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A review of 86 patients referred to a urological clinic with impotence showed that in 58% the causation was predominantly psychogenic. These patients were managed with psychosexual counselling. The various treatment options were discussed with those patients with organic impotence and 14 underwent the implantation of a penile prosthesis. A review of 130 patients who received penile prostheses in the period 1983 to 1987 was carried out to compare the complications and results obtained with the various types of prosthesis. The overall satisfaction rate was 81%; dissatisfaction usually arose as a result of complications of surgery. These were highest in patients with diabetes and priapism. The complications were also related to the type of prosthesis used.
Seven patients with penile rupture were treated surgically within a 9-month period. All were operated on as emergencies, with successful results, except in 1 case which was associated with urethral rupture. Sexual performance was satisfactory in 6 of 7 cases.
Little is known about changes in bladder compliance and bladder capacity in myelodysplastic patients following anti-reflux surgery. A study group of 70 patients was divided as follows: group A included 20 myelodysplastic patients who had been operated on for reflux and whose subsequent treatment was conservative. Group B comprised 31 myelodysplastic patients who had been treated conservatively; a third group of 19 non-myelodysplastic patients, treated by anti-reflux surgery because of primary reflux, formed the control group. The follow-up period for group A averaged 61 months (extending from a urodynamic study 3 months after surgery to the most recent test). In group B the mean follow-up period between the initial test and the latest test was 86 months. Bladder compliance in group A patients did not increase significantly (from 5.5 to 6.9), but patients in group B did show a significant increase (from 5.9 to 10.7). Compliance in the 19 non-myelodysplastic patients decreased only marginally 6 months after surgery (from 29.6 to 26.3). Changes in bladder capacity showed a similar trend. In their most recent test, however, the bladder capacity of group A patients increased to the same volume as that of group B. A high correlation between radiological bladder deformity and bladder compliance was found. We propose a bladder compliance of 10.0 as the lower limit for myelodysplastic patients' preferred range. It was concluded that anti-reflux operations prevent any improvement in bladder compliance (but not in bladder capacity) compared with conservative treatment.
The relationship between local recurrence and survival has been examined using the example of soft tissue sarcomas of the extremities. Studies that appear to indicate that local recurrence does not jeopardize survival are shown to have been inappropriately analysed, to have inadequate patient numbers, or both. A survival deficit due to local tumour recurrence cannot be excluded on present data, and clinical decisions regarding conservative versus radical surgery will therefore continue to involve an element of value judgement.
Ischaemia is a common clinical event leading to local and remote injury. Evidence indicates that tissue damage is largely caused by activated neutrophils which accumulate when the tissue is reperfused. If the area of ischaemic tissue is large, neutrophils also sequester in the lungs, inducing non-cardiogenic pulmonary oedema. Ischaemia reperfusion injury is initiated by production of reactive oxygen species which initially appear responsible for the generation of chemotactic activity for neutrophils. Later, once adherent to endothelium, neutrophils mediate damage by secretion of additional reactive oxygen species as well as proteolytic enzymes, in particular elastase. Therapeutic options for limiting ischaemia reperfusion injury include inhibition of oxygen radical formation, pharmacological prevention of neutrophil activation and chemotaxis, and also the use of monoclonal antibodies which prevent neutrophil-endothelial adhesion, a prerequisite for injury.
Endothelial cell seeding is a technique that has developed over the past 15 years in response to the need for a high performance synthetic vascular graft. This review details our present knowledge of seeding and examines the various problems that have hampered its introduction into clinical practice.
The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4.5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required.
Radiation detectors may allow the intraoperative localization of small cancer deposits following administration of radiolabelled tumour-associated antibodies. This technique was evaluated in 16 patients with colorectal tumours (14 cancers, one adenoma, one lipoma) with the 111In-labelled monoclonal antibody (MAb) ICR2 which recognizes the tumour-associated epithelial membrane antigen (EMA). At operation counting was carried out (3 x 20 s per site) using a hand-held radiation probe over the primary lesions and any palpable lymph nodes in the mesocolon. The tumour to normal colon (T/NC) ratio of counts recorded at operation was more than 1.5:1 in eight of the 14 patients with cancer (mean(s.d.), 1.54(0.41):1) and 0.91:1 and 1.06:1 respectively in the two patients with benign tumours. Node to normal colon ratios were higher in lymph nodes containing metastases. The uptake of radiolabelled antibody (T/NC ratio) was higher in EMA-expressing cancers than in those not expressing the target antigen (mean(s.d.), 2.45(0.65):1 versus 1.40(0.20):1, P = 0.019). An abdominal tumour model was also developed. Radioactively filled containers of 0.5-10 ml representing tumour deposits were suspended in a tank of 111In solution representing the background activity found in normal tissues. The ratio of radioactivity in the 'tumour' to that of background varied from 2:1 to 8:1. The 'tumour' was considered to be detectable if the mean counts recorded over the 'tumour' exceeded the mean of counts recorded over background by three standard deviations. At a ratio of 2:1 only 'tumours' greater than 5 ml could be detected with a sodium iodide probe and those over 10 ml could be detected with a cadmium telluride (CdTe) probe. At a ratio of 8:1, 'tumours' of 0.5 ml could be detected with either probe. At all ratios and counting periods the NaI probe was more sensitive than the CdTe.
Suture line recurrence is an important cause of failure after potentially curative resection for colonic carcinoma. Our aim was to determine whether suture technique affected the incidence of perianastomotic tumours in experimentally induced colonic cancer. Sprague-Dawley rats were randomized into three groups. A 1 cm longitudinal colotomy was repaired with four interrupted 6/0 polypropylene monofilament sutures, using either a transmural technique (n = 18) or a seromuscular technique (n = 18). Control animals (n = 18) had a sham laparotomy. All animals received nine, weekly, subcutaneous injections of azoxymethane (total dose 90 mg/kg) starting 6 weeks after laparotomy. Surviving animals were killed 32 weeks after laparotomy. Five animals from each group were given intraperitoneal bromodeoxyuridine (100 mg/kg) 1 h before being killed. At death, perianastomotic tumours occurred more frequently in animals with transmural sutures than in either controls or those with seromuscular sutures. This difference was associated with a greater mucosal bromodeoxyuridine crypt cell labelling index in the transmural suture group. We conclude that a transmural anastomotic suture technique promotes the development of experimental perianastomotic colonic tumours.
Since 1954, 34 patients have attended St. Mark's Hospital with pyoderma gangrenosum in association either with ulcerative colitis (22 patients) or Crohn's disease (12 patients). Lesions were multiple in 71 per cent and over half were situated below the knees. Ulcerative colitis was active in 11 patients (50 per cent) and Crohn's disease was active in nine (75 per cent) when pyoderma gangrenosum was diagnosed. Associated illnesses--most commonly a seronegative arthritis affecting large joints--were present in 55 per cent and 92 per cent of cases respectively. A diffuse pustular rash appeared in six patients, synchronously with pyoderma in five. In a further seven patients (two with ulcerative colitis, five with Crohn's disease) the onset or course of pyoderma might have been linked to the presence of non-dermatological suppuration. Pyoderma resolved without intestinal resection in two-thirds of patients. When present at the time of surgical resection (15 procedures in 13 patients), pyoderma healed promptly in six cases, only with additional therapy in four cases and very slowly or not at all in five cases. Pyoderma gangrenosum occurs in both ulcerative colitis and Crohn's disease. Healing after intestinal resection is unpredictable both with respect to timing and extent of resection.
We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy.
A perineal operation is described for the treatment of rectal prolapse. The surgery improves functional outcome by correcting the anatomical anomalies associated with the condition. In 17 elderly women, there was one perioperative death and one recurrence. At a median follow-up of 24 months, 13 patients were able to control solid stool and three were profoundly incontinent. The operation may be an alternative to the more invasive abdominal procedures for the treatment of the majority of patients with prolapse.
This study examined differences in anorectal function, with particular reference to anismus, which might explain why some patients with intractable constipation have slow and others have normal whole gut transit times. Twenty-four patients were studied; 13 with slow transit (all female, median age 32 years, range 16-52 years) and 11 with normal transit (eight women, three men, median age 37 years, range 21-60 years). Videoproctography with synchronous sphincteric electromyography and anorectal manometry was performed. There were no differences between the two groups, suggesting that slow transit constipation is not secondary to any abnormality in anorectal function and may therefore be a primary disorder of colonic motility. There was no correlation between electromyographic evidence of anismus (pelvic floor contraction on defaecation) and the ability of the patient to evacute the rectum or symptoms of obstructed defaecation. Electromyography findings alone can be misleading and should be related to proctographic evidence of incomplete rectal evacuation before functional anismus can be said to be present.
Ten women with symptoms and radiological features of outlet obstruction constipation underwent urodynamic bladder studies. The results were compared with ten age- and sex-matched controls. The mean (s.e.m.) peak flow rate for patients was 19.4 (6.4) ml/s compared with 32.1 (7.2) ml/s for controls (P less than 0.05). The mean (s.e.m.) voiding time for patients was 62.9 (23.7) s against a corresponding value of 15.6 (6) for controls (P less than 0.05). The mean (s.e.m.) bladder volume in patients was 482 (80) ml compared with a control value of 254 (112) ml (P less than 0.03). The mean (s.e.m.) detrusor pressure during the voiding phase was 53.3 (12) cmH2O. These results demonstrate that patients with outlet obstruction constipation have a generalized pelvic floor disorder resulting in obstructed urinary flow.
