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Biomedical subjects

R Malik

Publications and source records attributed to R Malik.

At least 163 records · Page 9Linked to original sources
PubMed1996

Bleeding from gastric antral vascular ectasia in marrow transplant patients.

BACKGROUND: Gastric antral vascular ectasia (GAVE) leads to blood loss in the disorders of "watermelon stomach" and portal gastropathy, but is not a commonly recognized complication of marrow transplantation. METHODS: GAVE was diagnosed when capillary ectasia, focal capillary thromboses, and fibromuscular hyperplasia were identified in antral mucosal biopsy specimens. Marrow transplant patients bleeding from GAVE were reviewed to ascertain common variables in their pretransplant, posttransplant, and bleeding course. RESULTS: Six patients developed bleeding due to GAVE. The onset of bleeding was 18 to 94 days after transplant and required an average of 37 U of blood (range, 2 to 130 U). Two patients stopped bleeding after restoration of platelet counts. Two patients had surgical antral resections; both died of multiorgan failure after surgery. Two patients had successful endoscopic laser ablation of vascular lesions and survived. Factors possibly associated with GAVE included male gender, VOD of the liver, oral busulfan as part of the conditioning regimen, and growth factor use after transplant. CONCLUSIONS: GAVE was a cause of gastric bleeding in six patients with marrow transplant patients. Restoration of platelet counts and endoscopic laser photocoagulation are the therapies of choice for ongoing bleeding in these patients.

Adolescent↗
PubMed1996

Glomerulopathy in dogs with congenital portosystemic shunts.

Kidney specimens from 12 dogs with congenital portosystemic shunts were examined histologically. Glomerulopathy of variable severity was present in the kidney sections of all 12. Marked irregular thickening of the glomerular capillary wall was the most prominent pathological change, the renal interstitium being largely unaffected. The severity of lesions was not correlated with the age of dogs at the time of necropsy. An immunoperoxidase technique failed to demonstrate significant IgA or IgG deposition in affected glomeruli. Proteinuria was generally mild or absent despite significant glomerular lesions, except in dogs with concurrent urinary tract infection.

Animals↗
PubMed1996

Combination chemotherapy of canine and feline cryptococcosis using subcutaneously administered amphotericin B.

Six cases (3 cats, 3 dogs) of cryptococcosis were cured using combination chemotherapy that included amphotericin B. We developed a simple, practical and inexpensive method of administering amphotericin B as a subcutaneous infusion during the treatment of these patients. For this, the calculated dose of amphotericin B (0.5 to 0.8 mg/kg) was added to 400 mL, for cats, or to 500 mL, for dogs, of 0.45% saline containing 2.5% dextrose. These amounts were given subcutaneously 2 or 3 times weekly over several months, to a total cumulative dose of 8 to 26 mg/kg body weight. Subcutaneous infusions were generally well tolerated by the animals, although concentrations of amphotericin B in excess of 20 mg/L resulted in local irritation. This protocol enabled the administration of larger, and thus more effective, quantities of amphotericin B without producing marked azotaemia.

Amphotericin B↗
PubMed1996

Suspected drug eruption in seven dogs during administration of flucytosine.

7 of 8 dogs receiving combination drug therapy consisting of flucytosine together with amphotericin B and/or a triazole for cryptococcosis or aspergillosis developed cutaneous or mucocutaneous eruptions during the course of treatment. Lesions resolved in all cases following discontinuation of flucytosine despite continued administration of other antifungals, suggesting the eruption was referable primarily to the flucytosine component of therapy. Lesions developed 13 to 41 days (median 20 days) after commencing flucytosine (105 to 188 mg/kg/day divided and given every 8 h; median dose rate 150 mg/kg/day). The cumulative dose of flucytosine given prior to the first signs of the drug eruption ranged from 1.7 to 6.8 g/kg (median 2.3 g/kg). The eruptions consisted of depigmentation, followed by ulceration, exudation and crust formation. The scrotum was affected in all 4 male dogs, the nasal plane in 6 of 7 cases, while the lips, vulva, external ear canal and integument were involved in a smaller number of cases. There was considerable variation in the severity of lesions, with changes being most marked when flucytosine was continued for several days after lesions first appeared. Some dogs experienced malaise and inappetence in association with the suspected drug eruption. Healing took a variable period, typically in excess of 2 weeks after discontinuing flucytosine, with up to 2 months being required for total resolution of the lesions. All lesions resolved eventually without scarring or permanent loss of pigment.

