Biomedical subjects

S M Graham

Publications and source records attributed to S M Graham.

At least 73 records · Page 4Linked to original sources

PubMed1997

Pectoralis major myofascial flap: a valuable tool in contemporary head and neck reconstruction.

BACKGROUND: The pectoralis major myofascial (PMMF) unit is rapidly mobilized, reliable, and extremely useful in a number of clinical situations calling for vascularized soft-tissue coverage in the head and neck. Although free-tissue transfer has emerged as the preferred method of reconstruction for a large variety of defects in the head and neck, the pectoralis major muscle should be considered when vascularized soft-tissue coverage is required in this area. METHODS: A retrospective chart review of 24 PMMF flaps performed at the University of Iowa Hospitals and Clinics between January 1, 1991, and May 1, 1996, was undertaken. Outcomes were evaluated relative to accomplishing the established preoperative surgical goals. RESULTS: Utilization of the PMMF flap was grouped according to four primary indications: (1) protection of threatened great vessels or free flap vascular pedicles in situations of wound breakdown due to fistula or infection (7 cases); (2) vascularized soft-tissue coverage of great vessels or free-flap vascular pedicles and prevention of potential wound breakdown in surgical defects in which compromised healing was anticipated (7 cases); (3) closure of small pharyngeal defects (2 cases); or (4) vascularized coverage of the mandible following debridement for osteoradionecrosis (8 cases). The PMMF flap was 100% successful when the surgical goal was to protect exposed vascular structures and promote wound healing in the presence of fistula or infection. The PMMF flap was 100% successful in the protection of vascular structures and prevention of wound breakdown in cases where compromised wound healing was anticipated. The PMMF flap provided closure, and a vascularized surface for mucosalization, when used to primarily reconstruct small pharyngeal defects. The PMMF flap provided definitive closure in 5 of 8 (62.5%) cases of osteoradionecrosis of the mandible when it was used to invest the remaining mandibular bone. Three of 8 cases (37.5%) required further surgical management and were considered failures. An acceptable cosmetic outcome was obtained in women undergoing this procedure by using an inframammary incision. The preoperative goal of the PMMF flap procedure was met in 21 of 24 (87.5%) cases. There was a major complication rate of 12.5% as well as a minor complication rate of 12.5%. CONCLUSION: In cases requiring the protection of vital vascular structures from infection, salivary secretions or skin flap breakdown, the PMMF flap should be considered. The PMMF flap is an excellent reconstructive option in selected clinical situations, where vascularized soft-tissue coverage is required in the head and neck.

Adult↗

PubMed1997

Psychomotor effects of the anxiolytic abecarnil: a comparison with lorazepam.

Abecarnil is a metabolically stable beta-carboline that binds with high affinity and selectivity to central benzodiazepine receptors. The effects on cognitive and psychomotor skills of abecarnil (ZK 112-119), 2.5 mg and 5.0 mg, were compared with lorazepam 2.0 mg and placebo. Twenty-four healthy, young males participated in a double-blind, four-way Latin square design and performed batteries of behavioral tests at predrug and at 20, 40, 60, 80, 100, 120, 180, 240, 360 and 480 min after drug administration. Abecarnil 5.0 mg and lorazepam 2.0 mg displayed similar impairment profiles in tests of cognitive functions including memory encoding. Abecarnil 2.5 mg was substantially less impairing than lorazepam. Impairment levels of the abecarnil and lorazepam treatments peaked at 2-3 h after oral administration. The two abecarnil doses showed dose-dependent effects on the cognitive and psychomotor tasks. All three drug treatments were well tolerated by the subjects, with no one terminating early due to adverse events. The incidence of reported adverse events for abecarnil was dose-dependent. The most frequent, statistically significant adverse effects were drowsiness, lack of concentration and visual disturbance for abecarnil 5.0 mg; and lack of concentration and dizziness for lorazepam 2.0 mg. There were no significant differences in adverse incidence rates between abecarnil 2.5 mg and placebo.