The total protein content (g/l) and white blood cell count (cells/mm3) diagnostic peritoneal lavage was assessed using a urine dipstick in 46 patients with suspected penetrating abdominal stab wounds and equivocal physical examination. Those patients with a protein content greater than or equal to 1 g/l and white blood cell count of greater than 500 cells/mm3 were submitted to laparotomy while those with lower values underwent observation and repeat physical examination. In all, 26 patients had a positive lavage and significant injuries were found in 23 of these. Of 18 patients with a negative lavage, 17 were managed successfully without operation while one patient died from complications related to central venous catheterization. In two patients the lavage results were equivocal. One underwent a negative laparotomy and the remaining patient recovered uneventfully. The test has a 100 per cent sensitivity and 86 per cent specificity and provides an accurate, cheap, and rapid means of diagnosis of intra-abdominal injury in penetrating trauma.
A total of 349 patients were randomized to undergo laparotomy through a lateral paramedian incision with layered closure (n = 137), a midline incision with mass closure (n = 104) or a midline incision using layered closure (n = 108), endeavouring to close the latter two incisions with a measured suture length to wound length ratio of greater than 4:1. After 18 months follow-up, no patient in the lateral paramedian group had developed an incisional hernia whereas 7 of 104 patients undergoing a midline incision with mass closure and 7 of 108 patients undergoing a midline incision with layered closure had incisional hernias (P less than 0.01). The mean suture length to wound length ratios for the three groups were 2.6 (range 1.3-6.2), 5.0 (range 3.0-8.7) and 3.7 (range 2.0-6.3) respectively (P less than 0.0001). The lateral paramedian incision remains superior to the midline incision closed with the mass technique and its integrity is independent of the suture length to wound length ratio.
The problem of the biochemical quantification of long term human wound healing was approached by measuring collagen synthesis in reincisions using specific radioimmunoassays for the wound fluid concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP). First-day wound fluid PICP concentration after reincising a 3 week old scar was 25 times higher than the mean value in 20 reference standard incisions but scars older than 3 months did not show this difference. Wound fluid taken in subsequent days demonstrated that the initial acceleration of synthesis disappeared by the fourth day. When wound fluid PIIINP was assessed, high concentrations were found in reincisions of wounds for up to 5 months after the previous operation. The acceleration was also lost more slowly during the first postoperative week. The duration of a high rate of type I collagen synthesis compares well with studies in experimental wounds which show increased gain of strength if they are made not more than 6 weeks after previous surgery. The longer activity of the metabolism of type III collagen related antigens could reflect their function in the regulation of collagen fibril formation.
Autologous blood transfusion in surgery for cancer has been avoided because of the metastatic potential of reinfused malignant cells. This study determined whether viable tumour cells remain in the red cell concentrate after separation and whether blood transfusion filters remove these tumour cells before reinfusion. Units of banked blood were inoculated with tumour cell lines: breast cancer SKBr3; colon cancer COLO 320; lymphoma Daudi; erythroleukaemia K562. After processing with the Cell Saver, aliquots of the red cell concentrate and waste saline wash were examined for tumour cells and cultured. Tumour cells from all four cell lines were identified in the red cell concentrate but not in the waste saline wash. All the cell lines except Daudi grew from the red cell concentrate. Experiments on two of the cell lines (SKBr3 and COLO 320) were performed in which the red cell concentrate was either unfiltered (control) or filtered with SQ40S blood transfusion filter or RC100 leucocyte depletion filter. Both cell lines were present in the control samples and after filtration with SQ40S filters, and cells from these samples grew normally in culture. No tumour cells were evident after filtration with the RC100 filters and no growth of either cell line was found after 1 week in culture. The Cell Saver in combination with RC100 filters may be suitable for use during the surgical treatment of malignant disease.
In all, 1490 patients underwent splenectomy in Western Australia between 1971 and 1983, giving 7825 person years exposure. Thirty-three patients developed severe late postsplenectomy infection (septicaemia, meningitis or pneumococcal pneumonia requiring hospitalization) and three developed overwhelming postsplenectomy infection. The incidence and mortality rates of severe late postsplenectomy infection were 0.42 and 0.08 per 100 person years exposure respectively and for overwhelming postsplenectomy infection the incidence and mortality rates were 0.04 per 100 person years exposure. There were 628 splenectomies after trauma, giving 3922 person years exposure. Eight patients developed severe late postsplenectomy infection of whom one had overwhelming postsplenectomy infection. Following trauma, the incidence of severe late postsplenectomy infection was 0.21 per 100 person years exposure, with the incidence and mortality rates of overwhelming postsplenectomy infection being 0.03 per 100 person years exposure. Patients undergoing splenectomy have a 12.6-fold increased risk of developing late septicaemia compared with the general population. Splenectomy following trauma gives an 8.6-fold increased risk of late septicaemia. The majority of severe late postsplenectomy infections did not occur within the first 2 years and 42 per cent of severe late postsplenectomy infections occurred greater than 5 years after splenectomy. The low incidence of severe late postsplenectomy infection and overwhelming postsplenectomy infection makes statistical evaluation of the effectiveness of prophylactic antibiotics, vaccination and splenic repair most difficult.
The mechanisms by which graduated compression stockings prevent deep vein thrombosis are not completely understood. Recent work has suggested that venous distension plays a role in initiating the process. Our previous work has shown that the deep veins of the lower limb distend in patients undergoing surgical procedures. We have investigated 40 patients receiving surgical treatment on the abdomen or neck. A medial gastrocnemius vein was studied using ultrasound imaging during the operations. In half the patients a graduated compression anti-embolism stocking was applied to the limb under study at the start of the operation, immediately after initial measurements of vein diameter. The median vein diameter in both groups was the same at the start of the operative procedures (control, 2.6 mm, interquartile range 2.1-3.3 mm; stocking, 2.6 mm, interquartile range 2.1-3.7 mm). After application of a stocking the median diameter in this group fell to 1.6 mm (interquartile range 1.3-2.8 mm) and then decreased slightly at the end of the operation. In the control group the vein diameter increased to 2.9 mm (interquartile range 2.3-4.0 mm) during the operative procedure.
Twenty-nine patients with advanced carcinoma of the bile duct or gallbladder underwent combined portal vein and liver resection. Segmental excision of the portal vein was performed in 16 cases and wedge resection of the vessel wall in 13. The operative mortality rate was 17 per cent. The median survival for the 24 patients who left hospital was 19.8 months. Actuarial survival rates at 1, 3 and 5 years for all 29 patients were 48 per cent, 29 per cent, and 6 per cent respectively, whereas the median survival for 46 patients with unresectable carcinoma was 3 months and the 1 and 3-year actuarial survival rates were 13 per cent and zero respectively. This difference in survival times between patients undergoing hepatectomy with portal vein resection and those with unresectable carcinoma were statistically significant (P less than 0.01). Combined portal vein and liver resection is recommended as a reasonable surgical approach in selected patients with advanced carcinoma of the biliary tract.
The brain weight and brain structure volumes of galliform and passeriform birds were calculated and related to body weight. The total brains and 14 brain regions were investigated in order to calculate factors by which these structures in passeriforms exceed those in galliforms in size. The larger passeriform brains have larger telencephala, especially ventral hyperstriata and neostriata. The enlargement of total brain and telencephalon resembles that in primates, compared to insectivores, within mammals. The enlargement of the ventral hyperstriata + neostriata in passeriforms is fundamentally similar to that of the isocortex in mammals: it reflects an expansion of multimodal integrational capacities, as the ventral hyperstriatum and neostriatum are occupied exclusively or primarily by multimodal integrational areas as is the isocortex.
To compare the ongoing electrical activity in possibly homologous structures of reptiles and mammals, the electrographic activity (micro-EEG) from major parts of the cortex of unanesthetized turtles (Pseudemys) and geckos (Gekko) was recorded with and without acute and chronic stimuli, physostigmine and atropine. Electrodes were placed in the medial cortex (MC) and in the dorsal cortex (DC), the possible homologs of the mammalian hippocampus and transitional or/and isocortex, respectively. The resting corticograms (1-50 Hz) are different in the two cortical areas. Both are wide-band; power falls steadily with frequency above a single maximum about 2 Hz. The MC has a nonrhythmic, low-voltage activity with occasional superimposed large sharp waves (LSWs), generally biphasic, 100-300 microV and lasting 0.25-0.75 s. The DC has smaller amplitudes (ca. 3-6 dB) at all frequencies and fewer LSWs. Reptilian LSWs are reminiscent of mammalian hippocampal sharp waves or spikes, a correlate of decreased arousal. The immobility-related rhythmic slow activity (theta), so characteristic of the hippocampus in a number of mammals, was not found in the cortex of either species of reptile under a variety of conditions. We cannot exclude the possibility of movement-related theta waves. Physostigmine injection does not produce theta, although it acts like an arousing stimulus, producing a disappearance of the LSWs and a substantial increase in the amplitude of the frequencies 12-24 Hz; these changes were more obvious in the DC. Atropine reversed the effects of physostigmine. Theta may represent a trait of the more highly differentiated hippocampal field of mammals. The condition represented by these reptiles, in which the EEG differs between parts of the pallium but without theta or reciprocal changes in the MC and DC, may be an earlier evolutionary stage. A distinctive reptilian EEG is not recognizable in Pseudemys and Gekko, but a number of differences from the EEG in familiar mammals are shared by these two neurologically quite different reptiles.
