Effects of acute and chronic midthoracic spinal cord injury on neural circuits for male sexual function. I. Ascending pathways.
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Normal male reproductive function, particularly ejaculation, requires the integrity of urogenital sensory input and its ascending spinal projections. After midthoracic chronic spinal cord injury, sexual dysfunction occurs in both rats and humans. Neurons in the medullary reticular formation (MRF) are involved in the processing of bilaterally convergent sensory inputs from multiple cutaneous, mucocutaneous, and visceral regions of the body, including the penis and male urogenital tract. A variety of acute and chronic lesions were used to determine the midthoracic location of ascending spinal pathways conveying sensory input from the penis and male urogenital tract to MRF. A total of 371 single neurons were recorded in the MRF of 34 urethan-anesthetized mature male rats. Twenty-seven rats received a chronic T8 dorsal (DHx) or lateral (LHx) hemisection or contusion (Cx) injury 30 days before the terminal electrophysiological experiments. In addition, nine dorsal nerve of the penis (DNP)-responsive MRF neurons in seven intact control animals were tested completely both before and after various select acute spinal cord lesions. The chronic lesion data indicate that low and high threshold input from the penis (mucocutaneous) and male urogenital tract (visceral) ascend bilaterally within the dorsal quadrant at T8 as opposed to high threshold input from the hindpaws (cutaneous), which ascends unilaterally in the ventrolateral quadrant (VLQ). The acute lesion data indicate that the low-threshold information conveyed from the penis and male urogenital tract ascends in the dorsal columns, as opposed to the high-threshold nociceptive inputs that ascend bilaterally in the dorsolateral quadrant (DLQ). These results, as well as previous data on ascending projections from female reproductive organs within the dorsal columns and DLQ to other caudal brain stem nuclei, provide evidence for ascending pathways conveying nociceptive information centrally via the DLQ. This spinal gray-DLQ pathway(s) conveying information from mucocutaneous/pelvic/visceral territories therefore differs from the traditionally recognized spinal gray-VLQ pathway(s), which is known to convey nociceptive information from cutaneous regions of the body. (+info)
Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections.
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The feasibility of administering a relatively high dose of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix by means of a needle-free injection device, which could be useful in the long-term treatment of sex-steroid-dependent disorders, was evaluated in a randomized, crossover study in 16 healthy females. Local tolerance and pharmacokinetics of ganirelix administered by MediJector versus conventional needle injections were compared. Additionally, the pharmacodynamic effect was evaluated. Two milligrams of ganirelix was administered s.c. once daily for 7 days by Medi-Jector or conventional needle in a randomized sequence, without a washout period. No apparent differences in local tolerance were observed. Most injections (87.5%) gave either no or only a mild reaction. Of the moderate reactions, swelling and redness were reported most frequently (overall 4.9 and 8.5% per injection, respectively). Administration by Medi-Jector was bioequivalent to conventional needle injection with respect to the peak concentration and area under the curve. A profound suppression of luteinizing hormone and follicle stimulating hormone was observed. Serum oestradiol and progesterone concentrations were relatively low prior to treatment and remained low during the entire study period. In conclusion, administration of a relatively high dose of ganirelix by Medi-Jector might be useful for long-term treatment of sex-steroid dependent disorders. (+info)
Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1.
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Platelet (P-) selectin and intercellular adhesion molecule-1 (ICAM-1) mediate accumulation of neutrophils in brain. However, the mechanisms regulating neutrophil accumulation and damage after traumatic brain injury (TBI) are poorly defined. We hypothesized that mice deficient in both P-selectin and ICAM-1 (-/-) would have decreased brain neutrophil accumulation and edema, and improved functional and histopathological outcome after TBI compared with wild-type (+/+). In Protocol I, neutrophils and brain water content were quantified at 24 h after TBI. No difference in brain neutrophil accumulation was observed between groups; however, brain edema was decreased in dual P-selectin and ICAM-1 -/- (P < 0.05 vs. +/+ mice). In Protocol II, after TBI, tests of motor and memory function and histopathology were assessed over 21 days. No difference in motor or memory function or histopathological damage was observed between +/+ and -/- mice. A role for adhesion molecules in the pathogenesis of brain edema independent of leukocyte accumulation in brain is suggested. (+info)
Domestic violence: the shaken adult syndrome.