Adult↗

PubMed1997

Case management of kwashiorkor: an intervention project at seven nutrition rehabilitation centres in Malawi.

OBJECTIVES: (1) To improve case management of kwashiorkor at seven Nutritional Rehabilitation Centres (NRCs) through 2-4 weekly paediatric supervisory visits. (2) To evaluate the impact of the use of routine tube-feeding and a micronutrient supplement (Nutriset). DESIGN: An intervention project with descriptive clinical data in which Nutriset was introduced halfway through the project, and routine tube-feeding at one NRC was compared to no tube-feeding at a similar one. SETTING: NRCs located at two central hospitals, two district hospitals and three rural clinics in southern Malawi. SUBJECTS: 1625 consecutive kwashiorkor admissions from January-December 1995. RESULTS: The overall case-fatality rate was 24.2% (393/1625), varying by facility level (central 30.5%, district 25.8% and rural 7.5%), reflecting different severity of cases. From ELISA testing and a clinical protocol, we estimate that 21.7% (353/1625) of these kwashiorkor cases were HIV-infected, including 121 breastfed children. Routine tube-feeding was associated with better weight gain (8.24 g/kg/d) than no tube-feeding (4.51 g/kg/d) at central NRCs, but with no reduction in mortality (31.4% vs 30.3%). The introduction of Nutriset was associated with improved weight gain (6.06 vs 4.66 g/kg/d) and a lower mortality (20.8 vs 25.8%), but was confounded by seasonal factors. CONCLUSIONS: From a clinical perspective, HIV infection has transformed kwashiorkor in this part of Africa. Routine tube-feeding was associated with improved body weight gain in the treatment of kwashiorkor. The benefit of paediatric supervision was limited by the infrequency of visits, by constraints of health worker motivation, by a lack of resources and by the severity of disease. Efforts need to focus-not just on case management protocols-but on how to actually improve clinical practice in this setting.

Case Management↗

PubMed1997

Pneumocystis carinii pneumonia in Malawian children.

Sixty children aged between 1 and 23 months admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi for diagnosis of acute lower respiratory tract infections (ALRI) were investigated for laboratory diagnosis of Pneumocystis carinii pneumonia (PCP) by indirect immunofluorescence assay on nasopharyngeal secretions. P. carinii was found in five of the 60 children. Three PCP cases had AIDS. The clinical presentation of children with PCP was of little diagnostic value and all the children were infants. Arterial oxygen saturation was significantly lower in PCP cases. Of the five PCP cases, four died, indicating that the marked hypoxaemia was associated with poor prognosis. These results indicate that an immunofluorescence assay on nasopharyngeal secretions could be used for first-line diagnosis of PCP in Africa.

AIDS-Related Opportunistic Infections↗

PubMed1997

Carriage of penicillin-resistant pneumococci in Malawian children.

In a prospective study of pneumococcal carriage in 200 Malawian children under 5 years of age, 47.5% were carriers. The carriage rate was highest in those aged 3-12 months and did not vary with family size, nor was it higher in those who had recently been admitted to hospital. Nasopharyngeal swabs were significantly more efficient than throat swabs in detecting carriers (p < 0.001) but nasopharyngeal swabs alone would have missed seven (8%) carriers. Pneumococcal isolates from 22% of carriers and from eight cases of meningitis and one of empyema showed intermediate resistance to penicillin (MIC 0.1-1.0 mg/l). All were sensitive to the 3rd-generation cephalosporin cefotaxime but one of the penicillin-resistant pneumococci and two of the clinical isolates had increased MICs of cefuroxime (0.5 mg/l).

Age Distribution↗

PubMed1997

Efficacy of tepid sponging versus paracetamol in reducing temperature in febrile children.

