Permanent iodine-125 implant and external beam radiation therapy for the treatment of malignant brain tumors. Survival data of 114 patients treated for malignant brain tumors with 125I interstitial radiation therapy at Henry Ford Hospital, Detroit, Mich. (1986-1990), are presented. The first 64 patients were treated with temporary 125I implants with a total prescribed dose of 60 Gy at a dose rate of 40 cGy/h. In order to reduce the risk of injury to the surrounding normal tissue associated with high-dose brachytherapy, a new approach was initiated using permanent implants with a lower dose rate; 50 patients were treated after surgical resection with permanent implantation of 125I seeds at a lower dose rate of 4-7 cGy/h, with a total dose of 10,000-12,000 cGy, and concurrent external radiation therapy of 5,000 cGy. The rationale of this protocol was to increase the effectiveness of the low-dose-rate implant by a concurrent 'daily' boost of external radiation, thus inhibiting the proliferation of tumor cells during the protracted low-dose radiation treatment. Survival was compared between groups with permanent and temporary implants in terms of effectiveness in tumor control as well as impact on clinical condition. Low-dose-rate implant with concurrent external radiation therapy seems to offer the best chance for long-term survival without deterioration in the clinical condition.


Fractionated stereotactic radiotherapy for intracranial neoplasms. Fractionated stereotactic radiotherapy is a method which attempts to combine the radiobiological advantages offered by dose fractionation with a technique for focal delivery of radiation. At McGill University, fractionated stereotactic radiotherapy is given with a linear accelerator-based dynamic stereotactic radiosurgery unit. The first treatment is given using the stereotactic frame for target localization and head immobilization. Subsequent treatments are given using skin tattoos and laser alignment for target placement within the isocenter of the linear accelerator, and a modified portable halo-ring device is used for skull immobilization. Typically, a marginal dose of 42 Gy was prescribed at the margins of the lesion, divided in 6 fractions and given over a 2-week period. We report the pathological profile and treatment results in a series of 21 patients with a variety of intracranial tumors, treated in this manner between May 1987 and April 1990. Fractionated stereotactic radiotherapy appears to be a worthwhile procedure for the treatment of well-selected patients with intracranial neoplasms.


Template-guided stereotactic implantation of malignant brain tumors for interstitial thermoradiotherapy. A phase I trial of 25 patients with anaplastic astrocytoma or glioblastoma multiforme is described. Hyperthermia and radiation were delivered stereotactically by means of template-guided interstitial catheters loaded with ferromagnetic wires and then 192Ir seeds. Implant volumes ranged from 15 to 113 ml (mean 54 ml) involving 9-38 catheters (mean 18); parallel catheters used hexagonal spacing of 1.0-1.5 cm. Patient tolerance of these procedures was excellent. Postoperative morbidity due to additional mass effect or edema was low, but there has been one death and one complication of hydrocephalus, bleeding and symptomatic pneumocephalus, each.


Clinical and technical results from spinal stimulation for chronic pain of diverse pathophysiologies. Spinal stimulation has been indicated for pain of peripheral deafferentation, but not for low-back pain. Technical and clinical records of 241 consecutive spinal stimulator recipients were reviewed, including: peripheral deafferentation pain (n = 44); predominant pain of low back, postlaminectomy (n = 96), and predominant pain of leg(s), postlaminectomy (n = 48). The groups were not statistically different with respect to important clinical features. For the postlaminectomy syndromes, only the technical results correlated significantly with outcome. Spinal stimulation actually yielded results as good for the 'failed back surgery syndrome' as for peripheral deafferentation pain, because newer technical methods were proven to stimulate the low back predictably.


Stereotactic mesencephalotomy for pain relief. A plea for stereotactic surgery. Rostral mesencephalic reticulotomy (RMR) for pain relief was performed in 34 patients with intractable pain. Most of these patients have been followed for a long period of time postoperatively, the longest follow-up period being 11 years. Contrary to the commonly prevailed bias in the past that mesencephalotomy may be a surgical intervention with potential risk, these patients of RMR have continued to substantial improvement postoperatively in terms of their preoperative intractable painful dysesthesia after a long period of time. The results of pain relief for denervation pain as well as for nondenervation pain are surprisingly good even after unilateral procedures. There was no operative mortality. Postoperative disturbance of ocular motility has been reduced. RMR has its scientific basis in that the medial part of the reticular formation rather than the classical lateral spinothalamic tract has more significance in the central conduction of nociceptive impulses through the midbrain level, which was verified by intraoperative neuronal recording with a tungsten microelectrode. The present report emphasizes that stereotactic mesencephalotomy, if performed meticulously and precisely, is a safe surgical procedure for pain relief. Results of MRI and sensory manifestations of a patient 11 years after RMR are also presented.


Bilateral MRI-guided stereotactic cingulotomy for intractable pain. As a treatment of patients with intractable cancer and noncancer pain, bilateral radiofrequency cingulotomy was performed in 10 patients. The technique involved stereotaxis using magnetic resonance guidance and local anesthesia, with the placement of a radiofrequency lesion (75 degrees, 60s). Of the 10 patients, 8 had metastatic lesions with musculoskeletal (6) or neurogenic (2) pain. Pain relief was judged excellent (4 patients), fair (1), poor (2) and excellent for 6 months poor in the last patient. The two benign lesions were neurofibromatosis with neurogenic pain and thalamic pain from an old stroke. Pain relief (with 1 year follow-up) in this group was judged excellent in one and poor in the other (thalamic pain).


MRI findings of DREZ-otomy lesions.

MRI findings of DREZ-otomy lesions. Pre- and postoperative MR findings in the spinal cord of 4 patients who underwent lesioning of the cervical dorsal root entry zone (DREZ-otomy) are reported. In 3 patients with root avulsion, MR images revealed spinal cord atrophy preoperatively and, after DREZ-otomy, long-lasting spinal cord enlargement and extensive intramedullary changes. In a case without root avulsion, the preoperative MR study showed no apparent abnormality and the only postoperative MR change was a discrete lesion well confined to the dorsal horn. The findings suggested basically different post-operative pathology among patients with root avulsion and those without. MRI can be a useful supplement to autopsy study in defining postoperative spinal cord changes after DREZ-otomy.


Trigeminal nucleus caudalis dorsal root entry zone: a new surgical approach. New radiofrequency lesion dorsal root entry zone (DREZ) electrodes for relief of facial pain were designed based on a neuroanatomic study in man of the trigeminal nucleus caudalis at the cervicomedullary junction. The human brainstems of 3 normal postmortem specimens were sectioned with measurements and relationships of the trigeminal nucleus caudalis, segmental tracts, spinocerebellar tracts and dorsal columns. Two right-angle DREZ electrodes were made by Radionics for producing DREZ lesions in the trigeminal nucleus caudalis to treat deafferentation facial pain.


Descending trigeminal tractotomy for trigeminal neuralgia after surgical failure. Percutaneous rhizotomy, microvascular decompression or rhizotomy by suboccipital craniotomy often cures medically untreatable trigeminal neuralgia with an acceptable complication rate. However, pain involving the same trigeminal distribution persists in a few patients despite both rhizotomies. For 7 patients with such surgically 'failed' trigeminal neuralgia, we performed descending trigeminal tractotomy. In all patients, neuralgia ceased immediately postoperatively and has not recurred during 9 months to 15 years follow-up. Descending trigeminal tractotomy provides a satisfactory solution to this relatively rare but paroxysmal pain syndrome.


Dorsal root entry zone stimulation for deafferentation pain. Dorsal root entry zone (DREZ) stimulation was performed in 12 patients with chronic pain syndromes after extensive trials of medical therapy, sympathectomy or peripheral nerve stimulation had failed, with 50% of them obtaining excellent long-term benefit. Evoked potential monitoring to facilitate positioning of electrodes under either general or spinal anesthesia, and postoperatively to explore the mechanism of action, revealed findings distinct from those reported with conventional spinal cord stimulation (SCS). DREZ stimulation may function on a different neurophysiologic basis than conventional SCS, involving intersegmental processing and influencing tract of Lissauer functions or the dorsal horn directly.


Percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia. Most percutaneous procedures for the treatment of pain are done under local anesthesia and considerable pain can be involved. If the patient is elderly or confused because of severe pain, it is difficult or impossible to perform these procedures successfully. We treated 3 elderly patients with trigeminal neuralgia and 1 patient with severe bone pain due to metastatic osteosarcoma in the lumbosacral region by percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia with intratracheal intubation. We conclude that percutaneous trigeminal rhizotomy and percutaneous cordotomy can be safely done under general anesthesia.


Relief from chronic pelvic pain through surgical lesions of the conus medullaris dorsal root entry zone. Dorsal root entry zone (DREZ) lesions are effective in treating specific pain syndromes, most notably post-brachial plexus avulsion. There is limited experience, however, with lesions in the conus medullaris. We review the case of a patient having pelvic pain and urinary retention who failed to improve despite multiple prior interventions. Her pain was completely relieved after DREZ lesions were placed bilaterally at S2, S3, S4 and S5. The intraoperative sensory and motor evoked potential monitoring used to define the level is described in detail.


