Country profile. South Africa.
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Biomedical subjects
Publications and source records attributed to M Jacobs.
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BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.
Human chorionic gonadotropin (hCG) free beta-subunit levels were determined in 709 control and 13 Down syndrome urine samples from the second trimester of pregnancy. Results were normalized to urine creatinine concentration and converted to multiples of the unaffected pregnancy medium (MOM). The concentration of free beta-subunit in Down syndrome cases was 3.9 MOM. Seven of 13 Down syndrome pregnancies (54 per cent) had free beta-subunit levels at or above the 95th centile of unaffected pregnancies. Urine free beta-subunit may potentially be useful as a screening test for Down syndrome.
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BACKGROUND: Expanding upon our experience with laparoscopic surgery for colonic benign and malignant processes and for bowel obstruction, we have reviewed our experience with minimal access laparoscopic surgery for complicated diverticular disease. We propose an approach of surgical care incorporating diagnostic laparoscopy in those not responding to medical therapy alone. METHODS: Our study includes data from two different surgical teams working in separate hospital-and-patient environments. Our theory that laparoscopy could be widely applicable to this complex disease process is borne out by experience in both locations. One hundred forty-eight patients were managed by laparoscopic or laparoscopically assisted methods with 18 patients requiring drainage only without resection. RESULTS: Our management of 148 of 164 patients (90%) by laparoscopic approach was successful, with a very acceptable morbidity of 5% in the elective cases and decreased ileus (20% of open vs 7% laparoscopic) in acute complicated cases. Elective resections required hospitalization of 4-5 days, demonstrating the benefits of incorporating laparoscopy in the care of these cases, particularly when compared to standard open procedures requiring 8 days' hospitalization. CONCLUSIONS: We believe complications of diverticular disease including abscess, perforation, fistula, and bleeding can potentially be managed in this way by minimal access procedures, decreasing postoperative wound problems, decreasing length of hospitalization and overall morbidity, and improving patient care.
We have developed a multiparameter magnetic resonance imaging (MRI) cluster analysis model of acute ischemic stroke using T2 relaxation times and the diffusion coefficient of water (ADCw). To test the ability of this model to predict cerebral infarction, male Wistar rats (n = 7) were subjected to 2 h of transient middle cerebral artery (MCA) occlusion, and diffusion and T2 weighted MRI were performed on these rats before, during and up to 7 days after MCA occlusion. MRI tissue signatures, specified by values of ADCw and T2 were assigned to tissue histopathology. Significant correlations were obtained between MRI signatures at different time points and histopathologic measurements of lesion area obtained at 1 week. In addition, we compared the temporal evolution of MRI tissue signatures to a separate population of animals at which histological data were obtained at select times of reperfusion. A significant shift (p < or = 0.05) within signatures reflecting tissue histopathology was demonstrated as the ischemic lesion evolved over time. Our data suggest, that the MRI signatures are associated with the degree of ischemic cell damage. Thus, the tissue signature model may provide a noninvasive means to monitor the evolution of ischemic cell damage and to predict final outcome of ischemic cell damage.
OBJECTIVES: Our objectives were twofold: (1) to determine cardiac and respiratory dependency of systemic venous pathway flow of patients having the Fontan operation with a total cavopulmonary connection and (2) to describe the velocity profile. Systemic venous pathway flow is hypothesized to be mostly respiratory dependent, to be laminar, and to have a smooth velocity profile. METHODS: Twenty-two patients having the Fontan operation (aged 8.6 +/- 4.7 years) underwent magnetic resonance blood tagging (bolus tagging). Systemic venous pathway spin-echo images parallel to the blood flow were used as a localizer. A saturation pulse labeled the blood, and a cine image was acquired at the inferior and superior venae cavae and midportion of the baffle in the systemic venous pathway, triggered to the electrocardiogram and gated to both end-expiration and end-inspiration. Repetition time was 50 msec. RESULTS: Flow in the systemic venous pathway was laminar throughout its course and was found to be phasic to both cardiac and respiratory cycles. Approximately 70% of flow was cardiac dependent, and the rest was respiratory. Highest flow occurred near end-systole and early diastole and in inspiration. Lowest flow occurred in diastasis. Velocity was highest and flow least "pluglike" in the mid-baffle area during cardiac or respiratory imaging (45 +/- 17 and 32 +/- 11 cm/sec, respectively). CONCLUSION: A substantial amount of pulmonary blood flow in patients who have undergone a total cavopulmonary connection type of Fontan operation has a cardiac component. Furthermore, we confirm that this flow is laminar but nonuniform across the systemic venous pathway. Highest flows occurred near end-systole and early diastole, as well as in inspiration, and the lowest flow occurred in diastasis. This information may help in designing the systemic venous pathway and optimizing medical management.