A block randomized clinical trial to compare the efficacy of tepid sponging with the use of paracetamol in febrile children was undertaken at the Queen Elizabeth Central Hospital, Blantyre. Eighty children aged between 6 and 54 months with axillary temperatures of between > or = 38.5 degrees C and < or = 40 degrees C and a clinical diagnosis consistent with upper respiratory tract infection and/or malaria were block randomized to receive either oral paracetamol (15 mg/kg) or tepid sponging. Children receiving tepid sponging were sponged from head to toe (except the scalp) by leaving a thin layer of water on the body. If the body became dry it was repeated and continued until the axillary temperature fell to < 38.5 degrees C. Axillary temperature and assessment of discomfort (convulsions, crying, irritability, vomiting and shivering) were recorded every 30 minutes for 2 hours. A significantly greater and more rapid reduction of fever was demonstrated with paracetamol than with tepid sponging. Tepid sponging without antipyretics is often used to reduce fever, but our results suggest that this is effective only during the 1st 30 minutes. Paracetamol is clearly more effective than tepid sponging in reducing body temperature in febrile children in a tropical climate.

Acetaminophen↗

PubMed1997

Whole-body protein kinetics in children with kwashiorkor and infection: a comparison of egg white and milk as dietary sources of protein.

This study tested the hypothesis that during treatment of kwashiorkor (including marasmic kwashiorkor) with infection there is a lower rate of amino acid oxidation when the dietary intake of amino acids resembles the amino acid composition of acute phase proteins (APPs). Twenty-two children in Blantyre, Malawi, with kwashiorkor and acute infection were fed an isoenergetic, isonitrogenous diet with either egg white or milk as a protein source. The whole-body amino acid oxidation rate was measured after 24 h by determining the plasma urea rate of appearance, and whole-body protein breakdown and synthesis rates were determined from the plasma leucine rate of appearance. Plasma concentrations of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h. The 11 children who received milk had a lower rate of amino acid oxidation than the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/- 66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences were found between the two groups in the rate of whole-body protein breakdown or protein synthesis. The TNF-alpha concentration correlated inversely with whole-body protein breakdown and synthesis rates, and the IL-6 concentration correlated directly with C-reactive protein. We conclude that by making the amino acid composition of the diet resemble that of APPs in the treatment of acute kwashiorkor, the rate of amino acid oxidation can be decreased.

C-Reactive Protein↗

PubMed1997

Resource utilization and patient morbidity in head and neck reconstruction.

Many papers have addressed the technical aspects of free tissue transfer in head and neck cancer patients. However, there has not been a critical assessment of the impact of free tissue transfer on resource utilization and patient morbidity compared with pedicle flap reconstructions. Two cohorts of patients derived from 245 consecutive reconstructions were tightly matched by age, site, stage, and histology, yielding 44 patient pairs differing in method of reconstruction. Patients undergoing free flap reconstruction spent more time in the operating room than those reconstructed with pedicled flaps (993 min vs. 777 min, P < 0.0001). The group with free flap reconstruction spent fewer days in the surgical intensive care unit and hospital (2 days vs. 2.5 days; 18.5 days vs. 22.6 days). This difference is attributed to the paucity of postoperative complications in the group with free flap reconstruction (fistula formation 4.5% vs. 21%, P < 0.04). These data indicate that the continued use of sophisticated reconstructive techniques in head and neck cancer patients is economically sound as assessed by patient morbidity and resource utilization.

Critical Care↗

PubMed1997

Combined endoscopic and subciliary orbital decompression for thyroid-related compressive optic neuropathy.

Compressive optic neuropathy is a feared, although unusual, complication of thyroid-related orbitopathy. A variety of surgical approaches have been described to achieve orbital decompression and alleviate the hallmark apical orbital crowding of this condition. We describe a subciliary anterior orbitotomy approach to the floor combined with an endoscopic medial wall resection. The anterior orbitotomy allows removal of the bones of the orbital floor both medial and lateral to the canal of the infraorbital nerve. The anterior orbital floor is retained for globe support. This combined approach retains the low morbidity of the endoscopic operation while achieving increased apical medial orbital wall and orbital floor decompression. We describe two illustrative cases where this approach produced a dramatic improvement in visual function. The surgical refinements associated with this combined approach offer technical advantages over other operations in the treatment of thyroid-related compressive optic neuropathy.

