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J Kulkarni

Publications and source records attributed to J Kulkarni.

At least 19 recordsLinked to original sources
PubMed2006

Permeation enhancers in the transmucosal delivery of macromolecules.

The present article presents a compilation of information regarding various chemical permeation enhancers useful for transmucosal delivery of macromolecules. In the recent past, biotechnology has provided a great number of macromolecules for treatment of various disorders. With the rise in importance of macromolecules, especially proteins and peptides, an enormous volume of research on various novel routes of drug delivery has been carried out. Inspite of its giving the highest and fastest bioavailability, the parenteral route is not a preferred option, due to its inconvenience and the noncompliance of patients. Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Transmucosal drug delivery with various bioavailability enhancers is receiving increasing attention as a possible alternative to parenteral delivery of macromolecules. Among the various bioavailability enhancers, chemical permeation enhancers have been most studied. Permeation enhancers reversibly modulate the permeability of the barrier layer in favor of drug absorption. Newer permeation enhancers like zonula occludin toxin, poly-L-arginine, chitosan derivatives etc have shown a significant increase in drug absorption through transmucosal routes without serious damage to the barrier layer. In particular delivery of macromolecules via the nasal and pulmonary routesusing newer permeation enhancers has emerged as a possible alternative to the parenteral delivery ofmacromolecules.

Animals↗
PubMed2005

Estrogen for schizophrenia.

BACKGROUND: In terms of clinical outcomes, women with schizophrenia seem to fare better then men, but appear more vulnerable to psychotic illness in the period after birth and menopause. As these vulnerable periods to psychosis are associated with estrogen withdrawal, this hormone has been proposed as a treatment for schizophrenia. OBJECTIVES: To evaluate the clinical effects of estrogens alone or in combination with progesterone, as a sole treatment or as an adjunctive therapy, for the treatment of schizophrenia or schizophrenia-like illnesses. SEARCH STRATEGY: Electronic searches of the Cochrane Schizophrenia Group's Register (October 2003) was supplemented with manual reference inspection of all identified studies. Authors of trials were contacted for further material and archive information. SELECTION CRITERIA: All randomised clinical trials comparing estrogens with or without progesterone, as a sole or adjunctive treatment for people with schizophrenia or other similar serious, non-affective psychotic illness. DATA COLLECTION AND ANALYSIS: We evaluated data independently and analysed on an intention to treat basis. For binary data we calculated the fixed effect relative risk (RR) and its 95% confidence interval (CI). For continuous non-skewed data, we calculated weighted mean differences. MAIN RESULTS: All available evidence relates to women. Four studies (n=108) compared estrogen only with placebo. Short-term scores for general mental state showed no significant difference between groups (n=24, 1 RCT, WMD PANSS for 100mcg comparison -2.26 CI -15.4 to 10.9). Data from all four studies showed overall loss from the studies was low ( 5%), with no significant differences between groups (n=96, 4 RCTs, RR 0.95 CI 0.2 to 6.1). Skewed continuous data from two studies showed no clear differences in ratings of movement disorders. One medium-term unpublished study (n=14) compared estrogen and progesterone with placebo. Data at six months showed no difference between groups for total scores (n=9, WMD PANSS -25.3 CI -51 to 0.1). For negative symptoms, results favoured the estrogen and progesterone group (n=9, WMD PANSS negative subscale -9.0 CI -17 to -0.9). For loss to follow up there was no difference between groups (n=10, RR 0.33 CI 0.02 to 6.7). This trial used many cognitive tests and one visual retention test showed statistically significant differences favouring the treatment group: total scores (n=8, WMD -3.5 CI -5.7 to -1.3). AUTHORS' CONCLUSIONS: Adjunctive estrogen with or without progesterone does not appear to offer convincing advantages over placebo. Before any more research is undertaken in this area, all completed and unpublished work should be made available in order to ensure that more trials are justified.

Estrogens↗
PubMed2005

Victimization of patients with schizophrenia and related disorders.