When an object is held stationary in the center of the receptive field of a tectal neuron in a toad and a textured background is moved for a period of time, some neurons produce a burst of discharges immediately after the movement of the background ceases. This effect was first found in a recent study and temporarily called 'neuronal motion after-response'. A total of 66 tectal neurons in toads were examined, and 29 out of them showed the effect. In the different neurons under investigation, the firing rate varied from a few spikes to discharges of very long duration. The appearance of the motion after-response was independent of either the object/background contrast (i.e. black against white vs. white against black) or the direction of the background movement. In order to induce this effect, however, the object must be of sufficient size, and the background must be moved for a sufficient length of time. For most tectal neurons, an 8 x 8 degree square was large enough to induce the motion after-response, but for several others, the size of the object had to be similar to that of the excitatory receptive field of the neuron. The duration of the background movement was also crucial: at least 20 s of background movement was necessary for the motion after-response to occur.
The distribution of the dipeptide carnosine was studied in the brain of the crested newt, Triturus carnifex, with immunohistochemical methods. Carnosine-like immunoreactivity (IR) is present in the cell bodies and processes of several areas of the central nervous system: in the telencephalon (especially in the medial pallium), in the diencephalon (pineal organ, thalamus, and hypothalamus), in the mesencephalon (optic tectum and tegmentum), and in the rhombencephalon (cerebellum, raphe region, and octavolateralis area). Double-labelling experiments show that carnosine IR is colocalized with tyrosine hydroxylase and neuropeptide Y IR in a few cells. Histochemical staining for heavy metals, the TIMM method, reveals that carnosine IR and TIMM labelling overlap in the medial pallium. These data indicate two primary conclusions: (a) In the crested newt brain, in contrast to those of mammals and birds, carnosine IR is not associated with glial cells but with neurons. Furthermore, carnosine is absent from the primary olfactory pathway in newts. (b) In the medial pallium of the crested newt, carnosine IR reliably identifies a population of neurons.
Microinjections of oxytocin and of an oxytocin antagonist into the dorsal vagal complex of the medulla oblongata were performed in order to study the possible role of the oxytocin containing axons that innervate this region in the regulation of pancreatic insulin secretion. No significant effect was produced by the intramedullary injection of the oxytocin vehicle alone or of 0.04 pM oxytocin. Injections of 4 and 20 pM oxytocin produced a reversible decrease of plasmatic insulin levels which fall to 59% of basal levels 15 min after the injection. Such an effect was abolished when 4 pM oxytocin was injected to animals which have been previously bilaterally vagotomized. In contrast to oxytocin, intramedullary injection of a specific antagonist of oxytocin to intact animals induced a marked increase of plasmatic insulin levels which raised 131% of basal levels 15 min after the injection. In animals receiving such an injection of oxytocin antagonist, a secondary injection of 4 pM oxytocin produced a slight but not significant decrease of plasmatic insulin levels. These data strongly suggest that the hypothalamic neurons producing oxytocin that densely project to the dorsal vagal complex may be involved in an inhibitory control of the vagal preganglionic neurons that innervate the pancreas.
The ability to bind iodine-labelled human growth hormone ([125I]hGH) was measured in different parts of the human brain. The choroid plexus contained the highest amount of binding sites (receptors) and was therefore selected for further studies. The binding between [125I]hGH and the receptor was saturable, of high affinity (Ka = 0.63 nM-1) and pH- as well as time-dependent. After solubilization with Triton X-100 the receptors retained their hormone-binding properties and eluted in the high molecular weight range (greater than 500,000) upon molecular sieve chromatography. Analysis by an affinity cross-linking technique indicated a hormone-binding unit of molecular weight 51,000. The molecular characteristics of the identified binding sites are discussed in comparison to those of growth hormone receptors of human and animal origin.
The inhibitory potency of ethanol upon excitatory amino acid induced depolarizations of rat hippocampal CA1 pyramidal cells was assessed in the presence and absence of magnesium (Mg2+) using the grease-gap technique. Ethanol shifted the N-methyl-D-aspartate (NMDA) dose-response curves to the right in a non-parallel manner. In the presence of Mg2+, ethanol appeared to be a more effective NMDA antagonist (IC50 47 mM) than in the absence of Mg2+ (IC50 107 mM). The IC50 for ethanol upon non-NMDA mediated CA1 pyramidal cell depolarizations was in excess of 170 mM. These results strongly suggest a preferential inhibitory action of ethanol against NMDA, rather than non-NMDA, mediated responses. Experiments in which ethanol and Mg2+ were covaried indicated that these substances act by two distinct mechanisms to antagonize the action of NMDA. These effects of ethanol, at concentrations which elicit intoxication (less than 50 mM) but not anesthesia, suggest that the NMDA receptor complex may play an important role in the acute effects of ethanol.
Most of the literature suggests that in sheep as in rodents nervous structures involved in female sexual behaviour are not necessarily identical to those involved in the LH surge. In rodents, oestradiol triggers female sexual behaviour by acting on a restricted area of the mediobasal hypothalamus whereas the concomitant induction of the preovulatory LH surge is at least partially under the control of more anterior structures. The central sites of oestradiol action, however, remained poorly defined in sheep. To provide this definition, 37 ovariectomized ewes were stereotaxically implanted unilaterally or bilaterally with a guide cannula in preoptic area (POA), anterior, mediobasal, lateral, or posterior hypothalamus (AH, MBH, LHT, PH). Experiments were made during the breeding season (Br) and the anoestrous period (An: unilat only) and females were primed with a peripheral treatment of progesterone and a dose of 17 beta-oestradiol subthreshold for both the LH surge and sexual behaviour. Intracranial implants (i.d. = 0.45 mm) of crystalline E2 were lowered 16 h after progesterone removal and left in the brain for 48 h. Whereas POA implants never had any significant effects on either the behaviour or the LH surge, all MBH implants caused receptivity (11 bilat, 5 unilat Br and 5 unilat An). Bilateral MBH implants also induced proceptivity in 9 of 11 ewes and increased the LH levels in 7 of them. These proportions do not differ significantly from those observed after a 25 microgram peripheral injection of E2. Unilateral MBH implants had no significant effect on proceptivity and LH increase but oestrous behaviour was induced by some implants placed laterally to the MBH (25 recept and 3/5 procept).(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of noradrenergic, serotonergic and dopaminergic drugs, and their interaction were studied in 8 adult spinal cats during the first week following spinalisation and up to 3 months, when the animals had reached a steady state in their locomotor pattern. During the first week, when no episodes of coordinated stepping were observed, injection of the serotonergic precursor (DL-5-HTP) or a dopaminergic agonist (apomorphine) failed to induce locomotion. In contrast, injection of either a noradrenaline precursor (L-DOPA) or an agonist (clonidine) induced locomotion when the hindlimbs were placed on a moving belt. The spinal animal demonstrated a bilateral foot placement on the plantar surface, as well as transient weight support of the hindquarters at a treadmill speed up to 0.80 m/s. The movement pattern and the electromyographic activity resemble those of the intact cat in many aspects. This locomotion-triggering effect of L-DOPA or clonidine was also observed when given after DL-5-HTP or apomorphine. At around 3 months following spinalisation, when the animal showed a stable and regular locomotor pattern, injection of clonidine increased the step cycle duration, resulting in a prolonged flexor and extensor burst duration as the EMG amplitude was unchanged or slightly increased. Injected in the same animal, quipazine, a serotonergic agonist, increased both the duration and the amplitude of flexor and extensor EMGs. In contrast to the serotonergic and the noradrenergic agonists, apomorphine and L-DOPA augmented mainly the flexor activity which could even lead to a sustained flexion when the dose was increased. When combining clonidine to a serotonergic drug, the characteristics of the modulation of the locomotor pattern resulting from each drug were retained. The present results demonstrate that (1) the noradrenergic system is probably the most important system for the initiation of locomotion; (2) the three monoaminergic descending systems (mimicked by the precursor and agonists) can modify rather specifically different aspects of the well established locomotor pattern in the same chronic spinal cat and (3) the effect of monoaminergic drugs are reproducible when given in similar time periods in different chronic spinal cats. The present study provides insight into the role of the noradrenergic, serotonergic and dopaminergic system in the initiation and in the modulation of the locomotion pattern following spinalisation. The above studies also provide a basis to investigate the effects of these drugs in spinal cord-injured patients.
