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Biomedical subjects

R Kulkarni

Publications and source records attributed to R Kulkarni.

At least 19 recordsLinked to original sources
PubMed2001

Therapeutic choices for patients with hemophilia and high-titer inhibitors.

Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The proceedings of a one-day workshop of physicians who specialized in treating patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In making a decision regarding the choice of product, physicians often consider the type of bleeding episode (life or limb threatening), age of the patient, volume of the reconstituted product, previous exposure to plasma derived products, cost, efficacy, and safety. For plasma naïve patients, to achieve rapid hemostasis a majority of the panelists used porcine FVIII (for patients who lack porcine inhibitory antibodies) or rFVIIa. For patients previously treated with plasma derived factors, in addition to the above concentrates, aPCCs were recommended. Although no data exists regarding safety and efficacy, switching products was routinely practiced either because of availability or cost. Furthermore, the panelists were uncertain about the efficacy of bypassing agents in the prevention of joint disease in inhibitor patients. The workshop participants felt that future research offers the best solution to resolve some of the dilemmas faced by clinicians and may help individualise treatment in a hemophilia patient with a high titer inhibitor.

Animals↗
PubMed2001

Successful treatment of high titer inhibitors in mild hemophilia A with avoidance of factor VIII and immunosuppressive therapy.

We describe two patients with mild hemophilia A (MHA) who developed high titer inhibitor (HTI) following intensive recombinant factor VIII (rFVIII) concentrate replacement for surgery and trauma. Intranasal desmopressin was instituted shortly following immunosuppressive therapy (IST) and activated prothrombin complex concentrate (APCC) in one case, and following APCC alone in the second case. Avoidance of factor VIII (FVIII) coupled with intranasal desmopressin prophylaxis three times a week resulted in undetectable inhibitor levels. Both patients have had no further bleeding episodes and have been maintained on desmopressin prophylaxis prior to activity for the past 2 to 3 years. Recombinant factor VIIa (rFVIIa) was used successfully prior to a second surgery in one patient without complication.

Adolescent↗
PubMed2001

Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance.

Several lines of investigation suggest that the hypothalamic neuropeptide melanin-concentrating hormone (MCH) regulates body weight in mammals. Obese mice lacking functional leptin overexpress the MCH message in the fed or fasted state. Acute intracerebroventricular injection of MCH increases energy intake in rats. Mice lacking the MCH gene are lean. To test the hypothesis that chronic overexpression of MCH in mice causes obesity, we produced transgenic mice that overexpress MCH (MCH-OE) in the lateral hypothalamus at approximately twofold higher levels than normal mice. On the FVB genetic background, homozygous transgenic animals fed a high-fat diet ate 10% more and were 12% heavier at 13 weeks of age than wild-type animals, and they had higher systemic leptin levels. Blood glucose levels were higher both preprandially and after an intraperitoneal glucose injection. MCH-OE animals were insulin-resistant, as demonstrated by markedly higher plasma insulin levels and a blunted response to insulin; MCH-OE animals had only a 5% decrease in blood glucose after insulin administration, compared with a 31% decrease in wild-type animals. MCH-OE animals also exhibited a twofold increase in islet size. To evaluate the contribution of genetic background to the predisposition to obesity seen in MCH-OE mice, the transgene was bred onto the C57BL/6J background. Heterozygote C57BL/6J mice expressing the transgene showed increased body weight on a standard diet, confirming that MCH overexpression can lead to obesity.

Adipose Tissue↗
PubMed2001

Nickel-titanium shape memory alloy Memokath 051 ureteral stent for managing long-term ureteral obstruction: 4-year experience.

PURPOSE: We present our 4-year experience with the thermo-expandable shape memory alloy Memokath 051 stent (Engineers and Doctors of Copenhagen, Copenhagen, Denmark) for managing long-term ureteral obstruction. MATERIALS AND METHODS: We used a nickel-titanium shape memory alloy ureteral stent to treat 28 patients 29 to 86 years old (mean age 59.2). Ureteral obstruction was caused by malignancy in 18 cases and by recurrent benign disease in 10. A total of 37 stents were inserted from November 1996 to November 2000 using general anesthesia. Mean followup was 19.3 months (range 3 to 35). RESULTS: Upper tract decompression was achieved in all cases. Currently 15 stents are functional in 13 patients, while 8 patients died with a total of 13 functioning stents in place. In 7 patients 9 stents were removed for various reasons. There has been no radiological evidence of encrustation to date. No patient has been rehospitalized with stent related sepsis pain or hematuria, resulting in improved quality of life. CONCLUSIONS: This stent seems to provide a significant benefit over conventional Double-J (Medical Engineering Corp., New York, New York) and other metallic stents. Its remarkable thermal memory permits removal, a feature that until recently was not available in any other metallic ureteral stent. Durable and complication-free decompression of the upper tract can be achieved with the Memokath 051.

