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Biomedical subjects

M A Jacobs

Publications and source records attributed to M A Jacobs.

At least 19 recordsLinked to original sources
PubMed1997

Counterregulatory hormone responses and symptoms during hypoglycaemia induced by porcine, human regular insulin, and Lys(B28), Pro(B29) human insulin analogue (insulin Lispro) in healthy male volunteers.

Lys(B28)Pro(B29) human insulin analogue (Lispro) is a newly developed monomeric insulin analogue with a rapid onset and short duration of action. The aim of the study was to compare the thresholds for the counterregulatory responses during a stepwise euglycaemic/hypoglycaemic clamp for insulin lispro (LP), human (H), and porcine (P) insulin in a randomized order in 12 healthy male volunteers (age 22.4 +/- 1.7 years, BMI 21.9 +/- 1.7 kg m-2). A euglycaemic period of 2 h was followed by three hypoglycaemic levels of 60 min each; from 150-210 min at 3.5 mmol l-1, 240-300 min at 3.0 mmol l-1 and 330-390 min at 2.5 mmol l-1. Plasma insulin levels during the 50 mU kg-1 h-1 infusions and blood glucose levels were not significantly different. The glucose requirements (mean +/- SD) during the last part of the euglycaemic period (90-120 min) tended to be higher during LP compared to those during H and P; 2239 +/- 702 and 1929 +/- 769, 1957 +/- 725 mg kg-1, P = 0.067, respectively. The thresholds (blood glucose level at which a sustained elevation of the counterregulatory hormones as compared to the mean at normoglycaemia level 4.0 mmol l-1, occurs) for the various hormones were very similar during LP, H, and P insulin infusions and occurred at 253.8 +/- 56.7, 256.3 +/- 55.3 and 257.5 +/- 70.0 min for adrenaline; 241.4 +/- 80.3, 260.5 +/- 82.5 and 225.0 +/- 75.9 min for noradrenaline; 307.5 +/- 65.5, 304.1 +/- 74.1 and 322.5 +/- 40.4 min for cortisol; 263.8 +/- 50.3, 255.0 +/- 63.6 and 249.6 +/- 50.9 min for growth hormone; 236.3 +/- 78.2, 200.0 +/- 73.1 and 226.3 +/- 65.5 for pancreatic polypeptide. The autonomic and neuroglycopenic symptoms were elicited at 240 and 300 min, respectively. In conclusion, our data indicate a tendency to a higher biological activity of approximately 10% for Lispro insulin. During a stepwise euglycaemic/hypoglycaemic clamp, the counterregulatory hormone responses to insulin lispro, human insulin, and porcine insulin were similar.

Adult↗
PubMed1997

Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human insulin analog in IDDM patients. A comparison with human regular insulin during a three-meal test period.

OBJECTIVE: The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/- SD]). RESEARCH DESIGN AND METHODS: After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day. RESULTS: During the treatment periods, glycemic control was stable during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48, NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels. CONCLUSIONS: Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h.

3-Hydroxybutyric Acid↗
PubMed1997

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) pathophysiology and anesthetic considerations.

HELLP syndrome in the parturient (hemolysis, elevated liver enzymes, and low platelet count) is associated with poor maternal and fetal outcomes. Maternal mortality has been estimated to be as high as 24%. Patients with HELLP syndrome are also at greater risk of pulmonary edema, adult respiratory distress syndrome, abruptio placentae, disseminated intravascular coagulation, ruptured liver hematomas, and acute renal failure. Perinatal mortality is equally high, ranging from 79 to 367 per 1,000 live births, and neonatal complications correlate with the severity of maternal disease. Many clinicians view HELLP syndrome as an entity of preeclampsia, and because of varied symptomatology, the initial diagnosis may be obscured. Prodromal signs include: (1) weakness and fatigue, (2) nausea and vomiting, (3) right upper quadrant and/or epigastric pain, (4) headache, (5) changes in vision, (6) increased tendency to bleed from minor trauma, (7) jaundice, (8) diarrhea, and (9) shoulder or neck pain. Before delivery, aggressive obstetric management is directed toward stabilization of the affected organ systems, if possible, and timely interruption of the pregnancy in the early phase of the accelerated disease progression. Definitive therapy is delivery. Parturients with HELLP syndrome are often critically ill; their infants are frequently premature and their conditions are compromised. Management criteria should include a multidisciplinary approach in a tertiary care center. Obstetric anesthesia personnel should perform a thorough preanesthetic evaluation and be familiar with the pathophysiologic changes of this syndrome. Determining the anesthetic of choice depends on the patient's condition, fetal well-being, and the urgency of the situation. In the presence of severe coagulopathy, regional anesthesia is contraindicated.