Stereotactic resection and its limitations in glial neoplasms. With imaging-based volumetric stereotactic techniques, it is possible to selectively and accurately remove any CT- or MRI-defined part or all of any intra-axial neoplasm. However, glial neoplasms are composed of two elements: tumor tissue and isolated tumor cells which infiltrate brain parenchyma. In high-grade gliomas and pilocytic astrocytomas, the tumor tissue component is most accurately defined by the volume of contrast enhancement. Tumor tissue in low-grade nonpilocytic gliomas is indistinguishable on imaging from infiltrated parenchyma. Stereotactic biopsy is presently the only method by which CT hypodense tumor tissue can be differentiated from infiltrated parenchyma, which is also hypodense. In eloquent brain areas, stereotactic resection is appropriate for the tumor tissue component only in patients harboring glial tumors.


Central pain in the absence of functional sensory thalamus. Since the pioneering publication by Dejerine and Roussy, the thalamus has been commonly implicated in the pathogenesis of central pain. It is well known that cerebral lesions that spare the thalamus as well as both small and large ones within that structure produce similar pain syndromes, but could such pain develop if the thalamus were completely destroyed? CT scans of our patients suggested that it could. Moreover, exhaustive physiological explorations of the thalamus with macro- and microstimulation and microelectrode recordings in 2 more patients in whom CT scans suggested thalamic preservation despite massive suprathalamic infarcts, for the purpose of carrying out deep brain stimulation (DBS), revealed no evidence of ascending or descending diencephalic function. Their sensory examinations were similar to those of patients with congenital hemiatrophy who had undergone hemispherectomy. In 1 case, microstimulation of periaqueductal grey-periventricular grey (PAG-PVG) on the unaffected side of the brain induced the spectrum of responses correctly associated with these areas and during acute stimulation nearly abolished the patient's allodynia and hyperpathia. These observations suggest that processes occurring at a subdiencephalic level (or possibly ipsilaterally) may be involved in the generation of pain. Stroke-induced central pain remains a therapeutic dilemma for the pain surgeon, and the mechanisms underlying this pain state remain a mystery.(ABSTRACT TRUNCATED AT 250 WORDS)


[Primary non-Hodgkin's malignant lymphoma of the central nervous system]. The incidence of primary central nervous system lymphoma (PCNSL) is increasing, not only in immunodeficiency states, but also in apparently normal individuals. The most common presentation of PCNSL is that of an intracranial mass lesion. Ocular involvement is associated in 20% of patients. CT/MR scan typically shows one or several periventricular tumors with indistinct margins that diffusely and densely enhance following contrast infusion. The diagnosis relies on lumbar puncture, vitreous biopsy, or stereotactic biopsy of a brain lesion demonstrating lymphomatous cells. If possible, corticosteroids should be used only after definite diagnosis. Corticosteroids have a cytotoxic effect responsible for transient remission in 40% of patients. Whole brain radiation therapy induces a complete or partial response in 80% of patients but recurrence always occurs and the median survival does not exceed 14-18 months. The addition of systemic and intrathecal chemotherapy seems to substantially improve the prognosis with median survival exceeding 3 years in some studies. PCNSL associated with AIDS generally occurs at a late stage of the disease and is the fourth cause of death in AIDS patients. Radiation therapy is useful but the median survival does not exceed 5.5 months because patients most often die of opportunistic infections.


[Genealogical study of oculopharyngeal dystrophy at Saguenay-Lac-St-Jean, Quebec, Canada]. The genealogies of 28 proband affected with oculopharyngeal dystrophy (OPD) distributed in 28 families from Saguenay-Lac-St-Jean, a geographically isolated region of northeastern Quebec, were reconstructed. The analysis of these genealogies showed that the Montmagny and L'Islet counties are the most likely center of diffusion of OPD among the French Canadians, as suggested by Barbeau in 1966. A unique founder couple, J.E.-M.B., common to all 28 genealogies was found. The children of this couple emigrated in the 17th century from Poitou (France), a region where several families with OPD were recently ascertained.


[Sublingual administration of apomorphine in the treatment of motor fluctuations in Parkinson disease]. Apomorphine, a mixed dopaminergic agonist was given sublingually to 12 patients with Parkinson's disease disabled by severe on-off fluctuations. The patient's mean age was 57 years and the duration of Parkinson's disease was 12 years. All patients were also given domperidone (60 mg/day). Apomorphine was administered as soon as the off periods appeared. On periods were observed in 11 patients, with a mean apomorphine dose of 40 mg for each administration (extremes values: 20-60 mg). One patient had no motor benefit after an apomorphine dose of 120 mg. The mean duration of daily off periods was reduced by 64 per cent in 11 patients, for a mean duration of 8 months (extremes values: 2-12 months). Four patients developed stomatitis or gingival edema and stopped treatment. This pilot study shows that sublingual apomorphine, during a mean period of 8 months, significantly decreases off periods in parkinsonian patients. Others studies are necessary to confirm these results.


[Autoantibodies in paraneoplastic polioencephalomyelitis: 8 cases]. Antibodies directed against the central nervous system were looked for by indirect immunohistochemistry in the sera of 8 patients with paraneoplastic neurological syndrome (group 1), 21 cancer patients without neurological signs, 23 patients with miscellaneous neurological diseases and 63 normal subjects (groups 2 to 4). Four patients in group 1 had very high titres of antibodies. In 2 patients with small-cell lung carcinoma associated with sensory neuropathy the antibody recognized the cytoplasm and nucleus of all neurons. A 37 Kd protein was recognized by Western blot. A woman with cancer of the ovary and cerebellar syndrome exhibited an antibody against Purkinje's cell cytoplasm with a band of about 50-55 Kd at Western blot. In a woman with chronic uveitis and cerebellar atrophy with disappearance of Purkinje's cells the antibody (in blood and CSF) recognized certain layers of the retina as well as glial cells and cells present in the subependymal areas of the brain. Two bands of 46 and 59 Kd were revealed by Western blot. Immunoglobulins were detected in the cytoplasm of white matter cells in the cerebellum and brain stem. Among the other groups, one patient with lung cancer had a moderate titre of neuronal antinuclear antibody. The Western blot test was negative. The relevance of these antibodies for the diagnosis and treatment is discussed.


[Autosomal dominant centronuclear myopathy]. In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.


[Death during migraine crisis].

[Death during migraine crisis]. A 42 year old man presented with a rapidly progressive syndrome, including headache, aphasia, fever, stiff neck and impaired consciousness. Following a transient improvement, the patient died after a six weeks course. The autopsy showed foci of ischaemic necrosis in the white matter of the brain. The patient's clinical history suggests the diagnosis of migraine.


[Isolated memory disorders disclosing antiphospholipid antibody syndrome]. Most of the neurological complications of the antiphospholipid syndrome are consequences of arterial or venous cerebral thromboses. We report the case of a 46-year-old woman presenting with the main signs of antiphospholipid syndrome: Raynaud's phenomenon, livedo, leg ulcers, repeated miscarriages, presence of a circulating anticoagulant and of antiphospholipid antibodies, who developed an isolated amnestic syndrome with a peculiar pattern; 1) almost complete sparing of the ability to learn new skills and of short-term recall; 2) deterioration, followed by disappearance of recent memories after a sufficient delay; 3) progressive alteration of increasingly old memories including knowledge memory suggested a gradual alteration of mnestic traces. The lack of neuroradiological signs of multiple infarcts suggests a direct intervention of antibodies in this patient's memorisation mechanisms.


[Marchiafava-Bignami disease. Interhemispheric disconnection, favourable outcome, neurological aspect]. We report two cases of Marchiafava-Bignami disease studied by CT and MR imaging. Both had hemispheric disconnection syndrome and favorable outcome. The only residual signs were agraphia with the left hand in the two cases and mild dementia in one. In one case, a control CT scan performed 3 weeks after the first one was normal whereas T2-weighted MR images showed high intensity signal in the corpus callosum. We conclude that: 1. there are benign forms of MB disease; 2. neuroimaging has diagnostic and prognostic value; 3. vitamin B deficiency may play a role in the pathogenesis of the disease.


[Nociceptive threshold and Parkinson disease]. It has now become possible to measure pain thresholds in man by the threshold or amplitude of the leg flexion nociceptive reflex (RIII reflex). These parameters accurately reflect the pain levels perceived by the patients. The aim of the present study was to assess pain thresholds in Parkinsonian patients, using the RIII reflex. Painful phenomena are often mentioned in Parkinson disease, but the perceived pain threshold level can be difficult to assess because of the depressive symptoms which are often associated with Parkinson disease. In 8 cases out of 10, the pain threshold was found to be higher in patients with Parkinson disease than in a control population of the same age: in 2 cases, naloxone injection led to recovery of the normal pain threshold level.


Immunohistochemical evidence of high concentrations of metallothionein in pancreatic hepatocytes induced by cadmium in rats. A recent study from our laboratory has shown that cadmium, a toxic heavy metal, is one of the most effective agents known for inducing hepatocytic transdifferentiation of the rat pancreas. With repeated injections of cadmium, the incidence of rats with pancreatic hepatocytic foci can be as high as 93%. Cadmium is also well known as a very potent inducer of metallothionein, a metal-binding protein that appears to be important in the biologic response to several toxic heavy metals in most tissues, including the pancreas. Therefore, the present study sought to determine if metallothionein was associated with cadmium-induced transdifferentiation of pancreatic cells. Expression of metallothionein was studied immunohistochemically by the peroxidase-antiperoxidase method in tissue sections of the pancreas of rats with pancreatic hepatocytes. High levels of metallothionein were localized primarily within the pancreatic hepatocytes. Surrounding normal pancreatic islet and acinar cells were not immunoreactive. Thus, metallothionein is expressed actively in cells transdifferentiated to hepatocytes by cadmium within the pancreas.


