Biomedical subjects
Publications and source records attributed to J Martin.
In this issue, we look at the business side of health care from two different vantage points. First, how will health care fare in 1995 in the context of the overall economy? We've gathered a panel of economic experts to make predictions. Their conclusions? In general, providers won't benefit from a probable upturn in the broader economy.
A genomic clone containing hemoglobin genes was isolated from a species of the chironomid genus Kiefferulus. Eight genes, including an apparent pseudogene, were sequenced and the amino acid sequences of the putative proteins were determined. By comparison to the previously described hemoglobins in the sister-genus Chironomus, they were identified as members of the dimeric Hb VIIB group. The results indicate that the existence of clusters of hemoglobin genes may be a common feature in chironomids and not just confined to Chironomus. The Kiefferulus genes show greatest similarity of amino acid sequence to Hb VIIB-7 from the Chironomus cluster. The results suggest that the ancestral cluster contained at least two gene types, one of which gave rise to VIIB-7 and the Kiefferulus genes while the other gave rise to the other Chironomus VIIB genes. Both clusters appear to have increased in size by duplication or unequal crossing over since the separation of the genera. It also appears that an unrelated gene present in the Chironomus cluster, Hb-Y, arose from a completely independent origin with no apparent equivalent gene anywhere in the genome of Kiefferulus or some other Chironomus species.
How precisely does the CNS control the timing of finger muscle contractions in skilled movements? For overarm throwing, it has been calculated that a ball release window of less than 1 ms is needed for accuracy in long throws. The objective was to investigate the timing precision of ball release and finge opening for 100 overarm throws made using only the arm. Subjects sat with a fixed trunk and threw balls fast and accurately at a 6-cm-square target when it was 1.5, 3.0 and 4.5 m away. Three-dimensional angular positions in space of the clavicle, upper arm, forearm, hand and distal phalanx of the middle finger were simultaneously recorded at 1000 Hz using the magnetic-field search-coil technique. Ball release was determined by pressure-sensitive microswitches on the proximal and distal phalanges of the middle finger (proximal and distal triggers). Variability of ball release, defined in terms of the standard deviation (SD) of the means of release times, was different when synchronized to different hand kinematic parameters. It was highest to the start of movement (when the hand started rotating vertically forward and up around a space-fixed horizontal axis) and was lowest when synchronized to the moment near ball release when the hand was vertical. These values did not depend on target distance. When throws were synchronized to vertical hand position, and SDs were averaged across the 10 subjects, the average interval for 95% of the throws (4xSD) was 9.6 ms for ball release and 10.0 ms for onset of finger opening. Thus, two independent measures of timing precision gave similar results. It is concluded that for 100 fast and accurate throws made by male recreational ball players, timing of finger opening and ball release was controlled precisely but not to fractions of a millisecond.
Current global developments as regards demographic growth and resource utilization represent one issue most difficult to tackle, in terms of (general and health) policy as well as in human terms. In the 1960s-1970s, the debate was active and led, among other things, to an expansion of technical cooperation programs aiming at fertility reduction. The 1974 World Population Conference in Bucharest saw controversy about the respective importance of family planning services, on the one hand, and overall development on the other. The debate was then less visible but has recently been given new impetus, in particular at the September 1994 Cairo International Conference on Population and Development. We have a serious, and in some ways seemingly unmanageable problem, marked by the political difficulties and social constraints which are bound to result from effective actions leading to reduction of resource consumption, or to fertility decrease. Public health professionals may make a significant contribution in promoting better information and dialogue and the view that health has to be an ecosustainable state.