Adult↗
PubMed1996

Biosynthesis of prothrombin: intracellular localization of the vitamin K-dependent carboxylase and the sites of gamma-carboxylation.

Prothrombin is a vitamin K-dependent blood coagulation protein that undergoes posttranslational gamma-carboxylation and propeptide cleavage during biosynthesis. The propeptide contains the gamma-carboxylation recognition site that directs gamma-carboxylation. To identify the intracellular sites of carboxylation and propeptide cleavage, we monitored the synthesis of prothrombin in Chinese hamster ovary cells stably transfected with the prothrombin cDNA by immunofluorescent staining. The vitamin K-dependent carboxylase was located in the endoplasmic reticulum and Golgi complex. Antibodies specific to prothrombin processing intermediates were used for immunocytolocalization. Anti-des-gamma-carboxyprothrombin antibodies stained only the endoplasmic reticulum whereas antiproprothrombin antibodies (specific for the propeptide) and antiprothrombin:Mg(II) antibodies (which bind the carboxylated forms of proprothrombin and prothrombin) stained both the endoplasmic reticulum and the Golgi complex. Antiprothrombin:Ca(II)-specific antibodies (which bind only to the carboxylated form of prothrombin lacking the propeptide) stained only the Golgi complex and secretory vesicles, and colocalized with antimannosidase II and anti-p200 in the juxtanuclear Golgi complex. These results indicate that uncarboxylated proprothrombin undergoes complete gamma-carboxylation in the endoplasmic reticulum and that gamma-carboxylation precedes propeptide cleavage during prothrombin biosynthesis.

Acylation↗
PubMed1996

Moving pictures and pulsed-field gel electrophoresis show only linear mitochondrial DNA molecules from yeasts with linear-mapping and circular-mapping mitochondrial genomes.

The mobility of mitochondrial DNA (mtDNA) in pulsed-field gel electrophoresis (PFGE) and its appearance in moving pictures from fluorescence microscopy were used to investigate the mitochondrial genome structure for five Pichia and Williopsis strains of yeast. An apocytochrome b-gene hybridization probe identified only linear mtDNA molecules for each strain when total cellular DNA was fractionated by PFGE. Most of the mass of DNA isolated from mitochondria for one linear-mapping and one circular-mapping mitochondrial genome was found in linear molecules much larger than the genome size of 50 kb; some molecules were as long as 1500 kb, but only a trace amount of apparently circular mtDNA was found for the strain with the circular-mapping genome. Probes for both the apocytochrome-b and mitochondrial small rRNA subunit genes hybridized strongly to mtDNA of approximately 50-100 kb, but weakly to the larger DNA from mitochondria of these two strains. For the four linear-mapping strains, PFGE revealed two or three distinct bands of linear mtDNA, larger than the genome size, within a smear of approximately 50-100 kb, but a smear without bands was found for the circular-mapping strain.

Chromosome Mapping↗
PubMed1995

The treatment of osteoarthritis of the knee with pulsed electrical stimulation.

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.

Adult↗
PubMed1994

Determinants of insulin sensitivity and consequences for lipoproteins and blood pressure in subjects with non-insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the possible determinants of insulin sensitivity and the relationships of these determinants and insulin sensitivity to lipoprotein levels and blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women, 20 men) treated either with diet alone or in combination with sulfonylureas. Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M value) with the hyperinsulinemic euglycemic clamp technique. In a multiple regression model, only percent body fat, waist to hip ratio (WHR), and resting energy expenditure (REE) emerged as significant independent determinants of the M value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c (HbA1c) level, thyroid function, fitness level, smoking status, alcohol consumption, and dietary habits did not contribute significantly. The M value was independently and negatively associated with the concentrations of triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively associated with high-density lipoprotein (HDL) cholesterol subfractions and apolipoprotein A1. In our predominantly normotensive subjects, we found no association between the M value and blood pressure. Moreover, fasting insulin contributed directly, ie, independent of the M value, to the variation of TG, but not to the other lipoproteins and not to blood pressure. The results suggest that in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and REE, (2) the insulin level determines the TG level directly, whereas the lipoproteins are influenced indirectly as a reflection of the degree of insulin resistance, and (3) insulin sensitivity is not related to blood pressure in a normotensive population.

