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Biomedical subjects

J C Marshall

Publications and source records attributed to J C Marshall.

At least 19 recordsLinked to original sources
PubMed1993

GnRH pulses--the regulators of human reproduction.

The data reviewed in this chapter provide evidence that the pattern of GnRH secretion appears to be an important factor in regulating gonadotropin subunit gene expression, gonadotropin synthesis and hormone secretion. The data on gonadotropin synthesis were obtained in rodents and hence, must be interpreted with caution when applied to primates. Despite this reservation, the data suggest a similarity of regulatory mechanisms in mammalian species. The data also provide an explanation for the mechanisms whereby a single gonadotropin-releasing hormone can differentially regulate the three gonadotropin genes and allow differential hormone secretion. In overall agreement with this view, the observations during pubertal maturation reveal increasing GnRH pulsatile secretion during puberty with an evolution from predominant FSH to a predominant LH secretion by the gonadotropes. In males, the patterns of GnRH secretion appear to be fairly consistent throughout adult life, but in women cyclic changes occur which perhaps are important in maintaining cyclic ovulation. It is proposed that once pubertal maturation has been established, GnRH is secreted at a relatively fast frequency (one pulse per hour), and an essential feature of repeated ovulatory cycles is the slowing of this GnRH stimulus during the luteal phase: to allow subsequent preferential FSH release. This slowing of GnRH secretion appears to be effected by estradiol and progesterone acting to enhance hypothalamic opioid activity. Similar mechanisms involving increased opioid tone appear to be causally related to the reduced frequency and irregular GnRH stimulus seen in hypothalamic amenorrhea and hyperprolactinemia. In contrast, some forms of polycystic ovarian disease may reflect abnormalities of the estradiol-progesterone/opioid/GnRH neuron feedback mechanisms, with failure to establish slowing in the peripubertal anovulatory cycles. The resulting persistent GnRH stimulus increases LH with consequent effects of abnormal follicular maturation and enhanced ovarian androgen production. Present data are supportive of these hypotheses, but future studies will determine whether these views prove to be correct. However, current data provide strong support for the view that the pattern of GnRH secretion is a critical factor in the regulation of differential gonadotropin synthesis and secretion in mammalian species.

Animals↗
PubMed1992

Modulation of macrophage procoagulant activity by arachidonic acid metabolites.

Macrophage (M phi)-mediated fibrin deposition via induction of procoagulant activity (PCA) is an important component of the host response during various infections. While endotoxin (LPS) is a well-known stimulus of PCA, the factors modulating its activity within the inflammatory microenvironment are unknown. The purpose of these studies was to determine the relative roles of two pathways of arachidonic acid metabolism, i.e., the cyclooxygenase (CO) and 5-lipoxygenase (5-LO) pathways, in modulating M phi PCA induction by LPS. Thioglycolate-elicited murine peritoneal M phi were treated with the CO inhibitor indomethacin (INDO), the 5-LO inhibitor nordihydroguaiaretic acid (NDGA), or control vehicle for 15 min prior to a 4-hr exposure to LPS (10 micrograms/ml). The ability of M phi to shorten the clotting time of plasma (i.e., PCA) was measured and clotting times were converted to PCA units via a thromboplastin standard. While CO blockade had no effect on PCA induction by LPS (without INDO 30 microM 446 +/- 131, with INDO 30 microM 546 +/- 193, mU/2 x 10(6) cells, n = 4), NDGA caused a dose-dependent inhibition (IC50 = 3 microM) without affecting cell viability (without NDGA 3 microM 446 +/- 131, with NDGA 3 microM 191 +/- 67, mU/2 x 10(6) cells, n = 6, P less than 0.05). Induction of PCA by Escherichia coli was similarly inhibited (E. coli 10(6) alone = 518 +/- 130; with NDGA 3 microM = 234 +/- 100, n = 2). Combined NDGA/INDO reduced PCA comparable to NDGA alone, ruling out the possibility that NDGA acted through generation of inhibitory prostanoids like PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury.