Amphotericin B↗
PubMed1996

A latex cryptococcal antigen agglutination test for diagnosis and monitoring of therapy for cryptococcosis.

A latex cryptococcal antigen agglutination test (LCAT) was performed on sera obtained during the first 14 days of treatment from 58 animals (46 cats, 9 dogs, 2 koalas and 1 long billed corella) with cryptococcosis. The same commercial kit was used for all samples, and most serum samples were treated with pronase before testing. Sera from all 58 cases tested positive with the qualitative LCAT protocol (using undiluted sera), while sera from all 26 cats without cryptococcosis tested negative. Titres determined using the quantitative protocol ranged from 1 to > or = 131 072 (median titre between 2048 and 4096), with 57 of 58 cases (including all 8 animals that presented for neurological signs) having titres > or = 2 and thus considered positive according to the manufacturer's recommendations. The LCAT titre was positively correlated with disease severity (r = 0.4169; P = 0.0011), and patients with disseminated skin and/or lymph node involvement had significantly higher titres than those that did not (P = 0.0157). The presence of neurological signs, the species of the patient, concurrent viral disease (in cats) and the biotype of the isolate had no significant association with the LCAT titre. Cats that died of active cryptococcosis despite treatment did not have significantly higher titres (P = 0.3010) than those that responded to treatment. Sequential LCAT determinations obtained in 37 patients during treatment provided a useful quantitative indication of clinical progress, although the decline in titre lagged somewhat behind clinical improvement. Generally, the antigen titre declined by 2 to 4 fold per month during successful therapy. Although there are insufficient data to make unequivocal recommendations, we suggest that either antifungal therapy be continued until the LCAT titre declines to less than 1, or therapy be discontinued after a 32 fold or greater reduction in titre, with periodic monitoring of the serum antigen titre. Treatment of serum samples with pronase substantially increased the sensitivity of the LCAT.

Agglutination Tests↗
PubMed1996

Natural environmental sources of Cryptococcus neoformans var. gattii.

We sought evidence for new environmental sources of Cryptococcus neoformans var. gattii by random amplification of polymorphic DNA (RAPD) analysis of isolates from 29 animals with a restricted territorial range in five Australian states. Twenty-three of the 29 isolates and 45 of 45 eucalypt isolates tested previously exhibited one RAPD profile, VGI. RAPD profile VGII was identified in 6 of 17 isolates from domesticated species but in none of 12 native species. Four VGII isolates originated from an area of Western Australia with no natural stands of known eucalypt host, indicating the existence of at least one unrecognized natural source of C. neoformans var. gattii.

Animals↗
PubMed1996

Effects of subliminal symbiotic stimuli on anxiety reduction.

The present study assessed the effectiveness of subliminal psychodynamic stimuli in reducing anxiety. 50 male and 50 female college students were tachistoscopically exposed to one of five stimuli: MOMMY AND I ARE ONE, DADDY AND I ARE ONE, I AM HAPPY WITH MYSELF, ONE, or a control stimulus MYMMO NAD I REA ENO. It was hypothesized that men would show a significant decrease in anxiety to the MOMMY stimulus, while women were expected to respond favorably to either the MOMMY or DADDY stimulus, or to both. Results showed that the subliminal stimuli did not produce differential effects on anxiety. This finding did not support previous claims for subliminal psychodynamic activation that the stimulation of symbiotic fantasy with the maternal figure produces positive behavioral effects. Despite this negative finding women's response to the MOMMY message was predicted by measures of self-perception.

Adaptation, Psychological↗
PubMed1996

The method of subliminal psychodynamic activation: do individual thresholds make a difference?

The present experiment investigated the effects of subliminal psychodynamic stimuli on anxiety as measured by heart rate. Following an anxiety-inducing task, male and female subjects were tachistoscopically shown, at their subjective thresholds, one of five subliminal stimuli, MOMMY AND I ARE ONE, DADDY AND I ARE ONE (symbiotic messages). MOMMY HAS LEFT ME (abandonment message), I AM HAPPY AND CALM (positively toned but nonsymbiotic phrase), or MYMMO NAD I REA ENO (control stimulus). It was hypothesized that men would exhibit a greater decrease in heart rate after exposure to the MOMMY stimulus than the control message. No definitive predictions were made for women. The abandonment phrase was expected to increase heart rate. A positively toned message was included to assess whether its effects would be comparable to those hypothesized for the MOMMY message. The results yielded no significant effects for stimulus or gender and so provided no support for the hypotheses.