We analyzed the membrane potential of 161 respiratory neurons in the medulla of decerebrate rats which were paralyzed and ventilated. Three types of inspiratory (I) neurons were observed: those displaying progressive depolarization in inspiration (augmenting I neurons), those which gradually repolarized after maximal depolarization at the onset of inspiration (decrementing I neurons) and those exhibiting a plateau or bell-shaped membrane potential trajectory throughout inspiration (I-all neurons). Three types of expiratory (E) neurons were also encountered: those in which the membrane potential progressively depolarized (augmenting E neurons), those in which the membrane potential repolarized during the interval between phrenic bursts (decrementing E or post-I neurons) and those exhibiting a plateau or bell-shaped membrane potential trajectory throughout expiration (E-all neurons). Axonal projections of these medullary neurons were identified in the cranial nerves (n = 34), or in the spinal cord (n = 19) as revealed by antidromic stimulation and/or by reconstruction following horseradish peroxidase (HRP) labeling. The other 108 neurons were not antidromically activated (NAA) by the stimulations tested, or had their axons terminating inside the medulla as revealed by HRP labeling. All these respiratory neurons, except for 3 which were hypoglossal motoneurons, had their somata within the ventrolateral medulla, in the region of the nucleus ambiguus, homologous to the ventral respiratory group (VRG) of the cat. No dorsal respiratory group (DRG) was detected within the medulla of the rats. Due to this absence of a DRG, it is concluded that the neural organization of respiratory centers is quite different in cats and rats.
Many recent studies have implicated the mesolimbic dopaminergic pathway as the central neurotransmitter system which is most likely responsible for the euphoria and abuse potential associated with cocaine self-administration. Nevertheless, cocaine also has well established interactions with the norepinephrine- and serotonin-containing pathways of the brain. In order to begin assessing potential non-dopamine-mediated actions of cocaine in central circuits, we have initiated a series of experiments using the cerebellar Purkinje neuron as an electrophysiological test system. The strategy was to use the same experimental protocols employed in previous investigations of noradrenergic influences on putative amino acid transmitter action to examine the effects of exogenously applied cocaine on gamma-aminobutyric acid (GABA)-induced depressant responses of Purkinje cells. Accordingly, the inhibitory responses of Purkinje neurons to microiontophoretically applied GABA were examined before and after systemic or local iontophoretic administration of cocaine. Drug-induced changes in the spontaneous firing rate and GABA responsiveness of individual cells were assessed by quantitative analysis of perievent histograms. The results indicate that, like norepinephrine, cocaine at parenteral or iontophoretic doses subthreshold for producing direct suppression of spontaneous discharge can augment Purkinje neuron responses to GABA. Such potentiating effects of cocaine on GABA-mediated inhibition were not evident in animals pretreated with the selective noradrenergic toxins DSP-4. These findings indicate that cocaine can enhance central neuronal responsiveness to GABA in a manner identical to that shown previously for norepinephrine. Such actions in noradrenergic target circuits throughout the brain could contribute to the net behavioral response observed following cocaine administration.
We examined whether testosterone (T) administered to female ferrets neonatally--a treatment known to enhance masculine coital capacity--induces formation of the sexually dimorphic male nucleus in the dorsal preoptic/anterior hypothalamic area (MN-POA/AH), and/or sensitizes dorsal POA/AH neurons to the stimulatory effect of later androgen treatment on somal dimensions. In males, the MN-POA/AH was present in all subjects, and exposure to androgen following castration at postnatal day 56 (P56) increased both MN-POA/AH volume as well as mean somal areas of MN-POA/AH neurons relative to oil-treated controls. Females given androgen from P5 to P20 and for one month beginning after ovariectomy on P56 failed to develop the MN-POA/AH, but displayed high levels of masculine sexual behavior. Somal areas of dorsal POA/AH neurons in females that received either T or a control neonatally did not increase following androgen treatment at P56. Thus, the correlation that exists between somal enlargement of dorsal POA/AH neurons and masculine sexual behavior in androgen-treated males is not found in behaviorally masculinized females. Masculine coital ability does not appear related to aspects of dorsal POA/AH morphology, supporting data from a previous study in which lesions of the MN-POA/AH caused negligible deficits in masculine sexual behavior of adult male ferrets.
A large number of estradiol-concentrating cells were visualized by autoradiography in a subpopulation of large neurons located in and around the sexually dimorphic male nucleus of the preoptic/anterior hypothalamic area (MN-POA/AH) of castrated male ferrets and in a comparable dorsal portion of the POA/AH of ovariectomized females. Considerably fewer estradiol-labelled cells were seen in the non-dimorphic ventral POA/AH nucleus of both sexes. Estrogen binding in cells in or around the MN-POA/AH may contribute to the formation of this sexually dimorphic nucleus in fetal males and may mediate specific estrogen-dependent behavioral functions in adulthood.
In order to study the role of trace elements as potential osteoblastic toxins, we measured bone aluminum, copper, and iron in 106 ambulant patients with histologically proven liver disease. We used analytical and histochemical methods and we correlated our results with serum biochemistry, forearm and spinal bone density, and dynamic bone histomorphometry. Patients with chronic liver disease had higher iron-stained perimeters than control subjects (P less than 0.001). However, the mean iron-stained perimeter was no greater than 5% of the total mineralized bone perimeter and did not correlate significantly with either the osteoblast perimeters or bone formation rates. The mean concentration of bone iron were 2.5 times (P less than 0.01) greater in the patients than in the controls although 80% of the patients fell within the normal range. There was a weak negative correlation between bone iron and the osteoblast perimeters (R = 0.18, P = ns) and between bone iron and bone formation (R = -0.30, P less than 0.05). There were 57 patients (56% of the total) with diminished bone formation, but only 16 had elevated bone iron concentrations. In a regression analysis, age, hypogonadism, and serum albumin concentrations were the most important predictors of osteoblast perimeters and bone formation rates. In vitro experiments using rat osteoblast-like osteosarcoma cells showed that an iron concentration of 400 mumol/liter was required to diminish cellular proliferation and function. Iron concentrations are elevated in the bones of patients with chronic liver disease. However, there is at present insufficient evidence that this metal is responsible for the osteoblast dysfunction seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The project concerned social and psychological treatment of patients with chronic health injuries of medium-severe character as a consequence of work with organic solvents. The treatment involved the spouse of the patient and their children, and took place in the family's home, often together with the family doctor, the children's teachers and other people. At a first step, the preliminary examinations have been carried out in the Clinic of Occupational Medicine, Aalborg Hospital, and a diagnosis has been made. In the light of the examinations, patients and their families were selected. The 19 patients and their families participated in the treatment for about 6 months. In other words, the project was divided into four phases, each dealing with 5 patients and their families. The treatment concerned the health status of the patients and the social, psychological and financial situation of their families as well. The results were better when the treatment followed immediately the diagnosis.
Bone mineral density (BMD) was determined in 32 excised vertebrae using three methods: (1) dual-energy quantitative computed tomography (QCT), (2) dual-photon absorptiometry (DPA) with 153-Gd in an anteriorposterior projection and (3) scanning slit X-ray absorptiometry (SSXA) in both AP and lateral projections. The QCT region-of-interest in the anterior vertebral body had a lower density than that of the total trabecular portion of the body, but was highly correlated to this larger region (r = 0.96; SEE = 8 mg/cm3). The anterior QCT region also correlated moderately with BMD from DPA (r = 0.77; SEE = 18 mg/cm3). Measurements of the vertebral body in lateral projection were less well correlated (r = 0.5-0.7) to QCT densities. Both the anterior QCT region (r = 0.81; SEE = 18 mg/cm3) and the BMD from DPA (r = 0.86; SEE = 16 mg/cm3) and the BMD from DPA (r = 0.86; SEE = 16 mg/cm3) were similarly predictive of density of the integral vertebral body. Differences among densitometric methods on the spine depend on the projection used and the region examined.
Since the independence in 1956, the health sector has scored a great deal of progress. Such a development has been observed also in other developing nations. The country is now facing a crucial issue. On one hand the resources devoted to the health sector are ever increasing and are likely to reach the limits acceptable to the national economy. On the other hand the citizens are seeking for more and better care and are no longer satisfied with the care and health insurance provided to them. On this background, the inequalities of health resources between the regions and areas of the country add an other aggravating factor.
Osteoporosis is one of the most common complications of streak gonad syndrome (SGS), however its pathogenesis is still unclear. Bone Gla protein (BGP) has been found to be a serum marker of bone turnover in various metabolic disease states. In the present study serum BGP and alkaline phosphatase (AP) were measured in 13 osteoporotic patients with SGS and in 56 healthy women. Mean (+/- SD) serum BGP levels were normal (7.5 +/- 2.0 ng/ml) in seven patients who had been on estrogen-progestin replacement therapy and became significantly elevated (P less than 0.001) 2 and 3 months after discontinuation of the treatment (15.3 +/- 2.3 and 13.2 +/- 1.0 ng/ml, respectively). Mean (+/- SD) serum AP (207 +/- 65 U/l) showed significant increases (P less than 0.05) 2 months after withdrawal of hormonal substitution (287 +/- 74 U/l). Mean (+/- SD) serum BGP (15.4 +/- 3.5) and AP (287 +/- 49) levels were significantly higher (P less than 0.001 and less than 0.05, respectively) in six patients with SGS who had not been on hormonal substitution. These findings are consistent with those obtained in postmenopausal women suffering from "high remodelling osteoporosis" and suggest that bone turnover in osteoporotic patients with SGS is increased and the skeletal loss is a consequence of accelerated bone loss rather than decreased bone formation.