The particular situation of the Swiss canton of Vaud (population 550,000) provides favourable observational conditions to assess the efficacy of a methadone treatment scheme in reducing the risk of human immunodeficiency virus (HIV) infection among drug users. On the one hand, the canton has a long tradition of methadone treatment dispensed by medical practitioners. On the other hand, no legal access to clean injection equipment was provided up to 1989. For the 754 drug addicts having entered at least one course of treatment at the end of 1988, HIV status was assessed through two surveys conducted at mid-1986 and at end 1988 among the private practitioners and in the screening centers, hospitals, medico-social institutions and prisons. The overall annual HIV seroconversion rate shifted only slightly from 13% in the first study period (1984 to mid-1986) to 11% in the second period (mid-1986 to end 1988). In both periods, patients no longer on treatment, mostly stable abstainers, were the less exposed to HIV infection with a relative risk of 0.65 (p < 0.05). For those still on treatment, the risk of infection was associated directly (p < 0.001) with the frequency of courses and inversely (p < 0.001) with the duration. Between patients with more than 18 months spent on treatment and those with less than 6 months, the relative risk gradient was 0.8 and 1.4 before mid-1986 and widened out to 0.3 and 2.1 later on. This is mainly due to an increasing HIV incidence among newcomers into treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
We previously reported no differences in estimates of gestational maturity between a cumulative score based on sonographic/obstetrical measurements and an EEG interpretation for healthy preterm neonates. For the present study, a rank order among 5 fetal sonographic measurements was used to estimate gestational age: head circumference, transcerebellar diameter, biparietal diameter, femur length, and abdominal circumference were compared with an electroencephalographic estimate and an arithmetic estimate of maturity (i.e., the mother's last menstrual period). A fetal sonographic study for each of 13 premature neonates (i.e., born at < 32 weeks estimated gestational age) was followed after birth by a neonatal EEG recording. EEG and sonographic estimates of maturity were assigned without knowledge of other clinical data. The mother's last menstrual period was obtained from the medical record. Principal component analysis determined that 86% of the variance was evenly distributed over the 5 sonographic measurements. Using a regression procedure, 61% of the variance (adjusted r2 = 0.61) was explained by EEG when compared with fetal sonographic estimates. Only 19% (adjusted r2 = 0.19) of the variance was explained by the estimate based on the mother's last menstrual period. Optimal subset selection determined that the rank order for prediction of gestational maturity among the fetal sonographic measurements was as follows: (1) head circumference; (2) transcerebellar diameter; (3) biparietal diameter; (4) femur length; (5) abdominal circumference. Cranial measurements on fetal sonography (i.e., head circumference, transcerebellar diameter, biparietal diameter) compared more closely with EEG estimates than non-cranial measurements (i.e., femur length and abdominal circumference). In conclusion, neonatal EEG estimates of gestational maturity compared more closely with sonographic measurements than estimates based on the time of the last menstrual period. These findings will be useful in situations when dates of conception are unknown or inaccurate, or when intrauterine growth restriction causes discrepancies in growth rates between cranial and non-cranial fetal measurements on sonography.
Ciliary neurotrophic factor (CNTF) is known to rescue motor neurones in animal models of injury and neurodegeneration and we have recently described regional changes of CNTF protein levels in spinal cord from patients with sporadic motor neurone disease of the amyotrophic lateral sclerosis (ALS) type. However, information is lacking about the CNTF receptor in this condition. We have therefore studied mRNA levels for the alpha subunit of the CNTF receptor (CNTFR alpha) and for CNTF itself in postmortem spinal cord and cerebral cortex in patients with sporadic ALS and matched controls. We report that in the spinal cord of ALS patients there is a marked increase in the hybridisation signal for CNTFR alpha subunit mRNA overlying motor neurones. In contrast, very little mRNA for CNTFR alpha subunit was found in the motor cortex and no differences were seen between ALS and controls. We were unable to detect any hybridisation signal for CNTF mRNA. Our findings provide evidence for regional differences in CNTF receptor expression in upper- and lower-motor neurones in ALS.
Protein folding in the cell requires molecular chaperones. The chaperone proteins of the hsp70 and hsp60 (chaperonin) classes stabilize unfolded or partially folded polypeptides, thereby preventing aggregation, and mediate folding to the native state in ATP-dependent reactions. Recent advances include a more detailed understanding of the mechanistic principles of hsp70 and hsp60 action, the solution of the crystal structure of the chaperonin GroEL, and the definition of pathways of chaperone-mediated protein folding.
