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Biomedical subjects

M Shah

Publications and source records attributed to M Shah.

At least 73 records · Page 4Linked to original sources
PubMed2000

Prospective analysis of Staphylococcus aureus bacteremia in nonneutropenic adults with malignancy.

PURPOSE: To determine the primary sources and secondary complications of Staphylococcus aureus bacteremia (SAB) in cancer patients, as well as predictors of outcome in cancer patients with SAB. PATIENTS AND METHODS: Fifty-two patients at Duke University Medical Center met entry criteria between September 1994 and December 1996 for this prospective cohort study involving hospitalized nonneutropenic adult cancer patients with SAB. All subjects were observed throughout initial hospitalization and were evaluated again at 6 and 12 weeks or until death. RESULTS: SAB was intravascular device-related in 42%, tissue infection-related (TIR) in 44%, and unidentifiable focus-related (UFR) in 13%. Seventeen patients (33%) were found to have metastatic infections or conditions, with eight (15%) developing infectious endocarditis (IE). Patients with TIR bacteremia were less likely than other patients to develop IE (4% v 24%, P =.06). The overall mortality rate was 38%, the SAB-related mortality rate was 15%, and the rate of SAB relapse was 12%. Methicillin resistance was not associated with adverse outcome. Inability to identify a point of entry (UFR bacteremia), however, was associated with a higher overall mortality rate (100% v 24%, P =.0006). Furthermore, a 72-hour surveillance blood culture positive for organisms was associated with an increased incidence of IE (P =.0006), metastatic infections or conditions (P =.0002), SAB relapse (P =.038), and SAB-related death (P =.038). CONCLUSION: SAB in cancer patients is associated with significant morbidity from frequent metastatic infections or conditions including IE, as well as considerable mortality. Unknown initial infection site and 72-hour surveillance cultures positive for organisms were predictive of a complicated course and poor final outcome.

Adolescent↗
PubMed2000

Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.

Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.

Aging↗
PubMed2000

Nutritional rickets still afflict children in north Texas.

Nutritional rickets is uncommon in North America, particularly in regions where sunlight is plentiful. Recent epidemics in North America occurred in dark-skinned toddlers with poor nutrition who had insufficient exposure to sunlight and whose parents were members of ethnic, social, and socioeconomic groups with predisposing practices. Nine children (8 toddlers and 1 infant) were referred to the Bone Metabolic Clinic at Texas Scottish Rite Hospital for suspected rickets between October 1997 and October 1998. The diagnosis of nutritional rickets was based on clinical, biochemical, and radiological evidence. All children were dark-skinned: 8 were African Americans and 1 was of Hispanic parentage. All children were breast-fed with minimal intake of dairy products; none received vitamin supplementation. All children were followed up by health care professionals. Two patients were children of upper-middle class parents. Birth order was not a contributing factor in the development of nutritional rickets. Radiological and biochemical rachitic changes remitted within 3 months of vitamin D therapy combined with dietary modification. Primary care providers should consider vitamin D supplementation in all infants with increased skin pigmentation and especially in those who are primarily breast-fed. Nutritional rickets can develop in dark-skinned infants of any social or ethnic background. Residing in a geographical area with abundant sunlight is not a guarantee against the development of nutritional rickets in dark-skinned children.

Female↗
PubMed2000

Functional correlation in amino acid residue mutations of yeast iso-2-cytochrome c that is consistent with the prediction of the concomitantly variable codon theory in cytochrome c evolution.

Fitch and Markowitz' theory of concomitantly variable codons (covarions) in evolution predicted the existence of functional correlation in amino acid residue mutations among present-day cytochromes c. Mutational analysis was carried out on yeast iso-2-cytochrome c, where hydrophobic core residues I20, M64, L85, and M98 and surface residue L9 were mutated, in selected combinations, to those found in mammalian and bird cytochromes c. The functionality assay is based upon the ability of yeast cells to grow in YPGE medium. Furthermore, experiments on the single M64L and M98L mutations as well as the double M64L/M98L mutation using NMR showed that the effects of these mutations are to perturb the structural integrity of the protein. We identified functional correlation in two cases of a pair of residue mutations, the I20-->V and M98-->L pair and the L9-->I and L85-->I pair. In both cases, only one of the two alternative, putative evolutionary pathways leads to a functional protein and the corresponding pairs of residue mutations are among those found in present-day cytochromes c. Since valine is predicted to be at position 20 in the ancestral form of cytochrome c, the present data provide an explanation for the ancient requirement of leucine rather than methionine in position 98. The present data provide further evidence for the role of those specific atom-atom interactions in directing a pathway in the evolutionary changes of the amino acid sequence that have taken place in cytochrome c, in accordance with Fitch and Markowitz.