Burn injury induces immune suppression and increases susceptibility to infection. Hypoalbuminemia is an early and consistent finding following thermal injury and is independently associated with gastrointestinal dysfunction and increased rates of infectious morbidity. This study assessed the effects of albumin resuscitation on burn-induced immunosuppression, bacterial translocation, and absorption of gut endotoxin. Male Sprague-Dawley rats, presensitized to keyhole limpet hemocyanin (KLH), underwent a 20% dorsal scald burn injury, followed by laparotomy and IVC catheterization for fluid resuscitation. Animals were randomized to one of three resuscitative regimens: Ringer's lactate 3 ml/kg/% burn, Ringer's lactate 9 ml/kg/% burn, or 5% human albumin 3 ml/kg/% burn. Delayed hypersensitivity (DTH) responses to KLH were depressed 24 hr following injury (preburn 8.9 +/- 0.2 mm, post-burn 3.1 +/- 0.3 mm, P less than 0.001) and were significantly lower in animals in whom gram-negative bacterial translocation had occurred (2.3 +/- 0.4 vs 3.6 +/- 0.2 mm, P less than 0.005). Serum albumin levels were lower and rates of gram-negative bacterial translocation higher for those animals receiving low volume crystalloid resuscitation; animals resuscitated with albumin or high volume crystalloid experienced similar degrees of postinjury hypoalbuminemia and bacterial translocation. Uptake of radiolabeled endotoxin was maximal in animals resuscitated with albumin. Bacterial translocation is believed to be responsible for a significant number of late nosocomial infections following trauma. These data suggest that the adequacy of early resuscitation rather than the type of resuscitative solution is the more important factor in minimizing translocation.

Animals↗
PubMed1992

Left visuo-spatial neglect: a meaningless entity?

Six patients with unilateral right hemisphere damage are reported. Each patient performed two tasks that are traditionally regarded as diagnostic for left (peripersonal) visuospatial neglect: target cancellation and horizontal line bisection. Two patients were unimpaired on both tasks, and two were impaired on both. The two remaining patients showed a classic (and reliable) double-dissociation between the tasks. One of the patients who scored within normal limits on both cancellation and bisection showed left sided omissions on representational drawing. We argue that these results question the validity of any unitary concept of unilateral visuo-spatial neglect in peripersonal space.

Adult↗
PubMed1992

Discrepant oral and written spelling after left hemisphere tumour.

Repetition, reading, confrontation naming, and oral and written spelling were studied in a 57 year-old man with a left hemisphere tumour. These tasks were repeated over a period of two weeks when the patient was being treated for brain oedema prior and subsequent to neurosurgical intervention. In the context of intact repetition and good reading, the most striking finding was a significant qualitative and quantitative discrepancy between oral and written spelling, with the latter task more severely affected. The pattern on oral spelling was that of lexical (or surface) agraphia. On written output, however, orthographic errors predominated. The relatively greater impairment of written spelling was not secondary to a motoric or visuo-spatial deficit. The observed patterns are not easily accommodated by current models of writing.

Agraphia↗
PubMed1992

Visuo-spatial neglect: qualitative differences and laterality of cerebral lesion.

From a large sample of patients who sustained a first stroke, 98 patients were selected with unilateral left brain damage and 92 with unilateral right brain damage. Examined on a visual search task (Star Cancellation) approximately four years after onset, we found a comparable incidence of visual inattention in the two groups. Despite this quantitative similarity, the qualitative pattern of performance was different in the two impaired samples. Patients with right brain damage showed a distinctive linear relationship whereby omission errors increased from right to left across the stimulus page. Within the left brain damaged sample, two subgroups could be discerned. As expected, one subgroup showed more contralesional than ipsilesional errors, but the other subgroup was comparable to the sample with right hemisphere damage. The reasons are discussed for these qualitative differences, drawing particular attention to the importance of motor/manual factors in the determination of performance on visual search tasks.

Aged↗
PubMed1992

Left on the right: allochiria in a case of left visuo-spatial neglect.

A patient with left visuo-spatial neglect after right fronto-parietal haemorrhage failed to cross out stimuli in left space on cancellation tests. Her bisections of horizontal lines were displaced significantly to the right of true centre. On drawing and copying tasks, she sometimes omitted features on the left (neglect) and sometimes transposed them to right space (allochiria). This co-occurrence of neglect and allochiria has been observed previously but has provoked little theoretical comment. We draw attention to aspects of the combination that seem critical to the interpretation of visuo-spatial neglect.

Aged↗
PubMed1992

Differential actions of thyrotropin (TSH)-releasing hormone pulses in the expression of prolactin and TSH subunit messenger ribonucleic acid in rat pituitary cells in vitro.

