Therapeutic strategies,including a high surgical ligation rate,for patent ductus arteriosus closure in extremely premature infants in a North American centre

OBJECTIVE:

To document the rate of surgical ligation of a patent ductus arteriosus (PDA) in extremely premature infants who had received more than one course of indomethacin. Outcomes were compared among three subgroups (ligation, further indomethacin and no further treatment) of infants who received at least one course of indomethacin, and between two subgroups (one course of indomethacin and more than one course) among infants who underwent ligation.

STUDY DESIGN:

A retrospective chart review of all 23 weeks+0 days to 26 weeks+6 days’ gestational age infants with a PDA born between 1994 and 2005 was performed. Secondary outcomes were compared among the subgroups.

RESULTS:

The final study population consisted of 196 extremely premature infants with a PDA. The rate of surgical ligation in the 88 infants who received more than one course of indomethacin was 64%. The ligation subgroup, in comparison with the no further treatment subgroup, spent a greater median time on mechanical ventilation (39 versus 29 days, P<0.001) and in hospital (115 versus 92 days P=0.002), while trending toward lower mortality (18% versus 40%, P=0.07). The PDA closed following the first course of indomethacin in only 20% of infants.

CONCLUSIONS:

A majority of extremely premature infants receiving more than one course of indomethacin underwent surgical ligation. Repeated indomethacin courses were generally well tolerated, but were mostly unsuccessful. Ligation appears to have potential risks and benefits. A randomized trial should be performed after studies define a hemodynamically significant PDA that will result in morbidity and/or mortality unless treated.     

R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations

Mutations in ACTA2 (smooth muscle cell-specific isoform of α-actin) lead to a predisposition to thoracic aortic aneurysms and other vascular diseases. More recently, the ACTA2 R179H mutation has been described in individuals with global smooth muscle dysfunction. We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune-belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune-belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal megacystis with a normal karyotype, particularly if the bladder diameter is 15?mm or more, to allow expectant parents to make an informed decision.     

Descriptive retrospective analysis of the diagnostic yield and morbidity of four vessel catheter-directed cerebral angiography and multidetector computed tomographic angiography (MDCTA) performed at Inkosi Albert Luthuli Central Hospital (IALCH)

Imaging studies are indispensable in order to determine the source, location and pattern of intra and extra-axial brain haemorrhages. In our study of 277 patients carried out over an 18 month period, the most common reason of referral was subarachnoid haemorrhage followed by trauma.Aneurysms were the most common diagnosis (36%) with anterior and posterior communicating arteries being the most common locations. Fifty percent (50%) of patients investigated had a normal study.Our findings show that the yield from MDCTA and conventional angiography was relatively comparable, however, conventional angiography was superior in detection of aneurysms; hence, in cases were the MDCTA result was found to be normal despite a high index of suspicion for a subarachnoid haemorrhage, a follow-up MDCTA study or conventional angiography is useful. Moreover, conventional angiography was superior in detection of multiple aneurysms.     

A comparison of immunomodulation therapies in mechanically ventilated patients with Guillain Barré syndrome

A comparison of the effectiveness of immunomodulatory therapies in patients with Guillain Barré syndrome (GBS) who require mechanical ventilation (MV) is important for patient treatment and cost. We aimed to compare the effectiveness of three modes of intervention on the outcome of patients with GBS receiving MV: intravenous immunoglobulin (IVIgG); small volume plasmapheresis (SVP) and large volume plasmapheresis (LVP). Patients with GBS satisfying National Institute of Neurological and Communicative Disorders and Stroke 1990 criteria and requiring MV between 1997 between 2007 were analyzed. The primary outcome parameters evaluated were mortality, duration of MV, hospital stay and Hughes scale at discharge from hospital. Of the 173 (Male: Female, 118:55) patients who required MV during the study, 106 patients received single modality treatment (IVIgG 31, LVP 45, SVP 30) based on availability, affordability and feasibility. Patients receiving IVIgG had a higher incidence of severe weakness and bulbar involvement. The mean duration of MV (p = 0.61), total hospital stay (p = 0.44) and Hughes scale at discharge (p = 0.31) did not differ among the three groups. Complications were similar in the three treatment groups except for hypoalbuminemia and anemia, which were more common in patients in the LVP group. In conclusion, the outcome of patients treated with these three immunomodulatory treatment modalities did not vary. The beneficial effects of SVP in our study warrant further randomized control trials especially in resource-constrained settings.     