Adult↗
PubMed1999

Current practices regarding newborn intracranial haemorrhage and obstetrical care and mode of delivery of pregnant haemophilia carriers: a survey of obstetricians, neonatologists and haematologists in the United States, on behalf of the National Hemophilia Foundation's Medical and Scientific Advisory Council.

We undertook this survey to determine institutional practices of obstetricians, neonatologists and haematologists regarding care of pregnant haemophilia carriers and newborns with haemophilia and intracranial haemorrhage (ICH). Our purpose was also to determine whether institutions had written guidelines to manage such patients. Questionnaires were sent to 1000 obstetricians and through the Haemophilia Treatment Centres (HTC) to 180 paediatric haematologists and 180 neonatologists, each representing an institution. Twenty-three per cent of obstetricians, 22% of neonatologists and 16% of paediatric haematologists returned completed surveys. Over 94% of the respondents had no written guidelines for management of pregnant haemophilia carriers or their newborns or for neurologic assessment of newborns. For known haemophilia carriers, 57% of the obstetricians routinely preferred vaginal delivery and 11% preferred caesarean section. Availability of perinatal services influenced prenatal management (P < 0.05). In term newborns with documented ICH, only 23% of neonatologists would evaluate for haemophilia, whereas in pre-term newborns with ICH, this number dropped even further to 3%. For all newborns with haemophilia, 40% preferred routine administration of clotting factor concentrates (CFC) immediately following birth to offset the trauma of delivery and 89% of paediatric haematologists favoured early prophylaxis with CFC. Guidelines are needed for management of pregnant haemophilia carriers as well as newborns with haemophilia. Physicians need to be made aware that ICH may be a presenting sign of haemophilia in both term as well as pre-term newborns, so that appropriate therapy can be instituted early in the event of a bleed.

Adult↗
PubMed1998

Left internal mammary artery perforation during Swan-Ganz catheter insertion.

A wide spectrum of complications is associated with invasive hemodynamic monitoring. We report an unusual case of perforation of the left internal mammary artery that occurred during percutaneous insertion of a Swan-Ganz catheter using the subclavian vein approach. To the best of our knowledge, this complication has not been previously reported.

Aged↗
PubMed1998

Effect of direct current shocks on left atrial mechanical function in patients with structural heart disease.

OBJECTIVES: This study examined the effect of endocardial and transthoracic direct current (DC) shocks on left atrial and left atrial appendage function in humans with structural heart disease. BACKGROUND: DC cardioversion of atrial fibrillation (AF) to sinus rhythm is associated with transient left atrial and left atrial appendage dysfunction and the development of spontaneous echo contrast (SEC). This phenomenon has been termed atrial "stunning" and may be associated with thrombus formation and embolic stroke. To what extent the shock itself contributes to atrial stunning is unclear. METHODS: Thirteen patients in sinus rhythm undergoing implantation of a ventricular implantable cardioverter defibrillator (ICD) were prospectively evaluated. All patients had significant structural heart disease. To evaluate the effects of DC shocks on left atrial and left atrial appendage function, biphasic R wave synchronized endocardial shocks of 1, 10 and 20 J were delivered between the right ventricular electrode and the left pectoral generator of the ICD in sinus rhythm. R wave synchronized transthoracic shocks of 360 J were also delivered between anteriorly and posteriorly positioned chest electrodes. Transesophageal echocardiography was performed to evaluate left atrial appendage velocities, mitral inflow velocities and the presence of SEC before and immediately after each DC shock. RESULTS: There were no significant changes in left atrial or left atrial appendage function after endocardial or transthoracic DC shocks. Left atrial SEC did not develop after endocardial or transthoracic DC shocks. CONCLUSIONS: Endocardial and transthoracic DC shocks are not directly responsible for left atrial and left atrial appendage stunning and do not contribute to the stunning that is observed after the cardioversion of AF to sinus rhythm.

Aged↗
PubMed1998

Astroblastoma: does histology predict biologic behavior?

Astroblastoma is a rare and controversial tumor about which little is known. We have made the diagnosis in seven patients since 1990 at Memorial Sloan-Kettering Cancer Center. Four patients had astroblastomas with anaplastic features, whereas three patients had tumors which were well-differentiated. All three patients with low grade lesions are alive and recurrence free after surgery alone (mean follow-up 29 months). All four patients with anaplastic astroblastoma were treated with surgery, radiotherapy and chemotherapy. One died of infection during induction chemotherapy. Two others died of tumor progression at 28 and 42 months. Radiographic response to chemotherapy was seen in one patient. The results of our series and other reports suggest that anaplastic histology is a prognostic factor in the setting of astroblastoma. More aggressive treatment is necessary for patients with anaplastic astroblastoma although the precise role of irradiation and chemotherapy cannot be defined at this time.

