ort tibial cartilage revealed an abundance of abnormal cells exhibiting numerous morphological changes. These resembled, but in some cases differed, from changes reported in classical apoptosis. The changes include abnormal distribution of chromatin, cell shrinkage, membrane blebbing and deposition of cell remnants (apoptotic bodies) in the lacuna space. Despite the TUNEL and EM changes, immunohistochemistry failed to detect any changes in the ratio of bax to bcl-2 in tibial chondrocytes of STR/ort mice. Both bcl-2 and bax levels decreased with age in morphologically normal STR/ort and control CBA cartilage. None of the caspases tested for was detected in tibial chondrocytes of either strain. CONCLUSION: Chondrocyte cell death is correlated with the progression of OA in STR/ort mice and has many of the morphological characteristics of classical apoptosis. Absence of changes in bax to bcl-2 ratio in STR/ort chondrocytes indicate that the mitochondrial pathway of apoptosis is unlikely to be involved. Failure to detect caspases could be due to low levels of enzyme expression, expression within a very brief time period, or to a caspase-independent mechanism of cell death.

Animals↗

PubMed2004

Consent for tonsillectomy.

Rulings in recent negligence cases reveal a shift towards what the 'reasonable patient' would expect in deciding the risks doctors must disclose to patients. This survey aimed to investigate whether the 'reasonable patient' and 'responsible body of medical opinion' agree about which risks should be discussed regarding tonsillectomy. Using questionnaires, surgeons were asked which of the 10 complications they routinely discussed and patients were asked how seriously they regarded these complications. The results were compared with the Test of Proportions. Most surgeons routinely mentioned otalgia, odynophagia, throat infection and re-operation. Most patients regarded potentially fatal bleeding, pneumonia and blood transfusion as very serious but only the minority of surgeons mentioned these (P < 0.001). When obtaining consent for tonsillectomy, surgeons do not routinely mention all the risks that the 'reasonable patient' would expect. The 'reasonable patient' would expect that re-operation, transfusion, pneumonia and fatal blood loss are discussed.

Blood Transfusion↗

PubMed2001

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗

PubMed2001

The spatial and temporal expression of calretinin in developing rat molars (Rattus norvegicus).

Calretinin is a 29-kDa calcium-binding protein abundantly expressed in central and peripheral neural tissues. The aim here was to determine its expression during various stages of odontogenesis. Five categories of embryonic (E) and postnatal (P) rats at various ages (E17, E18, E20, P0, and P7), both male and female, were used to represent the various stages of molar tooth development. The heads of the experimental animals were harvested at the appropriate time and each was cut mid-sagittally and coronally to locate the tooth germs. Selected sections were stained immunohistochemically with polyclonal rabbit anticalretinin at a concentration of 1:25 after microwave irradiation. The results showed that calretinin is distributed widely in epithelium-derived tissues during odontogenesis in rat molar tooth germs. It was expressed focally in the dental lamina, outer enamel epithelium, stellate reticulum and stratum intermedium at different stages. In contrast, it was expressed diffusely and intensely in the inner enamel epithelium and presecretory ameloblasts, although it was discontinuous over the cusp tips. In the secretory ameloblasts, the staining was less intense, being restricted to the cytoplasm, including Tomes' processes. This distribution suggests that calretinin may play a part in enamel formation.

Age Factors↗

PubMed2000

Sodium channel isoform-specific effects of halothane: protein kinase C co-expression and slow inactivation gating.