Spontaneous skin neoplasms in aged Sprague-Dawley rats. A total of 93 tumors of the epidermis, its appendages, and dermis were observed in 1,433 (717 males, 716 females) rats employed in oncogenicity studies over a 2-yr period. Mammary gland neoplasms will be reported separately. Fifty-seven (61.3%) were epithelial with 49 in males and 8 in females. Keratoacanthoma was the most frequent epithelial neoplasm in males (22) followed by squamous cell carcinoma (11) and papilloma (5). Sebaceous gland neoplasms seen in males (5) included both adenomas (3) and carcinomas (2). In males, there were also 3 trichoepitheliomas, 1 pilomatricoma, 1 basal cell tumor, and 1 malignant melanoma. Of the 8 epithelial neoplasms in females, there were 3 squamous cell carcinomas, 2 keratoacanthomas, and 1 each basal cell tumor, malignant melanoma, and trichoepithelioma. There were 21 mesenchymal neoplasms in males and 15 in females. The most frequent neoplasm was fibroma (7 males, 8 females) followed by lipoma (7 males, 4 females) and fibrosarcoma (4 males, 3 females). One male had a liposarcoma and 2 males each had hemangioma. The total neoplasm incidence of 70/717 (9.8%) in males and 23/716 (3.2%) in females showed that skin neoplasms were 3 time more common in males than in females. Epithelial neoplasms of the skin were 6 times more common in males than in females. Males were more than twice as likely to have epithelial rather than mesenchymal skin neoplasms whereas the reverse was seen in females.


Experimental renal papillary necrosis in the Mongolian gerbil (Meriones unguiculatus). Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total renal papillary necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post-treatment and progressed to occlusion by platelets adherent to exposed basement membranes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the development of BEA-induced RPN by its vasodilatory effect on the renal vasculature, not by blocking the endothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta.


Spontaneous corneal dystrophy and generalized basement membrane changes in Fischer-344 rats. Groups of young, sexually mature Fischer-344 rats (n = 25/sex) obtained from commercial breeders were examined ophthalmologically and histopathologically to determine the prevalence and severity of corneal basement membrane lesions (corneal dystrophy) and basement membrane changes in select nonocular tissues. Results disclosed a high incidence of corneal basement membrane dystrophy in rats of both sexes from all breeders; however, severity levels were significantly increased in rats obtained from one breeder when compared to others. Furthermore, rats that displayed the most advanced corneal lesions also exhibited more severe basement membrane changes in other organs, especially renal tubules and vascular internal laminae. These findings suggest that both ocular and nonocular dystrophic changes may have been linked through common physiologic (or genetic) mechanisms. Animals that displayed basement membrane lesions were not considered to represent compromised biologic test systems.


Nasal lesion development and reversibility in rats exposed to aerosols of dibasic esters. This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters (DBE). Young male rats were exposed, nose-only, to an aerosol/vapor mixture of DBE at a concentration of 5,900 mg/m3 for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells.


Studies of skin toxicity in vitro: dose-response studies on JB6 cells. There are many reasons for developing in vitro tests of toxicity including cost, speed, studies of mechanisms, and studies utilizing human cells and tissues. The present study focuses on the development of in vitro tests to predict in vivo toxicity by comparing them to data from the literature. A broad spectrum of model toxic compounds was evaluated for toxicity on mouse skin JB6 cells in culture. These included mercuric chloride, sodium lauryl sulfate, formaldehyde, dimethyl sulfoxide, benzoyl peroxide, and ionomycin, all of which have been proven to be positive in the Draize test or in cutaneous toxicity studies. Cell viability was evaluated every 15 min for up to 1 hr, and then after 24 hr of treatment using the Trypan Blue exclusion method; morphological changes were evaluated using phase-contrast and transmission electron microscopy. Dose- and time-dependent cell death and morphological changes were observed at concentrations ranging from 10(-14) to 10(-2) M. Arbitrary rankings were assigned based on 1) IC50 value estimated from the present data, and 2) in vivo toxicity reported in the Registry of Toxic Effects of Chemical Substances. Good correlation between in vitro and in vivo toxicity based on arbitrary rankings was observed. Thus, these findings suggest that the JB6 cell culture model can be used for predicting in vivo toxicity. In the future, it may be possible to utilize this system for the study of intracellular ionized calcium ([Ca2+]i), and the expression of oncogenes as early indicators of toxicity.


Parenteral aluminum compounds produce a local toxic myopathy in rats: importance of the anion. Aluminum lactate, injected in rats, produced skeletal muscle necrosis of diaphragm and abdominal wall subjacent to peritoneal surfaces. Deeper muscle cells (distal from inoculum) were less severely affected. Ultrastructural studies of diaphragm revealed inoculum coating collagen fibrils, aggregating next to muscle basal lamina and localized within phagocytes. Aluminum lactate penetrated lymphatic vessels and caused reactive changes on the pleural as well as peritoneal surfaces of diaphragm. In contrast, injection of aluminum citrate did not produce myopathy. Also, mixtures of aluminum lactate with aluminum citrate, sodium citrate, or another chelating agent failed to produce myopathy. Therefore, the regional myopathy produced by the lactate salt provides a model for in vivo cytotoxicity of aluminum in which anionic binding is a critical determinant.


Morphology of nasal lesions induced in Osborne-Mendel rats and B6C3F1 mice by chronic inhalation of allyl glycidyl ether. Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE-exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats.


Feeding studies in rats with mineral hydrocarbon food grade white oils. This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.


Quinolone arthropathy--acute toxicity to immature articular cartilage. A class effect of quinolone antibacterial agents observed during animal toxicity testing is a specific arthropathy (QAP). Despite the growing list of laboratory animals susceptible to QAP and reports of arthralgia in patients treated with quinolones, the potential for QAP development in humans remains unknown. This review discusses current concepts in the biology of articular cartilage and how these concepts elucidate QAP pathogenesis. Biomechanical forces within synovial joints and toxicokinetic properties of quinolones contribute to QAP induction. Since a limited number of mechanistic pathways exist for acute articular damage, QAP may serve as a research tool to probe the pathobiology of injury to articular cartilage.


Response of the esophageal epithelium to concomitant cis-dichlorodiammineplatinum(II) and radiation treatment. An electron microscopic study in rabbits. The rabbit esophageal mucosa was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose 2, 6, 10. 16 or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-dichlorodiammineplatinum (cis-DDP, cisplatinum) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of damage with cell loss and structural disarrangement of the microridges and whorls on the surface. However, with further treatment the esophageal mucosa exposed to cis-DDP and radiation normalized faster and more complete compared to the esophageal part exposed to cis-DDP alone. The difference may depend on an accelerated proliferation in the part of the trachea that is exposed to a combined treatment.


Ultrastructural effects of therapeutic irradiation on human epithelial tumors. Irradiation induces several cellular changes leading to death of cancer cells and normal cells which is followed by repairing processes of normal cells. We have studied the effects of therapeutic irradiation on head and neck cancers. Tissue samples taken before and during the radical irradiation (50-80 Gy) of the squamous cell carcinomas of the head and neck region were examined by light and electron microscopy. Nuclear atypia was most pronounced cellular change during irradiation. The tumor invasion pattern remained unchanged but the number of mitoses decreased. Lymphocytic infiltration increased at the beginning of the therapy (from 10 to 30 Gy) but decreased at the end of radiotherapy. The amount of neutrophils and the keratinization pattern remained almost unchanged at the light microscopical level. However, by electron microscopy, intracellular filaments and desmosomes tended increase slightly especially in tumors responding more favorable to the treatment. The changes in nuclear morphology pointing in a more undifferentiated direction are considered to be due to cell damage rather than to a more aggressive behavior of the tumor cells. This is in agreement with the simultaneous decrease in mitoses, which might partly be due to radiation induced arrest of tumor cells to the G2 phase. These observed changes correspond to animal studies in the literature and might be responsible for the disappearance of tumors during irradiation.


Information and misinformation regarding ischemia of heart muscle tissue. The cause of cell death during blood reperfusion and reactivation of heart muscle tissue after prolonged ischemia. An electron microscopic study of heart muscle tissue exposed to six hours ischemia and prepared according to the low denaturation embedding technique revealed a structural modification confined to the mitochondrial cristae. The modification consisted of a removal of Krebs cycle enzymes from the cristae. Reperfusion of the ischemic tissue after four hours ischemia led to extensive breakdown of the mitochondrial structure and contractility could not be restored. However, when after six hours ischemia the ischemic tissue was reperfused with blood, the composition of which had been modified to stimulate mitochondrial function, no additional structural changes were observed and contractility was restored. The structural damage caused by reperfusion with non modified blood is explained by a loss of control of plasma membrane permeability caused by impaired ATP production which makes the ionic composition of the cytosol approach that of blood plasma, stopping oxidative phosphorylation. A treatment to restore heart muscle function after long periods of ischemia and after heart transplantation is proposed. The structural damage revealed that the Krebs cycle and the respiratory chain enzymes are associated according to a regular periodic pattern and that the enzyme molecules are closely aggregated three-dimensionally. Earlier electron microscopic studies revealing massive structural deterioration of heart muscle cells already after 45 to 60 minutes ischemia leading to the conclusion that the cells are irreversibly damaged, is based on fixation artifacts caused by osmium fixation. This study has been carried out in collaboration with the research team of Gerald D. Buckberg at the Thoracic Surgery Division at University of California at Los Angeles.


