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Biomedical subjects

K Khan

Publications and source records attributed to K Khan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease.

BACKGROUND: The relationship between neuropathological lesions and mild, "preclinical," cognitive impairments of Alzheimer disease is poorly understood. Identification of the lesions that are most closely associated with the earliest symptoms of Alzheimer disease is crucial to the understanding of the disease process and the development of treatment strategies to affect its progression. DESIGN AND MAIN OUTCOME MEASURES: We examined the extent of neurofibrillary tangles (NFTs) in 4 neocortical regions, the hippocampus, the entorhinal cortex, and the amygdala in 65 elderly subjects with no dementia, questionable dementia, mild dementia, or moderate dementia as assessed using the Clinical Dementia Rating Scale (CDR). SETTING AND PATIENTS: Postmortem study of nursing home residents. RESULTS: Neurofibrillary tangles were present in the entorhinal cortex and the hippocampus of all subjects, including those without cognitive deficits. Neocortical NFTs were mostly absent in the nondemented (CDR score, 0.0) subjects. The density of NFTs in the questionably demented (CDR score, 0.5) subjects was not significantly increased (P>.20) relative to the nondemented group in any of the brain regions studied. Significant increases (P<.04) in NFT density become apparent first in the amygdala and the temporal cortex in subjects rated to be mildly impaired (CDR score, 1.0). By the time that cognitive impairments were judged to be moderately severe (CDR score, 2.0), all regions of the brain examined, except for the occipital cortex, were significantly (P<.05) involved. CONCLUSIONS: Some NFTs are present in the entorhinal cortex and hippocampus of most elderly individuals irrespective of their cognitive status, but the density of NFTs increases as a function of dementia severity.

Aged↗
PubMed1999

Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in the cortex during aging.

We previously noted that some aged human cortical specimens containing very low or negligible levels of amyloid beta-protein (As) by enzyme immunoassay (EIA) provided prominent signals at 6 approximately 8 kd on the Western blot, probably representing sodium dodecyl sulfate (SDS)-stable Abeta dimer. Re-examination of the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most commonly used for the quantitation of Abeta, capture SDS-dissociable Abeta but not SDS-stable Abeta dimer. Thus, all cortical specimens in which the levels of Abeta were below the detection limits of EIA were subjected to Western blot analysis. A fraction of such specimens contained SDS-stable dimer at 6 approximately 8 kd, but not SDS-dissociable A(beta) monomer at approximately 4 kd, as judged from the blot. This A(beta) dimer is unlikely to be generated after death, because (i) specimens with very short postmortem delay contained the A(beta) dimer, and (ii) until 12 hours postmortem, such SDS-stable A(beta) dimer is detected only faintly in PDAPP transgenic mice. The presence of A(beta) dimer in the cortex may characterize the accumulation of A(beta) in the human brain, which takes much longer than that in PDAPP transgenic mice.

Adult↗
PubMed1999

Role of gender in the toxicity of norcocaine.

Gender differences may significantly influence the toxicity of cocaine in mammals. In this study, the influence of gender on the toxicity of norcocaine, a pharmacologically active metabolite of cocaine, was compared with its parent compound in adult male and female rats. In addition, the plasma and tissue norcocaine concentrations were evaluated after the administration of norcocaine and cocaine. Norcocaine or cocaine was administered intravenously at a rate of 2 mg/kg/min until circulatory collapse. Arterial blood samples as well as heart, liver, and brain tissues were obtained at circulatory collapse for the measurement of concentrations of norcocaine as well as cocaine and its major metabolites. There were no gender-related differences in the doses of norcocaine required to produce circulatory collapse; however, there were significant gender-related differences in the norcocaine tissue-to-plasma concentration ratios (T:P ratios). After the administration of norcocaine, T:P ratios for heart, liver, and brain tissue were significantly greater in males. Furthermore, after cocaine administration, the hepatic norcocaine T:P ratio was approximately 3-fold greater in the male rats than in the female rats. In contrast, female rats had a greater percentage of norcocaine in the plasma at circulatory collapse after acute cocaine administration. Although no gender differences in the lethality of norcocaine were observed, it remains to be seen whether the gender differences in the distribution and uptake of norcocaine play a role in the hepatotoxicity of the drug, particularly after chronic exposure.

Animals↗
PubMed1999

Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma.

BACKGROUND/AIMS: Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours. METHODS: Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms. RESULTS: Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver. CONCLUSIONS: Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.

Bile Duct Neoplasms↗
PubMed1999

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia.

This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

Adolescent↗
PubMed1999

Laparoscopic management of ectopic pregnancy.

The incidence of ectopic pregnancy has been rising over the last 20 years. The cause is multifactorial. The technical advancement in the field of minimal access surgery has greatly enhanced the possibility of both diagnosing and treating the condition effectively. The management of ectopic pregnancy can be expectant and surgical; the latter can be by open or laparoscopic methods. Laparoscopic surgery is usually performed when the patient is haemodynamically stable, the hCG is <6000 IU/L, the history is suggestive of minimal pelvic adhesions and when the pregnancy is confined within the tube. This procedure is, however, vastly dependent on the experience and expertise of the surgeon and the equipment facilities available. There are various means of treating ectopic pregnancy by laparoscopy. This includes laparoscopic salpingectomy, salpingotomy, and direct injection of cytotoxic agents. This article will present an overview to ascertain the effectiveness of minimal access surgery in managing ectopic pregnancy. There seems little doubt that laparoscopic management should be the first line of treatment. The way to realize its full potential is by formulating clear guidelines regarding the indication and implementation of laparoscopic surgery and emphasising the role of a fully structured training program to achieve the goals.