The influence of TRH pulse pattern on PRL and TSH alpha- and beta-subunit gene expression was examined in vitro. Pituitaries from adult female rats were dissociated and plated for 48 h to allow attachment to collagen-coated microcarrier beads. The beads were perifused for 24 h with TRH (pulses or continuous). To examine the effects of TRH pulse amplitude, TRH pulses (0.032-100 nM) were given every 60 min (controls received either medium pulses or continuous 100 nM TRH). PRL mRNA rose progressively to a peak at 4 nM TRH/pulse (93% increase vs. medium-pulsed controls), but higher TRH pulse amplitudes were less effective. alpha-Subunit mRNA also rose with increasing TRH pulse dose, with maximal (137%) elevations after 100-nM pulses. TSH beta mRNA concentrations were increased by TRH pulse doses between 0.8-20 nM, but a clear dose-response pattern was not seen. Continuous TRH (100 nM) resulted in PRL, TSH beta, and alpha mRNAs that were less than the values in medium-pulsed controls. To assess the effects of pulse frequency, 4-nM TRH pulses were given at intervals between 15-240 min (controls received medium pulses or continuous 4 nM TRH). PRL mRNA was increased (55-107% increase) after all pulse intervals, except 240 min, and rose to a similar degree after 4 nM TRH given continuously. alpha-Subunit mRNA concentrations increased by a lesser degree and also did not rise after the slowest (240 min) pulse interval. In contrast, TSH beta mRNA levels increased progressively as pulse intervals were increased, and maximal (85%) elevations were seen after 240-min pulses. Continuous 4 nM TRH did not alter alpha or TSH beta mRNAs. These results show that pulsatile TRH is more effective than continuous TRH in stimulating PRL, TSH beta, and alpha mRNAs. Further, the pattern of TRH pulsatile signals can influence the expression of these pituitary hormone genes in a differential manner.

Animals↗
PubMed1992

Enhanced effectiveness of pulsatile 3',5'-cyclic adenosine monophosphate in stimulating prolactin and alpha-subunit gene expression.

cAMP is involved in the regulation of secretory activity in lactotrope, thyrotrope, and gonadotrope cells. The present study examined whether pulsatile or intermittent changes in cAMP are more effective than a continuous stimulation in increasing pituitary hormone gene expression. Pituitaries from adult female rats were dissociated, plated for 48 h (7-8 x 10(6) cells per well) to allow attachment to Matrigel-coated plastic coverslips, then inserted into perifusion chambers (five to eight chambers per group). After 24 h of treatment, the cells were recovered, RNA extracted, and messenger RNAs (mRNAs) determined by dot blot hybridization. Perfused cells were exposed to either hourly pulses of monobutyryl cAMP (Bt cAMP, 0.01, 0.1, or 1 mM; 1 mM butyrate pulses to controls), or continuously to forskolin (10 microM). Bt cAMP pulses increased both PRL and alpha-subunit mRNAs, maximal after the 0.1 mM dose for PRL (51% increase vs. butyrate controls) and after the 1 mM dose for alpha (60% increase). However, forskolin was ineffective in increasing PRL or alpha mRNA concentrations. TSH, LH, and FSH beta-subunit mRNAs were not altered by Bt cAMP pulses or forskolin. To confirm the different effects of pulsatile vs. continuous cAMP on PRL and alpha-subunit mRNAs, the response to pulsatile 8-bromo cAMP (1 mM) or Bt cAMP (0.5 mM) was compared to continuous Bt cAMP (0.5 mM). PRL and alpha-subunit mRNAs were increased by both cAMP analogs given in a pulsatile manner but not by continuous Bt cAMP. PRL and LH secretory responses (determined in perifusate samples after 2 h and 22 h of treatment) revealed that both PRL and LH release was increased by cAMP stimulation, given either in a pulsatile or continuous manner. These results show that PRL and alpha-subunit gene expression were sensitive to changes in cAMP stimulation, whereas that of TSH, LH, and FSH beta were unaltered. Only intermittent cAMP stimuli were effective in increasing PRL and alpha mRNAs. These data suggest that pulsatile fluctuations in intracellular cAMP may be essential for maximal expression of the PRL and alpha genes. Thus, intermittent changes in intracellular second messengers may be a necessary part of the pathway involved in the transduction of signals from the plasma membrane to the nucleus.

Animals↗
PubMed1992

Acute effects of testosterone infusion and naloxone on luteinizing hormone secretion in normal men.