OBJECTIVES: The objectives of this study were to define physiologic effects on and a clinical correlate to coronary blood flow during volume unloading surgery in patients with aortic atresia. METHODS: Twenty-two patients with aortic atresia (group I, 13 patients with stage I reconstruction undergoing hemi-Fontan operation; group II, 9 patients with hemi-Fontan undergoing Fontan operation) underwent perioperative transesophageal echocardiography. Doppler spectral patterns, peak velocity, velocity time integral, and blood flow in the native ascending aorta were measured. Preoperative hemodynamics and postoperative clinical data were analyzed. Significance was defined as p < 0.05. RESULTS: Higher values of coronary blood flow (982.9 +/- 321.7 vs 548.6 +/- 333.8 ml/min per square meter), velocity time integral (20.7 +/- 5.6 vs 12.6 +/- 4.0 cm), and peak velocity (96.1 +/- 21.4 vs 51.0 +/- 18.2 cm/sec) were found before operation in group I than after operation and in group II at both times. Flow changed from predominately systolic in preoperative group I to both systolic and diastolic after operation and in group II. Before operation in groups I and II, a number of hemodynamic parameters such as superior vena cava oxygen saturation correlated with coronary blood flow dynamics. After operation in group II, urine output (r = 0.86) and central venous pressure (r = -0.85) correlated with coronary blood flow dynamics. CONCLUSION: Coronary blood flow parameters were higher in group I as a result of the increased energy needs required to pump to two circulations. No changes were found in group II. A number of coronary blood flow parameters correlated with preoperative hemodynamics and postoperative clinical data. These parameters appear to be useful in assessing the performance status of the myocardium after the Fontan operation, consistent with the notion that myocardial perfusion relates directly to ventricular function.
A cDNA clone encoding a monofunctional aspartate kinase (AK, ATP:L-aspartate 4-phosphotransferase, EC 2.7. 2.4) has been isolated from an Arabidopsis thaliana cell suspension cDNA library using a homologous PCR fragment as hybridizing probe. Amplification of the PCR fragment was done using a degenerate primer designed from a conserved region between bacterial monofunctional AK sequences and a primer identical to a region of the A. thaliana bifunctional aspartate kinase-homoserine dehydrogenase (AK-HSDH). By comparing the deduced amino acid sequence of the fragment with the bacterial and yeast corresponding gene products, the highest identity score was found with the Escherichia coli AKIII enzyme that is feedback-inhibited by lysine (encoded by lysC). The absence of HSDH-encoding sequence at the COOH end of the peptide further implies that this new cDNA is a plant lysC homologue. The presence of two homologous genes in A. thaliana is supported by PCR product sequences, Southern blot analysis and by the independent cloning of the corresponding second cDNA (see Tang et al., Plant Molecular Biology 34, pp. 287-294 [this issue]). This work is the first report of cloning a plant putative lysine-sensitive monofunctional AK cDNA. The presence of at least two genes is discussed in relation to possible different physiological roles of their respective product.
Mutagenesis and subsequent selection of Arabidopsis thaliana plantlets on a growth inhibitory concentration of lysine has led to the isolation of lysine-resistant mutants. The ability to grown on 2 mM lysine has been used to isolate mutants that may contain an aspartate kinase with altered regulatory-feedback properties. One of these mutants (RL 4) was characterized by a relative enhancement of soluble lysine. The recessive monogenic nuclear transmission of the resistance trait was established. It was associated with an aspartate kinase less sensitive to feedback inhibition by threonine. Two mutants (RLT 40 and RL 4) in Arabidopsis, characterized by an altered regulation of aspartate kinase, were crossed to assess the effects of the simultaneous presence of these different aspartate kinase forms. A double mutant (RLT40 x RL4) was isolated and characterized by two feedback-desensitized isozymes of aspartate kinase to, respectively, lysine and threonine but no threonine and/or lysine overproduction was observed. Genetical analysis of this unique double aspartate kinase mutant indicated that both mutations were located on chromosome 2, but their loci (ak1 and ak2) were found to be unlinked.
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In 1994 ten NIH institutes sponsored an interagency workshop focusing on biobehavioral pain research. The workshop had three major goals: (1) to review the current status of biobehavioral pain research (2) to identify critical research needs, and (3) to enhance interdisciplinary and interagency cooperation in pain research. The purpose of this article is to summarize the presentations at this meeting and to highlight some of the key research recommendations. Research topics addressed include (a) understanding critical interfaces between biology and behavior; (b) pain, suffering, and emotion; (c) pain and behavior; (d) behavior-related interventions; (e) commonalities and differences in pain expression, experience, and treatment; and (f) pain in special populations. The article concludes with a summary of NIH pain research activities that have taken place since the workshop.
PURPOSE: We set out to assess the development of pursuit eye movements in normal infants in an objective, longitudinal fashion. We asked whether smooth pursuit (SP) was present under 2 months of age and how the saccade ratio changed with increasing infant age. METHODS: Smooth pursuit was recorded longitudinally from 25 infants aged 1-7 months, using DC electro-oculography, in a clinically practical manner. Four uninstructed adults acted as controls. RESULTS: Smooth pursuit was present under 2 months of age. The gain of SP increased with increasing infant age. However, it had still not reached adult levels by 6 months of age. Latency decreased with increasing infant age. Monocular SP asymmetry was present in the younger infants. CONCLUSIONS: Smooth pursuit is present under 2 months of age, but at 6 months SP has still not reached adult levels. The traditional model of SP development is questionable.