Dual-energy X-ray absorptiometry (DEXA) and single-photon absorptiometry (SPA) were used to quantitate the structural strength and local material properties of healing tibial osteotomies in 32 dogs. Dogs were divided into four equal groups, euthanatized at either 2, 4, 8, or 12 weeks, and imaged with DEXA and SPA. Invasive techniques were used to determine (1) the torsional properties of the bone, (2) the local stiffness properties and calcium content within the bone, and (3) new bone formation and porosity by histology. There were no differences between SPA and DEXA in their associations with the torsional properties of bone. SPA and DEXA had strong correlations with the ultimate torque (R2 = 0.76, 0.51) and the torsional stiffness (R2 = 0.68, 0.53) of bone. SPA and DEXA of periosteal callus, endosteal callus, and cortical bone had similar associations with indentation stiffness, calcium content, new bone formation, and porosity. SPA of gap tissue had significantly stronger associations with these four parameters than DEXA (P less than 0.05). Correlation coefficients (R2) with these local material properties ranged as high as 0.82 for SPA with new bone formation in the gap tissue and 0.73 for DEXA with indentation stiffness of periosteal callus.
The mechanism of calcification in bone and related tissues is a matter of current interest. The mean size and the arrangement of the mineral crystals are important parameters difficult to obtain by electron microscopy. Furthermore, most studies have been carried out on poorly calcified model systems or chemically treated samples. In the work presented here, native bone was studied as a function of age by a quantitative small-angle X-ray scattering method (SAXS). Bone samples (calvariae and ulnae) from rats and mice were investigated. Measurements were performed on native bone immediately after dissection for samples up to 1 mm thick. The size, shape, and predominant orientation of the mineral crystals in bone were obtained for embryonal, young, and adult animals. The results indicate that the mineral nucleates as thin layers of calcium phosphate within the hole zone of the collagen fibrils. The mineral nuclei subsequently grow in thickness to about 3 nm, which corresponds to maximum space available in these holes.
Laser Doppler Flowmetry (LDF) has been shown to be a useful tool in the experimental and clinical measurement of bone blood flow. Two LDF receiving fiber channel systems, one with a 2mW He-Ne tube laser source and the other with an infrared diode laser source, were compared with specific reference to their light attenuation through three types of bone as well as their threshold thickness for the same specimens. The threshold thickness was higher for the infrared diode system for all three bone types whereas the attenuation was identical. The demonstrated differences were most likely due to the criteria established for flow detection; the infrared diode system has a greater degree of amplification of the output signal, yielding a higher value at each thickness of bone. The two systems will produce similar output data when used for experimental analysis of bone blood flow.
Study of crystals of calcium oxalate monohydrate grown from gels exposed to 0, 5.6x, 12.5x, 26.2x, 52.5x, 100x, 200 x 10(-7) M nephrocalcin indicate that this protein profoundly affects their habit, size, and crystal structure. By the time nephrocalcin concentration is 26.2 x 10(-7) M calcium oxalate monohydrate undergoes a phase change in its basic structure and both crystal size as well the resolution of its diffraction pattern are severely curtailed. These effects are magnified when the protein is 52.5 x 10(-7) M, since long-range disorder becomes extreme and, out of the entire diffraction pattern, only the 0k0's, h00's and a few other nonaxial reflections remain from the ordered part of the crystal structure. Finally, once the concentration of nephrocalcin is raised to 100 and 200 x 10(-7) M, growth is so inhibited that calcium oxalate monohydrate no longer grows as distinct individuals but rather as aggregates of very small crystallites. All of this is caused by the ability on the part of nephrocalcin to disturb the juxtaposition of the (101) layers along c by disrupting the organization of both the C(3)-C(4) oxalate groups and the water molecules. Such interaction is modulated by the efficiency with which nephrocalcin adsorbs upon the (101) planes; this process is stereospecific.
Localization of a approximately 66 kD glycosylated phosphoprotein during morphogenesis of the embryonic chick tibia has been accomplished using immunohistochemistry. Although initial expression of the tibial osteoblast phenotype is detected as early as stage 28.5, with the deposition of osteoid matrix beginning at stage 30, little or no immunoreactivity against the approximately 66 kD glycosylated phosphoprotein is observed in pre-osteoblasts, osteoblasts, osteocytes, or in the uncalcified osteoid matrix during the early events of tibia development. Immunoreactivity was first observed at stage 32 when mineralization of the osteoid matrix is initiated. At this and all later stages, the phosphoprotein is located almost exclusively in the extracellular matrix at the mineralization front with essentially no detectable staining in the adjacent unmineralized osteoid matrix. Similarly, no cellular staining is observed when even the lightly mineralized extracellular matrix is strongly immunoreactive. Only scant immunostaining is present over the heavily mineralized regions, although demineralization of these areas with EDTA exposes a low intensity, punctate staining pattern. Additionally, cryosections of developing calvaria stained with this antiserum only display reactivity in regions of bone matrix undergoing mineralization. These localization studies support the hypothesis that this phosphoprotein is intimately associated with the process of bone matrix mineralization in the developing chick long bone.
Serum levels of creatine kinase isoenzyme BB (CK-BB) were measured spectrophotometrically and by electrophoresis in 17 patients with autosomal dominant osteopetrosis (ADO) and compared with those of age- and sex-matched controls. Eight patients had ADO type 1 and nine patients had ADO type II. CK-BB was significantly increased (p less than 0.002) in type II but normal in type I compared with controls. This finding supports heterogeneity of ADO, and it may indicate a potential role for CK-BB as a marker of immature osteoclasts.
Calcium and phosphate were allowed to diffuse into gelatin and Type I collagen gels which were then cut into slices and analyzed for ion concentrations. Solutions of calcium and phosphate were then prepared, with ion concentrations equivalent to the highest levels in the slices, and mixed together, whereupon a rapid and copious precipitation of hydroxyapatite (HA) was observed. In contrast, HA bands were not visible in the gels until 1 to 2 1/2 days after analysis. These results indicate that Type I collagen exerts a considerable inhibitory effect on HA proliferation, probably by steric blockage of nuclei and crystal formation and growth. It thus appears that Type I collagen should be added to the list of agents that perform a regulatory role in bone mineral formation.
To determine whether individuals exhibiting the type A behaviour pattern have a different extent of prostacyclin or thromboxane production after relaxation or after a structured interview compared to individuals exhibiting the type B behaviour pattern.
Subjects were randomized to receive prospectively either a relaxation session or a mildly stressful interview first. Each then received the alternate treatment second.
Students attending an introductory psychology course at the University of Manitoba received a relaxation session (20 mins lying down listening to a tape) and an interview session (the structured interview of Rosenman).
Type A/B behaviour pattern was rated using the structured interview of Rosenman. Production of 6-keto prostaglandin F1-alpha and thromboxane B2, metabolites of prostacyclin and thromboxane A2, respectively, were measured in response to a standardized vascular injury-bleeding time.
No significant differences were observed in the length of bleeding time, in bleeding time thromboxane production or in prostacyclin production after relaxation between individuals exhibiting type A and B behaviour patterns. Prostacyclin production after the interview was lower in type A individuals (3.29 +/- 0.29 pg/min) than in individuals exhibiting type B behaviour (4.76 +/- 0.63 pg/min) (P = 0.04). No significant post interview differences in bleeding time or in thromboxane production were seen.
After relaxation, type A and B subjects are similar in their prostacyclin and thromboxane responses to vascular injury. However, type A individuals show a less favorable prostacyclin response than type B when confronted with the structured interview; type A individuals responded in an aggressive or hostile fashion, while the type B individuals exhibited a more relaxed response.
This study was conducted to determine the value of propafenone in patients with resistant malignant ventricular arrhythmias. Forty patients with either sustained ventricular tachycardia (n = 34) or primary ventricular fibrillation (n = 6), who had failed an average of four previous drug trials, were studied prospectively. The mean age was 68 years. Thirty-five had had a previous infarction, and left ventricular ejection fractions ranged from 14 to 57% (mean 36%). Noninvasive evaluation, consisting of ambulatory monitoring and exercise testing, was used to guide therapy in 12 patients, and invasive electrophysiological study was employed in the other 28. The initial daily dose was 450 mg, and electrocardiographic intervals were used to titrate the dose upward to a maximum of 900 mg per day or to tolerance. Five of the 12 noninvasively studied patients had complete abolition of ventricular tachycardia salvos. Only five of the 28 patients were rendered noninducible, but another four had adequate rate slowing with good hemodynamic tolerance of their arrhythmias. In an additional six patients, the addition of a second antiarrhythmic drug produced supplemental rate slowing. Side effects occurred in 30 patients and necessitated drug withdrawal in 13. The most serious adverse effects were congestive heart failure (in eight patients, and three withdrawn) and proarrhythmia (in four patients, and all withdrawn). The 20 patients with an adequate response were discharged on propafenone. During a mean follow-up of 12 months, there have been three cardiac deaths, one of which was sudden, and three recurrences of sustained ventricular tachycardia. Efficacy and side effects did not correlate with dose or degree of increase in electrocardiographic intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Almost exclusive use of Carpentier-Edwards porcine bioprostheses for cardiac valve replacement in 1194 patients between 1975 and 1987 at the authors' institutions has afforded the opportunity for a more scientific basis for prosthesis selection for subsets of patients, with regard to age and valve-related complications. The present study, performed according to previously established guidelines, investigated the influence of patient age and valve position as determinants of durability of 1315 porcine implants in terms of the following valve-related complications: structural valve deterioration, nonstructural dysfunction, thromboembolism, antithromboembolic therapy-related hemorrhage and prosthetic valve endocarditis. Age groups were as follows: 35 years and younger, 36 to 50 years, 51 to 65 years, and 66 years or older. Thromboembolism was found to be less common in the younger age groups, and significantly less common in patients following aortic compared to mitral valve replacement. The age group assessment for antithromboembolic therapy-related hemorrhage, nonstructural dysfunction and prosthetic valve endocarditis revealed no difference between positions or age groups. Patient age was found to be the major predictor of, and inversely related to, structural valve deterioration. In addition, porcine bioprostheses in the aortic position were shown to have durability superior to that of similar valves in the mitral position. Structural valve deterioration has very little influence on valve-related mortality and residual morbidity. This study thus supports the implantation of porcine bioprostheses in somewhat younger patients than would be advisable for mitral prostheses. The authors now recommend the selective implantation of porcine bioprostheses in the aortic position in patients over 65 years of age, and in the mitral position in patients over 70 years of age.