The modulatory effect of protein kinase C (PKC) on the response of Xenopus oocyte-expressed Na channel alpha-subunits to halothane (2-bromo-2-chloro-1,1,1-trifluroethane) was studied. Na currents through rat skeletal muscle, rat brain and human cardiac muscle Na channels were assessed using cell-attached patch clamp recordings. PKC activity was increased by co-expression of a constitutively active PKC alpha-isozyme. Decay of macroscopic Na currents could be separated into fast and slow exponential phases. PKC co-expression alone slowed Na current decay in neuronal channels, through enhancement of the amplitude of the slower phase of decay. Halothane (1.0 mM) was without effect on any of the three isoforms expressed alone but, after co-expression of PKC, there was enhancement of Na current decay with reduction in charge movement through skeletal muscle and neuronal channels. Cardiac channels were relatively insensitive to halothane. Enhanced Na current decay resulted from suppression of the slow phase, without effect on the faster phase or on either decay tau. Suppression of Na current through skeletal muscle channels was concentration-dependent over the therapeutic range and was described by third order reaction kinetics, with an IC(50) of 0.55 mM. We conclude that the halothane suppresses skeletal muscle and brain Na channel activity in this preparation through a reduction in the slow mode of inactivation gating, but only after PKC co-expression. Cardiac Na channels were relatively insensitive to halothane. The mechanism is likely to involve phosphorylation of the channel inactivation gate, although phosphorylation of other sites in the channel may account for the isoform specific differences.

Animals↗

PubMed2000

Effect of coupling medium temperature on rate of intramuscular temperature rise using continuous ultrasound.

OBJECTIVE: We determined the effects of coupling medium temperature on the rate of intramuscular temperature rise (RTR) during continuous ultrasound. DESIGN AND SETTING: Ultrasound was applied in a continuous mode at a frequency of 1 MHz and intensity of 1.5 W/cm(2). Each subject received 3 treatments, using water-based coupling gel at temperatures of 18 degrees C, 25 degrees C, and 39 degrees C. All treatments were performed in an athletic training room under controlled environmental conditions. SUBJECTS: Eighteen healthy male subjects (mean age = 23.6 +/- 3.5 years; height = 177.8 +/- 6.9 cm; weight = 76.6 +/- 8.2 kg; calf size = 37.6 +/- 2.4 cm) participated in this study. MEASUREMENTS: A thermistor was inserted into the left medial triceps surae at a depth of 5 cm, and baseline tissue temperatures were recorded before treatment. Intramuscular temperature was recorded every 30 seconds until the temperature rose 4 degrees C above baseline or until discomfort was felt. RTR was calculated by dividing the absolute temperature change by treatment time. RESULTS: A 1-way, repeated-measures analysis of variance revealed a significant difference in RTR among gel temperatures, RTR was significantly faster using the 25 degrees C gel compared with the 18 degrees C and 39 degrees C gels. There was no difference between the 18 degrees C and 39 degrees C gel treatments. CONCLUSIONS: These results suggest that the use of a cooled or heated gel may be counterproductive when maximal thermal effects are desired within a given time frame.

Journal Article↗

PubMed1999

Protein kinase C co-expression and the effects of halothane on rat skeletal muscle sodium channels.

1. Voltage-gated Na channels, which are potential targets for general anaesthetics, are substrates for PKC, which phosphorylates a conserved site in the channel inactivation gate. We investigated the idea that PKC modulates the effect of volatile anaesthetics on Na channels via phosphorylation of this inactivation gate site. 2. Na currents through rat skeletal muscle Na channel alpha-subunits expressed in Xenopus oocytes were measured by two-microelectrode voltage clamp in the presence of the volatile anaesthetic agent halothane (2-bromo-2-chloro-1,1,1-trifluroethane). PKC activity was modulated by co-expression of a constitutively active PKC alpha-isozyme. 3. Halothane (0.4 mM) had no effect on Na currents. With co-expression of PKC, however, halothane dose-dependently enhanced the rate of Na current decay and caused a small, but statistically significant reduction in Na current amplitude. 4. The enhancement of Na current decay was absent in a Na channel mutant in which the inactivation gate phosphorylation site was disabled. Effects of halothane on amplitude were independent of this mutation. 5. Co-expression of a PKC alpha-isozyme permits an effect of halothane to hasten current decay and reduce current amplitude, at least in part through interaction with the inactivation gate phosphorylation site. We speculate that the interaction between halothane and Na channels is direct, and facilitated by PKC activity and by phosphorylation of a site in the channel inactivation gate.