BACKGROUND: There is an inverse relationship between the soluble interleukin-2 receptor (sIL-2R) and serum albumin, cholesterol, transferrin, prealbumin, and hemoglobin. Inasmuch as low serum albumin and cholesterol have been associated with excess mortality, we hypothesized that elevated sIL-2R would predict mortality in older adults. OBJECTIVE: To determine if elevated sIL-2R predicts mortality in patients on a geriatric rehabilitation unit. DESIGN: Prospective cohort. SETTING: University-affiliated VA medical center. PARTICIPANTS: Seventy-two male patients aged greater than 60 years admitted to a geriatric rehabilitation unit. Patients with severe hepatic or renal disease were excluded. MEASUREMENTS: We measured serum albumin, prealbumin, cholesterol, transferrin, hemoglobin, body mass index (BMI), C-reactive protein (CRP), and sIL-2R upon admission. Subjects were followed for 1 year. RESULTS: Low serum albumin, prealbumin, and hemoglobin and high sIL-2R and CRP predicted 1-year mortality on univariate analysis. When these predictors were included as covariates in a Cox regression model, only sIL-2R was a significant independent predictor of mortality (P = .043). Multiple linear regression with the above covariates revealed that only sIL-2R predicted time to death at (P = .003). CONCLUSIONS: High sIL-2R and CRP and low albumin, prealbumin, and hemoglobin predicted mortality using univariate analysis on a rehabilitation unit. However, with multivariate analysis, sIL-2R was the sole predictor of mortality.
Low density lipoprotein (LDL) plays an important role in atherogenesis. Focal accumulation within the arterial intima of excess amounts of cholesterol-rich LDL leads to the migration and recruitment of monocytes, which then differentiate into macrophages after taking up large amounts of oxidatively modified LDL via their scavenger receptors and become lipid-laden 'foam cells' within the subendothelial space. It is generally accepted that oxidized LDL and hyperlipidaemia impair endothelial-dependent vascular relaxation, yet the existing literature on the effects of oxidatively modified LDL on endothelium-derived nitric oxide (NO) and prostacyclin (PGI2) release is inconclusive, since oxidized LDL has been reported to enhance or reduce NO and PGI2 production. Our studies using cultured human endothelial and smooth muscle cells have established that basal rates of L-arginine (NO precursor) transport, NO and PGI2 production and soluble guanylyl cyclase activity are unaffected by pretreatment (for 1 or 24 h) with native LDL, or with mildly or highly oxidized LDL. In contrast, highly oxidized LDL inhibited histamine-stimulated release of NO and PGI2 from human endothelial cells and induced an adaptive increase in the level of intracellular glutathione in human smooth muscle cells, a response which was prevented by the chain-breaking antioxidant alpha-tocopherol. Although initial rates of L-arginine transport and basal NO and PGI2 release from human endothelium are unaffected by oxidized LDL, agonist-stimulated release of these vasodilators is markedly attenuated. Elucidation of the mechanisms regulating these responses and their sensitivity to dietary antioxidants could lead to alternative strategies for reducing atherogenesis.
Combined chemoradiotherapy is superior to radiotherapy alone for stage III and IV squamous cell carcinoma of the head and neck, and concurrent use of both offers the advantage of synergistic interactions. Our prior trial demonstrated the ease and convenience of administering carboplatin during radiotherapy. Since paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has activity in squamous cell carcinoma of the head and neck and can act synergistically with both radiotherapy and platinum drugs, we initially added paclitaxel at 45 mg/m2/wk to carboplatin given at 100 mg/m2 during radiotherapy given at conventional fractions. The initial dose of paclitaxel was subsequently reduced to 40 mg/m2/wk. Thirteen of 18 patients entered so far have sufficient follow-up data; 12 are assessable for toxicity and 11 are assessable for response. One died early of progressive disease, two achieved a complete response, six achieved a partial response, and two had stable disease. Toxicities have so far been manageable for the 76 weekly doses administered. Chemotherapy dose reduction was needed in 10 patients. For the planned 100 doses of chemotherapy, 53 (53%) were administered as planned, 23 (23%) were reduced, and 24 (24%) were withheld due to neutropenia or mucositis. There were no toxic deaths, and no patient stopped therapy for toxicity. Paclitaxel/carboplatin can be administered during radiotherapy for squamous cell carcinoma of the head and neck with acceptable toxicities, and further accrual is needed to evaluate the effect of this combination.
This study examined the impact of exposure to fashion magazines on women's body image satisfaction. Participants were 39 undergraduate women, randomly assigned to two experimental conditions: half viewed fashion magazines prior to completing a body image satisfaction survey, and the remaining half, news magazines. Mean height and weight did not differ for the two groups. As hypothesized, women who viewed fashion magazines preferred to weigh less, were less satisfied with their bodies, were more frustrated about their weight, were more preoccupied with the desire to be thin, and were more afraid of getting fat than were their peers who viewed news magazines.