Aged↗

PubMed1997

The pattern of tuberculosis in Queen Elizabeth Central Hospital, Blantyre, Malawi: 1986-1995.

SETTING: Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. OBJECTIVE: To determine the pattern of tuberculosis (TB) cases over a period of ten years. DESIGN: TB registers for QECH for the years 1986-1995 (January 1st to December 31st) were obtained and clinical information on the type of TB in each patient was recorded. Human immunodeficiency virus (HIV) test results of adults with smear-positive pulmonary TB (PTB) and children with TB between 1993 and 1996 were recorded from case notes. RESULTS: There were 19,377 TB cases, 10,982 men and 8,395 women, registered over the ten-year period. Of these, 4,691 (24%) cases were in children aged 0-14 years and 11,890 (61%) cases were in adults aged 15-44 years. The number of cases increased from 657 in 1986 to 2,734 in 1995, and the proportion of cases with extra-pulmonary TB (EPTB) rose from 11% in 1986 to 33% in 1995. The largest increase in cases was in children and in young adults aged 15-44 years. In all age groups, PTB was more common than EPTB. There were significant increases in the proportion of adult TB cases with pleural effusion. Of those who were tested, 72% of adults with smear-positive PTB and 64% of children with TB were found to be HIV-seropositive. CONCLUSION: There has been a dramatic increase in cases of TB and changes in disease pattern in QECH during the last 10 years, which is related to the HIV epidemic.

AIDS-Related Opportunistic Infections↗

PubMed1997

Utility of the nasal model in gene transfer studies in cystic fibrosis.

Despite advances in the treatment for cystic fibrosis (CF), life expectancy for affected patients remains dramatically curtailed. Recent years have produced a spectacular increase in our understanding of the genetic, molecular and physiological bases of this disease. Gene transfer is a new and conceptually-attractive potential treatment for CF. A number of centres have undertaken preliminary human gene-therapy trials. Central to these trials has been the use of the nasal model in gene transfer studies. While the eventual target of gene therapy in CF will be the lungs, the nasal administration of vector offers a number of advantages over the tracheobronchial tree in early experimentation. Implicit in the use of the nasal model is the potential for rhinologic variables to influence the results. We review our own gene transfer studies as well as series from other institutions, considering the role of nasal factors in the experiments' outcomes. Rhinologic variables may, at least partially, potentially explain the sometimes disparate results reported in this emerging area of scientific interest.

Adenoviridae↗

PubMed1996

Chloramphenicol-resistant bacterial meningitis in Malawi.

Three recent cases of chloramphenicol-resistant pyogenic meningitis are reported from Malawi. The implications of the emergence of antibiotic-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae type b causing childhood meningitis are discussed.

Child↗

PubMed1996

Lactobacillus GG and acute diarrhoea in young children in the tropics.

A prospective, placebo controlled, triple blind clinical trial was undertaken in Thailand to determine the effect of Lactobacillus GG on recovery from acute diarrhoea in children. Thirty-nine children (mean age = 8 months) were enrolled and following rehydration received either oral Lactobacillus GG (n = 20) as a freeze-dried preparation or placebo (n = 19) twice daily for 2 days. The clinical characteristics of the study groups were similar. There was no significant difference overall in clinical response detected between the study groups. When only those with acute non-bloody diarrhoea (n = 26) were considered, the mean duration of diarrhoea was significantly shorter in the lactobacillus group (1.9 days) than in the placebo group (3.3 days) (P < 0.055). Stool frequency was less on the second day in the lactobacillus group (P < 0.05). The results suggest that Lactobacillus GG accelerates recovery from acute watery diarrhoea in young children in a tropical setting.