To evaluate the role of endogenous opioid pathways in the acute suppression of LH secretion by testosterone (T) infusion in men, we studied eight normal healthy volunteers who received a saline infusion, followed 1 week later by a T infusion (960 nmol/h) starting at 1000 h and lasting for 33 h. After 2 h of infusion (both saline and T), four iv boluses of saline were given hourly, and after 26 h of infusion, four hourly iv boluses of naloxone were given. Blood was obtained every 15 min for LH and every 30 min for T. T infusion increased the mean plasma T concentration 2.1-fold (18.7 +/- 2.1 to 39.5 +/- 3.5 nmol/L, saline vs. T infusion, P < 0.01). The mean plasma LH concentration was 7.9 +/- 0.5 IU/L during the saline control study and was decreased to 6.9 +/- 0.6 IU/L by the infusion of T (P < 0.05). LH pulse frequency was similar during both saline and T infusions (0.48 +/- 0.02 vs. 0.43 +/- 0.04 pulses/man.h, saline vs. T infusion). The mean LH pulse amplitude decreased from 4.3 +/- 0.4 IU/L during saline infusion to 3.3 +/- 0.2 IU/L during T infusion (P < 0.05). The administration of naloxone increased the mean plasma LH concentration significantly during saline infusion (7.6 +/- 0.4 to 10.0 +/- 0.9 IU/L, saline vs. naloxone boluses, P < 0.01), but not during T infusion (6.9 +/- 0.6 vs. 7.3 +/- 0.6 IU/L). LH pulse frequency increased significantly after the administration of naloxone during both saline and T infusions (0.54 +/- 0.04 to 0.71 +/- 0.08 pulses/man.h, saline vs. naloxone boluses during saline infusion, and 0.46 +/- 0.08 to 0.60 +/- 0.07 pulses/man.h during T infusion; P < 0.05). LH pulse amplitude was suppressed by T infusion, but administration of naloxone did not reverse this suppression. The mean amplitude of the LH response to exogenous GnRH (250 ng/kg) was decreased by T infusion from 48 +/- 13.5 to 31.2 +/- 8.5 IU/L (P < 0.01). Therefore, in men, the administration of naloxone increases LH pulse frequency during both saline and T infusions, but the acute suppression of LH pulse amplitude seen with T infusion was not reversed by naloxone. This pattern contrasts sharply with the effects of T infusion in pubertal boys, as elucidated by our earlier studies. The negative feedback effects of T on LH secretion are primarily hypothalamic in early pubertal boys and change to pituitary suppression in men.

Adult↗
PubMed1992

Gonadal steroids effect similar regulation of gonadotrophin subunit mRNA expression in both male and female rats.

Gonadal steroids can act both indirectly via gonadotrophin-releasing hormone (GnRH) and directly on the pituitary to regulate gonadotrophin subunit gene expression. Recent studies to assess a possible direct action at the pituitary have shown that testosterone, when given to males in the absence of endogenous GnRH action, selectively increases FSH-beta mRNA concentrations. Conversely, in females, oestradiol appears to regulate gonadotrophin subunit mRNAs primarily via GnRH. The present study was designed to determine whether these differing results reflect specific actions of the gonadal steroids themselves or different responses of the pituitary gonadotroph cells in males and females. Rats which had been castrated 7 days earlier were given silicone elastomer implants (s.c.) containing oestradiol (plasma oestradiol 68 +/- 4 ng/l) in males or testosterone (plasma testosterone 3.5 +/- 0.3 micrograms/l) in females in the absence or presence of a GnRH antagonist. Seven days later pituitaries were removed and steady-state mRNA concentrations measured by dot-blot hybridization. In males, oestradiol reduced LH-beta and FSH-beta but not alpha mRNA. The antagonist reduced levels of all three subunit mRNAs in males and the addition of oestradiol had no further effect, suggesting that oestradiol regulates gonadotrophin subunit gene expression in males by suppressing GnRH secretion. In females, testosterone reduced all three subunit mRNAs though FSH-beta remained threefold higher than in intact animals. The GnRH antagonist was as effective as testosterone alone and reduced alpha and LH-beta to levels found in intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nosocomial infection in the surgical intensive care unit.