Anesthetics, Inhalation↗

PubMed1998

Temperature changes in deep muscles of humans during upper and lower extremity exercise.

OBJECTIVE: To examine the effect of 15 minutes of upper and lower extremity exercise on raising intramuscular temperature in the triceps surae to 39 degrees C to 45 degrees C (the therapeutic range). DESIGN AND SETTING: Intramuscular temperature was measured 5 cm deep in the triceps surae using a 23-gauge thermistor needle microprobe connected to a monitor. Each subject was tested under 3 conditions: 15 minutes of rest, 15 minutes of jogging on a treadmill, and 15 minutes of handpedaling an upper-body ergometer. Exercise bouts were performed at 70% of each subject's maximum heart rate. SUBJECTS: Six males, either sedentary or recreational athletes (age = 21.3 +/- 2.9 years; ht = 176.8 +/- 6.0 cm; wt = 72.7 +/- 11.6 kg; resting heart rate = 57.8 +/- 6.74 bpm; target heart rate = 156.5 +/- 3.0 bpm), volunteered to participate in this experiment. MEASUREMENTS: Intramuscular temperature was measured at a depth of 5 cm before and after each test condition. RESULTS: Data analyses consisted of analyses of variance with repeated measures and a Tukey post hoc test (P < .05). The results showed a significant temperature increase over baseline after exercise on the treadmill (2.2 degrees C +/- 0.63 degrees C); however, it did not yield temperature increases >/= 39 degrees C. No significant temperature change occurred after exercise on the upper-body ergometer (-0.45 degrees C +/- 0.80 degrees C). CONCLUSIONS: Active exercise increased intramuscular temperature in working muscles but did not affect intramuscular temperature in nonworking muscles. In addition, 15 minutes of jogging on a treadmill at 70% of maximum heart rate was not sufficient to raise intramuscular temperature to 39 degrees C to 45 degrees C.

Journal Article↗

PubMed1995

The internal oblique repair of abdominal bulges secondary to TRAM flap breast reconstruction.

The internal oblique repair, a new method for repair of abdominal bulging following TRAM flap breast reconstruction, involves identification and repair of the internal oblique fascia. To assess the usefulness of this repair and to compare it with simple plication of the deep abdominal fascia, we retrospectively reviewed all abdominal bulge repairs performed by the first author over the past 7 1/2 years. Of 30 abdominal bulge repairs, the internal oblique repair was used in 14 patients and plication in 16 others. The bulge recurrence rate was lower after the internal oblique repair (21 percent) than after the plication repair (69 percent; p = 0.028). When synthetic mesh reinforcement was added to the internal oblique repair, the bulge recurrence rate dropped to 13 percent. We conclude that the internal oblique repair is the preferred technique for the correction of abdominal bulges secondary to TRAM flap breast reconstruction.

Abdominal Muscles↗

PubMed1994

Quantitative analysis of collagen accumulation during protein malnutrition.

It is generally believed that protein malnutrition is detrimental to proper wound healing. However, there is limited evidence in the literature to support this. The authors studied the effect of protein depletion on the accumulation of collagen to determine the quantitative changes taking place in the healing wound. Polytetrafluoroethylene (PTFE) wound cylinders were implanted subcutaneously in 30 male Sprague-Dawley rats. The rats were divided into two groups and fed either chow (C) (n = 12) or an isocaloric protein-free (PF) diet (n = 18). Seven, 14, and 21 days later, the rats were weighed, bled, and wound cylinders harvested. PTFE cylinder collagen content, hematologic parameters, total serum protein, and serum albumin were determined. The rats with the PF diet had significant (P < .001) weight loss at all time-points (day 7, PF = 176.2 +/- 3.2, F = 252.4 +/- 3.8; day 14, PF = 154.8 +/- 3.6, F = 289.3 +/- 9.2; day 21, PF = 150.8 +/- 3.9, F = 307.6 +/- 12.2). Total serum protein was also depleted as compared with controls (P < .001). White blood cell counts were significantly higher on day 7 (PF = 7.5 +/- 0.9, C = 4.4 +/- 0.9, P < .03) in the PF group; however, this was not sustained, and there was no difference between the groups on days 14 and 21. Collagen content (micrograms of 5-hydroxyproline [OHP] per centimeter PTFE) was diminished on day 7 (PF = 12.7 +/- 2.0, C = 24.7 +/- 3.4, P < .03). No difference was seen on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Differential acceleration of healing of surgical incisions in the rabbit gastrointestinal tract by platelet-derived growth factor and transforming growth factor, type beta.