Acute Disease↗

PubMed1996

Laparoscopic splenectomy in patients with hematologic diseases.

OBJECTIVE: The authors review their initial experience with laparoscopic splenectomy in patients with hematologic diseases. Efficacy, morbidity, and mortality of the technique are presented, and other patient recovery parameters are discussed. SUMMARY BACKGROUND DATA: Laparoscopic splenectomy is performed infrequently and data regarding its safety and efficacy are scarce. Factors such as a high level of technical difficulty, the potential for sudden, severe hemorrhage, and slow accrual of operative experience due to a relatively limited number of procedures are responsible. The potential patient benefits from the development of a minimally invasive form of splenectomy are significant. METHODS: Clinical follow-up, a prospective longitudinal database, and review of medical records were analyzed for all patients referred for elective splenectomy for hematologic disease from March 1992 to March 1995. RESULTS: Laparoscopic splenectomy was attempted in 43 patients and successfully completed in 35 (81%). Therapeutic platelet response to splenectomy occurred in 82% of patients with immune thrombocytopenic purpura and hematocrit level increased in 60% of patients with autoimmune hemolytic anemia undergoing successful laparoscopic splenectomy. The morbidity rate was 11.6% (5 of 43 patients), and the mortality rate was 4.7% (2 of 43 patients). Return of gastrointestinal function occurred in patients 23.1 hours after laparoscopic splenectomy and 76 hours after conversion to open splenectomy (p < 0.05). Mean length of stay was 2.7 days after laparoscopic splenectomy and 6.8 days after conversion to open splenectomy (p < 0.05). CONCLUSION: Laparoscopic splenectomy may be performed with efficacy, morbidity, and mortality rates comparable to those of open splenectomy for hematologic diseases, and it appears to retain other patient benefits of laparoscopic surgery.

Adolescent↗

PubMed1996

Flexible endoscopy for the diagnosis of esophageal trauma.

The role of flexible endoscopy in the diagnosis of esophageal trauma remains undefined. This study evaluates the use of immediate flexible fiberoptic esophagogastroduodenoscopy (EGD) as the primary diagnostic tool for detection of esophageal injury in trauma patients. Flexible EGD was performed on 31 patients for this purpose from August 1991 through January 1994. There were 28 males and 3 females with a mean age of 24.3 years (range, 16-54 years). Twenty-four of 31 patients (77%) were intubated at the time of the examination. Mechanism of injury was penetrating in 24 patients (20 gunshot wounds, four stab wounds) and blunt (motor vehicle crash) in seven patients. Penetrating injuries were located in the neck in 5 of 24 patients, in the chest in 15 of 24 patients, and in both the neck and chest in 4 of 24 patients. Upper gastrointestinal contrast studies were performed for 3 of 31 patients (10%), computed tomography was performed for eight patients (26%), bronchoscopy was performed for 13 patients (42%), angiography was performed for 17 patients (55%), and rigid esophagoscopy and laryngoscopy were each performed for one patient (3%). Evidence of esophageal trauma during EGD was seen in 5 of 31 patients. True-positive studies occurred for four patients, false-positive results occurred for one patient, true-negative results occurred for 26 patients (as demonstrated by exploration in five and clinical follow-up in 21), and no false-negative examinations occurred. Sensitivity of flexible EGD was 100%, specificity was 96%, and accuracy was 97%. No complications occurred related to the performance of EGD. Flexible fiberoptic endoscopy seems to be a safe and effective method for both detection and exclusion of esophageal trauma.

Adolescent↗

PubMed1996

TC21 causes transformation by Raf-independent signaling pathways.