Adult↗
PubMed1995

Catecholamines in human keratinocyte differentiation.

Human keratinocytes have the capacity to synthesize catecholamines from L-tyrosine, which in turn is produced from L-phenylalanine via phenylalanine hydroxylase. This enzyme activity is controlled by the supply of the essential cofactor/electron donor (6R)5,6,7,8 tetrahydrobiopterin (6-BH4). Undifferentiated keratinocytes express high levels of the rate-limiting enzymes for the de novo synthesis of 6-BH4, i.e., GTP-cyclohydrolase-1, and for its recycling, i.e., 4a-hydroxytetrahydrobiopterin dehydratase. As a consequence of 6-BH4 synthesis, phenylalanine hydroxylase is activated, yielding L-tyrosine, which in the presence of excess 6-BH4 turns on the biosynthesis of catecholamines via the rate-limiting enzyme tyrosine hydroxylase. Therefore, undifferentiated keratinocytes contain high levels of the catecholamine system yielding sufficient levels of norepinephrine and epinephrine, required for the induction of beta-2-adrenoceptors. Stimulation of beta-2-adrenoceptors by epinephrine causes a rise in intracellular calcium via extracellular influx. This event corresponds with keratinocyte differentiation. In differentiated keratinocytes, all enzyme activities involved in 6-BH4, L-tyrosine, and epinephrine biosynthesis are decreased, resulting in significantly lower levels of epinephrine and a concomitant decrease in the expression of beta-2-adrenoceptors. These data strongly suggest a connection between catecholamine biosynthesis, beta-2-adrenoceptor expression, calcium flux, and the differentiation of keratinocytes in human epidermis.

Biopterins↗
PubMed1995

Ventricular septal defect repair in a small dog using cross-circulation.

A haemodynamically significant ventricular septal defect was diagnosed in a 3-month-old male Cavalier King Charles Spaniel. A median sternotomy was performed and the 6.5 kg dog placed on cardiopulmonary bypass using pump-assisted cross-circulation. A 10 mm diameter peri-membranous ventricular septal defect was closed using a continuous suture of 4-0 polypropylene, via a 2.5 cm incision in the right ventricular outflow tract. The duration of cardiopulmonary bypass was 90 minutes. Complications in the immediate postoperative period were mild and easily managed.

Animals↗
PubMed1995

Analysis of leucocytes and lymphocyte subsets in cats with naturally-occurring cryptococcosis but differing feline immunodeficiency virus status.

Although cryptococcosis is a well-characterised disease of cats, the factors predisposing individuals to infection are unknown. As an indication of the immune status of an individual, lymphocyte subsets can be analysed. Reference ranges for feline lymphocyte subsets (Pan T+, CD4+, CD8+ and B cells) were established using a rapid whole blood technique and flow cytometry. There were no effects of age or sex on lymphocyte subset values. The numbers of circulating leucocytes and lymphocyte subsets were determined in FIV-positive and FIV-negative cats with cryptococcosis and compared with a group of healthy control cats. There were only minor differences in the numbers of lymphocyte subsets among the subgroups of cats examined in the study and the predisposition to cryptococcosis in cats could not be explained by deficiencies in lymphocyte subsets. There was a tendency for FIV-negative cats with cryptococcosis to have reduced numbers of circulating CD4+ cells and lower CD4:CD8 ratios compared with normal cats, although the interpretation of this finding was complicated by the wide reference range for normal cats. The extent to which this is the cause of the fungal infection was not determined. The only difference in leucocyte or lymphocytes subset values between FIV-negative cats with cryptococcosis and FIV-positive cats with cryptococcosis was that the CD4+ percentage was lower in the FIV-positive cats. The absolute CD4+ count was similar however, in FIV-positive and FIV-negative cryptococcosis cases. On the basis of this and other available information, the categorisation of cryptococcosis as a disease defining the AIDS phase of FIV infection may be incorrect.