In the present study cultured human glomerular epithelial cells (HGEC) were used to examine the potential role for these cells in the turnover of the glomerular basement membrane (GBM) through the secretion of matrix metalloproteinases. The cells were shown by substrate gel electrophoresis to secrete gelatinase activity of molecular weights 72 kDa and 92 kDa. The gelatinolytic activity was inhibited by EDTA (10 mM), and by both TIMP-I and TIMP-II, but was not inhibited by PMSF (2.5 mM), indicating that the enzymes belonged to the metalloproteinase family. The identity of the enzymes was confirmed by the use of specific antisera to gelatinase A and gelatinase B. In addition, reverse transcription polymerase chain reaction (RT PCR) amplification of HGEC mRNA using specific primers to the two enzymes yielded single bands of amplified DNA and served to verify the identity of the enzymes. In supplementary experiments using both specific antiserum and PCR primers it was shown that HGEC express message and secrete both the specific metalloproteinase inhibitors TIMP-I and TIMP-II. These results indicate that the synthesis and secretion of degradative enzymes and their controlling inhibitors by HGEC have the potential to be involved in the turnover of the extracellular matrix.
Ciliary neurotrophic factor (CNTF) rescues motor neurons in animal models of injury and neurodegeneration, and disruption of the mouse CNTF gene results in motor neuron degeneration in mature adults. Glial cells increase nerve growth factor (NGF) expression in neuropathological conditions, and the sensory system can be affected in the amyotrophic lateral sclerosis (ALS) type of motor neuronic disease. We therefore studied CNTF and NGF levels in post mortem spinal cord and cerebral cortex from patients with ALS and matched controls. We report a marked decrease of CNTF in the ventral horn of spinal cord in ALS, with no change in cerebral motor cortex. In contrast, NGF levels were decreased in ALS cerebral motor cortex, where the corticospinal tract originates, but increased in the lateral column of spinal cord, which includes the region of corticospinal tract degeneration in ALS. Both CNTF and NGF levels were decreased in ALS dorsal spinal cord.
Calcitonin gene-related peptide (CGRP), a 37-amino-acid peptide, is a member of a small family of peptides including amylin or islet amyloid polypeptide and salmon calcitonin. These related peptides have been shown to display similar effects on in vitro and in vivo carbohydrate metabolism. The present study was initiated to identify and characterize the binding sites for these peptides in lung and nucleus accumbens membranes prepared from pig and guinea pig. Both tissues in either species displayed high-affinity (2-[125I]iodohistidyl10)humanCGRP alpha ([125I]hCGRP alpha) binding (IC50 = 0.4-7.7 nM), which was displaced by hCGRP8-37 alpha with equally high affinity (IC50 = 0.4-7.3 nM). High-affinity binding for [125I]Bolton-Hunter human amylin ([125I]BH-h-amylin) was also observed in these tissues (IC50 = 0.2-6.0 nM). In membranes from the nucleus accumbens of both species, salmon calcitonin competed for amylin binding sites with high affinity (IC50 = 0.1 nM) but was poor in competing for amylin binding in lung membranes. Rat amylin8-37 competed for [125I]hCGRP alpha binding with higher affinity (IC50 = 5.4 nM) compared with [125I]BH-h-amylin binding (IC50 = 200 nM) in porcine nucleus accumbens, whereas in guinea pig nucleus accumbens, the IC50 values for rat amylin8-37 were 117 and 12 nM against [125I]hCGRP alpha and [125I]BH-h-amylin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the effects of 42 weeks of progressive weight-lifting training on dynamic muscle strength, peak power output in cycle ergometry, symptom limited endurance during progressive treadmill walking and stair climbing, knee extensor cross-sectional areas, and bone mineral density and content in healthy males and females aged 60-80 years, currently enrolled in a 2-year resistance training program. Subjects were randomized into either exercise (EX) or control (CON) groups (60-70 years: 38 males and 36 females; 70-80 years: 25 males and 43 females). EX trained several muscle groups twice per week for 42 weeks at intensities ranging from 50-80% of the load that they could lift once only (1 RM); CON did usual daily activities. After the 10 months there was no change in 1 RM strength in CON, but significant gains (mean increases up to 65%) in EX (no independent age or gender effects); 30% and 47% of the increase in 1 RM had occurred by 6 and 12 weeks, respectively. In EX, the 7.1% increase in peak cycling power output was significantly greater than in CON (+1.1%). The 17.8% improvement in symptom limited treadmill walking endurance was also greater than in CON (+3.4%), but the difference between groups during stair climbing was not significant (EX + 57%, CON + 33%). The cross-sectional areas of the knee extensors increased significantly by 5.5% in EX but were unchanged in CON. There were no changes in bone mineral density or content in either group. We conclude that long-term resistance training in older people is feasible and results in increases in dynamic muscle strength, muscle size, and functional capacity.