The effect on the ultrastructure of dental enamel of excimer-dye, argon-ion and CO2 lasers. This study aimed to investigate the ultrastructural changes that occur in dental enamel irradiated with pulsed excimer-dye, continuous-wave (CW) argon-ion and CW CO2 lasers. The pulsed excimer-dye laser produced deep craters, rough damaged surfaces with underlying porosity and amorphous vitrified material. The vitrification of the enamel indicated that the temperature in these areas must have been at least in the range 1280 to 1600 degrees C. The CW argon-ion laser irradiation produced a changed non-cratered surface with inter-crystalline porosity and a mixture of small and some large irregularly packed recrystallized enamel crystals. The CW CO2 laser produced shallow craters, surface crazing and lifting off the removal of the surface layer to expose the underlying roughened enamel. The ultrastructure revealed inter- and intra-crystalline porosity, a mixture of small but variable size irregularly packed recrystallized enamel crystals and also well packed large crystals which indicated further grain growth. The porosity in lased enamel was overall very similar to that seen in enamel heated in an electric furnace to a temperature of 600 degrees C. The presence of recrystallized enamel crystals indicated a temperature rise of approximately 1000 degrees C and the grain growth indicated that a temperature > or = 1000 degrees C existed for some time after the laser irradiation. In general the excimer-dye laser produced most surface destruction because of its higher power density and shorter interaction time and the argon-ion laser produced least damage. These results indicated that the lasers used in this study require much more refinement before they can find therapeutic application to dental enamel, and this may well be the case for other lasers being investigated for clinical dental practise.


Dentinogenesis and the calciotraumatic response to the injection of lead or fluoride ions. A number of ions can disturb the formation of dentine resulting in a calciotraumatic response. The calciotraumatic response following the injection of sodium fluoride was investigated using backscattered electron imaging in the scanning electron microscope and compared with the response to lead acetate. With fluoride, there was formation of a hypermineralized band succeeded by a relatively hypomineralized band, but with lead acetate, only a hypomineralized band was produced. However, there were some differences in the response between the labial and lingual dentine with both ions. In the labial dentine following injection of sodium fluoride, the onset of hypermineralization was less abrupt than in the lingual dentine. Furthermore, the transition from hypermineralization to relative hypomineralization was more abrupt in the labial dentine. Sometimes there was an increased thickness of labial dentine between the hypermineralized layers towards the apex of the tooth and this dentine was less homogeneously mineralized. Normal incremental lines were occasionally seen both labially and lingually. Lead acetate produced a more severe disruption of dentine formation labially than lingually. These differences in response may be related to the pattern of mineralization labially and lingually and to the systemic effects following the injection of sodium fluoride.


Microwear studies of early African hominid teeth. Studies of microwear on fossil hominid teeth have become an important approach in paleoanthropology. Since there are very few samples of early hominids from East Africa with suitable teeth, this paper presents a review of the occurrence of some dental wear characteristics to provide a data base for reconstructing the diet of the early hominids. Distinctive microwear features such as furrows, crenulations, stress lines and deep grooves, are interpretive tools that can be used in a biomechanical approach. Occurrence of the same dental microwear patterns in extant species with known dietary differences is indicative of foods that have probably been exploited in fossils.


Scanning electron microscopy of intracellular organelles in the young odontoblasts of rats. Intracellular structures of the odontoblasts were studied by scanning electron microscopy (SEM) using a modified AODO (aldehyde prefixed-osmium-DMSO-osmium) method. Well-developed flattened and layered rER (rough endoplasmic reticulum), paved with its associated ribosomes on its outer surface, were clearly observed in the odontoblast. Branched tubular mitochondria with nodules and swollen endings, interposing between and passing through the fenestrated layered rER, were demonstrated in the functional cells. Oblique and cross-sections of both the rER system and tubular mitochondria showed orthodox configurations similar to those usually described in transmission electron microscopy (TEM) studies. Many finger-like projections constructing the cristae directing towards the inner mitochondrial chamber were observed, and external chamber extending into the tubular cristae was also demonstrated.


Microvasculature of normal and hydropic labyrinth. The microvasculature of the inner ear in guinea pigs and humans was observed with a scanning electron microscope using corrosion casting method. Alterations in the inner ear vasculature which occurred in association with experimental endolymphatic hydrops were also investigated. The results thus obtained are summarized as follows: 1. In the cochlea and vestibule, the arteries, coiled arterioles, and the veins are endowed with their respective characteristic morphologic features and play a role in the regulatory mechanisms of circulation. 2. The point in humans which is most different from guinea pigs was that coiled arterioles in the cochlea and the coil-like traveling of the anterior vestibular artery is not outstanding. 3. Arteriovenous anastomoses were demonstrated to exist in lateral wall of cochlea and utricular macula, a finding suggesting the existence of a regulatory mechanism for local blood flow. 4. Endolymphatic hydrops was noted to be preferentially associated with vascular abnormalities in the lateral wall of the cochlear duct and in the saccular macula, among other vestibular structures.


Scanning electron microscopy of nerve fibers in the dog cochlea. The nerve fiber arrangement inside the organ of Corti in the dog was studied. Thick sections were cut serially from celloidin-embedded cochleas and observed with a scanning electron microscope (SEM). The nerve fibers in the organ of Corti were clearly exposed in sections cut in the horizontal plane. The arrangement of nerve fibers in the dog showed considerable difference from that of other species. The tunnel basilar fibers in the dog curved basalward, and took a long longitudinal course to form a broad bundle in the center of the tunnel floor. This bundle has not been found in adult animals of other species. Two distinct types of tunnel radial fibers, upper tunnel radial fibers and underpassing radial fibers, were recognized. The latter type of radial fibers ran beneath the bundle of basilar fibers, and seemed to be characteristic of the dog cochlea. From the morphological characteristics, these underpassing radial fibers were thought to be efferent in nature.


Cochlear and vestibular epithelia from a patient with Menière's disease: a case study. Scanning electron microscopy observations were carried out on the cochlear and vestibular epithelia of the left temporal bone of a Menière's patient. There was almost complete absence of hair cells in the basal turn of the cochlea. The outer hair cells of the second turn presented an abnormal shortening of the shorter stereocilia within a tuft, reminiscent of the specific atrophy of the short and middle stereocilia in the ciliary tufts of outer hair cells in the guinea pig with experimental hydrops. The cilia of the inner hair cells showed fusion and giant cilia formation. Hair cells were observed in the apical turn which showed no pathological features in particular. In the saccular epithelium there were a number of striking features including, loss of the kinocilium, loss of ciliary tufts, swelling of the sensory cells, holes in the epithelium, and sensory cells pushed out and lying on the surface. The utricular epithelium was less perturbed and showed only relatively small protrusions from the epithelial surface. Similar observations have earlier been made on the vestibular epithelium in experimental hydrops. After taking into consideration the relatively long delay to fixation (12 hours) it appeared that the sacculus was more fragile and prone to autolysis than the other organs suggesting that the in-vivo pathology was manifested in particular in that organ as would be predicted from Menière's symptoms.


Comparison of cryopreparation techniques for electron probe microanalysis of cells as exemplified by human erythrocytes. Erythrocytes in human blood were used to evaluate the reliability of cryopreparation techniques for electron probe X-ray microanalysis of biological cells and tissues. The elemental content determined by X-ray microanalysis of ultrathin freeze-dried cryosections was found to be consistent with data known from the literature. Considerable redistribution of the intracellular elemental composition was found after freeze-substitution as well as after freeze-drying followed by resin embedding. Two conclusions are drawn from this study: 1. Erythrocytes in human blood are a suitable reference specimen for evaluation of specimen preparation techniques for microanalysis. 2. At present, freeze-dried cryosections are the most reliable specimen type for quantitative electron probe microanalysis of cells.


Effect of chronic treatment with diuretics on mouse liver: a morphological and microanalytical investigation. In an attempt to produce an animal model for the disease cystic fibrosis (CF), mice were treated chronically with the diuretics amiloride and furosemide, in order to cause chronic inhibition of transepithelial ion transport. Experiments were carried out on adult mice (2 months treatment); in addition, pregnant mice were treated with diuretics, and tissue from offspring 2 and 7 days post partum was investigated. Since biliary cirrhosis is a common occurrence in CF, hepatocytes in the treated mice were investigated by X-ray microanalysis and by light and electron microscopy. Treatment with amiloride caused a significant decrease in cellular Na concentration in adult animals and in in utero treated mice 2 days after birth. The decrease in Na was paralleled by a decrease in Cl, but K levels were not affected. Furosemide caused a slight increase of cellular Na concentrations, especially in animals aged 7 days. In the adult animals, both amiloride and furosemide caused a significant decrease of the cellular Na and Cl levels. No signs of cirrhosis could be observed. Inconsistent changes in the accumulation of lipid droplets in hepatocytes of adult animals treated with amiloride were observed by electron microscopy. It can be concluded that chronic treatment with diuretics, even though it causes some, possibly pathological, changes of the liver, is only of very limited value for generating an animal model to study liver disease in CF.