Amino Acid Substitution↗
PubMed1999

The prognostic implications of outpatient diuretic dose in heart failure.

In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).

Aged↗
PubMed1999

Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome.

STUDY OBJECTIVES: To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle. DESIGN: Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs). SETTING: The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs. PATIENTS: Nine patients (mean age 59.8+/-11.3 years [range: 33-72]; 4 males, 5 females) with clinically severe idiopathic RLS. INTERVENTIONS: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring. MEASUREMENTS AND RESULTS: Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circadian rhythm appeared to be within the normal range for age. CONCLUSIONS: An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Adult↗
PubMed1999

Misregulation of connexin43 gap junction channels and congenital heart defects.

Although there is general agreement that gap junction channels formed by the connexin43 (Cx43; alpha 1) protein most likely have important roles during heart development, evidence to support this view has been equivocal. Lacking this information, it is difficult to understand the basis of heart malformations found in the Cx43 knockout mice and in children with a severe form of visceroatrial heterotaxia that coincides with missense mutations of the Cx43 gene. To address this issue we used a combination of western blots to follow the emergence of Cx43 in heart, and in vitro and in vivo phosphorylation to assess the effect of mutation on Cx43 phosphorylation. We evaluated the activity ratios of cAMP-dependent protein kinase and protein kinase C in hearts of 8.5-day-old mouse embryos through to birth. The results demonstrate that Cx43 is present in the native phosphorylated species in day 8.5 hearts and thereafter. Further, the activities of cAMP-dependent protein kinase and protein kinase C are mirror images of each other during the 8.5-10.5 days of early heart development. From these results we conclude that Cx43 gap junction channels are present and capable of being regulated by day 8.5 of embryonic heart development.

Amino Acid Sequence↗
PubMed1999

Role of elevated plasma transforming growth factor-beta1 levels in wound healing.

Transforming growth factor (TGF)-beta1 plays a central role in wound healing. Wounds treated with neutralizing antibody to TGF-beta1 have a lower inflammatory response, reduced early extracellular matrix deposition, and reduced later cutaneous scarring, indicating the importance of local tissue TGF-beta1. By contrast, increasing the local, tissue levels of TGF-beta1 increases the early extracellular matrix deposition but does not alter scar formation. Increased levels of plasma TGF-beta1 correlate with increased fibrogenesis in the lung, kidneys, and liver. The aim of the present study was to investigate the role of elevated systemic levels of TGF-beta1 on wound healing. We used transgenic mice that express high levels of active TGF-beta1 and have elevated plasma levels of TGF-beta1 and wild-type mice of the same strain as controls. Incisional wounds and subcutaneously implanted polyvinyl alcohol (PVA) sponges were analyzed. Surprisingly, cutaneous wounds in transgenic, TGF-beta1-overexpressing mice healed with reduced scarring accompanied by an increase in the immunostaining for TGF-beta3 and TGF-beta-receptor RII and a decrease in immunostaining for TGF-beta1 compared with wounds in control mice. By contrast, the PVA sponges showed the opposite response, with PVA sponges from transgenic mice demonstrating an enhanced rate of cellular influx and matrix deposition into the sponges accompanied by an increase in the immunostaining for all three TGF-beta isoforms and their receptors compared with PVA sponges from control mice. Together, the data demonstrate that increased circulating levels of TGF-beta1 do not always result in increased expression or activity in selected target tissues such as the skin. The two wound models, subcutaneously implanted PVA sponges and cutaneous incisional wounds, differ significantly in terms of host response patterns. Finally, the data reinforce our previous observations that the relative ratios of the three TGF-beta isoforms is critical for control of scarring.

Animals↗
PubMed1999

Synthesis and biological evaluation of novel 2-deoxy-4-thio-imidazole nucleosides.

A study on the use of 3'-directing groups for the synthesis of imidazole 2'-deoxy-4'-thionucleosides led to varying alpha:beta ratios in the glycosylation reaction. The para-nitrobenzoyl group gave the optimum result in the glycosylation step; therefore, this protected thiosugar 10b was used for the synthesis of a series of novel 2'-deoxy-4'-thio-imidazole nucleosides which have been evaluated for antiviral activity in vitro.

Antiviral Agents↗
PubMed1999

Survey of surgical emergencies in a rural population in the Northern Areas of Pakistan.