BACKGROUND: Previous research has predominately focused on patients with mental illness as the instigators, rather than the victims, of violence and criminal activity. However, patients with schizophrenia appear to experience a higher degree of victimization compared to general community samples. We aimed to establish the 1-month prevalence of violent and non-violent victimization in a sample of patients with schizophrenia spectrum disorders and to investigate the determinants of victimization. METHOD: Reports of violent and non-violent victimization were recorded in 348 patients in Dandenong, an outer metropolitan suburb of Melbourne, Australia along with the subjective perception of patients as to their degree of protection from being robbed or attacked. Patients reporting victimization were compared with those who did not, across a range of clinical and psychosocial variables. RESULTS: 11.2% of the sample reported being the victim of non-violent crime and 4.3% the victim of violent crime in the 1-month period. 23.2% reported dissatisfaction with their protection against being attacked or robbed. The major determinant of victimization was the lack of any meaningful daily activity. CONCLUSIONS: Patients with schizophrenia spectrum disorders are at increased risk of victimization, both of the violent and non-violent type. Further research is required to understand the pathways through which victimization occurs and to understand whether psychosocial interventions can reduce victimization in this patient population.

Activities of Daily Living↗
PubMed2005

Chronic low back pain in traumatic lower limb amputees.

OBJECTIVE: To ascertain the prevalence of back pain amongst traumatic lower limb amputees attending a regional rehabilitation centre and to determine the possible causes of back pain. DESIGN: All traumatic lower limb amputees given a semi-structured questionnaire to complete and a comparative subgroup of amputees with back pain and without back pain underwent physical examination, gait analysis, magnetic resonance scanning (MRI) and gait/standing stability analysis. SETTING: A subregional amputee rehabilitation centre. RESULTS: Transfemoral amputees were more likely to suffer from back pain (81 %) than transtibial amputees (62%) (p<0.05) and of those suffering from severe back pain, 89% and 81% also suffered from severe pain in the phantom limb and severe stump pain respectively. In two comparative subgroups of amputees there was no significant difference between back pain and pain-free groups except those with pain were more likely to have a body mass index (BMI) ratio above 50% of the recommended ratio. No difference in degeneration or disc disease between the groups on MR scans was found. Impact ground reaction forces during walking, irrespective of limb, were significantly greater (p < 0.05) in the pain-free group than in the pain group, as was walking speed. Gait asymmetry measures were similar in both groups. Centre of pressure displacement measures during standing were greater in the pain group than in the pain-free group. CONCLUSIONS: Low back pain in amputees is a significant problem equal to that of pain in the phantom limb and a biomechanical (myofascial) rather than a degenerative aetiology is suggested.

Adolescent↗
PubMed2004

Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia.

BACKGROUND: Schizophrenia may be characterized by abnormal plastic modulation in cortical neuronal circuits. Activation of premotor cortex using repetitive transcranial magnetic stimulation (rTMS) produces suppression of cortical excitability in primary motor cortex. We hypothesized that premotor rTMS would cause less suppression of motor cortical excitability in patients with schizophrenia than in control subjects. METHODS: Twelve patients diagnosed with schizophrenia and twelve healthy control subjects underwent subthreshold rTMS to the premotor area in a 15-min conditioning train. Measurements of primary motor cortical excitability (motor evoked potential; MEP), the resting motor threshold (RMT), and cortical inhibition (CI) were taken before and after the rTMS. RESULTS: There was no difference in RMT between groups at baseline, although the patient group had less CI than the control group at baseline. Following rTMS, the change in both MEP size and RMT between groups was significant. After rTMS, MEP size was suppressed in the control group and increased in the patient group, whereas RMT increased in the normal control group and decreased in the patient group. CONCLUSIONS: Patients with schizophrenia demonstrate abnormal brain responses to rTMS applied to the premotor cortex that appear to relate to reduced motor cortical inhibition.

Adult↗
PubMed2004

Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study.