Atomic force microscopy of DNA on mica and chemically modified mica. Atomic force microscopy (AFM) was used to image circular DNA adsorbed on freshly cleaved mica and mica chemically modified with Mg(II), Co(II), La(III), and Zr(IV). Images obtained on unmodified mica show coiling of DNA due to forces involved during the drying process. The coiling or super twisting appeared to be right handed and the extent of super twisting could be controlled by the drying conditions. Images of DNA observed on chemically modified surfaces show isolated open circular DNA that is free from super twisting, presumably due to strong binding of DNA on chemically modified surfaces.


Investigation of living cells in the nanometer regime with the scanning force microscope. Membrane structures of different types of cells are imaged in the nanometer regime by scanning force microscopy (SFM). The images are compared to those obtained with a scanning electron microscope (SEM). The SFM imaging can be done on the outer cell membrane under conditions that keep the cells alive in aqueous solutions. This opens up the possibility of observing the kinematics of the structures that determine the interaction of a cell with its environment. Therefore, STM observations, together with information obtained with the electron microscope, open up new ways of studying the development of biological structures. With the currently possible resolution, the SFM gives access to processes such as antibody binding or endo- and exocytosis, including processes correlated to the infection of cells by viruses.


The arthritis of familial Mediterranean fever. Familial Mediterranean fever (FMF) is a disease of unknown etiology and pathogenesis. In addition to fever, arthritis is among its most frequent manifestations. The arthritis of FMF is typically an acute, episodic, self-limited process with no sequelae. The radiographic features of FMF arthritis are usually limited to transient, often severe osteoporosis. Synovial fluid analysis many mimic septic arthritis with very high white blood cell counts; cultures are uniformly negative. The course of FMF is almost always benign, with no residual articular incapacity. Some patients, limited to certain ethnic groups, develop renal amyloidosis. Colchicine therapy modifies the natural history of the disease by decreasing the attack frequency and preventing amyloid deposition. At present, a lipocortin deficiency appears to be the likely candidate for a pathogenic mechanism. An unusual case with dramatic periarticular features (periostitis) and a protracted course with an excellent response to synovectomies is reported here. There is no explanation for the exuberant periarticular bone formation noted in this case, but a variety of recently discovered growth factors may be implicated.


POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature. A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.


Rheumatic complications of alcohol abuse. The purpose of this report is to review rheumatic complications associated with alcoholism. Data were collected by an English-language literature search using MEDLINE (1966 to December 1991) and references from identified articles. Studies in humans, including case reports of joint disease and allied disorders associated with alcoholism, were reviewed. According to the data identified, alcoholism is associated with many rheumatic problems, including neuropathic arthropathy, hyperuricemia with gouty arthritis, septic arthritis, and joint hypermobility. Osteoporosis, osteonecrosis, and myopathy also are common. Several other rare musculoskeletal complication have been described. Early recognition of these problems is important for management. Further studies are needed to examine the effect of alcohol on connective tissue components in joints.


Dyslipoproteinemia in the course of active rheumatoid arthritis. Concentrations of serum lipids and serum very low-density lipoproteins and low-density lipoproteins (VLDL+LDL, originally called beta lipoproteins) were measured and agarose gel electrophoresis of serum lipoproteins was performed in 69 patients with active rheumatoid arthritis (RA), 40 patients with psoriatic arthritis (PA), 21 patients with osteoarthritis (OA), and 65 healthy blood donors. These lipid parameters were also compared in 21 RA and 40 PA patients during periods of severe disease activity (SA) versus minimal disease activity (MA). RA patients had significantly decreased concentrations of total serum lipids, total serum cholesterol, cholesterol in LDL, and cholesterol in high-density lipoproteins (HDL) compared with healthy blood donors. RA patients with SA had significantly decreased cholesterol in LDL and HDL compared with patients with MA. As the disease activity decreased, RA patients had normalization of almost all serum lipid concentrations. Electrophoresis of serum lipoproteins showed heterogeneous patterns in RA patients. Patients with PA also had some evidence of dyslipoproteinemia. Serum lipids changed with disease activity in PA patients in a manner similar to that in RA patients. These data show that patients with RA and PA have a dyslipoproteinemia that is related to disease activity.


Geographic distribution of rheumatoid arthritis in ancient North America: implications for pathogenesis. The fifth centennial of Columbus stimulates renewed interest in New World origins of disease. The earliest documentation of rheumatoid arthritis was in the New World. Subsequent study of its distribution in the New World in antiquity defines localization to a very specific geographic region. The absence of rheumatoid arthritis in 63 archaeological sites surrounding the original "catchment area" and in five Old World sites, with documented spread over time, suggests that it is a vector (microorganism or allergen)-transmitted disease.


Diseases associated with calcium pyrophosphate deposition disease. Although many metabolic and endocrine diseases have been reported to predispose to calcium pyrophosphate dihydrate crystal deposition, the validity of many of these associations remains unclear. A critical review of the literature relating to these associations, with illustrative cases and data derived from the authors' own experience, is presented. It is concluded that there is good evidence to associate hypophosphatasia, hypomagnesemia, and hyperparathyroidism with chondrocalcinosis and acute attacks of "pseudogout." Meta-analysis also suggests a small but significant association between hypothyroidism and chondrocalcinosis. Hemochromatosis stands alone in clearly associating not only with chondrocalcinosis but also with structural change and chronic arthropathy. The biochemical mechanisms that may produce these various associations are discussed. Recommendations are made concerning appropriate screening for metabolic and endocrine disease in patients with chondrocalcinosis.


Laryngeal involvement in systemic lupus erythematosus. Laryngeal involvement in systemic lupus erythematosus (SLE) can range from mild ulcerations, vocal cord paralysis, and edema to necrotizing vasculitis with airway obstruction. In this report, four cases showing the range of severity of this disease manifestation are presented, accompanied by a comprehensive review of the literature. The clinical course of 97 patients with laryngeal involvement with SLE are reviewed, of whom 28% had laryngeal edema and 11% had vocal cord paralysis. In the majority of cases, symptoms such as hoarseness, dyspnea, and vocal cord paralysis resolved with corticosteroid therapy. Other, less common causes of this entity included subglottic stenosis, rheumatoid nodules, inflammatory mass lesions, necrotizing vasculitis, and epiglottitis. The clinical presentation of laryngeal involvement in patients with SLE follows a highly variable course, ranging from an asymptomatic state to severe, life-threatening upper airway compromise. With its unpredictable course and multiple causations, this complication remains a diagnostic and therapeutic challenge to physicians involved in the care of patients with SLE.


Penetrating trauma audit--TRISS analysis. Quality assurance in trauma care is of major importance in assessing the efficacy of a trauma service and in identifying areas for improvement. Trauma scores and the TRISS methodology are at present the most accurate tools for quality assurance purposes. In this prospective study, the TRISS methodology was used to analyse the results in a group of 629 patients with penetrating trauma.


[Partial ileal bypass for familial hypercholesterolemia]. The extent of reduction in cholesterol levels, the maintenance of low levels in the long-term, the morbidity and mortality as well as the acceptance of side-effects of the partial ileal bypass (PIB) is reviewed. The mean reduction in cholesterol levels following PIB was 35.2% in males and 35.8% in female patients. The reduction is significant and it is maintained over a 10-year period. The morbidity and mortality is low and side-effects are well tolerated. Our results indicate that the PIB may play an important role in the cholesterol-lowering armamentarium.


A review of carcinoma of the colon and rectum over a 3-year period at Hillbrow Hospital, Johannesburg. Fifty-one patients with adenocarcinoma of the large bowel seen at Hillbrow Hospital over a 36-month period are reviewed. The mean age at diagnosis was 53 years. Advanced disease was present in at least 60%. Carcinoma of the rectum constituted 48% and colonic carcinoma 52%. Cancer and polyps of the large bowel in urban blacks are no longer a rarity in urban hospitals.


An unusual rectal carcinoma. A case report. The case history of a patient whose barium enema radiographs confirmed the clinical diagnosis of a stenosing rectal carcinoma is presented. Two years previously, the patient had undergone sub-total gastrectomy for carcinoma of the gastric antrum. An abdominoperineal excision of the rectum was performed, and histological examination of the tumour showed it to be not primary large bowel in origin, but a metastatic manifestation of the original gastric cancer.


Total gastrectomy for gastric cancer associated with situs inversus totalis. A report of 2 cases. A 69-year-old man and a 54-year-old woman with situs inversus totalis were admitted to our hospital for surgery for gastric malignant disease. The diagnosis was made radiologically and successful total gastrectomies were performed.


The management of clinically occult breast lesions. A Johannesburg learning experience. There is an increase in demand for pre-operative radiologically guided percutaneous localisation of occult breast lesions. Specific problems in the progression from mammographic identification to histological diagnosis are cited. Accurate pre-operative localisation should always be followed by specimen radiography.