Cumulative pregnancy rates and pregnancy outcome analysis are useful methods for advising an infertile couple of the probability of in-vitro fertilization (IVF) success. All 5209 IVF cycles in 2391 couples at University Hospital, London, Ontario, Canada, over 10 years were studied. Cumulative pregnancy rates were estimated using life table analysis. The Cox proportional hazards model was used to estimate the influence of covariates. Oocyte retrieval and embryo transfer were achieved in 84 and 64% of cycles initiated respectively. There were 644 intra-uterine and 24 ectopic pregnancies (13%/cycle initiated, 15%/oocyte retrieval and 20%/embryo transfer). Cumulative pregnancy rates following six cycles were: tubal 55%, idiopathic 65%, endometriosis 60%, multifactorial 63% and male 40%. There were 68 spontaneous abortions (10.6%) and three induced abortions for congenital anomalies. The multiple gestation rate was 22%. Caesarean section and preterm delivery rates were 35 and 20% respectively, due in part to the high proportion of multiple gestations. Of 15 deliveries which resulted in stillbirths and/or neonatal deaths, 12 were multiple gestations; 18 pregnancies (3.3%) were complicated by congenital malformations. No increases in congenital malformations or spontaneous abortions were identified. Cumulative pregnancy rates were lower in cases of male infertility. Success rates did not decline with successive IVF cycles. IVF is an evolving infertility treatment.
We previously demonstrated that rats experienced renal injury when exposed for 3-12 h to 50 ppm or more of a vinyl ether called Compound A [CF2 = C(CF3)OCH2F], a compound produced by CO2 absorbents acting on sevoflurane. These durations of exposure exceed the average duration of clinical anesthesia. We now report the effect of a 1-h exposure to 0, 100, 150, 200, 400, 600, or 800 ppm of Compound A in oxygen in 145 Wistar rats. Twenty-four hours after exposure, we obtained kidney and liver specimens for microscopic examination, applying hematoxylin and eosin, and (separately) an immunochemical marker (PCNA) for cell proliferation (regeneration). Compared with results from control rats (those breathing oxygen for 1 h), renal injury (defined as necrosis of the outer strip of the outer medullary layer or "corticomedullary junction necrosis") occurred at and above 200 ppm. Exposure to 150 ppm produced cell regeneration (i.e., stimulated cell proliferation). We conclude that the threshold concentrations for nephrotoxicity (i.e., minimal toxicity) for a 1-h exposure to Compound A exceed the maximum concentrations (particularly those at low inflow rates) reported in clinical practice by a factor of 2-3. If these threshold effects in rats apply to humans, one 1-h exposure to sevoflurane probably would not alter usual measures of renal function.
We address four major issues related to physicians' fear of litigation: What are physicians' attitudes and beliefs toward malpractice? To whom or what do they attribute the "malpractice crisis"? Is fear of litigation associated with demographic and practice variables? What measures do physicians take to reduce risk? Hospital physicians in a southeastern health science center were surveyed (N = 356). Physicians attributed the malpractice crisis to circumstances outside medicine and beyond their control, perceived some patients as suitprone, and reported altering their practice to avoid being sued. Litigation fear was associated with physicians who were female, younger, not board certified, less clinically experienced, more clinically active, defendants in prior lawsuits, and in high-risk specialties. Physicians who were especially fearful of litigation placed less value in risk-management techniques. The findings are important in understanding how the prospect of litigation is perceived by physicians and how that perception may affect medical practice.
The enormous media interest in the frequency and effects of child sexual abuse (CSA) has been paralleled in the past year by significant advances in our empirical knowledge about this childhood risk factor for adult psychosocial problems. Progress has been made in the diagnostic procedures employed in CSA physical examinations, in our understanding of the link between CSA and subsequent psychiatric morbidity, and in our cognizance of the effects that trauma, such as CSA, may have on memory.
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