Biomedical subjects
Publications and source records attributed to K Desai.
A 20-day-old female neonate presented with an immature teratoma in the midline posterior fossa. The tumor was totally removed but the patient died of pneumonia. Teratoma is a rare tumor, but very difficult to treat as the patients tend to be young, and the outcome is very poor.
A rare case of primary malignant melanoma in the cerebello-pontine angle, in a 17 year old girl is presented. The patient presented with one month history of headache, diplopia, facial asymmetry and ataxia. The computerised tomography (CT) scan and magnetic resonance imaging (MRI) revealed a large cerebello-pontine angle mass with features suggestive of a melanoma. The typical black coloured, solid and vascular melanoma was excised completely. Cerebello-pontine angle melanoma are extremely rare tumours with dismal long term outcome in majority of these cases.
Sinus pericranii is a rare vascular anomaly. A case of sinus pericranii at the nasion with an orbital extension is presented. The drainage was into the superior sagittal sinus. The pathogenesis is discussed and the literature is reviewed.
Cardiomyopathy is a major cause of morbidity and mortality. Ventricular conduction delay, as shown by prolonged deflections in the electrocardiogram caused by delayed ventricular contraction (wide QRS complex), is a common feature of cardiomyopathy and is associated with a poor prognosis. Although the G(i)-signaling pathway is up-regulated in certain cardiomyopathies, previous studies suggested this up-regulation was compensatory rather than a potential cause of the disease. Using the tetracycline transactivator system and a modified G(i)-coupled receptor (Ro1), we provide evidence that increased G(i) signaling in mice can result in a lethal cardiomyopathy associated with a wide QRS complex arrhythmia. Induced expression of Ro1 in adult mice resulted in a >90% mortality rate at 16 wk, whereas suppression of Ro1 expression after 8 wk protected mice from further mortality and allowed partial improvement in systolic function. Results of DNA-array analysis of over 6,000 genes from hearts expressing Ro1 are consistent with hyperactive G(i) signaling. DNA-array analysis also identified known markers of cardiomyopathy and hundreds of previously unknown potential diagnostic markers and therapeutic targets for this syndrome. Our system allows cardiomyopathy to be induced and reversed in adult mice, providing an unprecedented opportunity to dissect the role of G(i) signaling in causing cardiac pathology.
We reviewed the pattern of involvement of the calvarium by tuberculosis (TB) in five patients and the role of imaging in its management. Four patients presented with localised scalp swelling and one with generalized seizures. Radiographs revealed lucent lesions with minimal surrounding sclerosis in the frontal (2), parietal (2) and occipital (1) bones. CT showed lesions involving the entire thickness of the calvarium and accompanying contrast-enhancing soft tissue. The patient presenting with seizures had a ring-enhancing lesion in the parietal lobe in addition to the extra-axial lesions. Although radiographs in all cases demonstrated calvarial TB, CT showed the extent of the defect, involvement of adjacent soft tissues, and in one case an intra-axial lesion. Radiographs suffice for follow-up of these patients.
OBJECT: The authors analyzed the cases of 163 patients with syringomyelia to assess the appropriate surgical procedure. METHODS: Depending on the aetiological factors and treatment considerations the series was classified into three groups. Group I were cases where there was no definite demonstrable aetiological factor; Group II cases had basilar invagination and/or Chiari malformation; and Group III consisted of cases where the syrinx was secondary to an obvious aetiology, such as a mass lesion either in the posterior cranial fossa or in the spine or a severe kyphotic spinal deformity. Post-traumatic syringomyelia and syrinx in association with spina bifida were not studied. CONCLUSIONS: We concluded that for Group I cases syringosubarachnoid shunting is the ideal form of treatment. In Group II cases foramen magnum bony decompression is satisfactory and physiological. Good results were obtained even in cases where either a foramen magnum decompression alone or in combination with a syringo-subarachnoid shunt was done. Only syringosubarachnoid shunt (without a foramen magnum decompression) in Group II cases was found to produce poor outcome. Group III cases should be treated for the primary aetiological problem. Only syrinx drainage procedure without treatment of aetiology in these cases produced poor results. It was observed that clinical outcome rather than radiological improvement is the reliable indicator of the surgical result.
Restructuring healthcare delivery systems within limited budgets presents multiple management challenges. As hospitals have downsized, the demand for in-home services has increased. The involvement of multiple provider agencies and professionals has heightened duplication and fragmentation of services and has complicated the need to develop client-focused, evidence-based approaches. In response to these challenges, community-based case management has burgeoned.