Catheter ablation of ventricular tachycardia was performed in a patient without evidence of structural heart disease. ECG showed ventricular tachycardia and a right bundle branch block QRS configuration with left axis deviation induced by exercise and atrial pacing. At electrophysiology, presystolic activation was found in the low septal region of the left ventricle. Radiofrequency energy delivered to this site failed to prevent tachycardia. Three direct current shocks (total energy 400 J) delivered in this region rendered the tachycardia noninducible. There were no complications. During the follow-up period of six months the patient has remained free from arrhythmia on no medication. This report expands the use of catheter ablation to patients with idiopathic ventricular tachycardia ('verapamil responsive' ventricular tachycardia) originating in the left ventricle.
Leiomyosarcomas are extremely rare primary cardiac tumours. A 46-year-old woman presenting with symptoms and signs of rapidly progressive left ventricular failure and apparent systemic lupus erythematosus was subsequently found to have a grade III/III left atrial leiomyosarcoma which was confirmed surgically. Pathology showed a cellular neoplasm arranged in fascicles with multinucleated giant cells, with areas of high grade sarcomatous change. The patient died seven months postoperatively with intractable heart failure. At autopsy, tumour infiltrated the pericardium, both atria and the right ventricle, with invasion of the diaphragm and posterior mediastinum. The current world literature is reviewed with respect to this rare and often misdiagnosed tumour.
Four coronary lesions, including a severe left main stenosis, were successfully dilated in a patient with poor left ventricular function; the procedure was supported by percutaneous cardiopulmonary bypass. During left main occlusion there was a loss of phasic systemic arterial pressure, while pulmonary arterial pressure was maintained. The ischemic myocardial depression occurring during left main occlusion was not prevented by percutaneous cardiopulmonary bypass, indicating inadequate myocardial protection.
Aortic valve insufficiency may occur in a number of backgrounds. A unique etiology is illustrated in a 53-year-old man with terminal cardiac failure due to ischemic heart and aortic valvular disease. Nodular calcification complicated a congenital bicuspid valve and caused erosion through a valve cusp, producing a chronic cusp defect and valvular insufficiency.
The authors present clinical experience with 28 cases of ruptured anterior cerebral artery (ACA) aneurysms managed personally during a 36 month period, and 10 unruptured ACA aneurysms. The cases included five giant aneurysms and four distal ACA aneurysms. Management strategy was uniform and included early operative intervention (except in the setting of deteriorating neurologic deficit, not attributable to hydrocephalus or hematoma), and vasospasm prophylaxis including calcium channel blockers and hypervolemic hemodilution and arterial hypertension. Modern diagnostic adjuncts including transcranial doppler were used as they became available. Good outcome (outcome grade 1 or 2) was observed at 6 months in 71% (20/28) of ruptured cases and in 90% (9/10) of unruptured cases; fair outcome (outcome grade 3) was observed in 14% (4/28) of ruptured cases and in 10% of unruptured cases; bad outcome (outcome grade 4 or 5) was observed in 14% (4/28) of ruptured cases. There were no instances of rebleeding after admission to the hospital. There was a single mortality in a patient moribund on admission. Delayed ischemic deterioration (DID) was documented in 46% (13 of 28) of the ruptured cases, and was a major source of morbidity in 7 of the 9 instances of fair or poor outcome in the series. Management outcome, including the occurrence of subtle neuropsychological difficulties commonly described in cases with ACA aneurysms, is discussed with relation to the incidence of DID, the clinical course of DID, and the possible impact of various therapeutic strategies.
Thiamine status was evaluated using the erythrocyte transketolase activation assay in 20 alcoholic patients admitted on a voluntary basis to a Detoxification Unit. Electromyographic evaluation revealed significant reductions of motor and sensory conduction velocities in the alcoholic group. 38% of alcoholic patients showed significant erythrocyte transketolase activation deficits indicative of severe thiamine deficiency. In the case of peroneal nerve, reduced conduction velocities were negatively correlated with abnormal transketolase parameters. These findings are consistent with a contributory (but not exclusive) role of thiamine deficiency in the pathogenesis of alcoholic peripheral neuropathy. Deficiencies of other vitamins as well as direct neurotoxic effects of alcohol could also be involved in this phenomenon.
The value of CT as a routine screening procedure in the investigation of cognitive impairment is being increasingly challenged. To address this issue, we reviewed the records of 175 patients with intellectual deficits admitted to a Behavioural Neurology Unit over a two-year period. In the vast majority of cases, ie. 82%, the CT served essentially to confirm the clinical impression and added no new diagnostic information that impacted the management of the presenting problem. In 15% of cases the CT scan was helpful for diagnosis, especially in the differentiation between Alzheimer's disease and multi-infarct dementia.
Mitral valve prolapse has been associated with an increased risk of transient or lasting ischemic events. Recurrence is uncommon after initiation of antiplatelet or anticoagulant therapy. In this communication we report two patients, both female, who had mitral valve prolapse as the major risk factor for cerebrovascular disease and who developed cerebral infarction despite anticoagulation. The cerebral infarctions were bilateral and extensive in one patient and led to the patient's death. In the second case, three infarctions resulted in moderate disability.
Cerebrovascular accidents due to Moyamoya disease, a disorder characterized by arterial stenosis at the base of the brain accompanied by typical net-like collateral vessels, occurred in two young Japanese women with Graves' disease when they were in thyrotoxicosis. In one patient, a second attack of cerebral infarction occurred with the recurrence of thyrotoxicosis. Association of Moyamoya disease and Graves' thyrotoxicosis is rare and the pathegenetic relationship is discussed.
220 patients with isolated and idiopathic spasmodic torticollis were followed and treated over a 14 year period. Each patient was given a short questionnaire leading to the present retrospective data analysis. In most areas, including female preponderance and frequency of postural tremor, the findings confirmed previous studies and highlighted particular points: importance of psychopathological antecedents and association with stressful life-events. The discussion deals with some of the conflicting debates surrounding this unusual disorder. What is the role of psychopathological factors? What is the therapeutic prognosis? The best therapeutic results were obtained by combining anticholinergic drugs, local injections and rehabilitation.
Three fundamental types of cephalic axial skeletal-neural dysrapic disorders are analyzed, including: cranioschisis aperta with encephaloschisis (anencephaly and/or exencephaly), cranioschisis occulta with occipital encephalocele, and the Chiari malformation (occipital bone hypoplasia) with compression, deformation and displacement of hindbrain, cerebellum, and medulla. Both clinical and experimental (vitamin A induced) examples of these malformations are used. The study establishes that these are not simple neurological (neural tube defects) disorders as it has been generally assumed, but complex developmental malformations affecting primarily the formation of the axial basicranium (causing skeletal defects) and the elevation of the neural folds and neurocranium (causing neural defects), and, secondarily, the topography of the facial skeleton or viscerocranium (causing oropharyngeal defects). The pathology of these skeletal, neural, and oropharyngeal defects is analyzed, their embryonic origin explored, and their developmental interrelationships discussed. The study proposes that an early paraxial mesodermal insufficiency may be the original anomaly common to all the different malformations that constitutes this heterogeneous group of dysraphic disorders. At any time during the segmental formation of the embryonic skeletal-neural axis a simple reduction in the number of paraxial mesodermal cells produced by the Hensen node/primitive streak complex, could impair the formation of the axial skeleton as well as the elevation of the neural folds thus interfering with their closure. The final type of malformation is determined by variations of the degree, time of occurrence, and duration of the paraxial mesodermal insufficiency.
Cerebral dysgenesis encompasses varied disorders of brain development. Based on the understanding of these conditions provided by histopathologists, embryologists, radiologists and developmental pediatricians, surgeons are able to appropriately assist in the care of these patients. The surgeon can offer assessment of the ventriculomegaly that commonly accompanies cerebral dysgenesis in addition to providing methods to control hydrocephalus, to reconstruct cranial and facial malformations and to remove dysfunctional tissue. For most patients, surgical intervention is only one of the many factors that determine developmental prognosis. Based on the foundation built by other specialists, this review discusses cerebral dysgenesis from the perspective of historical and current surgical interventions.