Postoperative intensive care and the South African Society of Anaesthetists' patient category. A group of 412 postoperative patients admitted to an intensive care unit of an academic hospital were evaluated in terms of their need for intensive care. The Acute Physiology and Chronic Health Evaluation score, the Therapeutic Intervention Scoring System (TISS) and the South African Society of Anaesthetists' (SASA) patient category were utilised to determine the level of care required by each patient. A further objective of the study was to determine if the SASA patient category, on its own, adequately described the need for intensive care in postoperative patients. Evaluation of the data indicated that, in terms of TISS, 66% of the patients required intensive care. These patients were distributed throughout all three SASA categories. Of the 137 patients who, according to TISS, did not require intensive care, 122 were SASA category 3 patients. However, of the total number of category 3 patients, just less than half required intensive care. In order to identify better those patients within a specific SASA category who require intensive care we suggest further subdivision of each category into groups A, B and C, according to the number of TISS points scored at 24 hours postoperation. In this way a retrospective audit using SASA categories would clearly identify those postoperative patients who required intensive care.


Extending patient-controlled analgesia to patient-controlled neuroleptanalgesia. A trial was conducted (among 22 patients) to assess a new use of patient-controlled devices. Using a patient-controlled analgesia (PCA) pump under the anaesthetist's guidance, the patients self-administered a neurolept mixture consisting of droperidol and alfentanil. The patients were then able to undergo minor surgery (dilatation and curettage). The majority remained detached, sedated and pain-free, while able to control the PCA pump during the procedure. Patient-controlled neuroleptanalgesia or PCNA, as we propose to call this technique, appeared practical, effective and safe. The method was generally well accepted and highly rated by the patients.


Long-term results of Charnley low-friction arthroplasty of the hip. The long-term results of 488 Charnley low-friction arthroplasties, performed by one surgeon, were analysed. Radiological changes were assessed using the CART nomenclature. If sepsis (1.4%) is excluded, the mechanical failure rate of one or both components requiring revision surgery was 6.5%. The incidence of radiological loosening of components was 4.7%. Kaplan-Meier survival analysis predicts an 88% mechanical survival of components at 10-12 years.


Traumatic dislocation of the hip in children. A report of 4 cases. During a 1-year period 4 children, aged 4-14 years, suffering from traumatic dislocation of the hip were treated at H. F. Verwoerd Hospital. This is a rare injury and constitutes 0.335% of injuries seen in this unit. Two cases of anterior dislocations, which are even more rare, are included in this study. This article emphasises the importance of this injury in all cases of children subjected to severe trauma. However, as illustrated by 1 case, mild trauma may be sufficient to cause a dislocated hip in the young child.


[Does a correlation exist between positive wound cultures at the end of an operation and later wound and prosthetic sepsis?]. A prospective study was carried out on 51 patients in whom a reconstructive vascular procedure was performed in order to determine whether any correlation between positive wound cultures at the end of the operation and later wound and/or prosthetic sepsis exists. Swabs were taken from all surgical wounds and cultured for aerobic and anaerobic organisms. The patients were monitored for 72-89 months and all instances of wound or prosthetic sepsis thoroughly investigated. The incidence of positive wound cultures was 13%, with a variety of organisms present. No increased incidence of wound or prosthetic sepsis was observed in patients with positive wound cultures. The incidence of wound sepsis was 3.7% and of prosthetic sepsis 2%. No correlation was found between organisms cultured during operation and organisms isolated from septic wounds. The 1 case of prosthetic sepsis (at 19 months postoperatively) was probably due to secondary haematogenous infection.


Hypocalcaemia during surgery for ruptured De Bakey type III thoracoabdominal aneurysm. A case report. A case of a leaking De Bakey type III thoraco-abdominal aneurysm is reported. The ischaemic liver resulting from prolonged aortic cross-clamping, extensive blood loss, citrated homologous blood replacement and low calcium levels is discussed. It is suggested that during aortic clamping the ischaemic liver cannot metabolise the excess citrate in homologous blood and recommend that homologous blood is avoided during this period--crystalloids and heparinised blood being used instead of citrated blood.


Free plantaris (or tendo Achillis) osseotendinous transfer to restore finger flexion. A new method to restore flexion of fingers is described whereby the plantaris tendon (or part of the tendo Achillis), with its bony insertion, is transferred to the finger. Strong bony anchorage is achieved in the distal phalanx, while a sound interweaving suture technique proximally in the palm will ensure enough strength to allow immediate mobilisation.


[Abnormalities of ion movements in cardiac hypertrophy and failure]. Main sources of transmembrane ionic current that lead to cellular electrical activity are described. In hypertrophied myocardium, action potentials are usually markedly prolonged. Current modifications that could be responsible for this are not well established. However, despite divergent observations, one can postulate that calcium current density (current per area unit) is maintained to its normal level and that action potential lengthening can be related to a prolonged Na-Ca exchange current, a prolongation due to the lengthening of the calcium transient (systolic increase of intracellular calcium). In heart failure, calcium current appears reduced. It is markedly depressed in dilated human atria which greatly shortens action potential plateau. In cat, during the initial overload phase which triggers right ventricle hypertrophy, action potential plateau is also transiently reduced, which could correspond to an initial reduction of calcium current before its normalisation. Several effects are probably related to fiber stretch and appear to involve different types of stretch sensitive ionic channels.


Approaches to experimental arrhythmias in heart failure. Sudden cardiac death accounts for at least 50% of the mortality of patients with heart failure. Available clinical evidence suggests that lethal ventricular arrhythmias are responsible for the vast majority of cases of sudden death in heart failure. However, despite extensive clinical investigation over the last decade, there has been relatively little experimental study of the mechanisms underlying the development of lethal ventricular arrhythmias in heart failure. In addition to the original process leading to myocardium alterations, the role of other arrhythmogenic mechanisms such as ventricular overload and neuro endocrine activation remains to be elucidated. In ventricular hypertrophy both reentry and triggered activity may induce arrhythmias. Some studies on experimental models of heart failure did not provide consistent results concerning electrophysiological modifications and their relations with arrhythmias. Few studies in man in vivo are in favor of prolongation as well as increased dispersion of repolarisation in patients undergoing heart transplantation for idiopathic dilated cardio-myopathy. Further studies will need to be undertaken to clarify mechanisms underlying arrhythmias in heart failure.


[Ventricular pro-arrhythmic effects of anti-arrhythmia drugs]. Ventricular pro-arrhythmic effects of antiarrhythmic drugs correspond either to an aggravation of a pre-existing arrhythmia or to the development of a new arrhythmia not yet observed for a patient. More easily inducible ventricular tachycardias (VT) take part in this latter category. The incidence of ventricular pro-arrhythmias is difficult to evaluate but should be close to 3 to 10% during antiarrhythmic treatments. Two main mechanisms can be involved in pro-arrhythmia: 1) reentry can cause sustained VT complicating a pre-existing cardiopathy when a sodium channel blocker is prescribed, 2) early post depolarizations can result in the occurrence of torsades de pointes complicating an antiarrhythmic treatment which prolongs ventricular repolarization and QT interval. The main risk factors of pro-arrhythmia are in the first case the existence of antecedents of VT or V fibrillation with an altered ventricular function and in the second case an important prolongation of QT with bradycardia and hypokalemia. The incidence of pro-arrhythmia should decrease when these risk factors are taken into consideration. However the diagnosis of pro-arrhythmia should be systematically evoked by clinicians since these unwanted side-effects can occur with any class Ia, Ic and III antiarrhythmic drug and any drug which prolongs QT. If this diagnosis is confirmed, the need for an antiarrhythmic treatment should then be systematically evaluated in any patient taking into consideration the benefit/risk ratio of the treatment.


Adverse cardiovascular effects of anti-arrhythmia drugs. Part I: Proarrhythmic effects. Antiarrhythmic drugs are able to save patients from emergency dysrhythmic situations or to avoid symptomatic disorders when used in a prophylactic goal. However they can also induce adverse effects. Cardiovascular adverse effects, and especially proarrhythmic effects, are the most dreaded. Analysis of the underlying mechanisms of the onset and perpetuation of sustained arrhythmias could lead to a better understanding of causes of proarrhythmic effects and thus to a limitation of their occurrence. Antiarrhythmic drugs can modulate the three principal factors which are involved in the onset of arrhythmias: individual predisposing factors, trigger mechanisms and environmental factors. This multiparameter modulation will conduct either to suppress the arrhythmic disorders (antiarrhythmic effect) or to impair it (proarrhythmic effect). According to the numerous factors which take part in the onset and perpetuation of arrhythmia, incidence of proarrhythmic effect of antiarrhythmic drugs is very difficult to evaluate.


Adverse cardiovascular effects of anti-arrhythmia drugs. Part II: Inotropic effects and specific pharmacokinetic properties. The antiarrhythmic drugs are unfortunately not devoid of adverse effects. A good watching of their safety is necessary, according to their cardiovascular adverse effects which are the most dreaded. Among these and beside the proarrhythmic effects, the negative inotropic effects can impair cardiac function. Different mechanisms could explain the negative inotropic effects of antiarrhythmic drugs: reduction of adrenergic sensitivity, decrease of calcium concentration in the cardiac cells. Pharmacokinetic properties of antiarrhythmic drugs can modulate their cardiovascular adverse effects. As a matter of fact the plasmatic concentration of the unbound drug, which could be correlated to the adverse effects, fluctuates according to the protein binding of the drug. In an other way the first pass hepatic effect of a drug can be saturable so that the resulting dose-concentration curve becomes exponential. Drug disposition might also be very different from one patient to another depending on kidney and/or hepatic function and genetically determined metabolic pathways.