Although the Ras-related protein TC21/R-Ras2 has only 55% amino acid identity with Ras proteins, mutated forms of TC21 exhibit the same potent transforming activity as constitutively activated forms of Ras. Therefore, like Ras, TC21 may activate signaling pathways that control normal cell growth and differentiation. To address this possibility, we determined if regulators and effectors of Ras are also important for controlling TC21 activity. First, we determined that Ras guanine nucleotide exchange factors (SOS1 and RasGRF/CDC25) synergistically enhanced wild-type TC21 activity in vivo and that Ras GTPase-activating proteins (GAPs; p120-GAP and NF1-GAP) stimulated wild-type TC21 GTP hydrolysis in vitro. Thus, extracellular signals that activate Ras via SOS1 activation may cause coordinate activation of Ras and TC21. Second, we determined if Raf kinases were effectors for TC21 transformation. Unexpectedly, yeast two-hybrid binding analyses showed that although both Ras and TC21 could interact with the isolated Ras-binding domain of Raf-1, only Ras interacted with full-length Raf-1, A-Raf, or B-Raf. Consistent with this observation, we found that Ras- but not TC21-transformed NIH 3T3 cells possessed constitutively elevated Raf-1 and B-Raf kinase activity. Thus, Raf kinases are effectors for Ras, but not TC21, signaling and transformation. We conclude that common upstream signals cause activation of Ras and TC21, but activated TC21 controls cell growth via distinct Raf-independent downstream signaling pathways.

3T3 Cells↗

PubMed1996

Adenovirus-mediated gene therapy for head and neck squamous cell carcinomas.

Advanced head and neck squamous cell carcinomas (HNSCCs) have a poor prognosis despite aggressive multimodal therapy. The goal of our study was to test the feasibility of gene transduction as a novel therapy for head and neck cancer. Three human HNSCC cell lines were transduced in vitro with a replication-deficient recombinant adenovirus containing the lacZ marker gene (Ad2/CMV beta gal). Gene transduction efficiency was dependent on multiplicity of infection, duration of exposure to the virus, and viral concentration. Next, the HEp-2 cell line was transduced with an adenoviral vector (Ad.RSVtk) containing the herpes simplex virus thymidine kinase (HSVtk) gene, which, when expressed, sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in complete tumor cell killing. These results suggest that adenovirus-mediated transfer of HSVtk and administration of GCV has potential as a new therapy for HNSCC.

Adenoviridae↗

PubMed1995

Farnesyltransferase inhibitors are inhibitors of Ras but not R-Ras2/TC21, transformation.

Recent results from several laboratories including ours strongly suggest that farnesyltransferase (FT) inhibitors belonging to distinct chemical classes block growth of oncogenic Ras transformed cells at concentrations that do not affect the growth and viability of normal cells. This is despite blocking the farnesylation and thus the membrane association of Ras in both cell types. This is a paradox given the requirement for Ras function in normal cell growth. Recent evidence that R-Ras2/TC21 utilizes components of Ras signal transduction pathways to trigger cellular transformation (Graham et al., MCB 14, 4108-4115, 1994) prompted us to consider the possibility that R-Ras2/TC21 is involved in some aspects of the growth regulation of normal cells. If so, R-Ras2/TC21 may be compensating for Ras function in untransformed cells treated with FT inhibitors. In this study, we demonstrated that a cell active bisubstrate analog FT inhibitor, BMS-186511, completely blocked the function of oncogenic Ras, but did not affect the function of oncogenic R-Ras2/TC21, as determined by several criteria including inhibition of anchorage dependent and independent growth, reversal of transformed morphology and restoration of actin cytoskeleton. While it is known that TC21 protein becomes prenylated, it is not known whether it is farnesylated or geranylgeranylated. Our in vitro prenylation experiments indicate that R-Ras2/TC21 protein serves as a good substrate for FT as well as geranylgeranyltransferase I (GGTI) and thus provide the apparent molecular basis for these differences. Overall, these results, coupled with the ubiquitous expression of R-Ras2/TC21 in many cells including untransformed NIH3T3 cells, are consistent with the possibility that R-Ras2/TC21 may be one of the factors that render normal cells insensitive to the growth inhibitory action of FT inhibitors.

3T3 Cells↗