This review identifies the fundamental anatomical and physiological processes that provide the substrates of maturation in the developing nervous system. Cerebral malformations may be viewed from the perspective of aberrations in one or more of these processes. The maturational processes are generally sequential but with considerable temporal precision and overlap: 1) neuronogenesis and gliogenesis, including neural induction by the notochord and primary segmentation of the nervous system; 2) programmed cell death of excess neuroblasts and glioblasts; 3) neuroblast migration; 4) formation and growth of neurites; 5) development of membrane polarity and excitability; 6) synaptogenesis; 7) biosynthesis of neurotransmitters and other secretory products; and 8) myelination of axons. The anatomical and synaptic organization of the fetal brain differs greatly from the mature state. An excess of axonal collaterals, dendritic branches, spines and synapses are formed and later selectively deleted Transitory neurons, specialized glial cells, synaptic circuits and transient neurotransmitter systems serve as functional elements for a limited time. The clinical expression of these transitory features of the fetal brain are incompletely understood, particularly in the context of embryonic cerebral plasticity.
To compare the adverse effects, particularly generalized aching, of a trivalent, inactivated whole-virion vaccine (WVV) and split-virion vaccine (SVV) for influenza in hospital personnel.
Recipient-blinded study; first-time vaccinees were randomly assigned to receive either of the vaccines from one manufacturer in the 1989-90 influenza season. Subjects were asked to complete a symptom questionnaire during the 48 hours after immunization.
Annual influenza program for staff of a tertiary care children's hospital.
Volunteers were sought among approximately 2200 members of the hospital staff. Of the 358 vaccinated for the first time, 333 (93%) returned the questionnaire.
During the 48 hours after vaccination 13% of the SVV recipients reported generalized aching, as compared with 26% of the WVV recipients (p less than 0.01). Also, the SVV group reported fewer visible local reactions and more transient arm soreness, but the actual differences between the two groups were small. The occurrence of mild symptoms was equally common in the two groups (local reactions in at least 70% of cases, systemic reactions in at least 33%). In each group 1% of the subjects reported missing work because of the vaccination.
The use of SVV reduces the rate of the most objectionable of the common adverse effects of influenza vaccination. Therefore, as with children, it might be more acceptable to health care workers than the current use of WVV.
To describe trends in the use of acute care hospital services for diseases of the circulatory system in Ontario.
Observational study.
Information on diagnoses, procedures and demographic characteristics was obtained from routinely collected computerized abstracts of separations from all acute care hospitals in Ontario during 1979-80, 1983-84 and 1988-89. The data were combined with population estimates to calculate overall separation rates and rates specific for age, diagnosis and procedure. Resource intensity weights were used to estimate changes in resource use.
The overall separation rate increased by 3% and the resource-intensity-weighted separation rate by 12% from 1979-80 to 1988-89. The overall medical separation rate increased by 2%, whereas the surgical rate increased by 12%. The surgical separation rate increased among patients 55 to 79 years of age but decreased in all the other adult age groups. The separation rates for coronary artery bypass surgery and cardiac valve surgery increased rapidly among patients 65 years of age or older. The medical separation rate decreased for patients of all ages except those less than 5 years and those 80 years or more. The medical separation rates decreased by less than 1% for diagnoses related to ischemic heart disease (IHD) and increased dramatically for coronary artery revascularization.
The increasing elderly population has not resulted in large increases in acute care hospital utilization for diseases of the circulatory system. The impact of an aging population has been balanced by decreased utilization rates in the younger groups. The intensity of hospital care has risen primarily because of increases in surgical rates, especially in the elderly population. The large decrease in the rate of death from IHD over the past two decades has not been associated with similar decreases in acute care hospital utilization for this disorder.
Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting.
Ten patients with malignant pericardial effusion were treated with intrapericardial injection of OK-432 (penicillin-treated and heat-treated lyophilized powder of the substrain of Streptococcus pyogenes A3). After intrapericardial insertion of a catheter, a maximal volume of pericardial fluid was withdrawn with cytologic confirmation of malignancy. Five or 10 Klinische Einheit (KE) (KE is a unit used to express the strength of a preparation) of OK-432 diluted in 20 ml of saline was injected into the pericardial space in seven and three patients, respectively. It was repeated in case of reaccumulation. Seven patients were treated only once and the remaining three required a second treatment. Complete control of pericardial effusion was achieved in all patients for an average of 329 days (range, 54 to 790 days). Fever and chest pain were experienced in six and five patients, respectively, but were controlled with antipyretics. Two of three patients who received 10 KE of OK-432 experienced hypotension that was successfully controlled with vasopressor drugs with or without reaspiration of pericardial fluid. Rapid reactive reaccumulation of the pericardial fluid was thought to be a cause of hypotension. A follow-up computed tomography (CT) scan was performed in seven patients and a thickened pericardium was noticed in five; no patients had constrictive pericarditis. These results suggest that intrapericardial administration of 5 KE of OK-432 is an effective and safe treatment for malignant pericardial effusion.
Fifty-six previously untreated patients with biopsy-proven, locally advanced or metastatic and measurable adenocarcinoma of the pancreas were treated with the combination of a protracted intravenous infusion of 5-fluorouracil (5-FU) and low dose weekly bolus cisplatin administered continuously for 10 weeks followed by a 2-week rest period. The objective response rate was 16% with two patients (4%) achieving a complete response (confidence intervals, 8% to 29%). The median survival time for all treated patients was 5.8 months; however, 26% of all patients were alive at 1 year. Both median survival time and the proportion alive at 1 year exceed that of prior reports involving large patient groups, possibly due to better patient selection.
One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first-line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty-eight percent of the patients had short-term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).
Three hundred forty-five patients with Stage IB squamous cell carcinoma of the cervix were treated at the University of Michigan Medical Center from 1970 to 1985. The overall cumulative 5-year survival rate was 89% and the mean age was 44.6 years. In 213 patients undergoing radical hysterectomy the cumulative 5-year survival rate was 92%; 14 patients were explored for radical hysterectomy that was not performed due to high risk features and their survival rate was 50%. Ninety-seven patients underwent radiation therapy as initial treatment and had a 5-year survival rate of 86%. There was no significant difference when radiation therapy was compared with radical hysterectomy (P = 0.098). The survival rates for lesions 3 cm or smaller were 94% for radical hysterectomy and 88% for radiation therapy. When the lesion was larger than 3 cm, the survival rates were 82% with radical surgery and 73% with radiation therapy. Metastatic disease to lymph nodes was present in 26 of the 213 patients undergoing radical hysterectomy. When 1 to 3 nodes were involved 16 of 19 patients survived and when 4 to 10 nodes were involved 3 of 7 patients survived. The addition of radiation therapy did not influence survival. Complications were similar in both treatment groups. Fistulas occurred in 4 of 213 patients undergoing radical hysterectomy and 1 of 111 undergoing radiation. Second surgery for a complication was required in 6 of 213 patients undergoing radical hysterectomy and 7 of 111 undergoing radiation. Survival and complication rates in early stage squamous cell carcinoma of the cervix are equal with either radical surgery or radiation therapy.
A dose escalation study of daily oral etoposide and cisplatin was carried out on 22 patients with advanced cancer using starting doses of 20 mg/m2/d of etoposide given orally for 21 days and 80 mg/m2 of cisplatin given intravenously (IV) on day 1. A total of 40 courses were given. Myelosuppression was the major dose-limiting toxicity, with a maximum tolerated dose of 50 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. Doses of 40 mg/m2/d of etoposide for 21 days plus 80 mg/m2 of cisplatin for 1 day in four of eight courses (50%) were associated with Grade 3 or worse leukopenia that occurred between days 18 and 26. However, no Grade 3 or worse thrombocytopenia occurred at this dose level. Nausea and vomiting occurred in most patients at each dose level but were mild and could be controlled by antiemetics. Alopecia also occurred frequently. Significant mucositis (Grade 4) occurred in one patient, but no other toxicities were observed. Four partial responses that lasted from 1.3 to 5.8+ months were observed in patients with cervical (one patient), small cell lung (one patient), and squamous cell lung cancer (two patients); one of them had been heavily pretreated with platin analogue-containing regimens. The recommended doses for Phase II studies on this schedule are 40 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. A combination regimen on this schedule seems particularly effective in patients with etoposide-sensitive malignancies.
From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival.
This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05).
Estrogen receptors (ER) were examined in cytosol, nuclear potassium chloride (KCl) extractable fraction, and nuclear KCl unextractable fraction by the dextran-coated charcoal adsorption method in various gastric cancer tissue. The overall ER-positive rate in the cytosol and nuclear fraction was 19.2%. The maximum binding site (Bmax) was 36.0 to 175.0 fmol/mg of protein, and the dissociation constant (Kd) was 0.6 to 1.6 X 10(-9) in cytosol fraction. In the nuclear fraction, Bmax was 7.5 fmol/mg of DNA and Kd was 2.3 X 10(-9). Estrogen receptors were characterized in cytosol protein. In cytosol, the estrogen (E2)-ER complex was sedimented at approximately the 5S and 8S regions by 5% to 20% linear sucrose gradient centrifugation. A steroid specificity study of ER showed the presence of an binder in gastric cancer tissue. In conclusion, these results that gastric cancer tissue has E2 binding sites with the same biochemical characteristics as in breast cancer and endometrial cancer strongly suggest the hormonal dependency of gastric cancer.