BACKGROUND: Abnormalities in brain plasticity, possibly related to abnormal cortical inhibition (CI), have been proposed to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation (TMS) provides a dynamic method for non-invasive study of plastic processes in the human brain. We aimed to determine whether patients with schizophrenia would exhibit an abnormal response to repetitive TMS (rTMS) applied to the motor cortex and whether this would relate to deficient cortical inhibition. METHODS: Measures of motor cortical excitability and cortical inhibition were made before and after a single 15-min train of 1-Hz rTMS applied to the motor cortex in medicated and unmedicated patients with schizophrenia as well as healthy controls. RESULTS: All three groups had equal motor cortical excitability prior to rTMS, although both patient groups had a shorter cortical silent period (CSP) and less cortical inhibition than the control group. Cortical excitability, as assessed by motor threshold levels, did not reduce in both medicated and unmedicated patients in response to rTMS as was seen in the control group. Significant differences were also seen between the groups in response to the rTMS for motor-evoked potential (MEP) size and cortical silent period duration. CONCLUSIONS: Both medicated and medication free patients with schizophrenia demonstrated reduced brain responses to rTMS and deficits in cortical inhibition.

Adult↗
PubMed2003

A confirmatory factor analytic evaluation of the pentagonal PANSS model.

The positive and negative syndrome scale (PANSS) is widely used in psychiatric research. Reflecting this common use, considerable attention has been applied to the psychometric properties of this instrument. However, despite the publication of numerous studies and analyses, it remains uncertain how best data from the PANSS should be analysed to best model the symptoms of schizophrenia. A resolution to these concerns seemed to be offered following the publication in 1997 of a large multisite factor analysis that produced the 'pentagonal model', which has subsequently been included in the 2000 revision of the PANSS user manual. However, to date, an independent confirmatory analysis of this model has not yet been published. The aim of this study was to test this model in a new independent sample with confirmatory factor analysis (CFA). Independent confirmation of the fit of the model is required to ensure that its implementation is informed by confirmation of its psychometric properties. CFA was performed in a sample of 347 subjects with schizophrenia. The analysis found that the model had inadequate goodness of fit. The use of the pentagonal model has similar difficulties as earlier models and more research is required to ascertain the optimal method for measuring symptom dimensions in research and clinical settings.

Adult↗
PubMed2002

A study of transcallosal inhibition in schizophrenia using transcranial magnetic stimulation.

A considerable body of imaging research has demonstrated morphological changes in the corpus callosum (CC) of patients with schizophrenia. Transcranial magnetic stimulation (TMS) allows the possibility for the in vivo investigation of a variety of aspects of brain function including the spread of information across the CC. We aimed to investigate whether patients with schizophrenia demonstrate abnormalities of transcallosal inhibition (TCI), a TMS parameter measured with both single and paired pulse experiments. 25 patients with DSM-IV schizophrenia and 20 normal volunteers participated in the study. Electromyographic (EMG) recordings from the bilateral abductor pollicis brevis (APB) muscle were made during focal TMS stimulation to the motor cortex. Experimental paradigms were utilised to measure both the timing and degree of the effect of TCI. The patient group demonstrated a reduction in the degree of TCI at rest and during a sustained muscle contraction. TCI commenced at the same time in the patient and the control group but was of prolonged duration in the patient group although the length of TCI correlated with medication dose. Patients with schizophrenia demonstrate a reduction in the degree of TCI that appeared independent of medication dose. The latency of TCI is not altered in the patient group suggesting that cortical inhibitory mechanisms, rather than corpus callosal ones, are likely to be the cause of these TCI alterations.

Adult↗
PubMed2002

A transcranial magnetic stimulation study of the effects of olanzapine and risperidone on motor cortical excitability in patients with schizophrenia.