[Study of the influence of the time of administration on the antihypertensive effect and nitrendipine tolerance in mild to moderate essential hypertensive patients. Value of ambulatory recording of blood pressure on 24 hours]. Forty-one patients with mild to moderate hypertension were included in a multicentre trial. The objective was to assess the influence of the time at which nitrendipine (Nidrel 20 mg) is taken on its efficacy and tolerance. The drug was administered once daily either in the morning or in the evening during 2 consecutive periods of 28 days. Efficacy was assessed on an ambulatory recording of blood pressure over 24 hours. Globally, nitrendipine results in a statistically significant drop in blood pressure which is not influenced by the time of administration. Treatment response varies greatly according to the initial value of ambulatory diastolic blood pressure. There is a clear antihypertensive effect if ADBP is greater than or equal to 90 mmHg and no hypotensive effect if ADBP is less than 90 mmHg. The incidence of adverse effects did not vary according to the time the drug was taken. Biological tolerance was excellent. Nitrendipine, administered once daily alone appears to be an efficient antihypertensive agent, well tolerated both clinically and biologically. Its efficacy is maintained over a 24-hour period regardless of the time at which the drug is taken.


[Study of the association of bladder cancer and phenacetin use. Problems set by a pharmaco-epidemiological study]. In a survey of the literature, phenacetin appears to be responsible for an increased risk of urothelial tumours in humans, especially renal pelvis tumour. Few observations have suggested an association between bladder cancer and phenacetin containing analgesics however. To assess this association in France, a case-control study of bladder cancer (143 cases, 120 controls) was undertaken. We point at some methodological difficulties, such as difficulties of recall, definition of a control group, non-responses, possible French distinctive features of analgesics use. Results are not able to confirm the suspected relationship between bladder cancer and phenacetin use.


Characterization, self-assembly and reattachment of S layer from Clostridium botulinum type E saroma. S layer of Clostridium botulinum type E Saroma and its subunits were isolated and characterized for their chemical and morphological properties. The S layer was composed of a number of subunits with apparent molecular weights ranging from about 10 to 150 kDa. The isolated S layer subunits possess the ability to assemble into recrystallized flat sheets in the absence of any supporting layer and to reattach to the cell wall from which they have been removed. Immunoblot analysis using an antiserum against whole cells of the organism showed that 60 kDa and 90 kDa subunits of the S layer were major somatic antigens of the organism. Immunogold-labeling using monospecific antiserum raised to the individual 60 and 90 kDa proteins revealed that both subunits were exposed evenly over the entire cell surface. The amino acid compositions of both subunits showed that aspartate and glutamate were predominant whereas cystine and methionine were poor. The amino acid composition and acidic property of the two subunits of the S layer agree well with the results obtained from the S layers of other bacterial species as well as other pathogenic clostridia.


The characteristics of interval breast cancer in mass screening. To investigate the characteristics of interval breast cancer in mass screening, comparisons were made of the following three groups: interval group (21 interval breast cancer cases), mass screening group (87 breast cancer cases detected by mass screening) and outpatient group (266 breast cancer cases diagnosed at outpatient clinics). There were no differences among the three groups in terms of the case distribution by age or obesity, but significant differences in the case distribution according to nodal involvement and tumor size. Histological grading of the malignancy of the primary tumors disclosed that the incidence of breast cancer showing frequent mitoses was high in the interval group compared to the mass screening and outpatient groups. The 7-year cumulative disease-free survival rate was 75.3% in the interval group, 90.0% in the mass screening group and 83.1% in the outpatient group. The mean tumor size of the interval cases at the time of mass screening, back-calculated on the basis of the estimated tumor doubling time, was 1.5 cm in diameter, smaller than that of the mass screening group. It is surmised that interval breast cancer is characterized by marked proliferation of the tumor cells and has a poorer prognosis than the other group cases. These findings might be due to the marked proliferation of interval breast cancer rather than because of cases having been overlooked at the time of the last screening.


[Tolerance of famotidine. Study of network of sentinel physicians in pharmaco-vigilance]. This paper presents the results of an intensive surveillance based on a network of general practitioners and following 200 patients treated by famotidine 40 mg per day during 6 to 8 weeks. Four patients with a previous experience of adverse reaction to another H2 antagonist did not relapse with famotidine. None interaction was reported with drugs such as beta-blockers, oral anticoagulants, theophylline, benzodiazepines, calcium antagonists. Twenty four clinical side effects were reported; For 5 patients (2.5%) the treatment had to be stopped. The most common side effects were neurological. The results are compared with those of previously published studies.


Radioactive cesium in dirt accumulations on the roof of buildings. The concentrations of 137Cs and 134Cs in dirt deposits on the roofs of buildings are much higher than those in the surface of soil at ground level. Thus dirt on roofs concentrates radioactive cesium in fall-outs. The 137Cs concentration in dirt deposits on the roofs of older buildings is not consistently higher than that on the roofs of new ones, but the 137Cs/134Cs ratio is higher in deposits on older buildings constructed before the first half of the 1970s, and decreases exponentially with decrease in age of the buildings gradually reaching 1.9 +/- 0.2, the value in the air-borne dust at the time of the Chernobyl accident. From this relationship, the contribution of Chernobyl radioactivity to accumulated 137Cs was calculated as 32% on buildings constructed in 1962. The radioactive cesium concentrations in dirt deposits in gutters of private houses and on the roofs of university buildings in Japan were also determined.


[Comparison of tacrine hepatotoxicity in patients with Alzheimer disease or AIDS]. Previously used in Alzheimer disease Tacrine (THA): tetrahydroaminoacridine has shown a rise of hepatic transaminase enzyme activity (TEA) in 18% of patients for Summers and 19% for Ames. Although studies using THA from USA or Canada have noticed a rise of TEA in 30% of the patients, after a treatment course with French THA we also have noted a rise of TEA in 12% of the Alzheimer patients. However, these secondary effects yielded to the end of treatment. These studies have been done with THA from different origins and different associations. Summers, the Canadian group and the French one have used THA in association with lecithin, when american group study has been made with no additional product. Therefore we have initiated a trial with oral THA in AIDS patients. 52 patients with HIV infection (26 in the IVC1 group and 26 in IVC2 group) have been treated with the same THA as the one used for Alzheimer french group. The common dosage was 150 to 200 mg (3 to 4 of 50 mg dosing capsules per day). The THA has been synthetized such as having an over 99% pureness product. After a period of 260 months/patient no elevation of TEA has been noted in any patients of our group. These results observed in HIV advanced patients with this THA are discordant with the one observed in Alzheimer's study. The dosage used in AIDS is twice higher than the one used for Alzheimer which gives us credit to the lack of hepatic toxicity in HIV advanced patient after 7 months of treatment.


Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes. A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid.


Two sudden death cases of idiopathic ventricular tachycardia. It is said that the prognosis of idiopathic ventricular tachycardia (IVT) without organic heart disease is good in general. In this paper, two sudden death cases of IVT are reported. The first case was a 44-year-old male, who was referred to our hospital for further examination and treatment of ventricular tachycardia. Echocardiography did not show obvious organic heart disease. After the patient was diagnosed with IVT, he was given drug therapy at the outpatient clinic. However, about six months later, he died suddenly while playing mahjong late at night. The second case was a 17-year-old male. He was also referred to our hospital by another hospital after being diagnosed with ventricular tachycardia. A diagnosis of IVT was made, for which he was given drug therapy at outpatient clinic. However, the patient discontinued receiving the drug therapy. The patient died suddenly about 3 months after discontinuation of the therapy. Some idiopathic ventricular tachycardia cases have poor prognosis like the present ones. It was considered necessary to thoroughly control and guide patients with their daily life and monitor them carefully about the ingestion of anti-arrhythmic agents.


Unusual cases of benign stricture of the biliary tract. Three patients, i.e., two adults and one child, with unusual benign stricture of the extrahepatic biliary duct are reported. Case 1 is a 63-year-old male with obstructive jaundice caused by a sclerotic vascular ring formed by the right hepatic artery and its branch. Case 2 is an 18-year-old male with obstructive jaundice due to stricture of the common bile duct caused by compression of enlarged collateral varicose veins, so-called cavernous transformation following extrahepatic obstruction of the portal vein. Case 3 is a 19-month-old boy complicated with biliary obstruction resulting from ischemic changes of the biliary duct at 10 months after extended right hepatectomy for mesenchymal hamartoma of the liver. The definitive diagnosis was made on the basis of imaging evaluations and the surgical findings. They have been free of jaundice and have shown an uneventful clinical course after the surgical interventions.


A case of femoral hernia in a child.

A case of femoral hernia in a child. A 9-year-old boy with a painless reducible swelling in the right groin was admitted to our hospital. The diagnosis of a right external inguinal hernia was made, but no inguinal hernial sac was found at operation. On further examination, the diagnosis of femoral hernia was confirmed. Radical operation for the femoral hernia was performed using McVay's procedure, and there has been no recurrence since the operation. In the Japanese literature, 25 cases of femoral hernias have been reported in children aged 1 month-9 year (average age, 4 years). The sex ratio of M:F was 2:3. Eleven cases were on the right side, 7 were on the left, and 5 were bilateral. The rate of irreducible femoral hernia was 48% (12/25 cases). Femoral hernias in children are very rare and often misdiagnosed as inguinal hernias. Correct diagnosis was made in only three cases (12%). Careful examination and awareness of the possibility of femoral hernia in children are very important when dealing with groin swelling in children.