OBJECTIVE: To determine the incidence of specific surgical emergencies in a mountainous rural community in the Northern Areas of Pakistan and to assess use of existing health services, and outcomes related to acute surgical illness events. METHOD: A cross-sectional population-based survey was conducted. Interviewers visited each of 118 villages in the study area (population 100000), selected a random sample from a total of 9900 households, and interviewed the oldest premenopausal female member (n = 836). Questions were focused on injury, acute abdomen, and/or maternal morbidity occurring in the past year. Cases were included as surgical emergencies when one or more index clinical features indicating a potential for surgical intervention were present. Mortality from a wider range of surgical emergencies was also elicited based on the respondent's lifetime knowledge of the household. RESULTS: The incidence rates were 1531/100000 persons per year for injuries; 1364/100000 for acute abdomen, and 16462/100000 for maternal morbidity. The rate of injuries was 2.7 times higher and that of acute abdomen twice as high in males as in females. The injury rate decreased with advancing age, being 13 times higher in children < 5 years than in adults > 40. By contrast, the rate for acute abdomen showed a rise with advancing age, being 8 times higher in the > 40 age group than in under-fives. Burns, falls and road accidents, in that order, were the commonest forms of injury accounting for 82% of 138 cases. Of 43 burn casualties, 46% were in the age group < 5 years; there was no gender bias. Of 71 casualties from falls and road accidents, 85% were aged 6-40 years; there was 6 : 1 male predominance. The maternal morbidity rate was highest in the age group 25-35 years and may be attributed to the high pregnancy rate in this age bracket. Of 408 patients with acute surgical illness, 85% were managed initially at home or close to home in a health centre, dispensary or civil hospital; 32% eventually sought specialist surgical care. The overall rate for minor and major surgical procedures was 411/100000 persons per year (lowest estimate), and appeared to be low. The rate of operative deliveries at 11.8/1000 deliveries (lowest estimate) was particularly low. The mortality rates were correspondingly high: 55/100000 persons per year for injuries and for acute abdomen (lowest estimates). The maternal mortality ratio was particularly high at 8.9/1000 deliveries (lowest estimate). Annual mortality rates derived from deaths recalled during the respondent's lifetime in the household (mean period = 26 years), tended to corroborate the results of the 1-year survey. CONCLUSION: The incidence rates for broad categories of serious acute surgical illness in the study population far exceeded the rates of acute surgical intervention. Mortality rates were correspondingly high. Such evidence points to a large unmet surgical need and ought to spur improvements in the health service.

Abdomen, Acute↗
PubMed1999

Malignant lymphoma of the gastrointestinal tract.

AIMS: The gastrointestinal tract (GIT) is the most common site of extra-nodal lymphoma. Most of these lymphomas arise from mucosa associated lymphoid tissue (MALT). We attempt in this study to define the natural history and treatment outcome of this type of lymphoma. METHODS: We carried out a retrospective study of patients presenting at our centre with histopathological diagnosis of primary GIT lymphoma between 1990 and 1994. RESULTS: Equal numbers of cases of stomach and small bowel lymphoma were found. Vomiting and feeling of fullness were the two most common presenting symptoms. Large cell type and high grade tumours were found to be the commonest histological types. All the patients were treated with surgery followed by chemotherapy. A 5-year disease-free survival (DFS) rate of 73%) was observed with a confidence interval of 0.65-1.35. Survival in stomach cancer was 73.5% (95% CI 0.26-1.74) while it was 76.4% in small bowel tumours (95% CI 0.54-1.46). The difference in survival was not statistically significant. CONCLUSIONS: Although there is no consensus regarding treatment of primary GI lymphoma, surgery and adjuvant chemotherapy yield good survival.

Diagnosis, Differential↗
PubMed1999

Subcutaneous adrenaline infiltration in paediatric burn surgery.

Paediatric burn surgery may be associated with significant blood loss and postoperative pain. To investigate methods of reducing these symptoms, we studied a prospective series of 29 children with small to medium sized burns. Presurgically both the burn wound and split skin graft donor sites were injected with a 1:500,000 adrenaline solution, to which bupivicaine had been added. No patient required blood transfusion and no patient developed systemic side effects from the injected solution. Four patients required parenteral analgesia, two in the immediate postoperative period and two at first dressing change. In all other patients pain was controlled with oral analgesia alone. Mean graft take in our series was 95%, indicating that this technique does not compromise burn depth assessment, nor impair graft survival.

Anesthetics, Local↗
PubMed1999

Neonatal rabbit proximal tubule basolateral membrane Na+/H+ antiporter and Cl-/base exchange.