The critically ill surgical patient is at high risk for the development of ICU-acquired infection. Normal mucosal defenses are breached by surgical incisions or by intravascular devices, urinary catheters, and endotracheal tubes. The integrity of the gastrointestinal epithelium is compromised by the lack of enteral nutrition and episodes of hypoperfusion, resulting in translocation of normal or disturbed enteric flora. The indigenous microbial flora, an important component of normal host defenses against invasive infection, is disrupted through the use of broad-spectrum antibiotics or by poorly understood influences associated with critical illness. Systemic immunity is altered, and multiple abnormalities of specific and nonspecific immune function can be documented. Infections acquired within the ICU are commonly caused by endogenous organisms of low intrinsic pathogenicity, and the contribution of these infections to ICU outcome is controversial. Diagnosis is established by directed investigations, focusing on surgical sites and invasive devices. Therapy is primarily physical (drainage of infected collections or removal of contaminated devices), and antimicrobial therapy should employ narrow-spectrum agents guided by the results of Gram stain and culture. The prevention of ICU-acquired infection is based on timely and definitive surgical therapy, judicious use of invasive devices and antibiotics, and early enteral feeding. Infection-control measures aimed at endogenous reservoirs show some preliminary promise for certain subsets of patients, but remain, at present, experimental.

Cross Infection↗
PubMed1991

Left neglect for near but not far space in man.

It has been suggested that, among the many visual areas of the human brain, there might be one set of spatial maps specialized for 'near' (peripersonal) and another for 'far' (extrapersonal) space. A distinction between 'grasping distance' and 'walking distance', or between a 'reaching field' and a pointing or throwing field has commonly been made. Evidence for such a division has been found in monkeys. Unilateral ablation of the frontal eye field (area 8) produces a more prominent inattention (or 'neglect') for objects in contralesional far space than in near space; by contrast, unilateral ablation of frontal area 6, which receives direct projections from area 7b (the rostral part of the inferior parietal lobules) results in inattention to visual stimuli limited to contralesional near space. Despite predictions that comparable dissociations should be found in man, there has been no convincing evidence. We report here such evidence in a patient with a unilateral right hemisphere stroke. Within peripersonal space, he showed severe left visuo-spatial neglect on conventional tests, including the highly sensitive task of line bisection. When line bisection was performed in extrapersonal space, neglect was abolished or attenuated.

Brain↗
PubMed1991

Hemispheric activation vs spatio-motor cueing in visual neglect: a case study.

We report a case of mild visuo-spatial neglect consequent upon right-hemisphere stroke. At the time of testing, the patient had a complete left visual field deficit but only a very slight left hemiparesis. Under conventional testing conditions, line bisection performed with the right hand showed more severe left neglect than when performed with the left hand. This pattern of performance could, however, be modified, both quantitatively and qualitatively, by changing the starting position of the patient's hand when bisecting horizontal lines. The results suggest that spatio-motor cueing has a more profound effect upon task performance than does differential hemispheric activation per se. We also provide a demonstration that, in a normal subject, the starting position of the hand is likewise a crucial determinant of task performance. In this case, however, there is also an interaction between the hand (and hence hemisphere) deployed and the position of that hand in space.

Adult↗
PubMed1991

Figural modulation of visuo-spatial neglect: a case study.

We report a case of severe left visuo-spatial neglect consequent upon right-hemisphere stroke. In Experiment 1, horizontal and vertical (radial) line bisection is performed; the patient displays left neglect and "altitudinal" (radial) neglect, placing his transections too far to the right and to the top, respectively. In Experiment 2, the patient is required to place a dot at the centre of squares and circles, the horizontal and vertical extents of which are identical to the length of the lines employed in Experiment 1. Performance is now extremely accurate. In Experiment 3, the height of the rectangular or elliptical figure whose midpoint is to be estimated is held constant whilst length varies. In Experiment 4, the length of the figure is held constant whilst height is varied. Both manipulations exert a profound, lawful influence on the patient's estimate of each figure's midpoint. We provide some preliminary hypotheses concerning how configurational constraints may affect perceptual and attentional processes in visual neglect.

Attention↗
PubMed1991

The ecology and immunology of the gastrointestinal tract in health and critical illness.

Interactions between the indigenous flora of the gastrointestinal tract and immunologically competent cells in the gut mucosa, gut-associated lymphoid tissues and liver play an important role in normal immune homeostasis. The microbial flora of the normal gut is complex, yet remarkably constant over time. The relative sterility of the upper gut is maintained by multiple factors including gastric acid, bile salts, normal motility and mucosal IgA, while the lower gut is densely colonized with a complex flora. An intact Gram-negative flora is a prerequisite for normal immunological maturation. On the other hand, overgrowth of the gut, particularly by Gram-negative bacteria or fungi, facilitates the translocation of bacteria into the host, and results in suppression of T-cell responses and altered hepatic Kupffer cell function. Bacterial overgrowth and the consequences of the interactions of this potentially pathogenic flora with the gut immune system may contribute to the septic state in critical illness, and to the syndrome of multiple organ failure.

Critical Illness↗