Antineoplastic Agents↗
PubMed1997

Altered excitability of the crayfish lateral giant escape reflex during agonistic encounters.

The excitability of the lateral giant escape reflex of socially dominant and submissive crayfish at rest and during agonistic encounters was studied and compared. During agonistic encounters the excitability of the lateral giant reflex falls, substantially in subordinates and slightly in dominants, whereas at rest excitability seems to be independent of social status. Thus, paradoxically, socially dominant animals are more likely to execute lateral giant escape reactions during interactions than are subordinates. It is suggested that subordinates under threat of attack tend to engage circuitry involved in flexible, nonreflex ("voluntary") types of escape not mediated by giant neurons and therefore inhibit giant neuron-mediated reflex circuitry that produces prompt, but less adaptive, responses. In contrast, dominants go about their business, mainly ignoring their conspecifics and relying on reflex escape to protect them from unexpected attack. Consistent with this view, escape of subordinates during agonistic encounters is mediated by nongiant, not reflex, circuitry. These observations and their interpretation suggest a possible functional role for recently described social status-dependent serotonergic modulation of the lateral giant reflex, which is inhibitory in sign in subordinates and facilitatory in dominants.

Agonistic Behavior↗
PubMed1995

Coronary angioplasty in unstable angina: contemporary experience.

OBJECTIVE: To evaluate the role of percutaneous transluminal coronary angioplasty (PTCA) in the treatment of patients with unstable angina. DESIGN: Retrospective analysis of administrative records of all acute care hospital discharges at Robert Wood Johnson University Hospital from 1987 to 1993 with International Classification of Diseases, 9th revision, codes for coronary angioplasty and corresponding catheterization laboratory reports. SETTING: Tertiary care teaching hospital. RESULTS: Of 4826 PTCA cases, unstable angina was identified in 780 as the main indication for the procedure. Baseline clinical features of patients with unstable angina were not different from those in patients with stable angina. The overall success rate for PTCA in patients with unstable angina was significantly higher (707 of 780, 91%) than the success rate in patients with stable angina (3466 of 4046, 86%). The major complication rate in unstable angina patients was low (29 of 780, 3.7%) and did not differ from that in stable angina patients (136 of 4046, 3.4%). The success and complication rates in patients with unstable angina were analyzed in terms of time of PTCA, ie, early (less than 48 h from admission) versus late (48 h or more from admission). The procedure was successful in 343 of 380 (90%) patients treated early and 364 of 400 (91%) patients treated late (not significant), and the complication rates were low (12 of 380, 3.2% versus 17 of 400, 4.3%; not significant in both groups). However, length of hospital stay was considerably shorter for patients treated early than for patients treated late (4.5 +/- 3.3 days versus 10.4 +/- 6.6 days, respectively, P < 0.0001). CONCLUSION: Contemporary results of PTCA in patients with unstable angina parallel those reported for stable angina. Thus, PTCA appears to be an effective and safe treatment for unstable angina patients, and treating these patients soon after admission does not appear to affect the success or complication rates.

Angina, Unstable↗
PubMed1993

Halothane acts on many potassium channels, including a minimal potassium channel.

There has been considerable controversy over whether general anesthetics act directly on membrane proteins, and if so, whether there are uniquely sensitive protein targets upon which they act. Here, we examine the actions of halothane on a diverse collection of voltage-gated potassium channels expressed in Xenopus oocytes, and find that they are all sensitive at clinically relevant concentrations. To investigate further the molecular basis of this commonality, human and rat minimal potassium (minK) channels, which have exceedingly short amino acid sequences, were examined. Current through these channels is reversibly reduced to 68% of control values by 0.5% (0.34 mM) halothane. A double deletion mutant of the 130-amino acid minK protein, in which 30 amino acids of the N-terminus, thought to be extracellular, and 37 amino acids of the putative intracellular C-terminus are deleted (resulting in a protein in which more than half of both the extracellular and intracellular domains have been removed) responds to low halothane concentrations similarly to the parent channel. While alternative explanations are possible, this result is consistent with a model whereby halothane interacts with the channel protein from within the lipid bilayer.

Animals↗
PubMed1993

Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.

Forty-one patients with hemophilia A were studied for the prevalence of serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic marker for previous hepatitis B infection; four of these 31 patients (13%) also demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%) patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but positive for anti-HBs; all of these nine patients were HIV antibody positive, although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100% demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C, respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the patients demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C infections, respectively. The difference between HIV antibody positive and HIV antibody negative groups was not significant for hepatitis A but was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31 patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of 10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