The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.
Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.
In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hürthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men.
Sixteen cases of esophageal carcinoma invading the submucosa were analyzed in terms of growth patterns. Seven were classified into the massively penetrating (down growth) type, four into the superficially spreading (spreading growth) type, and five into the unclassified type. In the down growth type, the ratio of the submucosal area to the total (mucosa and submucosa) area was more than 0.2 (one fifth), and in the others that ratio was less than 0.2. The down growth type is characterized by a tendency toward elevated lesions, a high incidence of vessel invasions and lymph node metastasis, and a poor prognosis after surgery. Lymphatic and/or vascular invasions were recognized in six of seven cases, and the 5-year survival rate was 0%. In contrast, the spreading growth and unclassified types was characterized by superficial lesions, a low incidence of vessel invasions and lymph node metastasis, and a favorable prognosis. In only one with the spreading growth type was there lymphatic invasion. Three of the four with the spreading growth type survived over 5 years, and the other one with the spreading growth type and all of five with the unclassified type are alive without recurrences 15 to 52 months after surgery. Thus, growth patterns reflect well the prognosis of the submucosal carcinoma of the esophagus.
The immunoreactivity of monoclonal antibody (MoAb) B72.3 with ovarian serous tumors of borderline malignancy from 44 women who were pregnant, were on hormone medication containing a progestin, or were known to be in the secretory phase of the menstrual cycle, was compared with that of similar tumors of 32 patients who were not known to be in any of these three categories. All 76 borderline tumors expressed the tumor-associated glycoprotein (TAG-72) recognized by MoAb B72.3. Striking staining differences (P less than 0.0001) were observed between the hormone-related and the nonhormone-related tumors. Differences were also noticed between the staining of tumors from pregnant patients and that of previous, persistent, or recurrent tumors of the ipsilateral or contralateral ovaries when the same patients were not pregnant. Tumor MoAb B72.3 reactivity increased with progressive gestational age and fell to lower levels at term and during the postpartum period. Although it has been suggested by cell culture studies, enhanced TAG-72 expression in human tumors under hormonal stimulation has not been described before.
Peripheral blood from 167 B-chronic lymphocytic leukemia (B-CLL) and 119 reactive lymphocytosis (RLC) patients were analyzed to evaluate the immunophenotypic diagnostic value of mouse rosettes (M-rosette), and weak expression of monoclonal surface immunoglobulin (SIg). In B-CLL, 145 cases were M-rosette+ (86.83%), 135 surface immunoglobulin (SIg)+ (80.84%), and 117 M-rosette+ SIg+ (70.06%). Of 32 SIg- cases, 28 were M-rosette+; and of 22 M-rosette-cases, 18 were SIg+. By combining results of the two assays and accepting positivity of either one or both as sufficient for diagnosis, B-CLL was diagnosed in 163 cases (97.60%). CD5 was performed in 49 cases of the 167 with paired data for SIg and M-rosettes. By combining the results of the three assays and accepting positivity of any two or all three as sufficient for diagnosis, all 49 cases (100%) were diagnosed. Correlation analysis showed no significant association between M-rosette, SIg, and CD5 expression. The results demonstrate the independent expression of the three markers, and their complementary role in immunophenotyping B-CLL. In RLC, all 119 cases were T-lineage and SIg-, and 115 were M-rosette-, indicating the role of the two markers in differentiating B-CLL from RLC. Three of the four M-rosette+ T-RLC were subsequently diagnosed as B-CLL, suggesting the necessity of follow-up of such cases.
Clinicopathologic features and prognostic significance of duodenal invasion were studied in a retrospective study on 593 patients who underwent gastrectomy for adenocarcinoma in the antrum. The patients were grouped into three, according to the histologic extent of duodenal invasion: Group A (80 patients), obvious invasion beyond the pyloric ring; Group B (61 patients), invasion up to the pyloric ring; and Group C (452 patients), no evidence of duodenal invasion. Five-year survival rates in Groups A, B, and C were 7.9%, 31.6%, and 57.6%, respectively (P less than 0.001). Cox's regression analysis showed that duodenal invasion is an independent prognostic factor in cases of a gastric antrum carcinoma. Gastric cancer with duodenal invasion (Groups A and B) most often was infiltrative and the incidence of serosal invasion, lymphatic and vascular invasion, and lymph node metastasis was high. Duodenal invasion was direct through submucosal or subserosal layers or through submucosal lymphatics.
The authors describe a rapidly growing soft tissue tumor of predominantly histiocytic composition in an 8-year-old child. The tumor cells were identified as elements of the mononuclear phagocyte system by histologic, histochemical, immunologic, and electron microscopic study. Despite the presence of a minor fibroblastic component, the tumor did not conform to established criteria for a diagnosis of malignant fibrous histiocytoma. Formation of frequent desmosome-like intercellular junctions raised the possibility of dendritic reticulum cell differentiation, since the latter cells seem to be the only elements of the mononuclear phagocyte system that display such specialized cell junctions. The results of immunostaining were discrepant with those reported for normal dendritic reticulum cells, but the currently available information makes it doubtful that the entire neoplastic spectrum of dendritic cell differentiation can currently be diagnosed in surgical pathology.
In a prospective study of 262 consecutive patients with nasopharyngeal carcinoma (NPC), using computed tomography (CT) as their baseline evaluation, erosion of the base of the skull and intracranial extension into the middle cranial fossa were found in 31.3% and 12.2% of patients, respectively. Thirty-four of these patients had cranial nerve involvement at presentation; 30 of them had involvement of one or more of the third to sixth cranial nerves. Most cases of intracranial extension of tumor were accompanied by erosion of the base of the skull, but the reverse was not true. All patients with cranial nerve palsy involving the third to sixth cranial nerves had associated erosion of the ipsilateral base of the skull. The CT evaluation of patients with cranial nerve involvement who are believed to harbor NPC should include thin cuts of the base of the skull for detection of subtle bone erosion. This may be the only clue to the presence of a small NPC. The prognostic significance of cranial nerve involvement, base of the skull erosion, and intracranial extension of the tumor on the survival of the group of 84 patients who had T4 tumors was evaluated with regression analysis using the Cox model. Only cranial nerve involvement was found to be a significant factor influencing survival.
Twenty long-term survivors of childhood cancer underwent exercise echocardiography to evaluate possible late anthracycline-induced cardiac toxicity. Ten patients ages 10 to 20 years had received anthracyclines, and ten patients ages 8 to 27 years had not received anthracyclines as part of their medical regimen. Both groups had normal cardiac function at rest. Patients who had not received anthracyclines had a greater increase in M-mode shortening fraction (P less than 0.005), velocity of circumferential fiber shortening (P = 0.05), and Doppler aortic peak flow velocity (P = 0.01) than patients receiving anthracyclines. There were no significant differences in work performed, or increase in heart rate or blood pressure with exercise between the groups. These results suggest that subtle abnormalities in myocardial function exist which become apparent only after exercise in survivors of childhood cancer who have received anthracyclines and have normal resting cardiac function.
From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar.
The Area Committee on Microbiology of the National Committee for Clinical Laboratory Standards has responsibility for the development of guidelines and standards in the field of clinical microbiology. Through the consensus process, representatives from government, industry, and professional societies have developed standards on antibacterial susceptibility testing (M2, M7, and M11), antimycobacterial susceptibility testing (M24), quality assurance on commercially prepared microbiological culture media (M22), evaluation of production lots of dehydrated Mueller-Hinton agar (M6), and preparation and testing of fetal bovine serum for use as cell culture growth supplement (M25) and guidelines on bactericidal tests (M26), protection of laboratory workers from infections transmitted by blood, body fluids, and tissue (M29), blood film examination for parasites (M15), and development of in vitro susceptibility testing criteria and quality control parameters (M23).
Pneumocystis carinii has been recognized as a cause of pneumonia in immunocompromised patients for over 40 years. Until the 1980s, Pneumocystis pneumonia (pneumocystosis) was most often seen in patients undergoing chemotherapy for malignancy or transplantation. Infection could be prevented by trimethoprim-sulfamethoxazole prophylaxis; thus, it was an uncommon clinical problem. With the onset of the AIDS epidemic, Pneumocystis pneumonia has become a major problem in the United States because it develops in approximately 80% of patients with AIDS and because almost two-thirds of patients have adverse reactions to anti-Pneumocystis drugs. Thus, physicians and laboratories in any community may be called upon to diagnose and provide care for patients with Pneumocystis pneumonia. The classification of the organism is currently controversial, but it is either a protozoan or a fungus. P. carinii appears to be acquired during childhood by inhalation and does not cause clinical disease in healthy persons but remains latent. If the person becomes immunosuppressed, the latent infection may become activated and lead to clinical disease. Damage of type I pneumocytes by Pneumocystis organisms leads to the foamy alveolar exudate which is characteristic of the disease. Diagnosis is established by morphologic demonstration of Pneumocystis organisms in material from the lungs. Current efforts to find better anti-Pneumocystis drugs should provide more effective therapy and prophylaxis.