Anastomotic dehiscence is a major cause of morbidity and mortality in gastrointestinal surgery. A unique model system of a gastric incision was developed to test the potential of polypeptide growth factors to enhance wound healing. Paired, deep partial-thickness incisions to but not including the gastric mucosa were made. A single topical application of transforming growth factor, type beta 1 (TGF-beta), platelet-derived growth factor, or control vehicle at the time of wounding was given. Wound breaking strength and detailed histologic analyses of wounds were evaluated as a function of time after wounding. TGF-beta (0.1 to 2.0 micrograms/wound) demonstrated a bimodal, dose-dependent acceleration of wound breaking strength 7 days after gastric wounding. An approximate 4-day acceleration of gastric wound breaking strength by TGF-beta (2 micrograms/wound) was seen at 7 and 11 days. Wounds treated with platelet-derived growth factor (10 micrograms/wound) displayed an increased cellular response but no enhancement of breaking strength at 7 and 11 days. These results demonstrate the ability of TGF-beta to accelerate gastrointestinal tissue repair by topical application and suggest significant potential for the use of growth factors in enhancing repair of surgical wounds of the gastrointestinal tract.

Animals↗

PubMed1983

Organ culture studies of human prostatic adenocarcinomas.

The proliferative responses of human prostatic carcinoma have been evaluated in organ culture using [125I]-iododeoxyuridine ([125I]UdR) to monitor DNA synthesis. The morphological preservation was not influenced by the addition of fetal calf serum or insulin (5 mu gm/ml), transferrin (10 mu gm/ml), and thyrotropin releasing hormone (10(-9) M) to the active medium. Testosterone (4 X 10(-7) M) stimulated [125I]UdR uptake, whereas diethylstilboestrol (4 X 10(-6) M) had no direct effect on uptake. Both estramustine phosphate (4 X 10(-6) M) and oestradiol-17 beta (4 X 10(-6) M) inhibited uptake in a similar manner. Thus while explants of human prostatic carcinoma derived from transurethrally resected specimens can be well maintained in organ culture for a few days, proliferative responses are small and difficult to measure for individual patients.

Adenocarcinoma↗

PubMed1982

Proliferative responses of cultured rat prostate and human benign prostatic hyperplasia.

The proliferative responses of rat prostate and human benign prostatic hyperplasia have been followed in organ culture using [125I] iododeoxyuridine uptake to monitor DNA synthesis. In serum-free cultures, testosterone induced a marked increase in DNA synthesis (three-fold) in 4- to 6-month-old rat prostates at concentrations of 4 x 10(-9) to 4 x 10(-6) M, whereas in greater than 12-month-old rat prostates the response was less marked. Human benign prostatic hyperplasia also showed an increased uptake at similar testosterone concentrations and of a similar magnitude to the response of greater than 12-month-old rat prostates. At 10(-5) M DNA synthesis was markedly suppressed in cultures of both rat and human prostate. The proliferative response of human benign prostatic hyperplasia increases up to days 3 to 4 in culture and then declines in both control and hormone-treated groups and may represent repair processes which appear to be hormone dependent.

Animals↗