A case of primary Ewing's sarcoma involving a large portion of the petrous temporal bone in an eighteen month old child is reported. The lesion was treated by radical surgery and adjuvant chemotherapy and radiotherapy. An extremely rare age of presentation, an unusual location and an excellent response to treatment are the highlights of this case.
An 8-year-old boy with no evidence of von Recklinghausen's disease presented with an unusual neurinoma manifesting as a gradually progressive swelling in the suboccipital region over 2 years. The lesion was massive and had widely eroded the posterior aspects of the atlas, axis, and suboccipital bone. The tumor had involved the dura of the sigmoid and transverse sinuses, was highly vascular, and had encased the ipsilateral vertebral artery. The tumor was almost completely resected although with considerable loss of blood through a large rent in the right sigmoid sinus. This unusual benign neurinoma most probably arose from the second cervical ganglion.
Sixty patients with anterior clinoid meningiomas (mean age 48 years) were surgically treated. There was a slight female predominance. Headache and visual impairment were the commonest clinical symptoms at presentation. The patients were classified on the basis of extent of the visual impairment, size of the tumor, and the tumor relationship with the internal carotid artery. A grading system was designed using the total scores in these classifications on the scale of 2-10. The classifications and the grading system were assessed for planning of the operative strategy, anticipating the extent of resectability, possible difficulties in dissecting the carotid artery and optic nerve during the operation, and prognosis. Total resection was achieved in 42 cases (scores 4-8), subtotal resection in 17 cases (scores 7-10), and only partial resection in one case (score 10). Vision improved in 14 cases. Three patients died following surgery. Mean follow up was 26 months. There was one recurrence. Fifty-four patients are leading independent and active lives.
This 58-year-old man presented with a left frontal bone lesion that had been growing over a 2-year period. The lesion increased in size, resulting in proptosis that affected the patient's visual acuity and eyeball movement. On computerized tomography and x-ray studies, a huge lesion located between the widened frontal diploic bone and involving the orbital roof and paranasal sinuses was noted. The entire lesion was radically resected. The authors unexpectedly found that an intradiploic organized hematoma had caused the swelling.
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Treatment of rats with ethylbenzene (EB) modulates the hepatic expression of many P450s, with those induced after a single intraperitoneal hydrocarbon injection differing from those induced after more prolonged (3 day) administration. The goals of the current studies are (1) to characterize the induction response after prolonged hydrocarbon exposure, (2) to explain why the elevation of these P450s is attenuated after continued treatment, and (3) to determine how P450 2B protein remains elevated without an elevation of P450 2B1/2 RNA. P450 2C11 protein was decreased after a single EB injection and remained depressed throughout the treatment period. P450 2C11 RNA was only decreased with prolonged, but not acute treatment. P450 2E1 was induced after a single EB injection; however, the initial induction was attenuated with more prolonged treatment. P450 2B1 and P450 2B2 RNAs exhibited a similar response, being elevated after acute administration, but returned to control levels with prolonged EB administration. Interestingly, P450 2B protein levels remained elevated despite the decrease in P450 2B1 and P450 2B2 RNA to control levels. We then tested the possibility that the multiphasic induction pattern of P450 2E1 and P450 2B1/2 RNA was due to differences in the pharmacokinetics of EB. The disappearance of EB with time was measured in rats that were either (1) untreated, (2) pretreated with EB for 1 day, or (3) pretreated with EB for 3 days. These results demonstrated that prior hydrocarbon exposure caused an increase in EB clearance, which decreased the overall levels of EB in the body. Consequently, EB levels were sufficiently diminished to decrease EB's effectiveness as an inducer leading to the decrease in P450 2E1 protein and P450 2B1 and P450 2B2 RNA after continued EB administration. A further consequence of the decreased overall EB concentration is that the hydrocarbon was capable of producing only a transient elevation of P450 2B1 RNA levels. This transient elevation appears to be sufficient to maintain elevated P450 2B protein.
Given that interesting HIV vaccine candidates, including live preparations and DNA plasmids, exist and that the first phase III vaccine (AIDSVAX) testing is due to begin this summer, 1998, in the U.S., adequately addressing trial preparedness is a pressing issue. Despite double-blind randomized controlled clinical trial design, there may be difficulties with interpretation and use of the usual measures of vaccinal efficacy and calculation of sample size. Difficulties arise from vaccine characteristics (e.g. mode of action, time-lag, waning) and population heterogeneities (e.g. differences in susceptibility, sexual behaviour, mixing preferences) causing frailty effects that can exacerbate bias and time-dependent effects already known to exist in simple cases. Since vaccine properties, particularly mode of action, are unlikely to be known before the onset of clinical trials, choosing an efficacy measure and the associated analyses and sample size calculations will be problematic. Interim analyses designed to decide whether a study will be prolonged may be tenuous if based on a time-dependent measure and will influence sample size determination. Despite shortcomings, general recommendations can be made to minimise pernicious effects. The objectives of this paper are principally to review the current state of knowledge of the different stages in the preparation of large phase III HIV vaccine efficacy trials, the methodological difficulties related to their design, and the analysis of data collected from them. Mathematical models and trial simulations are used to demonstrate that further research is necessary to study the behaviour of vaccine efficacy measures under heterogeneous conditions of population, vaccine action, and trial design and identify a time-independent efficacy measure. Alternative methods to validate sample size calculations have to be developed in older to reduce the chances of unnecessary economic and human cost in phase III HIV vaccine trials.