The present in vitro microperfusion study examined the maturation of Na+/H+ antiporter and Cl-/base exchanger on the basolateral membrane of rabbit superficial proximal straight tubules (PST). Intracellular pH (pHi) was measured with the pH-sensitive fluorescent dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in neonatal and adult superficial PST. Na+/H+ antiporter activity was examined after basolateral Na+ addition in tubules initially perfused and bathed without Na+. Neonatal Na+/H+ antiporter activity was approximately 40% that of adult segment (9.7 +/- 1.5 vs. 23.7 +/- 3.2 pmol. mm-1. min-1; P < 0.001). The effect of bath Cl- removal on pHi was used to assess the rates of basolateral Cl-/base exchange. In both neonatal and adult PST, the Cl-/base exchange activity was significantly higher in the presence of 25 mM HCO-3 than in the absence of HCO-3 and was inhibited by cyanide and acetazolamide, consistent with Cl-/HCO-3 exchange. The proton flux rates in the presence of bicarbonate in neonatal and adult tubules were 14.1 +/- 3.6 and 19.5 +/- 3.5 pmol. mm-1min-1, respectively (P = NS), consistent with a mature rate of Cl-/HCO-3 exchanger activity in neonatal tubules. Basolateral Cl-/base exchange activity in the absence of CO2 and HCO-3, with luminal and bath cyanide and acetazolamide, was greater in adult than in neonatal PST and inhibited by bath DIDS consistent with a maturational increase in Cl-/OH- exchange. We have previously shown that the rates of the apical membrane Na+/H+ antiporter and Cl-/base exchanger were approximately fivefold lower in neonatal compared with adult rabbit superficial PST. These data demonstrate that neonatal PST basolateral membrane Na+/H+ antiporter and Cl-/base exchanger activities are relatively more mature than the Na+/H+ antiporter and Cl-/base exchangers on the apical membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Selective and reversible blockage of a fatty acid odour response in the olfactory bulb of the frog (Rana temporaria).

The lectin concanavalin A (ConA) when applied to the olfactory mucosa (OM) of frog and rat, is reported to partially inhibit electro-olfactogram (EOG) responses to fatty acid odours. Control odours like isoamyl acetate were not affected. We have now studied in the frog whether this treatment affects the corresponding olfactory bulb (OB) response. The OB surface was impregnated with a voltage-sensitive dye (RH 414). Spatial and temporal patterns of odour response were measured by changes in dye fluorescence that occur when OB neurons fire. The apparatus, consisted of an epi-fluorescent microscope coupled to a 64 x 64 pixel CCD photodetection camera. This allowed imaging over an 0.9 mm2 area of the OB glomerular layer to high resolution. When the frog OM was bathed with 5 mg ml(-1) ConA in Ringer's solution, the n-butyric acid odour response in the OB largely disappeared while the isoamyl acetate response did not change. When this experiment was repeated in the presence of 20 mM methyl alpha-D mannopyranoside (a ConA inhibitor), ConA failed to inhibit the n-butyric acid response. Moreover the ConA effect was partially reversible. A Ringer's wash of the OM after ConA treatment, partially restored the OB response to n-butyric acid. Thus the olfactory bulb results seem compatible with the EOG results and reinforce the notion that ConA selectively prevents n-butyric acid sensitive olfactory receptor neurons from firing. Chemical modification of the OM and their effect on OB response patterns may provide a useful approach to investigate olfactory quality coding.

Animals↗
PubMed1998

Interferon-alpha-associated focal segmental glomerulosclerosis with massive proteinuria in patients with chronic myeloid leukemia following high dose chemotherapy.

BACKGROUND: Acute renal failure, with or without massive proteinuria, is a rare idiosyncratic toxicity of interferon (IFN)-alpha therapy. The authors sought to review their experience with this toxicity as well as the world literature on the subject. METHODS: The authors describe two patients with chronic myeloid leukemia treated with IFN-alpha following high dose chemotherapy who developed renal failure and proteinuria after 3 and 4 weeks of IFN-alpha therapy, respectively. Fifteen previously reported cases of renal failure and proteinuria associated with IFN-alpha therapy are also reviewed. RESULTS: Renal biopsies performed on the authors' two patients revealed focal segmental glomerulosclerosis. However, the other reported patients with IFN-alpha-associated renal failure and massive proteinuria had an assortment of pathologic findings. CONCLUSIONS: The specific renal pathology associated with proteinuria may be a consequence of the condition and not its cause; differences in renal pathology may be caused by other predisposing factors. Patients treated with IFN-alpha following high dose chemotherapy, with or without autologous transplantation, should be followed for the development of proteinuria and renal failure.

Adult↗