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A case of domestic violence is reported. The patient presented with the triad of injuries associated with the shaking of infants: retinal haemorrhages, subdural haematoma, and patterned bruising; this has been described as the shaken adult syndrome. This case report reflects the difficulties in diagnosing domestic violence in the accident and emergency setting. (+info)
Mechanisms of ventricular arrhythmias induced by myocardial contusion: a high-resolution mapping study in left ventricular rabbit heart.
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BACKGROUND: The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. METHODS: Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. RESULTS: The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. CONCLUSIONS: Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle. (+info)
Effects of acute and chronic midthoracic spinal cord injury on neural circuits for male sexual function. II. Descending pathways.
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In normal animals, microstimulation of the medullary reticular formation (MRF) has two effects on efferent neurons in the motor branch of the pudendal nerve (PudM). MRF microstimulation depresses motoneuron reflex discharges (RD) elicited by dorsal nerve of the penis (DNP) stimulation and produces long latency sympathetic fiber responses (SFR). The midthoracic spinal location of these descending MRF-PudM projections was studied electrophysiologically using a variety of acute and chronic lesions. Chronic lesions, in 27 mature male rats, included dorsal (DHx) or lateral (LHx) hemisections or moderate/severe contusions (Cx) at spinal level T(8). Behavioral data (sexual reflex latency, bladder voiding) obtained throughout the recovery period revealed a significant impairment of urogenital function for the DHx and severe Cx groups of animals. Microstimulation-induced PudM-RDs and PudM-SFRs, obtained in terminal electrophysiological experiments 30 days postinjury in the same 27 rats (urethan-anesthetized), were tested for a combined total of 1,404 bilateral MRF sites. PudM-RD was obtained for LHx and moderate Cx groups of animals but not for DHx or severe Cx groups. PudM-SFRs were obtained for LHx, DHx (although significantly weakened) and moderate Cx groups but not for those having received either an over-DHx or a severe Cx injury. PudM responses also were tested for 6 MRF sites in six intact control rats both before and after various select acute spinal cord lesions. For MRF sites producing a robust PudM-RD and PudM-SFR, acute bilateral lesions confined to the dorsolateral quadrant (DLQ) eliminated the PudM-RD but failed to eliminate PudM-SFRs. A deeper lesion encompassing additional white matter located dorsally in the ventrolateral quadrant (VLQ) was necessary to eliminate PudM-SFRs. Overall, these electrophysiological results provide evidence for descending projections conveying information between MRF and the lower thoracic/lumbosacral male urogenital circuitry within the DLQ and the dorsal-most aspect of VLQ at the midthoracic level of spinal cord. The alterations of supraspinal projections observed after chronic injury are likely of important clinical significance for functional recovery in cases of clinically incomplete spinal cord injury at midthoracic spinal cord. (+info)
Evaluation of physical abuse in children.
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Family physicians who are involved in the care of children are likely to encounter child abuse and should be able to recognize its common presentations. A history that is inconsistent with the patient's injuries is the hallmark of physical abuse. A pattern of physical findings, including bruises and fractures in areas unlikely to be accidentally injured, patterned bruises from objects, and circumferential burns or bruises in children not yet mobile, should be viewed as suspicious for child abuse. Family physicians who suspect physical abuse are mandated to make a report to the state child protective services agency and to assure the ongoing safety of the child. (+info)
An unusual cause of bruising in an 80-year-old woman.
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PRESENTATION: a previously fit 80-year-old woman presented with a 2-week history of spontaneous and extensive bruising affecting all four limbs. The severity was such that she required a transfusion of 8 units of blood. RESULTS OF INVESTIGATIONS: a markedly prolonged activated partial thromboplastin time which was only partially corrected with normal plasma; tests for lupus anticoagulant were negative. Factor VIII levels were reduced and the Bethesda assay indicated an acquired inhibitor to factor VIII. She was treated with a combination of intravenous immunoglobulin and immunosuppression. OUTCOME: the response to treatment was excellent, with a marked reduction in anti-factor VIII antibody levels and resolution of the bruising over the next few weeks. (+info)