Animals↗
PubMed1995

Post-prandial serum bile acid concentrations and ammonia tolerance in Maltese dogs with and without hepatic vascular anomalies.

Post-prandial serum bile acid concentrations were measured in 200 Maltese dogs in an attempt to identify those with subclinical portosystemic shunts. Five of these were later shown to have hepatic pathology or abnormal liver function. In the other 195 Maltese, bile acid concentrations ranged from 1 to 362 mumol.L-1 (mean +/- SD, 70 +/- 50 mumol.L-1; median, 65.0 mumol.L-1). Of these, 79% were above the reference range (0 to 31 mumol.L-1) established from 23 mixed-breed control dogs. It was therefore not possible to determine the prevalence of subclinical portosystemic shunts on the basis of bile acid determinations. Further investigation of liver function was performed to investigate why bile acid concentrations were increased in these dogs. Rectal ammonia tolerance tests were normal in 102 of 106 Maltese tested and liver samples (11 dogs) and plasma biochemistry profiles (9 dogs) demonstrated no significant hepatic disease or dysfunction. Of 2 Maltese with hyperammonaemia after administration of ammonium chloride, one had a large congenital portosystemic shunt that was confirmed at surgery. In the other there were no macroscopic portosystemic communications, but a liver biopsy showed histological changes consistent with microscopic portovascular dysplasia. Total serum bile acid concentrations were consistently lower when assessed by high-performance liquid chromatography than by an enzymatic spectrophotometric method. This discrepancy was substantially larger in Maltese than in control dogs, suggesting the presence of an additional reacting substance in the serum of Maltese dogs.

Ammonia↗
PubMed1994

Vascular factors in diabetic neuropathy.

Despite considerable research we still do not have a comprehensive explanation for the pathogenesis of diabetic neuropathy. Although chronic hyperglycaemia is almost certainly involved, it is not known whether the primary pathology is metabolic, microvascular, or an interaction between the two. Hyperglycaemia-induced polyol pathway hyperactivity associated with nerve sorbitol accumulation and myo-inositol depletion may play a part in the genesis of diabetic neuropathy. The case for microvascular disease in diabetic neuropathy is now strong. Fibre loss in human sural nerve is multifocal, suggesting ischaemia. The degree of vessel disease has been related to the severity of neuropathy. People with chronic obstructive pulmonary disease develop the so called "hypoxic neuropathy" in which similar microvascular changes occur as in diabetic neuropathy. In rats with experimental diabetic neuropathy nerve blood flow is reduced and oxygen supplementation or vasodilator treatment improved the deterioration in conduction velocity and nerve blood flow. Similarly, in human diabetic neuropathy, there is impaired nerve blood flow, epineurial arterio-venous shunting and a reduction in sural nerve oxygen tension. At what stage during the development of nerve damage these changes occur is yet to be determined.

Animals↗
PubMed1994

Pharmacokinetics of fluconazole in cats after intravenous and oral administration.

Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13.8 [2.6] hours) was similar to that observed after oral dosing (12.4 [3.0] hours). The plasma clearances (intravenous 0.9 [0.1], oral 0.9 [0.2] ml min-1 kg-1) and the volumes of distribution at steady state (intravenous 1.1 [0.1], oral 1.0 [0.1] litre kg-1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2.6 hours after oral dosing and the drug was completely bioavailable (1.09 [0.05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre-1.

Administration, Oral↗
PubMed1994

Congenital portosystemic shunts in Maltese and Australian cattle dogs.

Congenital portosystemic shunts were definitively diagnosed in 62 dogs over a period of 15 years. Maltese and Australian Cattle Dogs were significantly overrepresented, accounting for 14 and 13 cases, respectively. Maltese invariably had a single extrahepatic shunt derived from the left gastric or gastrosplenic vein, whereas Cattle Dogs usually had large intrahepatic shunts involving the right liver lobes. The clinical syndromes resulting from anomalous portosystemic communications were indistinguishable in the 2 breeds. Fasting blood ammonia concentration was elevated in 20 of 22 dogs tested, providing a minimally invasive and effective means of diagnosis. Complete or partial shunt attenuation was performed successfully in all 9 Maltese and in 2 of 6 Cattle Dogs in which it was attempted.

Ammonia↗