Aged↗
PubMed1994

Influences on weight loss in type 2 diabetic patients: little long-term benefit from group behaviour therapy and exercise training.

The aim of our study was to assess the long-term (24 months) efficacy of a comprehensive weight reduction programme as compared to that of a conventional programme. The Comprehensive Programme comprised, besides the Conventional Programme (diet counselling), behavioural modification and exercise training. The 2-year follow-up period was completed by 53 patients (19M/34F; 88.3%). The differences (95% confidence intervals; CI) between the change in body weight of patients in the Comprehensive Programme compared to the Conventional Programme after 6 and 24 months of treatment were -2.2 (-4.0, -0.3) kg, p = 0.03 and -1.3 (-3.3, 0.7) kg, p = 0.21, respectively. In comparison to the Conventional Programme, the Comprehensive Programme resulted in a greater decrease (95% CI) of HbA1c after 6 months: -0.8 (-1.2, -0.2)%, p = 0.01, but not after 2 years: -0.4 (-1.0, 0.1)%, p = 0.12. The effects on blood pressure and serum lipids of the Comprehensive Programme and the Conventional Programme were comparable. Changes in body weight at 6 months correlated well with changes in HbA1c, fasting plasma insulin, and blood pressure, whereas at 24 months no such correlation was found with HbA1c. Pretreatment variates that were associated with the greatest 2-year weight loss were a high HbA1c value, a low energy per cent carbohydrate intake and a low percentage of obese subjects within the family. In conclusion, the long-term outcome of the Comprehensive Programme was not different from that of the Conventional Programme. The achieved body weight reduction was associated with a sustained fall in blood pressure, but with only a transient beneficial effect on the glycaemic control in the Type 2 diabetic patient.

Adult↗
PubMed1993

Total hip replacement without cement for non-inflammatory osteoarthrosis in patients who are less than forty-five years old.

Forty-two patients (forty-four hips) who, at an age of less than forty-five years, had a total hip replacement without cement for the treatment of non-inflammatory osteoarthrosis, were followed for three to seven years (average, four and one-half years). At the latest follow-up evaluation, thirty-seven hips (84 per cent) had an excellent Harris rating; three (7 per cent), good; one (2 per cent), fair; and three (7 per cent), poor. The mean Harris hip score was 92 points, compared with 43 points before the operation. Two hips (5 per cent) had a revision due to complications. In another hip, there was a progressive radiolucent line around the femoral component, increased shedding of beads, and a low score for fixation and stability, according to the criteria of Engh et al. We concluded that total hip arthroplasty without cement, at least for the time-period studied, has a high rate of success for the management of patients less than forty-five years old who have non-inflammatory osteoarthrosis of the hip.

Adult↗
PubMed1993

The pharmacodynamics and activity of intranasally administered insulin in healthy male volunteers.

The objective of the study was to assess the bioavailability and absorption dynamics of intranasal insulin (with di-decanoyl-alpha-phosphatidylcholine, DDPC, as absorption enhancer) in two potencies (U200 and U500). Toward this aim, the euglycemic clamp technique combined with somatostatin (100 micrograms/h) was used. Insulin was administered to 12 healthy males: 5 IU intravenously (20-min infusion); 10 IU subcutaneously; 50 IU (U200) and 50 IU, 100 IU, and 150 IU (U500) intranasally. Peak insulin levels (mean +/- SD) were reached at 17.9 +/- 2.6, 77.9 +/- 38.3, 23.3 +/- 5.4, 25.4 +/- 8.4, 26.2 +/- 8.3, and 27.5 +/- 5.8 min, respectively. For the 50 IU dose, peak glucose requirements during the clamp and time to peak were not significantly different for U200 and U500: 548.8 +/- 279.5 vs. 452.4 +/- 232.9 mg/min and 41.3 +/- 16.2 vs. 51.5 +/- 29.9 min, respectively. Compared with intravenous insulin, the bioavailability calculated from the total area under the insulin curve was 13.2% (95% confidence interval 7.9, 21.9) and 8.8% (95% confidence interval 5.6, 13.8), and compared with subcutaneous insulin, the bioavailability was 14.8% (95% confidence interval 8.7, 25.2) and 9.9% (95% confidence interval 6.4, 15.4) for the U200 and U500 preparations, respectively. An apparent nonlinear dose-dependent relation was found for the U500 potency. The within-subject variability of the areas under the curves of plasma insulin after the administration of 100 IU was 43.6% (range 20.7-85.7). In conclusion, this nasal insulin preparation has promising absorption and action profiles in both potencies, which makes it suitable for further exploration of clinical applications.