RATIONALE: There has been a progressive increase in interest in the functioning of the main inhibitory and excitatory neurotransmitters in the pathophysiology of schizophrenia. Limited information is available as to how these neurotransmitters are affected by commonly prescribed antipsychotic agents. OBJECTIVES: We investigated whether the atypical antipsychotics olanzapine and risperidone differ in their effects on inhibitory and excitatory cortical markers measured with transcranial magnetic stimulation. METHODS: Electromyographic recordings from the abductor pollicis brevis muscle were made during focal transcranial magnetic stimulation to the contralateral motor cortex and during bilateral cortical stimulation. Twenty patients on each drug and 22 controls were studied with measures of the resting motor threshold, motor evoked potential size, post-excitatory silent period duration, cortical inhibition and facilitation to paired-pulse transcranial magnetic stimulation and transcallosal inhibition. RESULTS: The patient groups differed from the controls in the silent period and transcallosal inhibition measures, both of which assess cortical inhibitory activity. The two medication groups differed in the magnitude of the resting motor threshold and several measures of transcallosal inhibition that reflect the spread of inhibitory activity between hemispheres. CONCLUSIONS: These findings suggest that olanzapine and risperidone differ subtly in their effects on cortical inhibitory mechanisms. Further evaluation is required to establish whether these differences may reflect or underlie differences seen between these medications in their clinical profiles, including their effects on cognitive symptoms of schizophrenia.

Adult↗
PubMed2002

A clinical trial of adjunctive oestrogen treatment in women with schizophrenia.

A double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 microg transdermal estradiol or b) 100 microg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 microg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 microg estradiol or placebo groups. The addition of 100 microg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia.

Administration, Cutaneous↗
PubMed2002

Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability.

OBJECTIVES: This study explored whether the effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal excitability are dependent on the stimulation intensity and examined the effect of rTMS on inhibitory function. METHODS: Nine normal volunteers received 15min of 1Hz rTMS at 85 and 115% of the resting motor threshold (RMT). Cortical excitability was measured before and after rTMS. RESULTS: rTMS at both intensities produced an increase in the RMT but only 115% stimulation reduced the size of motor evoked potentials (MEPs). rTMS had no effects on the cortical silent period or cortical inhibition measured with paired pulse TMS. CONCLUSIONS: The effects of 1Hz rTMS on motor cortex excitability are partially dependent on stimulus intensity and the effects of rTMS on motor thresholds and MEP size may differ.

Adult↗
PubMed2001

Estrogen - a potential treatment for schizophrenia.

Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems - the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N=12 in each group) who received standardized antipsychotic medication plus 50mcg transdermal estradiol or 100mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50mcg estradiol and placebo groups. Women receiving 50mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100mcg estradiol group had significantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50mcg and placebo groups. The addition of 100mcg adjunctive transdermal estrogen significantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50mcg versus 100mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.

Administration, Cutaneous↗
PubMed2001

Subject and observer-rated quality of life in schizophrenia.

OBJECTIVE: We aimed to explore the relationship between objectively rated quality of life and subjective measures of social functioning and life satisfaction. METHOD: Participants of the Schizophrenia Care and Assessment Program (SCAP) study at Dandenong in Australia were included in this analysis. Subjective ratings of several domains of social functioning and life satisfaction were taken from the SCAP instrument and comparisons made with data from the Quality of Life scale rated by research staff as well as several psychopathology measures. RESULTS: Subjectively reported life satisfaction was not related to positive or negative symptoms of schizophrenia but did correlate with depressive symptoms. Quality of Life scale measures correlated with negative symptoms on most domains. There was very limited overlap in domain items between the life satisfaction and quality of life measures. CONCLUSION: Life satisfaction and objectively rated quality of life are not closely related and appear to have different determinants in patients with schizophrenia.

Adult↗
PubMed2001

A foot care program for diabetic unilateral lower-limb amputees.