A SEARCH FOR UNHAPPY ABDOMEN: PREVALENCE OF IRRITABLE BOWEL SYNDROME IN GENERAL POPULATION

The irritable bowel syndrome is the commonest gastrointestinal disorder seen in practice but its exact prevalence in India is not known. This study was carried out to determine the prevalence of symptoms compatible with this diagnosis in general population. A cross sectional random sample survey was conducted in various strata of urban population in Wanoworie area of Pune. Survey utilized personal interviews based on a questionnaire. Symptoms were evaluated as per Manning criteria and the diagnosis of irritable bowel syndrome was defined by Kruis diagnostic index. Of the 1010 subjects interviewed, 370 (37%) reported more than 6 episodes of abdominal pain in previous 6 months, with 333 reporting symptoms consistent with the the diagnosis of irritable bowel syndrome. At least one of the Manning''s symptoms was present in 307 out of 370 subjects (83%). The male female ratio was 5.3:1. Among males, 288 (35%) and among females 82 (53.2%) persons had at least some degree of abdominal discomfort. Other common symptoms were: excessive passage of wind (42.2%), irregular bowel habits (33%), excessive belching (30.8%), constipation (27.5) and feeling of incomplete evacuation(28.1%). About one third of the symptomatic subjects (134 or 36.2%) had seen a doctor or wanted to be seen by a specialist. Overall prevalence of the symptoms consistent with irritable bowel syndrome thus, is 33 per cent though only about a third of these may possibly consult a doctor. Follow up of all these patients for a mean duration of 8.3 months showed that no case of organic disease was picked up either by the scoring system or by the gastroenterologist. Symptoms consistent with the diagnosis of irritable bowel syndrome are see in almost one third of the study population residing in Wanoworie area of Pune.KEYWORDS: Irritable bowel syndrome, Kruis diagnostic index, Manning''s symptoms     

Hormone Receptors,Her-2/Neu and Chromosomal Aberrations in Breast Cancer

Background

There is a great deal of disparity in the incidence of breast cancer in rural and urban India on one hand and between India and Western population on the other.

Methods

We analysed steroid receptor status in cases of breast cancer in a small sample of patients in armed forces. Infiltrating duct carcinomas of breast recorded histologically in mastectomy specimens in last two years were accessioned in the present study with reference to patient and tumour characteristics.

Result

In contrast to the higher rates reported in western literature, only 33 % of the tumours expressed estrogen receptors (ER) and progesterone receptors (PR), of which 24% were ER positive and 30% PR positive. Negative steroid receptor status did not correlate with presence or absence of metastatic nodes, however it was predominant amongst the high grade infiltrating duct carcinomas in this study. Necrosis and lymphovascular invasion demonstrated an inverse relationship with the ER/ PR reactivity. 70% of the node positive cases expressed Her –2/ Neu, reflecting a higher immunoreactivity in this subset of patients. Aneusomy for chromosomes 1, 11 and 17 was common in node positive cases.

Conclusion

Evaluation of chromosomal aberrations by Fluorescent In Situ Hybridization (FISH) technique correlates well with traditional histological parameters.Key Words: Breast carcinoma, Hormone receptors, Her –2/ Neu     

EARLY DIAGNOSIS IN POST RENAL TRANSPLANT OPPORTUNISTIC INFECTIONS: A FRESH LOOK

A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.KEY WORDS: Immune diagnosis, Opportunistic infections, Transplantation