Administration, Intranasal↗
PubMed1992

Quantitative effects of cerebral infarction on spatial learning in rats.

Outcome following stroke is difficult to measure because the behavioral response to infarction is variable. We hypothesized that cognitive function, such as spatial learning, may be a reproducible and sensitive outcome variable. We developed an animal model of multifocal cerebral ischemia in order to study the effects of infarction on learning. To cause ischemia, several hundred microspheres were injected into the internal carotid arteries of rats. After ischemia, behavior was measured using a global rating and a Morris water maze. Postmortem serial brain sections were stained and the size of the infarctions was measured. We found that intracerebral microspheres caused cortical infarction and an impairment of spatial learning. This impairment was not due to occlusion of the internal carotid artery and was not found in animals who received a sham injection of saline. The degree of learning impairment was not correlated with the volume density of the infarctions or with the volume density of the remaining cerebral hemisphere. The learning impairment clearly differentiated normal from lesioned animals, and the impairment was probably due to a delay in acquisition of spatial information rather than a defect in retention or retrieval. Measurement of learning deficit after cerebral ischemia is an efficient and sensitive method for evaluating new stroke treatments and possibly for exploring structure function relationships.

Animals↗
PubMed1989

Bladder leiomyoma.

We herein present a case of leiomyoma of the urinary bladder discovered during evaluation for stress urinary incontinence. The histologic findings of this benign tumor and its urologic implications are reviewed.

Adult↗
PubMed1989

Intertrochanteric osteotomy for avascular necrosis of the femoral head.

Of 24 intertrochanteric osteotomies for avascular necrosis of the femoral head, 22 were followed up for an average of 63 months. Sixteen of the 22 cases had good or excellent results, including 5 of the 6 cases with Stage II disease and 11 of the 16 with Stage III changes. Success seemed to be inversely related to the size of the lesion. There were six major orthopaedic complications, but despite these we feel that the operation has a definite role in the treatment of the young active patient.

Adult↗
PubMed1989

Core decompression of the distal femur for avascular necrosis of the knee.

From 1974 to 1981, we performed 28 core decompressions of the distal femur for pathologically confirmed avascular necrosis. At a mean follow-up of 54 months (range 20 to 140 months) and using the Ficat stages, all seven cases in stage I and stage II had good results. Of 21 cases in stage III, 11 cases had good results, four had poor results, and six needed total knee replacement. There were no significant orthopaedic complications. The procedure is worthwhile and will be more accurate with new methods of imaging.

Adult↗
PubMed1989

Osteotomy of the tibial tubercle during total knee replacement. A report of twenty-six cases.

The cases of twenty-four patients who had twenty-six osteotomies of the tibial tubercle in conjunction with total knee replacement were analyzed with regard to complications and technical considerations. The patients were followed for a minimum of two years (average, three years and six months). Major complications related to the surgical technique occurred in 23 per cent of the knees and complications not related to the technique, in an additional 8 per cent. Rheumatoid arthritis and a history of at least one previous operation about the knee were predisposing factors for these complications.

Adult↗
PubMed1989

Revision of septic total knee arthroplasty.

Nine patients with septic total knee arthroplasties (TKA) were treated between 1980 and 1984; six were gram-positive infections and three were gram-negative. Initial treatment included the maintenance of all solidly fixed components. Patients with loose components were treated with removal of all prosthetic material and subsequent reimplantation after a six-week course of antibiotics. At follow-up examination six of nine patients had satisfactory results. One patient maintained his original femoral and tibial components and one patient required a knee fusion to treat his recurrent gram-negative infection. Overall, complications were associated with chronic infection, gram-negative infection, and abnormalities of the extensor mechanism.

Arthritis, Infectious↗
PubMed1988

Revision total knee arthroplasty for aseptic failure.

Twenty-four patients with 28 failed total knee arthroplasties replaced with porous-coated anatomic (PCA) primary or revision components were studied over a two- to four-year period. Overall, there were 68% good and excellent results and three failures. When evaluated according to mode of failure, 83% of the patients who had a definable mechanical problem achieved good or excellent results. Patients who had revision operations for incapacitating pain or in whom no clearly definable problem could be ascertained before operation were not significantly improved. Complications that led to poor results were deep sepsis, wound necrosis, and extensor mechanism abnormalities.

Aged↗