A case of concealed WPW syndrome with three different reciprocal tachycardias due to triple AV nodal pathways. Triple atrioventricular nodal pathways (TAVNP) occur occasionally, but it is rare for them to produce more than two different tachycardias. Here we report a case of concealed WPW syndrome with three different tachycardias. During electrophysiologic studies, three different reciprocal tachycardias were induced. Tachycardia #1 was characterized by a cycle length of 230 msec and an A'-H interval of 70 msec. For tachycardia #2, these parameters were 300 msec and 140 msec, while they were 370 msec and 200 msec for tachycardia #3. During all three tachycardias, the earliest atrial activity was observed in the left atrium. Ventriculoatrial conduction occurred following ventricular stimulation, and the earliest atrial activity was observed in the left atrium, indicating the existence of left-sided accessory pathway. Persistence of tachycardia for 15-30 min caused marked pulmonary congestion. The heart rate was very high (260 beats/min) during tachycardia #1, and the pulmonary arterial pressure rose to 40/30 mmHg, with the pulmonary arterial diastolic pressure remaining at about 30 mmHg throughout the tachycardia. It seems that the pulmonary venous pressure rises abnormally during paroxysmal supraventricular tachycardia with a very high heart rate and that pulmonary congestion can easily occur during a short period of tachycardia.


In vitro self-assembly of the S layer subunits from Clostridium difficile GAI 0714 into tetragonal arrays. Regularly arrayed surface component (S layer) of Clostridium difficile strain GAI 0714 was isolated with 4 M guanidine hydrochloride from the cell wall of the organism, and examined for self-assembly in vitro. The S layer was composed of two different protein subunits with molecular weights of 32 kDa and 45 kDa. Optical diffraction analysis revealed that the morphological units of both native and self-assembled S layer were essentially identical and composed of a rhombus possessing each side of 8.1 nm and interior angle of 88 degrees. The self-assembly of S layer subunits were induced in the presence of divalent cations such as Ca2+ or Zn2+, but Ba2+ or monovalent cations including K+, Na+ and Li+ failed to induce self-assembly. These results suggest that Ca+2 or Zn+2 may act as bridges to link negatively charged surface subunits.


Sudden unexplained death syndrome. A review and update. Sudden unexplained death syndrome (SUDS) among young healthy Thai construction workers in Singapore has been given much publicity recently. From May 1982 to July 1990, 226 SUDS were reported among them. In this article we review and compare studies on SUDS in the United States and South-east Asia. So far, studies to identify the causal factors have been inconclusive and they cannot explain the male preponderance and occurrence of death during sleep. Current hypotheses about the cause of SUDS have included stress, genetic factors, dietary deficiency (particularly thiamine), potassium deficiency, melioidosis and sleep disorders. The following areas are suggested for further research: epidemiological investigations on SUDS at its source; in-depth case studies of families with and without SUDS; role of dietary factors, biochemical studies with respect to thiamine, pyruvate and potassium metabolism in the victims and susceptibles; and histopathological studies of cases and controls.


Malaria in infants whose mothers received chemoprophylaxis: response to amodiaquine therapy. In October 1988, a project was implemented for assessing the malaria chemoprophylactic efficacy of weekly chloroquine (CQ) and daily proguanil (PROG) during pregnancy in Muheza-Tanzania. Resultant CQ and PROG-cohorts of infants were followed up for prompt diagnosis and treatment of malaria. Infections were primarily treated with 25 mg base amodiaquine/kg over 3 days. By September 1990, 49 and 60 infants from PROG and CQ cohorts respectively had completed one year follow up. Thirty-five (71%) infants of PROG and 44 (73%) for CQ-cohort were infected with malaria before 3 months of age. The one year mean infection episode rates were 7 (PROG-cohort) and 6.6 (CQ-cohort). Amodiaquine cleared 209 (80%) of PROG's total infections and 224 (81%) for CQ-cohort, and significantly reduced the infection load among clearance failures. Clearance failures had high pre-treatment parasite densities whilst post-treatment densities were higher in the CQ-cohort than PROG-cohort. Low malaria immunity and chloroquine's long residence time could explain these differences. We conclude that early infancy malaria is common and should always be suspected, looked for and adequately treated. Amodiaquine is better than chloroquine for malaria primary therapy during infancy and early childhood.


Age-related prevalence of Strongyloides stercoralis infection in Okinawa, Japan. Age-prevalence of Strongyloides stercoralis infection was studied in six areas of Okinawa, Japan. In all localities, most of the infected inhabitants were aged over 40 years of age and females were less infected than males. The peak prevalence was found in inhabitants in their fifties in high endemic groups and shifted to higher age in lower endemic groups. This age-prevalence pattern resembles more that of schistosome infections than that of other gastrointestinal helminthic infections.


Helicobacter pylori and dyspepsia in an Arab population. To determine the incidence and significance of the detection of Helicobacter pylori in an Arab population, 116 patients with dyspepsia were studied. 89 percent of these patients had H. pylori detected by culture or/and histological definition of Campylobacter-like organisms. By the modified rapid urease test (RUT) 80% of the patients had H. pylori (sensitivity of 91%, specificity of 75%). Irrespective of the endoscopic diagnosis, the presence of H. pylori was associated with histologic evidence of gastritis. A heavy growth of H. pylori on culture was associated with active gastritis. There was no difference in the incidence rates of H. pylori with regard to various diagnoses by endoscopy. It is suggested that H. pylori may be hyperendemic among Arab patients with dyspepsia. Its presence is associated with varying severity of gastritis with or without additional endoscopically recognised findings.


Comparative studies of live neonates in maternal sickle cell haemoglobinopathy in Ghana. This study assessed the current status of live neonates born to sickle cell mothers when compared with those of normal (control) women. Birth weight, placental weight, fetoplacental ratio, and gestational age for live neonates in singleton births by twenty-nine haemoglobin SS (HbSS), fifty-two haemoglobin SC (HbSC), and fifty-one (normal) haemoglobin AA (HbAA) mothers were statistically compared. Neonates of HbSS mothers had a statistically lower than normal mean birth weight and gestational age, but only a shorter mean gestation significantly distinguished those of the HbSC and HbAA mothers. Inferentially, neonates delivered by HbSS women were both underweight and preterm, whereas those of HbSC women were preterm but not underweight, and apparently large for gestational age (LGA). No statistical differences were found between neonates in terms of placental weights or fetoplacental ratios.


Growth and sexual maturation of Brazilian patients with sickle cell diseases. Growth and sexual maturation was studied of 125 Brazilian patients with sickle cell disease whose ages ranged from 7 months to 42 years. Height and weight were significantly lower when compared with the unaffected population. The height and weight deficit increased in the age range of 11-19 years as compared with patients less than 11 years of age. Age of menarche, breast and pubic hair staging in girls, and genitalia staging and testicular volume measurements in boys indicated a delayed sexual maturation for both sexes. The comparison of adult and young patients, however, demonstrated that although puberty is delayed, a normal sexual maturation is attained later in life by most patients.


A reappraisal of underlying pathology in adult patients presenting with pancytopenia. An analysis of the underlying pathology and different clinico-haematological features of 202 adult pancytopenic patients is presented. Aplastic anaemia (40.6%), megaloblastic anaemia (23.26%) and acute myeloblastic leukaemia (12.8%) together accounted for most of the cases. Our aplastic anaemia cases showed several different features compared to the cases reported in western literature. Aplastic anaemia and megaloblastic anaemia patients revealed significant differences in the incidence of hepatosplenomegaly, anisocytosis, circulating erythroblasts, relative lymphocytosis (P < 0.001 for all) and reticulocytosis (P < 0.01). The present study stresses the importance of physical and peripheral blood findings in the management of pancytopenic patients.


Hemoptysis in rheumatic heart disease.

Hemoptysis in rheumatic heart disease. 107 Consecutive patients with rheumatic valvular heart disease (41 males, 66 females, average age 24.2 years) being followed at an Ethiopian cardiology referral clinic were examined and questioned about their experience of hemoptysis. 51 Patients (48%) gave a history of hemoptysis; 11 described their usual hemoptysis as frank blood, 40 as blood-streaked sputum. 29 patients had frequent hemoptysis, 13 had several episodes, and 9 only 1 occurrence. Prevalence of hemoptysis did not vary significantly by sex, physical findings, New York Heart Association classification, or valvular lesion, including the presence or absence of mitral stenosis. A majority (64) had been tested for tuberculosis, with 5 having been treated for active disease. Hemoptysis is a common manifestation of rheumatic heart disease, and is usually well tolerated.


Renal papillary necrosis in Kuwait.

Renal papillary necrosis in Kuwait. In 2,158 consecutive routine urograms, 85 patients (51 males and 34 females) were found to have typical changes of renal papillary necrosis, an incidence of 3.9% (2.8% in males, 9.4% in females). The changes were bilateral in 60 patients (71.6%) and unilateral in 25 (29.4%). 3 patients were diabetics, 4 had sickle cell anaemia and 7 had obstructive uropathy. 19 patients admitted to analgesic abuse. The remaining 52 patients were idiopathic but a combination of analgesic abuse and dehydration may have been the cause in this group. The possible reasons for the high incidence of RPN especially in females in this hot desert environment are discussed. The literature on the subject is briefly reviewed.