OBJECTIVE: To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees. RESEARCH DESIGN AND METHODS: Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of approximately 3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient. RESULTS: For the patients referred to the foot care program, there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 +/- 0.04) compared with the unilateral amputees (0.90 +/- 0.03, mean +/- SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 +/- 2.16 vs. 31.20 +/- 0.85 mmHg, P < 0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient. CONCLUSIONS: PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.

Aged↗
PubMed2001

Peripheral vascular and nerve function associated with lower limb amputation in people with and without diabetes.

Multiple factors, including peripheral vascular disease and neuropathy, contribute to the development and perpetuation of complications of the lower extremities in diabetes. The main aim of the present study was to assess the peripheral vascular and nerve status of diabetic and non-diabetic subjects that had undergone lower limb amputation. Various non-invasive tests of peripheral vascular and nerve function were carried out on subjects who had undergone unilateral lower limb amputation and were now attending a Rehabilitation Centre. The control group (n=23), the diabetic amputee group (n=64) and the non-diabetic amputee group (n=32) were age-matched. Only the diabetic amputee group had evidence of medial arterial calcification. Transcutaneous oxygen levels were significantly lower in the diabetic amputee group (median 43 mmHg; interquartile range 33-49 mmHg) than in the control (59; 56-74 mmHg) and non-diabetic amputee (57; 43-65 mmHg) groups (control compared with diabetic amputee group, P<0.001; diabetic amputee compared with non-diabetic amputee group, P<0.01). The same trend was found for carbon dioxide levels in the skin [mmHg: diabetic amputees, 25 (21-37); controls, 38 (32-42); non-diabetic amputee, 34 (31-39)] (control compared with diabetic amputee, P<0.01; diabetic amputee compared with non-diabetic amputee, P<0.05). Vibration and pressure perception measurements (which assess Abeta nerve fibre function) showed that both the diabetic amputee and non-diabetic amputee subjects had significantly greater impairment than the controls. However, measures of Aalpha and C nerve fibre function were abnormal only in the diabetic amputee group. Thus the peripheral vascular and nerve functions of age-matched diabetic and non-diabetic subjects having undergone lower limb amputation show specific differences, with non-diabetic amputees exhibiting signs of neuropathy. This indicates that factors characteristic of diabetes (such as hyperglycaemia and non-enzymic glycation) are associated with calcification, lower oxygen and carbon dioxide levels in the skin, and abnormal Aalpha and C nerve fibre function.

Aged↗
PubMed2000

Estrogen affects cognition in women with psychosis.

Estrogen has been reported to affect aspects of cognition and psychopathology in women, both normal and with psychosis. This study aimed to replicate and extend this research by investigating the effect of estrogen on cognition over the menstrual cycle in a group of normal women and women with psychosis. The sample consisted of 31 premenstrual normal control subjects, and 29 women with psychosis. Subjects were tested twice, 2 weeks apart on a number of cognitive tests. There was no difference in Positive and Negative Symptom Scale scores between the follicular and luteal phases of the menstrual cycle. Both groups of women performed better on the Revised Mental Rotation Test and Trails A during the follicular phase when estrogen levels were low. Contrary to expectation, during the luteal phase, when estrogen was high, the control subjects showed no significant improvement in performance on verbal articulatory-motor tasks, and the women with psychosis performed significantly worse on the Purdue Pegboard. The unexpected adverse effect of high levels of estrogen on motor performance in the psychotic women was hypothesized to be related to their disease process.

Adult↗
PubMed2000

Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses.

Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. To date, compliancy has most commonly been assessed with the Drug Attitude Inventory (DAI) developed by Hogan et al. (Hogan, T.P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol. Med. 13, 177-183). The present study identified several deficiencies in the DAI. Using the partial credit version of the Item Response Theory measurement model, the DAI was refined with the aim of greater validity and clinical utility. The new inventory was administered to 66 patients, the majority of whom were diagnosed with schizophrenia. When available, lithium levels and carer ratings of compliance were also recorded and used to verify compliancy. The new inventory appears to be a valid and reliable measure of compliancy for psychoactive medications.

Adult↗