A 12 year old boy with acute lymphoblastic leukaemia had received prophylactic cranial irradiation (2000 cGy/15 days) and intrathecal methotrexate. Six years later he was diagnosed to have glioblastoma in left temporoparietal region. There is a strong possibility that the glioma may have been radiation and/or chemotherapy induced.
The authors present five cases of intracranial hydatid cysts managed at the department of Neurosurgery, King Edward Memorial Hospital, Mumbai, between 1984-1997. The mean age of presentation was 13.4 years. Four patients (80%) were in the first decade of life. All patients presented with focal neurological deficit and clinical features of raised intracranial pressure. Radiological investigations included computerised tomography (CT) scan in three cases, CT and magnetic resonance (MR) scan in one case and accidental cystogram in one case. Two patients had multiple intracranial cysts. One patient had a solitary cyst in the lateral ventricle. Commonest location was in the parietal lobe (3 cases). Total excision of the cyst was done in all five cases. Recurrence was seen in two cases, probably as a result of rupture of the cyst during first surgery. The features of this rare disease are retrospectively analyzed in this presentation and the literature is reviewed.
Perchloroethylene (Per)-induced nephrotoxicity and nephrocarcinogenicity have been associated with metabolism by the glutathione (GSH) conjugation pathway to form S-(1,2,2-trichlorovinyl)glutathione (TCVG). Formation of TCVG was determined in incubations of Per and GSH with isolated renal cortical cells and hepatocytes from male and female Fischer 344 rats and with renal and hepatic cytosol and microsomes from male and female Fischer 344 rats and B6C3F1 mice. The goal was to assess the role of metabolism in the sex and species dependence of susceptibility to Per-induced toxicity. A key finding was that GSH conjugation of Per occurs in kidney as well as in liver. Although amounts of TCVG formation in isolated kidney cells and hepatocytes from male and female rats were generally similar, TCVG formation in subcellular fractions showed marked sex, species, and tissue dependence. This may be due to the presence of multiple pathways for metabolism in intact cells, whereas only the GSH conjugation pathway is active in the subcellular fractions under the present assay conditions. TCVG formation in kidney and liver subcellular fractions from both male rats and mice were invariably higher than corresponding values in female rats and mice. Amounts of TCVG formation in rat liver subcellular fractions were approximately 10-fold higher than in corresponding fractions from rat kidney. Although rats are more susceptible to Per-induced renal tumors than mice, amounts of TCVG formation were 7- to 10-fold higher in mouse kidney subcellular fractions and 2- to 5-fold higher in mouse liver subcellular fractions of both sexes compared to corresponding fractions from the rat. Hence, although the higher amounts of TCVG formation in liver and kidney from male rats correspond to their higher susceptibility to Per-induced renal tumors compared with female rats, the markedly higher amounts of TCVG formation in mice compared with rats suggest that other enzymatic or transport steps in the handling of Per in mice contribute to their relatively low susceptibility to Per-induced renal tumors
OBJECT: The authors analyzed the cases of 190 patients with basilar invagination that was diagnosed on the basis of criteria laid down in 1939 by Chamberlain to assess the appropriate surgical procedure. METHODS: Depending on the association with Chiari malformation, the anomaly of basilar invagination was classified into two groups. Eighty-eight patients who had basilar invagination but no associated Chiari malformation were assigned to Group I; the remainder of the patients, who had both basilar invagination and Chiari malformation, were assigned to Group II. The principal pathological characteristic was observed to be direct brainstem compression due to odontoid process indentation in Group I and a reduction in posterior cranial fossa volume in Group II. CONCLUSIONS: Despite the anterior concavity of the brainstem in both groups, transoral surgery was the most suitable procedure for those patients in Group I and decompression of the foramen magnum was found to be appropriate for patients in Group II. After surgical decompression, a fixation procedure was found to be necessary in most Group I cases, but only in a small minority of Group II cases.