Female↗
PubMed1999

Complications of long operations: a prospective study of morbidity associated with prolonged operative time (> 6 h).

Reconstructive surgical procedures often take a long time to perform and duration of surgery is frequently cited as a major risk factor for postoperative complications. Whether operative time is an independent risk factor is unknown, as patients undergoing long operations may have numerous other risk factors. From September 1996 to September 1997, we prospectively assessed those patients undergoing reconstructive surgery lasting 6 h or more. A total of 62 patients were studied and they were grouped into three categories: head and neck surgery (n = 23), breast reconstruction (n = 18) and upper and lower limb surgery (n = 21). Postoperative complications were recorded and the results of each group compared. Each of the three patient categories had a similar mean duration of surgery but there were large differences in postoperative morbidity between the three groups, e.g. within the head and neck group postoperative respiratory and wound complications occurred in 43% and 26% of patients, respectively. In the limb surgery group, however, only 5% of patients had respiratory complications and 5% had wound complications. Despite having similar duration of surgery the differences in postoperative complications between the three groups suggest that duration of surgery alone is not a major determinant of postoperative morbidity and that the type of surgery performed and the patient's general health are more important predictors of outcome.

Adult↗
PubMed1999

Long term outcome of early active mobilization following flexor tendon repair in zone 2.

We reviewed 34 patients with 65 zone 2 flexor tendon injuries in 39 digits whose outcome had been prospectively studied in an earlier investigation at a mean of 10.6 years after repair. Grip strength was assessed using a Jamar dynamometer. Outcome of grip strength in relation to normal data indicated an excellent or good outcome in 94% of patients, fair in 3% and poor in 3%. Using the grading system recommended by the American Society for Surgery of the Hand, the active range of motion was graded as excellent or good in 75% of digits, fair in 15% and poor in 10%. These results compare favourably with those of the original study with 5/39 of digits showing an improvement from good to excellent. Sixteen of the 34 of patients continued to suffer from cold sensitivity.

Adolescent↗
PubMed1999

Paediatric hand injuries caused by spiked railings.

We report five cases of hand injuries caused by spiked palisade railings. One patient sustained an open fracture of the distal phalanx with a disruption of the nail bed, and two patients had digital nerve injuries. Two patients presented with the railing still impaled in the fingers, one of whom had an ischaemic digit at presentation. All patients were male, between 9 and 12 years of age, and presented in the course of 1 month. Railings of this type would appear to be a significant cause of hand injuries, which may be prevented by legislation or a change in railing design.

Accidents↗
PubMed1999

Effect of mixed meal ingestion on fuel utilization in the whole body and in superficial and deep forearm tissues.

Six healthy lean male adults, given a mixed meal containing 3190 kJ (16% from protein, 44% from carbohydrate and 40% from fat) were studied for the next 370 min using arteriovenous cannulation techniques across superficial and deep forearm tissues. The meal produced no significant change in forearm blood flow or skin temperature. The major differences between superficial and deep forearm tissues were (a) creatinine release by deep tissues but not superficial tissues; (b) the release of non-esterified fatty acids (NEFA) by superficial tissues and uptake by deep tissues; and (c) the more prolonged large positive arteriovenous concentration difference for glucose across deep than superficial tissues. The similarities were (a) general pattern of individual amino acid exchanges and transient positive amino acid N balance after meal ingestion; (b) consistent uptake of glutamate and release of glutamine (the main carrier of N out of superficial and deep forearm tissues); (c) the magnitude of the arteriovenous concentration differences for glucose, NEFA and total amino acids were related to the changes in their circulating concentrations and to the oxidation of carbohydrate, fat, and protein in the whole body; and (d) increases in the arterio-deep venous and arterio-superficial venous differences for glucose did not result in increased release of lactate, alanine or pyruvate, implying no increase in the activity of glucose-lactate and glucose-alanine cycles between forearm tissues and the liver. This study suggests that in a number of ways superficial and deep tissues can be regarded, at least qualitatively, as behaving as a 'single metabolic unit'.

Adipose Tissue↗
PubMed1998

Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease.

BACKGROUND: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? DESIGN AND OUTCOME MEASURES: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). SETTING AND PATIENTS: Postmortem study of nursing home residents. RESULTS: Even questionable dementia (CDR, 0.5) was associated with a significant (P = .04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR = 2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P < .001), even when subjects with a CDR of 0 were excluded. CONCLUSIONS: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia.

Aged↗
PubMed1998

Analysis of antisense oligonucleotides by on-capillary isotachophoresis and capillary polymer sieving electrophoresis.

An attempt was made to evaluate the stability of an antisense oligonucleotide against nucleases present in HBL 100ras cells. To detect nanomolar concentrations of the oligonucleotide, a sensitive detection system was required. A combination of capillary electrophoresis/laser-induced fluorescence (CE-LIF) with fluorescence derivatization did not improve the sensitivity significantly and also resulted in loss of separation of the derivatized sample. On-column isotachophoresis for the preconcentration of oligonucleotide samples in DB-17 coated capillaries filled with hydroxyethyl cellulose solution could be an alternative. The isotachophoresis (ITP) step allows injection of up to 40% of the capillary volume without loss in peak resolution and peak efficiency. Using ITP-capillary polymer sieving electrophoresis (CPSE), the limit of quantitation at a signal-to-noise ratio of 10 was 73 ng/mL for a 12-mer oligonucleotide. Using these conditions, the gain in sensitivity was 125.

Breast↗